A mathematical model is presented for the description of transdermal drug delivery from a matrix-type delivery device. The model is partly diffusional and partly compartmental in nature. The matrix and stratum corneum are both considered to be diffusion layers, connected to a three-compartment model representing the viable epidermis/dermis, plasma, and peripheral tissues. The diffusion equation was solved numerically for the two diffusion layers under non-sink conditions. The ordinary differential equations for the compartmental model were also solved numerically. Combination of the two numerical solutions yielded a model which directly relates the properties of the matrix to the profile of drug mass in the plasma and the urinary excretion profile. The model was first used to analyse data obtained from an in vivo trial of a matrix-type transdermal delivery device for the drug clenbuterol. Fitting of the model to the profile of drug concentration in the plasma, the urinary excretion profile, and the mass of drug remaining in the matrix with a modified simplex method yielded values for the model constants. These compared very favourably with independent values taken from the literature. Simulations of the influences of drug diffusivity within the stratum corneum, drug loading in the matrix, matrix thickness and drug diffusivity within the matrix on the profile of drug concentration in the plasma were then made. The model is not restricted to a steady state nor does it specify particular drug release kinetics from the matrix. It does assume isotropic diffusion layers and spontaneous partitioning at boundaries.
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