Skip to main content
2024 PharmSci 360 Main banner
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.
Back

Formulation and Delivery - Biomolecular

(T0930-05-26) On-Demand Multi-Indication Fast-Disintegrating Tablets for HIV Prevention and Birth Control: Formulation Development and In Vitro Evaluation

Tuesday, October 22, 2024
9:30 AM – 10:30 AM MT
Purpose: The Multipurpose Prevention Technology (MPT) development space is dominated by candidates that contain hormonal contraceptives and HIV/STI prevention drugs. We aim to develop on-demand vaginal MPT fast-disintegrating tablets (FDTs) containing non-hormonal acid-buffering contraceptives and non-antiretroviral (non-ARV) HIV entry inhibitor Q-Griffithsin (QGRFT). The non-hormonal contraceptive components may reduce health risks due to contraceptive hormones and have the potential to be used by women who are breastfeeding or are unable/unwilling to use hormonal contraception. Meanwhile, QGRFT, an oxidation-resistant derivative of Griffithsin with potent anti-HIV activity, could protect against HIV. 

Methods: Non-hormonal-contraceptive ingredients were prepared using combinations of biocompatible acids and optimized to match the buffer capacity of a marketed non-hormonal contraceptive gel (Phexxi). FDTs containing contraceptive ingredients and tablet excipients were prepared by tablet compression (LFA, TX). The formulations were developed, optimized, and evaluated for their appearance, disintegration time in aqueous solution by Vaginal Tablet Tester (Copley Scientific, UK), buffer capacity by pH meter (Thermo Fisher Scientific, MA), moisture content by Karl Fischer titrator (Mettler Toledo, OH), hardness by hardness tester (SOTAX, MA) and friability by friability tester (SOTAX, MA). The top four formulations (AAL1C, AAL1Z, AAL1.3C, and AAL1.3Z) that meet the quality targeted product profile were selected for future development into vaginal MPT. Pre-formulation studies were performed for QGRFT compatibility with the contraceptive actives, where the recovery of QGRFT was assayed by UPLC (Waters, NJ). MPT FDTs were formulated by incorporating QGRFT into formulations AAL1C, AAL1Z, AAL1.3C, and AAL1.3Z. The physicochemical properties of the MPT FDTs were characterized, and QGRFT content was assayed via UPLC. The MPT FDT formulations’ in vitro anti-sperm and anti-HIV activities were assessed. Finally, the QGRFT recovery from FDT formulations was evaluated at 4°C and 30°C/65% RH for 4 weeks.   

Results: FDT formulations AAL1C, AAL1Z, AAL1.3C, and AAL1.3Z with and without QGRFT appear off-white with smooth finish and promptly disintegrate in an aqueous environment within 1 min. They exhibit moisture content below 3%, hardness of at least 18N, and friability below 5%. The pH after the dissolution of the FDIs is within the range of pH 3.5-4.5, equivalent to healthy vaginal pH and comparable to marketed contraceptive gel. Through anti-sperm assessment, the formulations inhibit sperm motility in <5 min at 1:10 dilution. QGRFT is stable upon 72h exposure with contraceptive actives used in the formulation, confirmed by UPLC analysis. The UPLC spectra showed negligible changes in the QGRFT area under the curve (AUC), peak height, and retention time. There was no sign of peak splitting, implicating an absence of degradants formed during the compatibility study. The MPT FDTs showed effective anti-HIV activity in TZM-bl assay with EC50 < 0.2 nM QGRFT, implicating that QGRFTs in the formulations are stable and biologically active. Lastly, the QGRFT recovery remained within the acceptable limit after being stored for 4 weeks at 4°C and 30°C/65% RH, indicating that the QGRFT stability was maintained.

Conclusion: We successfully developed FDTs combining a biologic anti-HIV drug with non-hormonal contraceptive small molecules, which showed efficient anti-sperm and anti-HIV activities in vitro. These findings show promise for advancing FDTs as innovative on-demand MPTs to help protect women from unintended pregnancy and HIV transmission. We envision that the fast-dissolving attribute of the vaginal MPT FDTs permits their use for pre-coital administration. Furthermore, as a solid dosage form, FDIs have the advantage of portability and ease of use over MPT gel counterparts.

Acknowledgements: The research was supported by NIH/NIAID under award number R01AI150324, "Novel pre-coital, non-hormonal multipurpose prevention technology (MPT).


A. Representative image of lead MPT Fast-Disintegrating Tablets (FDTs), B. Buffer capacity of lead FDTs and marketed contraceptive gel, and C. QGRFT recovery plots of lead MPT FDTs stored at 4°C and 30°C/65% RH for 1 month.