title: Self-microemulsifying drug-delivery system for improved oral bioavailability of pranlukast hemihydrate: preparation and evaluation.
abstract: The purpose of the present investigation was to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) for improving the oral absorption of a pranlukast hemihydrate (PLH), a very poorly water-soluble drug. An efficient self-microemulsifying vehicle for PLH was selected and optimized using solubility testing and phase diagram construction. The formulations were characterized by assessing self-emulsification performance, droplet size analysis, in vitro drug release characteristics and formulation stability studies. Optimized formulations for in vitro dissolution and bioavailability assessment were Triethylcitrate (TEC; 10%), Tween 20 (50%), Span 20 (25%), triethanolamine (5%), and benzyl alcohol (10%). The SMEDDS readily released the lipid phase to form a fine oil-in-water microemulsion with a narrow distribution size. Saturated solubilities of PLH from SMEDDS in water, pH 4.0 and 6.8, were over 150 times greater than that of plain PLH. The release of 100% PLH from SMEDDS was considerably greater compared to only 1.12% in simulated intestinal fluid (pH 6.8) from plain PLH after 2 hours. The PLH suspension with 0.5% sodium carboxymethylcellulose or 3% PLH-loaded SMEDDS was administrated at a dose of 40 mg/kg as PLH to fasted rats. The absorption of PLH from SMEDDS resulted in about a threefold increase in bioavailability compared with plain PLH aqueous suspension. Our studies illustrated that the potential use of the new SMEDDS can be used as a possible alternative to oral delivery of a poorly water-soluble drug such as PLH.
authors: Life Science R&D Park, SK Biopharmaceuticals Co, LTD, Daejeon, Republic of Korea.
authors: Myoung-Ki
authors: MK
authors: Baek
authors: Jong-Hwa
authors: JH
authors: Lee
authors: Young-Ho
authors: YH
authors: Cho
authors: Hak-Hyung
authors: HH
authors: Kim
authors: Gye-Won
authors: GW
authors: Lee
mesh_terms: D000818:Animals; D002867:Chromones / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D051381:Rats; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D002867:Chromones; D004655:Emulsions; D009821:Oils; D013501:Surface-Active Agents; C047681:pranlukast
keywords: PLH; SMEDDS; bioavailability; pranlukast hemihydrates; solubility