Adsorptive Crystallization of Organic Substances in Silica ...

Adsorptive Crystallization of Organic Substances in Silica Aerogels

from Supercritical Solutions

Der Technischen Fakultät der

Universität Erlangen-Nürnberg

zur Erlangung des Grades

DOKTOR-INGENIEUR

vorgelegt von

M.Sc. Babu Suresh Kumar GORLE

aus Hyderabad, Indien

Erlangen – 2009

II

Als Dissertation genehmigt von

der Technischen Fakultät der

Universität Erlangen-Nürnberg

Tag der Einreichung: 06.04.2009

Tag der Promotion: 10.06.2009

Dekan: Professor Johannes Huber

Vorsitzender: Professor Axel König

1. Berichterstatter: Professor Wolfgang Arlt

2. Berichterstatter: Professor Irina Smirnova

3. Berichterstatter: Professor Wilhelm Schwieger

weiteres prüfungsberechtigtes Mitglied: Professor Peter Wellmann

III

Acknowledgement

During my last three and half year, I worked on my PhD work at Chair of Separation and

Technology, University of Erlangen. During this time, I worked in close co-operation with many

people spent one quality time with lots of friends, whom I sincerely wish to acknowledge in this

section.

Thanks to Prof. Wolfgang Arlt for accepting me for a PhD position at his chair and for

supervising my work. His critical remarks on the research work helped me to have an eye on

finer details in the research work. His popularity in the research community always helped me to

get in contact with other research groups where I need to conduct some experiments.

Special thanks to Prof. Irina Smirnova (presently Chair of Institut für Thermische

Verfahrenstechnik, Technical University of Hamburg and Harburg), who initiated this PhD

research project and guided me through my work. I am truly indebted for her continuous

inspiration, timely appreciation and encouragement which helped me to keep going during the

three and half years of my project. Her enormous abilities of generating new ideas, discussions

and explanations lead to a new direction in the present research work ‘adsorptive crystallization’

which is presented in this work.

I would like thank Prof. Mark A. McHugh for his remarks, comments, suggestion on the PhD

work during his sabbatical at the Chair of Separation and Technology, University of Erlangen.

Interacting with him has taught me how to look at finer details of the experimental data. I cherish

long discussions and explanations of various phenomena’s with him has given a new path to the

present research work.

Thanks to Prof. Axel König for his help in performing DSC experiments. Discussion with him

always helped to understand the results of DSC. I am grateful his comments and suggestions. I

am also thankful to Prof. Wilhem Schwieger for providing me the MCM41 and Zeolite samples. I

would like thank his student; Ayyapan, Sai, Abhijeet for helping me to do some TGA/MS

experiments and also sharing me their knowledge about Zeolite and MCM41 materials.

IV

I would like to thank Detlef and Martin Drescher for their great help in built the plant for my

experiments. I would like thank Edelgard for her help in analysis all my samples and preparing

aerogels. During my work with her gave me a chance to understand the German social and

culture exposure. Thanks to Petra Kiefer for help in analysis samples and making some nice

digital pictures for my work. Thanks to Petra Koch for her help in performing BET of my aerogel

samples and also placing the chemical orders for me. Thanks to Rosa, Jorge, Jose for helping me

to make DSC analyses for me.

I would like thank the work shop team Matthias, Hans for their continuous help in solving my

experimental setup problems. I appreciate Matthias help and idea in solving the problems that

occurred during my work without his help it would not have been possible to continue to the

experimental work. I am also thanks full to Wolfgang Gäckel for his help in fixing all my

experimental problems.

Thanks to Reddy who was always free and ready to discuss my results and to share some private

talks. I am thankful to my German friends at the chair; Martin, Alexander, Florian, Sussa, Lissi,

Tanya, and Ulrike, the time I spent with them both in private and in the chair, who taught me the

German culture which includes beer. I am thankful to Dirk Weckesser for his help in solving my

computer problems. It was great to share small chats during coffee time with Jinglan, Bo-Hyun,

Liping, Mirjana, Ludmilla, Vladimar, Jose, and Jorge. Special thanks to Bo Hyun for correcting

formatting of my PhD thesis. Thanks to Ludmilla for her critical remarks on research work and

presentations. I would like thank the students who worked on my project during my work;

Fatima, Daniel, Muard, Katharina, Sudhanshu, Abhishek, Rustem.

Last but not least, I am thankful to my family members for their continuous telephone or personal

talks with me during my stay in Germany, without which I would not have realized my PhD

work.

Finally, I would like to thank all the people who were not mentioned above but have helped me

in some or the other way to complete my work successful.

V

Nomenclature

-OR Alkyl group

VOC’s Volatile organic compounds

TMOS Tetramethylorthosilicate

MEOH Methanol

BET Brunauer, Emmett, and Teller

BJH Barrett Joiner Halenda

-CH3 Methyl

CHN Carbon Hydrogen and Nitrogen

Tm Melting temperature

DSC Differential scanning calorimeter

CP1 Critical point of substance 1

CP2 Critical point of substance 2

UCEP Upper Critical Point End

LCEP Lower Critical Point End

SLG Solid Liquid Gas

TP2 Triple point of substance 2

TLCEP Temperature of LCEP

TUCEP Temperature of UCEP

Tmin Temperature minimum

XRD X- ray diffraction

m(p,T)absolute mass of solute/solvent adsorbed(g)/(g) aerogel

m(p,T)excess mass of solute/solvent adsorbed(g)/(g) aerogel

Vb Volume of basket

Vs Volume of sample (aerogel)

Vads Volume of adsorbed CO2

ρb Bulk density of CO2 or CO2 + solute

ρadsorbed density of adsorbed CO2

∆m Weight difference due to adsorbed

VI

solute/solvent

SANS Small angle neutron scattering

RESS Rapid Expansion form Supercritical Solutions

GAS Gas anti solvent

SAS Supercritical Anti Solvent

PGSS Particles from Gas Saturated Solutions

CO-RESS co-precipitation during the rapid expansion of

supercritical solutions

SCF Supercritical fluids

Table of Contents

7

1. Introduction and Objective of the work .....................................................................14

2. Theory ........................................................................................................................16

2.1 Silica aerogels...................................................................................................16

2.1.1 Synthesis of silica aerogels and their properties...................................17

2.1.2 General applications of silica aerogels .................................................23

2.1.3 Impregnation of bioactive, inorganic, and organic substances in aerogels 23

2.2 Methods of solute precipitation / crystallization from supercritical CO2 .........25

2.2.1 Supercritical fluids as solvent...............................................................25

2.2.2 High pressure binary mixture (CO2 + Solute) phase diagrams ............27

2.2.3 Different methods of SCF particle formation technologies..................30

2.3 Physical state (crystalline / amorphous form) of drugs in a carrier..................33

2.3.1 General stabilization methods and problems of amorphization ...........33

2.3.2 Characterization of amorphous state: relevant techniques ...................34

2.4 High pressure adsorption isotherms on adsorbents at supercritical conditions 35

2.4.1 Adsorption measurements using Magnetic Suspension Balance (MSB)35

2.4.2 Data analysis of MSB adsorption measurements .................................35

2.4.3 Analytical adsorption isotherms ...........................................................37

3. Materials and Methods ...............................................................................................41

3.1 Materials 41

3.1.1 Materials used for silica aerogel synthesis ...........................................41

3.1.2 Materials used for adsorption & crystallization in aerogels .................41

3.1.3 MCM 41, Zeolite NAY, Trispor glass..................................................42

3.2 Preparation methods of silica aerogels .............................................................42

3.2.1 Sol - gel process and drying methods ...................................................42

3.2.2 Methods used for hydrophobization of aerogels ..................................43

3.3 Choice of crystallization temperature...............................................................44

3.4 Experimental techniques...................................................................................44

Table of Contents

8

3.4.1 Adsorption measurements using Magnetic Suspension Balance .........45

3.4.2 Adsorption experiments using an autoclave .........................................46

3.4.3 Crystallization experiments using an autoclave ...................................47

3.4.4 Drug release experiments .....................................................................48

3.5 Characterization techniques used .....................................................................49

3.5.1 Measuring of the bulk density of aerogels............................................49

3.5.2 Nitrogen Adsorption and Desorption; BET analysis ............................49

3.5.3 Elementary Analysis.............................................................................50

3.5.4 UV - Vis Spectroscopy .........................................................................50

3.5.5 Gas Chromatography (GC)...................................................................51

3.5.6 IR spectroscopy ....................................................................................51

3.5.7 Differential Scanning Calorimeter........................................................51

3.5.8 X - Ray Diffraction...............................................................................51

3.5.9 TGA / TGA - MS analysis....................................................................52

4. Results and Discussions .............................................................................................53

4.1 Properties of aerogels synthesized and other carriers used ..............................53

4.2 Adsorption and crystallization of polar solutes in silica aerogels ....................58

4.2.1 Adsorption and crystallization of benzoic acid in silica aerogels ........58

4.2.1.1 Stability of aerogels under pressure .......................................58

4.2.1.2 CO2 adsorption on aerogels ....................................................59

4.2.1.3 Excess binary adsorption of CO2 + benzoic acid ...................62

4.2.1.4 Static adsorption of benzoic acid in silica aerogels................64

4.2.1.5 Crystallization of benzoic acid in silica aerogels by CO-RESS65

4.2.1.6 Effect of the aerogel properties on the crystallization process67

4.2.1.7 Crystallinity of benzoic acid in aerogels ................................70

4.2.1.8 Crystallization of benzoic acid in other porous carriers.........73

4.2.1.9 IR analysis of loaded benzoic acid .........................................74

Table of Contents

9

4.2.2 Adsorption of 1-menthol in silica aerogels...........................................76

4.2.2.1 Menthol adsorption in silica aerogels.....................................76

4.2.2.2 TGA of menthol - loaded, hydrophilic aerogels.....................82

4.2.2.3 TGA of menthol - loaded, hydrophobic aerogels ...................85

4.2.2.4 IR analysis of loaded menthol ................................................87

4.2.2.5 Long - term stability of menthol at room temperature ...........88

4.3 Adsorption and crystallization of moderately polar solutes in silica aerogels .91

4.3.1 Adsorption and crystallization of naphthalene in silica aerogels .........91

4.3.1.1 Excess binary adsorption of CO2 + naphthalene in aerogels..91

4.3.1.2 Static adsorption of naphthalene in aerogels ..........................92

4.3.1.3 Crystallization of naphthalene in silica aerogels by CO-RESS94

4.3.1.4 Crystallinity of naphthalene in aerogels .................................99

4.3.1.5 IR analysis of loaded naphthalene........................................101

4.3.2 Adsorption of 2-Methoxy pyrazine in silica aerogels ........................104

4.3.2.1 Methoxy pyrazine adsorption in aerogels.............................104

4.3.2.2 TGA analysis of methoxy pyrazine loaded aerogels............106

4.3.2.3 Long - term stability of methoxy pyrazine at room temperature108

4.4 Adsorption and crystallization of nonpolar solutes in silica aerogels ............110

4.4.1 Adsorption and crystallization of octacosane in silica aerogels .........110

4.4.1.1 IR analysis of loaded octacosane..........................................113

4.4.2 Adsorption of dodecane in silica aerogels ..........................................115

4.5 Summarized table of loadings, physical form of loaded solutes ....................117

4.6 Extension of the method to other porous carriers: comparison of drug release profiles 119

4.6.1 Synthesis of the MCM - 41 materials .................................................119

4.6.2 Characterization of MCM41...............................................................120

4.6.3 Loading of MCM41s with Ibuprofen .................................................121

4.6.4 Release of ibuprofen from MCM41 in the phosphate buffer solution122

Table of Contents

10

5. Conclusions ..............................................................................................................125

6. Outlook.....................................................................................................................127

7. Appendix ..................................................................................................................128

7.1 GC column data ..............................................................................................128

7.2 Stability of aerogels at CO-RESS process......................................................128

7.3 Multiple additive loading................................................................................128

7.4 Benzoic acid results ........................................................................................129

7.5 MSB adsorption..............................................................................................134

7.6 Menthol results ...............................................................................................136

7.7 Naphthalene results.........................................................................................137

7.8 Error Propagation ...........................................................................................139

8. References ................................................................................................................142

Abstract

11

Abstract

In this work, adsorption and crystallization of various organic substances (1-menthol, 2-Methoxy

pyrazine, Naphthalene, Benzoic acid, Octacosane, Dodecane, Ibuprofen) in silica aerogels are

studied. Supercritical CO2 is used as an effective solvent to deliver these compounds into the

aerogel pores. The effect of density, physical properties (surface area, pore volume, pore size

distribution), surface functional groups (-OH, -OR) on adsorption, crystallization, and physical

state (amorphous/ crystalline) of loaded solutes are investigated. It is shown that the adsorptive

properties of silica aerogels play a significant role on the loading and physical state of the loaded

solutes during crystallization. To understand the influence of the adsorption process on

crystallization, binary adsorption isotherms of the above solutes and CO2 at different

temperatures and pressures are measured using a magnetic suspension balance. The results are

further confirmed by a static method. The results of the adsorption experiments allow to

distinguish which amount of the solute is adsorbed on the aerogel surface and which is

precipitated in the pores of aerogels during crystallization process by Rapid Expansion of

Supercritical Solutions (CO-RESS). It was found that the adsorbed layer of solute on the surface

of aerogels influenced crystallization, i.e., the adsorbed solute acts as a kind of active surface

during crystallization. Thus, in the case of polar solutes, hydrophilic aerogels are loaded with

higher amount of solutes compared to hydrophobic aerogels during CO-RESS process due to

high amount of adsorbed solute in hydrophilic aerogels. Whereas, in the case of non polar

solutes, there is nearly no difference in the loading during CO-RESS process as there is no

difference in the amount of adsorbed solute in both aerogels. The loaded solute particles in both

aerogels are in the range of 20 nm to 2 mm depending on the process conditions. To further

confirm the influence of the adsorbed solute on precipitation, solutes are loaded in commercially

available porous carriers (MCM41, Trisopor glass, Zeolite). It is also found that the adsorbed

solute influenced the overall crystallization process. It is shown that the physical state of solutes

can be controlled based on solute - surface interactions. Strong interactions (e.g. polar solute /

polar surface) favor the precipitation of amorphous particles, whereas, weak interactions (non

polar solute / polar surface) favor crystal formation. Thus, it is possible to get stable amorphous

or crystalline forms of the solute by tailoring the surface properties of the aerogel matrix. The

potential of this process as ‘adsorptive crystallization’ will be discussed.

Zussamenfassung

12

Zussamenfassung

Deutscher Titel: „Adsorptiv-Kristallisation organischer Substanzen in Silika-Aerogelen aus

überkritischen Lösungen“

Die vorliegende Arbeit behandelt Adsorption und Kristallisation verschiedener organischer

Verbindungen (1-Menthol, 2-Methoxypyrazin, Naphthalin, Benzoesäure, Octacosan, Dodecan,

Ibuprofen) in Silika-Aerogelen. Überkritisches CO2 wird hierbei als Lösungsmittel verwendet,

um die organischen Verbindungen in die Poren des Aerogels zu transportieren. Der Einfluss

verschiedener physikalischer und molekularer Parameter wie Dichte, Moleküloberfläche,

Porenvolumen, Porengröße und funktioneller Gruppen (-OH, -OR) auf Adsorption,

Kristallisation und den strukturellen Zustand (amorph/ kristallin) beladener organische

Substanzen wird untersucht. Es wird gezeigt, dass die Adsorptionseigenschaften der Silika -

Aerogele während des Kristallisationsprozesses starken Einfluss auf die Beladung und

strukturelle Ausprägung der eingebrachten organischen Substanzen nehmen. Um den Einfluss

von Adsorptionsprozessen auf das Kristallisationsverhalten zu verstehen, wurden mittels einer

Magnetschwebewaage binäre Adsorptionsisothermen der oben genannten organischen

Verbindungen und CO2 bei verschiedenen Temperaturen und Drücken aufgenommen. Die

Ergebnisse wurden anhand einer statischen Methode bestätigt. Die Ergebnisse der

Adsorptionsexperimente ermöglichen es, zwischen der Menge an oberflächenadsorbierter

Substanz und der in den Aerogelporen durch Kristallisation mittels „Rapid Expansion of

Supercritical Solutions“ (CO-RESS) entstanden an Substanzmengen zu unterscheiden. Es zeigte

sich, dass die auf der Aerogeloberfläche adsorbierte Substanzschicht Einfluss auf die

Kristallisation nimmt. Adsorbierte Substanz fungiert während der Kristallisation als eine Art

„aktive Oberfläche“. So wird bei Verwendung von polaren Substanzen im CO-RESS Verfahren

eine höhere Beladung auf hydrophilen Aerogelen erreicht als bei vergleichbaren hydrophoben

Aerogelen, was auf eine erhöhte Menge an adsorbierter organischer Substanz zurückzuführen ist.

Verwendet man hingegen unpolare Substanzen, so zeigt sich zwischen hydrophilen und

hydrophoben Aerogelen nahezu kein Unterschied bei der Beladung. Um den Einfluss der

adsorbierten Moleküle auf die Struktur ausgebildeter fester Phasen der organischen

Verbindungen weiter zu untermauern, werden handelsübliche poröse Träger (MCM41, Trisopor

Zussamenfassung

13

glass, Zeolite) mit organischen Verbindungen beladen. Auch hierbei wurde festgestellt, dass

adorbierte Substanz den Kristallisationsprozess beeinflusst. Es ergibt sich also die Möglichkeit,

die physikalische Stoffstruktur mittels der spezifischen Wechselwirkungen zwischen

Trägeroberfläche und Adsorbat zu kontrollieren. Starke Wechselwirkungen (z.B. polare Substanz

↔ polare Oberfläche) begünstigen die Bildung amorpher Partikel, wohingegen schwache

Wechselwirkungen (unpolare Substanz ↔ polare Oberfläche) vermehrt zur Entstehung von

Kristallstrukturen führen. Aus den genannten Ergebnissen wird die Möglichkeit ersichtlich,

stabile amorphe oder kristalline Stoffstrukturen mit Hilfe von Oberflächenmodifikationen der

Aerogelmatrix zu erzeugen. Das Potential dieses Verfahrens wird unter dem Begriff ‚Adsorptiv-

Kristallisation’ diskutiert.

Introduction and Objective of the work

14

1. Introduction and Objective of the work

Silica aerogel is an amorphous transparent porous substance consisting mainly of silicon oxide. It

has a highly cross - linked network with a pore size ranging from 20 to 100 nm which results in a

high surface area (400 - 1500 m2 / g). The density of silica aerogels varies from 0.003 to 0.25 g /

cm3. Their surface properties can be tailored by the amount and the nature of the functional

groups (-OH, - OR). Their versatile properties have attracted a lot of applications, especially as

drug delivery systems, since silica aerogels are biocompatible. Many organic, inorganic materials

and pharmaceutical compounds were adsorbed and doped in silica aerogels. The drugs adsorbed

on aerogels exhibit tailorable release properties and improved bioavailability. However, the

loading capacity of aerogels with several drugs by adsorption is rather small, which is a serious

disadvantage for their application as a drug delivery system (the needed amount of the carrier is

too large). To overcome this problem, crystallization of drugs in aerogels as an alternative to

adsorption is proposed in this work. Besides the higher loading, particles formed inside the pores

of aerogels would be less sensitive to oxidation and less reactive compared to the pure micro - or

nanoparticles of the same compound. Furthermore, the main problem of the handling of

nanoparticles, their agglomeration, can be avoided because the particles are separated from each

other by the walls of the pores. Precipitation of solutes inside the pores of silica aerogels is

controlled not only by process parameters, such as pressure, temperature, bulk concentration of

the target compound, etc., but, at a more fundamental level, by the physico - chemical properties

of the carrier - aerogels. Thus the fundamental understanding of the effect of the adsorptive

properties of the carrier (silica aerogels) on the crystallization or precipitation of solute in its

pores is needed. Based on this information, a new process “adsorptive crystallization” in aerogels

is introduced in this work. This process is discussed as a method / tool to adjust the loading and

physical state of solutes / drugs, for the future potential applications in pharmaceutical, food,

storage, and other allied industries. Especially, in the case of pharmaceutical industry the

bioavailability of the drug is an important factor, which is influenced by state of the drug, i.e.,

amorphous form of drugs have higher bioavailability compared to their corresponding crystalline

form of the drugs. The instability of the amorphized pharmaceuticals is a major factor precluding

their more wide spread use in solid dosage system. To overcome this problem of stabilization, in

Introduction and Objective of the work

15

this work, precipitation of drugs / solutes in the pores of aerogels is proposed as a novel way to

stabilize and control the physical state of solute.

For this purpose, precipitation of various organic substances inside the pores of silica aerogels

having different physical and surface properties should be investigated. Supercritical CO2 is

chosen as a solvent since high super - saturation rates are needed to initiate the precipitation,

which can be achieved by simply reducing the pressure. The aim is to understand the influence of

the adsorptive properties of the carrier (aerogel) and surface - solute interactions on the loading

and physical form (crystalline or amorphous form) of the solutes. Some commercially well

known porous carriers (Trisopor glass, MCM41, Zeolite) are also used for the comparison. A

wide variety of solutes (1-Menthol, 2-Methoxy pyrazine, Naphthalene, Benzoic acid, Octacosane,

Dodecane, Ibuprofen) ranging from polar to non - polar are selected for this purpose.

First, high pressure adsorption isotherms of solutes from CO2 on aerogels should be measured at

different pressures and temperatures. Two different techniques are available for this purpose:

static adsorption measurements and online (in-situ) measurements by Magnetic Suspension

Balance (MSB).

Then, crystallization of solutes in pores of aerogels will be performed from solvent CO2 at same

conditions as the online adsorption measurements by Rapid Expansion of Supercritical Solution

(CO-RESS). A corresponding apparatus is built and optimized in this work. For performing

crystallization phase diagrams of solute - CO2 system should be used to find the right operating

region to avoid destruction of aerogel pores. The influence of the adsorbed solute on the amount

of solute crystallization and physical state of solute in aerogels are further investigated by

comparing the adsorption data. The long term stabilization of crystalline or amorphous form of

solutes in the pores of aerogels is also investigated.

Theory

16

2. Theory

2.1 Silica aerogels

Historical and industrial review of aerogels for the past 80 years

Silica aerogels are highly porous, transparent, low density foams filled with air. They are made of

primary particles of silicon oxide with diameter of 1 - 3 nm. Steven Kistler from College of

Pacific in Stockton, California, made the first wet gels of solid network [1]. After few

unsuccessful attempts to dry the wet gels at atmospheric conditions, he removed the liquid from

the wet gels by supercritical drying without damaging the solid network and proved the existence

of continuous solid network in gels. Dating back to 1931, after the invention of aerogels by

Kistler, not much progress was done until 1962. Kistler´s invention of aerogels was industrialized

by Monsanto company in 1950, but within a short time the company stopped the production due

to high cost of production which limited the wide spread applications. Renewed interest in

aerogels started after 1962 as the French government produced silica aerogels to store oxygen

and rocket fuel in their pores [2, 3, 4]. There was not much progress until 20 years in the research

area of aerogels, in 1980, potential application of aerogels as detector for Cherenkov radiation

was realized, they were produced in huge quantities in Germany by DESY (Deutsches Elektronen

Synchrotron) [5], CERN, Switzerland, University of Lund, Sweden [6]. The Swedish Company

Airglass has commercialized the production of silica aerogels in this year. BASF also

commercialized the production of silica aerogel by the name BASOGEL. In 1984, the

Microstructured Materials Group, Lawrence Berkeley National Laboratory, USA, have

contributed to the increased research efforts in the synthesis, new drying methods, application of

silica aerogels [7]. The research performed on aerogels has found applications in space programs

like NASA and in many other military programs. Many research groups have reviewed synthesis

of aerogels with many materials apart from silica, their characterization methods, gelation

process and functionalization [8, 9, 10, 11, 12, 13]. A review by Dorcheh et al. [14] in 2008

summarized the latest production methods and application of aerogels in many fields. In recent

years, many companies have commercialized aerogels production on a large scale (Aspen

Theory

17

Aerogels, Cabot Nanogels, Dunlop Aerogels, and MarceTech) due to an increased market for

aerogel applications.

2.1.1 Synthesis of silica aerogels and their properties

Figure 1 shows the three steps involved in producing silica aerogels: (1) preparation of a sol, (2)

gelation and ageing of the gel, (3) drying of the gel to obtain an air filled gel (Aerogel).

Figure 1. Production steps of silica aerogels.

Preparation of gel

A gel is a solid matrix filled with a solution (solvent, catalyst, precursor), which is formed during

the condensation of the colloidal particles (1 - 3 nm size) of the precursors as shown in step 1 (see

Figure 1). The wet gel consists of a three - dimensional continuous solid network. Several general

modifications of silica gel processes are described in literature.

Sodium silicate was the first precursor used in early 1940`s to produce silica aerogels, the gels

produced using these precursors required laborious steps for manufacturing aerogels. Soon, the

Theory

18

sodium precursors were replaced by silicon oxide precursors. Presently, tetraalkoxysilanes

(Si(OR)4) (R =CnH2n + 1, n = 1,2.…) are used to produce silica aerogels (also in this work). The

synthetic routes from a silicon source have produced alcogels (gels filled with alcohol), as a

result the steps of washing and drying became much simpler and efficient. The chemical

reactions involved in forming silica gel can be described by two steps:

1. Hydrolysis (formation of primary colloidal particles; step1 in Figure 1)

ROHOHSiOHORSicatalyst +−≡ →←+−≡ 2

2. Condensation (alcohol and water condensation, formation of three - dimensional solid

network; step 2 in Figure 1)

ROHSiOSiSiHOORSicatalyst

+≡−−≡ →←≡−+−≡

OHSiOSiSiHOOHSicatalyst

2+≡−−≡ →←≡−+−≡

The two standard methods used for gel synthesis from silicon source precursor are: A) one step

method, B) two step method.

A) One step method: All the reactants along with the catalyst are mixed in one step. Thus, the

hydrolysis and condensation of the silicon alcoxide takes place simultaneously forming a solid

network. Brinker and Scherer [15] have reported the process conditions: temperatures,

concentrations, and pH’s to control the gel physical properties. The aerogels obtained by this

method generally exhibit limited transparency, cracking of aerogels, formation of low density

aerogels, and low mechanical stability.

B) Two step method: The two step method of synthesis of aerogels overcomes the problems of

the one step method. Brinker et al. [16] and Pajnok [17] have developed this method. Here the

hydrolysis and condensation reactions are performed separately in a controlled manner by

adjusting the amount of water needed during each step of the reaction. First, hydrolysis is carried

out using an acidic catalyst for 30 minutes with a low amount of water, and then the condensation

Theory

19

reaction is performed by adding the desired amount of water and a basic catalyst. Even though

the process was optimized, a long gelation time is required due to presence of alcohol which

shifts the equilibrium to alkoxy groups. Tillotson and Hrubresh [18] have proposed a modified

two step method by replacing the alcohol in the gels by aprotic solvents which overcomes this

problem. The aerogel production method of Tillotson and Hrubresh is used as a standard method

of today’s silica aerogel synthesis with slighter modifications. Smirnova et al. [19] reduced the

gelation time for low density aerogels drastically by adding CO2 during the gelation process.

Ageing of silica gels

The gels formed are aged in the solution for few hours to few days depending on the gel targeted

density to attain stronger solid network of the gel. The increased strength of aged gels would

prevent the shrinkage during drying [8, 9, 15].

Drying of the gels

The gels aged need to be dried to remove the solution from the pores of gels. Two possibilities to

remove the pore fluid are: ambient drying and supercritical drying. Ambient drying of the wet

gels leads to xerogels, since the capillary pressure exerted by evaporating fluid destroys the pore

walls. Thus formed gels have an almost negligible pore volume (see step 3 in Figure 1).

Therefore, the supercritical fluid drying method is used to overcome this problem. Supercritical

fluids are the fluids which have densities like liquids and transport properties like gases, and have

nearly no surface tension above a certain critical temperature and pressure (see Figure 2). The

drying generally is performed by transforming liquid in the pores to supercritical fluids or by

extracting the pore fluid by using supercritical CO2 [9]. There are also many other ways to

perform drying, a very comprehensive review of these methods are described by Smirnova et al.

[20]. The process of drying using CO2 for extraction of the solvent from the gels is described

here. Supercritical CO2 is preferred, since CO2 is non toxic, inflammable and low critical

temperature and pressure to reach supercritical state (73.8 bar, 31°C).

The autoclave is heated to the desired temperature above critical temperature, and then gels are

placed inside the autoclave and pressurized with CO2 to a supercritical state as seen from Figure

Theory

20

2. The pressure is fixed to a value above critical pressure, CO2 is pumped continuously into the

autoclave and at the same time a similar amount of CO2 is vented out using a needle valve. The

supercritical CO2 dissolves the fluid from the pores of aerogels which is being extracted

continuously. After complete extraction of pore fluid, CO2 is vented out slowly until ambient

pressure is reached, to avoid cooling by Joule - Thompson effect which will lead to aerogel pores

destruction by the condensed CO2.

0

20

40

60

80

100

-90 -70 -50 -30 -10 10 30 50

Temperature (°C)

Pre

ssu

re (

bar)

Solid Liquid

Vapor

Supercritical

region

Triple point

(Tc,Pc)

Figure 2. A typical supercritical CO2 drying process of silica aerogels.

Hydrophobicity of silica aerogels

The aerogels dried using supercritical CO2 are hydrophilic in nature due to the presence of

unconverted -OH groups. The major drawback of these aerogels in technical applications is their

instability under humid atmosphere. In this section the possibilities to hydrophobize the

hydrophilic aerogels by various methods are discussed.

− Aerogels dried by converting the pore fluid (organic solvent like methanol or ethanol) to

supercritical state directly leads to hydrophobic aerogels (Si - (OR)).

Theory

21

− Modification of surface functional groups can be performed via synthesis route, i.e.,

precursor like chlorotrimethylsilanes are used as reactant, which results in hydrophobic

surface of the aerogels [21]. Schwertfeger et al. produced hydrophobic aerogels using a

mixture of tetraalkoyxsilane and trimethoxysilanes [22].

− Rao et al. [23, 24, 25] produced hydrophobic aerogels by modification of surface –OH

groups by –OR groups by placing the aged gels in the solvent present with the modifiers

(TMES, TMCS, HMDS, MTMS) for 48 hours before drying.

− Lee et al. [26] have modified the surface of hydrophilic aerogels using gas phase reaction

of methanol with aerogel surface at 180°C. This method provides an opportunity to

produce aerogels of nearly similar physical properties with different surface functional

groups.

Characterization techniques

A comprehensive overview about the characterization methods of aerogels were reported by

Scherer [27, 28]. The aerogels are normally characterized using N2 adsorption / desorption to

obtain the data like surface area, pore volume, and average pore size distribution. Usually, helium

pyknometry and mercury porosimetry is used to determine the skeleton and pore volume.

Electron microscopy (SEM, TEM, STEM) are used to determine the particle size of colloidal

silica (walls) and morphology of the aerogels. Other technique like SAXS, SANS, NMR, AFM

describe the molecular and fractal dimensions of the aerogels [14]. CHN elementary analysis is

used to characterize the degree of hydrophobicity.

Properties of silica aerogels

Table 1 provides a brief overview of the important properties of the silica aerogels which makes

the aerogels interesting for many applications. These properties of silica aerogels are tuneable by

varying the synthesis routes and process conditions.

Theory

22

Table 1. Selected properties of silica aerogels [20].

Property Value Remark

Apparent Density 0.003 - 0.35

g/cm3

Most common density is 0.1g/cm3

Internal Surface Area 600 - 1000 m2/g

As determined by nitrogen adsorption /

desorption

% Solids 0.13 - 15% Typically 5% (95% free space)

Mean Pore Diameter 20 nm As determined by nitrogen adsorption /

desorption (varies with density)

Primary Particle

Diameter 2 - 5 nm Determined by electron microscopy

Refraction Index 1.0 - 1.05 Very low for a solid material

Thermal Tolerance To 500 °C

Shrinkage begins slowly at 500 °C,

increases with increasing temperature.

Melting point is >1200 °C

Coefficient of Thermal

Expansion 2.0 - 4.0x10

– 6 /K Determined using ultrasonic methods

Poisson's Ratio 0.2 Independent of density, similar to dense

silica.

Young's Modulus 106 - 10

7 N/m

2

Very small (<104x) compared to dense

silica

Tensile Strength 16 kPa For density = 0.1 g/cm3.

Fracture Toughness 0.8 kPa·m1 / 2

For density = 0.1 g/cm

3. Determined by 3

- point bending

Dielectric Constant 1.1 For density = 0.1 g/cm

3. Very low for a

solid material

Sound Velocity Through

the Medium 100 m/sec

For density = 0.07 g/cm3. One of the

lowest velocities for a solid material

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23

2.1.2 General applications of silica aerogels

Figure 3 illustrates various applications of aerogels [8, 9, 17, 15]. Due to their versatile

properties, aerogels are used in many applications in chemical, electronic, optical, insulation,

catalyst, and pharmaceutical industries.

Figure 3. Application of silica aerogels [29].

Aerogels applications in food and pharmaceutical areas are discussed in more details since they

are in close connection to the present work.

2.1.3 Impregnation of bioactive, inorganic, and organic substances in aerogels

Impregnation or doping of different substances (bioactive substances, organic and inorganic) in

silica aerogels has attracted lot of attention during past few years. The doped substances exhibited

better stability, superior properties, high solubility and dissolutions rates compared to pure

substances. Relevant literature and applications of doped compound are described here.

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24

Doping of bioactive substances in aerogels: Buisson et al. [30] encapsulated enzyme lipase

(pseudomonas cepacia) in silica and aluminosilicate directly during the synthesis of gels (see

Figure 3).

Figure 4. Principle of encapsulation of Enzyme in aerogels and Xerogels (taken from Buisson et

al. [30]).

The encapsulation of the enzyme lipase in aerogels leads to stabilization of enzyme. The

biocatalytic activity of enzyme in aerogels is higher compared to xerogels for the reaction of

esterfication of lauric acid from 1 - octanol. El Rassy et al. [31] have performed extensive

research on activity of encapsulated enzymes in aerogels for biocatalysis. Power et al. [32] doped

aerogels with green fluorescent protein (GFP) and baceteria to detect bacteriophages

(biosensors). Aerogels doped with the insecticides were used to protect the grains in the food

industry [33].

Doping of inorganic substances in aerogels: Yoda et al. doped TiO2 in aerogels [34] to remove

VOC`s from air, Yao et al. doped PbS nanocrystals in aerogels [35], Lorenz et al. doped zinc

Theory

25

oxide nanocrystals in aerogels [36], Goodwin et al. doped gallium nitride in aerogels [37], Yoda

et al. doped titanium oxide in aerogels [38], Merzbacher et al. doped ruthenium oxide in aerogels

[39], and Morely et al. doped silver nano particles in aerogels [40].

Doping of drugs / organic substances in aerogels: Schwertfeger et al. [41] described the use of

inorganic aerogels (SiO2, Al2O3, ZrO2) as a drug carrier for many pharmaceutical active

compounds. Goud et al. described the use of aerogels in the inhalents due to their low bulk

density, as the aerogels float in the respiratory system [42]. Smirnova et al. reported the use of

low density silica aerogels a drug delivery system. Various pharmaceutically active compounds

were adsorbed from supercritical solutions on the surface of silica aerogels [20, 19, 29]. The

loading of drugs and the release rates are tailored by controlling the physiochemical properties of

the silica aerogels. This extensive research performed on silica aerogels as drug delivery carrier

forms the basis for the present research work.

2.2 Methods of solute precipitation / crystallization from supercritical CO2

Supercritical CO2 is used as solvent in the present work to crystallize organic substances / drugs

in silica aerogels. Therefore, in this section some relevant aspects of supercritical CO2 and phase

behavior of binary mixture solute - SCF are shortly discussed along with SCF methods for

particle formation.

2.2.1 Supercritical fluids as solvent

Supercritical fluids (SCF) exhibit the benign properties of both gases and liquids after a certain

critical temperature and pressure (see Figure 5). Supercritical fluids properties combine liquid

like density and gas - like properties of diffusivities and viscosities [43, 44, 45]. Small change in

temperature and pressure near and beyond the critical point can change the densities significantly.

Since the density is a measure of fluid solvent strength, it is possible to tune the solubility of

compounds. Thus precipitation can be initiated by pressure change. Apart from its unique

properties, supercritical fluids posses certain physicochemical properties to adjust the solubilities.

Table 2 lists the critical data of various solvents used for aerogel synthesis.

Theory

26

Temperature (°C)

Pre

ssu

re (

bar)

Solid Liquid

Vapor

Supercritical

region

Triple point

Tc

Pc

Figure 5. Typical P - T Phase diagram of a pure component.

Table 2. Critical temperature and pressures of some commonly used SCFs.

Solvents Critical Temperature

(°C)

Critical Pressure

(bar)

Carbon

dioxide

31.1 73.8

Ethane 32.2 48.8

Propane 96.7 42.5

Water 374.2 220.5

Methanol 239.4 80.9

Ethanol 243.0 63.0

Acetonitrile 247.7 47.7

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27

The most widely used supercritical fluid is carbon dioxide (CO2) due to it mild critical

temperature and pressure. Furthermore, CO2 is cheap, and its traces left after the process are

acceptable (green process). Since last 75 years, SC-CO2 have been applied as solvents for

processing foods, nutraceuticals, and polymeric materials, as reaction media for polymerization

processes, as environmentally preferable solvents for solution coatings, powder formation,

impregnation, encapsulation, cleaning, crystal growth, anti - solvent precipitation, and as mixing /

blending aids for crystalline or viscous materials [46]. Supercritical CO2 has limited solubility of

high molecular weight substance, which can be improved by adding small amount of co-solvents

like methanol, ethanol, acetone, or dimethyl suphoxide. In the last 20 years, SC-CO2 is used as a

solvent to produce fine (micro to nano size) particles of pharmaceutical substances, organic

substances, and polymers. To generate particles by using SC-CO2, phase behavior of binary

mixture solute - SCF is needed to control the properties of particles.

2.2.2 High pressure binary mixture (CO2 + Solute) phase diagrams

Phase diagrams of binary mixtures CO2 + solute are critical to understand the regions where

small organic particles can be formed using supercritical fluids. Phase behavior differs

considerably depending on molecular size, structure, polarity, and intermolecular interactions.

Broadly, the mixtures can be divided into two types. A) Symmetric solid - SCF phase behavior,

B) Asymmetric solid - SCF phase behavior.

A) Symmetric solid mixture phase behavior:

Figure 6 shows a symmetric P - T phase diagram of a binary system solute - SCF [47, 48, 49].

Curve CD and MH are the pure component vapor pressure curves of the solvent and solid

component respectively. Curve EM is the pure solid component sublimation curve and MN is

pure solid (solute) component melting curve. Point D and H are the critical points of the two

components respectively. Critical mixture curve runs continuously through the critical points of

both components. Three phase continuous solid - liquid - vapor (SLV) line of binary mixture

(solute - SCF) begins at the normal melting point (TM2) of heavy compound, bends back towards

Theory

28

the lower temperature as the pressure is increased and finally ends at the temperature below the

critical temperature of lighter component (SCF). Generally, by increasing hydrostatic pressure the

melting point of pure solids increases. But, when the solid is compressed in presence of SCF, the

melting point of solid component seems to decrease as more SCF is dissolved in the solid

component. Thus, the melting point depression occurs due to the presence of SCF in the solid

component.

Figure 6. P - T diagram for a heavy solid–supercritical fluid system (on the basis of [49]).

B) Asymmetric solid mixture phase behavior:

Figure 7 shows the phase behavior of a typical asymmetric binary mixture [47, 48, 49, 50], which

is representative for the system solute – CO2. CP1 and CP2 are the critical points of solvent and

solute correspondingly. The curves between UCEP and CP2, LCEP and CP1 are the critical

curves of the mixtures. The interaction of a solid solute and SCF is lower in comparison to

symmetric binary mixture. The melting point depression of the solute in asymmetric binary

mixture is not as significant as in the case of symmetric binary mixture. The three phase line

(SLG) begins at normal melting point of the solute (TP2), decreases up to a certain pressure,

Theory

29

then, rises with increasing pressure to a point where it intersects the critical mixture curve at

UCEP (upper critical end point). Thus the decrease of melting point at low pressures is due to

solubility of SCF in the solute. At high pressures the melting point increase is due to negligible

solubility of SCF in the solute as a result the effect of hydrostatic pressure on solid substance is

observed. The region between LCEP (lower critical end point) and SLV line is the only region

where solid - supercritical fluid phase equilibrium exists at each pressure. In this region excellent

transport properties of the supercritical solution allow the solute to reach all pores of a porous

carrier. Below TLCEP and above TUCEP liquid - solid or fluid–liquid equilibrium exists depending

on the composition. The choice of temperature is of crucial importance for the crystallization in

the porous carrier like silica aerogels. Upon contact with liquids, the structure of aerogels

collapses due to the high capillary pressure in the pores. Thus, the experimental conditions should

be chosen so that no liquid phase exists in the autoclave during the entire process. For these

reasons, it is favorable to start the process at the conditions where the mixture of the solute and

CO2 is in supercritical state (T > TLCEP) and no liquid phase can occur (T < Tmin) (see Figure 7).

Figure 7. Sketch of P - T diagram of a typical asymmetric binary mixture (on the basis of [49,

51]).

Theory

30

2.2.3 Different methods of SCF particle formation technologies

The versatile properties of supercritical fluids provide a possibility to produce particles ranging

from microns to nanometers. Especially, controlling of drug particle size and its morphology has

a significant importance in pharmaceutical industry. Table 3 lists the general SCF technologies

and their principles developed for producing particles. Several review articles are published

summarizing the recent development and breakthrough [49, 52, 53, 54, 157, 55] in the particle

formation by various SCF methods [56, 57, 58].

Table 5 lists the comprehensive reviews reported for last 20 years in the literature on SCF

methods of particle formation, influence of physical property of drugs, nucleation, growth rate,

characteristic polymers, various applications, operational parameters, pre - expansion

temperatures and pressures, nozzle geometry.

The process of ‘Rapid Expansion of Supercritical Solutions’ (RESS) and CO-RESS will be

discussed since they are used in the present study. RESS is the first supercritical process

developed in 1980s. This process requires solubility of chosen solute in supercritical fluids. The

solute is first dissolved in the supercritical fluid and this solution is rapidly depressurized through

a nozzle leading to solute precipitation (see Figure 8). Along with the pressure decrease, the

solution also experiences a temperature decrease during the process due to Joule - Thompson

effect. If the operating temperatures are chosen based on solute - SCF mixture phase behavior,

multiple phase formations during the process can be avoided. CO-RESS differs from RESS by

the fact that a porous carrier is placed in the autoclave along with the solute. The carrier should

be stable in the supercritical solvent (no solubility, no destruction of carrier surface / pores with

SCF). The dissolved solute from SCF is precipitated in the pores of the carrier by rapid expansion

of supercritical solution, i.e., CO-RESS (see a Figure 8). Türk et al. [59] reported the deposition

of pharmaceuticals in carrier cyclodextrines, termed this process as “controlled particle

deposition (CPD)”. In this study CO-RESS process is firstly used for aerogel impregnation. The

physical state (crystalline of amorphous form) of the particles generated by RESS or CO-RESS

processes depends on the nature of solute, crystal formation, thermodynamic stability of the

phase, and interaction between surface and solute in the case of CO-RESS. In general, most of

the pharmaceuticals / solutes are preferred in the amorphous state due to their enhanced

bioavailability in comparison to their crystalline state.

Theory

31

Figure 8. Schematic representation of RESS and CO-RESS processes.

Table 3. General methods of particle formation technologies using supercritical fluids

Theory

32

Table 5. Review articles published on SCF particle formation technologies.

Review subject Year Corresponding author

RESS (general review) 1991 Debenedetti [60]

RESS, GAS, SAS (pharmaceutical processing) 1997 Subramaniam [61]

GAS, SAS (general review) 1999 Reverchon [58]

RESS, SAS, SEDS, PGSS (phase behavior) 1999 York [62]

RESS, GAS, PGSS (general review) 2000 Marr [63]

RESS, SAS, SEDS (polymer processing) 2001 Cooper [64]

RESS, SAS, SEDS, PGSS (general review) 2001 Perrut [65]

RESS, GAS, SAS (drug delivery system) 2001 Kompella [66]

RESS, GAS, SAS, SEDS (pharmaceutical powders) 2001 Williams III [67]

RESS, SAS, SEDS, PGSS (pharmaceutical application) 2001 Tan [68]

RESS, GAS, SAS, PGSS (drug delivery, polymer) 2002 Foster [69]

RESS, SAS (nano materials) 2003 Wai [70]

RESS, SAS , SEDS, PGSS (polymers) 2005 Kiran [71]

RESS, CO-RESS (Aerogels, Pharmaceuticals) 2008 Arlt [55,157]

Table 4. General methods of particle formation technologies using supercritical fluids.

Process Role of supercritical

Fluid

Role of organic solvent Mode of phase separation

RESS Solvent Co - solvent Pressure / temperature - induced

GAS Antisolvent Solvent Solvent – induced

SAS Antisolvent Solvent Solvent – induced

SEDS Antisolvent/

dispersing agent

Solvent / non - solvent Solvent – induced

PGSS Solute Pressure /temperature / solvent –

induced

Theory

33

2.3 Physical state (crystalline / amorphous form) of drugs in a carrier

Recent years, amorphization of crystalline solids received a great importance in

pharmaceutical industry, because amorphous form of substance exhibit increased solubility

and bioavailability [72, 73]. Amorphous solids have higher Gibbs free energy and entropy

than the corresponding crystals [74] and exhibit better compressibility because of lower

bonding energy.

Standard methods to produce amorphous solids are: solvent method, hot melt technology,

milling, freeze and spray drying, drying of solvated crystals, extrusion, and loading in porous

carriers. All the above amorphization techniques follow generally two routes: (1) direct

amorphization of elementary substances, (2) amorphization of drugs using crystallization

inhibitors. The most common amorphization method is the rapid cooling of substance below

its melting point (Tm), which leads to so called supercooled liquid or rubbery state. In the

“hot melt” method [75] a carrier (polymer) and drug substances are melted together above

eutectic point and then cooled down. Important prerequisite is the miscibility of the drug and

the carrier in the molten form. In solvent method [76], a drug and a carrier are dissolved in a

mutual solvent and then solvent is evaporated under vacuum to produce a solid solution [77].

Nanoconfinement of the drug in porous carrier is used to control the morphology [91, 92, 93].

Review of Szabo et al. lists the sequence of choice of correct amorphization route for API

(active pharmaceutical ingredients) [78]. Review by Hancock et al. describes the methods,

uses, and significance of amorphous state of pharmaceutical systems [79].

2.3.1 General stabilization methods and problems of amorphization

Amorphous solids can crystallize or undergo structural relaxation with respect to their

corresponding crystals. Molecular mobility and relaxation behavior is an important criteria for

the stability of amorphized drug [80]. These properties depend on the magnitude and

temperature dependence of the apparent activation energy of molecular motions of the

compounds near and above glass transition temperature (Tg) in supercooled liquids [81, 82].

To date no single method exists that allows to predict the stability of amorphous products, as

stability is governed by Tg, fragility, configurational heat capacity (generally by the

thermodynamic driving force). Storage of amorphous drug samples at Kauzmann temperature

(TK) has previously been suggested [83, 84], however it does not guarantee sufficient

Theory

34

stability over the desired shelf time, recrystallization can occur even well below the glass

transition temperature (Tg) [85, 86, 87].

Some organic compounds have remarkable conformational flexibility which leads to reduced

degree of crystallization and favors amorphization [88]. Stabilization of such substances

during processing and storage can be done by using additives, and carrier - drug interactions,

i.e., selective hydrogen bonding between stabilizing excipients and drug molecules [89]. For

instance adsorption of water decreases the Tg, since it acts as a plasticizer, increases the

molecular mobility [90] and thus retains the amorphous form of drug.

Confinement in porous host systems with strongly interacting pore walls is shown to be a

powerful method to increase the lifetime of amorphous drugs based on changes in

thermodynamic and crystallization kinetics in nano - sized systems [91, 92, 93]. This indicates

that the confined drug has spatial inhomogenous mobility and density. If the critical diameter

of the nuclei for the crystalline form is larger than pore diameter than the nuclei cannot reach

the size necessary for exergonic crystal growth, thus the amorphous state would be

thermodynamically stable [94].

2.3.2 Characterization of amorphous state: relevant techniques

General characterization techniques used for the characterization of the amorphous solids are:

DSC [95, 96], XRD [97], configurational heat capacity [98], and scanning rate dependence of

Tg (estimation of the relaxation time). Some other special methods used for characterization

are: use of gas displacement pyknometry for quantifying the amorphous content of partially

crystalline pharmaceuticals systems described by Saleki - Gerhardt et al. [99]. The most

characteristic property of the amorphous state is its viscosity, the greater free volume and

molecular disorder of an amorphous material compared to its crystalline counterpart can be

seen with the change in viscosity [100, 101, 102]. Spectroscopic techniques; NMR, IR, and

electron spin resonance [103, 104, 105, 106] are used to measure glass transition

temperatures, amorphous content, and mean molecular relaxation times.

Theory

35

2.4 High pressure adsorption isotherms on adsorbents at supercritical

conditions

2.4.1 Adsorption measurements using Magnetic Suspension Balance (MSB)

In the year 1940, Holmes [107], Clark [108], and Beams [109] were the first to design and

develop the Magnetic Suspension Balances (MSB), a balance in which the material to be

weighed is freely suspended. They used MSB for the experiments where weighing must be

carried out in an evacuated or closed cell or under a transparent liquids. The limited

sensitivity and stability of MSB balances prevented its application for many years. Since, 50

years from the first design of MSB, many researchers have designed and developed various

kind of laboratory MSB’s and reported the experimental and modeled adsorption date of pure

gases, binary, ternary mixtures on many solids adsorbents. Recently, a very accurate and

stable magnetic suspension balance was developed by the company Rubotherm (Germany) to

measure the adsorption of gases under high pressures and temperatures and density of the

bulk phase (in-situ) simultaneously during the measurements [110, 111]. A variety of high

pressure adsorption isotherms were measured using MSB. High pressure adsorption and

modeling of CO2 on activated carbon is studied by many researchers; Keller et al. [112, 113,

130], Humayun et al. [113], Vaart et al. [114], Fitzgerlad, et al [115, 116], Chen, et al. [117],

and Dreisbach et al. [122, 110, 113]. Similarly high pressure adsorption of methane, N2, H2 is

studied on activated carbon [112, 118, 110, 113, 114]. Some of the literature on high pressure

adsorption of gases on silica gel and zeolites is also reported. Adsorption of N2 and CO2 on

zeolites and silica gel is reported by Zhou et al. [119], Gao [120], and Hocker et al. [121].

Binary mixture adsorption of CO / H2 is reported by Dreisbach et al. [122]; binary and ternary

mixture of CO2 / CH4 / N2 / Ar is reported by Keller et al. [112, 113, 130], Vaart et al. [114],

Dreisbach et al. [122, 110]. The main difficulty is the analysis of the raw data obtained from

MSB. This point is addressed in the following chapter.

2.4.2 Data analysis of MSB adsorption measurements

Handling of raw data obtained from MSB

Following values are measured by MSB: p: pressure, T: temperature: ∆m: difference between

the initial weight in vacuum at respective T and weight at conditions p and T; and ρb: bulk

Theory

36

density. The buoyancy acts on the adsorbent and basket (includes the permanent magnet and

the connection holdings the basket and permanent magnet). This effect needs to be corrected,

so the volume of basket, volume of adsorbent sample, volume of the adsorbed solute on the

adsorbent, and bulk density are required. The equations are as follows:

Absolute mass of the adsorbed substance on the adsorbent (aerogel):

Equations of the adsorbing systems:

[ ]adssb

b

absolute VVVTpTpmTpm +++∆= ),(),(),( ρ Equation 1

[ ]adssb

bVVVTptermcorrectionBuyouncay ++),(:ρ Equation 2

adsorbedabsoluteads TpmwhereV ρ*),(= Equation 3

Excess amount adsorbed

[ ]sb

b

excess VVTpTpmTpm ++∆= ),(),(),( ρ Equation 4

Where, m(p, T)absolute (g / g) is the absolute amount of substance (solute / solvent) adsorbed

per gram of the adsorbent, m(p, T)excess (g / g) is defined as excess adsorbed amount by Gibbs

definition. The volume of the adsorbed molecules is usually neglected. Vb (cm3) is the volume

of basket and VS (cm3) is the volume of sample. Both the volumes are measured using helium

as a non - adsorbing medium.

In-situ bulk density measurement of fluids in MSB cell

In one of the MSB measuring point, both basket and sinker are lifted. At this conditions (ρb,

T), the density of the fluid (pure or binary mixture) inside the measuring cell can be

determined by Equation 5. The mass and volume of sinker (titanium cylindrical piece) are

Theory

37

previously calibrated and it is assumed, that there is no adsorption of gases (solute or solvent)

on sinker.

kersin

21kersin ),(),(

V

TMTMM bb

bρρ

ρ−+

= Equation 5

Thus, it provides an opportunity to measure the bulk density of fluid (pure gases and

mixtures) in-situ.

Volume (Vb, VS) determination by helium measurements

To determine the volume of the basket (Vb) and adsorbent sample (Vs), helium is used. MSB

cell with empty basket is pressurized stepwise with helium with different pressure steps to

measure the reduced weight of the basket. Applying Equation 4 with the assumption that the

adsorption of the helium on the basket (or adsorbent) is negligible (mHe(p,T)excess= 0), the

reduced mass of basket is measured at different pressures of helium. The slope of the linear

plot between reduced mass and density of pure helium gives the total volume of basket (Vs).

Later, the adsorbent is placed in the empty basket and similar procedure is repeated to obtain

the adsorbent volume. The volume obtained in the case of porous adsorbent samples is the

skeleton volume of adsorbent. Thus, the obtained volumes are used to correct the buoyancy

effects of the measured data from MSB. Therefore, the direct measurable values are the

excess adsorbed amount and the bulk density of solvent. The absolute adsorption can be

derived from the measured data by assuming an analytical form of adsorption isotherms [123,

124, 125, 126]. The experiment data of excess adsorbed amount for various densities is used

to fit the parameters of analytical adsorption isotherms along with unknown Vads or ρads.

2.4.3 Analytical adsorption isotherms

Isotherms of supercritical CO2 and both CO2 and solute on aerogels are expected to be of

IUPAC type I. The most general analytical isotherms used for the fitting of such data are as

follows: Langmuir, Toth, and UNILAN isotherms [127, 128, 129].

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38

Langmuir isotherm

Langmuir isotherm with fractal exponent α, and density has been used instead of using

pressure because of practical advantages in parameter optimization [130].

α

α

ρ

ρα

)),(*(1

)),(*(* ´

´

Tpb

Tpbmm

b

b

analytical+

= ∞ Equation 6

m ∞= indicates the mol number of the adsorbate at saturation (density of adsorptive ρb → ∞),

´b is the reciprocal density of the adsorptive necessary to get half load of total loading, α is

characteristic exponent related to the radius r of the adsorbed molecules and fractal dimension

of the adsorbate .

By substituting Equation 6 in Equation 1 which will lead to parameter optimization function

of Langmuir isotherm as shown:

ads

b

b

b

excess VTpb

TpbmTpm *

)),(*(1

)),(*(*),( ´

´

ρρ

ρα

α

α

−+

= ∞ Equation 7

Equation 7 is optimized assuming the volume of the adsorbate to be constant. Alternatively,

one can introduce Vads = m(p,T)analytical / ρads in Equation 7 leads to an equation with adsorbed

density as an unknown parameter:

−

+= ∞

ads

b

b

b

excessTpb

TpbmTpm

ρ

ρ

ρ

ρα

α

α

1)),(*(1

)),(*(*),( ´

´

Equation 8

These equations can be used to fit the parameters Vads or ρads along with Langmuir isotherm

parameters by least square fitting procedure for the data of mexcess and bulk density obtained

from MSB measurements. In some cases modified Langmuir called ‘dual site Langmuir’

isotherms are used [130, 128].

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39

Toth isotherm

In 1984, Toth [131] has introduced an analytical form for Type I isotherms. This isotherm

takes into account of the energetical heterogeneity of the surface. Therefore, it is widely used

for the fitting adsorption data and the analytical expression is as follows:

+

= ∞αα

α

ρ

ρ

/1´

))),(1

)),((

Tpb

Tpmm

b

b

analytical Equation 9

By introducing Equation 9 in Equation 1 which will lead to parameter optimization function

for Toth isotherm with unknown parameter Vads or ρads:

ads

b

b

b

excess V

Tpb

TpmTpm *

))),(1

)),((),(

/1´

ρ

ρ

ρ

αα

α

−

+

= ∞ Equation 10

or

−

+

= ∞

ads

b

b

b

excess

Tpb

TpmTpm

ρ

ρ

ρ

ρ

αα

α

1))),(

1)),((

),(/1

´

Equation 11

Equation 10 and Equation 11 are used to find the unknown parameters for the excess

adsorption isotherm data.

UNILAN isotherm

UNILAN isotherm is an empirical relation which account for heterogeneity by assuming

patch wise topography on the surface with ideal patches. The local Langmuir isotherm applies

on each patch [132].

Theory

40

+

+=

−

∞

),(**1

),(**1

2 ´

´

TPeb

TpebLn

mm

b

b

analytical

ρ

ρ

α α

α

Equation 12

By introducing Equation 12 in Equation 1 which will lead to parameter optimization

function for UNILAN isotherm with unknown parameter Vads or ρads. The following are the

equations:

ads

b

b

b

excess VTPeb

TpebLn

mTpm *

),(**1

),(**1

2),(

´

´

ρρ

ρ

α α

α

−

+

+=

−

∞ Equation 13

or

−

+

+=

−

∞

ads

b

b

b

excess

TPeb

TpebLn

mTpm

ρ

ρ

ρ

ρ

α α

α

1),(**1

),(**1

2),(

´

´

Equation 14

Equation 13 and Equation 14 are used to find the unknown parameters for the excess

adsorption isotherm data.

In this work all the excess adsorption isotherms of gases are modeled using the above

isotherms. Commercially available program ‘TableCurve’ is used in this work to fit and

optimize the parameters for the excess adsorption isotherm data.

Materials and Methods

41

3. Materials and Methods

3.1 Materials

3.1.1 Materials used for silica aerogel synthesis

The chemicals used for aerogel synthesis are: Tetramethylorthosilicate (TMOS) (Fluka, ≥

98.0%), Methanol (MEOH) (Merck, ≥ 99.9%), Tetramethylethoxysilane (TMES) (Fluka, ≥

99.0%), Acetonotrile (Merck, ≥ 99.8%), Water (H2O) (distill water), Hydrochloric acid (HCL)

(0.00001 wt %), Ammonium hydroxide (NH4OH) (0.01 wt%). CO2 (Technical grade purity >

99.8%) is obtained from Linde and used for drying and loading experiments. The chemical

are used as received.

3.1.2 Materials used for adsorption & crystallization in aerogels

Table 6 summarizes the properties of the solutes used in this work. Benzoic acid (Fluka,),

Naphthalene (Merck), 1-Menthol (Merck), 2-Methoxy pyrazine (Merck), Octacosane

(Merck), Ibuprofen (Caelo) and Dodecane (Fluka) are used as received.

Table 6. Selected properties of solutes loaded in aerogels.

Name Structure Mw

(g / mol)

Tmelt

(°C)

Tboil

(°C)

1Log

Pow

Purity

(≥

Wt%)

l - menthol

HO

H3C

H3C

CH3

156.3 45.0 212 3.2 99.0

2-methoxy

pyrazine N

N

O CH3

110.1 - - - 61.0 0.75 99.0


42

naphthalen

e

128.2 80.3 218.0 3.5 99.0

benzoic

acid

122.1 122.4 249.0 1.9 99.5

dodecane 170.3 - 9.6 216.2 7.2 99.0

octacosane

394.8 60.0 440.0 15.0 99.0

ibuprofen H2CHC

CH3

CH3

CH

C

CH3

O

OH

206 76 212 –

251 3.7

Ph, Eur.

5.0

1Where Log Pow = partitioning of the substance in Octanol to Water, which represent degree of

hydrophobicity / polarity

3.1.3 MCM 41, Zeolite NAY, Trispor glass

MCM 41s (Si / Al = 50, Si / Al = ∞) synthesized and calcined were obtained from Chair of

Chemical Reaction Technology, University of Erlangen (Group of Prof. Schwieger). Zeolite

NAY from Grace Davison Company, Trispor samples (controlled porous glass) from

company Vitra Bio GmbH.

3.2 Preparation methods of silica aerogels

3.2.1 Sol - gel process and drying methods

Silica aerogels are produced by using a two step sol-gel process [133].

Tetramethylorthosilicate (TMOS) is mixed with methanol (MEOH), water, and hydrochloric

acid (HCL) in a mol ratio: 1 TMOS: 2.4 MEOH: 1.3 H2O: 0.00001 HCl. The mixture is

stirred for 30 min at room temperature, and then pure water and aqueous ammonia solution

are added to obtain a mixture with a mol ratio as: 1 mol TMOS: 2.4 mol MEOH: 4 mol H2O:


43

10 - 5 mol HCl: 10 - 2 mol NH4OH. Acetonitrile is added to the mixture to obtain the desired

target density of the aerogel, calculated from ρ

t arg et= m

SiO2/ V

mixture, where mSiO2 is the mass of

SiO2 in the mixture and Vmixture is the measured volume of the mixture. Five milliliters of the

mixture are transferred to a cylindrical vessel sealed with parafilm to avoid solvent

evaporation. After a fixed time, depending on the target density, a gel forms and is then aged

for 12 hours. The liquid remaining in the pores of the gel is extracted with supercritical CO2 at

40°C and 100 bar.

3.2.2 Methods used for hydrophobization of aerogels

The hydroxyl groups on hydrophilic aerogels can be divided into surface (reactive or free) and

bulk (or bound) -OH groups [134]. The hydroxyl groups of hydrophilic silica aerogels are

esterified by placing the aerogels in a reactor heated to 180°C (see Figure 9). Methanol or

Trimethylethoxysilane solvent vapors are passed continuously through the reactor depending

on the surface functional group requirements (- OCH3 or O - Si (CH3)3). The vapors are

condensed back to the boiling sump using two condensers and the whole process runs

continuously. Previously, the process was semi batch, where the condensate is collected and

refilled during the process, and this work second condenser was connected to have continuous

process. The reaction time depends on the amount of OH groups which should be replaced by

functional groups, although after 48 hours saturation is achieved [29]. Aerogels are removed

after different reaction times from the reactor to get the required amount of - OCH3 or O - Si -

(CH3)3 groups. In the obtained hydrophobic aerogels most of the free hydroxyl groups are

replaced by ester groups during modification with a bulky ester groups, and the unconverted

hydroxyl groups present are bound ones. The major advantage of this method is that the

obtained hydrophobic aerogels contains nearly similar physical properties corresponding to

hydrophilic aerogels. Thus, the aerogels of different surface functional groups can be

produced with similar physical properties. Elementary analysis (CHN) is used to determine

the amount of -OCH3 or O - Si - (CH3)3 groups in hydrophobic aerogels.


44

Figure 9. Schematic diagram of the hydrophobization setup of hydrophilic aerogels.

3.3 Choice of crystallization temperature

For asymmetric binary phase behavior solute - CO2 system; naphthalene - CO2, benzoic acid -

CO2, and octacosane - CO2, the operating temperatures are chosen based on the phase

diagrams. The minimum temperature of the SLG curve for naphthalene and CO2 is 60 - 62°C

[135, 136, 137], for benzoic acid and CO2 is 100 - 102°C [138, 139, 140], and for octacosane

- CO2 is 52 - 55°C [141], therefore temperatures of 58°C for naphthalene, 65°C for benzoic

acid, and 50°C for octacosane were chosen for crystallization experiments. For symmetric

binary system for solutes - CO2; menthol [142], 2-Methoxy pyrazine [143], and dodecane

[144] temperature of 50°C is used.

3.4 Experimental techniques

Three different experimental methods used in this work are as follows:

1) Adsorption measurements using Magnetic Suspension Balance (MSB)

2) Adsorption measurement using an autoclave

3) Crystallization experiments using an autoclave


45

3.4.1 Adsorption measurements using Magnetic Suspension Balance

In-situ adsorption isotherms of solid solute and CO2 on aerogels are measured by using

magnetic suspension balance (MSB) from company Rubotherm (Bochum, Germany), which

is modified with a circulation pump to have a proper mixing of solid solute in CO2. Maximum

possible values of pressure and temperature in the MSB setup is 450 bar and 250°C

respectively, and the weight of the sample is measured with an accuracy of 0.01 mg. MSB is

kept at desired constant temperature using a heating jacket (oil). Figure 10 depicts the

schematic diagram of the working principle of MSB. The balance consists of a permanent

magnet which contains a basket with an adsorbent (aerogel) and a titanium sinker element

(mass is known and volume is calibrated) are suspended.

Figure 10. Working principle of magnetic suspension balance (MSB); different measuring

positions of MSB setup from Rubotherm (Bochum, Germany).

The permanent magnet is magnetically coupled to an electric magnet outside the high

pressure cell and it is connected to a control system. The control system always keeps the

permanent magnet under suspension by adjusting the magnetic force of electromagnet. In

position 1 (zero point), permanent magnet is only lifted, and at different conditions zero point

is different, these values will be used to correct the offset from zero position. In position 2

(sorption measurements), the basket containing adsorbent alone is lifted while the sinker is at


46

rest. In position 3 (density measurement), both the basket with adsorbent and sinker are lifted.

All the data acquisition is done by the software delivered with MSB setup using a computer.

In this study, the sample basket is filled with the desired amount of aerogels which is placed

in the MSB cell, and then vacuum is applied to remove the adsorbed water on the surface of

the aerogels for 4 hours at operating temperature. After that, helium is introduced stepwise

into the MSB cell, each pressure step being kept constant for 20 minutes. The reduced mass of

basket plus the sample (adsorbent) is measured and plotted as function of density of helium.

The slope gives the total volume of basket and the adsorbent. By subtraction of basket

volume, the skeleton volume of the sample is measured.

Adsorption of CO2: MSB cell is evacuated after helium measurements, and the adsorption of

CO2 is measured on the aerogels by stepwise increment of the pressure ranging from 1 bar to

350 bar at constant temperature, each pressure step being held constant for 30 minutes.

Adsorption of CO2 + solid solute: In this case required amount of solute is placed in the

bottom of MSB cell. The amount is chosen so that saturated solution is achieved at all

pressures. CO2 is introduced stepwise and the recycling pump is switched on to have proper

mixing of solute in CO2, each step is kept constant for 30 minutes until 70 bar is reached.

From 70 bar to 350 bar the equilibrium time for each pressure step is increased to 4 hours. At

the end of adsorption experiments the MSB is flushed with fresh CO2 to extract all possible

solute inside MSB cell before releasing the pressure, so that precipitation can be avoided

during the pressure release. Thus obtained aerogels after the flushing experiment contains

mostly the adsorbed solute, which is analyzed by UV spectroscopy.

3.4.2 Adsorption experiments using an autoclave

Figure 11 depicts a schematic diagram of the apparatus built and used for both adsorption and

crystallization experiments in this work. The experiments are performed in a 557.3 ml

autoclave equipped with borosilicate glass windows (maximum operating temperature =

150°C, max. operating pressure = 400 bar) which is connected to a circulating pump to

maintain a proper mixing of solutes. The experimental pressure and temperature are recorded

using a data acquisition program (Labview 7.0).


47

PI

1

400 bar-100°C

MAX

PT

1

TI

1

Borosilicate glass

window

PI

2 SV

CO2

Circulating pump

Saftey valveCompressor

Figure 11. Schematic sketch of the experimental setup for the adsorption and crystallization

experiments.

In a typical experiment adsorption experiments aerogels are first heated for 30 min at 200°C

to remove adsorbed water, weighed and quickly loaded into the autoclave. A known amount

of solute is placed in autoclave, and then CO2 is added to the autoclave preheated to targeted

temperature with a pressure range of 85 to 350 bar. These conditions are maintained for 24

hours. A low bulk concentration of solute in CO2 is maintained which is far away from the

saturation at targeted pressures and temperatures. As a result only adsorption of solute in

aerogels will occur whereas crystallization or precipitation is avoided during the pressure

release. Then, the pressure is released gradually to avoid Joule - Thompson cooling that could

lead to the condensation of CO2 and result in pore collapse of aerogels. Thus, the obtained

aerogels contains only adsorbed solute in pores of aerogels, no crystallization or precipitation

of solutes in the pores of aerogels occurs.

3.4.3 Crystallization experiments using an autoclave

In the case of crystallization experiments a known amount of solute is placed in an autoclave,

which is at the saturated condition at the targeted temperatures and pressures, contrary to

adsorption experiments along with the aerogels. Similar to adsorption experiments, a known

amount of CO2 is then added to the autoclave preheated to desired temperature with a

pressure range of 85 to 350 bar, and these conditions are maintained for 48 hours. Then, the

pressure is released by rapid expansion of supercritical solution to generate particles inside

the pores of aerogels (CO-RESS). The rapid pressure release is conducted in two steps to

avoid the formation of liquid phase of CO2 which will destroy the pores of aerogels, Step 1:

release of CO2 from targeted pressure to 90 bar in less than 0.4 sec, step 2: release of CO2


48

from 90 bar to 1 bar in 25 minutes. Other different porous carriers are loaded with solute

similar to crystallization procedure in aerogels. The amount and the physical state of the

solute in aerogels is further analyzed by the characterization techniques described in chapter

3.5.

3.4.4 Drug release experiments

The dissolution rate of drug form the carrier was performed in phosphate buffer (pH = 7.2)

solution. The dissolution experimental setup consists of a covered glass vessel, a motor, a

metallic drive shaft with a six - bladed agitator and a cylindrical basket (see Figure 12). The

sample (drug crystals or loaded carrier powder) was weighed and placed in the basket. To

fulfill the sink conditions [145] the amount of the drug was chosen so that the final

concentration is equal to 10% of the maximal solubility of this drug in the buffer solution.

Required amount of drug loaded carrier is placed in the basket, which is fixed on the agitator

and immersed into the vessel containing 500 ml of buffer medium at 37°C. The stirring speed

was 100 min - 1. Samples of 2 ml were withdrawn at predetermined time intervals, filtered

through a 0.45mm Nylon filter and analyzed by UV - spectrometry. The percentage of drug

released at different time intervals is calculated.

Figure 12. Experimental setup of drug release studies.


49

3.5 Characterization techniques used

All the characterization techniques used in this study are briefly described here. The specific

experimental procedure of the present work is reported here rather than the principles of the

analytical methods which are well known and well reported in literature [163].

3.5.1 Measuring of the bulk density of aerogels

To measure the bulk density of aerogels, the dried aerogel sample is first heated to 200°C for

30 minutes to remove any adsorbed moisture and weighed. The dimensions of the aerogels

are measured with a precision micrometer. The measurements are repeated for five times and

the average is taken as a reference.

3.5.2 Nitrogen Adsorption and Desorption; BET analysis

Nitrogen adsorption and desorption is used to characterize the properties of porous carriers

[146]. The information obtained from the analysis is: surface area, pore volume, average pore

diameter. Figure 13 shows the typical Type 4 isotherm for mesoporous substance (silica

aerogel). Hysteresis observed during desorption is due to well known bottle neck effect.

0.0

400.0

800.0

1200.0

1600.0

2000.0

2400.0

2800.0

3200.0

0.00 0.20 0.40 0.60 0.80 1.00

Relative pressure, P/P0

Volu

me

(cc/g

)

Adsorption

Desorption

Figure 13. Typical adsorption isotherm of type 4 (mesoporous solid substance) [146].


50

Surface analyzer Nova 3000e (Quantachrom Instruments) is used for analysis. The aerogel

samples (30 mg) are pretreated under vacuum at temperature 150°C to remove the adsorbed

water. In the case of volatile solute loaded aerogels, pretreatment is not performed to avoid

the solute loss. Then, the samples are subjected for N2 adsorption and desorption. Methods

used for evaluation of the raw data are as follows:

− surface area: BET analytical method,

− pore volume: filling the pores completely with liquid nitrogen at P / P0 = 0.99,

− average pore size distribution: BJH desorption method.

3.5.3 Elementary Analysis

Elementary analysis (Euro EA elementary analyzer) is used to determine the amount of

Carbon, Hydrogen, and Nitrogen (CHN). 2 - 3 mg of aerogel samples are burned at 1000°C

in flowing oxygen. The obtained vapors containing CO2, N2, NXOY, and H2O are analyzed

using thermal conductivity detector. Thus, the amount of CHN is measured with an accuracy

of ± 0.03 wt%, especially; this method quantifies the amount of -CH3 groups in hydrophobic

aerogels.

3.5.4 UV - Vis Spectroscopy

Ultra Violet - Visible radiation spectrometer from company Perkin Elmer, Lambada 650 is

used to determine concentration of solutes in aerogels. The aerogel samples filled with solutes

are crushed, dispersed in the solvent and stirred for 1 hr. The solution is filtered and analyzed.

Similar procedure is used for other porous carriers (MCM 41, Zeolites, Trispor glass). In the

present work three solutes are measured using this method (see Table 7).

Table 7. UV wavelength of organic substances used.

Substances λ (nm)

benzoic acid 272.0

naphthalene 287.8

ibuprofen 220.0


51

3.5.5 Gas Chromatography (GC)

HP 5890 Series II, Gas Chromatography (GC) is used to determine the concentration of

solutes in aerogels. The aerogels samples filled with solutes are crushed, dispersed in the

solvent and stirred for 1 hr. 1 - 3 µl of filtered extract solution is injected into the column

along with internal standard. The concentration of the solutes quantified by this method are as

follows: 1-menthol, 2-Methoxy pyrazine, octacosane, dodecane. Details of the GC used are

mentioned in Appendix.

3.5.6 IR spectroscopy

The chemical stability of the solute loaded in silica aerogels is measured using Infra - Red

(IR) spectroscopy from Company Perkin Elmer FT - IR spectrometer. IR spectroscopy helps

to qualitatively determine the characteristic peaks of particular groups of the solute and

aerogels [147]. The aerogel loaded with solutes are powdered, 2 - 5 mg of samples is mixed

with KBr and then compressed to a cylindrical tablet. The tablet is kept inside IR

spectrometry and the transmission / absorption of the IR light (450 - 4000 cm - 1) is measured.

3.5.7 Differential Scanning Calorimeter

Differential Scanning Calorimeter (DSC) from company NETZSCH (DSC 200 F3) is used to

analyze the physical state of solute loaded in the aerogels. For this, loaded aerogels samples

are powdered and 5 - 7 mg of sample is placed inside the aluminum pan and compressed. The

samples are subjected to a temperature ramp of 10 °C / minute to determine the melting peaks

of the solute in the aerogels. Different temperature rates are used to study the effect of heat

transfer limitations. The samples are heated from - 10°C to desired temperature and then

cooled back and heated again. Thus, the melting points are determined for the solutes inside

the aerogels. DSC analysis of the mechanical mixture of pure solute and pure aerogel is

performed to overcome the question of sensitivity of DSC at these concentrations.

3.5.8 X - Ray Diffraction

X - Ray Diffraction from company Philips, (XPERT - Pro, Cu Kα1) is used to analyze the

physical state of substance (crystalline or amorphous state) [148]. The crystalline substance

exhibit the diffraction of X - rays, which is the main principle in this method (Bragg’s law).


52

The powdered samples of solute loaded aerogels (100 - 200 mg) are loaded in XRD pans and

subject to X - rays at angles of 2 - 50° (2θ). Crystalline substances exhibit the characteristic

peaks and amorphous substances shows no peaks during analysis.

3.5.9 TGA / TGA - MS analysis

Thermal Gravimetric Analysis (TGA, TA instruments) is used to study the strength of solute

interaction with aerogel surface. 10 - 15 mg of solute loaded aerogel sample is placed in a

metal pan and subject to different temperature steps from 20 to 600°C with a ramp of 10°C /

minute. Each temperature step is kept constant (isothermal) for 45 - 60 minutes. The weight

loss of solute loaded in aerogels is measured. TGA combined with mass spectroscopy (MS) is

used to determine the stability of compound at elevated temperatures.

Results and Discussions

53

4. Results and Discussions

A step wise approach is followed to study the influence of adsorptive properties of carrier

(silica aerogels) on crystallization of solutes and physical state of solutes in the pores of

aerogels. To study these influences aerogels of different physical and surface functional group

are synthesized at our lab. Different solutes ranging from polar solutes (benzoic acid, 1-

menthol), moderately polar solutes (naphthalene, 2-Methoxy pyrazine), nonpolar solutes

(octacosane, dodecane) are chosen to study these effects. First adsorption of solutes in

aerogels is conducted, to further understand the influence of the adsorbed solutes precipitation

of the solutes in performed in the pores of aerogels by CO-RESS. For the liquid solutes only

adsorption is conducted to study the strength of solute - surface interactions on loadings.

Further, the influence of properties of aerogels on the physical state of the loaded solutes is

investigated. Other mesoporous carrier materials like MCM41s, Trisopor glass (which are

similar to aerogels) are also used for the comparison purpose.

4.1 Properties of aerogels synthesized and other carriers used

Table 8 summarizes the properties of the silica aerogels synthesized and used for adsorption

experiments and crystallization experiments in this study. Hydrophilic aerogels are

synthesized first and then some of them undergo the gas phase modification to produce

hydrophobic aerogels. An advantage of this post - treating method is that the pore volume,

pore size distribution, and surface area of the material do not change significantly during this

process. Hence, it is possible to study the influence of the aerogel’s functional groups on the

adsorption and crystallization by comparing hydrophilic and hydrophobic aerogels samples

having essentially the same structural properties. Aerogels of different hydrophobicity are

produced based on the reaction times from the reactor to study the influence of degree of

hydrophobcity. It should be noted that the BET analysis of hydrophilic aerogels essentially

requires the thermal treatment since samples are rather hydroscopic. In case of hydrophobic

aerogels it is not so significant. The corresponding values can be found in Table 8. The

hydrophobic aerogels have higher bulk density compared to hydrophilic aerogels. The

increase of the bulk density in case of hydrophobic aerogels is due to the replacement of –OH

groups with O - Si - (CH3)3.

Table 8. Selected properties of silica aerogels used in this study.


54

Hydrophilic aerogels (-OH) Hydrophobic aerogels (- O - Si(CH3)3)

Sample

ID

Bulk

density (g /

cm3)

(±0.003)

Surface

area (m2

/ g) (±20)

Pore volume

(cc / g)

(±0.2)

Average Pore

diameter (nm)

(±0.4)

Bulk density (g

/ cm3)

(±0.003)

Surface area

(m2 / g)

(±20)

Pore

volume

(cc / g)

(±0.2)

Average

Pore

diameter

(nm) (±0.4)

%CH3 from

CHN

analysis

(±0.03)

A1 0.07 860 10.8 25.1 0.09 725 10.9 30.2 6.3

A2 0.10 1182 10.0 18.4 0.10 864 10.1 23.2 8.4

A3 0.15 1112 9.5 17.2 0.15 900 11.3 25.2 8.1

A4 0.09 1113 8.8 15.8 0.18 1000 10.5 21.0 8.7

A5 0.09 971 9.6 19.8 0.10 988 11.4 23.0 6.8

A6 0.18 1218 9.1 22.0 0.19 916 8.0 14.0 7.5

A7 0.08 941 5.3 21.7 0.08 758 4.6 24.3 4.3

A8 0.09 687 5.2 30.1 7.5

A9

0.09 661 5.3 31.6 8.2

A10 0.13 1076 5.50 20.3 0.14 1011 4.9 19.4 5.5

A11 0.15 859 4.9 24.1 7.8

A12

0.15 833 5.5 26.0 8.2


55

Hydrophilic aerogels (-OH) Hydrophobic aerogels (- O - Si(CH3)3)

Sample

ID

Bulk

density (g /

cm3)

(±0.003)

Surface

area (m2

/ g) (±20)

Pore volume

(cc / g)

(±0.2)

Average Pore

diameter (nm)

(±0.4)

Bulk density (g

/ cm3)

(±0.003)

Surface area

(m2 / g)

(±20)

Pore

volume

(cc / g)

(±0.2)

Average

Pore

diameter

(nm) (±0.4)

%CH3 from

CHN

analysis

(±0.03)

A13 0.11 1176 5.70 19.5 0.12 891 4.1 18.2 7.5

A14 0.12 901 5.1 25 0.13 947 4.7 21 5.3

A15 0.16 972 4.8 20 0.17 966 4.5 22 5.5

A16 0.21 1014 4.6 19 0.24 1054 4.1 20 6.2

A17 0.10 1112 9.1 16.1 0.11 1263 12.0 18.9 7.4

Note: a) Hydrophilic aerogels (of each density) are synthesized in different batches; corresponding batches are modified to hydrophobic aerogels. b)

wt% of CH3 is < 0.5 wt% in all hydrophilic aerogels.


56

Aerogels surface properties reported in Table 8 are from N2 adsorption and desorption

experiments. The surface area of all hydrophobic aerogels is lower compared to hydrophilic

aerogels, average pore diameter in hydrophobic aerogels is higher compared to hydrophilic

aerogels due to the replacement of –OH groups with O - Si - (CH3)3 groups. The reason is that

during BET measurements nitrogen molecule cannot be adsorbed on the hydrophobic aerogel

surface as the group O - Si - (CH3)3 sterically hinder the adsorption of N2 on the surface as a

result the surface area is lower. The average pore size increases in hydrophobic aerogels as

volume of the small pores decreases due to the presence of –O - Si - (CH3)3 groups inside the

pores (see Table 8). Thus, the average pore diameter measured increases to a higher value.

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

0 20 40 60 80 100

Pore diameter (nm)

Po

re v

olu

me (

cc/n

m/g

)

Hydrophilic aerogel

Hydrophobic aerogel

Figure 14. Pore size distribution of hydrophilic and hydrophobic aerogel (ρaerogel = 0.09 g / cm3

(sample ID: A1)).

In all the loading experiments in the following sections bulk density of hydrophilic aerogels is

taken as reference to avoid much data on the graphs (all the corresponding details are given in

Table 8). The degree of the replacement was characterized by elementary analysis (CHN). Table

9 shows the properties of other carriers used in this study.


57

Table 9. Selected properties of different porous carrier used in this study.

Sample ID. Carrier Surface area

(m2 / g) (±20)

Pore volume

(cm3 / g) (±.2)

Average pore

diameter (nm) (±.4)

A18 Activated carbon 851 2.4 3.4

A19 Zeolite NAY 870 0.8 2.6

A20 MCM41 calcined 1100 0.4 3.5

A21 Zeolite BEA 458 0.0 0.65

A22 *Trispor1 68 1.0 63

A23 *Trispor2 20 0.7 172

A24 *Trispor3 14 0.7 299

* Trispor samples are made from controlled porous glass


58

4.2 Adsorption and crystallization of polar solutes in silica aerogels

4.2.1 Adsorption and crystallization of benzoic acid in silica aerogels

In this work, adsorption and crystallization of polar solute benzoic acid (also used as a drug for

curing skin diseases) in different porous carriers from supercritical CO2 solution is studied. The

influence of the adsorptive properties of the carrier - aerogels with different surface and structural

properties on further crystallization of benzoic acid in the aerogel matrix is investigated. To

understand the influence of the adsorption process on crystallization, high pressure binary

adsorption isotherms data of the benzoic acid and CO2 on aerogels is measured in-situ by

Magnetic Suspension Balance (MSB). Comparison of adsorption and crystallization of benzoic

acid in aerogels will provide an insight into influence of adsorbed benzoic acid / CO2 on the

crystallization and physical state of benzoic acid in silica aerogels.

4.2.1.1 Stability of aerogels under pressure

Stability of the aerogels are measured by placing them in CO2 at pressure of 250 bar and a rapid

pressure release of CO2 is performed similar to the experimental conditions.

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

0 20 40 60 80 100

pore diameter (nm)

po

re v

olu

me c

c/n

m/g

Pure aerogel

Aerogel pretreated with CO2 (250 to 1 bar)

Figure 15. Comparison of pore size distribution of pure aerogel and pretreated aerogel with CO2

(pressure release from 250 bar to 1 bar (sample ID: A2)).


59

Figure 15 shows the change in the pore size distribution of pure and pretreated aerogels (after

pressure release). The aerogels structure remained stable at the experimental conditions, thus, the

experimental procedure will not affect the properties of the aerogels used in this study.

4.2.1.2 CO2 adsorption on aerogels

First, CO2 adsorption is performed on silica aerogels before measuring the adsorption of benzoic

acid from benzoic acid - CO2 solution. Adsorption experiments are performed in-situ by using

Magnetic Suspension Balance (MSB). MSB should be validated before conducting the adsorption

measurements on silica aerogels. The following section reports the validation of MSB.

Validation of the MSB measurements

MSB measurements were validated by comparing with the systems available in the literature.

Figure 16 A shows the excess adsorption isotherm of CO2 on activated carbon. The data are in

good agreement with those of Humayun et al. [149] and Roni et al. [150].

0

0.1

0.2

0.3

0 0.2 0.4 0.6 0.8 1

Density of pure CO2 (g/cm3)

Excess a

mo

un

t ad

so

rbed

CO

2 (

g)/

(g

)

Acti

vate

d c

arb

on

This work (~45°C)

Roni et al. 2006 (45.4°C)

Humayun et al. 2002 (45°C)

A)


60

0.43

0.53

0.63

0.73

0.83

0.93

90 120 150 180 210 240 270

Pressure (bar)

(CO

2+

nap

hth

ale

ne)

de

nsit

y (

g/c

m3)

~43°C (this work)

~42.5 (Anil et al. 1999 )

B)

Figure 16. Validation of MSB: A) excess adsorption of pure CO2 on activated carbon (sample ID:

A18), B) density of a binary mixture naphthalene + CO2.

The experimental points near the critical region (75 bar to 110 bar) are scattered which is a well

known problem [149]. The density measurements of well known binary system of naphthalene -

CO2 (see Figure 16 B) are in good agreement with literature data measured using other

techniques [151].

After the validation of the setup, CO2 adsorption on different porous materials is measured.

Figure 17 shows the comparison of absolute adsorption isotherms of activated carbon (Filtrasorb

400, Chemviron Carbon), Zeolite NAY, hydrophilic and hydrophobic aerogel. Langmuir

isotherm is used to calculate the absolute adsorption [152, 153, 154,155]. Remarkably large

amount of CO2 is adsorbed on both aerogels compared to both commercially well known

adsorbents. Figure 17 shows the adsorbed density (values from isotherm fit) of CO2 adsorbed on

aerogels and activated carbon, which are in good agreement with the literature data.


61

Figure 17. Absolute adsorption isotherms of activated carbon (sample ID: A18), Zeolite NAY

(sample ID: A19) and hydrophilic (sample ID: A5) and hydrophobic aerogels (sample ID: A5) at

40°C; P = 1 - 450 bar. (See Table 8 and Table 9 for all detail of the samples).

Table 10. Comparison of adsorbed density from MSB measurements with literature.

Substances Reference T (°C)

Adsorbed Density

(g / cm3)

Humayun et al. [149] 40 1.02

Humayun et al. [149] 45 1.01

This work 40 0.99

Activated Carbon

This work 45 0.99

Hydrophilic aerogel Y.B. Melnichenko et al.

[156] 35 and 80 1.07*

Hydrophilic aerogel This work 40 1.01

Hydrophobic aerogel This work 40 1.08

* Measured experimentally by optical method using SANS


62

4.2.1.3 Excess binary adsorption of CO2 + benzoic acid

Since, the aerogels have high adsorption capacity in respect to CO2; the adsorption of benzoic

acid from CO2 is expected to be competitive adsorption. Figure 18 compares the adsorption of

pure CO2 on aerogel with binary adsorption of benzoic acid and CO2 on the same aerogel.

As seen from Figure 18, the binary adsorption isotherms of benzoic acid + CO2 on aerogels is

different from that of pure CO2. The excess adsorption isotherm for hydrophilic aerogel can be

divided into three regions. Region 1(P ≤ 75 bar): solubility of benzoic acid in CO2 is low, mainly

pure CO2 is adsorbed; region 2: competitive adsorption of CO2 and benzoic acid, the excess

adsorbed amount of CO2 + benzoic acid in this region is lower than the adsorption of pure CO2;

region 3: solubility of benzoic acid increases rapidly, adsorption of benzoic acid also increases.

Figure 18. Excess adsorption isotherms of pure CO2 and benzoic acid + CO2 on aerogels.

Conditions: (65°C, 1 - 350 bar, ρaerogel = 0.10 g / cm3, Sample ID: A2). Standard deviation of the

data: ±0.02, number of measurements for each isotherm = 4.

Contrary to the hydrophilic aerogels, there is no big shift of excess amount adsorbed between

pure CO2 - hydrophobic aerogel and (CO2 + benzoic acid) - hydrophobic aerogel in region 3.


63

There might be a very strong competitive adsorption between CO2 and benzoic acid on the non -

polar surface of hydrophobic aerogel. However, hydrophilic aerogels adsorb more of benzoic

acid -CO2 mixture, compared to hydrophobic ones in all cases. The “jump” in adsorption in case

of hydrophilic aerogels at ρb=0.46 could result from the re-orientation of the adsorbed molecules

on the aerogel surface.

Still it is not easy to calculate single component adsorption from these data. As a first

assumption, a simple subtraction can be done between excess adsorbed amount of CO2 + benzoic

acid and pure CO2. In this case it is assumed that there are enough active sites for both benzoic

acid and CO2 and their adsorption is independent from each other. The difference in the excess

adsorption (∆m) would then give us the approximation of the amount of benzoic acid adsorbed

on aerogels. Table 11 shows the difference of excess adsorbed amount between hydrophilic - CO2

and hydrophilic aerogel - (CO2 + benzoic acid). The percentage difference is more than 100% at

density of fluid 0.76 g / cm3. After this experiment the system was flushed with CO2, pressure

was released and the sample was analyzed by UV spectroscopy. 15wt% of benzoic acid was

observed in this aerogel. This is in contradiction with the MSB data.

Table 11. Data of the difference of hydrophilic aerogels excess adsorption values of CO2 +

benzoic acid and CO2 and UV analysis.

Density of fluid

(g / cm3)

Hydrophilic aerogel:

∆m (wt%)

Hydrophobic aerogel:

∆m (wt%)

0.52 21 - 9.4

0.76 103 8.8

UV analysis

(After MSB flush)

15 9.3

Where ∆m = (Excess adsorbed amount of CO2 + benzoic acid - Excess adsorbed amount of CO2) / Excess adsorbed

amount of CO2).

In the case of adsorption of CO2 + benzoic acid - hydrophobic aerogel and pure CO2 -

hydrophobic aerogel there is negative and positive difference in the excess adsorbed amount, but

from the MSB flushing experiments, 9 wt% of benzoic acid in hydrophobic aerogel is observed.

The adsorption of CO2 + benzoic acid measurements is repeated for four times to avoid any


64

artifacts, and the measurements were reproducible. Therefore, it can be concluded that the above

assumption is not valid and one can not determine the amount of benzoic acid adsorbed from the

binary adsorption by simple subtraction of 2 isotherms.

4.2.1.4 Static adsorption of benzoic acid in silica aerogels

Additionally to MSB measurements static adsorption experiments are performed. These

experiments can be conducted only at lower concentrations, far away from saturation, so that no

precipitation occurs and thus don’t represent the saturated conditions at which crystallization is

performed. Still they give us more insight into the strength of benzoic acid - aerogel surface

interactions.

Figure 19 shows the adsorption of benzoic acid in hydrophilic and hydrophobic aerogels at

pressures 110 to 350 bar. High adsorption of benzoic acid even at these low bulk concentrations

indicates the strong affinity of benzoic acid to the aerogel surface. The adsorption data are fit to

the Langmuir equation:

KC

KCQQ m

a+

=1

Equation 15

Where Qa is the amount of additive (in mol) adsorbed per unit weight of adsorbent (in g), Qm is

the maximum loading (mol / g), C is the concentration of adsorbate in the bulk phase (mol / kg

solution), and K is the Langmuir constant. The parameters determined for the benzoic acid -

hydrophilic aerogel system are Qm = 1.34 (mol / g), and K = 0.147, and for the benzoic acid -

hydrophobic aerogel system are Qm = 1.02 (mol / g), and K = 0.108. Again, hydrophilic aerogel

adsorbs more benzoic acid than hydrophobic one at all concentrations which is in agreement with

the MSB results. It is expected that this difference in adsorption behavior would lead to the

corresponding difference in the crystallization process. It should be noted that there are no visible

changes in the aerogel (loaded) transparency is observed.


65

0.00

0.04

0.08

0.12

0.16

0.20

0.00 0.20 0.40 0.60 0.80 1.00

Cbenzoic acid in CO2, mol/Kg

Qa

, m

ol/

g

Hydrophilic aerogel

Langmuir, Qm=1.34, K= 0.147

Hydrophobic aerogel

Langmuir, Qm=1.02, K= 0.108

Figure 19. Impact of hydrophobicity on the adsorption of benzoic acid onto silica aerogels from

benzoic acid - CO2 solutions at 65°C, Loading time = 24hr, slow pressure release (ca. 30

minutes), ρaerogel = 0.10 g / cm3 (Sample ID: A2).

4.2.1.5 Crystallization of benzoic acid in silica aerogels by CO-RESS

After the study of adsorption behavior, crystallization of benzoic acid in different carriers was

conducted. Typical aerogel samples loaded with benzoic acid from the saturated solutions are

shown in Figure 20. Particles formed inside the pores are in the range of 20 nm - 50 µm, some of

them being larger than the pore size. The size of solute particles formed inside the pores of

aerogels during crystallization depends on the properties of aerogels and on the pressure release

rate since the nucleation process and particle growth are driven by supersaturation inside the

pores [157]. The effect of pressure release rate on particle size in the aerogels pores is optimized

with crystallization of moderately polar solute naphthalene (see section 4.3.1). Therefore, the

pressure release rate of (350 bar /s) is used for precipitating benzoic acid in aerogels.


66

Figure 20. Light microscopic picture of aerogel loaded with benzoic acid (two different scales).

Experimental conditions: bulk concentration of benzoic acid - CO2 = 0.65 wt% (165 bar, 64.5°C),

ρ = 0.15 g / cm3 (sample ID: A3), two step pressure release: step 1: fast release of pressure 165 -

90 bar (350 bar / sec); step 2: slow release of pressure 90 to 1 bar (3 bar /s).

Continuous particle distribution of benzoic acid in the pores of aerogels is observed ranging from

20 to 50µ. Due to continuous distribution of particles in pores, it is not possible to determine the

smallest particles inside the pores of the aerogels. Therefore, N2 adsorption / desorption of

following samples is performed to quantify the structural changes of the following aerogel

samples: (a) virgin aerogel, (b) benzoic acid loaded aerogels, (c) benzoic acid loaded aerogels

treated with vacuum to remove the precipitate. All the samples (a - c) were subjected to vacuum

at 40°C to remove any adsorbed water without significant loss of benzoic acid especially in case

of loaded samples. Figure 21 shows the typical pore size distribution of the samples. As expected

the maximum of the pore volume of the loaded hydrophilic aerogel (b) is reduced in comparison

to virgin hydrophilic aerogel (a) since the pores are occupied with benzoic acid. Vice versa, the

maximum of the pore volume of evacuated loaded aerogel (c) increases compared to loaded

aerogel (b), as the benzoic acid is removed from the pores of the aerogel by evacuation. The re -

appearance of the small pores after the vacuum treatment indicates that there might be particles of

ca. 20 nm in the pores. The larger pores might be destroyed or merged during the big particles

formation during the precipitation and as a result the pores ranging from 20 nm to 80 nm cannot

be retained after evacuation (however, some pores might be still occupied by the rest benzoic


67

acid present since 4-5 wt% of benzoic remains in the pores of the aerogels after vacuum

treatment as proved by UV analysis).

0

5

10

15

20

25

0 10 20 30 40 50 60 70 80

Pore diameter(nm)

Po

re v

olu

me

(c

c/n

m/g

)

(a) pure hydrophilic aerogel

(b) Loaded hydrophilic aerogel (27wt%)

(c) Loaded hydrophilic aerogel(evacuated)

Figure 21. Comparison of structural changes of pure, benzoic acid loaded, evacuated loaded

hydrophilic aerogel (sample ID: A2).

4.2.1.6 Effect of the aerogel properties on the crystallization process

Crystallization of benzoic acid is performed for a fixed aerogel density at different saturated bulk

concentrations of benzoic acid in CO2. Figure 22 shows the dependence of aerogel loading

(adsorption + precipitation) on the bulk concentration of benzoic acid in CO2. Rather high overall

loadings (up to 31 wt%) have been achieved. As expected, the loading increases with the

increasing benzoic acid concentration, but in all cases hydrophilic aerogels exhibited higher

loading than hydrophobic ones even though the physical properties are nearly similar expect the

surface functional groups. Similar trend was observed for aerogels of different bulk densities

(0.07 to 0.22 g / cm3) (see appendix). The overall loading is a sum of 2 processes: adsorption of

benzoic acid and further precipitation in the pores, so it is interesting to know if this difference in

the overall loading is equal to the difference in adsorbed solute. The answer could be given by


68

comparing the results of the crystallization with those for adsorption at the same conditions.

However, binary high pressure isotherms cannot be used for this purpose. Still, taking into

account the sample analysis after the MSB experiment (Table 11) one could answer this question.

This data have an uncertainty resulting from CO2 flushing: on the one hand, some precipitation

might occur if the flushing is too short, on the other hand desorption can take place if the flushing

is too long.) However, it is worth to compare the corresponding values. At the bulk density of

0.76 g / cm3, 15.0 wt% of benzoic acid was adsorbed in case of hydrophilic aerogel and 9.3 wt%

in case of hydrophobic one (see Table 11, UV analysis). So the difference in adsorption is equal

to 5.7 wt%. The difference in overall loading (adsorption + crystallization, see Table 11) is equal

to 9.4 wt%. So the difference in overall loading cannot be simply explained by the difference in

adsorption.

The prior adsorbed benzoic acid might act as a kind of nuclei for further crystallization during

CO-RESS process. The presence of larger amount of adsorbed benzoic acid favored larger

amount of precipitation in hydrophilic aerogels compared to hydrophobic ones.

0

4

8

12

16

20

24

28

32

0.64 0.83 1.49 2.52

Bulk concentration of benzoic acid in CO2 (%)

wt

(%)

of

be

nzo

ic a

cid

in

ae

rog

el

Hydrophilic Hydrophobic

Figure 22. Loading of benzoic acid on silica aerogels for varying initial benzoic acid

concentration in bulk CO2 for a fixed aerogel density of 0.10 g / cm3 (sample ID: A2),

conditions: T = 65°C , P = 270 - 140 bar.


69

To further elucidate the influence of functional groups on the amount of loading, the amount of –

O - Si - (CH3)3 groups is varied and crystallization of benzoic acid is performed on these aerogels

(see table 2 for the aerogel properties). Figure 23 shows that the loading of benzoic acid in

aerogels decreases with increasing of the amount of –O-Si-(CH3)3 groups on the aerogels surface.

It proves additionally that hydroxyl groups play a major role in adsorption process and the overall

amount of loading in the aerogels can be tailored based on the amount of surface functional

groups.

0

5

10

15

20

25

30

0.08 0.15

density of aerogel (g/cm3)

wt

(%)

of

be

nzo

ic a

cid

in

aero

ge

l ~ 0.5% CH3

~ 4.3% CH3

~ 7.5% CH3

~ 8.2% CH3

~ 0.5% CH3

~ 5.5% CH3

~ 7.8% CH3

~ 8.2% CH3

Figure 23. Effect of loading of benzoic acid in silica aerogels (with a different degree of

hydrophobized aerogels): <0.5 wt% to 8.5 wt% of carbon. (Conditions: P = 195 bar, T = 64.7°C,

time of loading = 24 hours, bulk concentration of benzoic acid in CO2 = 2.3 wt %; ρaerogel = 0.08:

sample ID: A7 - A9; ρaerogel = 0.15: sample ID: A10 - A12).

Benzoic acid is crystallized in aerogels of different density. The effect of the aerogel’s density is

less pronounced, however small increase in overall loading is observed in case of hydrophilic

aerogels (Figure 24). Since the surface area increases with the increasing aerogel density, it is

probably a reason for this effect being in agreement with our previous results on adsorption of

other organic substances on aerogels [158].


70

0

5

10

15

20

25

30

0.07 0.10 0.15 0.18

ρρρρ (g/cm3)

wt

(%)

of

be

nzo

ic a

cid

in

ae

rog

el


Figure 24. Benzoic acid loading in hydrophilic and hydrophobic aerogels with different bulk

densities of aerogels. Crystallization conditions: initial bulk concentration of benzoic acid in CO2

is 0.83 wt%; T = 65.2°C, Pinitial = 179 bar (sample ID: A1, A2, A3, A6).

From all the results discussed so far, it can be concluded that not only adsorption but also the

crystallization of benzoic acid depends mainly on the surface properties of aerogels and thus, it

allows one to influence the crystallization process by changing the adsorption properties of

aerogels (adsorptive crystallization).

4.2.1.7 Crystallinity of benzoic acid in aerogels

Differential Scanning Calorimetry (DSC) is used to investigate the physical state of benzoic acid

particles loaded inside the pores of aerogels. Figure 25 A and B shows the DSC curves of

aerogels loaded with benzoic acid along with the corresponding physical mixture. DSC curves of

physical mixture (pure benzoic acid + hydrophilic aerogel) exhibit an endothermic peak and the

melting temperature is observed at 105 °C. This shift of 17°C degrees in case of hydrophilic


71

aerogels (Tm of benzoic acid=122°C) might be due to the interactions of benzoic acid with

hydrophilic aerogel during mechanical mixing and confirms once more a high affinity of

hydrophilic aerogels to benzoic acid. Physical mixture of pure benzoic acid and hydrophobic

aerogel exhibits an endothermic peak and the melting temperature is 122 °C similar to the pure

benzoic acid melting point, as there are few interactions of benzoic acid with hydrophobic

aerogel. DSC curves of hydrophilic aerogel loaded with benzoic acid until 27 wt% have shown

no crystallinity, but for loading of 31 wt% and 35 wt% a small endothermic peak appears at

80°C. It is an interesting fact showing that non-crystalline form of benzoic acid can be stabilized

in silica aerogels up to certain concentration. Melting point depression of the crystalline form in

the pores is a known effect [159, 160, 157]. Benzoic acid loaded hydrophobic aerogel shows no

melting peaks up to 15 wt% loading is achieved, whereas an endothermic peak appears for the

loading of 21 wt%. Weaker interactions with the hydrophobic aerogels matrix result in crystal

formation already at 21 wt%, compared to 27 wt% in case of hydrophilic aerogels. Melting point

shifts to a lower value to 90°C. The shift is smaller compared to loaded hydrophilic aerogel,

probably due to less interaction of benzoic acid with surface of aerogel. Hence, it can be conclude

that strong interaction of benzoic acid with aerogel surface results in amorphous form of benzoic

acid until a certain critical loading is reached.

Benzoic acid loaded aerogel samples were stored at atmospheric conditions for 5 months and

than analyzed again to prove the stability of the amorphous form. Same results were obtained. It

is important since the bioavailability of drugs in amorphous form is higher compared to

crystalline form, and the stabilization of amorphized drug is a key issue in pharmaceutical

industries [12, 161, 162]. Thus, these findings will have potential applications in the stabilization

of amorphous form of the drugs.


72

Figure 25. DSC curves: A) hydrophilic aerogel loaded with benzoic acid along with a physical

mixture of hydrophilic aerogel and benzoic acid, B) hydrophobic aerogel with loaded benzoic

acid and corresponding physical mixture. The heating rate is 10°C / min in all cases.

B)

A)


73

4.2.1.8 Crystallization of benzoic acid in other porous carriers

To broad the spectrum of possible porous carrier - solute interactions, other porous carriers

besides aerogels were studied. Carriers: MCM41 (a mesoporous carrier), Zeolite BEA

(microporous carrier), and three different types of controlled porous glass (Trisopor1, Trisopor2,

Trisopor3) are used. Benzoic acid loaded in porous carriers is also in amorphous form. XRD

analysis of benzoic acid in all porous carriers showed no sign of crystallinity. Table 12 shows the

loading of benzoic acid in the porous carriers where all the carriers contain hydroxyl groups.

Table 12. Selected properties of different porous carrier used in this study (beside aerogels).

Sample ID. Carrier Surface

area

(m2 / g)

aLoading

(Benzoic acid

(g) / m2

adsorbent)

A13 Activated carbon 851 -

A14 Zeolite NAY 870 -

A15 MCM41 calcined 1100 0.024

A16 Zeolite BEA 458 0.011

A17 *Trispor1 68 0.037

A18 *Trispor2 20 0.081

A19 *Trispor3 14 0.038

* Trispor samples are made from controlled porous glass, a Loading conditions: 65°C, bulk concentration of benzoic

acid in CO2: 0.79 wt%. (Note: hydrophilic and hydrophobic aerogel sample ID is A6 in Table 8, Refer Table 9 for all

the properties of other samples).

Large amount of benzoic acid is loaded in MCM41 due to higher surface area (more hydroxyl

groups) (see Table 9). Loadings in Trisopor samples are very low even though they offer a high

pore volume and pore diameter. Thus, the loading in a porous carrier is a function of surface area

rather than pore volume. This shows the importance of surface - solute interactions rather than

pore volume on the overall loading amounts.


74

4.2.1.9 IR analysis of loaded benzoic acid

Infra - Red analysis of the pure hydrophilic aerogel, pure benzoic acid, and loaded benzoic acid

in hydrophilic aerogel is performed. Figure 26 shows that there is no change in the characteristic

peaks of benzoic acid in the loaded state in the pores of aerogels.

Figure 26. IR spectrum of the pure benzoic acid, hydrophilic aerogel, loaded aerogels.

Figure 27. IR spectrum of the pure benzoic acid, hydrophobic aerogel, loaded aerogels.


75

The region 3600 - 3200 cm -1 is the region where water is adsorbed on hydroxyl groups on pure

hydrophilic aerogels. In the case of benzoic acid loaded aerogel this peak is sharpened due to the

hydrogen bonding between OH groups and benzoic acid carboxylic group. Thus, the loaded

benzoic acid is stabilized in the pores of silica aerogel even though amorphized after the loading.

Similar analysis is done for hydrophobic aerogels samples. Hydrophobic aerogels contains less

hydroxyl groups, as a result, in the region (3600 - 3200 cm-1) the peak is not so wide rather sharp

(see Figure 27). The benzoic acid loaded hydrophobic aerogels has week hydrogen bonding with

benzoic acid. Therefore, the peak in this region remains almost similar without any change. In

both cases the amorphized benzoic acid is stabilized.

Hence, the overall crystallization process is influenced by the adsorptive properties of aerogels

(prior adsorbed solute) ‘adsorptive crystallization’. Based on these observations of benzoic acid

loading in aerogels, further adsorption of another polar volatile solute 1-menthol on aerogels is

investigated to study the strength of solute - surface interactions on the stabilization of loaded

solute in aerogels.


76

4.2.2 Adsorption of 1-menthol in silica aerogels

In this work, adsorption of 1-menthol is conducted from supercritical CO2 at concentrations far

away from saturation in both the aerogels, thus, only adsorption of menthol occurs. Thermal

analysis of the loaded aerogels is performed to investigate the strength of interactions of menthol

with surface of aerogels. From now onwards, 1-menthol will be addressed as menthol in this

section.

4.2.2.1 Menthol adsorption in silica aerogels

Adsorption of menthol in silica aerogels is studied by the static adsorption method described in

section 3.4.2. It takes 60 minutes to reach the equilibrium adsorption in our experiments, as

measured online at 50°C and 100 bar using a magnetic suspension balance (see appendix).

Menthol, which contains a hydroxyl group, is expected to cross associate with the hydroxyl

groups in the hydrophobic and hydrophilic aerogels via hydrogen bonding. Figure 28 shows the

effect of the aerogel’s functional groups on the loading of menthol for five different menthol -

CO2 solutions ranging from 0.05 and 1 wt% menthol, respectively. The adsorption data are fit to


KC

KCQQ m

a+

=1

Equation 16

Where Qa is the amount of solute (in mol) adsorbed per unit weight of adsorbent (in g), Qm is the

maximum loading (mol / g), C is the concentration of adsorbate in the bulk phase (mol / kg

solution), and K is the Langmuir constant. As expected, the hydrophilic aerogel exhibits a higher

loading of menthol in all cases compared to the hydrophobic aerogel, due to hydrogen bonds with

the free –OH groups of the silica aerogels similar to benzoic acid experiments.


77

Figure 28. Impact of hydrophobicity on the adsorption of menthol on silica aerogels from

menthol - CO2 solutions at 50°C (sample ID: A13).

It should be noted that even with low bulk menthol concentrations in CO2 significantly high

loadings are observed, implying a very high affinity of menthol to the aerogel surface. However,

there are no apparent structural or transparency differences between the virgin and loaded

aerogels (Figure 29). The small cracks in the loaded aerogels appear when a part of the aerogel is

removed for analysis. Crystalline menthol is not observed by visual or microscopical observation.

Menthol is homogenously disturbed in the aerogels, as confirmed by measuring the concentration

of menthol from different sections of the aerogels.


78

Figure 29. Physical appearance of pure aerogel, hydrophilic aerogel loaded with 23.3 wt%

menthol, and hydrophobic aerogel loaded with 7.2 wt% menthol (sample ID: A13).

Although microscopic changes in the aerogels are not observed, changes in the internal aerogel

structure can be revealed by BET analysis. BET analysis of following samples is performed

(sample ID: A13). Loaded aerogels are not pretreated thermally prior to BET analysis to avoid

any menthol loss due to sublimation under heat and vacuum. Overall sample loss after the

analysis was less than 2 wt%. For comparison, the weight loss of pure menthol subjected to the

same vacuum / temperature conditions is at least 4 times larger, which highlights the exceptional

stability of adsorbed menthol on the silica aerogels even under vacuum.

Figure 30 shows that the maxima of the pore size distributions (PSD) are shifted to higher pore

diameters after loading with menthol. To check if this shift could result from the collapse of

small pores during the pressure release of CO2, a control experiment without any additive was

performed. There were no changes in the PSD or pore volume (see appendix). It is reasonable to

assume that during the loading of the aerogel the smallest pores are filled with solute as first and

cannot be accessed by nitrogen during the BET analysis.


79

Figure 30. A) Pore size distributions of virgin (open circles) and 23.3 wt% menthol - loaded

(open squares) hydrophilic aerogels, B) virgin (open circles) and 7.2 wt% menthol - loaded (open

squares) hydrophobic aerogels.


80

Table 13 shows the BET data of loaded and not pretreated virgin aerogels. Their surface area and

pore volume are much lower than those for virgin aerogels. The decrease in pore volume is due to

both surface coverage of the menthol and by filling or blocking of small pores in the loaded

aerogels. The differences in the surface areas and pore volumes of virgin and loaded aerogels

provide information that can be used to estimate amount of the adsorbed solute alternatively.

However, these calculations are nontrivial as they require reliable methods to determine

accurately the influence of adsorbate - surface group interactions on the molecular conformation

and density of the adsorbed compound and were not performed in this work.

Table 13. Comparison of the structural properties of pure and menthol - loaded aerogels. The

samples were not thermally treated.

Aerogel samples Surface area

(m2 / g)

Pore volume

(cm3 / g)

Average pore

diameter (nm)

Hydrophilic aerogel (no pretreatment) 967.0 4.6 19.0

Hydrophilic aerogel loaded with

23.3 wt% menthol 541.0 3.0 11.0

Hydrophobic aerogel (no

pretreatment)

798.0 3.8 19.1

Hydrophobic aerogel loaded with 7.2

wt% menthol

557.0 2.8 10.1

The aggregate state of the solute in the aerogel was analyzed by DSC. Figure 31A and B show

that both hydrophilic and hydrophobic menthol - loaded aerogels do not exhibit any melting

peaks, suggesting that the adsorbed menthol is amorphous. In contrast, a physical mixture

containing menthol and hydrophilic aerogel at the same concentration as in the loaded sample

exhibits an endothermic melting peak at 41°C, which is close to the normal melting point of pure

menthol.


81

Figure 31. Verification of the physical state of menthol loading into hydrophobic and hydrophilic

aerogels. A) DSC curves for a hydrophilic aerogel loaded with 23.3 wt% menthol (solid line) and


82

a 22.5 wt% menthol - hydrophilic aerogel physical mixture (open circles), B) DSC curves for a

hydrophobic aerogel loaded with 7.2 wt% menthol (solid line) and a 7.0 wt% menthol -

hydrophobic aerogel physical mixture (open circles). The heating rate is 10°C / min in all cases.

The difference in the melting temperatures of pure menthol and menthol - aerogel physical

mixture might be due to interactions of menthol with aerogel occurring during mixing or to

interactions with liquid menthol in the presence of hydrophilic aerogel during the DSC analysis.

The menthol - hydrophobic aerogel physical mixture exhibits an endothermic peak at 43°C. No

shift is observed since there are less interactions of menthol with the hydrophobic aerogel.

4.2.2.2 TGA of menthol - loaded, hydrophilic aerogels

After DSC measurements, TGA analysis is used to determine the thermal release profile of the

adsorbed solute and to reveal the strength of menthol - aerogel interactions. Figure 32 shows the

TGA curves of pure hydrophilic aerogel along with those for hydrophilic aerogel loaded with

23.3 wt% menthol. The samples are heated from 20 to 600°C with the heating rate of 10°C / min

in several intervals and at the end of each heating interval the temperature is held constant for 60

min. Both loaded and virgin aerogels remain physically stable up to 600°C, but some shrinkage is

observed at temperatures starting at 500°C. At 60°C the weight loss of the unloaded hydrophilic

aerogels is 8 wt% due to water desorption (TGA combined with Mass Spectroscopy shows the

presence of water). Surprisingly, the corresponding weight loss of the menthol - loaded

hydrophilic aerogel is approximately four times smaller which suggests that menthol occupies the

adsorption sites normally taken by water. Even though water is removed by pretreatment of both

aerogels some water is adsorbed during the time the aerogel is transferred to the autoclave.

Furthermore, technical grade CO2, which contain approximately 300 ppm water, is used and the

autoclave is not evacuated before charging with CO2 to avoid loss of the volatile additive. Hence,

it is not unexpected that some water loss from the aerogels is observed during the TGA

experiments.


83

Figure 32. TGA curves of 23.3 wt% menthol - loaded hydrophilic aerogel and virgin one.

For better understanding of loss menthol, Figure 33 is recasted from Figure 32 so that only the

loss of menthol and not the total loss (menthol + water) is presented. For comparison the

corresponding curve for pure menthol is shown. Pure menthol sublimes completely within 55

minutes at 60°C. In contrast, adsorbed menthol is released from the hydrophilic aerogel only after

the temperature reaches 400°C. Thus, the release of menthol is delayed due to the strong

hydrogen bonding of menthol with the free –OH groups on the hydrophilic aerogels.


84

Figure 33. Comparison of the thermal release of menthol from a 23.3 wt% menthol - loaded

hydrophilic aerogel (open squares) to that from pure methanol (open circles); menthol loss is

calculated as: 100*[(wt(t) - wt(t0)) / wt(t0)], where wt(t0)= weight of menthol in aerogel at

time=0, wt(t)= weight of menthol in aerogel at time = t.

Figure 34 shows the TGA / MS analysis of menthol - loaded hydrophilic aerogel, where the

effluent gases from the TGA are analyzed by a mass spectrometer. The release takes place in 2

steps: the menthol weakly bounded with the bulk –OH groups is released at temperatures up to

200°C, whereas the release of menthol strongly adsorbed on free surface –OH groups occurs at a

much higher temperature of 400°C.


85

Figure 34. Release profile of menthol from a 23.3 wt% menthol - loaded hydrophilic aerogel

(open squares). Any weight loss due to water desorption has already been taken into account for

the data shown here. The ramp rate is 10°C / minute to 600°C.

4.2.2.3 TGA of menthol - loaded, hydrophobic aerogels

TGA analysis of menthol loaded hydrophobic aerogel is performed. Menthol loss from a

hydrophobic aerogel is shown in Figure 35, where the weight loss due to water removal is taken


86

into account similar to the correction made to the menthol - loaded hydrophilic aerogel data

shown in Figure 33. Pure menthol rapidly sublimes as the temperature is ramped to 60 °C,

whereas the release of menthol from the hydrophobic aerogel is delayed. The rate of menthol

release is accelerated as the temperature is ramped from 60 to 150 °C. It should be noted that the

virgin hydrophobic aerogel and the menthol - loaded hydrophobic aerogel each lost 2 wt% water

at 60°C, whereas the weight loss of the virgin hydrophilic aerogel was four times greater than

that of the menthol - loaded hydrophilic aerogel (see Figure 32). This large difference in water

loading reflects the significant difference in the concentration of free –OH groups in the two

types of aerogels. Virtually all of the menthol is released from the hydrophobic aerogel at 150 °C

while close to 50% of the menthol remains loaded in the hydrophilic aerogel at the same

conditions.

Figure 35. Comparison of the release of menthol from the hydrophilic (23.3 wt% menthol, open

squares) and hydrophobic (7.2 wt% menthol open triangles) loaded aerogels and from pure

menthol (open circles).


87

This observation suggests that a desired temperature - release profile of an adsorbate can be

designed by partial functionalization of the internal surfaces of a hydrophilic aerogel. Citral

aroma is loaded on menthol loaded aerogels. Similar release behavior is observed with citral and

menthol (see appendix). Thus multiple flavors can be loaded on aerogels and released can be also

tailored.

4.2.2.4 IR analysis of loaded menthol

Infra - Red analysis of the pure hydrophilic aerogel, pure menthol, and loaded menthol in

hydrophilic aerogel is performed. Figure 36 shows that there is no change in the characteristic

peaks of menthol in the loaded state in the pores of aerogels. The region 3600 - 3200 cm -1 is the

region where water is adsorbed on hydroxyl groups on pure hydrophilic aerogel. In the case of

menthol loaded aerogel this peak is sharpened due to the hydrogen bonding between OH groups

and menthol. Due to hydrogen bonding of menthol with aerogel surface reduced the back bone

vibration menthol-aerogel compared to pure menthol.

Pure menthol

Menthol loaded aerogel

Hydrophilic aerogel

Pure menthol

Menthol loaded aerogel

Hydrophilic aerogel

Figure 36. IR spectrum of the pure menthol, hydrophilic aerogel, menthol loaded aerogels.


88

Figure 37. IR spectrum of the pure menthol, hydrophobic aerogel, menthol loaded aerogels.

Thus, the loaded amorphous menthol is stabilized in the pores of silica aerogel. Similar analysis

is done for hydrophobic aerogel samples. Hydrophobic aerogel contains less hydroxyl groups, as

a result, in the region (3600 - 3200 cm -1) the peak is not so wide rather sharp (see Figure 37).

The menthol loaded hydrophobic aerogel has week hydrogen bonding with menthol. Therefore,

the peak in this region remains almost similar without any change.

4.2.2.5 Long - term stability of menthol at room temperature

Figure 38 shows that more than 96 wt% of the loaded menthol is retained in both of the aerogels

left in an open container at room temperature for a five - week period. The slight variation in the

data is likely due to the adsorption of moisture from the surrounding air. These data suggest that

only the weakly bound menthol is released given that similar results were obtained with

hydrophobic and hydrophilic aerogels with different loading levels. It also shows that release of

menthol from both types of aerogels is similar at room temperature.


89

Figure 38. Weight loss of menthol from both hydrophilic and hydrophobic aerogels in an open

container at room temperature (22°C): 23.3 wt% menthol - loaded hydrophilic aerogel (open

squares) and 7.2 wt% menthol - loaded hydrophobic aerogel (open triangles).

This study shows that the internal surface area of an aerogel can be chemically tailored to control

the storage and release of highly volatile compounds. The chemical structure of the adsorbate

also has a significant effect on the release characteristics especially when the aerogel contains a

large amount of free surface hydroxyl groups available for interaction with the adsorbate. The

thermal release of menthol, revealed a two step release process where weakly bound adsorbate

that interacts with the bulk -OH groups is released first at temperatures greater than the adsorbate

normal melting temperature, and strongly bound adsorbate that interacts with free -OH groups is

released at very high temperatures, sometimes in excess of 400°C. These release temperatures

can be adjusted by changing the hydrophilic and hydrophobic content of the aerogel. Generally, it

can be concluded that menthol (volatile compound) can be stabilized in silica aerogels even at

elevated temperatures in excess of several hundred degrees in some cases.


90

It would be of scientific interest to further compare and contrast the observations made with both

polar solutes (benzoic acid and menthol) with the adsorption and crystallization on different type

of solutes in aerogels. Therefore, in the following section moderately polar substances

(naphthalene and 2-Methoxy pyrazine) are chosen to study these effects.


91

4.3 Adsorption and crystallization of moderately polar solutes in silica

aerogels

4.3.1 Adsorption and crystallization of naphthalene in silica aerogels

To further understand the influence of nature of solute on ‘adsorptive crystallization’ adsorption

and crystallization of moderately polar substance naphthalene in silica aerogels is conducted. The

effect of structural properties of aerogels and their adsorptive capacity on the crystallization

process is investigated. Similar experimental procedure of benzoic acid is used to conduct

adsorption and crystallization of naphthalene in aerogels.

4.3.1.1 Excess binary adsorption of CO2 + naphthalene in aerogels

To study the effect of adsorbed solute on crystallization adsorption of CO2 and naphthalene +

CO2 on hydrophilic and hydrophobic aerogels is conducted using Magnetic Suspension Balance

(MSB). Optimized conditions of benzoic acid experiments are used for conducting naphthalene

adsorption experiments. Naphthalene has 10 - 15 times higher solubility in CO2 at high pressures

compared to benzoic acid, as a result, huge amount of naphthalene need to placed inside the MSB

cell to have saturated conditions. Apart from this, low small temperature would create a big

difference in solubility of naphthalene at high pressures. As a result, the dissolved naphthalene in

CO2 crystallizes inside the MSB cell and in moving part of the recycle pump which limits the

adsorption measurements. This is a critical problem for measuring adsorption isotherms of highly

soluble solid solutes using MSB. Here, only the successful and reproducible results of adsorption

isotherms are presented. Figure 39 shows the adsorption isotherms of CO2 and naphthalene +

CO2 on aerogels. Binary excess adsorption isotherm of naphthalene + CO2 measured showed

similar trend like in the case of benzoic acid. These binary excess isotherms cannot be

recalculated to absolute isotherms due the adsorption of two substances. Hydrophilic aerogel

adsorbed higher amount of naphthalene + CO2 at all conditions compared to hydrophobic

aerogels. Lower amount of naphthalene + CO2 is adsorbed on both aerogels compared to benzoic

acid + CO2 adsorption at similar conditions. In the case of hydrophobic aerogel binary excess

adsorption isotherms measurements, the values near to critical region couldn’t be measured due


92

to large fluctuation in temperature. Also low adsorption is observed compared to pure CO2 due to

competitive adsorption of CO2 and naphthalene on the nonpolar surface of aerogels. MSB is

flushed with pure CO2 at the end of the experiment but it was not possible to avoid crystallization

of naphthalene due to its high solubility in CO2. It is not possible to calculate the single

component adsorption from the binary data, still one can conclude that higher amount of

naphthalene is adsorbed in hydrophilic aerogel compared to hydrophobic aerogels at all

pressures.

Figure 39. Excess adsorption isotherms of pure CO2 and naphthalene + CO2 on aerogels:

Conditions: 58°C, 1 - 350 bar, ρaerogel = 0.12 g / cm3 (sample ID: A 14)

4.3.1.2 Static adsorption of naphthalene in aerogels

Additionally to MSB measurements, static adsorption of naphthalene is done similar to benzoic

acid adsorption measurements. These experiments will give us more insight into the strength of


93

naphthalene - aerogel surface interactions. Loading is conducted at very low bulk concentration

of naphthalene in CO2, thus, it is expected that only adsorption of naphthalene occurs.

Figure 40 shows the adsorption of naphthalene in hydrophilic and hydrophobic aerogels at

pressures 110 to 300 bar. High adsorption of naphthalene even at these low bulk concentrations

indicates the strong affinity of naphthalene to the aerogel surface. The adsorption data are fit to


KC

KCQQ m

a+

=1

Equation 17

Where Qa is the amount of additive (in mol) adsorbed per unit weight of adsorbent (in g), Qm is

the maximum loading (mmol / g), C is the concentration of adsorbate in the bulk phase (mol / kg

solution), and K is the Langmuir constant. The parameters determined for the naphthalene -

hydrophilic aerogel system are Qm = 10.41 (mmol / g), and K = 0.05, and for the naphthalene -

hydrophobic aerogel system are Qm = 3.82 (mmol / g), and K = 0.103. Similar to benzoic acid

loadings, hydrophilic aerogels adsorbed higher amount of naphthalene compared to hydrophobic

aerogels. Naphthalene is normally considered as nonpolar, but due to presence of quadrapole

moment it exhibits moderately polar nature. Due to the difference in the type of interaction of

naphthalene with aerogel surface, there exists a difference in adsorption amounts between

hydrophilic and hydrophobic aerogels. Interestingly, even at these low bulk concentrations of

naphthalene in CO2 the difference in loading between aerogels exists which shows the strength of

aerogel surface - naphthalene interactions compared to solvent solubility holding strength. One

can expect this difference in loading will further influence the crystallization process by CO-

RESS.


94

0.0

0.2

0.4

0.6

0.8

1.0

1.2

0.0 0.5 1.0 1.5 2.0

Cbenzoic acid in CO2, mol/kg

Qa

,mm

ol/

g

Hydrophilic aerogel

Langmuir, Qm=10.41,K=0.05

Hydrophobic aerogel

Langmuir, Qm=3.82,K=0.11

Figure 40. Loading of naphthalene in silica aerogels at different bulk concentration of

naphthalene in CO2. Conditions: ρhydrophilic aerogel = 0.10 g / cm3, ρhydrophobic aerogel = 0.12 g / cm3,

58°C, P = 110 to 300 bar, time of loading = 24 hours, slow pressure release (ca. 30 minutes).

4.3.1.3 Crystallization of naphthalene in silica aerogels by CO-RESS

Crystallization was performed at different conditions and the aerogel samples loaded with

naphthalene from the saturated solutions are shown in Figure 41. The release rate of supercritical

solution was optimized in this case. As, it is expected that the size of naphthalene particles

formed inside the aerogel depends on aerogel’s properties and on the pressure release rate since

the nucleation process and particle growth are driven by supersaturation inside the pores. It is

known that a higher supersaturation is needed to initiate the nucleation in small pores in

comparison to bulk solutions [163]. Analogous to crystallization in gels, heterogeneous

nucleation is likely to take place in aerogels [164].

The particle size decreases with increasing release rate. In case of the slow pressure release, large

crystals and their agglomerates (up to 1 - 2 mm) are formed leading to the destruction of the


95

aerogel pores (Figure 41 a, b), whereas fast pressure release results in the particles of 20 nm - 5

µm range (Figure 41c).

Figure 41. Light microscopic picture of aerogel loaded with naphthalene (background of different

color). Experimental conditions: a) 40°C, 0.01 bar / s, b) 40°C, 0.1 bar / s, c) 45°C, 1.2 bar/s, d)

58°C, 350 bar/s.

However, in case of the fast pressure release considerable shrinkage of aerogels occurred due to

the CO2 condensation in the pores as a result of the Joule - Thompson effect. Aerogels were

broken in several pieces. To avoid this, pressure was released stepwise as shown in the Figure 42:

in step 1 the pressure is decreased rapidly from 220 to 90 bar (0.45 seconds) to create

supersaturation which is needed to initialize the crystallization; after that the pressure is released

slowly to 1 bar in step 2 (within 200 - 300 seconds). A typical pressure and temperature profiles

for the first and second step of such pressure release is shown in Figure 42. For all the solutes

during CO-RESS process this strategy of two step pressure release is used.


96

Figure 42. Pressure release during the crystallization experiment - stepwise release. a) step 1: fast

release of pressure, b) step 2: slow release of pressure.

The pressure fluctuations are due to the decrease of temperature with the decrease of pressure due

to well known Joule - Thompson effect. This procedure avoids shrinkage and to obtain

monolithic aerogel filled with naphthalene particles in 20 nm - 5 µm range (Figure 41d). One

sees, that the size of naphthalene particles is larger than the size of aerogel pores in all cases.

An interesting effect has been observed during the crystallization of naphthalene in hydrophilic

aerogels. When the pressure release was performed slowly, transparent aerogels filled with white

naphthalene particles were obtained. However, after the fast stepwise pressure release (as shown

in Figure 42), hydrophilic aerogels exhibit a blue color after the crystallization. This effect is

reproducible and the hydrophilic samples stay blue in color for several weeks. The corresponding

samples are shown in Figure 43. Several reasons could explain this fact. Firstly, different light

scattering of the aerogel samples could occur due to the difference in particle size of naphthalene.

Secondly, interactions between naphthalene and the aerogel matrix could vary due to the


97

presence of different functional groups (OH and OR). The different arrangement of naphthalene

molecules on silica aerogel surface could occur as well.

Figure 43. Aerogel samples after naphthalene crystallization in comparison to the initial aerogel.

Crystallization conditions: 58°C, 220 bar, 16 wt% of bulk naphthalene in CO2, ρaerogel = 0.16 g /

cm3.

Figure 44 shows the dependence of aerogel loading on the bulk concentration of naphthalene in

CO2. In loaded aerogels samples both adsorbed and crystallized naphthalene should be present.

The experimental method used in this work (extraction with an organic solvent) allows detecting

the overall loading (adsorbed + crystallized naphthalene) only. Rather high loadings (up to 45

wt%) have been achieved. As expected, the loading increases with the increasing naphthalene

concentration, but in all cases hydrophilic aerogels exhibit higher loading than hydrophobic ones.

Similar behavior is observed for different density aerogels (see appendix). The loadings are less

compared to benzoic acid loadings in aerogels at similar concentration due to less interactions of

naphthalene with the surface of aerogels.


98

0

5

10

15

20

25

30

35

40

45

50

2 4 8 11 16

wt (%) of naphthalene in bulk CO2

wt (%

) of

nap

hth

ale

ne

in a

ero

gel Hydrophilic aerogel

Hydrophobic aerogel

Figure 44. Loading of naphthalene on silica aerogels for varying initial naphthalene concentration

in bulk CO2 for a fixed aerogel density of 0.21 g / cm3, conditions: T = 58°C , P = 210 - 110 bar.

The same effect was observed for aerogels having different densities as shown in Figure 45. The

loading decreases with the increasing aerogel density due to decrease of the pore volume.

However, the hydrophilic aerogels exhibit a higher concentration of naphthalene compared to

hydrophobic ones. Similar trend is observed for varying bulk concentration of naphthalene in

CO2 (see appendix). Similar to benzoic acid, in this case (naphthalene) adsorbed solute

influenced the crystallization of naphthalene in the pores of aerogels.


99

0

10

20

30

40

50

60

0.12 0.16 0.21Density / g/cm3

wt

(%)

of

nap

hth

ale

ne

in a

ero

ge

l

Hydrophilic aerogelHydrophobic aerogel

Figure 45. Naphthalene concentration in hydrophilic and hydrophobic aerogels with different

densities. Crystallization conditions: initial bulk concentration of naphthalene in CO2 is 16 wt%;

T = 58°C, Pinitial = 210 bar. The standard deviation in determining of naphthalene concentration is

± 0.29 wt% (sample ID: A14 - A16).

4.3.1.4 Crystallinity of naphthalene in aerogels

The crystallinity of naphthalene particles in silica aerogels was characterized using X - ray

diffraction (XRD). Typical XRD peak of naphthalene is at an angle of 12 Theta for the plane 001

[165]. It is clearly seen from that silica aerogels itself are completely amorphous since no peak

appears in its XRD pattern, whereas a characteristic peak indicating the crystallites is seen in case

of loaded aerogels. The position of the peak is the same for hydrophilic and hydrophobic loaded

aerogels and it does not depend on the density of the aerogel as well. Thus, it can be conclude

that at least a part of naphthalene is present in aerogels in the crystalline state.


100

Figure 46. XRD results of the pure aerogel (pure silica aerogels) and naphthalene loaded

aerogels (all other curves).

Further, DSC experiments of loaded aerogel samples are performed to analyze the physical state

of loaded naphthalene. DSC curves of the hydrophilic and hydrophobic aerogels loaded with

naphthalene are shown in Figure 47. Pure naphthalene shows an endothermic peak typical for

crystalline substances at the melting point of 80.1°C (Tm of pure naphthalene = 80 - 81°C). In

case of naphthalene implemented in the pores of silica aerogels, similar endothermic peak are

observed confirming the crystalline state as shown before by XRD analysis. However, the

melting point is shifted to 60.8°C in the hydrophilic aerogels and to 63.8°C in hydrophobic ones.

Larger melting point depression in case of hydrophilic aerogels indicates either the smaller

particle size or the stronger interaction of naphthalene with the matrix. Therefore, naphthalene

precipitated inside the pores of aerogels leads to partly crystalline form in the aerogels. The

physical state of the solute can be adjusted based on solute - surface interactions. In the case of

benzoic acid loaded in the aerogels similar trend of melting point temperature shift was observed

and loaded benzoic acid was in the amorphous form due to stronger interactions.


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Figure 47. DSC curves for pure naphthalene and naphthalene loaded in hydrophilic and

hydrophobic aerogels (heating rate 10°C / min).

4.3.1.5 IR analysis of loaded naphthalene

Figure 48. IR spectrum of the pure naphthalene, hydrophilic aerogel, naphthalene loaded

aerogels.


102

Figure 49. IR spectrum of the pure naphthalene, hydrophobic aerogel, naphthalene loaded

aerogels.

Infra - Red analysis of the pure hydrophilic aerogel, pure naphthalene, and loaded naphthalene in


peaks of naphthalene in the loaded state in the pores of aerogels. The region 3600 - 3200 cm - 1 is

the region where water is adsorbed on hydroxyl groups on pure hydrophilic aerogel. In the case

of naphthalene loaded aerogel this peak is sharpened due to the hydrogen bonding between OH

groups and naphthalene. Thus, the loaded naphthalene is stabilized in the pores of silica aerogel

even though partially amorphized after the loading. Similar analysis is done for hydrophobic

aerogel samples. Hydrophobic aerogel contains less hydroxyl groups, as a result, in the region

(3600 - 3200 cm - 1) the peak is not so wide rather sharp (see Figure 49). The naphthalene loaded

hydrophobic aerogel has week hydrogen bonding with naphthalene. Therefore, the peak in this

region remains almost similar without any change. In both cases the partly crystalline

naphthalene is observed.

Similar to benzoic acid, adsorbed naphthalene (moderately polar solute) influenced the

crystallization process. High adsorption of naphthalene in hydrophilic aerogels leads to more

effective particle formation in their pores compared to hydrophobic aerogels. Contrary to benzoic

acid loading, due to less interactions of naphthalene with both aerogels, the loaded solute

particles remained crystalline. Therefore, the loading itself and the properties of the resulting


103

microparticles are influenced by the structural and surface properties of silica aerogels, in

particular by their adsorption capacity. Hence, the crystallization process is influenced by a prior

adsorption of naphthalene on the surface of the aerogels similar to the benzoic acid loading in

aerogels. Further adsorption of moderately polar liquid solute (volatile) 2-Methoxy pyrazine is

adsorbed in silica aerogels to study solute - surface interactions and stabilization on the surface of

aerogels.


104

4.3.2 Adsorption of 2-Methoxy pyrazine in silica aerogels

4.3.2.1 Methoxy pyrazine adsorption in aerogels

To study the influence of moderately polar volatile solute on loading in aerogels, adsorption of 2-

Methoxy pyrazine, a liquid at room conditions, is conducted in both silica aerogels by static

adsorption method. In the complete section 2-Methoxy pyrazine will be addressed as methoxy

pyrazine. Loading is performed at concentration of methoxy pyrazine - CO2 of 0.3 wt%, which is

well below the saturation conditions [166]. The hydrophilic aerogels exhibited higher loadings

with methoxy pyrazine (9.8 wt%) compared to the hydrophobic aerogels (3.3 wt%), although the

absolute loading levels are lower than those obtained with benzoic acid, naphthalene, and

menthol. Once again there were no macroscopic changes in appearance of the aerogel after

loading (see Figure 50). Menthol loading is referred for comparison as it the volatile solute

loaded on aerogels in this work.

Figure 50. Comparison of pictures of pure aerogel, 2-Methoxy pyrazine loaded hydrophilic and

hydrophobic aerogels (sample ID: A13).

Contrary to results with menthol (see section 4.2.2), the weight of the pyrazine - loaded aerogels

decreased by 5 wt% before and after BET analysis suggesting weaker interactions of the pyrazine

with the aerogel matrix.


105

Figure 51. A) Pore size distributions of virgin (open circles) and 9.8 wt% methoxy pyrazine -

loaded hydrophilic aerogels (open squares), B) virgin (open circles) and 3.3 wt% methoxy

pyrazine - loaded hydrophobic aerogels (open squares).


106

Figure 51 A and B show the same trend with the shift of the pore size distributions to higher

values although the effect is less pronounced compared to the results with menthol. With

pyrazine, where the interactions with the matrix are weaker, the adsorption in the pores takes

place more equally in large and small pores, so that not so many small pores are blocked.

Figure 51 the surface areas and pore volumes of the methoxy pyrazine - loaded aerogels decrease

by 10 - 30 % compared to virgin aerogels not thermally pretreated (see Table 14).

Table 14. Comparison of the structural properties of pure and methoxy pyrazine - loaded

aerogels. The samples were not thermally treated in this instance.

Surface area

(m2 / g)

Pore volume

(cm3 / g)

Average pore

diameter (nm)

Hydrophilic aerogel (no pretreatment) 967.0 4.6 19.0

Hydrophilic aerogel loaded with 9.8

wt% methoxy pyrazine

647.0 3.9 11.2

Hydrophobic aerogel (no pretreatment) 798.0 3.8 19.1

Hydrophobic aerogel loaded with 3.3

wt% methoxy pyrazine

715.0 3.3 9.1

4.3.2.2 TGA analysis of methoxy pyrazine loaded aerogels

After BET measurements, TGA analysis is used to determine the thermal release profile of the

adsorbed solute and to reveal the strength of methoxy pyrazine - aerogel interactions. Figure 52

shows the TGA curves of pure hydrophilic aerogel along with those for hydrophilic aerogel

loaded with 9.8 wt% methoxy pyrazine. The samples are heated from 20 to 450°C with the

heating rate of 10°C / min in several intervals and at the end of each heating interval the

temperature is held constant for 45 min.


107

75

80

85

90

95

100

0 100 200 300 400

Time (minutes)

Ae

rog

el

we

igh

t lo

ss (

wt%

)

0

50

100

150

200

250

300

350

400

450

500

Te

mp

era

ture

(°C

)

Virgin hydrophilic aerogel

Hydrophilic aerogel

+methoxy pyrazine (9.8 wt%)

Figure 52. TGA curves of 9.8 wt% methoxy pyrazine - loaded hydrophilic aerogel and virgin

one.

For better understanding of loss methoxy pyrazine, Figure 53 is recasted from Figure 52 so that

only the loss of methoxy pyrazine and not the total loss (methoxy pyrazine + water) is presented.

For comparison the corresponding curve for pure methoxy pyrazine is shown. Pure methoxy

pyrazine sublimes completely within 55 minutes at 60°C. Figure 53 shows the TGA curves of

methoxy pyrazine loss from methoxy pyrazine - loaded hydrophilic aerogels and methoxy

pyrazine - loaded hydrophobic aerogels. Pure methoxy pyrazine is vaporized completely by the

time the temperature reaches 60°C, which is very close to the normal boiling point of methoxy

pyrazine. Again, a two - step release profile is observed. The pyrazine is initially released rapidly

from the aerogel as the temperature is increased to 60 °C, the release slows considerably as the

temperature is increase further to 200 °C, and then the release increases to a rapid rate as the

temperature is increased further.

In contrast, the release of pyrazine from the hydrophobic aerogel is rapid and virtually constant

up to a temperature of 100°C due to the lack of free –OH groups available to interact with the


108

pyrazine. It is noted that the high loading of liquid methoxy pyrazine and its enhanced stability

suggests that aerogels can be effective carriers for volatile liquids, such as liquid pharmaceuticals,

that are thermally labile. Further on the stabilization of thermally labile flavors for food industry

can be also achieved by adsorption on aerogels. In this case the flavor can be released at desired

temperatures.

Figure 53. Comparison of the TGA curve for 9.8 wt% methoxy pyrazine - loaded hydrophilic

aerogel (open squares) to the curves for 3.3 wt% methoxy pyrazine - loaded hydrophobic aerogel

(open triangles) and pure methoxy pyrazine (open circles).

4.3.2.3 Long - term stability of methoxy pyrazine at room temperature

Figure 54 shows that more than 96 wt% of the loaded methoxy pyrazine retained in both of the

aerogels left in an open container at room temperature for a five - week period. The slight

variation in the data is likely due to the adsorption of moisture from the surrounding air. These


109

data suggest that only the weakly bound adsorbate is released given that similar results were

obtained with hydrophobic and hydrophilic aerogels with different loading levels.

Figure 54. Weight loss of menthol from both hydrophilic and hydrophobic aerogels in an open

container at room temperature: 9.8 wt% methoxy pyrazine - loaded hydrophilic aerogel (open

squares) and 3.3 wt% methoxy pyrazine - loaded hydrophobic aerogel (open triangles).

The thermal release of methoxy pyrazine, also revealed a two step release process where weakly

bound adsorbate that interacts with the bulk -OH groups is released first at temperatures greater

than the adsorbate normal melting temperature, and strongly bound adsorbate that interacts with

free -OH groups is released at very high temperatures. Thus, the release temperatures can be

adjusted by changing the hydrophilic and hydrophobic content of the aerogel.

Further, these investigations are extended to nonploar solutes (octacosane and dodecane) to study

the effect of nonpolar behavior of the solutes on adsorptive crystallization. The following section

reports the study of adsorption and crystallization of non polar solutes in aerogels.


110

4.4 Adsorption and crystallization of nonpolar solutes in silica aerogels

4.4.1 Adsorption and crystallization of octacosane in silica aerogels

Furthermore, to validate the influence of adsorbed solute on crystallization and physical state of

loaded solute, a non polar substance octacosane is adsorbed and crystallized in both silica

aerogels. Octacosane is fully saturated alkane and it is likely to have no strong interactions with

the aerogel surface. Based on our finding with menthol, benzoic acid, and naphthalene loading in

aerogels, it is expected that octacosane would readily form crystals in the pores of aerogels and

even the amount of substance crystallized inside pores of both aerogels should be almost similar

in hydrophilic and hydrophobic aerogels.

Similar to benzoic acid and naphthalene, adsorption is carried out to study the effect of solute

adsorbed on the crystallization amounts. Adsorption of octacosane in aerogels is conducted at

very low concentrations far away from saturated conditions.

0

0.1

0.2

0.3

0 0.01 0.02 0.03 0.04 0.05

Bulk concentration of octacosane in CO2 (wt%)

Loadin

g in a

ero

gels

(w

t%)

Hydrophilic hydrophobic

Figure 55. Adsorption of octacosane in aerogels at 50°C in both aerogels (ρhydrophilic aeogel = 0.10 g

/ cm3, ρhydrophobic aerogel = 0.11 g / cm3) (sample ID: A17 see Table 8).


111

Figure 55 shows the adsorption of octacosane for varying bulk concentrations in aerogels. Very

low adsorption of octacosane in silica aerogels is observed around 0.3 wt% which is in the error

limit of the experiments. There is nearly no difference in loading between hydrophilic and

hydrophobic aerogels. This is because the solute octacosane is saturated and shows nearly no

interactions with the functional group on the surface of aerogels. But the adsorption of benzoic

acid and naphthalene at these concentration were around 15 - 20 wt% loading in aerogels. This

shows that the adsorption is also a strong function of surface functional group of solute.

Later, crystallization of octacosane is conducted in aerogels by CO-RESS process. The loading of

octacosane in both aerogels is performed at temperature 50°C where solid - supercritical state

exist (phase diagram). Figure 56 shows a typical octacosane loaded particles in the hydrophilic

aerogels. The loading of octacosane in hydrophilic and hydrophobic aerogels at saturated bulk

concentrations of octacosane in CO2 is shown in the Figure 57.

Figure 56. Light microscopic picture of octacosane loaded hydrophilic aerogel. Conditions: 50°C,

P: 160 bar, ρaerogel = 0.10 g / cm3.

As expected, there is nearly no difference in the crystallized amount in hydrophilic and

hydrophobic aerogels, due to low and equal amount of octacosane adsorption in both aerogels.

Hence, these results once again conform that the adsorbed solute acts as kind of nuclei or active

surface for crystallization process in the pores of the carrier. The loading of octacosane on both

aerogels is very low in comparison to benzoic acid, menthol, and naphthalene at these conditions.


112

0

0.5

1

1.5

2

0.75 0.29

Bulk concentration of octacosane in CO2 (wt%)

wt%

of

octa

co

san

e i

n a

ero

gels


Figure 57. Crystallization of octacosane in aerogels by CO-RESS. Conditions: 50°C, P: 260 and

160 bar, ρhydrophilic aerogel = 0.10 g / cm3, ρhydrophobic aerogel = 0.11 g / cm3.

Octacosane loaded aerogel samples are characterized using DSC to determine the state of loaded

substance inside the pores of both aerogels. Contrary to benzoic acid and naphthalene loaded

aerogels, octacosane loaded aerogels (1.5 wt%) readily exhibited an endothermic peak as shown

in the Figure 58. The melting point depression occurred in the case of loaded octacosane

compared to pure octacosane (Tm = 59 - 60°C) which is known from the work of naphthalene

and benzoic acid crystallization in aerogels. However, the melting point is shifted to 56°C (only 4

°C shift) in both aerogels compared to pure octacosane 60°C, whereas in the case of benzoic acid

or naphthalene melting point temperature depression of 5 to 40 °C is observed in hydrophilic and

hydrophobic aerogel. There is no difference in melting point temperature (depression) in between

octacosane - hydrophilic and octacosane - hydrophobic aerogels. These results bring two aspects,

first, less interactions or nearly no interaction of octacosane with aerogel surface which results in

the crystallized form of octacosane even with low concentration of 1.5wt%. Second, there is

nearly no different type of interactions with hydrophilic or hydrophobic aerogels, as a result,

there is no difference in the melting temperature shift in both aerogels. The loaded dodecane in

the aerogels remained in the adsorbed state without any sign of crystallization.


113

20 30 40 50 60 70 80 90-0.4

-0.3

-0.2

DS

C (

mW

/mg

)

Temperature (°C)

Hydrophilic aerogel + octacosane (~1.5 wt%)

Hydrophobic aerogel + octacosane (~1.5 wt%)

Pure octacosane Tm= 60°C

Figure 58. DSC curves of octacosane loaded hydrophilic and hydrophobic aerogels (1.5 wt%)

and the heating rate is 10°C / min.

4.4.1.1 IR analysis of loaded octacosane

Infra - Red analysis of the pure hydrophilic aerogel, pure octacosane, and loaded octacosane in


peaks of octacosane in the loaded state in the pores of aerogels. The region 3600 - 3200 cm -1 is

the region where water is adsorbed on hydroxyl groups on pure hydrophilic aerogel. In the case

of octacosane loaded aerogels, the peak in this region remained similar to pure aerogel as there is

nearly no interactions of octacosane with –OH groups of aerogels.


114

Figure 59. IR spectrum of the pure octacosane, hydrophilic aerogel, octacosane loaded aerogels.

Figure 60. IR spectrum of the pure octacosane, hydrophobic aerogel, octacosane loaded aerogels.

Thus, the crystallized octacosane is stabilized in the pores of silica aerogel. Similar analysis is

done for hydrophobic aerogel samples. Hydrophobic aerogel contains less hydroxyl groups; as a

result, in the region (3600 - 3200 cm -1) the peak is not so wide rather sharp (see Figure 60). The

octacosane loaded in hydrophobic aerogel has no interaction with the surface of aerogel.

Therefore, the peak in this region remains almost similar without any change. Thus, in both the

cases the crystallized octacosane is obtained.


115

As observed, loading of octacosane was very low in comparison to other solutes studied at

similar concentrations. Thus, to study the influence of molecular size of nonpolar solute on the

loading of aerogels, dodecane is chosen. The following section reports the adsorption of

dodecane.

4.4.2 Adsorption of dodecane in silica aerogels

To further elucidate the influence of molecular weight on the amount of loading in aerogels, a

low molecular weight non - polar solute dodecane (liquid) adsorption is conducted on the same

aerogels at similar conditions of octacosane. Figure 61 shows the loading of dodecane at different

bulk concentration of dodecane - CO2. Dodecane loading is relatively high in comparison to the

loading of octacosane in aerogels at similar concentrations (Figure 57). There is no difference in

the amount of loading between hydrophilic aerogel and hydrophobic aerogel similar to

octacosane. This shows that the molecular weight (or molecular size) plays a significant role in

the case of loading of non polar additives. Lower the molecular weight of non - polar solute

higher is the amount of loading in aerogels. Aerogel structure remained stable even though

loaded with liquid additives similar to 2-Methoxy pyrazine loadings in aerogels.

0

2

4

6

8

10

0.79 0.28

Bulk concentration of dodecane in CO2 (wt%)

Do

dec

an

e in

aero

gels

(w

t%)



116

Figure 61. Loading of dodecane in aerogels. Conditions: 50°C, P: 258 and 161 bar, ρhydrophilic aeogel

= 0.10 g / cm3, ρhydrophobic aerogel = 0.11 g / cm3.

Thus, based on the experiments of adsorption and crystallization of solutes, (menthol, benzoic

acid, and octacosane) it can be concluded the adsorbed solute influences the overall

crystallization process. Therefore, this process of crystallization can be called as ‘adsorptive

crystallization’. A generalized table is reported in the next section to further summarize all the

adsorptive crystallization results with the various solutes.


117

4.5 Summarized table of loadings, physical form of loaded solutes

Table 15 summarizes loading of all solid solutes in hydrophilic and hydrophobic aerogels. Some

general conclusions can be drawn from the table. Higher amount of loadings are observed with

polar solutes (menthol, benzoic acid, naphthalene, ibuprofen) in hydrophilic aerogels (polar

surface). By adjusting the amount of polar surface function groups (degree of hydrophobicity) the

loading can be tailored. Not only the surface properties of the aerogel influence the loading but

also the surface groups on the solutes. The physical state of solutes can be adjusted based on type

of function groups on the aerogels. Stronger interactions of solute with aerogel surface leads to

amorphous form in the loaded state, example: menthol, benzoic acid. Weak interactions lead to

partly crystalline or complete crystalline form example: naphthalene, octacosane.

Benzoic acid remains amorphous upto 25 wt% in hydrophilic aerogels, and up to 15wt% in

hydrophobic aerogels. Moderately week interactions lead to partly crystalline form (naphthalene).

That is upto 15wt% of loadings of naphthalene remains amorphous and after these loadings,

solute loaded start to exhibit the crystalline form in the loaded state. Very week interactions lead

to crystalline form (octacosane), i.e., from 1.5 wt% onwards the crystalline state of loaded solute

in aerogels is observed. Thus, these threshold loading values observed can be used to control the

physical state of solute desired.

Apart from this, in the following section, this work is extended to other porous carrier. MCM41

were chosen as the carrier due to their adjustable properties and its structural stability in

dissolution medium. Drug ibuprofen was loaded in MCM41 and the release rate of the drug in the

liquid dissolution medium was conducted to investigate the influence of surface - solute

interactions.


118

Table 15. Comparison of the solute loading, physical state of various solutes in hydrophilic and hydrophobic aerogels.

Solute loaded in

Aerogels Type of solute Type of aerogel

Bulk Solute -

CO2 (wt%)

solute -

loading in

aerogels

(wt%)

nature of loaded

solute in aerogel

Pure solute

Tm (°C)

Tm (°C) solute

loaded in

aerogels

Hydrophilic 30.0

partly crystalline

(only at high

loadings)

80 Benzoic acid

Hydrophobic

2.50

21.0 partly crystalline

122

100

Hydrophilic 23.0 amorphous - - Menthol

Polar

Hydrophobic 0.26

7.0 amorphous 45

- -

Hydrophilic 12.0 Large crystalline

part 70

Naphthalene

Hydrophobic

2.00

9.0 Large crystalline

part

81

75

Hydrophilic 9.8 - - - - 2-Methoxy pyrazine

Moderately

polar

Hydrophobic 0.10

3.5 - - - -

- -

Hydrophilic 1.5 crystalline 59 Octacosane

Hydrophobic 0.79

1.5 crystalline 60

59

Hydrophilic 8.8 - - - - Dodecane

Non polar

Hydrophobic 0.78

8.2 - - - 9.8

- -


119

4.6 Extension of the method to other porous carriers: comparison of drug

release profiles

The main application of the aerogels targeted in this work is the drug delivery. In the previous

work of our research group the release of different drugs from silica aerogels was studied [167,

168, 169]. Release rates of drugs from aerogels were compared to those of pure crystalline drugs,

but no comparison with other porous carriers was done. Thus, in this part of the present work, it

is extended with the loading methods (adsorption from supercritical CO2) used for aerogels to

other porous carriers. Ibuprofen is chosen as a drug, since the loading and release in silica

aerogels are investigated in detail, and these data will be used as a reference for the comparison.

MCM 41 (Mobile Crystalline Material) is used as an alternative porous carrier. It is also a

mesoporous material, however, contrary to aerogels, it is stable in liquids, so that the drug would

rather be released by diffusion. In last decades MCM41 was investigated by many researchers as

a carrier for drug delivery [170, 171, 172, 173], Maria Vallet - Regi [173] has shown the

influence of pore size on the release rate of ibuprofen loaded in MCM41. The loading is

performed by conventional method: drug is dissolved in a solvent, then MCM41 is placed inside

this solution and adsorption from the liquid phase takes place [174, 175]. Adsorption from

supercritical CO2 was not described. Therefore, in this work ibuprofen is adsorbed on MCM41

from CO2 solutions. The influence of physical properties and drug - carrier interactions on the

loading and release rate are investigated.

4.6.1 Synthesis of the MCM - 41 materials

Synthesis of MCM41 was done at lab of chemical reaction technology (group of Prof.

Schwieger). The samples are used for loading in the given form. The synthesis method is

described here. Synthesis of MCM41 with silica to alumina ratios of 50 and ∞ denoted as

MCM41-1 and MCM41-2 respectively, these samples were made by the procedure from Kresge

et al. [176] and Beck et al. [177].The typical procedure for MCM41-1 is given below:


120

(A): 1.06 g of CTAB was added to 18.0 g of distilled water and stirred for 10 minutes; then 3.0 g

of TEOS was added. (B): 0.20 g of NaOH, 0.01 g of sodium aluminate was added to 5.71 g of

water and stirred for 10 minutes.(B) was added to (A) and stirred for 45 min.

In the case of synthesis of MCM41-2, the aluminium source (sodium aluminate) was omitted.

Finally, the synthesis mixtures had the following chemical composition: 0.17 Na2O: SiO2: X

Al2O3: 0.20 CTAB: 100 H2O where X = 0.02 for MCM41-1 and 0 for MCM41-2. The pH of the

synthesized mixtures was found to be alkaline (around 12.9) and mixture was transferred to 50 ml

stainless steel autoclave and heated to 100°C for 24 h under static conditions. Then the mixture

was filtered, washed with water and dried at 100°C for 24h. The obtained MCM41 materials

were calcined at 550°C for 9h to remove the surfactant Cetyltrimethylammoniumbromide

(CTAB). CTAB contains functional groups methyl and bromide groups.

4.6.2 Characterization of MCM41

Powder X ray - Diffraction patterns of MCM41s were recorded on a Philips X - ray

Diffractometer using CuKα radiation. All the samples were scanned in the 2theta range of 1 –50°

at a scan rate of 2 min - 1. The XRD patterns of the as synthesised and calcined MCM41 materials

are shown in Figure 62, which are in agreement with the standard MCM - 41 materials. MCM41

samples labled in this text are as follows: MCM41-1 (Si / Al = 50, with template), MCM41-1 cal

(Si / Al = 50, calcined (template removed)), MCM41-2 (Si / Al = ∞, with template), MCM41 - 2

cal (Si / Al =∞, calcined (template removed)).


121

2 3 4 5 6 7 8 9 10

MCM-41-2 cal

MCM-41-2

MCM-41-1 Cal

In

ten

sity (

a.u

)

2 Theta(degrees)

MCM-41-1

Figure 62. XRD patterns of as - synthesised and calcined MCM41-1 and MCM41-2 which are in

agreement with characteristic patterns for MCM41 materials.

4.6.3 Loading of MCM41s with Ibuprofen

Table 16 summarizes the amount of ibuprofen loading in different MCM41 from supercritical

CO2. MCM41-1 is loaded with higher amount of ibuprofen 20 wt%, whereas, MCM41-1 cal is

loaded with less amount of ibuprofen due to presence of template in the pores of MCM41-1. The

loading is higher because - COOH groups on ibuprofen interacts with methyl and bromide groups

of the template. Even though MCM41 - cal has higher surface area and pore volume compared to

MCM41-1, low loading of ibuprofen is observed. Hence, it clearly indicates that the loading is

influenced by the surface function groups of the carrier, .i.e., MCM41 (in this case template) -

ibuprofen interactions, which is also the case of loading of solutes in silica aerogel as observed in

this work. Similar trend is exhibited with MCM41-2 and MCM41-2 cal samples. MCM41-2 is

loaded with higher amount of ibuprofen compared to MCM41-2 cal due to the presence of the

template. The loading of ibuprofen MCM41-2 is lower compared to MCM41-1, as the pores are

completely filled with template as a result there is very low surface area (Table 16).


122

Table 16. Selected properties of MCM41s, and corresponding Ibuprofen loading.

Loading of ibuprofen in MCM41s, at 0.56 wt% ibuprofen - CO2

MCM41

samples

surface area

(m2 / g)

Pore volume

(cc / g)

Average pore

diameter (nm)

wt% loading

in MCM41

1 MCM41-1 289 0.20 2.8 20.6

2 MCM41-1 cal 883 0.52 2.4 13.5

3 MCM41-2 4.8 0.03 <0.5 8.2

4 MCM41-2 cal 655 0.35 2.2 7.2

4.6.4 Release of ibuprofen from MCM41 in the phosphate buffer solution

The release of ibuprofen from loaded MCM41s was performed in buffer medium (ph=7.2) at 37

°C to investigate the influence of physical properties and interaction of ibuprofen - MCM41 on

release of ibuprofen. The stability of MCM41 in this medium makes its possible to study these

influences which were not possible with aerogels where pore structure collapses [29]. Figure 63

shows the release rates of ibuprofen loaded on different MCM41s with time in comparison to

silica aerogels [29]. Pure crystalline ibuprofen release rates are compared with the release rates

of loaded ibuprofen in MCM41s. Ibuprofen is released at slower rate from MCM41-1 compared

to MCM41-1 cal. This is due to stronger interactions of ibuprofen with the template of MCM41-

1. The release rate of ibuprofen from MCM41-1 cal is almost similar to the release rate of

ibuprofen from hydrophilic and hydrophobic aerogels. Release rate of ibuprofen from MCM41-2

is faster compared to MCM41-2 cal, again due to the strong interaction of ibuprofen with the

template of the MCM41-2. In both MCM41-1 cal, MCM41-2 cal template is removed and they

contain some hydroxyl groups on the surface of the walls. In general, the release rate of loaded

ibuprofen is higher compared to pure ibuprofen except with MCM41-2. The release rate from

MCM41-1 (Si / Al =50) is higher compared to MCM41-2 (Si / Al = ∞), this might be due to

stronger interactions of ibuprofen due to presence of only silica in MCM41-2.


123

0

20

40

60

80

100

0 50 100 150 200 250 300 350 400 450 500

Time/ minutes

% r

ele

ase

of

ibu

pro

fen

MCM41-1

MCM41-1 cal

MCM41-2

MCM41-2 cal

Hydrophilic aerogel+ibp

Hydrophobic aerogel+Ibp

Pure ibuprofen

A)

0

20

40

60

80

100

0 200 400 600 800 1000 1200 1400 1600

Time/ minutes

% r

ele

as

e o

f ib

up

rofe

n

MCM41-1

MCM41-1 cal

MCM41-2

MCM41-2 cal

Hydrophilic aerogel+ibp

Hydrophobic aerogel+Ibp

Pure ibuprofen

B)

Figure 63. Release rate of pure Ibuprofen, loaded Ibuprofen from MCM41s in ph=7.2 buffet at

37°C. A) Release of ibuprofen for first 500 minutes B) release of ibuprofen for 1600 minutes.

Hence, by adjusting the type and amount of surface functional groups inside the pores of MCM41

material one can adjust the release rate and amount of loading of the drug. Thus, the

bioavailability of the drug can be enhanced by using a specific carrier. These finding can have


124

potential application in pharmaceutical industry in future as the bioavailability still a key and

challenging issue.

Conclusions

125

5. Conclusions

In this work ‘adsorptive crystallization’ is firstly introduced as a method to load mesoporous

carrier (aerogels, MCMs, Trispor glass) with organic substances to control the particle size and

crystallinity by adjusting the adsorptive properties of the carrier.

It was shown that the adsorptive properties of aerogels play a major role for crystallization

process: strong interactions between the aerogel surface and solutes lead to amorphous

precipitate, whereas weak interactions result in crystals inside the aerogel pores. The strength of

the interactions was quantified by TGA analysis. To investigate this, solutes of different polarity

were chosen. In case of strong adsorption (combination of polar solute - polar aerogel surface)

the absolute loading is very high and amorphous precipitate is preferably formed. This behavior

was observed for menthol and benzoic acid: upto 40 wt% amorphous menthol and 31 wt% of

amorphous benzoic acid could be stabilized in the hydrophilic (polar) aerogels. When the same

substances were adsorbed on less polar aerogels (esterified ones), benzoic acid tends to

crystallize at lower concentrations (above 15 wt% loading solute tends to be crystalline). Higher

melting point temperature shift of the loaded solutes was observed with polar aerogels compared

to less polar aerogels. Maximum melting point temperature depression of 40°C was observed.

Higher adsorption of solute prior to crystallization was observed with polar solute - polar aerogel

compared to polar solute - less polar aerogel. The adsorbed solute acted as kind of nuclei or

active surface during crystallization (CO-RESS process) i.e., higher amount of solute is

crystallized in pores of polar aerogel compared to less polar aerogel due to the presence of large

amount of the adsorbed solute.

In the case of loading of moderately polar solute in aerogels (combination of moderately polar

solute - polar aerogel surface), the absolute loading was lower compared to polar solutes, and the

solute starts to get crystalline with low loading. This is due to less interactions of naphthalene

with aerogel surface in comparison to benzoic acid. This behavior was observed for naphthalene:

upto 20 wt% amorphous form of naphthalene can be stabilized. When the same was adsorbed in

less polar aerogel, naphthalene tends to crystallize at low concentrations (from 12 wt% loading

solute tends to be crystalline). Higher melting point temperature shift of loaded naphthalene was

Conclusions

126

observed with polar aerogel compared to less polar aerogel. Maximum melting point temperature

depression of 10°C was observed. Similar to benzoic acid, higher amount of naphthalene was

adsorbed in polar aerogels compared to less polar aerogels, as a result, higher amount of

naphthalene was precipitated in the pores of aerogel during CO-RESS process. Similar trend was

observed with 2-Methoxy pyrazine adsorption experiments.

As for the loading of nonpolar solutes, (combination of nonpolar solute – polar aerogel surface)

the absolute loading of solute was very low compared with polar and moderately polar solutes

and crystalline form is obtained. This behavior was observed for octacosane: above 1.5 wt%

loading octacosane tends to be crystalline. When the same substance was loaded in less polar

aerogel same loading is observed due to similar type of interactions. Similar melting point

temperature shift of the loaded octacosane was observed in both aerogels. Melting point

depression of 3°C was observed. Due to less adsorbed octacosane on the surface of aerogel, less

amount of octacosane is precipitated in the pores of aerogel. Similar trend was observed in

adsorption of experiments of dodecane. Higher loading of dodecane was observed compared to

octacosane in aerogels.

Loading of solutes was extended to other porous carriers (MCMs, Zeolites, Trispor glass). In this

case also the adsorbed solutes influenced the precipitation of solutes in the pores. The

precipitated solute remained amorphous due to the stronger interaction with the surface of the

carrier (all these carriers have polar surface). Carrier surface - solute interaction influenced the

release rate of loaded solute in liquid medium. It was shown that the release rate can be tailored

by adjusting the adsorptive properties of the carrier. In the case of loaded volatile solutes

(menthol and methoxy pyrazine), it was shown that the thermal release of solute can be

controlled by adjusting the strength of carrier surface - solute interactions. Therefore, in this

work, it is shown with various solutes and carriers that the adsorptive properties of carrier

influence the loading and physical state of the solutes / drugs, therefore, process is termed as

‘adsorptive crystallization’. Hence, the results reported here provide an insight into the

application of porous carriers (silica aerogels, MCM41) as delivery / storage devices with

potential applications in the food, drug, flavors, catalysis (catalyst support) and other allied

industries.

Outlook

127

6. Outlook

These results forms a strong basis to further investigate adsorptive crystallization in

biodegradable gels made of natural materials like starch, algae, etc. Industrial and combined

academic interest would give much progress in this direction to further apply the engineering

theories to improve the drug delivery systems. Moreover, in the case of high pressure adsorption

isotherms reported in this work, which are the first efforts made to measure solid solute

adsorption on adsorbent, but, still modifications are needed in the MSB experimental setup to

measure the bulk concentration of solutes in-situ, like use of Optical Raman Spectrometry.

Strong thermodynamical modeling efforts are necessary to separate the solid solute and solvent

from binary adsorption isotherms.

Appendix

128

7. Appendix

7.1 GC column data

GC: HP 5890 Series II Autosampler, Packed column: fused silica, L= 12m, inner diameter = 0.22

mm, Film thickness = 0.1mm, Max temperature= 410°C.

7.2 Stability of aerogels at CO-RESS process

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2

0 20 40 60 80 100

pore diameter (nm)

po

re v

olu

me

cc/n

m/g

Pure aerogel

Aerogel pretreated with CO2 (250 to 1 bar)

Figure 64. Stability of pure aerogels physical structure during CO-RESS process

7.3 Multiple additive loading

Menthol loaded aerogel is loaded with Citral using SCF. The release rate of the loaded additives

is studied using TGA / MS. The Similar behavior is observed with citral loaded hydrophilic

Appendix

129

aerogels, first weekly bound citral is released along with menthol, and later, at high temperatures

strongly bound menthol and citral is released. Thus, multiple aromas can be release

simultaneously.

0 10 20 30 40 50 60

80

85

90

95

100

1E-13

1E-12

1E-11

0

100

200

300

400

500

600

T(°

C)

Ion

ch

arg

e

We

ight

loss

Time (minutes)

citral

menthol

7.4 Benzoic acid results

Loadings in aerogels at varying benzoic acid - CO2 bulk concentrations

Appendix

130

0

5

10

15

20

25

30

0.64 0.83 1.49 2.52

Bulk concentration of benzoic acid in CO2 (%)

wt

(%)

of

ben

zo

ic a

cid

in

aero

gel



concentration in bulk CO2 for a fixed aerogel density of 0.07 g / cm3, conditions: T = 65°C , P =

270 - 140 bar.

0

5

10

15

20

25

30

35

0.64 0.83 1.49 2.52

Bulk concentration of benzoic acid in CO2 (wt%)

wt

(%)

of

be

nzo

ic a

cid

in

aero

ge

l


Appendix

131


concentration in bulk CO2 for a fixed aerogel density of 0.18 g / cm3, conditions: T = 65°C , P =

270 - 140 bar.

0

5

10

15

20

25

30

0.07 0.10 0.15 0.18

ρρρρ (g/cm3)

wt

(%)

of

ben

zo

ic a

cid

in

aero

ge

l




is 1.48 wt%; T = 65.2°C, Pinitial = 228 bar. Stepwise pressure release: a) 228 - 90 bar: fast release

b) 90 - 1 bar: slow release.

Appendix

132

0

5

10

15

20

25

30

0.07 0.10 0.15 0.18

ρρρρ (g/cm3)

wt

(%)

of

be

nzo

ic a

cid

in

aero

ge

l






Loading at varying bulk density of aerogels for fixed benzoic acid - CO2 bulk

concentrations

Appendix

133

0

5

10

15

20

25

30

35

0.07 0.10 0.15 0.18

ρρρρ (g/cm3)

wt

(%)

of

ben

zo

ic a

cid

in

aero

ge

l






0.00 25 26 27 28 29 3010

15

20

25

Po

re d

iam

ate

r (n

m)

Wt% loading of benzoic acid in aerogel

Evacuated hydrophilic aerogel

Benzoic acid loaded hydrophilic aerogel

A)

25 26 27 28 29 302

3

4

5

6

B)

wt (%

) of ben

zo

ic a

cid

in

ev

ac

uate

d a

ero

ge

l



Appendix

134

0.00 25 26 27 28 29 303

4

5

6

7

8

9

10

C) Wt% loading of benzoic acid in aerogel

Po

re v

olu

me (

cm

3/g

)



0.00 25 26 27 28 29 3010

15

20

25

Po

re d

iam

ate

r (n

m)




D)

Figure 70. BET data of benzoic acid loaded and evacuated hydrophilic aerogel (80 - 100°C)

evacuation temperature) A) Surface area of loaded and evacuated aerogels along with virgin

aerogel B) wt% of benzoic acid remained in hydrophilic aerogel after evacuation under vacuum

along with virgin aerogel C) Pore volume of loaded and evacuated aerogels along with virgin

aerogel D) average pore diameter of loaded and evacuated aerogels. It should be noted that virgin

aerogel correspond to 0 wt% loading.

7.5 MSB adsorption

Appendix

135

0.0

0.1

0.1

0.2

0.2

0.3

0.3

0.4

0.4

0.5

0.5

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9

Density (g/cm3)

Ex

cess

am

ou

nt

ad

so

rbed

(g

)/

(g)

aero

ge

l

- Langmuir isotherm (R2 = 0.97, ρads =0.911)

- Toth isotherm (R2 = 0.98, ρads = 0.922 )

Figure 71. Langmuir fitting of CO2 experimental adsorption date in aerogels.

0

0.5

1

1.5

2

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Density/ g/cm3

g o

f C

O2/

g o

f su

bsta

nce

Hydrophilic aerogel at 40°C

Hydrophobic aerogel at 40°C

Activated carbon at 40°C

Hydrophilic 60 °C

Hydrophobic 60 °C

Figure 72. Absolute adsorption isotherm of pure CO2 adsorption on aerogels at 41° and 60°C

(activate carbon as reference).

Appendix

136

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0 0.2 0.4 0.6 0.8

Density /g/cm3

Ex

ces

s a

ds

orp

tio

n (

g)/

(g)

aero

gel

Pure CO2-Hydrophiilic

Pure CO2-Hydrophobic

BA+ CO2-Hydrophiilic

BA+ CO2-Hydrophobic

Figure 73. Excess adsorption data of CO2, CO2 + benzoic acid on aerogels (conditions: ρaerogel =

.15 g / cm3, T = 65°C, P = 1 - 350 bar).

7.6 Menthol results

Figure 74. Typical time required for equilibrium adsorption in the case of menthol.

Appendix

137

The time required to reach adsorption equilibrium for menthol and pyrazine is measured in-situ

using magnetic suspension balance (MSB). Adsorption equilibrium is reached in 60 minutes.

Figure A shows the signal from MSB as a function of time, indicating that a constant value is

reached after 60 minutes. In the graph, the weight appears to decrease with increasing time, but,

this is due to adsorption of menthol and thus the relative buoyancy acting on the sample

increases, as a result the signal shows a decrease.

7.7 Naphthalene results

Loadings in aerogels at varying naphthalene - CO2 bulk concentrations

0

10

20

30

40

50

2 4 8 11 16

Wt% of naphthalene in bulk CO2

wt%

of

nap

hth

ale

ne in

ae

rogel

Hydrophilic aerogel

Hydrophobic aerogel

Figure 75. Loading of naphthalene on silica aerogels for varying initial naphthalene concentration

in bulk CO2 for a fixed aerogel density of 0.090 g / cm3, conditions: T = 58°C , P = 210 - 110 bar.

Appendix

138

Loading at varying bulk density of aerogels for fixed naphthalene - CO2 bulk concentrations

0

2

4

6

8

10

12

14

16

0.1190 0.1550 0.2120

Density / g/cm3

wt%

of

naphth

ale

ne in a

ero

gel

Hydrophilic aerogel

Hydrophobic aerogel


densities. Crystallization conditions: initial bulk concentration of naphthalene in CO2 is 2wt%; T

= 58°C, Pinitial = 110 bar

0

5

10

15

20

25

30

35

40

45

0.1190 0.1550 0.2120

Density / g/cm3

wt%

of

na

ph

tha

len

e in

ae

rog

el

Hydrophilic aerogel

Hydrophobic aerogel

Appendix

139


densities. Crystallization conditions: initial bulk concentration of naphthalene in CO2 is 8wt%; T

= 58°C, Pinitial = 165 bar.

0

5

10

15

20

25

30

35

40

45

50

0.0900 0.1190 0.2120

Density / g/cm3

wt%

of

nap

hth

ale

ne

in a

ero

ge

l

Hydrophilic aerogel

Hydrophobic aerogel


densities. Crystallization conditions: initial bulk concentration of naphthalene in CO2 is 11wt%;

T = 58°C, Pinitial = 180 bar.

7.8 Error Propagation

All measurement contains errors due to instrument limitations, experimental limitations, and

human errors [178]. In general errors are classified as systematic errors and random errors.

Systematic errors in the experimental data occurs due to imperfect calibration, bad observation,

interference of surrounding conditions during measurements. Systematic errors need to subtracted

it cannot be removed by repeating the experiments. Random errors are the errors due to

unpredictable fluctuations in the measurement of data or interpretation of the data. This error can

be calculated by repeating the experiments and using statistical methods like standard deviation

and average deviation to account for the error. Both systematic error and random error will

propagate in the analysis of experimental data which need to be corrected and mentioned.

Appendix

140

In all the experiments systematic errors is reduced by correct calibration of all the instruments

and random error is measured by repeating the experiments for minimum of three times and the

average of the experimental data is taken to account for the error. Some general methods for

determining errors are as follows:

General statistical method where average and standard deviation (SD) of measured data is

calculated.

tsmeasuremenofnumbertheisnwheren

XXXX n ,

).......( 21 +++=

XXaXXaXXawheren

aaaSD nn

n −=−=−=+++

= ,....,,.....

2211

222

21

Error determination in measuring bulk density of aerogels

Error in the bulk density of the aerogel is determined by the following method. Bulk density of

cylindrical aerogel samples is defined as )/( samplesamplebulk Vm=ρ , The equations used to calculate

the error is as follows:

22

2

3

3

2

2

2

2

1

1

3332211 )()()()(

)(

∆+

∆=

∆

=

∆+

∆+

∆=

∆

∆±⋅∆±⋅∆±=

∆±=

V

V

x

x

V

m

l

l

l

l

l

l

V

V

cmllllllVVolume

gxxmmass

bulk

bulk

sample

sample

bulk

sample

sample

ρ

ρ

ρ

Appendix

141

In this way the error is defined for the measured data of bulk density in aerogels.

Cumulative errors

Cummulative error account for independent errors from different sources which propagates and

so called error propagation. Pentz et al. [178] have described the general rules to estimate these

errors. Errors estimation from two independent experiments A and B are discussed. Assuming,

the error from A is ∆A and from b is ∆B which are combined to give the result X which has an

error of ∆X. The following are the equation used to estimate the cumulative error emerging from

the independent experiments.

( ) ( )22BAX

BAX

BAX∆+∆=∆→

−=

+=

22

∆+

∆=

∆→

=

=

B

B

A

A

X

X

BAX

ABX

A

An

X

XAX n ∆

=∆

→=

A

A

X

Xalsobut

AkXkAX

∆=

∆

∆=∆→=

( ) ( )22BAkX

BkAX

BkAX∆+∆=∆→

−=

+=

22

∆+

∆=

∆→

=

=

B

B

A

A

X

X

BAkX

kABX

A

An

X

XkAX

n ∆=

∆→=

References

142

8. References

[1] Kistler, S.S, Aerogel synthesis, J of Phys. chem. 34, (1932), 52.

[2] Peri, J.B. Infrared study of OH and NH2 groups on the surface of a dry silica aerogel . J Phy

Chem-US. 70 (1966), 2937.

[3] Nicoloan, G.A., Contribution on l'etude des aerogels des silica. University of Lyon. 1968.

[4] Teichner, S.J., Nicoloan, G.A., US 3,672,833; Method of preparing inorganic aerogels (1972).

[5] Poelz, G., Aerogel cherenkov counters at DESY. Nucl Inst. Meth A. 248, (1986), 118.

[6] Henning, S., Svensson, L., A production facility for silica [7631-86-9] aerogel has been set up

in Lund. Aerogel is now produced in large quantities with the n of 1.03 and 1.05. The standard

block size is 18 × 18 × 3 cm3. Phys Scripta. 23, (1981), 697.

[7] Tewari, P.H., Hunt, A.J., Lofftus, K.D., Ambient-temperature supercritical drying of

transparent silica aerogels. Mater. Lett. 3, (1985), 363.

[8] Pierre, A.C., Pajonk, G.M., Chemistry of aerogels and their applications. Chem Rev. 102,

(2002), 4243.

[9] Fricke, J., Tillotson, T., Aerogels: Production, characterization, and applications. Thin Solid

Films. 297, (1997), 212.

[10] Hunt, A.J., Ayers, M.R., Cao, W., Aerogel composites using chemical vapor infiltration. J

Non-Cryst Solids. 185, (1995), 227.

[11] Hunt, A., Ayers, M. Silica Aerogels. http: //eande.lbl.gov/ECS/aerogels/satoc.htm. 1 Nov. 2

A.D.

[12] Hüsing, N., Schubert, U., Aerogels - Airy Materials: Chemistry, Structure, and Properties.

Angew Chem Int. Edit. 37, (1998), 22.

[13] Moner-Girona, M., Roig, A., Molins, E., Llibre, J., Sol-Gel route to direct formation of silica

aerogel microparticles using supercritical solvents. J Sol-Gel Sci. Techn. 26, (2003), 645.

[14]Soleimani, A., Dorcheh, M.H. Abbasi, Silica aerogel; synthesis, properties and

characterization. J Mater. process. Tech. 199, (2008), 10.

[15] Brinker, C.J., Scherer, G.W. Sol - Gel - Science. Academic Press: New York, 1990.

[16] Brinker, C.J., Keefer, K.D., Schaefer, D.W., Ashley C.S. Sol-gel transition in simple

silicates. J Non-Cryst Solids. 48, (1982), 47.

References

143

[17] Pajonk, G.M., some applications of silica aerogels. Colld. Poly. Sci. 281, (2003), 637.

[18] Tillotson, T.M., Hrubesh, L.W. Transparent ultralow-density silica aerogels prepared by a

two-step sol-gel process. J Non-Cryst Solids. 145, (1992), 44.

[19] Smirnova, I., Arlt, W., Synthesis of silica aerogels: Influence of the supercritical CO2 on the

sol-gel process. J Sol-Gel Sci Techn. 28, (2003), 175.

[20] Smirnova, I., Synthesis of silica aerogels and their applications as a drug delivery system.

Institut für Verfahrenstechnik, Fachgebiet Thermodynamik und thermische Trennverfahren,

Technische Universität Berlin. 2002.

[21] Pauthe, M., Despetis, F., Phalippou, J., Hydrophobic silica CO2 aerogels. J Non-Cryst

Solids. 155, (1993), 110.

[22] Schwertfeger, F., Frank, D., Schmidt, M. Hydrophobic waterglass based aerogels without

solvent exchange or supercritical drying. J Non-Cryst Solids. 225, (1998), 24-29.

[23] Venkateswara Rao, V., Wagh, P.B. Preparation and characterization of hydrophobic silica

aerogels. Mater Chem Phys. 53, (1998), 13-18.

[24] Venkateswara rao, A., Kulkarni, M. M., Hydrophobic properties of TMOS / TMES based

silica aerogels, Mater. Res. Bull. 37, (2002), 1667.

[25] Venkateswara rao, A., Einarsrud, E.N, M-A., Effect of precursors, methylation agents and

solvents on the physicochemical properties of silica aerogels prepared by atmospheric pressure

drying method. 22, (2001), 1223.

[26] Lee K.H., Kim S.Y., Yoo K.P. Low-density, hydrophobic aerogels. J Non-Cryst Solids. 186,

(1995), 18.

[27] Scherer, G.W., Adsorption in aerogel networks. J Non-Cryst Solids. 225, (1998), 192.

[28] Scherer, G.W. Characterization of aerogels, Adv. in Coll. Int. Sci., 76, (1998), 321.

[29] Suttiruengwong, S., Silica Aerogels and Hyperbranched polymers as drug delivery dystems,

PhD Thesis, (2005), University of Erlangen Nuremberg, Germany.

[30] Buisson, P., Hernandez, C., Pierre, M., Pierre, A.C. Encapsulation of lipases in aerogels. J

Non-Cryst Solids. 285, (2001), 295.

[31] El Rassy, H., Perrard, A., Pierre, A.C. Application of lipase encapsulated in silica aerogels to

a transesterification reaction in hydrophobic and hydrophilic solvents: Bi-Bi Ping-Pong kinetics.

J of Mol. Cat. B: Enzy. 30, (2004), 137.

References

144

[32] Power, M., Hosticka, B., Black, E., Daitch, C., Norris, P. Aerogels as biosensors: viral

particle detection by bacteria immobilized on large pore aerogel. J Non-Cryst Solids. 285, (2001),

303.

[33] Golob, P., Current status and future perspectives for inert dusts for control of stored product

insects. J Stored Prod Res. 33, (1997), 69.

[34] Yoda, S., Ohtake, K., Takebayashi, Y., Sugeta, T., Sako, T., Preparation of titania-

impregnated silica aerogels and their application to removal of benzene in air, Mater .Chem., 10,

(2000), 2151.

[35] Yao, L. Z., Ye, C. H., Mo, C. M., Cai, W. L., Zhang, L. D., Study of crystallization and

spectral properties of PbS nanocrystals doped in SiO2 aerogel matrix, J. Cryst. Growth, 216 (1),

(2000), 147.

[36] Lorenz, C., Emmerling, A., Fricke, J., Schmidt, T., Hilgendorff, M., L. Spanhel, L., Müller,

G., Aerogels containing strongly photoluminescing zinc oxide nanocrystals, J. Non-Cryst Solids,

238 (1-2), (1998), 1.

[37] Goodwin, T. J., Leppert, V. J., Smith, C. A., Risbu, S. H., Niemeyer, M., Power, P. P., Lee,

H. W. H., and Hrubesh, L. W., Synthesis of nanocrystalline gallium nitride in silica aerogels,

Appl. Phy. Lett., 69 (21), (1996), 3230.

[38]Yoda, S., Tasaka, Y., Uchida, K., Kawai, A., Ohshima, S., Ikazaki, F., SiO2-impregnated

SiO2 aerogels by alcohol supercritical drying with zeolite, J. Non-Cryst. Solids, 225 (1-3),

(1998), 105.

[39] Merzbacher, C. I., Barker, J. G., Long, J. W., Rolison, D. R., Morphology of nanoscale

deposits of ruthenium oxide in silica aerogels, Nanostr. Mater., 12 (1), (1999), 551.

[40] Morley, K .S., Marr, P.C., Webb, P.B., Berry, A. R., Allison, F. J., Moldovan, G., Brown, P.

D., and Howdle, S.M., Clean preparation of nanoparticulate metals in porous supports: A

supercritical route, J. Matter. Chem., 12, (2002), 1898.

[41] Schwertfeger, F., Zimmermann, A., and Krempel, H., US 6,280,744; Use of inorganic

aerogels in pharmacy (2001).

[42] Lee, K., Gould, G., WO02051389; Aerogel Powder Therapeutic Agents (2002).

[43] Hannay, J.B. Hogarth. J., 1879, on the solubility of solids in gases, II Proc. R. Soc. London

29, 484.

References

145

[44] Schneider, G.M., Physiochemical principles of extraction with supercritical gases, W.

Germany, Verlag Chemie, 1978.

[45] Yeob, S. Kiran, E., Formation of polymer particles with supercritical fluids: A review, J. of

Supercrit. Fluids 34, (2005), 287.

[46] McHugh, MA., Krukonis, VJ., Supercritical fluid extraction, principles and practice, 2nd ed.,

Boston, 1994.

[47] Diepen, G.A.M., F.E.C. Scheffer, on critical phenomena of saturated solutions in binary

systems, J. Am. Chem. Soc. 70, 4081, 1948.

[48] Streett, W.B. 1976, phase equilibira in gas mixtures at high pressures Icarus 29,173.

[49] McHugh MA., Krukonis VJ, Supercrit. fluid extraction, principles and practice, 2nd ed.,

Boston, 1994.

[50] Lemert, R.M., Jhonston, K. P. , Solid-Liquid Equlibria in mutlicomponent supercritical fluid

systems, Fluid Phase Equilibria, 45, (1989), 265.

[51] Türk, M., Diefenbacher, A., Upper, G., Phase behavior of organic solid solutes and

supercritical fluids with respect to particle formation process, Chapter 1.6, Supercritical Fluids as

Solvent and Reactions, Edited by G. Brunner, 2004.

[52] Tom, W., Debenedetti, P.G., Particle formation with supercritical fluids—a review, J.

Aerosol Sci. 22, (1991), 555.

[53] Subramaniam, B., Rajewski, R.A., Snavely, K., Pharmaceutical processing with supercritical

carbon dioxide, J. Pharm. Sci. 86, (1997), 885.

[54] Palakodaty, S., York, P., Phase behavioral effects on particle formation processes using

supercritical fluids, Pharm. Res. 16, (1999), 976.

[55] Gorle, B. S.K., Smirnova, I., McHugh, Mark A., Adsorption and thermal release of highly

volatile compounds in silica aerogels, J. Supercrit. Fluids 48 (1), (2009), 85.

[56] Jung, J., Perrut, M. Particle design using supercritical fluids: literature and patent survey, J.


[57] Vemavarapu, C., Matthew J. Mollan, Lodaya. M., Thomas e. Needham,

Design and process aspects of laboratory scale scf particle formation systems, Intern. J. of pharm.

292, (2005), 1.

References

146

[58] Reverchon, E., Adamia, R., Nanomaterials and supercritical fluids, J. Supercrit. Fluids 37.

(2006), 1.

[59] Türk, M., Upper, G., Steurenthaler, M., Hussein, K., Wahl, M. A., Complex formation of

Ibuprofen and β-Cyclodextrin by controlled particle deposition (CPD) using SC-CO2, J.

Supercrit. Fluids, 39(3), (2007), 435.

[60] Tom, W. Debenedetti, P.G., Particle formation with supercritical fluids—a review, J.

Aerosol Sci. 22, (1991), 555.

[61] Subramaniam, B., Rajewski, R.A., Snavely, K., Pharmaceutical processing with supercritical

carbon dioxide, J. Pharm. Sci. 86, (1997), 885.

[62] Palakodaty, S., York, P., Phase behavioral effects on particle formation processes using

supercritical fluids, Pharm. Res. 16, (1999), 976.

[63] Marr, R., Gamse, T., Use of supercritical fluids for different processes including new

developments—a review, Chem. Eng. Proc. 39, (2000), 19.

[64] Cooper, A.I., Polymer synthesis and processing using supercritical carbon dioxide, J. Mater.

Chem. 10, (2000), 207.

[65] Jung, J., Perrut, M., Particle design using supercritical fluids: literature and patent survey, J.


[66] Kompella, U.B., Koushik, K., Preparation of drug delivery systems using supercritical fluid

technology, Crit. Rev. Ther. Drug Carrier Syst. 18, (2001), 173.

[67] Rogers, T.L., Johnston, K.P., Williams III, R.O., Solution-based particle formation of

pharmaceutical powders by supercritical or compressed fluid CO2 and cryogenic spray-freezing

technologies, Drug Dev. Ind. Pharm. 27, (2001), 1003.

[68] Tan, H.S., Borsadia, S., Particle formation using supercritical fluids: pharmaceutical

applications, Expert Opin. Ther. Pat. 11, (2001), 861.

[69] Stanton, L.A., Dehghani, F., Foster, N.R., Improving drug delivery using polymers and

supercritical fluid technology, Aust. J. Chem. 55, (2002), 443.

[70] Ye, X., Wai, C.M., Making nanomaterials in supercritical fluids: a review, J. Chem. Educ.

80, (2003), 198.

[71] Sang-Do Yeob, Erdogan Kiran, Formation of polymer particles with supercritical fluids: A

review, J. of Supercrit. Fluids 34, (2005), 287.

References

147

[72] Watanabe, T. , et al., Int. J. Pharm. 241, (2002), 103.

[73] Huttenrauch, R. Acta Pharm. Technol., Suppl. 6, (1978), 127.

[74] Martin, A., 1993. Physical Pharmacy, fourth ed. Williams & Wilkins, Baltimore

[75] Sekiguchi, K., Obi, N., Studies on absorption of eutectic mixtures. I. A comparison of the

behavior of eutectic mixtures of sulphathiazole and that of ordinary sulphathiazole in man, Chem.

Pharm. Bull. 9, (1961), 866.

[76] Tachibana, T., Nakamura, A., A method for preparing an aqueous colloidal dispersion of

organic materials by using water-soluble polymers: dispersion of beta-carotene by

polyvinylpyrrolidone, Kolloid-Z. Polym. 203, (1965), 130.

[77] Mayersohn, M., Gibaldi, M., New method of solid-state dispersion for increasing dissolution

rates, J. Pharm. Sci. 55, (1966), 1323.

[78] Szabó-Révész, P., O. Laczkovich, R. Ambrus, A. Szts,Z. Aigner,., Protocols for

amorphization of crystalline solids through the application of pharmaceutical technological

processes. Eur. J. Pharm. Sci., 32, S1, (2007), 18.

[79] Hancock, B.C., Zografi, G., Characteristics and significance of the amorphous state in

pharmaceutical systems, J. Pharm Sci. 86, (1997), 1.

[80] Williams, M. L.; Landel, R. F.; Ferry, J. D. J. Am. Chem. Soc. 77, ( 1955), 3701.

[81] Angell, C. A. Proc. Nat. Acad. Sci., U.S.A. 92 (1995,), 6675.

[82] Angell, C. A. Science, 267,( 1995), 1924.

[83] Angell, C. A.; MacFarlane, D. R.; Oguni, M. Ann. N.Y. Acad.Sci. 1986, 484, 241.

[84] Ediger, M. D.; Angell, C. A.; Nagel, S. R. J. Phys. Chem. 100, (1996), 13200.

[85] Hancock, B.C., Shamblin, S., Zografi, G., Pharm. Res. 12, (1995), 799.

[86] Andronis, V., Zografi, G., Pharm. Res. 14, (1997), 410.

[87] Y. Aso, S. Yoshioka, S. Kojima, J. Pharm.Sci. 89, (2000), 408.

[88] Yu, L., Amorphous pharmaceutical solids: preparation, characterization and stabilization.

Adv.Drug Deliver. Rev., 48, (2001), 27.

[89] Crowe, J.H., Carpenter, J.F., Crowe, L.M., The role of vitrification in anhydrobiosis, Annu.

Rev. Physiol. 60, (1998), 73.

References

148

[90] Levine, H., Slade, L., Water as a plasticizer: Physicochemical aspects of low-moisture

polymeric systems. In Water Science Reviews; Franks, F., Ed.; Cambridge University:

Cambridge, (1987), 79.

[91] Bernstein, J., Polymorphism in Molecular Crystals; Clarendon Press: Oxford, 2002.

[92] Rengarajan, G.T., Pankaj, Enke, D., and Steinhart, M., Beiner, M., Manipulating the

Crystalline State of Pharmaceuticals by Nanoconfinement, Nano letters, 7, (2007), 1381.

[93] Rengarajan, G. T., Enke, D., Steinhartc, M., and Beiner, M., Stabilization of the amorphous

state of pharmaceuticals in nanopores, J. Mater. Chem., 18, (2008), 2537.

[94] Prasad, R., Lele, S., Philos. Mag. Lett., 70 (1994), 357 (b) Jackson, C. L., and. McKenna, G.

B., Chem. Mater., 8, (1996), 2128 (c) Alcoutlabi, M., McKenna, G. B. J. Phys. Condens. Matter,

17, (2005), R461.

[95] Sakellariou, P.; Rowe, R. C. J. Macromol. Sci., Pure Appl. Chem. A31, (1994), 1201.

[96] Fukuoka, E.; Makita, M.; Yamamura, S. Chem. Pharm. Bull. 37, (1989), 1047.

[97] Cassel, B., Twombly, B., Rapid DSC determination of polymer crystallinity, Am. Lab,

Jan.(1998), 24.

[98] Tsukushi, I.; Yamamuro, O.; Suga, H. J. Non-Cryst. Solids 175, (1994), 187.

[99] Saleki-Gerhardt, A.; Ahlneck, C.; Zografi, G. Int. J. Pharm. 101, (1994), 237.

[100] Koide, M.; Sato, R.; Komatsu, T.; Matusita, K. Phys. Chem.Glasses 36, (1995), 172.

[101] Parks, G. S.; Barton, L. E.; Spaght, M. E.; Richardson, J. W.Physics 5, (1934), 193.

[102] Hachisuka, H.; Takizawa, H.; Tsujita, Y.; Takizawa, A.; Kinoshita,T. Polymer 32, (1991),

2382.

[103] Oksanen, C. A.; Zografi, G. Pharm. Res. 10, (1993), 791.

[104] Glotin, M.; Mandelkern, L. Colloid Polym. Sci. 260, (1982), 182.

[105] Yoshimura, Y., Kanno, H. J. Solution Chem. 24,( 1995), 633.

[106] Strobl, G. R.; Hagedorn, W. J. Polym. Sci., Polym. Phys. Ed. 16,(1978), 1181.

[107] Holmes, F. T. , Rev. Sci. Inst. 8, (1937), 444.

[108] Clark, J.W. Rev. Sci. Inst. 18, (1948), 915.

[109] Beams, J. W., Rev. Sci. Inst. 21, (1950), 182,

References

149

[110] Dreisbach, F., Lösch, H.W., Harting, P., Highest Pressure Adsorption Equilibria Data:

Measurement with Magnetic Suspension Balance and Analysis with a New Adsorbent /

Adsorbate-Volume, Adsorption, 8, (2002), 95.

[111] Pinni, R., Ottiger, S., Rajendran, A., Stroi, G., Mazzoti, M., Reliable measurements of

near-critical adsorption by gravimetric method, Adsorption, 12, (2006), 393.

[112] Staudt, R., Saller, G., Tomalla, M., Keller, J.U., A note of gravimetric measurements of gas

adsorption equilibria, Ber. Bunsenges. Phys. Chem. 97, (1993), 99.

[113] Humayun, R. Tomasko, D.L., High-Resolution Adsorption Isotherms of Supercritical

Carbon Dioxide on Activated Carbon, AIChE, 46, (2000), 10.

[114] Van Der Vaart, R., Huiskes, C., Bosch, H., Reith, T., Single and mixed gas equilibria of

carbon dioxide / methane on activated carbon, Adsorption 6, (2000), 311.

[115] Fitzgerald, J.E., Sudibandriyo, M., Pan, Z., Robinson Jr., R. L., Gasem, K.A.M., Modeling

the adsorption of pure gases on coals with SLD model, Carbon 41, (2003), 2203.

[116] Sudibandriyo, M., Pan, Z., Fitzgerald, J.E., Robinson Jr., R.L, Gasem, K.A.M., Adsorption

of methane, nitrogen, carbon dioxide and their binary mixtures on dry activated carbon at 318.2

K and pressures upto 13.6 pa, Langmuir 19, (2003), 5323.

[117] Chen J. H, D. S. H. Wong, C. S. Tan, Adsorption and desorption of carbon dioxide onto

and from activated carbon at high pressures, Ind. Eng. Chem. Res. 36, (1997), 2808.

[118] Keller, J. U., Dreisbach, F., Rave, H., Staudt. R., Tomalla, M., Measurements of gas

mixture adsorption equilibria of natural gas compounds on microporous sorbents, Adsorption 5,

(1999), 199.

[119] Zhou, L., Bai, S., Zhou, Y., Yang, B., Adsorption of nitrogen on silica gel over a large

range of temperatures, adsorption 8, (2002), 79.

[120] Gao, W., Butler, D., Tomasko, D.L., High pressure adsorption of CO2 on NAY Zeolite and

model prediction of adsorption isotherms, Langmuir, 20, (2004), 8083.

[121] Hocker, T., Rajendran, A., Mazzotti, M., Measuring and modeling supercritical adsorption

in porous solids. Carbon dioxide on 13X Zeolite and on silica gel. Langmuir 19, (2003), 1254.

[122] Dreisbach F., Reza Seif A.H., H. W. Lösch, Gravimetric measurement of adsorption

equilibria of gas mixture CO / H2 with a magnetic suspension balance, Chem. Eng. Tech.

Comm., 25, (2002), 11.

References

150

[123] Myers, A.L., J.A. Calles, G. Calleja, Comparision of molecular simulation of adsorption

with experiments, Adsorption, 3, (1997), 107.

[124] Keller, J.U., F. Dreisbach, H. Rave, R. Staudt. M. Tomalla, Measurements of gas mixture

adsorption equilibria of natural gas compounds on microporous sorbents, adsorption 5, (1999),

199.

[125] Dreisbach, F., R. Staudt, J.U. Keller, Experimental investigation of the kinetics of

adsorption of pure gases and binary gas mixtures on activated carbon, fundamentals of adsorption

6(FoA6), F. Meunier (Ed.), (1999), 1219.

[126] Dreisbach, F., Lösch, H.W., Harting, P., Highest Pressure Adsorption Equilibria Data:



[127] Specovious, J., Findenegg, G. H., Study of fluid / solid interface over a wide density range

including the critical region. I. surface excess of ethylene / graphite. Ber.Bunsen-Ges. Phys.

Chem., 84, (1980), 690.

[128] Sircar, S., Gibbsian surface excess for gas adsorption-revisited. IECR, 38, (1999), 3670.

[129] Menon. Adsorption at high pressures. Chem. Rev., 68, (1967), 277.

[130] Keller, J.U., Equation of state of adsorbents with fractal dimensions, Physica A, 166,

(1990), 180.

[131] Toth, J., Isotherm Equations for monlayer adsorption of gases on heterogenous solids

surfaces, in proceeingd of the 1st intl. Conference on fundamentals of adsorption, Germany, A. L.

Myers and G. Belfort (EDs.), 1984.

[132] Do, D.D., Adsorption analysis; Equilibria and kinetics, Imperial college press, London,

1998.

[133] Tillotson, T.M, Hrubesh, L.W., Transparent ultralow-density silica aerogels prepared by a

two-step sol-gel process, J. Non-Cryst. Solids, 145, (1992), 44.

[134] Davydov, V. Ya., Kiselev, A.V., Zhuravlev, L. T., Study of the surface and bulk hydroxyl

groups of silica by infrared spectra and D2O-exchange, Trans. Faraday Soc.,60, 504, (1964),

2254.

[135] McHugh, M.A., An experimental investigation of the high pressure fluid phase equilibrium

of highly asymmetric binary mixtures, PhD Thesis, (1981), University of Delware.

References

151

[136] Diefenbacher, A., Türk, M., Phase equilibria of organic solid solutes and supercritical

fluids with respect to the RESS process, J. Supercrit. Fluids, 22, (2002), 175.

[137] Lamb, D. M., Barbara, T. M., Jonas, J., NMR Study of solid naphthalene solubility’s in

Supercritical Carbon Dioxide near the Upper Critical End Point, Gen. Phys. Chem, 90, (1986),

4210.

[138] Fukné-Kokot, K., König, A. Kneza, Ž. Škerget, M., Comparison of different methods for

determination of the S–L–G equilibrium curve of a solid component in the presence of a

compressed gas, Fluid Phase Equilibria, 173, (2000), 297.

[139] Bertakis, E., Measurement and thermodynamic modeling of solid–liquid–gas equilibrium

of some organic compounds in the presence of CO2, J. of Supercrit. Fluids, 41, (2007), 238.

[140] Harris, R.A., High pressure vapor–liquid equilibrium measurements of carbon dioxide with

naphthalene and benzoic acid, Fluid Phase Equil. 260, (2007), 60.

[141] McHugh, M.A., Seckner, A.J., Yoga, T.J., High-pressure phase behavior of binary

Mixtures of octacosane and carbon dioxide, Ind. Eng. Chem. Fundem. 23, (1984), 493.

[142] Mukhopadhyay, M., Shyamal, K. De., Fluid phase Behavior of close molecular weight fine

chemicals with supercritical carbon dioxide, J. Chem. Eng. Data 40, (1995), 909.

[143] Shen, Z., Li, D., McHugh, M.A., Solubility of pyrazine and Its derivatives in supercritical

carbon dioxide, J. Chem. Eng. Data 51, (2006), 2056.

[144] McHugh, M.A., Andrew, S., Yogan, J., Thomas J., High-pressure phase behavior of binary

mixtures of octacosane and carbon dioxide, Ind. Eng. Che. Fundam., 23, (1984), 493.

[145] Smirnova, I., Suttiruengwong, S., Arlt, W., J of Non-Crystal Solids, 350, (2004), 54.

[146] Brunauer S., Emmett P.H., Teller E., Adsorption of Gases in Multimolecular Layers. J Am

Chem Soc. 60, (1938), 309.

[147] Mannahan S.E., Quantitative Chemical Analysis. Brooks / Cole Publishing Company:

Monterey, California, 1986.

[148] Ewing G.W. Instrumental methods of chemical analysis. McGraw-Hill Book Company:

New York, 1985.

[149] Humayun, R, Tomasko, D.L., High-Resolution Adsorption Isotherms of Supercritical

Carbon Dioxide on Activated Carbon, Adsorption, 46, (2000), 10.

References

152

[150] Pini, R., Ottiger, S., Rajendran, A., Storti, G., Mazzotti, M., Reliable measurement of near-

critical adsorption by gravimetric method, Adsorption 12, (2006), 393.

[151] Kalaga, A., Trebble, M., Density Changes in Supercritical Solvent + Hydrocarbon Solute

Binary Mixtures, J. Chem. Eng. Data 44, (1999), 1063.

[152] Myers, A.L., J.A. Calles, G. Calleja, Comparision of molecular simulation of adsorption

with experiments, Adsorption, 3, (1997), 107.

[153] Keller, J.U., F. Dreisbach, H. Rave, R. stuadt. M. Tomalla, Measurements of gas mixture

adsorption equilibria of natural gas compounds on microporous sorbents, adsorption 5, (1999),

199.

[154] Dreisbach, F., R. Stuadt, J.U. Keller, Experimental investigation of the kinetics of

adsorption of pure gases and binary gas mixtures on activated carbon, Fund. of Ads. 6, (1999),

1219.

[155] Dreisbach, F., lösch, H.W., Harting, P., Highest Pressure Adsorption Equilibria Data:



[156] Melnichenkoa, Y. B., Wignall, G.D., Cole, D.R., Frielinghaus, H., Adsorption of

supercritical CO2 in aerogels as studied by small-angle neutron scattering and neutron

transmission techniques, The J of Chem. Phys. 124, (2006), 204711.

[157] Gorle, B. S. K., Smirnova, I., Dragan, I. M., Dragan, S., Arlt, W., Crystallization under

supercritical solutions in aerogels, J of supercrit. fluids, 44, (2008), 78.

[158] Smirnova, I., Suttiruengwong, S., Arlt, W., Aerogels: Tailor made carriers for immediate

and prolonged drug release, KONA, 23, (2005), 86.

[159] R. Goswami, P. Ryder, K. Chattopadhyay, The melting and solidi® cation of nanoscale Bi

particles embedded in a glassy and crystalline matrix, Phil. Magaz. Lett., 79, (1999), 481.

[160] Grosse, K., Ratke, L., Feuerbacher, B., Solidification and melting of succinonitrile within

the porous network of an aerogel, physical review B, 55, (1997), 2894.

[161] Roberts, C. J., DeBenedetti, P. G., AIChE J., 48,( 2002), 1140.

[162] Hancock, B. C., Parks, M., Pharm. Res., 17, (2000), 397 (b) Zhou, D., Zhang, G. G. Z.,

Grant, D. J. W., and Schmitt, E. A. , J. Pharm. Sci., 2002, 91, 1863.

[163] Scherer, G.W., Crystallization in pores, J. Non-Cryst. Solids, 155, (1999), 1347.

References

153

[164] Andreazza, P., Lefaucheux, F., Mutaftschiev, B., Nucleation in confined space: Application

to the crystallization in gels, J. of Cryst. Growth, 92 (3-4), (1988), 415.

[165] Abrahams, S.C., Monteath Robertson, J., White, J.G., The crystal and molecular structure

of naphthalene. I. X-ray Measurement, Acta Cryst. 2, (1949), 233.

[166] Shen, Z., Li, D., McHugh, M.A., Solubility of pyrazine and Its derivatives in supercritical

carbon dioxide, J. Chem. Eng. Data 51, (2006), 2056.

[167] Smirnova, I., Mamic, J., Arlt, W., Langmuir 19(20), (2003), 8521.

[168] Smirnova, I., Suttiruengwong, S., Seiler, M., Arlt, W., Pharm. Devel. Tech. 9(4), (2004),

443.

[169] Smirnova, I., Suttiruengwong, S., Arlt, W., J of Non-Crystalline Solids, 350, (2004) 54.

[170] Langer, R. Nature 392, (1998), 5.

[171] Yoshida, R. Sakai, K., Okano, T., Sakurai, Y., Adv. Drug Delivery Rev. 11, (1993), 85.

[172] Kataoka, K., Harada, A., Nagasaki, Y., Adv. Drug Delivery Rev. 47, (2001), 113.

[173] Maria Vallet-Regi Chem. Eur. J. 12, (2006), 5934.

[174] Charnay, C., Be´gu, S., Tourne´-Pe´teilh, C., Nicole, L., Lerner, D.A., Devoisselle, J.M.,

European J of Pharm. Biopharm., 57, (2004), 533.

[175] Ramila, A., Munoz, B., PEerez-pariente, J., vallet-refi,.M., J of Sol-Gel Sci. Tech. 26,

(2003), 1199.

[176] Kresge, J., et al., Nature, 359, (1992), 710.

[177] Beck, J. S., et al., J. Am. Chem. SOC., 114( 27), ( 1992), 10835.

[178] Pentz, M., Shott, M., Aprahamian F. Handeling Experimental Data. Open University

Press: London, 1988.

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