Microagglomeration of pulverized pharmaceutical powders using the Wurster process I. Preparation of highly drug-incorporated, subsieve-sized core particles for subsequent microencapsulation by film-coating

A novel agglomeration process of pulverized pharmaceutical powders into subsieve-sized agglomerates (microagglomeration) was designed for manufacturing highly drug-incorporated core particles for subsequent microencapsulation by film-coating. The microagglomeration of pulverized phenacetin powder, whose mass median diameter was 9 mu m, was performed by spraying an aqueous colloidal dispersion of acrylic polymer, Eudragit(R) RS30D, as a binding/coating agent using a spouted bed assisted with a draft tube (the Wurster process), and the effect of process variables was examined. An appropriate spray liquid flow rate made it possible to produce microagglomerates of 20-50 mu m with 60% yield. However, 10% of the product still survived as particles smaller than 10 mu m even at the elevated liquid flow rate. In contrast, the survived particles smaller than 10 mu m tended to be predominantly reduced to 2%, while coarse agglomerates larger than 53 mu m were not excessively produced, by additionally setting a fixed bed of glass beads in the spouted bed apparatus. The length of the draft tube influenced compaction of the agglomerates as well as their surface-smoothening. Equipping the fixed bed of the glass beads and the long draft tube in the spouted bed allowed us to prepare microagglomerates of 20-50 mu m at yield of 55% applicable as highly drug-incorporated, free-flowing, surface-smoothed, narrowly size-distributed core particles for subsequent microencapsulation by film-coating. (C) 1999 Elsevier Science B.V. All rights reserved.