Inhibit diffusion of the small molecule drug lidocaine hydrochloride in dissolving microneedles based on a phase separation approach

Dissolving microneedles (DMNs) have emerged as a promising transdermal drug delivery modality. However, in the case of small-molecule drug delivery, there is a tendency for the drug to disperse from the needle layer into the backing layer, resulting in reduced drug concentration at the needle site and consequently compromising drug delivery efficiency. In this study, lidocaine hydrochloride (Lido) was employed as a model drug to prepare a series of Lido dissolving microneedles (Li-DMNs) through a two-step casting method. We detail their fabrication process and the composition of needle and backing solutions, conduct in vitro characterization, and investigate the impact of viscosity and phase separation effects on drug distribution. Li-DMNs exhibit excellent visual appearance, adequate mechanical strength, favorable puncture permeability, and effective transdermal release property which can effectively facilitate the transdermal delivery of Lido. The phase separation effect significantly impedes Lido diffusion into the backing layer during DMNs preparation. This approach holds immense potential for broad applications and bears great significance in enhancing both drug loading capacity and transdermal delivery efficiency of DMNs.