title: Characterization and In Vitro Evaluation of the Complexes of Posaconazole with β- and 2,6-di-O-methyl-β-cyclodextrin.
abstract: Posaconazole is a triazole antifungal drug that with extremely poor aqueous solubility. Up to now, this drug can be administered via intravenous injection and oral suspension. However, its oral bioavailability is greatly limited by the dissolution rate of the drug. This study aimed to improve water solubility and dissolution of posaconazole through characterizing the inclusion complexes of posaconazole with β-cyclodextrin (β-CD) and 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD). Phase solubility studies were performed to calculate the stability constants in solution. The results of FT-IR, PXRD,1H and ROESY 2D NMR, and DSC all verified the formation of the complexes in solid state. The complexes showed remarkably improved water solubility and dissolution rate than pure posaconazole. Especially, the aqueous solubility of the DM-β-CD complex is nine times higher than that of the β-CD complex. Preliminary in vitro antifungal susceptibility tests showed that the two inclusion complexes maintained high antifungal activities. These results indicated that the DM-β-CD complexes have great potential for application in the delivery of poorly water-soluble antifungal agents, such as posaconazole.
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, 610065, China.
authors.forename: Peixiao
authors.initials: P
authors.lastname: Tang
authors.affiliation: Sichuan Guang'an Food and Drug Administration, Guang'an, 638000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, 610065, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, 610065, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xu
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, 610065, China.
authors.forename: Xinnuo
authors.initials: X
authors.lastname: Xiong
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, 610065, China.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Liao
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu, 610065, China. lihuilab@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry; D002152:Calorimetry, Differential Scanning / Q000379:methods; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014230:Triazoles / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; D047392:beta-Cyclodextrins; D014867:Water; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; C101425:posaconazole
keywords: characterization; cyclodextrin; in vitro antifungal testing; inclusion complex; posaconazole