Optimising microneedle arrays to increase skin permeability for transdermal delivery of drugs

Improving drug permeability in skin is considered as one of the most important issues for designing new methods of transdermal drug delivery. Consequently, many techniques have been proposed to more effectively deliver drugs across the stratum corneum, including chemical enhancers or physical enhancer techniques, e.g., iontophoresis and ultrasound. Standard hypodermic injection is an effective method for drug delivery, but it causes difficulties in using it, either due to needle phobia or possibility of having skin infections. Patches is an alternative way for drug delivery across skin. However, this approach generally delivers drugs with low molecular weight and show difficulties in permeability of high molecular solutes in skin. Microneedle is a new technology to enhance transdermal delivery of high molecular weight. This combines the concepts of transdermal drug delivery across the skin using patches and the hypodermic injections. The microneedles have been shown experimentally to increase the skin permeability by order of magnitude in vitro for a range of drugs varying in molecular size and weight. Different microneedle designs have been manufactured for transdermal drug delivery during the last 10 years. Recently, other questions appeared while using these microneedles, e.g., how to reduce needle diameters by which the hole produced to be as small as possible to exclude bacteria and other foreign particles. Another issue that has come up in this regard is how to correlate the skin thickness and microneedle length with the skin permeability. In this work, we have developed a framework which considers different classifications of skin thickness, arising from different races, sex groups, age and anatomical regions. This is done because of their implications in enhancing the process of transdermal drug delivery using microneedles. It is also obvious that in order to know the optimum design of these microneedles, the effect of the microneedle geometry on skin should be determined. However, this necessitates development of an optimization framework for skin permeability from these systems which includes many parameters (e.g., number of microneedles, microneedle radius, surface area of the patch, etc.). In the presented work an optimization algorithm for improving skin permeability to drugs using microneedle arrays is presented. The outcome of this work will be used to suggest optimum microneedle designs based on the parameters of interest. NOMENCLATURE A Surface area of the array (cm) Ah Patch surface area of hollow microneedles (cm) Amin Minimum patch surface area (cm) Amax Maximum patch surface area (cm) Astep Patch surface area increment for the search iteration of A loop(cm) As Patch surface area of solid microneedles (cm) Aopt Optimum patch surface area (cm) D Diffusion coefficient (cm/s) f fractional skin area (-) g optimization function (-) gopt Maximum value of g for the given input data (-) K skin permeability (cm/s) L Thickness of epidermis (cm)