title: Preparation and evaluation of valsartan by a novel semi-solid self-microemulsifying delivery system using Gelucire 44/14.
abstract: The aim of the present study was to develop a novel semi-solid self-microemulsifying drug delivery system (SMEDDS) using Gelucire(®) 44/14 as oil with strong solid character to improve the oral bioavailability of poorly soluble drug valsartan. The solubility of valsartan in various excipients was determined, the pseudo-ternary phase diagram was constructed in order to screen the optimal excipients, and DSC analysis was performed to evaluate the melting point of SMEDDS. The optimal drug-loaded SMEDDS formulation was consisted of 30% Gelucire(®) 44/14 (oil), 40% Solutol(®) HS 15 (surfactant), and 30% Transcutol(®) P (cosurfactant) (w/w) with 80 mg valsartan/g excipients. The average droplet sizes of the optimized blank and drug-loaded SMEDDS formulations were 26.20 ± 1.43 and 33.34 ± 2.15 nm, and the melting points of them were 35.6 and 36.8 °C, respectively. The in vitro dissolution rate of optimal semi-solid SMEDDS was increased compared with commercial capsules, resulting in the 2.72-fold and 2.97-fold enhancement of Cmax and AUC0-t after oral administration in rats, respectively. These results indicated that the novel semi-solid SMEDDS formulation could potentially improve the oral bioavailability of valsartan, and the semi-solid SMEDDS was a desirable system than the traditional liquid SMEDDS because it was convenient for preparation, storage and transportation due to semi-solid state at room temperature and melted state at body temperature.
authors: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , P.R. China ;
authors: Kun
authors: K
authors: Zhao
authors: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , P.R. China ;
authors: Yue
authors: Y
authors: Yuan
authors: b Department of Internal Medicine , Cardiovascular Research Center, University of Michigan , Ann Arbor , MI , USA.
authors: Hui
authors: H
authors: Wang
authors: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , P.R. China ;
authors: Panpan
authors: P
authors: Li
authors: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , P.R. China ;
authors: Zhihong
authors: Z
authors: Bao
authors: a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , P.R. China ;
authors: Yue
authors: Y
authors: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002214:Capsules / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D000068756:Valsartan / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D002214:Capsules; D004655:Emulsions; D013501:Surface-Active Agents; C104509:gelucire 44-14; D011092:Polyethylene Glycols; D000068756:Valsartan
keywords: Bioavailability; SMEDDS; in vitro release; lauroyl macrogol-32 glycerides; pseudo-ternary phase diagram