Controlled solvent removal dynamics during fabrication of microneedle patches for the sustained release of etonogestrel.

Abstract

Biodegradable polymer-based microneedle (MN) patches enable self-administered, long-acting drug delivery. Controlled drug release from MNs requires controlled material distribution and minimal porosity in the MNs. MN detachment in the skin requires MNs without film formation beyond the MN base. To achieve these goals, we studied solvent removal dynamics during MN patch fabrication by a solvent-casting method to better control distribution of polymer and drug in the MN patch mold. More specifically, we designed casting solvents to control (i) solvent evaporation rate, (ii) solvent absorption rate into polydimethylsiloxane (PDMS) molds, and (iii) solubility of biodegradable polymer (poly (lactic acid)) and drug (etonogestrel, for long-acting contraception) in the solvent. We found that polymer film formation was prevented by using solvents with minimal mold absorption and moderate evaporation rates. We further demonstrated that solvent-nonsolvent mixtures titrated to the solubility limit of the polymer and beyond the solubility limit of the drug (forming a suspension of fine precipitate) also produced MNs without films. This occurred even when using solvents that absorbed into the molds. To better achieve sustained drug release, we showed that centrifuge-based casting and heat annealing reduced surface and bulk MN porosity. The resulting MNs achieved efficient detachment in porcine skin and sustained release of etonogestrel for two months in-vitro. This study establishes a framework to control solvent removal dynamics during MN patch fabrication to optimize biodegradable polymer MNs for long-acting delivery of etonogestrel and other drugs.