Interpreting properties of microbicide drug delivery gels: Analyzing deployment kinetics due to squeezing

Prophylactic efficacy of topical microbicidal drug delivery formulations against HIV may depend upon their abilities to coat and be retained on epithelial surfaces where infection begins. Rheological and surface properties play paramount roles in governing coating. While fundamental fluid mechanical studies of epithelial coating mechanisms have begun, their results have not previously addressed questions of practical value to formulators in the pharmaceutics community. The present theoretical study began this process. We focused upon squeezing flows of seven vaginal gels which are models for future microbicides or a candidate formulation in clinical trials. Each formulation is based upon one of three different macromolecules: cellulose, polyacrylic acid (PAA), or carrageenan. We addressed: (1) properties with greatest influence on squeezing flow; (2) alterations of properties to improve measures of coating dynamics; and (3) effects of polymer concentration and temperature on coating dynamics. We found that yield stresses dominated flows of PAA gels, and that surface slip, while small, significantly influenced coating by cellulose gels. Decreases in consistency, increases in shear-thinning, and increases in temperature led to thinner coatings. Details of altered coating rates depended upon parameter values and time. Specific polymer concentration effects differed between cellulose and PAA gels, though trends were similar.