title: Stabilizer choice for rapid dissolving high potency itraconazole particles formed by evaporative precipitation into aqueous solution.
abstract: The objective of this study was to investigate the influence of stabilizer type on the physicochemical properties, including dissolution, of ultra-high potency powders containing itraconazole (ITZ) formed by evaporative precipitation into aqueous solution (EPAS). ITZ was dissolved in dichloromethane, which was then atomized through a heated coil at 80 degrees C into an aqueous solution over precise periods of time. Stabilizers were present in either the aqueous, organic or both phases. The dispersions were centrifuged and the supernatant was removed. Three hydrophilic stabilizers were investigated, including polysorbate 80, polyvinyl pyrrolidone and poloxamer 407. Rapid dissolving ultra-high potency of ITZ powders was successfully produced. Greater than 80% of ITZ was dissolved in 5 min compared to only 13% of ITZ bulk powders. The resulting stabilizer-coated drug particles had high drug-to-stabilizer ratios greater than 12, corresponding to potencies (wt drug/wt drug+wt surfactant) as high as 93%. An increase in dissolution rate was correlated with the amount of stabilizer adsorbed and the wettability. The combination of polysorbate 80 and poloxamer 407 present in the aqueous and organic phases, respectively, was superior in achieving high wetting and rapid dissolving ITZ powders. The ability to control the adsorption behavior of stabilizers by using synergistic combinations affords the opportunity to achieve high dissolution rates with higher potencies compared to previously reported values.
authors.affiliation: College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Prapasri
authors.initials: P
authors.lastname: Sinswat
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Gao
authors.forename: Miguel J
authors.initials: MJ
authors.lastname: Yacaman
authors.forename: Robert O
authors.initials: RO
authors.lastname: Williams
authors.forename: Keith P
authors.initials: KP
authors.lastname: Johnston
mesh_terms: D000327:Adsorption; D000935:Antifungal Agents / Q000737:chemistry / Q000493:pharmacokinetics; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D017964:Itraconazole / Q000737:chemistry* / Q000493:pharmacokinetics; D008752:Methylene Chloride / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D044367:Phase Transition; D011208:Powders / Q000737:chemistry; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D005079:Excipients; D011208:Powders; D012996:Solutions; D014867:Water; D017964:Itraconazole; D008752:Methylene Chloride