title: Increasing the dissolution rate and oral bioavailability of the poorly water-soluble drug valsartan using novel hierarchical porous carbon monoliths.
abstract: In the present study, a novel hierarchical porous carbon monolith (HPCM) with three-dimensionally (3D) ordered macropores (∼ 400 nm) and uniform accessible mesopores (∼ 5.2 nm) was synthesized via a facile dual-templating technique using colloidal silica nanospheres and Poloxamer 407 as templates. The feasibility of the prepared HPCM for oral drug delivery was studied. Valsartan (VAL) was chosen as a poorly water-soluble model drug and loaded into the HPCM matrix using the solvent evaporation method. Scanning electron microscopy (SEM) and specific surface area analysis were employed to characterize the drug-loaded HPCM-based formulation, confirming the successful inclusion of VAL into the nanopores of HPCM. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) demonstrated that the incorporated drug in the HPCM matrix was in an amorphous state and the VAL formulation exhibited good physical stability for up to 6 months. In vitro tests showed that the dissolution rate of HPCM-based formulation was increased significantly compared with that of crystalline VAL or VAL-loaded 3D ordered macroporous carbon monoliths (OMCMs). Furthermore, a pharmacokinetic study in rats demonstrated about 2.4-fold increase in oral bioavailability of VAL in the case of HPCM-based formulation compared with the commercially available VAL preparation (Valzaar(®)). These results therefore suggest that HPCM is a promising carrier able to improve the dissolution rate and oral bioavailability of the poorly water-soluble drug VAL.
authors: School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, China. Electronic address: yanzhuozhang@126.com.
authors: Yanzhuo
authors: Y
authors: Zhang
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Erxi
authors: E
authors: Che
authors: Pharmaceutical Division, Jiangsu Hengrui Pharma,Lianyungang 222047, China.
authors: Miao
authors: M
authors: Zhang
authors: Pharmaceutical Division, Jiangsu Hengrui Pharma,Lianyungang 222047, China.
authors: Baoxiang
authors: B
authors: Sun
authors: School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, China.
authors: Jian
authors: J
authors: Gao
authors: School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, China.
authors: Jin
authors: J
authors: Han
authors: School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, China.
authors: Yaling
authors: Y
authors: Song
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002244:Carbon / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019073:HT29 Cells; D006801:Humans; D016062:Porosity; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013777:Tetrazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000068756:Valsartan; D014867:Water / Q000737:chemistry
chemical_list: D000959:Antihypertensive Agents; D004337:Drug Carriers; D013777:Tetrazoles; D014867:Water; D002244:Carbon; D000068756:Valsartan; D014633:Valine
keywords: Dissolution rate; Drug delivery; Oral bioavailability; Porous carbon monolith; Solubility