Development and characterization of a vaginal film containing dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), for prevention of HIV-1 sexual transmission

Abstract

Dapivirine, a non-nucleoside reverse transcriptase inhibitor, is a potent and promising anti-HIV molecule. It is currently being investigated for use as a vaginal microbicide in two dosage forms, a semi-solid gel and a silicone elastomer ring. Quick-dissolving films are promising and attractive dosage forms that may provide an alternative platform for the vaginal delivery of microbicide drug candidates. Vaginal films may provide advantages such as discreet use, no product leakage during use, lack of requirement for an applicator for insertion, rapid drug release and minimal packaging and reduced wastage. Within this study the in vitro bioactivity of dapivirine as compared to the NNRTI UC781 was further established and a quick dissolve film was developed for vaginal application of dapivirine for prevention of HIV infection. The developed film was characterized with respect to its physical and chemical attributes including water content, mechanical strength, drug release profile, permeability, compatibility with lactobacilli and bioactivity. The anti-HIV activity of the formulated dapivirine film was confirmed in in vitro and ex vivo models. Importantly the physical and chemical properties of the film as well as its bioactivity were maintained for a period of 18 months. In conclusion, a vaginal film containing dapivirine was developed and characterized. The film was shown to prevent HIV-1 infection in vitro and ex vivo and have acceptable characteristics which make this film a promising candidate for testing as vaginal microbicide.

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

“…First, the film was wrapped in butter paper as one layer and above which a second layer of aluminum foil was tightly applied. Samples of the optimized films were stored at 40 C/75% RH for a period of 12 weeks (Akil et al, 2011;Farid et al, 2015). Periodically, samples were withdrawn at different predetermined time intervals (0, 1, 2, 4, 6, 9, and 12 weeks) and examined physically for any changes in color, appearance thickness, and surface pH as well as chemically for their drug content.…”

Characterization of UC781-Tenofovir Combination Gel Products for HIV-1 Infection Prevention in an Ex Vivo Ectocervical Model

“…UC781 and d 4 -UC781 were detected with a mass spectrometer under a positive-mode MRM scan. The mass transitions (m/z) were 360 to 268.1 for UC781 and 340 to 270.4 for d 4 …”

“…In preclinical evaluations of microbicide products, assessment of the ability of drugs to permeate cervicovaginal tissue provides insight into the diffusion of drug candidates into the target tissue in vivo. The abilities of several anti-HIV-1 drugs developed as microbicide products to permeate tissue were previously evaluated in the Franz cell model using human ectocervical tissue, demonstrating drug levels that would achieve protection in vitro (4,33).…”

Electrospun Solid Dispersions of Maraviroc for Rapid Intravaginal Preexposure Prophylaxis of HIV

“…Tablets and films, while they can be used immediately before sex, often require 30 min to dissolve fully before the start of intercourse. Moreover, microbicide films reported in literature have low drug loadings (less than 1.5 wt%) (6,7), which when coupled with their small dosage size limits their application to only highly potent antiretroviral (ARV) drugs. Recently, Ball et al and Huang et al demonstrated that electrospun fibers could release a range of active ARV drugs and spermicides (8) and that such release could occur in response to stimuli, such as a semen-induced rise in pH (9).…”