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.
