Chemical release from topical formulations across synthetic membranes: Infinite dose

Drug release rates from topical preparations are sometimes measured by monitoring the cumulative mass of drug appearing in a receptor solution (M(R)). If the topical formulation and receptor solution are in direct contact, then M(R) increases linearly with root t. When a synthetic membrane is placed between the topical formulation and receptor solution, drug appearance in the receptor solution is delayed and M(R) is not immediately linear in root T. As a result, linear regressions of M(R) with root t produce positive values for the root t-intercept. Here, we mathematically model chemical release from an infinite-dose, topical formulation across synthetic membrane to quanitiatively determine the physical meaning of the root t-intercept. To correctly determine drug diffusivity in the topical formulation, the experiment must be conducted long enough that M(R) is lineal in root t. Theoretically based procedures are presented for testing which data should not be used in linear regression of M(R) with root t. Theoretical predictions are compared with previously published experimental results for ethyl salicylate across a poly(dimethylsiloxane) (Silastic) membrane and for hydrocortisone across several different synthetic membranes.