Preparation and in vitro characterization of tretinoin-containing microspheres suited for dermatological preparations

Abstract

Preparation of tretinoin-containing microspheres with the aim of reducing undesirable skin reactions towards trans retinoic acid (TRA) and thus, improving patient compliance is of particular interest. These microspheres have to be smaller than 30 mm to avoid causing gritty feel when applying on the skin, and slow the release of drug to minimize its skin side effects. Following preliminary evaluations on process conditions for preparation of microspheres by an emulsification-solvent extraction technique, a 2³ full factorial design was employed to investigate the influence of various formulation variables including cellulose acetate (CA) concentration, polyvinyl alcohol (PVA) concentration and TRA to polymer weight ratio on physical properties and release behavior of microspheres. The particle size of microspheres increased with increasing CA concentration and TRA to polymer weight ratio, but was not much influenced by PVA concentration. The drug encapsulation efficiency increased in microspheres made at higher PVA concentration or with lower CA and TRA concentrations. Examining release data by Korsmeyer-Peppas equation indicated that the Fickian mechanism was basically involved in the drug release from all formulations. In general, a slower drug release rate (i.e. greater mean dissolution time) and smaller dissolution efficiency values were obtained where lower PVA concentration, higher CA concentration or lower drug to polymer weight ratio were used to prepare microspheres. Our results indicated that TRA-containing microspheres of suitable drug release profile and optimal particle size can be prepared by a simple emulsification-solvent extraction technique, provided that the process conditions are appropriately adopted and that polymer, emulsifier and drug concentrations are properly selected.