In vitro release studies of ferulic acid in semi-solid formulations with optimized synthetic membrane

Cutaneous release assays are a fast, low-cost procedure, which allows to obtain essential preliminary results for the development of topical formulations containing new active substances. In this sense, this study aimed to obtain and characterize a low-cost and easy-to-reproduce membrane model, based on a biodegradable polymeric cellulose acetate membrane, which had similarity with the lipid composition of skin and then mimicked its barrier function. For this purpose, membranes prepared by impregnation of a lipid solution in a synthetic membrane were tested for ferulic acid (FA) release from semi-solid and stable formulations using Franz diffusion cells. Thermal features of impregnation were investigated by Differential Scanning Calorimetry, while membranes were structurally characterized by Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). Gel and cream-gel formulations containing 0.5% (w/w) FA were submitted to in vitro skin release tests in phosphate-buffered saline + Tween 80, pH 7.4, using either the synthetic membrane or that optimized by Franz diffusion cell testing. AFM demonstrated membrane impregnation through a change in surface roughness, while SEM showed significant reduction of pore size as well as lipid deposition in the polymer network of the synthetic membrane. With the optimized membrane the gel formulation released almost the same FA percentage (52.36%) as the cream-gel one (52.40%), while with the synthetic one the release was slower and less effective, even if the former formulation performed better than the latter (49.55 vs. 46.04%). Whereas with the synthetic membrane the two formulations showed the same release profile, the optimized membrane was more selective for FA diffusion, thus leading to different release profiles. The results of this study suggest that the optimized membrane may be applied in a simple and accessible way to both initial screening of topical formulations and in vitro release tests. [Display omitted]