Mathematical modeling of transdermal drug delivery.

Abstract

A dynamic mathematical model for transdermal drug delivery is developed on the basis of the bi-layer skin/twocompartment body model. The effects of metabolism reaction in the viable skin, the drug binding and reservoir function in the stratum corneum, and the solubility and diffusivity of the drug in the skin on the permeation ratetime profile are extensively simulated. The effects of the pharmacokinetic parameters on the plasma concentration profile are also analyzed. The present model is useful not only for analyzing the rate of skin permeation but also for predicting the plasma concentration after transdermal drug delivery.

Transdermal drug delivery by coated microneedles: Geometry effects on effective skin thickness and drug permeability

“…The first transdermal patch was developed by Alza Corporation as a treatment for motion sickness (Tojo, 1987). Since then, patches have been used in applications such as hormonal therapy, pain relief and as an aid to smoking cessation.…”

“…When considering a model for transdermal diffusion, it is usually assumed that the skin acts as a bi-layer membrane which consists of the stratum corneum and the viable skin. Drug that permeates through the viable skin is rapidly absorbed by the microcirculation (Tojo, 1987). It 60 is clear that the stratum corneum is the main barrier to diffusion through the skin.…”

“…It 60 is clear that the stratum corneum is the main barrier to diffusion through the skin. The diffusion coefficient of drug molecules within the stratum corneum is usually at least 500 -10,000 times smaller than within the viable skin (Tojo, 1987). In general, there are several ways in which its barrier ability can be reduced or bypassed and hence achieving better transdermal drug delivery.…”

“…Skin binding involves drug molecules becoming bound to active sites on macromolecules, which can cause a reduction of the diffusion coefficient to an 'effective value' that is a function of drug concentration (Tojo, 2005). Drug binding tends to be prevalent in the stratum corneum rather 140 than the viable skin, so ignoring it is a reasonable approximation.…”

“…Metabolism by the living cells in the viable skin however can lead to an appreciable decrease in the systemic delivery of the drug (Tojo, 2005). To our best knowledge, there is no data to quantify the effect of skin metabolism on various drugs, particularly for those drugs that have 145 not typically been used in transdermal delivery before.…”