title: Bioadhesive tablets containing cyclodextrin complex of itraconazole for the treatment of vaginal candidiasis.
abstract: Itraconazole (ITR) is commonly used in the treatment of Candida infections. It has a nephrotoxic effect and low bioavailability in patients who suffer from renal insufficiency, and its poor solubility in water makes ITR largely unavailable. Cyclodextrins (CyDs) are used to form inclusion complexes with drugs to improve their aqueous solubility and to reduce their side effects. In this study, ITR was complexed with γ-cyclodextrin (γ-CyD), hydroxypropyl-β-cyclodextrin (HP-β-CyD), methyl-β-cyclodextrin (Met-β-CyD) and sulphobutyl ether-β-cyclodextrin (SBE7-β-CyD) to increase its water solubility and to reduce the side effects of the drug without decreasing antifungal activity. Complex formation between ITR and CyDs was evaluated using SEM, (1)H NMR and XRD studies. The antifungal activity of the complexes was analyzed on Candida albicans strains, and the susceptibility of the strains was found to be higher for the ITR-SBE7-β-CyD complex than for the complexes that were prepared with other CyDs. Vaginal bioadhesive sustained release tablet formulations were developed using the ITR-SBE7-β-CyD inclusion complex to increase the residence time of ITR in the vagina, thereby boosting the efficacy of the treatment. The swelling, matrix erosion and bioadhesion properties of formulations and the drug release rate of these tablets were analyzed, and the most therapeutically effective vaginal formulation was determined.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey. Electronic address: ecevher@istanbul.edu.tr.
authors.forename: Erdal
authors.initials: E
authors.lastname: Cevher
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
authors.forename: Ayşe
authors.initials: A
authors.lastname: Açma
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
authors.forename: Genada
authors.initials: G
authors.lastname: Sinani
authors.affiliation: Santa Farma Pharmaceuticals, Istanbul, Turkey.
authors.forename: Buket
authors.initials: B
authors.lastname: Aksu
authors.affiliation: Department of Pharmacy, University of Hertfordshire, College Lane, Hatfield, United Kingdom.
authors.forename: Mire
authors.initials: M
authors.lastname: Zloh
authors.affiliation: Department of Infectious Diseases and Clinical Microbiology, School of Medicine, Marmara University, Istanbul, Turkey.
authors.forename: Lütfiye
authors.initials: L
authors.lastname: Mülazımoğlu
mesh_terms: D000269:Adhesives / Q000737:chemistry*; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy*; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D017964:Itraconazole / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D008958:Models, Molecular; D008968:Molecular Conformation; D012995:Solubility; D013607:Tablets; D014621:Vagina / Q000737:chemistry / Q000382:microbiology; D014623:Vaginal Diseases / Q000382:microbiology*
chemical_list: D000269:Adhesives; D000935:Antifungal Agents; D003505:Cyclodextrins; D004337:Drug Carriers; D013607:Tablets; D017964:Itraconazole
keywords: Cyclodextrin; Itraconazole; Mucoadhesion; Vaginal candidiasis; Vaginal tablet