Dissolving microneedles incorporating kopexil multicomponent crystals for improved transdermal delivery

Abstract

Notwithstanding the rapid advancements in microneedle research, the applications of multicomponent crystals (MCCs) within microneedle drug delivery landscape remain largely underexplored. This study aimed at integrating crystal engineering with powder-carrying microneedle technology to overcome the current therapeutic obstacles in androgenetic alopecia (AGA). Kopexil (KPX), a minoxidil analog for AGA treatment, was successfully synthesized into MCCs with benzoic acid (BA) and salicylic acid (SA), yielding KPX-BA·H 2 O cocrystal hydrate and KPX-SA·H 2 O salt hydrate. The solid-state properties of the resulting MCCs were thoroughly characterized. Single-crystal analysis indicated that MCCs were stabilized by acid-aminopyrimidine heterosynthons. The KPX MCC powders were further formulated into dissolving microneedles (MNs). In vitro membrane diffusion tests demonstrated KPX MCCs encapsulated in MNs achieved a 1.86-fold and a 3.20-fold reduction in the amounts of KPX diffused compared to KPX·H 2 O at 4 h. The diffusion of KPX MCCs was positively correlated with their solubilities, following the first-order kinetic model. With the absence of prior reports on KPX MCCs, these findings can inform the broader development of MCCs for APIs that have yet to be explored. The use of pharmaceutically accepted coformers, scalable fabrication methods, predictable release profiles, favorable biocompatibility, and painless self-application microneedle patches collectively offer a viable strategy for the potential clinical translation of this platform for AGA.

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