Modelling transdermal delivery of high molecular weight drugs from microneedle systems

Abstract

In the past few years, a number of microneedle designs have been proposed for transdermal drug delivery of high molecular weight drugs. However, most of them do not increase the drug permeability in skin significantly. In other cases, designs developed based on certain criteria (e.g. strength of the microneedles) have failed to meet other criteria (e.g. drug permeability in skin, throughputs of the drugs, etc.). It is obvious therefore that in order to determine the 'optimum' design of these microneedles, the effect of different factors (e.g. length of the microneedle, surface area of the patch, etc.) along with various transport properties of drug transport behaviour using microneedles should be determined accurately. Appropriate mathematical models for drug transport from these systems into skin have the potential to resolve some of these issues. To address this, a parametric analysis for transdermal delivery of a high molecular weight drug from a microneedle is presented in this paper. The simulations have allowed us to identify the significance of various factors that influence the drug delivery while designing microneedle arrays. A scaling analysis is also done which shows the functional dependence of drug concentration on other variables of skin and microneedle arrays.

Transdermal Drug Delivery by Microneedles: Does Skin Metabolism Matter?

“…(5) All the verapamil molecules are assumed to be taken up by the blood circulation (Al-Qallaf et al, 2007). This assumption has been previously explained in detail in previous publications e.g.…”

“…(7) At x=h (Figure 1), the concentration of verapamil is defined to be zero (sink condition) (Al-Qallaf et al, 2007;Mori et al, 2003;Tojo, 2005). This assumption has also been previously explained in detail in Al-Qalaf et al (2009c) and Davidson et al (2008).…”

“…Consequently the skin permeation and blood concentration of the drug have been modelled assuming no drug metabolism in the viable skin. For example, we have previously evaluated the effects of volume of distribution (V b ) and elimination rate constant (K e ) on the fentanyl concentration in blood without considering the skin metabolism (Al-Qallaf et al, 2007;McAllister et al, 2003). Other general mathematical models for molecule transport across skin have also been proposed which have not included the influence of skin metabolism, see e.g., the reviews by Godin and Touitou (2007) and, Yamashita and Hashida (2003).…”

“…A number of mathematical frameworks have been developed for evaluating both the skin permeation and blood concentration of drug delivered using microneedle arrays (Al-Qallaf and Das, 2009a;Das, 2009b, Davidson et al, 2008;Al-Qallaf et al, 2007;Lv et al, 2006;McAllister et al, 2003). In most of these cases, the metabolism of the drug has not been considered.…”

“…Improving upon our previous work (Davidson et al, 2008;Al-Qallaf et al, 2007) we have introduced mono and bi-layer diffusion models with two compartment model to estimate verapamil concentration in blood when either applied as a patch or injected using microneedle. In all cases, the cumulative amounts of verapamil permeated per unit area of skin with and without skin metabolism have been numerically determined.…”