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Investigation of the Physicochemical and Physicomechanical Properties of a Novel Intravaginal Bioadhesive Polymeric Device in the Pig Model

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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.

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Acknowledgments

This research is supported by the Norwegian Agency for Development Co-operation (NORAD)-NORWAY, and by grants from the National Research Foundation (NRF) of South Africa and the Faculty Research Committee, University of Witwatersrand, Johannesburg, South Africa. St. John’s University of Tanzania is sincerely acknowledged.

Ethical Approval

Ethics clearance for this study was obtained from the Animal Ethics Committee of the University of the Witwatersrand (Ethics clearance no. 2007/25/05).

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Authors and Affiliations

  1. Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193,, Johannesburg, South Africa

    Valence M. K. Ndesendo, Viness Pillay, Yahya E. Choonara & Lisa C. du Toit

  2. Department of Gynecology and Obstetrics, Chris Hani Baragwanath Hospital, Bertsham, 2013, Johannesburg, South Africa

    Eckhart Buchmann

  3. Central Animal Services, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa

    Leith C. R. Meyer

  4. Department of Industrial Chemistry, Integral University, Lucknow, 226026, India

    Riaz A. Khan

  5. Research and Development Unit, PharmaNatura (Pty) Ltd., Sandton, 2012, South Africa

    Uwe Rosin

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  1. Valence M. K. Ndesendo
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  3. Yahya E. Choonara
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Correspondence to Viness Pillay.

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Ndesendo, V.M.K., Pillay, V., Choonara, Y.E. et al. Investigation of the Physicochemical and Physicomechanical Properties of a Novel Intravaginal Bioadhesive Polymeric Device in the Pig Model. AAPS PharmSciTech 11, 793–808 (2010). https://doi.org/10.1208/s12249-010-9439-3

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