title: Increasing the oral bioavailability of poorly water-soluble carbamazepine using immediate-release pellets supported on SBA-15 mesoporous silica.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Zhouhua
authors.initials: Z
authors.lastname: Wang
authors.forename: Bao
authors.initials: B
authors.lastname: Chen
authors.forename: Guilan
authors.initials: G
authors.lastname: Quan
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Wu
authors.forename: Linghui
authors.initials: L
authors.lastname: Dian
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Dong
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000327:Adsorption; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002220:Carbamazepine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry*; D017155:Wettability
chemical_list: D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D053769:Nanocapsules; C509969:SBA-15; D014867:Water; D002220:Carbamazepine; D012822:Silicon Dioxide