title: Nanomemulsion of megestrol acetate for improved oral bioavailability and reduced food effect.
abstract: Megestrol acetate (MGA) belongs to the BCS class II drugs with low solubility and high permeability, and its oral absorption in conventional dosage form MGA microcrystal suspension (MGA MS) is very limited and greatly affected by food. In this study, MGA nanoemulsion (MGA NE) was formulated based on solubility, phase-diagram and release studies. Then oral bioavailability of MGA NE and MGA MS was evaluated. A randomized two-way crossover trial was conducted on six male dogs under fed and fasting conditions. Blood concentrations of MGA were analyzed using LC-MS/MS. MGA NE yielded 5.00-fold higher oral bioavailability in fasting conditions and displayed more stable absorption profiles after food intake compared with MGA MS.
authors.affiliation: Department of New Drug Development and NCEED, School of Medicine, Inha University, Incheon, 400-712, South Korea.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of New Drug Development and NCEED, School of Medicine, Inha University, Incheon, 400-712, South Korea.
authors.forename: Chung Kil
authors.initials: CK
authors.lastname: Song
authors.affiliation: Department of New Drug Development and NCEED, School of Medicine, Inha University, Incheon, 400-712, South Korea.
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of New Drug Development and NCEED, School of Medicine, Inha University, Incheon, 400-712, South Korea.
authors.forename: Hyosang
authors.initials: H
authors.lastname: Lim
authors.affiliation: Department of New Drug Development and NCEED, School of Medicine, Inha University, Incheon, 400-712, South Korea.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Division of Gastroenterology & Hepatology, Inha University Hospital, Incheon, 400-712, South Korea.
authors.forename: Don Haeng
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of New Drug Development and NCEED, School of Medicine, Inha University, Incheon, 400-712, South Korea. Sugeun.Yang@inha.ac.kr.
authors.forename: Su-Geun
authors.initials: SG
authors.lastname: Yang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004285:Dogs; D004655:Emulsions; D018565:Food-Drug Interactions; D008297:Male; D019290:Megestrol Acetate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D053758:Nanoparticles; D011897:Random Allocation; D012995:Solubility; D053719:Tandem Mass Spectrometry
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004655:Emulsions; D019290:Megestrol Acetate
keywords: BCS class II drugs; Food-effect; Megestrol acetate; Nanoemulsion; Oral bioavailability