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International Journal of Pharma and Bio Sciences

FORMULATION, !"!LOPM!NT AN !"ALUATION OF M!TFORMIN

#$RO%#LORI! SUSTAIN! R!L!AS! TABL!TS

R&'L'S!NT#IL&UMAR AN R'P'!#I(ILMUT#UPadma)athi %olle*e of Pharmac+, Peri+anahalli, harmauri'

R!"I!- ARTI%L! P#ARMA%!UTI%S

ABSTRA%T

There is a continuously growing interest in the pharmaceutical industry for

extended release

oral drug delivery systems. There is also high interest for design of dosage

formulations that

allow high drug loading, particularly for actives with high water solubility. TheStudy was

undertaken with an aim to formulation development and evaluation of Metformin

sustained

release tablets using dierent polymers as release retarding agent. It is

concluded that

formulation of sustained release tablet of Metformin containing ! " #$M% &''

with binder

$($ &!' i.e. batch I) can be taken as an ideal or optimi*ed formulation ofsustained release

tablets for ' hour release as it ful+lls all the reuirements for sustained release

tablet.

R&'L'S!NT#IL&UMAR

Padma)athi %olle*e of Pharmac+, Peri+anahalli, harmauri'

This article can .e do/nloaded from ///'i0.s'net

P 1 23

&!$ -ORS

Metformin sustained release diabetes

INTROU%TION

-iabetes a global public health problem is a

chronic disease and is now growing as an

epidemic in both developed and developing

countries. round /' million people suer from

diabetes in the world out of which above !/



million are Indians. %urrent drugs used for

managing T0$1 II -iabetes and its precursor

syndromes, such as insulin resistance, fall within

+ve classes of compound such as the biguanides,thia*olidinediones ,the sulfonylureas,ben*oic

acid derivatives and alpha glucosidase inhibitors.

Metformin is an oral antidiabetic drug from the

biguanide class. Metformin is the most popular

antidiabetic drug in the united state and one of

the most prescribed drug in the country overall

with nearly !/ million prescription +eld in 2''3

for generic Metformin alone. The aim of any drug

delivery system is to provide therapeutic amount

of drug to appropriate site in the body to achieve

immediate therapeutic response and to maintain

the desired drug concentration. In the recent

years sustained release 4S56 dosage forms

continue to draw attention in the research for

improved patient compliance and decreased

incidence of adverse drug rections. In general

the goal of sustained release dosage form is to

maintain therapeutic blood or tissue level of the

drug for extended period of time. This is

generally accomplished by attempting to obtain

7*ero order8 release from the dosage form.

9ero order release constitutes drug release

from the dosage form which is independent of

the amount of drug in the delivery system.

Sustained release system generally do not

attain this type of release and usually try to

mimic *ero order release by providing drug in

slow 7+rst order8 fashion 4i.e. concentration



dependent6.

!4P!RIM!NTAL M!T#O

Identifcation: The procured sample of

Metformin was tested for its identi+cation byusing :TI5 Spectra study .Then bulk

characteri*ation of the drug is done .The

manufacturer also was con+rmed of uality and

purity of sample.


P 1 25

Compatibility study o drug and Excipient

The drug and excipient compatibility was done

at 2/'% ; 3'" < /" 5#, !''% ; 3/" < /"

5# and =''% ; >/" < /" 5#. ?pen and

closed vial methods were used. The result

does not show any physical change to the

mixture after = weeks .%hemical compatibility

was analy*ed by #$@% method as per I$

speci+cation. This fact concluded that the drug

and excipients are compatible with each other.

Selection o Excipient:

The selection of excipient was

completely based on article review .The utility

of polymer as sustained release pro+le was

already proved.

Initial Trial:

Aefore compression of batches all the polymer

were tested with uantity of glidant and

lubricant to observe the Bow property .The

amount was +xed after successive initial trials

Control o Amount:

The initial batches were of directly compression



method which needs higher amount of excipient

to reduce the friability and improve hardness

indirectly which aect the release of drug from

polymer .The total weight 3/' mg was usedsuccessfully to meet all criteria.

DISSOLTIO! STD"

Dissolution discussion:

The dissolution was carried out by using

dissolution medium water and the release of

Metformin from sustained release tablet of

various formulations varied according to amount

and grade of dierent polymer. In case of

dierent concentration of polymer such as / "

#$M% &'' shows release pro+le C!./>" in (I

hour. Then /" #$M% &'' shows release

pro+le DC./" in (I hour. Then D" #$M%

&'' shows release pro+le C3.=/ in )th hour.

! " #$M% &'' shows release pro+le CD.3C

in )th hour within speci+cation limit and /"

#$M% &'' shows release pro+le >.3D" of

drug release in )th hour itself.

The #$M% &'' combined with #$M%

&/M taken as three trails in dierent

concentration but the three trials are not

showing the drug release in speci+c time

interval. Then the three trials taken as dierent

binder concentration such as $($ &!', Starch,

and #ydroxypropylcellulose.

The binder solution starch with water

create capping problem during compression.

The binder solution #$% with I$ shows

hardness is heavy so drug release is less i.e.



>/.D3 " in )th hour .so the binder solution


P 1 36

$($ &!' with I$ shows drug release in speci+c interval of time as per I$ @imits%omarati)e issolution ro7le of

Batch 8188

'

2'

='

3'

D'

''

2'

' 2 ! = / 3 > D C '

Time in 9hours:

%umulati)e ; ru*

release

Aatch

Aatch 2

Aatch !

Aatch =

Aatch /

Aatch 3

Aatch >

Aatch D

Aatch C

Aatch '

Aatch

Compression # E$aluation:

The sustained release tablets of

Metformin were prepared by weight granulation

and direct compression. The granules for the



matrix tablet were prepared according to the

formula given in related table and characteri*ed

with respect to angle of repose, moisture

content, bulk density and total drug content.ngle of repose was less than !/'% for all

batches of granules indicating satisfactory Boe

behavior moisture content of less than ! "

indicates optimum drying of granules. ?ther

parameters for granules were also found to be in

acceptable range.

Stability:5esults of stability studies of batch ix

indicate that it is stable at 2/'%< 2'% 3'"5#,

!''% < 2'%,3/"5#, =''% < 2'%,>/"5# as

there was no signi+cant dierence observed for

dissolution and other physical parameter of

tablet after ! month.

R!SULT AN IS%USSION

Identi+cation The procured sample of Metformin

was tested for its identi+cation by using :TI5

Spectra study. nd the %ompatibility study of

drug and 1xcipientThe drug and excipient

compatibility was done at 2/'% ; 3'" < /" 5#,

!''% ; 3/" < /" 5# and =''% ; >/" < /"

5#. ?pen and closed vial methods were used.

Selection of 1xcipient was completely based

on article review .The utility of polymer as

sustained release pro+le was already proved.

Initial Trial% Aefore compression of batches all

the polymer were tested with uantity of glidant

and lubricant to observe the Bow property .The

amount was +xed after successive initial trials .

Tablet $arameter% In guidance of industrial



scientist dierent parameter of tablet like Bow

property, dimension hardness, drug content

etc. were studied with results in successful

trials.Idea after dissolution study. The amount

released in +xed duration was of more

importance and were performed with precision

and accuracy, the change in amount of

polymer was largely dependent of viscosity

grade the dissolution study suggested many

parameter to control of next batches. :inal

batch the batch I) immerge as a successful

delivery system it was completely dependent of

gel swelling and diusion behavior of #$M%.

The dierent viscosity grades of #$M% were

used successfully.Etility of polymerFThe use of

#$M% in dierent concentration shows

dierent dissolution study. The drug release in

speci+c time interval is taken as ideal

concentration of polymer.


P 1 38

%ON%LUSION

:rom the above results and discussion it is

concluded that formulation of sustained release

tablet of Metformin containing ! " #$M%

&'' with binder $($ &!' i.e. Aatch I) can be

taken as an ideal or optimi*ed formulation of

sustained release tablets for ' hour release

as it ful+lls all the reuirements for sustained

release tablet and our study encourages for the

further clinical trials and long term stability



study on this formulation

R!F!R!N%!

GH E.S.$. %onvention &rowcy*ynski, @.,

extended release dosage forms, %5S press,Inc. :lorida, CD>, =.

G2H @achman, @., @iebermann, #.., &anig .@.,

1ds., In, 7The theory and practice of

Industrial $harmacy,8 III 1dn., @ea and

:ebiger, $hiladelphia, CD>, =!'J=/3.

G!H Arahmankar, -.A., aiswal, S.A., InF

Aiopharmaceutics and $harmacokinetic,

treatise, (allabh $rakashan, Kew -elhi, st

1dn., CC/, !!/J!/>.

G=H @ee, (.#., 5obinson, .5., in 7Sustained and

controlled release drug delivery systems8

Marcel -ekker, Kew 0ork, >J2.

G/H @apidus, ., @Lordi, K.., . $harm. Sci., />,

C3D, 2C2J!'.

G3H %olumba, $., Aettini, 5., Minima, . $harm.

Sci., D3, CCNCC2, DJC.

G>H Silvia . Aravo, Maria %.@amas , %laudio

.Salomon, 42''26 7 In O (itro Studies of

-iclofenac Sodium %ontrolled O5elease

from biopolymeric hydrophilic matrices8

ournal of $harmaceutical Science /4!6,

page no 2!N2C.

GDH . -i %olo , S.:alchi , 0.9ambite 42''26 7 InN

(itro 1valuation of System for p# %ontrolled

peroral delivery of Metformin 8ournal of

%ontrolled 5elease volume D', issues N!

page no. CN2D

GCH 0iN #ung Tsai , $ao O%hu Pu, 0awNAin



#uang 2''! 8

7$reparation and 1valuation of Sustained

5elease microspheres of potassium chloride

prepared with ethyl cellulose8. International Journal of Pharmaceutics edition 23'

page no./ O 2'

G'H & ' 5aghuram 5eddy , Mutalik S, 5eddy S

, 2''! 7 ?nce daily Sustained release

matrix tablets of Kicorandil , formulation

and InN(itro 1valuation8 AAPS Pharm Sci

Tech =4=6,3.

GH 1bube &. Kkere, lan A.ones ., 42''=6

Sustained release of acetaminophen from

a heterogeneous mixture of hydrophilic

non ionic cellulose coated tablet 7

International Journal of

Pharmaceutics8 , 2>2, CN2>.

G2H Manthena, (.S. (arma., args. 42''=6 , 7

:actor Qs aecting mechanism and kinetic

of drug release from matrix based oral

controlled drug delivery system8

American Journal of dru* deli)er+ ,

246, =!N/>.

G!H ?wen .I %orrigan , 42''=6 7Swelling and

erosion properties of #$M% matrices8

International Journal of Pharmaceutics

edition 2>C year page no .=N /2.

G=H Marina @evina, :iona $almer, liraRabi O

Siaboomi42''/6, 7 Investigation of a

directly compressible Metformin #cl

/''mg extended release formulation

based on hypromellose8 %olorcon



Poster reresentation controlled

release societ+ annual meetin* une

2''/.

G/H ?uyang -, Kie S, @i P, uo #42''/6 , 7-esign and evaluation of compound

Metformin;glipi*ide elementary osmotic


P 1 3<

pump tablets8. The Journal of Pharmac+

and Pharmacolo*+ rticle />4>6 page no.

D>ND2'.

G3H Mohammed 5e*a siahi, 42''/6, 7-esign and

evaluation of and ! layer matrics of

(erapamil for sustained release8 AAPS

Pharma Sci Tech 34=6 rticle 4>6.

G>H sh $atel , Subha Arata 5ay 5amShrnagat

Thakur , 7InN(itro 1valuation and

optimi*ation of %ontrolled release Boating

drug delivery system of Metformin

hydrochloride 8 ARU volume = page

no. />N3=.

GDH 5achel # 42''36 7Metformin extended

release is a novel gastricNretentive

formulation of ant hyperglycemic agent8

International Journal of Pharmaceutics

GCH @ianN-ong #u,Tang x , 9han 42''36, 7

$reparation and in vitro ; in vivo

evaluation of S5 release Metformin #cl

pellets 8. !ur' J' Pharmaceutics and

Bioharmaceutics edition 3=426 pages

no D/NC2.

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