title: Posaconazole/hydroxypropyl-β-cyclodextrin host-guest system: Improving dissolution while maintaining antifungal activity.
abstract: This study aimed to prepare and characterize the inclusion complex between posaconazole (POS) and hydroxypropyl-β-cyclodextrin (HP-β-CD). Phase solubility study was conducted to investigate the drug/CD interaction in solution, including the stoichiometry and apparent stability constant. The solid complex (HP-β-CD-POS) obtained was characterized through Fourier transform infrared spectroscopy, powder X-ray diffraction, (1)H and ROESY 2D nuclear magnetic resonance, differential scanning calorimetry, and scanning electron microscopy. These approaches confirmed the formation of the inclusion complex. The HP-β-CD-POS inclusion complex exhibited better water solubility and higher dissolution rate than the free POS did; the water solubility of POS was increased by 82 times and almost 90% of the loaded drug dissolved after 10 min in the dissolution media. In addition, preliminary in vitro antifungal susceptibility testing revealed that HP-β-CD-POS maintains a high level of antifungal activities. Therefore, the HP-β-CD complex may be useful in the delivery of posaconazole.
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Peixiao
authors.initials: P
authors.lastname: Tang
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: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
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: Bin
authors.initials: B
authors.lastname: Tang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, China. Electronic address: lihuilab@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D009181:Mycoses / Q000188:drug therapy; D012995:Solubility; D014230:Triazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D014230:Triazoles; D047392:beta-Cyclodextrins; D014867:Water; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C101425:posaconazole
keywords: Acetone (PubChem CID: 180); Characterization; Dissolution; Heavy water (PubChem CID: 24602); Hydroxypropyl-beta-cyclodextrin (PubChem CID: 14049689); Hydroxypropyl-β-cyclodextrin; In vitro anti-fungal; Inclusion complex; Methanol (PubChem CID: 887); Posaconazole; Posaconazole (PubChem CID: 468595)