title: Development and characterization of a solid dispersion film for the vaginal application of the anti-HIV microbicide UAMC01398.
abstract: The purpose of this work was to design and evaluate a vaginal film delivery system for UAMC01398, a novel non-nucleoside reverse transcriptase inhibitor currently under investigation for use as an anti-HIV microbicide. UAMC01398 (1mg) films consisting of hydroxypropylmethylcellulose (HPMC) and polyethylene glycol 400 (PEG400) in different ratios were prepared by solvent evaporation. Based on its flexibility, softness and translucent appearance, the 30% PEG400 and 70% HPMC containing film was selected for further assessment. The vaginal film formulation was fast-dissolving (<10 min in 1 mL of vaginal fluid simulant), stable up to at least one month and safe toward epithelial cells and lactobacilli. Furthermore, formulating UAMC01398 into the film dosage form did not influence its antiviral activity. Powder X-ray diffraction revealed the amorphous nature of the UAMC01398 film, resulting in enhanced compound permeation across the epithelial HEC-1A cell layer, presumably owing to the induction of supersaturation. The in vivo vaginal tissue uptake of UAMC01398 in rabbits, as measured by systemic concentrations, was increased compared to the previously established non-solubilizing gel (significant difference) and sulfobutyl ether-β-cyclodextrin (5%) containing gel. To conclude, we identified a film formulation suitable for the vaginal delivery of UAMC01398.
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Carolien
authors.initials: C
authors.lastname: Grammen
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Appeltans
authors.affiliation: Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Michiels
authors.affiliation: HIV/STD Reference Laboratory, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Tania
authors.initials: T
authors.lastname: Crucitti
authors.affiliation: Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Ariën
authors.affiliation: Laboratory of Medicinal Chemistry, University of Antwerp, Antwerp, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Augustyns
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
authors.affiliation: Drug Delivery and Disposition, KU Leuven, Leuven, Belgium. Electronic address: joachim.brouwers@pharm.kuleuven.be.
authors.forename: Joachim
authors.initials: J
authors.lastname: Brouwers
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects; D005079:Excipients / Q000737:chemistry; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D065347:Hypromellose Derivatives / Q000737:chemistry; D007778:Lactobacillus / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D011817:Rabbits; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D014621:Vagina / Q000187:drug effects*; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage* / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D019380:Anti-HIV Agents; D005079:Excipients; D018894:Reverse Transcriptase Inhibitors; D012997:Solvents; D014622:Vaginal Creams, Foams, and Jellies; D047392:beta-Cyclodextrins; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; C031215:betadex
keywords: In vitro epithelial permeation; In vivo rabbit study; Microbicide; Solid dispersion; Supersaturation; Vaginal film