title: Highly ordered mesoporous carbon nanomatrix as a new approach to improve the oral absorption of the water-insoluble drug, simvastatin.
abstract: Three different kinds of highly ordered mesoporous carbon (HMC) matrices with different morphologies (hexagonal, spherical and fibrous), particle sizes (700 nm, 400-900 nm and 1-4 μm) and pore diameters were compared as drug carriers for a model drug, simvastatin (SIM). The physicochemical properties of the SIM-loaded composites were studied using field emission scanning electron microscopy (FESEM), specific surface area analysis, differential scanning calorimetry (DSC), wide-angle X-ray scattering (WAXS), HPLC, solubility measurement and dissolution testing. Furthermore, the oral bioavailability of SIM-loaded SHMC (spherical HMC nanomatrix) in beagle dogs was compared with that of the reference formulation (Zocor®). The results obtained showed that SIM molecules are encapsulated in a noncrystalline state due to geometric confinement in the nanopores of HMC. In vitro dissolution testing showed that the dissolution rate of SIM released from monodispersed SHMC was significantly faster compared with that of crystalline SIM and other SIM-loaded composites. In addition, in vivo bioavailability study demonstrated that the relative bioavailability of SIM and SIM β-hydroxy acid (an active metabolite of SIM) for SIM-loaded SHMC formulation was 138.42% and 163.55%, respectively. In conclusion, monodispersed SHMC appear to be a more promising candidate as a new oral drug delivery vehicle providing a rapid drug release and enhanced oral bioavailability.
authors.affiliation: Department of Pharmaceutics, Xuzhou Medical College, 209 Tongshan Road, Quanshan District, Xuzhou, Jiangsu Province 221004, China. yanzhuozh@yahoo.cn
authors.forename: Yanzhuo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Cunqiang
authors.initials: C
authors.lastname: Gao
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Lusi
authors.initials: L
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002244:Carbon / Q000737:chemistry*; D004285:Dogs; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008297:Male; D049329:Nanostructures / Q000737:chemistry*; D019821:Simvastatin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility
chemical_list: D004337:Drug Carriers; D002244:Carbon; D019821:Simvastatin
keywords: Bioavailability; Crystalline state; Mesoporous carbon; Nanomatrix; Solubility; Water-insoluble drugs