Preparation of osthole-polymer solid dispersions by hot-melt extrusion for dissolution and bioavailability enhancement.
The aim of this study was to investigate the potential of solid dispersion to improve the dissolution rate and bioavailability of osthole (Ost), a coumarin derivative with various pharmacological activities but with poor aqueous solubility. In present studies, the Ost solid dispersions were prepared with various polymers including Plasdone S-630, HPMC-E5, Eudragit EPO, and Soluplus by hot-melt extrusion method. In vitro characterizations were performed with differential scanning calorimetry (DSC), X-ray powder diffraction (XPRD), Fourier transform infrared (FT-IR) spectroscopy, and in vitro dissolution studies. In addition, in vivo pharmacokinetic studies of Ost solid dispersions were also conducted in rats after a single oral dose. In comparison to the untreated Ost coarse powder and the physical mixture with polymers, the solid dispersions prepared with Plasdone S-630 or HPMC-E5 (drug/polymer: 1:6) showed a significant enhancement of dissolution rate (∼3-fold higher D30). In addition, such preparations exhibited a significantly decreased Tmax, ∼5-fold higher Cmax and ∼1.4-fold higher AUC when comparing with Ost coarse powder. In conclusion, solid dispersion prepared with appropriate polymer could serve as a promising formulation approach to enhance the dissolution rate and hence oral bioavailability of Ost.
['Yun|Fei|F|', 'Kang|An|A|', 'Shan|Jinjun|J|', 'Zhao|Xiaoli|X|', 'Bi|Xiaolin|X|', 'Li|Junsong|J|', 'Di|Liuqing|L|']
D000284:Administration, Oral D000818:Animals D001682:Biological Availability D002152:Calorimetry, Differential Scanning D002626:Chemistry, Pharmaceutical D003374:Coumarins D018360:Crystallography, X-Ray D004337:Drug Carriers D008297:Male D011108:Polymers D033362:Powder Diffraction D011208:Powders D017207:Rats, Sprague-Dawley D012995:Solubility D017550:Spectroscopy, Fourier Transform Infrared D013678:Technology, Pharmaceutical
Solid dispersion Hot-melt extrusion Bioavailability Dissolution rate Osthole Solubility parameter