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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'
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&!$ -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 !/
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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
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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.
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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
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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.
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>/.D3 " in )th hour .so the binder solution
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$($ &!' 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
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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 $arameter% In guidance of industrial
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scientist dierent parameter of tablet like Bow
property, dimension hardness, drug content
etc. were studied with results in successful
trials.Idea after dissolution study. The amount
released in +xed duration was of more
importance and were performed with precision
and accuracy, the change in amount of
polymer was largely dependent of viscosity
grade the dissolution study suggested many
parameter to control of next batches. :inal
batch the batch I) immerge as a successful
delivery system it was completely dependent of
gel swelling and diusion behavior of #$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.
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%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
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study on this formulation
R!F!R!N%!
GH E.S.$. %onvention &rowcy*ynski, @.,
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Marcel -ekker, Kew 0ork, >J2.
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G3H %olumba, $., Aettini, 5., Minima, . $harm.
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Siaboomi42''/6, 7 Investigation of a
directly compressible Metformin #cl
/''mg extended release formulation
based on hypromellose8 %olorcon
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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
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GDH 5achel # 42''36 7Metformin extended
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