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Ethyl cellulose–ethanol (ECE) is emerging as a promising formulation for ablative injections, with more controllable injection distributions than those from traditional liquid ethanol. This study evaluates the influence of salient injection parameters on forces needed for infusion, depot volume, retention, and shape in a large animal model relevant to human applications. Experiments were conducted to investigate how infusion volume (0.5 mL to 2.5 mL), ECE concentration (6% or 12%), needle gauge (22 G or 27 G), and infusion rate (10 mL/h) impacted the force of infusion into air using a load cell. These parameters, with the addition of manual infusion, were investigated to elucidate their influence on depot volume, retention, and shape (aspect ratio), measured using CT imaging, in an ex vivo swine liver model. Force during injection increased significantly for 12% compared to 6% ECE and for 27 G needles compared to 22 G. Force variability increased with higher ECE concentration and smaller needle diameter. As infusion volume increased, 12% ECE achieved superior depot volume compared to 6% ECE. For all infusion volumes, 12% ECE achieved superior retention compared to 6% ECE. Needle gauge and infusion rate had little influence on the observed depot volume or retention; however, the smaller needles resulted in higher variability in depot shape for 12% ECE. These results help us understand the multivariate nature of injection performance, informing injection protocol designs for ablations using gel ethanol and infusion, with volumes relevant to human applications. [ABSTRACT FROM AUTHOR]

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 polyacorylic 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. [DOI: 10.1115/1.2206198] Keywords: squeezing flows, non-Newtonian, rheology, polymeric drug delivery, vagina, HIV, microbicide

Dual compartment suppositories are being developed to prevent HIV and other sexually transmitted infections. Such products, for use in the rectum, the vagina, or both, could have a significant public health impact by decreasing global incidence of these diseases. In this study, 16 women each used two rheologically distinct suppositories in their vagina and rectum. User Sensory Perception and Experience (USPE) scales assessed sensory experiences during sexual activity to understand whether, and how, women perceive formulation properties in the vagina and rectum. Qualitative data from individual in-depth interviews captured women's descriptions and comparisons of the experiences. Significant differences and large Cohen's d effect sizes between vaginal and rectal experiences of suppository-A were found for three scales: Application (APP): Product Awareness, SEX: Initial Penetration; and SEX: Effortful. Qualitative data provided user experience details that credibly align with these score differences. Near significant differences and large effect sizes were found for two additional scales: SEX: Perceived Wetness with suppository-A and SEX: Messiness with suppository-B. In addition, other scale scores showed medium-to-large effect sizes that correspond to hypothesized sensations associated with biophysical properties of the suppositories. Statistical significance combined with large effect sizes and qualitative data accurately represent the hypothesized perceptibility of suppository properties and identifies performance characteristics relevant to acceptability and adherence; together these data provide discernment of factors that can guide the development of dual compartment products. The Clinical Trial Registration number: NCT02744261. [ABSTRACT FROM AUTHOR]