title: Solid dispersion formulations of megestrol acetate with copovidone for enhanced dissolution and oral bioavailability.
abstract: In order to enhance the dissolution profile and oral bioavailability of megestrol acetate (MA), solid dispersions of MA (MASDs) were formulated with copovidone and crystal sugar as a hydrophilic polymeric carrier and an inert core bead, respectively. Solvent evaporation method and fluidized bed coating technique were employed. MASDs were categorized as crystalline solid dispersion by the characterization of differential scanning calorimetry and X-ray diffraction. The mass-median diameters of MASDs were in a range of 1.4 to 2.6 μm. Based on drug to polymer ratio, MASD (1:1) and (1:2) were considered as optimized formulations, resulting in a smooth-surfaced homogeneously coated layer with enhanced dissolution rate. Dissolution of MASD was gradually increased up to 15 min, after which it reached a plateau. For the initial period, dissolution rates were in the decreasing order of MASD (1:2) ≥ MASD (1:1) > MASD (1:3) > MASD (1:5) > MASD (1:0.5) > MA powder. In the comparative pharmacokinetic study with Megace OS, a reference drug product, MASD (1:1) showed improved bioavailability of over 220% with 2-fold higher C(max) and 30% faster T(max). We conclude that MASD (1:1) is a good candidate for the development of oral solid dosage forms.
authors.affiliation: Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, Korea.
authors.forename: Soon Wook
authors.initials: SW
authors.lastname: Hong
authors.forename: Bong Sang
authors.initials: BS
authors.lastname: Lee
authors.forename: Su Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Hong Ryeol
authors.initials: HR
authors.lastname: Jeon
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Moon
authors.forename: Mean Hyung
authors.initials: MH
authors.lastname: Kang
authors.forename: Sang Han
authors.initials: SH
authors.lastname: Park
authors.forename: Sung-Up
authors.initials: SU
authors.lastname: Choi
authors.forename: Woo Heon
authors.initials: WH
authors.lastname: Song
authors.forename: Jaehwi
authors.initials: J
authors.lastname: Lee
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Choi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000880:Anthraquinones / Q000737:chemistry; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D005079:Excipients / Q000737:chemistry*; D008297:Male; D019290:Megestrol Acetate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D011759:Pyrrolidines / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013395:Sucrose / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000880:Anthraquinones; D018931:Antineoplastic Agents, Hormonal; D005079:Excipients; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); C036239:cyanine green G base; D013395:Sucrose; D019290:Megestrol Acetate