Suppression of agglomeration in fluidized bed coating. IV. Effects of sodium citrate concentration on the suppression of particle agglomeration and the physical properties of HPMC film

We previously reported that sodium citrate (Na citrate), which is a high or der salt in the Hofmeister's series, greatly suppressed particle agglomerat ion in fluidized bed coating (Pharm. Res., 16 (1999), 1616-1620). In this p aper, we studied the effects of Na citrate concentration on the particle ag glomeration in fluidized bed coating and on the structure of coated film on the particles. Spherical granules made of crystalline cellulose (Celphere( R)) containing phenacetin were coated in a fluidized bed with the aqueous c oating solution of hydroxypropylmethyl cellulose (HPMC) containing Na citra te at various concentrations. The particle diameter and drug release profil e of coated particles, and the physical properties, i.e. tensile strength, elongation percentage at break, porosity and pore size distribution, of the HPMC cast film were investigated. The particle agglomeration was suppresse d with the increasing Na citrate concentration. It is considered that the i ncrease in the suppression effect was caused by the salting-out effect of t he increased Na citrate. In the HPMC cast film system, the tensile strength and elongation percentage decreased and the porosity and cumulative pore v olume increased with an increase in Na citrate concentration. It is conside red that the increase in the porosity by adding Na citrate resulted from a phase separation due to the salting-out during the film forming process. Th e drug release rate From coated particles also increased with the increasin g Na citrate concentration. It can be concluded that the increase in the re lease rate was due to the increase in porosity of the HPMC coated film caus ed by the increased Na citrate concentration. (C) 2001 Elsevier Science B.V . All rights reserved.