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.
Olmesartan medoxomil (OLM) is an antihypertensive angiotensin II receptor blocker. OLM has a low bioavailability (BA), approximately 26% in humans, due to its low water solubility and efflux by drug resistance pumps in the gastrointestinal tract. Self-microemulsifying drug delivery system (SMEDDS), which is easily emulsified in aqueous media under gentle agitation and digestive motility, was formulated to increase the oral BA of OLM. Among the surfactants and oils studied, Capryol 90, Tween 20, and Tetraglycol were chosen and combined at a volume ratio of 1:6:3 on the basis of equilibrium solubility and phase diagram experiments. The mean droplet size of SMEDDS was 15 nm. In an oral absorption study in rats, SMEDDS formulation brought faster absorption compared to suspension, showing a T(max) value of 0.2 hr. The C(max) and AUC values of SMEDDS formulation were significantly higher than those of suspension, revealing a relative BA of about 170%. Our study demonstrated the potential usefulness of SMEDDS for the oral delivery of poorly absorbable compounds, including OLM.
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