Controlled release of nifedipine from gelatin microspheres and microcapsules: in vitro kinetics and pharmacokinetics in man

Abstract

Nifedipine was embedded in a gelatin matrix to develop a prolonged release dosage form. The effects of polymer/drug ratio, size of the beads, cross-linking with formaldehyde and ethylcellulose coating of the gelatin microspheres on the in vitro release rate of the drug were investigated. The data were analysed according to different laws that can govern the release mechanism: first-order, Higuchi square root of time, spherical matrix and zero-order. The in vitro release kinetics of nifedipine from gelatin microspheres were mainly first-order; from formaldehyde hardened gelatin microspheres, complied with the diffusion model for a spherical matrix, and from ethylcellulose-coated gelatin microspheres, obeyed zero-order kinetics. These findings suggest the possibility of modifying the formulation in order to obtain the desired controlled release of the drug for a convenient oral sustained delivery system. The pharmacokinetic parameters of nifedipine, after adminstration of a single oral dose of nifedipine-loaded hardened gelatin microspheres to volunteers, suggest that the preparation can be considered as a sustained release delivery system for nifedipine.