title: Preparation of osthole-polymer solid dispersions by hot-melt extrusion for dissolution and bioavailability enhancement.
abstract: 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.
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Street, Nanjing 210046, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yun
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Street, Nanjing 210046, China.
authors.forename: An
authors.initials: A
authors.lastname: Kang
authors.affiliation: First College of Clinical Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Street, Nanjing 210046, China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Shan
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Street, Nanjing 210046, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Street, Nanjing 210046, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Bi
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Street, Nanjing 210046, China.
authors.forename: Junsong
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Street, Nanjing 210046, China. Electronic address: diliuqing@hotmail.com.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Di
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D008297:Male; D011108:Polymers / Q000737:chemistry*; D033362:Powder Diffraction; D011208:Powders; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D003374:Coumarins; D004337:Drug Carriers; D011108:Polymers; D011208:Powders; C046627:osthol
keywords: Bioavailability; Dissolution rate; Hot-melt extrusion; Osthole; Solid dispersion; Solubility parameter