MEASUREMENT OF DRUG DIFFUSIVITY IN STRATUM-CORNEUM MEMBRANES AND A POLYACRYLATE MATRIX

Diffusivities have been determined for the drug clenbuterol for three non-sink, diffusional problems: diffusion out of a polymer matrix, diffusion through excised, human stratum corneum, and the combined case of diffusion out of a polymer matrix through contiguous, excised stratum corneum. Numerical solution of the diffusion equation for these problems yeilds theoretical values of drug mass in the acceptor phase, m(a)(t)th, vs time. Diffusion was then measured experimentally and the best value for diffusivity obtained by comparing the values of drug mass in the acceptor phase, m(a)(t)exp, with the corresponding m(a)(t)th data. In this fashion it was possible to obtain diffusivities for diffusion out of the polymer matrix for various values of drug loading and matrix thickness. For the problem of diffusion through stratum corneum a value for the partition coefficient of clenbuterol as well as for its diffusivity could be determined. The two diffusivities obtained for the combined model (i.e., D(m) within the matrix and D(s) within the stratum corneum) agree quite well with those obtained for the two separate problems, but are more scattered. Partition coefficients could not be accurately determined for diffusion out of the matrix or the combined problem.