Posture influences vaginal gel distributions in women: theoretical models and in vitro simulations of gravitational flows.

Abstract

Objective: Using mathematical models and in vitro experimental flow simulations, this study analyzed the effects of biophysical factors (such as changes in posture and rheological properties) that govern the flow of vaginal gel formulations due to the force of gravity. These gels serve as biophysical models for future microbicidal formulations. Design: Commercial spermicidal and lubricant formulations of two molecular compositions were compared: 3 cellulose-based gels (Conceptrol, Gynol II, KY Jelly, Advanced Care Products) and 3 polyacrylic acid-based gels (Advantage-S and Replens, Columbia Laboratories; and KY Plus, Advanced Care Products). The estimated yield stresses of the formulations at 37°C and the appropriate rheological parameters (Herschel-Bulkley model) were calculated and used as model input. Several measures of coating distribution were determined from theoretical models and experimental simulations, and results were compared. Materials/Methods: Yield stresses were estimated from measured residual stresses. The mechanistic mathematical theory incorporated rheological properties, estimates of yield stress, and vaginal geometry. A first-generation sliding apparatus was constructed, and experimental simulations of formulation flow were begun. An inclined surface (variable inclination) was placed in a humidified, temperature-controlled (37°C) chamber. A bolus of formulation was loaded onto the upper end of the inclined plane, and the subsequent flow was recorded using video image processing, and analyzed using Scion Image analysis software. A set of measures of the coating thickness distribution was obtained. Results: Similar to measurements at 25°C, the polyacrylic-acid based gels exhibited residual stresses, while the cellulose-based gels did not. The mathematical theory showed that the rheological properties of the gel and the geometrical configuration combined in a nonlinear way to govern the tendency of the gel to spread. As the surface inclination becomes steeper and the thickness of the layer increases, the gels flow faster. However, the presence of yield/residual stresses inhibits flow for thinner layers at less steep inclinations. Preliminary simulation results (on a dry surface) revealed that KY Plus did not slide at all, Conceptrol spread down the incline in a similar manner to Gynol II, and KY Jelly moved the fastest down the incline. Conclusions: The theoretical prediction curves of gel coating distributions had the same trends as the curves of data from the initial experimental simulations. Comparisons of theory and simulations revealed differences in sliding behavior across the test formulations. For biologically motivated conditions, model calculations showed that the rank order of gel sliding velocities from fastest to slowest was: KY Jelly > Conceptrol > Gynol II > Advantage > Replens > KY Plus. For the slowest three gels (all polyacrylic acid-based), the yield stress played a dominant role in determining rank order under these conditions. The higher the estimated yield stress, the less distance was traveled. For the fastest three gels (all cellulose-based), the consistency index (m of the Herschel-Bulkley rheological model) was the most influential parameter. As m increased, the distance traveled decreased. Supported By: NIH Cellular and Biosurface Engineering Training Grant and the FDA.