title: Chemical release from topical formulations across synthetic membranes: infinite dose.
abstract: Drug release rates from topical preparations are sometimes measured by monitoring the cumulative mass of drug appearing in a receptor solution (MR). If the topical formulation and receptor solution are in direct contact, then MR increases linearly with square root of t. When a synthetic membrane is placed between the topical formulation and receptor solution, drug appearance in the receptor solution is delayed and MR is not immediately linear in square root of t. As a result, linear regressions of MR with square root of t produce positive values for the square root of 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 square root of t-intercept. To correctly determine drug diffusivity in the topical formulation, the experiment must be conducted long enough that MR is linear in square root of t. Theoretically based procedures are presented for testing which data should not be used in linear regression of MR with square root of 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.
authors.affiliation: Chemical Engineering and Petroleum Refining Department, Colorado School of Mines, Golden 80401, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Parks
authors.forename: R L
authors.initials: RL
authors.lastname: Cleek
authors.forename: A L
authors.initials: AL
authors.lastname: Bunge
mesh_terms: D000287:Administration, Topical; D004058:Diffusion; D008567:Membranes, Artificial; D008956:Models, Chemical; D010599:Pharmacokinetics; D012044:Regression Analysis
chemical_list: D008567:Membranes, Artificial