Formulation and evaluation of microspheres of diltiazem hydrochloride

Abstract

Microspheres of diltiazem hydrochloride were formulated using combination of polyethylene glycol 6000 and Eudragit RS 100 and Eudragit RS 100 alone by solvent evaporation and non-solvent addition methods with an aim to prolong its release. Six formulations prepared by using different drug to polymer ratios, were evaluated for relevant parameters and compared with marketed SR capsules. Depending upon the drug to polymer ratio, the entrapment, loading and encapsulation were found to range between 77.45±0.22 to 91.08±0.62% , 34.76±0.15 to 52.46±0.25% and 66.09±0.19 to 82.7 ±0.57%, respectively. The microspheres were spherical, discrete and compact and size distribution was between 4 to 24 µm. In vitro studies were carried out at different pH for a period of 12 h and compared with marketed formulation. As similarity factor f2 was 92.8 for FVI, it was subjected to further study. Formulations prepared using the combination of the retardants exhibited first order of drug release and zero order for preparations containing Eudragit RS 100 alone. The analysis of regression values of Higuchi plot and Korsmeyer-Peppas plot and n values of Korsmeyer-Peppas model suggested a combination of diffusional and dissolutional mechanism indicating the drug release from the formulations was controlled by more than one process. Drug polymer interaction was absent as evidenced by FT-IR and DSC thermograms. In vivo pharmacokinetic study of the formulation proved that prolongation of drug release was obtained by formulating as microspheres.