Design of a new multiparticulate system for potential site-specific and controlled drug delivery to the colonic region

A multiparticulate dosage form consisting of a hydrophobic core coated with a pH-dependent polymer is proposed for colonic specific delivery of drugs. Different approaches for colon-specific drug delivery have been studied over the last decade, including prodrugs, polymeric coating using pH-sensitive or bacterial degradable polymers and matrices. In this work, we present a new multiparticulate system to deliver active molecules to the colonic region, which combines pH-dependent and controlled drug release properties. This system was constituted by drug loaded cellulose acetate butyrate (CAB) microspheres coated by an enteric polymer (Eudragit(R) S). Both, CAB cores and pH-sensitive microcapsules, were prepared by the emulsion-solvent evaporation technique in an oily phase. Ondansetron (OS) and budesonide (BDS), two interesting drugs with a potentially new application for the local treatment of intestinal disorders, were efficiently microencapsulated in CAB microspheres at different polymer concentrations (6 and 8%). These hydrophobic cores (about 60 and 110 mu m in size, respectively) were then microencapsulated with Eudragit(R) S, resulting in multinucleated structures, except in the case of BDS-CAB microspheres prepared at 8% CAB concentration, in which more mononucleated microcapsules were obtained. The in vitro drug release studies of pH-sensitive microcapsules containing the hydrophobic cores showed that no drug was released below pH 7. After that, CAB microspheres efficiently controlled the release of BDS, the release behavior being affected by the different polymer concentration used in their preparation. However, OS-CAB microspheres did not maintain their controlled-release properties once the enteric polymer dissolved. The extraction of the drug by the Eudragit(R) solvent during the second microencapsulation process was in this case the cause for the failure of the controlling release mechanism. (C) 1998 Elsevier Science B.V.