title: Preparation and characterization of pH-independent sustained release tablet containing solid dispersion granules of a poorly water-soluble drug.
abstract: Sustained release (SR) tablets containing solid dispersions (SD) granules of a poorly water-soluble drug were prepared to investigate the controlled pH-independent release of the drug. Losartan potassium (LST), an anti-hypertensive agent was chosen as a model drug because of its pH-dependent solubility and short elimination half-life. Poloxamer 188 was used as an SD carrier. A free-flowing SD granule was prepared by adsorbing the melt of the drug and poloxamer 188 onto the surface of an adsorbent, Aerosil 300 (fumed silicon dioxide), followed by direct compression with polyethylene oxide (PEO, 5 × 10(6)) to obtain an SD-loaded SR (SD-SR) matrix tablet. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) revealed partially amorphous structures of the drug in the SD granules. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) images indicated adsorption of SD granules onto the surface of the adsorbent. The SD granules dissolved completely within 10 min, a dissolution rate much higher than that of pure LST. Moreover, pH-independent sustained release of LST from the SD-SR tablet was achieved for 2h in gastric fluid (pH 1.2) and for 10h in intestinal fluid (pH 6.8). A combination of SD techniques using surface adsorption and SR concepts is a promising approach to control the release rate of poorly water-soluble drugs in a pH-independent manner.
authors.affiliation: Bioavailability Control Laboratory, College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Huyen Thi Thanh
authors.initials: HT
authors.lastname: Tran
authors.forename: Jun Bom
authors.initials: JB
authors.lastname: Park
authors.forename: Ki-Hyuk
authors.initials: KH
authors.lastname: Hong
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Han
authors.forename: Jaehwi
authors.initials: J
authors.lastname: Lee
authors.forename: Kyung Taek
authors.initials: KT
authors.lastname: Oh
authors.forename: Beom-Jin
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D005750:Gastric Juice / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007419:Intestinal Secretions / Q000737:chemistry; D019808:Losartan / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008855:Microscopy, Electron, Scanning; D020442:Poloxamer / Q000737:chemistry; D012995:Solubility; D013052:Spectrometry, X-Ray Emission; D013499:Surface Properties; D013607:Tablets; D013817:Thermography
chemical_list: D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D013607:Tablets; D020442:Poloxamer; D019808:Losartan