Modeling the Impact of Hollow Microneedle Geometry on Iontophoretic Drug Transport Through Age-Variant Skin Surfaces.

Transdermal drug delivery has emerged as a promising alternative to conventional invasive methods, offering advantages such as reduced pain, lower infection risk, and improved patient compliance. However, the influence of age-related skin topography, particularly wrinkle-induced variations, on delivery efficacy in terms of time delay and geometry-dependent total dose remains underexplored. This study presents a computational investigation of iontophoretic drug transport using hollow conical microneedles, focusing on age-variant skin profiles characterized by sinusoidal wrinkle patterns. The transdermal delivery of the ionic dermatological agent Dexamethasone Sodium Phosphate is modeled at initial concentrations of 1-5 mg/L, using microneedle lengths of $100~\mu $ m and $150~\mu $ m. The spatial and temporal concentration profiles of drug diffusion within the dermis are simulated over a 30-minute period. COMSOL Multiphysics is employed to optimize microneedle and electrode design parameters by analyzing applied power, terminal resistance, and the time constant of drug permeation. Skin resistance is modeled across a $1000~\mu $ m surface span under three distinct skin conditions: a) smooth/flat skin, b) increased wrinkle amplitude (deeper crests), and c) increased wrinkle frequency (denser undulations). The results provide quantitative insights into how microneedle geometry and age-related skin surface morphology influence iontophoretic transport efficiency. This study offers design guidelines for age-responsive microneedle systems and informs future regulatory considerations in developing transdermal biomedical devices.