Release of Tenofovir from Carrageenan-Based Vaginal Suppositories

Abstract

Microbicides are an active area of research for HIV prevention, being developed as a woman-initiated method of prevention during unprotected coitus. Along with safety and efficacy, assessing and improving compliance is a major area of research in microbicide development. We have produced microbicide prototypes in the form of semisoft vaginal suppositories prepared from carrageenan and conducted both qualitative and quantitative studies using these prototypes to determine the physical properties that drive acceptability and possibly adherence. In order to ensure that the suppositories function as effective drug delivery vehicles, we have conducted in vitro dissolution studies in water, vaginal simulant fluid (VSF) and semen simulant fluid (SSF) with suppositories loaded with the antiretroviral drug, tenofovir (TFV). TFV was released via diffusion and matrix erosion in water or by diffusion out of the matrix in VSF and SSF. Diffusion studies were conducted in two different volumes of VSF and SSF. The volume of VSF/SSF into which TFV diffused and the size of the suppositories determined the rate of diffusion from the suppositories. About 45%–50% of the encapsulated TFV diffused out of the suppositories within the first two hours, irrespective of suppository size, diffusion medium (VSF/SSF) and the volume of medium. Prior work indicates that a short waiting period between insertion and coitus is highly desired by women; present data suggest our microbicide prototypes have rapid initial release followed by a slow release curve over the first 24 h.

Innovative sensory methods to access acceptability of mixed polymer semisoft ovules for microbicide applications

“…For diffusion into 5 mL VSF, 45-50 % of TFV was released in the first 2 h, 60 % within 6 h and 70 % in 24 h (Figure 7). Previous studies with 5 mL of dissolution medium indicated that release plateaus at 24 h [21]. Recognizing the limitation of insufficient sink conditions, for the 5 mL drug diffusion studies, the dissolution medium was replenished with fresh VSF at 24 h to stimulate additional release.…”

“…The carrageenan-based semisoft suppositories are being developed to release the active pharmaceutical ingredient (API) and slowly disintegrate within the body so that any resultant discharge mimics vaginal mucous secretions. Our initial prototypes formulated with carrageenan alone successfully released drug [21], but did not disintegrate when exposed to a simulated vaginal environment (i.e., a small volume (5 mL) of vaginal simulant fluid at 37 °C). Accordingly, we are investigating addition of other polymers, such as carbopol, to carrageenan formulations to aid with breakdown in a simulated vaginal environment.…”

On-demand microbicide products: design matters

“…Vaginal suppositories have been previously used to deliver probiotics for general vaginal health. Microbicides formulated into vaginal suppositories have also been reported [96]. Zaveri et al has shown incorporation of TFV into semisoft vaginal suppositories prepared using a carrageenan base, which offered evidence of anti-HIV activity [96].…”

“…Microbicides formulated into vaginal suppositories have also been reported [96]. Zaveri et al has shown incorporation of TFV into semisoft vaginal suppositories prepared using a carrageenan base, which offered evidence of anti-HIV activity [96]. Similar to gels, suppositories can be prepared as dual compartment products.…”

Development of Fluconazole Suppositories for the Treatment of Candida Infection of Genitourinary Tract

“…But, the main problems with vaginal films and vaginal gels are their low drug content, wetting and leakage. [20][21][22] Similarly, vaginal tablets cause irritation, hypertonic and discomfort as it takes more time for disintegration. Hence, there is a need to explore an intermediate product for the treatment of this infection which exist between gels/ films and tablets.…”