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

Abstract

Zhouhua Wang,1,2 Bao Chen,1 Guilan Quan,1 Feng Li,1 Qiaoli Wu,1 Linghui Dian,1 Yixuan Dong,1 Ge Li,2 Chuanbin Wu1,21School of Pharmaceutical Sciences, 2Research and Development Center of Pharmaceutical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaBackground 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 characterization 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 evaluated 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 provide a feasible approach for development of a rapidly acting oral formulation for this poorly water-soluble drug and with better absorption.Keywords: ordered mesoporous silica, poorly water-soluble drug, carbamazepine, extrusion, spheronization, pellets, bioavailability