Investigation of the physicochemical and physicomechanical properties of a novel intravaginal bioadhesive polymeric device in the pig model.
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.
Ndesendo
Valence M K
VM
Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193,, Johannesburg, South Africa.
Pillay
Viness
V
Choonara
Yahya E
YE
du Toit
Lisa C
LC
Buchmann
Eckhart
E
Meyer
Leith C R
LC
Khan
Riaz A
RA
Rosin
Uwe
U
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*
D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D014014:Tissue Adhesives; D015215:Zidovudine
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