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

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.