`RESEARCH PAPER
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`Received 4th February, 1997.
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`Accepted 26th July, 1997
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`Indian J. Pharm. Scl., 1997, 59(5) pp. 232-235
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`In-Vitro studies on Buccal strips of Glibenclamide using Chitosan
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`R. ILANGO?, S. KAVIMANI, A. R. MULLAICHARAM ANDB. JAYAKAR.
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`Dept. of Pharmaceutics, Periyar College of Pharmaceutical Sciencesfor Girls, Trichy, Tamil Nadu - 620 021.
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`Asglibenclamide is metabolised completelyin theliver, the principal metabolite being only very weakly
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`active, buccal strip glibenclamide maybe very useful for the treatment of diabetes moreefficiently. The
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`objective of this workis to investigate the possibility of obtaining a slow release, relatively constant
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`effective levels of glibenclamide from buccalstrips using chitosan. Here attempts were made to develop
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`suitable chitosan- based buccalstrips and to characterise It using differentin vitromethods. Chitosan-
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`basedstrips of glibenclamide showedsuitability over Eudragit-based glibenclamide buccalstrips for
`controlled release behaviour,
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`& drug, used in the treatment of maturity onset
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`LIBENCLAMIDE is a Sulphonylurea group of
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`diabetes as an oral hypoglycaemic" 2, Glibenclam-
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`ide, chemically is 1-(p-(2-(5-chloro-O-anisamido),
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`ethyl), phenyl), sulfonyl)-3-cyclohexyl urea. The
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`plasmahalf life is about 5-10 h. In the present work
`an attempt has been made to develop a buccal
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`mucodhesive dosage form’ of glibenclamide for
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`improving and enhancing bioavailability. it may also
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`be possible to bypass the hepatic first pass effect
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`by administering it through the buccal mucosa, which
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`is richly perfused with blood vessel and offers greater
`permeability than the skin*. The required therapeutic
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`plasma concentration of glibenclamide can possibly
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`be achieved morerapidly by using such buccal dos-
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`age forms. Chitosan is (1-4)-2-amino-dexoy-fD-
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`glucan.
`It has similar structural characteristics as
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`that of glycosaminoglycans. It is tough, biodegrad-
`able and non- toxic®®,
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`METHODS
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`Glibenclamide (I.P), chitosan, Eudragit L 100,
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`EudragitS 100, Polyvinylpyrrolidone (Kollidone), pro-
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`pyleneglycol, acetic acid were the chemicals used.
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`’ *For correspondence
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`Polyvinylpyrrolidone was used as a mucoadhes-
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`ive polymer. Propylene glycol (5% v/v) was used as
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`a plasticizer and penetration enhancer. One percent
`wiv of chitosan was prepared in 5% v/v of acetic
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`acid. Glibenclamide in concentration of 1% and 2%
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`were used. The chitosan buccal strips were prepared
`by casting technique'®. Mixed quantity of chitosan
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`that was required to produce 1% w/vofits solution
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`with 5% v/v of acetic acid. Allowed to stand for one
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`and half weeks with moderatestirring for the first
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`3-4 days. The solution was thenfiltered through a .
`muslin cloth to remove debris and suspended
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`particles, Polyvinylpyrrolidone was accurately
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`weighed and dissolved in ethanol alongwith accu-
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`rately weighed quantity of chitosan solution and pro-
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`pylene glycol (5% v/v) were addedto obtain a viscous
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`solution. The drug was then dispersed uniformly in
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`the viscous solution with continousstirring. The re-
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`sulting mass was then poured into glass moulds
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`lined with Aluminium foil. The solvent was evaporated
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`at room temperature for about 24 hours. The dried
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`strip thus obtained wascut into required size con-
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`sisting of required amount of the drug and stored
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`in a dessicator. Strips having an oval form of 4 cm
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`length and 3 cm width, 40 micron thickness and
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`density 1.2031+0.5 were usedfor the studies.
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`232
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`Indian Journal! of Pharmaceutical Sciences
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`September — October 1997
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`Dr. Reddy's - EX1005
`Page 1
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`Dr. Reddy's - EX1005
`Page 1
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`Table 1: Composition of glibenclamide buccalstrips
`—eeLSS——
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`Eudragit strip
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`Ingredients
`' Chitosan strip
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`2% Drug 1% Drug 2% Drug1% Drug ControlTS
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`Glibenclamide
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`Chitosan
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`Eudragit
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`Acetic Acid
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`Ethanol
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`500 mg
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`500 mg
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`Poly vinyl
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`pyrrolidone
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`5% 5% 5% 5%Propylene Glycol 5%
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`1%
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`1%
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`2%
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`1%
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`5%
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`1%
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`1%
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`2%
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`1%
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`2%
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`5%
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`500 mg
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`5%
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`500 mg
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`5%
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`500 mg
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`Table 2 : Swelling studies of buccal strips* (in Cf.1)
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`Eudragit buccal strip
`Chitosan buccalstrip
`Time in
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`2% Drug
`1% Drug
`2% Drug
`1% Drug
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`0
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`3.0
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`3.0
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`3.0
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`3.0
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`10
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`3.2 + 0.002
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`3.8 + 0.05
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`4.2 + 0.03
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`4.3+0.2
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`3.3 + 0.002
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`3.6 + 0.04
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`4.0+0.1
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`4.2+0.4
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`3.05 + 0.002
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`3.09 + 0.006
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`3.15 + 0.005
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`3.2 + 0.001
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`3.04 + 0.002
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`3.08 + 0.004
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`3.15 + 0.07
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`3.18 + 0.06
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`5, 10, 30 and 60 minutesintervals blotted with filter
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`paper to removethe water present on their surface
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`and weighed accurately. The percent swelling was
`calculated using the following formula'’,
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`Percentage Sweliing = Wet Norwich nt x 100
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`A
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`A
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`|
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`* Average of Three Trials with Standard deviation
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`For Eudragit buccal strip preparation (1:1) ratio
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`of Eudragit L 100 and Eudragit S 100 were used
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`instead of chitosan solution. Ethanol was used as
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`solvent for Eudragit buccal strips. Drug free strips
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`were prepared for comparison.
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`Evaluation of Buccal strips
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`Buccal strips of 4 cm Jength and 3 cm width
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`were placed petridishes, 50 ml water was added
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`and surface diameter was measuredat 0, 5, 10, 30
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`and 60 minutesintervales. Four replications of each
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`test were carried out. Buccal strips of equal density
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`(1.203) were weighed accurately and kept immersed
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`in 50 ml of water. Strips were taken out carefully at
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`Density Determination of the strips was made
`employing thefilm thickness and byusing therelation
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`D=m/v
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`Where D = Density of free strips
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`M= Wtofstrip samples in grams
`and V = Volumeof strip sample (cm)
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`September — October 1997
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` (cid:9)
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`Indian Journal of Pharmaceutical Sciences
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` (cid:9)
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`233
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`Page 2
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`Page 2
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`Effect of concentration on drug release a
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`B
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`¢
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`A — Chitosan Strip (1% Drug)
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`B — Eudragit Strip (1% Drug)
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`C — Chitosan Strip (2% Drug)
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`D — Eudragit Strip (2% Drug)
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`Gal“
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`< 4R
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`E
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`PERCENTAGECFDRUG
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`Table 3: Percentage swelling of chitosan
`buccal*strips
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`Chitosan stips
`Chitosan strips
`Time in
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`2% Drug
`1% Drug
`Minutes
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`5
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`10
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`30
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`60
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`24 +0.02
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`27 + 0.05
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`29 +2.3
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`31+3.2
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`32+ 2.21
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`20+ 0.02
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`26 + 0.02
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`28.5 + 2.5
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`30 + 1.6
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`31.5 + 0.06
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`* Values expressed as the meanof four readings with
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`S.D.
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`The thickness of each film was measured in the
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`centre and around the periphery with a horizontal
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`metroscope.All thickness and weight measurements
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`were made after residual moisture has been removed
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`from the samples by storing in a dessicator for
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`1 week,
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`In Vitro release study
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`The strip was carefully pressed on to a micro-
`scopic slide. The slide was placed at an angle of 45°
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`in a 250 ml beaker containing 200 ml of pH 7.4 buffer
`preheated to 37°. The beaker was kept
`in 37°
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`waterbath. A non agitated system was selected to
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`eliminate any effect of turbulence on the release rate
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`as to assure that no disruption of the strip occured.
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`Periodic assay samples were obtained by removing
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`the slide, stirring the solution and pipetting a 5 ml
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`sample with a graduated pipette, whose tip was
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`covered with a piece of muslin cloth. The slide was
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`quickly reinserted, making sure that the strip re-
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`mained completely immersed throughout the release
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`study. The beaker was kept covered through-out the
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`run to prevent evaporation. All samples were an-
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`alysed using an UV spectrophotometerat 226 nm.
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`RESULTS AND DISCUSSION
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`There is no interaction between chitosan and
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`glibenclamide which was confirmed by Infrared
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`spectrum of physical mixture of chitosan and
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`glibenclamide.
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`Chitosan buccalstrips with 1% and 2% drug and
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`Eudragit buccal strips with 1% and 2% drug were
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`prepared and evaluated. The content uniformity of
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`glibenclamide in the prepared buccalfilm was found
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`to be satisfactory and was within 5% variation. Poly-
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`vinylpyrrolidone was used as the mucoadhesive
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`polymer which have a molecular weight of 49,000.
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`This is water soluble hydrocolloid, mucoadhesive by
`the dissolution kinetics of the polymeric carrier. Thus
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`the polymer dissolution wasthe rate controlling step
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`in drug release. When a swellable polymeric matrix
`was madeby incorporating chitosan or Eudragit with
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`the polymer solution, delay in the dissolution of poly-
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`mer due to swelling of the incorporated substances
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`occurs. This leadsto controlled release of drug from
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`mucodhesivestrips.
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`Chitosan swells more than Eudragit, which may
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`lead to controlled release of drug in case of buccal
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`strips prepared with chitosan. The Eudragit polymer
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`solution consisting of equal proportion of (1:1) Eu-
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`dragit S 100 and Eudragit L 100. Eudragit S 100
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`has swelling property whereas Eudragit L 100 has
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`no swelling property.
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`234
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`Indian Journal of Pharmaceutical Sciences
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` (cid:9)
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`September ~ October 1997
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`Page 3
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