Poly(lactic‐co‐glycolic acid) microsphere loaded dissolving microneedles for sustained and coordinated transdermal delivery of desogestrel and ethinyl estradiol

Abstract Minimally invasive drug delivery systems that improve patient compliance have gained increasing attention. Dissolving microneedles (MN) incorporating PLGA microspheres offer a promising platform for sustained transdermal delivery of hormones. We developed PLGA microspheres encapsulating desogestrel (DS) and ethinyl estradiol (EE) and fabricated dissolving microneedles incorporating these microspheres. Their physicochemical properties, drug release profiles, permeability through STRAT‐M® membranes, and skin irritation potential were evaluated. Although differences in dissolution profiles were observed between DS‐P753H MN and EE‐P753H MN, with cumulative releases of approximately 76.6% and 55.7% at 120 h, respectively, both formulations exhibited comparable permeation behavior in Franz diffusion cell studies, indicating consistent transdermal delivery performance. Reproducibility of microsphere and microneedle fabrication was confirmed through independent batch preparation, showing low variability and comparable release profiles (f 2 >60). Slight skin irritation observed with the drug‐loaded microneedles was attributed to the incorporated drugs rather than the microneedle matrix itself. Notably, irritation scores decreased gradually. Therefore, the dissolving microneedle system demonstrates strong potential as a minimally invasive, long‐acting contraceptive platform.