Development and pharmacokinetic evaluation of once-daily sustained-released matrix capsules of nifedipine using solid dispersion technique

Abstract

The purpose of this study was to develop once-daily sustained-release matrix capsules of nifedipine (F1) using the combination of solid dispersion and drug controlled release techniques. F1 were prepared by the wetting granules methods using hydroxypropyl methyl cellulose (HPMC) as hydrophilic retard drug release agent and ethylcellolulose (EC) ethanol solution based on the polyvinyl pyrrolidone / stearic acid solid dispersion. In vitro drug release kinetic model of F1 was fitted well with the zeroorder kinetic equation: Q=0.0736 t+0.0871 (R=0.993) in the range of 0-6 h, the first-order kinetic equation: Ln (1-Q) =-0.0934 t-0.1375 (R=0.999) in the range of 6-24 h, respectively. The relative bioavailability of F1 was studied in rabbits after oral administration using a commercial available controlled release tablet (F2) as a reference. The pharmacokinetic results showed no significant differences in Cmax, MRT and AUC (0-24h). The relative oral bioavailability value from F1 in comparison with F2 was 97.12 %. The results of both in vitro and in vivo studies indicated that once-daily sustainedrelease matrix capsules of NFD prepared by the optimized formulation exhibited excellent sustainedrelease effects and high relative oral bioavailability.