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Solid dispersion formulations of megestrol acetate with copovidone for enhanced dissolution and oral bioavailability

Hong, S.W.; Lee, B.S.; Park, S.J.; Jeon, H.R.; Moon, K.Y.; Kang, M.H.; Park, S.H.; Choi, S.-U.; Song, W.H.; Lee, J.; Choi, Y.W.

Archives of Pharmacal Research 34(1): 127-135

2011


ISSN/ISBN: 1976-3786
PMID: 21468924
DOI: 10.1007/s12272-011-0115-2
Accession: 055837326

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.

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