A poly( d, l-lactide-co-glycolide) microsphere depot system for delivery of haloperidol

Abstract

Haloperidol-loaded biodegradable poly( d, l-lactide-co-glycolide) (PLG) microspheres, with theoretical mean particle sizes of about 0.8, 2 and 8 μm, have been successfully prepared by using an emulsification–solvent evaporation method. The effect of various processing parameters such as the content of polymer in dichloromethane, the content of polyvinyl alcohol in the aqueous phase, and the stirring speed of emulsification on the particle size and size distribution of microspheres has been investigated and three optimal procedures suggested. The influence of particle size on drug content and incorporation efficiency of haloperidol-loaded PLG microspheres also has been evaluated. In vitro a linear release of haloperidol from PLG microspheres over an extended period 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 haloperidol from PLG microspheres was also studied together with the reproducibility of drug content and release profile from batch-to-batch with different particle sizes.