![]() |
![]() |
||||||||||||
|
02689 EFFECTS OF SQUEEZING FLOWS ON DISTRIBUTION/RETENTION OF MICROBICIDE FORMULATIONS: EXPERIMENTAL SIMULATIONS & MATHEMATICAL MODELS Kieweg, Sarah* Microbicide vaginal distribution depends on formulation properties, ambient fluids, vaginal geometry, and applied forces. Macroscopic forces gravitational and squeezing significantly affect vaginal coverage and retention. We characterize the macroscopic flows via experiments in vitro and theoretical mechanistic models. We measured rheological properties of 7 formulations: 3 cellulose gels (Conceptrol, Gynol II, and KY Jelly), 3 polyacrylic acid (PAA)-based gels (Advantage, KY Plus, and Replens), and a carrageenan gel (Carraguard). Squeezing experiments applied physiologically-relevant forces and monitored the resulting thickness and strain. Unlike cellulose and carrageenan gels, PAA gels exhibited yielding and non-yielding regions, as well as a limiting coating thickness, which ranked KY Plus > Replens > Advantage. For all gels, the coating was dependent on applied force and initial thickness (applied volume). The non-PAA gels experienced the most strain, with strain rankings: Carraguard > KY Jelly > Conceptrol/Gynol > Advantage > Replens > KY Plus. These strain rankings relate to squeezing distribution in vivo. Theoretical models of squeezing flows are compared to in vitro experiments and are used to specify formulation properties that optimize distribution and retention in vivo. For example, differences in rheological properties of Carraguard and KY Jelly may produce a 30% difference in epithelial coverage and a 40% difference in coating thickness. A 43% increase in applied volume may produce an 18% increase in coverage. The above results reveal large differences between formulations and suggest distribution differences in vivo due to squeezing flows. (Supported by NIH #AI48103) Sarah L. Kieweg |
|||||||||||||