Microspheres based on poly(3-hydroxy)butyrate for prolonged drug release

Abstract

The kinetics of the controlled release of the antiproliferative drug dipyridamole from microspheres based on the biocompatible and biodegradable polymer poly(3-hydroxy)butyrate is studied. As carriers for dipyridamole, microspheres prepared from a solution of poly(3-hydroxy)butyrate by single emulsion method are used. Under in vitro conditions, the kinetic curves describing the release of dipyridamole from microspheres with diameters of 19, 63, and 92 μm show two characteristic regions: the region of fast drug release within a short time period and a well-pronounced continuous linear region. For microspheres with a diameter of 4 μm, the linear region is missing. Analysis of the kinetic curves illustrating controlled drug release together with the measurements on polymer degradation shows that their kinetic profiles depend on the diffusion-controlled process and hydrolytic degradation of poly(3-hydroxy)butyrate. The diffusion kinetic equation describing both linear and nonlinear regions of dipyridamole released from the microspheres involves the sum of two terms: desorption from the sphere via the diffusion-controlled mechanism and drug release via the zero-order reaction. The linear region of the drug release curve is explained by the zero-order hydrolysis of poly(3-hydroxy)butyrate. The diffusion coefficients and kinetic constants are calculated. For bigger microspheres, the existence of the continuous linear region in the corresponding kinetic curves makes it possible to use microsystems based on poly(3-hydroxy)butyrate and dipyridamole as novel systems for local prolonged drug delivery.