Squeezing Flows of Vaginal Gel Formulations Relevant to Microbicide Drug Delivery

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Abstract
Efficacy of topical microbicidal drug delivery formulations against HIV depends in part on their ability to coat, distribute, and be retained on epithelium. Once applied to the vagina, a formulation is distributed by physical forces including: gravity, surface tension, shearing, and normal forces from surrounding tissues, i.e., squeezing forces. The present study focused on vaginal microbicide distribution due to squeezing forces. Mathematical simulations of squeezing flows were compared with squeezing experiments, using model vaginal gel formulations. Our objectives were: (1) to determine if mathematical simulations can accurately describe squeezing flows of vaginal gel formulations; (2) to find the best model and optimized parameter sets to describe these gels; and (3) to examine vaginal coating due to squeezing using the best models and summary parameters for each gel. Squeezing flow experiments revealed large differences in spreadability between formulations, suggesting different coating distributions in vivo. We determined the best squeezing flow models and summary parameters for six test gels of two compositions, cellulose and polyacrylic acid (PAA). We found that for some gels it was preferable to deduce model input parameters directly from squeezing flow experiments. For the cellulose gels, slip conditions in squeezing flow experiments needed to be evaluated. For PAA gels, we found that in the absence of squeezing experiments, rotational viscometry measurements (to determine Herschel-Bulkley parameters) led to reasonably accurate predictions of squeezing flows. Results indicated that yield stresses may be a strong determinant of squeezing flow mechanics. This study serves as a template for further investigations of other gels and determination of which sources of rheological data best characterize potential microbicidal formulations. These mathematical simulations can serve as useful tools for exploring drug delivery parameters, and optimizing formulations, prior to costly clinical trials.