Formulation Development and Evaluation of Innovative Two-Polymer (SR-2P) Bioadhesive Vaginal Gel
Journal Title: AAPS PharmSciTech - Year 2014, Vol 15, Issue 4
Abstract
The most prevalent sexually transmitted diseases are AIDS and herpes simplex virus (HSV) infection, which are caused by two opportunistic pathogens and lead to progressive failure of the immune system (1). Globally, over 33 million individuals are infected with HIV, and AIDS continues to date to be the most destructive known pandemic. HSV-2 infection is also a global epidemic, with nearly 20% of all sexually active adults being carriers; about 80% of HIV-infected adults are coinfected with HSV-2 (2). Over the past few decades, specifically in the developing nations, women have represented the fastest growing demographic of the HIV/AIDS pandemic. Reports in the literature suggest that biological and socioeconomic vulnerability makes women at higher risk for HIV (3,4). The current methods of preventing HIV infection, such as abstinence, condoms, and monogamy, are frequently ineffective and often outside a woman’s control (5). The failure of existing methods of HIV prevention contributes to women’s greater susceptibility to HIV infections. Furthermore, failures of the existing prevention approaches and the rapid surge of infection rates strongly indicate the need for woman-controlled preventive strategies. One of the most promising prophylactic woman-controlled strategies is the use of topical vaginal microbicides to protect women against male-to-female sexual transmission of HIV. Microbicides may function as a physical barrier or deliver antiviral agents singly or in combination. The success of 1.0 wt.% tenofovir gel in the CAPRISA 004 microbicide trial is a historic milestone in the field of microbicides and reinforces the hope for preventive strategies in the fight against HIV (6). The gel used in that trial was composed of 40 mg of 9-[(R)-2-phosphonomethoxy) propyl] adenine monohydrate (6) in a solution of purified water with edetate disodium, citric acid, glycerin, methylparaben, propylparaben, and hydroxyethycellulose (HEC). The placebo gel used in the trial was the “universal” HEC placebo gel, which has been shown to have minimal anti-HIV activity (6). We hypothesize that our patented bioadhesive formulation (7), composed of two FDA-approved polymers, Pluronic® F-127 (polyoxyethylene polyoxypropylene co-polymer, polaxomer) and Noveon® AA-1 (polyacryclic acid), will [1] be a more efficacious platform for delivery of the antiviral drugs tenofovir and acyclovir, [2] offer protection against viral infection, and [3] have a long residence time because it will form micelle-like particles that adhere to the vaginal wall. The epithelium of the vagina contains glycogen, which is broken down by enzymes and bacteria into lactic acid to maintain low vaginal pH between 4 and 5, which is inhospitable to pathogens (8). A patented mucoadhesive formulation platform developed at SRI International (Menlo Park, CA) showed promise as a vaginal bioadhesive (7). This proprietary formulation (denoted as “SR-2P”; Fig. 1 ) offers many advantages as a potential bioadhesive microbicide gel candidate. A microbicide is a vaginal formulation containing antiviral agents. Unlike a solution dosage form, which is easily washed off, a mucoadhesive gel formulation, containing antiviral agents, on application to vaginal mucosa results in longer drug exposure. The overall goal of this investigation was to identify a lead bioadhesive gel candidate from several prototype gel compositions suitable for loading of anti-HIV/HSV agents. Towards this objective, various prototype gels were prepared and pH, osmolality, buffering capacity, viscosity changes, and bioadhesivity were studied under simulated physiological conditions. The vaginal irritation potential of the SR-2P were studied, in a mouse model developed earlier at SRI International (9).
Authors and Affiliations
Satheesh Podaralla, Carsten Alt, Gita N. Shankar
Keywords
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- EP ID EP682409
- DOI 10.1208/s12249-014-0124-9
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