A POLY(D,L-LACTIDE-CO-GLYCOLIDE) MICROSPHERE DEPOT SYSTEM FOR DELIVERY OF HALOPERIDOL

Haloperidol-loaded biodegradable poly(D,L-lactide-co-glycolide) (PLG) microspheres, with theoretical mean particle sizes of about 0.8, 2 and 8 mu m, have been successfully prepared by using an emulsification-so lvent evaporation method. The effect of various processing parameters such as the content of polymer in dichloromethane, the content of poly vinyl alcohol in the aqueous phase, and the stirring speed of emulsifi cation on the particle size and size distribution of microspheres has been investigated and three optimal procedures suggested. The influenc e of particle size on drug content and incorporation efficiency of hal operidol-loaded PLG microspheres also has been evaluated. In vitro a l inear release of haloperidol from PLG microspheres over an extended pe riod of time without a significant burst effect has been achieved; the time of 50% drug release (T-50%) being around 55 days. The effect of drug content and particle size on the cumulative release of haloperido l from PLG microspheres was also studied together with the reproducibi lity of drug content and release profile from batch-to-batch with diff erent particle sizes. (C) 1998 Elsevier Science B.V. All rights reserv ed.