title: Itraconazole solid dispersion prepared by a supercritical fluid technique: preparation, in vitro characterization, and bioavailability in beagle dogs.
abstract: This research aimed to develop a supercritical fluid (SCF) technique for preparing a particulate form of itraconazole (ITZ) with good dissolution and bioavailability characteristics. The ITZ particulate solid dispersion was formulated with hydroxypropyl methylcellulose, Pluronic F-127, and L-ascorbic acid. Aggregated particles showed porous structure when examined by scanning electron microscopy. Powder X-ray diffraction and Fourier transform infrared spectra indicated an interaction between ITZ and excipients and showed that ITZ existed in an amorphous state in the composite solid dispersion particles. The solid dispersion obtained by the SCF process improved the dissolution of ITZ in media of pH 1.0, pH 4.5, and pH 6.8, compared with a commercial product (Sporanox(®)), which could be ascribed to the porous aggregated particle shape and amorphous solid state of ITZ. While the solid dispersion did not show a statistical improvement (P=0.50) in terms of oral bioavailability of ITZ compared with Sporanox(®), the C max (the maximum plasma concentration of ITZ in a pharmacokinetic curve) of ITZ was raised significantly (P=0.03) after oral administration. Thus, the SCF process has been shown to be an efficient, single step process to form ITZ-containing solid dispersion particles with good dissolution and oral bioavailability characteristics.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai, People's Republic of China ; Changzhou Pharmaceutical Factory, Changzhou, People's Republic of China.
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Yin
authors.affiliation: Crystec Pharma Tianjin Research Centre, Tianjin, People's Republic of China.
authors.forename: Linda Sharon
authors.initials: LS
authors.lastname: Daintree
authors.affiliation: Changzhou Pharmaceutical Factory, Changzhou, People's Republic of China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ding
authors.affiliation: Crystec Pharma Tianjin Research Centre, Tianjin, People's Republic of China.
authors.forename: Daniel Mark
authors.initials: DM
authors.lastname: Ledger
authors.affiliation: Changzhou Pharmaceutical Factory, Changzhou, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Crystec Pharma Tianjin Research Centre, Tianjin, People's Republic of China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai, People's Republic of China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education, Shanghai, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Han
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001205:Ascorbic Acid / Q000737:chemistry; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004285:Dogs; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives / Q000737:chemistry; D017964:Itraconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D020442:Poloxamer / Q000737:chemistry; D012995:Solubility
chemical_list: D000935:Antifungal Agents; D005079:Excipients; D020442:Poloxamer; D017964:Itraconazole; D065347:Hypromellose Derivatives; D001205:Ascorbic Acid
keywords: HPMC; Pluronic F-127; ascorbic acid; dissolution; gas anti-solvent; in vivo