title: Dissolution enhancement of itraconazole by hot-melt extrusion alone and the combination of hot-melt extrusion and rapid freezing--effect of formulation and processing variables.
abstract: We investigated the effects of the hot-melt extrusion (HME) process on the properties of itraconazole (ITZ) amorphous solid dispersions made by thin film freezing (TFF) technology. The ITZ-HPMCAS L (1:2) TFF composition exhibited limited drug release in acidic media. HME of the ITZ-HPMCAS TFF composition with hydrophilic carriers improved the drug release rate in acidic media. The type and level of hydrophilic carrier in the composition affected the dissolution profiles of the extrudates. A design of experiments (DoE) study was conducted to elucidate those effects. Hot-melt extrusion processing variables such as extrusion temperature and screw configuration also played a critical role on the properties of the extruded compositions. A higher degree of mixing reduced the crystallinity of semicrystalline excipients and favored the drug release in the acidic media; moreover, the drug precipitation rate in the neutral pH media was reduced.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin , 2409 University Avenue, Mail Stop A1920, Austin, Texas 78712, United States.
authors.forename: Bo
authors.initials: B
authors.lastname: Lang
authors.forename: James W
authors.initials: JW
authors.lastname: McGinity
authors.forename: Robert O
authors.initials: RO
authors.lastname: Williams
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D005079:Excipients / Q000737:chemistry*; D005615:Freezing; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D017964:Itraconazole / Q000737:chemistry*; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D005079:Excipients; D017964:Itraconazole; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose