title: Novel valsartan-loaded solid dispersion with enhanced bioavailability and no crystalline changes.
abstract: With the aim of developing a novel valsartan-loaded solid dispersion with enhanced bioavailability and no crystalline changes, various valsartan-loaded solid dispersions were prepared with water, hydroxypropyl methylcellulose (HPMC) and sodium lauryl sulphate (SLS). Effects of the weight ratios of SLS/HPMC and carrier/drug on both the aqueous solubility of valsartan and the drug-release profiles of solid dispersions were investigated. The physicochemical properties of solid dispersions were characterized using scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The bioavailability of the solid dispersions in rats was evaluated compared to valsartan powder and a commercial product (Diovan). Unlike the conventional solid dispersion system, the valsartan-loaded solid dispersion had a relatively rough surface and did not change the crystalline form of the drug. It was suggested that the solid dispersions were formed by attaching hydrophilic carriers to the surface of the drug, thus changing from a hydrophobic to a hydrophilic form without changing the crystalline form. The drug-loaded solid dispersion composed of valsartan/HPMC/SLS at a weight ratio of 3/1.5/0.75 improved the drug solubility by about 43-fold. It gave a higher AUC, C(max) and shorter T(max) compared to valsartan powder and the commercial product. The solid dispersion improved the bioavailability of the drug in rats by about 2.2 and 1.7-fold in comparison with valsartan powder and the commercial product, respectively. Thus, the valsartan-loaded solid dispersion would be useful for delivering poorly water-soluble valsartan with enhanced bioavailability and no crystalline changes.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Kyungsan, Kyungbuk 712-749, South Korea.
authors.forename: Yi-Dong
authors.initials: YD
authors.lastname: Yan
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Sung
authors.forename: Kun Kook
authors.initials: KK
authors.lastname: Kim
authors.forename: Dong Wuk
authors.initials: DW
authors.lastname: Kim
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Beom-Jin
authors.initials: BJ
authors.lastname: Lee
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D004339:Drug Compounding; D057927:Hydrophobic and Hydrophilic Interactions; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; 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: D047228:Angiotensin II Type 1 Receptor Blockers; D004337:Drug Carriers; D011208:Powders; D013777:Tetrazoles; D014867:Water; D012967:Sodium Dodecyl Sulfate; D065347:Hypromellose Derivatives; D000068756:Valsartan; D008747:Methylcellulose; D014633:Valine