Probing the effect of vehicles on topical delivery: Understanding the basic relationship between solvent and solute penetration using silicone membranes

Purpose. In the present study we examined the relationship between solvent uptake into a model membrane (silicone) with the physical properties of the solvents (e.g., solubility parameter, melting point, molecular weight) and its potential predictability. We then assessed the subsequent topical pene tration and retention kinetics of hydrocortisone from various solvents to d efine whether modifications to either solute diffusivity or partitioning we re dominant in increasing permeability through solvent-modified membranes. Methods. Membrane sorption of solvents was determined from weight differenc es following immersion in individual solvents, corrected for differences in density. Permeability and retention kinetics of H-3-hydrocortisone, applie d as saturated solutions in the various solvents, were determined over 48 h in horizontal Franz-type glass diffusion cells. Results. Solvent sorption into the membrane could be related to differences in solubility parameters, MW and hydrogen bonding (r(2) = 0.76). The actua l and predicted volume of solvent sorbed into the membrane was also found t o be linearly related to Log hydrocortisone flux, with changes in both diff usivity and partitioning of hydrocortisone observed for the different solve nt vehicles. Conclusions. A simple structure-based predictive model can be applied to th e sorption of solvents into silicone membranes. Changes in solute diffusivi ty and partitioning appeared to contribute to the increased hydrocortisone flux observed with the various solvent vehicles. The application of this pr edictive model to the more complex skin membrane remains to be determined.