Influence of coacervation-inducing agents and cooling rates on the preparation andin vitrorelease of bleomycin hydrochloride microcapsules

Abstract

Two types of coacervation-inducing agents (EVA, PIB) and three cooling rates (0.01998, 0.03482 and 0.06725 degrees C/min) affecting the preparation, micromeritic and drug release properties of bleomycin hydrochloride microcapsules were investigated. Particle size distribution of microcapsules induced by EVA significantly depended on the cooling rate, but that induced by PIB was independent of the cooling rate. Higher viscosity of PIB led to a smaller particle size of microcapsules than when EVA was used. The surface topography of the microcapsules for both types of coacervation-inducing agents was obviously different. We found that the release behaviour of bleomycin hydrochloride from the microcapsules also depended on the type of coacervation-inducing agent and the cooling rate. In general, the slower the cooling rate the more prolonged the release of the drug. Higuchi matrix model was followed for bleomycin hydrochloride released from the microcapsules. T50 of both types of microcapsules decreased with the increase of the cooling rate. To simulate the absorption behaviour of the GI tract, the continuous flow dialysis method was modified for drug release from the microcapsules. The data indicate that the diffusion of the dissolution medium and dissolved drug through the ethylcellulose wall of the microcapsules is the rate-limiting step before dialysis. This also implies that the release rate of the drug from dosage form significantly determined the absorption in the GI tract.