title: Comparative interaction of 2-hydroxypropyl-beta-cyclodextrin and sulfobutylether-beta-cyclodextrin with itraconazole: phase-solubility behavior and stabilization of supersaturated drug solutions.
abstract: Cyclodextrins can increase the apparent solubility and dissolution rate of poorly water-soluble drug candidates improving their biopharmaceutical performance. The current data assess the ability of hydrophilic cyclodextrins to solubilize compounds via stabilization of supersaturated drug solutions presumably by inhibition of nucleation and arresting crystal growth. To these points, the effects of 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) and sulfobutylether-beta-cyclodextrin (SBEbetaCD) on equilibrium solubility was assessed via phase-solubility analysis as were the interactions of these excipients on drug solubility under conditions favoring supersaturation. Phase-solubility analysis indicated that different profiles were generated as a function of the cyclodextrin examined and the pH of the complexing medium. When kinetic solubility measurements were completed, the cyclodextrins were found to stabilize concentrations of itraconazole significantly in excess of their equilibrium solubility when supersaturated solutions were formed using the co-solvent/solvent quench approach. These solutions were stable over 240 min falling in concentration at the 24 h time point of the experiment unlike those formed using surfactants and other polymers which demonstrated a rapid decrease in concentration over time. These data suggest that hydrophilic cyclodextrins might be useful formulation adjuncts in supersaturating drug delivery systems.
authors.affiliation: Pharmaceutical Sciences, Chemical and Pharmaceutical Development, Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium. mbrewste@prdbe.jnj.com
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Brewster
authors.forename: Roger
authors.initials: R
authors.lastname: Vandecruys
authors.forename: Jef
authors.initials: J
authors.lastname: Peeters
authors.forename: Peter
authors.initials: P
authors.lastname: Neeskens
authors.forename: Geert
authors.initials: G
authors.lastname: Verreck
authors.forename: Thorsteinn
authors.initials: T
authors.lastname: Loftsson
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000465:Algorithms; D005079:Excipients / Q000737:chemistry*; D017964:Itraconazole / Q000737:chemistry*; D008823:Micelles; D012995:Solubility; D012996:Solutions; D013501:Surface-Active Agents / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D005079:Excipients; D008823:Micelles; D012996:Solutions; D013501:Surface-Active Agents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C093196:SBE4-beta-cyclodextrin; D017964:Itraconazole