Development and characterization of topical formulations of adefovir dipivoxil for the prevention of HIV infection

Background: HIV infection has been a global health issue for past three decades. Around 2 million new cases of HIV are reported every year, and if left untreated will result in AIDS. Currently, there are no vaccines available to prevent acquisition and transmission of HIV. However, preventative measures in the form of pre-exposure prophylaxis (PrEP) have provided an approach to reduce the sexual transmission of the virus. Currently, several clinical trials are ongoing to evaluate the efficacy of local (vaginal or rectal) delivery of anti-HIV drugs for reducing the sexual transmission of HIV infection. Adefovir dipivoxil (ADV) is an FDA-approved nucleotide reverse transcriptase inhibitor used for the treatment of chronic HBV infection. However, recent studies have demonstrated that ADV also has significant activity against HIV-1.

Objective: To develop vaginal films containing ADV for the prevention of HIV infection.

Materials and Methods: Various polymers were evaluated for the development of the placebo vaginal film. The placebo films were prepared using a solvent casting technique. The films were then cut into the desired dimensions. After optimizing the placebo film formulation, films containing ADV were prepared. Finally, an in vitro release test using a Franz diffusion cell was used to measure cumulative drug release from the optimized film formulation with ADV.

Results: The films prepared with the polymer HPMC K100 LV (3%) and PVP K-30 (1%) as well as the HPMC K100 LV (3%) and ethylcellulose 7 cps (0.5%) showed acceptable organoleptic and physical properties. The films containing 5 mg of ADV/7.5 cm2 area exhibited good physicochemical and in vitro drug release.

Conclusion: Vaginal films impregnated with ADV films may be used as a vaginal microbicide product that could effectively provide pre-exposure prophylaxis against sexual transmission of HIV.