Development and evaluation of a matrix controlled-release formulation of gliclazide
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Date
2008
Authors
Adebaibi, Mahmoud
Journal Title
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Abstract
Two hydrophobic polymers, Kollidon® SR and Eudragit® RSPO as well as two
hydrophilic hydroxypropyl methylcellulose polymers, namely, HPMC KlOOLV and
HPMC Kl5M were evaluated as matrix tablet forming materials for sustaining the
release of gliclazide. It was found that drug release could be modified in a
predictable manner by varying the content of the polymers, whereby increasing the
polymer content resulted in a more sustained rate of drug release. At the same
polymer content, the drug release was most sustained with tablets prepared using
HPMC Kl5M, followed by Kollidon® SR, HPMC Kl OOLV and lastly Eudragit®
RSPO. A similar comparison of several grades of HPMC showed that the drug
release was more sustained with HPMC Kl OOM, followed by HPMC Kl5M, HPMC
K4M, HPMC KIOOLV, HPMC E4M and HPMC El5. The amount and the
composition of granulation fluid as well as the particle size range of the polymer
were also found to have a significant impact on the drug release from a 30%
Kollidon® SR matrix. Increasing the amount of granulation fluid and the ratio of
isopropyl alcohol to water as well as using a higher proportion of Kollidon® SR
polymer with larger particle size led to a decrease in the rate of drug release.
The gliclazide release from a formulation containing 30% of Kollidon® SR was
found to be pH-dependent, with the highest release rate occurring at pH 7 .4, followed
by at pH 1.2 and the slowest at pH 4.0. However, when Kollidon® SR was evaluated
using two other hydrophilic drugs, namely diltiazem HCl and theophylline, their
release rate was found to be faster than that of gliclazide in all the three pH values.
Incorporation of maltodextrin, dibasic calcium phosphate or Plasdon® S-630 into the
Kollidon® SR matrix also failed to overcome the slow and pH-dependent release of
gliclazide. Thus, Kollidon® SR was found not suitable to be used as matrix forming
materials.
HPMC KlOOLV was further studied for its suitability to be used as the matrix
materials for gliclazide. A formulation with 30% HPMC KlOOLV and 30% dibasic
calcium phosphate could produce drug release profiles quite similar or matching to
those of reference preparation, Diamicron® MR at the different pH conditions when
evaluated using the differential (F 1) and similarity (F2) factors. Different methods of
tablet preparation, namely, wet granulation, direct compression and dry granulation
were also found to affect the rate of gliclazide release. The drug release profiles of
tablets prepared "by wet granulation were more comparable to those of Diamicron®
MR, revealing that this method was preferred for tablet preparation. Moreover, the
drug release profiles of the tablets produced using the wet granulation method was
found to be stable after 6 months of study.
Description
Keywords
Controlled-release , Gliclazide