Metabolism and retention of verapamil dictate microneedle-based drug delivery: analytical and numerical study

This study systematically investigates, both analytically and numerically, transdermal drug delivery using a microneedle (MN) array. The drug released from the MN tip disperses through the viable skin before being absorbed in the blood compartment. Reversible uptake kinetics between the blood and tissue compartments, together with reversible specific binding of the drug with its receptors in the tissue, have been taken into account. The governing equations are solved analytically and numerically in an explicit manner. Simulations predict that the metabolism in the viable skin, irreversible uptake and specific binding have a stabilizing effect on the free and bound verapamil concentrations. In addition, a longer MN and a larger skin–blood interface area contribute to higher concentrations of all drug forms in the blood and tissue compartments. The results suggest that the lack of binding in the tissue compartment might overestimate the transdermal delivery of verapamil. A thorough sensitivity analysis has been performed to account for uncertainties in some of the parameters involved. The analysis of verapamil retention in the tissue and its relationship to the length of the MN, the time of application, the area of the skin–blood interface, the rate of metabolism and the reversible uptake kinetics between compartments constitute the novel aspect of this analytical and numerical work. Our reduced model is in excellent agreement with the results available in the literature.