title: Preparation and in vitro/in vivo characterization of tranilast-AMP clay complex for improving drug dissolution and bioavailability.
abstract: The present study aimed to develop an effective oral formulation of tranilast (TL), a poorly soluble anti-inflammatory drug, via the formation of drug complex with 3-aminopropyl functionalized magnesium phyllosilicate (AMP clay) and improve the pH-dependent drug dissolution and bioavailability of TL. The drug-clay complex (TL-AMP complex) was prepared by co-precipitation method and its structural properties were characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy and transmission electron microscopy. The dissolution profiles of TL-AMP complex were evaluated at different pHs. The formation of TL-AMP complex significantly improved the dissolution rate as well as the extent of drug release at acidic pHs, while the dissolution of untreated TL was negligible at pH 1.2 and 4.0. TL-AMP complex also achieved faster drug release than untreated drug (about 90 vs 30 % within 30 min) at pH 6.8. After oral administration to rats, TL-AMP complex enhanced significantly (p < 0.05) oral drug exposure and increased Cmax and AUC by six- and threefolds, respectively, compared to untreated TL. In conclusion, TL-AMP complex may be promising to improve the pH-dependent dissolution as well as bioavailability of TL.
authors.affiliation: BK Plus Project Team, College of Pharmacy, Dongguk University-Seoul, Dongguk-ro-32, Ilsan-Donggu, Goyang, Korea.
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.forename: Yating
authors.initials: Y
authors.lastname: Shao
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Han
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D017633:Magnesium Silicates / Q000737:chemistry*; D008297:Male; D046529:Microscopy, Electron, Transmission; D011437:Propylamines; D017207:Rats, Sprague-Dawley; D012821:Silanes / Q000737:chemistry*; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013997:Time Factors; D014961:X-Ray Diffraction; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D017633:Magnesium Silicates; D011437:Propylamines; D012821:Silanes; D062367:ortho-Aminobenzoates; C012293:tranilast; C477625:amino-propyl-triethoxysilane