Increasing the oral bioavailability of poorly water-soluble carbamazepine using immediate-release pellets supported on SBA-15 mesoporous silica

Abstract

Background and methods: The aim of this study was to develop an immediate-release pellet formulation with improved drug dissolution and adsorption. Carbamazepine, a poorly water-soluble drug, was adsorbed into mesoporous silica (SBA-15-CBZ) via a wetness impregnation method and then processed by extrusion/spheronization into pellets. Physicochemical character-ization of the preparation was carried out by scanning electron microscopy, transmission electron microscopy, nitrogen adsorption, small-angle and wide-angle x-ray diffraction, and differential scanning calorimetry. Flowability and wettability of the drug-loaded silica powder were evalu-ated by bulk and tapped density and by the angle of repose and contact angle, respectively. The drug-loaded silica powder was formulated into pellets to improve flowability. Results: With maximum drug loading in SBA-15 matrices determined to be 20% wt, in vitro release studies demonstrated that the carbamazepine dissolution rate was notably improved from both the SBA-15 powder and the corresponding pellets as compared with the bulk drug. Correspondingly, the oral bioavailability of SBA-15-CBZ pellets was increased considerably by 1.57-fold in dogs (P, 0.05) compared with fast-release commercial carbamazepine tablets. Conclusion: Immediate-release carbamazepine pellets prepared from drug-loaded silica pro-vide a feasible approach for development of a rapidly acting oral formulation for this poorly water-soluble drug and with better absorption. © 2012 Wang et al, publisher and licensee Dove Medical Press Ltd.