Sustained Release of Diltiazem Hydrochloride from Chitosan Microcapsules

S.   Ayesha   Farhana; S.   M.   Shantakumar; Laxmi      Narasu

doi:10.2174/156720109788680840

Abstract

The objective of the present study was to develop sustained release formulation of Diltiazem hydrochloride (DH) using biodegradable polymers. For this purpose microcapsules embedded Diltiazem hydrochloride were prepared using chitosan alone and also by incorporating some co polymers like methyl cellulose(MC), sodium carboxy methyl cellulose (SCMC) and poly vinyl pyrollidone (PVP) by employing complex emulsion method of microencapsulation. Glutaraldehyde saturated toluene solution is used as cross linking agent. Microcapsules were prepared in various core : coat ratios to know the effect of polymer and co polymers on drug release. Overall eight formulations were prepared and evaluated for flow behaviour, sieve analysis, drug entrapment efficiency, in vitro dissolution studies, stability studies, including scanning electron microscopy. The resulting microcapsules were discrete, large, spherical and also free flowing. The drug content in all the batches of microcapsules was found to be uniform. The release was depended on core: coat ratio and nature of the polymers. FTIR analysis revealed chemical integrity between diltiazem hydrochloride (DH), chitosan and between the copolymers. Among the three copolymers used methyl cellulose retarded the drug release more than the other two, hence the same formulation was subjected for in vivo studies. The drug release from the microcapsules was found to be following non fickian diffusion. Mechanism of drug release was diffusion controlled first order kinetics. Drug diffusion co efficient and correlation co efficient were also assessed using various mathematical models. In vivo result analysis of pharmacokinetic parameters revealed that t max of reference and test formulations were the same. From the study it was concluded that, sustained release Diltiazem hydro chloride microcapsules could be achieved with success using chitosan alone and also in combination with other biodegradable polymers.

Keywords: Microencapsulation, Diltiazem hydrochloride, Sustained release, Chitosan, Biodegradable polymers, Methyl cellulose, Sodium carboxy methyl cellulose, Poly vinyl pyrollidone