Preparation of Controlled Releasing Acrylic Polymer Microspheres of Acebutolol Hydrochloride and Those Powder Coated Microspheres with Sodium Alginate in a Polymeric Spherical Crystallization System

摘要

Acrylic polymer (Eudraglt-RS 100 or -RS PM) microspheres of acebutolol hydrochloride, a highly water soluble model drug, were prepared by the polymeric spherical crystallization technique with a good solvent (acetone + ethanol), a bridging liquid (water) and a poor solvent (cyclohexane) system. The microspheres were produced through coacervation of the drug and polymer in quasi-emulsion droplets of the good solvent and the bridging liquid mixture, but were dissolved when dispersed in the poor solvent. The preparation mechanism and the ratios of solvents employed for inducing the coacervation were determined by constructing a solubility phase diagram of the polymer in the good and poor solvent systems. To improve the sustained releasing properties of the microspheres, they were coated directly with sodium alginate powder in the same preparation batch of microspheres. The treatments of the microspheres and coated microspheres with triethyl citrate significantly retarded the drug release rates from each due to the improved embedding of the drug in the polymer. When they were formulated into capsules or tablets, the drug release rates were prolonged much further because of their gelled matrix structures formed during dis-solution. The drug release mechanism was described by the square root time model by the diffusion of drug through the gelled layer of polymer.