Formulation and evaluation of ivermectin-loaded dissolving microarray patches for rosacea disease

Purpose This investigation aims to develop and characterise dissolving microarray patches (MAPs) loaded with ivermectin (IVM) for rosacea therapy. Methods Tween (R) 80 and Soluplus (R) were evaluated to enhance the water solubility of IVM powder. Three dissolving MAPs were fabricated using a two-layer casting method, pure IVM-loaded (F1), IVM-Tween (R) 80 (F2), and IVM-Soluplus (R) (F3) loaded patches. Formulations were evaluated for drug content, in vitro and ex vivo mechanical performances, ex vivo skin dissolution time, dermatokinetics, in vitro biocompatibility and activity against rosacea. Results IVM solubility in water was improved with surfactants, reaching 1206.42 +/- 53.78 and 130.78 +/- 12.78 mu g/mL in Tween (R) 80 and Soluplus (R) solutions, respectively. The MAPs, featuring bubble-free, perfectly shaped pyramidal needles of approximately 800 mu m, exhibited considerably higher IVM content in F2 and F3 than in F1 (2.31 +/- 0.26 mg for F1, 3.58 +/- 0.15 mg for F2, and 3.19 +/- 0.22 mg for F3). All formulations demonstrated mechanical robustness and penetrated the skin to a depth of 650 mu m. The highest IVM deposition in the skin at 24 h was achieved by F2, selected as the lead formulation (F1 = 1456.35 +/- 266.90 mu g; F2 = 2165.24 +/- 130.13 mu g; F3 = 1684.74 +/- 212.09 mu g). Furthermore, F2 and F3 provided faster IVM deposition, most likely due to the quicker dissolution rate of microneedles in the skin. F2 proved biocompatible to skin cells in vitro and effectively inhibited the inflammatory cascade associated with rosacea diseases. Conclusion This study encourages further investigation into IVM-loaded dissolving MAPs formulated with Tween (R) 80 for rosacea therapy.