Maximizing drug loading in cavity microneedles through precision cavity engineering and centrifugal techniques.

Cavity microneedles achieve powder drug loading through the cavity structure within the needle, reducing drug loading limitations related to solubility and stability, and effectively increasing drug loading capacity. However, the unclear mechanisms for cavity formation, the compromised mechanical performance induced by internal cavities, and the low efficiency and poor reproducibility of existing centrifugal drug loading methods are critical application challenges. To address these issues, this study implemented three interconnected strategies: first, the cavity formation principle was investigated through analysis of material properties and preparation processes; second, the mechanical properties were optimized by two-step casting method; and third, the centrifugal loading process was refined using discrete element simulation (DEM). The results indicate that substrate concentration and viscosity are key factors affecting cavity formation. Based on simulations of particle motion, increasing centrifugal speed effectively improves the drug loading capacity of cavity microneedles and shortens the centrifugation time. The Coriolis effect was identified as a critical mechanism contributing to the direction-dependent non-uniform drug loading observed in unidirectional centrifugal methods. According to DEM simulation results, a 'clockwise + counterclockwise' directional centrifugal method was proposed, which successfully achieved uniform drug loading by reversing the direction of the Coriolis force. In an acute pain model, analgesic efficacy tests confirmed the potential of cavity-structured microneedles as a high-capacity drug delivery platform. This study establishes a 'process-property-drug loading' optimization chain system for the design of soluble cavity microneedles, providing a robust theoretical foundation for effective and standardized drug loading in cavity microneedles and their clinical translation.