Glassy Drug Microneedle Array Design: Drug Glass-Forming Ability and Stability.

Abstract

Glassy microneedles, composed only of drug, provide an intradermal alternative to oral or parenteral drug delivery. Compared to microneedles composed of drug-polymer solid dispersions, they offer higher drug loading while possessing mechanical strength for skin penetration. However, their microneedle structure and associated mechanical strength are reliant on the component glass stability. This study investigates relationships between the glass stability of drug-only microneedles and drug glass-forming ability (GFA), determined by differential scanning calorimetry (DSC) analysis. The glass stability of microneedles fabricated from six drugs was evaluated at 2-8 °C under nitrogen, 25 °C/60% relative humidity (RH), and 40 °C/75% RH. Drug glass stability was determined by visual assessment of microneedle appearance, together with DSC and powder X-ray diffraction analysis of the drug melt cooled outside the microneedle molds. Glassy microneedle structure was retained for all drugs stored at 2-8 °C under nitrogen for 3 months. Drug GFA classes informed glass stability under dry (nitrogen) environments at temperatures below their glass transition temperature. Under controlled humidity conditions, all glass microneedles crystallized, except for itraconazole. Drug GFA did not inform microneedle glass stability when exposed to water vapor during storage due to water absorption and glass plasticization. Itraconazole's glass stability was attributed to the interaction of absorbed water with liquid crystalline phases present in the itraconazole glass. The results highlight how glassy microneedle stability is informed by storage below T_g and glass interaction with moisture vapor. Results also demonstrate how the skin penetration efficiency of glassy microneedles is maintained during storage by selecting stabilizing storage conditions.