Coating of Pharmaceutical Powders by Fluidized Bed Process. II. : Microcapsules Produced by Layering of Fine Powder on Coarse Particles and Subsequent Aqueous Enteric Coating

Abstract

The Wurster process (Glatt GPCG-1) could produce particles whose outer layer consisted of fine phenacetin particles (70% under 20μm) adhering to or fixed on lactose particles (90μm), when a mixture of both powders was fluidized and sprayed with a binder solution. The enteric coating of layered particles was performed with an aqueous methacrylic acid-ethylacrylate (MA-EA) copolymer suspension (Eudragit L30D-55).The simple MA-EA microcapsules of coarse lactose crystals (120μm) exhibited a delayed release characterized by a lag time in the JP XI disintegration 1st fluid (pH 1.2), as previously reported. The layered phenacetin and hydroxypropylcellulose used as the binder in this study had no significant effect on the delayed relase of lactose. However, phenacetin was released according to biphasic zero-order kinetics, different from the case of directly coated coarse crystals (128μm). The apparent dissolution rate increased after the first slow release. The formation of a fine phenacetin suspension within microcapsules after the dissolution of lactose accounted for such an enhanced release.When polvinylpyrrolidone (PVP) was used as the binder, the lag times of the release of phenacetin and lactose were remarkably prolonged. The release rate of phenacetin after the lag time increased. The water intake into the microcapsules enhanced by PVP, which induced an extremely large expansion of the particles, and the reduction of viscosity accounted for these phenomena.The results showed that when PVP was used as the binder, the enteric coating through the layering process was sufficiently protective against the release of both phenacetin and lactose at the 50% coating level.