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Vaginal Film Drug Delivery of the Pyrimidinedione IQP-0528 for the Prevention of HIV Infection

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ABSTRACT

Purpose

Polymeric quick-dissolving films were developed as a solid dosage topical microbicide formulation for the vaginal delivery of the highly potent and non-toxic, dual-acting HIV nonnucleoside reverse transcriptase inhibitor (NNRTI) pyrimidinedione, IQP-0528.

Methods

Formulated from approved excipients, a polyvinyl alcohol (PVA) based film was manufactured via solvent casting methods. The film formulations were evaluated based upon quantitative physicochemical evaluations defined by a Target Product Profile (TPP)

Results

Films dosed with 0.1% (w/w) of IQP-0528 disintegrated within 10 min with over 50% of drug released and near 100% total drug released after 30 min. The IQP-0528 films were found to be non-toxic in in vitro CEM-SS and PBMC cell-based assays and biologically active with sub-nanomolar efficacy against HIV-1 infection. In a 12 month stability protocol, the IQP-0528 films demonstrated no significant degradation at International Conference on Harmonization (ICH) recommended standard (25°C/65% relative humidity (R.H.)) and accelerated (40°C/75% R.H.) environmental conditions.

Conclusions

Based on the above evaluations, a vaginal film formulation has been identified as a potential solid dosage form for the vaginal delivery of the topical microbicide candidate IQP-0528.

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ACKNOWLDEGMENTS & DISCLOSURES

We would like to acknowledge the International Partnership for Microbicides (IPM) for their initial work in vaginal film formulations as a microbicides which assisted in the development of this study.

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Authors and Affiliations

  1. ImQuest BioSciences Inc., 7340 Executive Way, Suite R, Frederick, Maryland, 21704, USA

    Anthony S. Ham, Ashlee Boczar, Lu Yang, Karen W. Buckheit & Robert W. Buckheit Jr.

  2. Magee-Womens Research Institute, Pittsburgh, Pennsylvania, 15213, USA

    Lisa Cencia Rohan

Authors
  1. Anthony S. Ham
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  2. Lisa Cencia Rohan
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  3. Ashlee Boczar
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  4. Lu Yang
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  5. Karen W. Buckheit
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  6. Robert W. Buckheit Jr.
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Corresponding author

Correspondence to Anthony S. Ham.

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Ham, A.S., Rohan, L.C., Boczar, A. et al. Vaginal Film Drug Delivery of the Pyrimidinedione IQP-0528 for the Prevention of HIV Infection. Pharm Res 29, 1897–1907 (2012). https://doi.org/10.1007/s11095-012-0715-7

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  • DOI: https://doi.org/10.1007/s11095-012-0715-7

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