Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10158195 | Journal of Pharmaceutical Sciences | 2018 | 10 Pages |
Abstract
Precoital, on-demand topical microbicides to reduce a woman's risk of sexually transmitted infections have been in development for nearly 3 decades, but no product has been approved due to acceptability issues and poor adherence in clinical trials. We set out to develop a self-administered vaginal fast-dissolving insert (FDI) produced by freeze-drying that would deliver safe and effective amounts of the antiviral agents griffithsin (GRFT) and carrageenan (CG) and would have properties women and their partners find acceptable. We evaluated FDI physical criteria, attributes of the gel produced upon dissolving, and GRFT stability. The lead formulation, FDI-024, was selected from 13 candidates and contains 4 mg of GRFT, 15 mg of CG, and excipients (the cryoprotectant sucrose and bulking agents dextran 40 and mannitol). The FDI exhibits good friability and hardness and is stable for at least 6 months at up to 40°C/75% relative humidity. It disintegrates in less than 60 s in a physiologically relevant volume (â¼1 mL) of simulated vaginal fluid, forming a viscous semi-solid gel with favorable mucoadhesive and spreading properties. The formulation retains the antiviral activity of GRFT and CG against HIV type 1 and human papillomavirus, respectively, in cell-based assays.
Keywords
HECBritish PharmacopoeiaPBSGRFTSVFEC50USPFDTUnited States PharmacopeiaMucosal drug deliveryProtein deliverySolid state stabilityRelative humidityFDIsimulated vaginal fluidhalf-maximal effective concentrationSolid dosage formFormulationPhosphate-buffered salinehydroxyethyl cellulosepolymerase chain reactionPCRHIV-1Human papillomavirusHPVStabilizationCarrageenanGriffithsinFreeze-drying/lyophilization
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Manjari Lal, Manshun Lai, Shweta Ugaonkar, Asa Wesenberg, Larisa Kizima, Aixa Rodriguez, Keith Levendosky, Olga Mizenina, José Fernández-Romero, Thomas Zydowsky,