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

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 Wu<sup>1,2

1</sup>School of Pharmaceutical Sciences, ²Research and Development Center of Pharmaceutical Engineering, Sun Yat-sen University, Guangzhou, People’s Republic of China

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 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

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