title: Investigation of the physicochemical and physicomechanical properties of a novel intravaginal bioadhesive polymeric device in the pig model.
abstract: The purpose of this study was to develop and evaluate the bioadhesivity, in vitro drug release, and permeation of an intravaginal bioadhesive polymeric device (IBPD) loaded with 3'-azido-3'-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Modified polyamide 6,10, poly(lactic-coglycolic acid), polyacrylic acid, polyvinyl alcohol, and ethylcellulose were blended with model drugs AZT and PSS as well as radio-opaque barium sulfate (BaSO4) and then compressed into caplet devices on a tableting press. One set of devices was coated with 2% w/v pentaerythritol polyacrylic acid (APE-PAA) while another remained uncoated. Thermal analysis was performed on the constituent polymers as well the IBPD. The changes in micro-environmental pH within the simulated human vaginal fluid due to the presence of the IBPD were assessed over a period of 30 days. Textural profile analysis indicated that the bioadhesivity of the APE-PAA-coated devices (3.699 +/- 0.464 N; 0.0098 +/- 0.0004 J) was higher than that of the uncoated devices (1.198 +/- 0.150 N; 0.0019 +/- 0.0001 J). In addition, BaSO4-facilitated X-ray imaging revealed that the IBPD adhered to pig vaginal tissue over the experimental period of 30 days. Controlled drug release kinetics was obtained over 72 days. During a 24-h permeation study, an increase in drug flux for both AZT (0.84 mg cm(-2) h(-1)) and PSS (0.72 mg cm(-2) h(-1)) was realized up to 12 h and thereafter a steady-state was achieved. The diffusion and dissolution dynamics were mechanistically deduced based on a chemometric and molecular structure modeling approach. Overall, results suggested that the IBPD may be sufficiently bioadhesive with desirable physicochemical and physicomechanical stability for use as a prolonged intravaginal drug delivery device.
authors.affiliation: Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193,, Johannesburg, South Africa.
authors.forename: Valence M K
authors.initials: VM
authors.lastname: Ndesendo
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Eckhart
authors.initials: E
authors.lastname: Buchmann
authors.forename: Leith C R
authors.initials: LC
authors.lastname: Meyer
authors.forename: Riaz A
authors.initials: RA
authors.lastname: Khan
authors.forename: Uwe
authors.initials: U
authors.lastname: Rosin
mesh_terms: D000268:Adhesiveness; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000138:chemical synthesis*; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D005260:Female; D013499:Surface Properties; D013552:Swine; D013718:Tensile Strength; D014014:Tissue Adhesives / Q000138:chemical synthesis*; D014621:Vagina / Q000737:chemistry*; D015215:Zidovudine / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D014014:Tissue Adhesives; D015215:Zidovudine
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