Development of in vivo impedance spectroscopy techniques for measurement of micropore formation following microneedle insertion.

Microneedles (MNs) provide a minimally invasive means to enhance skin permeability by creating micron-scale channels (micropores) that provide a drug delivery pathway. Adequate formation of the micropores is critical to the success of this unique drug delivery technique. The objective of the current work was to develop sensitive and reproducible impedance spectroscopy techniques to monitor micropore formation in animal models and human subjects. Hairless guinea pigs, a Yucatan miniature pig, and human volunteers were treated with 100 MN insertions per site following an overnight prehydration period. Repeated measurements were made pre- and post-MN treatment using dry and gel Ag/AgCl electrodes applied with light verses direct pressure to hold the electrode to the skin surface. Impedance measurements dropped significantly post-MN application at all sites (p < 0.05, irrespective of electrode type or gel application), confirming micropore formation. In the Yucatan pig and human subjects, gel electrodes with direct pressure yielded the lowest variability (demonstrated by lower %relative standard deviation), whereas dry electrodes with direct pressure were superior in the guinea pigs. These studies confirm that impedance measurements are suitable for use in both clinical and animal research environments to monitor the formation of new micropores that will allow for drug delivery through the impermeable skin layers.