A New Paradigm for Numerical Simulation of Microneedle-Based Drug Delivery Aided by Histology of Microneedle-Pierced Skin

Abstract

Microneedle (MN) is a relatively recent invention and an efficient technology for transdermal 8 drug delivery (TDD). Conventionally, the mathematical models of MNs drug delivery define the 9 shape of the holes created by the MNs in the skin as the same as their actual geometry. 10 Furthermore, the size of the MN holes in the skin is considered to be either the same or a 11 certain fraction of the lengths of the MNs. However, the histological images of the MN treated 12 skin indicate that the real insertion depth is much shorter than the length of the MNs and the 13 shapes may vary significantly from one case to another. In addressing these points, we propose 14 a new approach for modelling MN based drug delivery, which incorporate the histology of MN 15 pierced skin using a number of concepts borrowed from image processing tools. It is expected 16 that the developed approach will provide better accuracy of the drug diffusion profile. A new 17 computer program is developed to automatically obtain the outline of the MNs treated holes and 18 import these images into computer software for simulation of drug diffusion from MN systems. 19This method can provide a simple and fast way to test the quality of MNs design and modelling, 20 as well as simulate experimental studies, e.g., permeation experiments on MN pierced skin 21 using diffusion cell. The developed methodology is demonstrated using two dimensional (2D) 22 numerical modelling of flat MNs (2D). However, the methodology is general and can be 23 implemented for 3D MNs if there is sufficient number of images for reconstructing a 3D image 24 for numerical simulation. Numerical modelling for 3D geometry is demonstrated by using 25 images of an ideal 3D MN. The methodology is not demonstrated for real 3D MN as there are 26 not sufficient numbers of images for the purpose of this paper. 27

Microneedle-assisted transdermal delivery of Zolmitriptan: effect of microneedle geometry, in vitro permeation experiments, scaling analyses and numerical simulations

“…The MATLAB programme was use to process the histological sections images of skin treated with MNs and these processed images were further coupled with the experimental permeation parameter, e.g., passive diffusion coefficient and imported into COMSOL simulator software 13,20 .…”

Application of Microneedle Arrays for Enhancement of Transdermal Permeation of Insulin: In Vitro Experiments, Scaling Analyses and Numerical Simulations

“…4b, c) and COMSOL (Fig. 4d) softwares, based on in vitro passive diffusion coefficient values and histological section images (of corresponding MN geometry) were able to provide information regarding drug distribution within the skin at any time point and depth (14). The similarity factor (f 2 ) for the in vitro permeation profile and the simulated profile was found to be 50.…”

“…It is well known now that owing to the viscoelastic nature of the skin, the microconduits created do not have the same dimensions as the MN, but may vary significantly (8,19), thereby limiting the applicability of MN design parameters to carry out such simulations. Microphotographs of histological sections can provide an efficient way of predicting the extent of skin disruption by different MNs, which may be used to develop accurate simulations of the drug(s) permeation process (14). The numerical simulations carried out using MATLAB (Fig.…”

“…passive diffusion coefficient obtained from the in vitro studies were imported into a simulator software, COMSOL Multiphysics (COMSOL Multiphysics Pvt. Ltd., Stockholm, Sweden), in order to simulate the insulin transport behaviour across the skin and predict the permeation profiles of insulin as per the procedures reported by Han and Das (14).…”

“…Moreover, the obtained data was subjected to mathematical treatment using scaling analyses to obtain correlations between dimensionless amount of insulin permeated (C t /C s ) and various other dimensionless variables of the study such as the surface area (S a /L 2 ) and thickness (h/L) of the skin based on the Buckingham π theorem (13). Numerical simulations of the in vitro experiments using histological section images and passive diffusion coefficient values were also carried out in order to simulate the insulin permeation process under realistic conditions and gain insights into the phenomenon of insulin transport behaviour and insulin distribution in the MN-treated skin (14). Commercially available MN arrays (AdminPatch®) with four different needle lengths (0.6, 0.9, 1.2 and 1.5 mm) and MN density were utilized for the purpose of this study.…”