Mixed Micelles Loaded Dissolving Microneedles for Enhanced and Sustained Transdermal Delivery of Indomethacin

Indomethacin is widely used for the treatment of chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis. However, long-term oral administration of indomethacin can damage the gastrointestinal tract. Transdermal delivery of indomethacin was investigated in the present study using mixed micelles loaded dissolving microneedles. Indomethacin loaded mixed micelles were prepared from Soluplus® and Poloxamer F127 using thin-film hydration method. The obtained mixed micelles showed good stability during storage at 4 ºC and 30 ºC for 60 days. The mixed micelles loaded dissolving microneedles were fabricated by means of a two-step molding method. Ex vivo indomethacin permeation was remarkably improved by the mixed micelles loaded dissolving microneedles compared to a commercial patch. Pharmacokinetic study indicated that the relative bioavailability of the mixed micelles loaded dissolving microneedles with respect to the commercial patch was 4.1. Furthermore, mixed micelles loaded dissolving microneedles showed much shorter lag time compared to the commercial patch, and steadier plasma concentration compared to the absence of mixed micelles. These results indicate that enhanced and sustained transdermal delivery of indomethacin could be achieved by the mixed micelles loaded dissolving microneedles.