title: Carboxylated mesoporous carbon microparticles as new approach to improve the oral bioavailability of poorly water-soluble carvedilol.
abstract: The main objective of this study was to develop carboxylated ordered mesoporous carbon microparticles (c-MCMs) loaded with a poorly water-soluble drug, intended to be orally administered, able to enhance the drug loading capacity and improve the oral bioavailability. A model drug, carvedilol (CAR), was loaded onto c-MCMs via a procedure involving a combination of adsorption equilibrium and solvent evaporation. The physicochemical properties of the drug-loaded composites were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and HPLC. It was found that c-MCM has a high drug loading level up to 41.6%, and higher than that of the mesoporous silica template. Incorporation of CAR in both drug carriers enhanced the solubility and dissolution rate of the drug, compared to the pure crystalline drug. After loading CAR into c-MCMs, its oral bioavailability was compared with the marketed product in dogs. The results showed that the bioavailability of CAR was improved 179.3% compared with that of the commercial product when c-MCM was used as the drug carrier. We believe that the present study will help in the design of oral drug delivery systems for enhanced oral bioavailability of poorly water-soluble drugs.
authors.affiliation: Department of Pharmaceutics, Xuzhou Medical College, Xuzhou 221004, PR China. yanzhuozh@yahoo.cn
authors.forename: Yanzhuo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhizhuang
authors.initials: Z
authors.lastname: Zhi
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.forename: Yaling
authors.initials: Y
authors.lastname: Song
mesh_terms: D000284:Administration, Oral; D000327:Adsorption; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002152:Calorimetry, Differential Scanning; D002227:Carbazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D002244:Carbon / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry* / Q000633:toxicity; D000077261:Carvedilol; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004285:Dogs; D004337:Drug Carriers; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D010316:Particle Size; D016062:Porosity; D033362:Powder Diffraction; D011412:Propanolamines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry*
chemical_list: D002227:Carbazoles; D002264:Carboxylic Acids; D004337:Drug Carriers; D011412:Propanolamines; D012997:Solvents; D014867:Water; D000077261:Carvedilol; D002244:Carbon
keywords: Bioavailability; Carboxylated ordered mesoporous carbon; Carvedilol; Crystalline state; Drug delivery; Poorly water-soluble drugs