title: Application of carrier and plasticizer to improve the dissolution and bioavailability of poorly water-soluble baicalein by hot melt extrusion.
abstract: The objective of this study was to develop a suitable formulation for baicalein (a poorly water-soluble drug exhibiting high melting point) to prepare solid dispersions using hot melt extrusion (HME). Proper carriers and plasticizers were selected by calculating the Hansen solubility parameters, evaluating melting processing condition, and measuring the solubility of obtained melts. The characteristic of solid dispersions prepared by HME was evaluated. The dissolution performance of the extrudates was compared to the pure drug and the physical mixtures. Physicochemical properties of the extrudates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Relative bioavailability after oral administration in beagle dogs was assessed. As a result, Kollidon VA64 and Eudragit EPO were selected as two carriers; Cremophor RH was used as the plasticizer. The dissolution of all the extrudates was significantly improved. DSC and PXRD results suggested that baicalein in the extrudates was amorphous. FTIR spectroscopy revealed the interaction between drug and polymers. After oral administration, the relative bioavailability of solid dispersions with VA64 and EPO was comparative, about 2.4- and 2.9-fold greater compared to the pure drug, respectively.
authors.affiliation: Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.
authors.forename: Yilan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Luo
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Xue
authors.initials: X
authors.lastname: Ke
authors.forename: Danrong
authors.initials: D
authors.lastname: Hu
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Han
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004285:Dogs; D004337:Drug Carriers; D004355:Drug Stability; D044950:Flavanones / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D006358:Hot Temperature; D008297:Male; D008956:Models, Chemical; D044367:Phase Transition; D010968:Plasticizers / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry*; D033362:Powder Diffraction; D011759:Pyrrolidines / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods*; D014753:Vinyl Compounds / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D044950:Flavanones; D010968:Plasticizers; D011109:Polymethacrylic Acids; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D014867:Water; C022131:cremophor; D011092:Polyethylene Glycols; C006680:baicalein; C518398:Eudragit E PO