PREPARATION AND EVALUATION OF CHITOSAN - GLICLAZIDE MICROPARTICULATE DRUG DELIVERY SYSTEMS BY AN EMULSIFICATION- DESOLVATION- CROSSLINKING TECHNIQUE

Recently much emphasis is being laid on the development of microparticulate DDS in preference to single unit systems 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 and evaluate microparticulte drug delivery systems of Gliclazide using chitosan, a mucoadhesive polymer for oral controlled release. A new technique namely emulsificationdesolvation-crosslinking method was tried for the preparation of chitosan microparticles. The Chitosan- Gliclazide microparticles prepared were evaluated for various physical and drug release characteristics. Spherical Chitosan- Gliclazide microparticles could be prepared by the emulsification-desolvation-crosslinking method. The method is industrially feasible as it involves emulsification and removal of the solvent, which can be controlled precisely. The emulsification-desolvation-crosslinking method was reproducible with regard to size and size distribution of the microparticles. About 68-75 % of microparticles in each batch were in the size range 35/50 mesh (398.5µm). Encapsulation efficiency was in the range 97.1-99.5 % in the preparation of microparticles. Gliclazide release from the chitosan microparticles was slow and spread over longer periods of time. The drug release depended on the proportion of core: coat in the microparticles. A good linear relationship (R² = 0.874) between percent coat and release rate (K0) was observed. The relationship could be expressed by the linear equation, y = 11.849-0.3035 x where x is percent coat and y is release rate (K0). Gliclazide release from the chitosan microparticles prepared was by diffusion mechanism. Fickian diffusion was observed in the case of microparticles which gave relatively rapidly release (F1 and F2) and the release was by non-Fickian diffusion in the case of microparticles which gave slow release of gliclazide ( F3 and F4). Microparticles (F3) prepared using a core: coat ratio of 8:2 gave slow and controlled release of Gliclazide over 12 hours similar to that of commercial gliclazide SR tablets. A microparticle (F3) is considered as a promising microparticulate DDS for oral controlled release of Gliclazide over 12 hours for b.i.d administration. Key words: Microparticulate drug delivery systems, Chitosan, Gliclazide, Emulsification-desolvation-crosslinking method, Oral controlled release