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Karakteristik larutan… 

Penyusun larutan : solut dan solvent

Keuntungan larutan;

1. Nyaman utk pediatric dan geriatric2. Efek lebih cepat dibandingkan sediaan… 

3.  lebih homogen dibandingkan suspensi atau

emulsi

4. Mengurangi efek samping obat yg iritatif thdsal cerna jika tdk diberikan dalam btk larutan

(aspirin, KBr)

5. Flexible dose

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1. bulky

2. sulit menutupi rasa/bau yg tidak enak utk

obat tertentu

3. takaran kdg2x sulit utk tepat dosis 4. stabilitas < sediaan padat

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Solvent : aqeous (keuntungan &

kerugiannya ??),

macamnya: (potable water, pharmacopeal

purified water, aromatic water)

non aqeous (fixed oil/vegetable oil, alkohol,

micellaneous: gliserol, propilenglikol)

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Bagaimana larutan bisa terbentuk ?

(solut terion solvated/hidrated

Intermoleculer interaction

Bedakan antara terlarut (dissoloved) dan

terjadinya reaksi…… 

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Faktor penting yang perlu diperhatikan dlm

pembentukan larutan :

 solubility

stability

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dissolution rates generally increase with:

a. smaller particle sizes

b. effective stirring

c. lower viscosities

d. increased temperature.

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1. Buffers

2. Viscosity enhancer

3. Preservative (syarat nya:…… 

1. effective against a wide spectrum of

microorganisms

2. stable for its shelf life

3. non toxic, non sensitizing4. compatible with the ingredients in the

dosage form

5. free of taste and odour

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1. gol. Alkohol (etanol, propilenglikol)

2. acid (as. Benzoat, as. Sorbat)

3. ester (paraben = ester dari

parahidroksibenzoic acid, metil, etil,propil, butil), perhatikan pH efektifnya….. 

4. gol. Ammonium kuarterner (Benzalkonium chloride )

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Agent  pH Range

Benzoic acid 2.5-4.0

Sorbic acid 3.0-6.5 

Proprionic acid 2.5-5.0 

Acetic acid 3.0-5.0 

Parabens 3.0-9.0 

Sulfites 2.5-5.0 

Nitrites 4.0-5.5

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4. Antioxidants (propil &oktil ester dr asam galat,tokoferol, sod sulfit, ascorbic acid)

oksidasi dpt diinisiasi oleh heat, light , heavy metal (solusi……) 

5. Sweetening agentsex: Sucrose 

  Advantages: Colourless, highly water soluble, stable over awide pH range (4-8), increase the viscosity, masks both saltyand bitter taste, has soothing effect on throat.

Polyhydric alcohols (sorbitol, mannitol and glycerol)possess sweetening power and can be used for diabeticpreparations.

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6. Flavours and perfumes

Natural products: fruit juices, aromatic oil

(peppermint, lemon)

 Artificial perfumes are cheaper, morereadily available and more stable than

natural products.

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physical and chemical stability

clarity, colour, odour, taste and viscosity over

its shelf life.

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1- Loss of flavour

2- Change in taste

3- Presence of off flavours due to interaction

with plastic bottle 4- Loss of dye

5- Precipitation

6- discoloration

The effect: Change in smell or feel or taste

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COOHO

CH3

OH2

COOH

OHCH

3COOH+

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Dissolved O2 from air

Catalyzed by trace transition metals

Cu, Ni, Fe, Mn, Co, etc.

Contaminants from drug and solutes from which

solution was made

Ex: captopril

Strategies

Purge with inert gas, usually N2

Antioxidants, EDTA (chelates free metal ions)

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NSH

CH3

O

HOOC

N   NS

CH3

O

HOOC

S

CH3

O

COOH

O2

Cu2+

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Dapat dicegah dengan:

1- suitable packing in amber coloured bottles

2- cardboard outers

3- aluminium foil over wraps

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1- pHThe acidity or the alkalinity of a solution hasa profound influence on the decomposition

of drug compound.- Aspirin buffered solution is maximum stable

at a pH of 2.4, above a pH of 10 thedecomposition rate rapidly increases.

pH can also influence the rate of oxidation.

- The system is less readily oxidized when thepH is low.

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2- ComplexationComplex formation reduces the rate of

hydrolysis and oxidation.

e.g. caffeine complexes with local anesthetics,such as benzocaine, procaine and tetracaime

to cause a reduction in their rate of

hydrolytic degradation.

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3- SurfactantsNonionic, cationic and anionic surfactants

when added to solutions containing drugs

form micelle and the drug particles becometrapped in the micelle.

The hydrolytic groups such as OH cannot

penetrate this micelle cover and reach thedrug particles, hence hydrolysis rate is

decreased.

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4- Presence of heavy metals

Heavy metals, such as copper, iron, cobalt

and nickel increase the rate of formation of

free radicals and enhance oxidativedecomposition.

5- Light and humidity

Light, especially ultraviolet light enhances

photolysis and humidity enhances hydrolytic

decomposition.

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1- TemperatureAll the drug products are stored at suitable

temperatures to avoid thermal acceleration

of decomposition. Three varieties oftemperatures are suggested for storage ofdrug products. Room temperature, coolstorage and cold storage.

2- LightLight sensitive materials are stored in

ambered colour bottles.

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3- Humidity

Packing materials are chosen (usually glassand plastic) to prevent exposure of drugproducts to high humid condition.

4- Oxygen

Proper packing keeping the oxygen contentof the solution less and leaving very littlehead space in the bottle above the drugproducts are methods to fight againstoxidation.

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5- Chelating AgentsChelating agents form complexes with heavymetal ions and prevent them from catalyzing

oxidative decomposition.e.g. ethylenediamine tetracetic acid (EDTA)derivatives and salts, citric acid and tartaricacid.

6- SolventsBy the addition of a suitable solvent

hydrolysis rate may be decreased

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(1) suitably designing the containers

(2) usually using single dose containers

(3) sticking to proper storage conditions

(4) adding an antimicrobial substance aspreservative.

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1. gelas

2. plastik

Plastics

The problems with plastic are:1.Migration of the drug through the plastic into the

environment.

2.Transfer of environmental moisture, oxygen, and

other elements into the pharmaceutical product.3.Leaching of container ingredients into the drug.

4.Adsorption of the active drug or excipients by

the plastic.

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3. Metals

- Various alloys and aluminium tubes may beutilized as containers for emulsions,ointments, creams and pastes.

- Limitation:  They may cause corrosion andprecipitation in the drug product.

- Overcome: Coating the tubes with polymersmay reduce these tendencies.

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4. Rubber

- Rubber also has the problems of extraction of

drug ingredients and leaching of container

ingredients.

- The pretreatment of rubber vial stoppers and

closures with water and steam reduces

potential leaching

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No dissolution phase

Major concern is physicochemical stabilityand interaction with other substances in GIfluid Change in pH

Dilution of cosolvent

Formation of insoluble complexes Ciprofloxacin with Fe2+, Ca2+, Mg2+ etc.

Viscosity of solution may slow absorption Assuming spherical drug molecule

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ƒ 6

kT kT   D

r  

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1. Simple Solution (by stirring or heating) 

2. Solution by Chemical Reaction (by reacting

two or more solutes with each other in a

suitable solvent)3. Solution by Extraction (Plant or animal

products)