Development of 5-fluorouracil loaded poly(acrylamide-co-methylmethacrylate) novel core-shell microspheres:: In vitro release studies

Novel poly(acrylamide-methylmethacrylate) copolymeric core-shell microspheres crosslinked with N,N'-methylene bisacrylamide have been prepared by free radical emulsion polymerization using varying amounts of acrylamide (AAm), methylmethacrylate (MMA) and N,N'-methylene bisacrylamide (NNMBA). 5-Fluorouracil was loaded into these microspheres during in situ polymerization (method-I) as well as by the absorption and adsorption technique (method-II). The core-shell microspheres have been characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (X-RD) to understand about the drug dispersion in microspheres. Scanning electron microscopy (SEM) was used to assess the surface morphology of particles prepared. In vitro release of 5-fluorouracil has been studied in terms of core-shell composition, amount of crosslinking agent and amount of 5-fluorouracil in the microspheres. Core-shell microspheres with different copolymer compositions have been prepared in yields ranging 80-85%. DSC and X-RD techniques indicated a uniform distribution of 5-fluorouracil particles in core-shell microspheres, whereas SEM suggested the formation of well-defined core-shell structures. The in vitro drug release indicated that particle size and release kinetics depend upon copolymer composition, amount of crosslinking agent used and amount of 5-fluorouracil present in the microspheres. Prolonged and controlled release of 5-fluorouracil was achieved when drug was loaded by method-I instead of method-II. (c) 2006 Elsevier B.V. All rights reserved.