Method to Increase the Systemically Delivered Amount of Drug from Dissolving Microneedles

Abstract

To increase the absorbed amount of a drug from dissolving microneedles (DMs), three DM array chips were prepared in which (1) the drug was localized at the acral portion of DMs, (2) the drug was loaded in each whole DM, and (3) the drug was loaded in DMs and the chip. Fluorescein free form (FL) and its sodium salt (FLNa) were used as model drugs. The DM array chip had 15-mm diameter with 225 DMs, each 500-µm long with a 300-µm diameter base. The respective FLNa contents in the three chips were (1) 0.18±0.03, (2) 0.64±0.07, and (3) 10.95±1.07 mg. The FL contents were (1) 0.20±0.01, (2) 0.68±0.03 and (3) 12.47±1.01 mg. The in vitro release of fluorescein from FLNa DMs was faster than that from FL DMs. In vitro permeability experiments showed that (3) produced the greatest increase in the permeability of fluorescein through rat skin, especially in FLNa loaded DMs. In vivo rat absorption study by application of DM array chips to the rat abdominal skin for 6 h demonstrated that the systemically absorbed amount of fluorescein increased from 0.18±0.02 mg, 0.53±0.19 mg, to 5.38±1.99 mg from systems (1) and (2)-(3). By decreasing the application time of DMs to the rat skin, the absorbed amount of fluorescein decreased along with the application time. The physiological state of the skin recovered within 30 min after chip removal. Using a type (3) DM array chip, more than 1.0 mg of water-soluble drug can be delivered to the systemic circulation.