Microneedles integrated with crystallinity control for poorly water-soluble drugs: Enhanced bioavailability and innovative controlled release system

• Microneedles integrated with drug crystallinity control for regulated release were developed. • Microneedles were fabricated with varying drug-to-povidone weight ratios. • Crystalline and amorphous microneedles showed sustained-release and fast-dissolving. • Both optimized microneedles demonstrated improved transdermal bioavailability in rats. The purpose of this study was to develop innovative microneedles with drug crystallinity control for the fast or sustained release of poorly water-soluble drugs. Povidone was determined as a suitable polymer following hydrophilic polymer testing using solubilization screening technique. Microneedles were fabricated by altering the drug-to-polymer weight ratios. Their mechanical properties, crystallinity, solubility, release, skin permeability and transdermal pharmacokinetics in rats were assessed. The optimal crystalline and amorphous microneedles were composed of drug/polymer at weight ratios of 1:0.03 and 1:2.5, respectively. They showed excellent insertion in rat skin with a puncture rate above 80%. Compared to drug powder or solution, they increased drug solubility, release and skin permeability. Crystalline microneedles gave sustained release and plasma concentration profiles, while amorphous microneedles provided a fast profile. Amorphous microneedles offered significantly faster T max and two-fold higher area under the concentration–time curve (AUC), indicating better transdermal bioavailability. In the safety test, microneedle-treated rat skin was recovered to normal within three days without any irritations. Thus, the drug crystallinity could play a significant role in the release of microneedles, suggesting their potential as a transdermal drug delivery system for controlling the release of poorly water-soluble drugs and improving their transdermal bioavailability.