Technical challenges and quality considerations for dissolving microneedles

Dissolving microneedles (DMNs) deliver therapeutic molecules by bypassing the stratum corneum upon skin insertion. While DMNs show potential for transdermal delivery, developing formulations with optimal critical quality attributes (CQAs), particularly mechanical properties ensuring effective skin insertion and drug release, remains challenging. Also, lack of standardized quality control methods has made product development difficult. This study investigates testing methods and how polymer-to-API ratio impacts key CQAs including microneedle formation, morphological characteristics, mechanical properties, spatial drug distribution, and drug release/permeation. DMNs were manufactured using varying polyvinyl alcohol (PVA) concentrations with metoprolol succinate as the model drug, maintaining constant drug content across formulations. Microscopic imaging with AI segmentation confirmed successful formation of pyramidal DMNs with consistent dimensions. Intensity-distance analysis provided a measure of the drug distribution from the supportive layer to the needle tips. The fracture force per needle increased proportionally with higher PVA content, enhancing structural integrity. However, the polymer-to-API ratio did not affect skin insertion capability or the needle disintegration kinetics. Higher PVA content resulted in slower drug release from DMN arrays, indicating that polymer content was a critical release-controlling parameter. Permeation profiles from the microneedles were consistent with the distribution of drug within the microneedles, suggesting that localization influences permeation behavior of drug across the skin. Optimizing PVA-to-drug ratio and controlling drug distribution in DMNs are necessary for improving performance, particularly regarding drug release and permeation characteristics. These findings provide insights for advancing DMN development and addressing quality control challenges in DMN systems.