Optimizing preparation and solidification of drug crystal, amorphous and co-amorphous nanoparticles for microneedles

This study established a top-down methodology for nano-amorphous rutin production, with systematic evaluation of amorphous state effects (polymer-based vs. small molecule-based) on both manufacturing processes and microneedle formulations. Experimental data coupled with molecular dynamics simulations confirmed that strategic selection of small-molecule co-formers with optimized ratios could generate smaller nanoparticles (288 nm) exhibiting superior physical stability compared to polymer-based nano-amorphous systems. Radial distribution function analysis of the amino acid-rutin system detected robust intermolecular interactions (708.8103 kcal/mol), where the formed hydrogen-bonding network effectively suppressed rutin recrystallization. The dual strategy combining nanotechnology with amorphization technology achieved remarkable dissolution enhancement (85 % drug release), substantially exceeding the performance of microparticulate systems. This effect was further amplified through lyophilization using a ternary excipient system (hyaluronic acid-povidone-polyvinyl alcohol), which improved mechanical resilience. The nano-co-amorphous powder demonstrated 69.87 μg/mL transdermal flux, representing significant advancement over nanocrystalline formulations (49.86 μg/mL). The developed rutin-lysine nano-co-amorphous microneedles exhibited clinically relevant wound healing efficacy, validating their therapeutic potential.