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.

The Crystal Structure of Shiga Toxin Type 2 with Bound Disaccharide Guides the Design of a Heterobifunctional Toxin Inhibitor

“…Although polyacrylamide was employed here, multivalent agonists employing a biocompatible polymer such as copovidone, approved for oral use as an excipient (47), could be employed to complex toxin released in a combination therapy with antibiotics. Perhaps even more attractive is the discovery of univalent low molecular weight antagonists after screening of focused libraries informed by the solved structure of the Stx2a-2 complex (48).…”

Hot melt extrusion method for preparation of ibuprofen/sucroester WE15 solid dispersions: evaluation and stability assessment

“…This result could be used to tailor the required release profile by increasing the percentage of SEs in the formula. While, SE ® WE15 succeeded to sustain the IBU release rate up to 8 hours from hot melt extrudates, however, it was used previously to enhance the release of poorly soluble compounds: 17-Estradiol (Hülsmann et al, 2000) and Nifedipine (Badr, 2006). Szűts et al, 2008 used the melt technology (i.e.…”

“…The two major processes of preparing SDs are melting (fusion) and solvent evaporation methods ( Van den Mooter, 2006;Vilhelmsen et al, 2005;Won et al, 2005). Other various approaches include co-evaporation (Hong et al, 2011), hot spin mixing (Dittgen et al, 1995), roll-mixing or co-milling (Breitenbach, 2002), freeze-drying (Sekikawa et al, 1983), spray drying (Caron et al, 2011), and supercritical fluid processing (SFP) (Gong et al, 2005). In the 1980s, hot melt extrusion (HME) was used for the first time in the formulation of pharmaceuticals (Stanković et al, 2013).…”

“…Previous literature had discussed various preparations of IBU/ SDs for improving its dissolution using different carriers (Dabbagh and Taghipour, 2007;Esnaashari et al, 2005;Islam et al, 2010;Newa et al, 2007;Newa et al, 2008a;Newa et al, 2008b;Newa et al, 2008c;Park et al, 2009;Xu et al, 2007). SDs prepared by fusion method was used to enhance the solubility, dissolution rate and absorption of IBU using PEG 6000 (Gawai et al, 2013), mixture of tween 80 & span 80 (Shahrin and Huq, 2012) and polyethylene glycol (PEG) 8000 (Ofokansi et al, 2016).…”

Spray coating as a powerful technique in preparation of solid dispersions with enhanced desloratadine dissolution rate

“…Traditionally, rotary evaporator method for removing residual solvent does not allow the removal of the solvent from the coprecipitates to an acceptable level, because the coprecipitates become more and more viscous during the drying process, which prevents further evaporation of the residual solvent 13,14 . Lately, several new drying techniques (spray drying, fluid-bed and spray coating) have been applied to produce solid dispersion powders that afterwards may be formulated into a variety of dosage forms 5,9,[15][16][17][18] . These techniques are highly efficient in solvent removal, while drying and micronizing are effected simultaneously to produce amorphous drug/carrier powders, which can be further formulated with other excipients into dosage forms.…”