Abstract

PREPARATION AND IN VITRO AND IN VIVO PHARMACODYNAMIC EVALUATION OF GLICLAZIDE MICROPARTICLES USING STARCH ACETATE AND CHITOSAN

P. Veera Lakshmi, K. P. R. Chowdary*, A. Prameela Rani and S. V. U. M. Prasad

ABSTRACT

Recently much emphasis is being laid on the development of microparticles because of their potential benefits such as increased bioavailability, reduced risk of systemic toxicity, reduced risk of local irritation and predictable gastric emptying. The objective of the present study is to prepare gliclazide microparticles using starch acetate (a new modified starch) and Chitosan (a mucoadhesive polymer) and to evaluate the resulting microparticles by in vitro and in vivo Pharmacodynamic methods. A comparative evaluation of the two types of microparticles was made. An emulsification-solvent evaporation method was used to prepare starch acetate microparticles. A new method namely emulsification-desolvation-crosslinking method was used for the preparation of chitosan. Spherical, discrete and free flowing microparticles of gliclazide could be prepared by emulsification-solvent evaporation method with starch acetate and by emulsification -desolvation -crosslinking method with Chitosan. The methods are reproducible with regard to size and size distribution, drug content and encapsulation efficiency of the microparticles. Gliclazide release from the microparticles was slow and spread over longer periods of time and the drug release was depended on the polymer used and proportion of core: coat ratio. Good linear relationships were observed between percent coat and release rate (Ko) with both the polymers indicating their rate controlling effect. Chitosan microparticles gave relatively slow release of gliclazide than starch acetate microparticles. Gliclazide release from the microparticles prepared was by diffusion controlled mechanism. Non Fickian (anomalous) diffusion was the release mechanism in the case of all starch acetate microparticles and Chitosan microparticles CHF3 and CHF4. In the case of CHF1 and CHF2 the release was by Fickian diffusion. In the in vivo Pharmacodynamic evaluation gliclazide gave a rapid reduction in serum glucose levels, 55.3% at 1.0 h, and the glucose levels recovered rapidly to the normal level within 6-8 h. In the case of microparticles, the reduction in glucose levels was slower and the reduced blood glucose levels were sustained over longer periods of time. A significant hypoglycemic effect was maintained during the period from 0.5 h to 4 h in the case of gliclazide pure drug. Whereas the hypoglycemic effect was maintained during 0.5 h to 5.0 h in the case of SAF2 and from 2 h to 12 h in the case of CHF3 microparticles. Chitosan microparticles exhibited hypoglycemic effect over longer periods of time than starch acetate microparticles. The hypoglycemic effect of gliclazide could be sustained over 12 h with CHF3 microparticles.

Keywords: Gliclazide, Starch Acetate, Chitosan, Microparticles, Pharmacodynamic study.