A Comprehensive Study on Needle-Free Injection Technology Combined with Midazolam Nanosuspension

Abstract

Needle-Free Injection Technology (NFIT), which administers medication through a high-pressure transdermal jet, is limited to a delivery volume of no more than 1 mL due to device constraints. This poses challenges for the administration of poorly water-soluble drugs. Despite its potential for intramuscular delivery of nanocrystal drugs, research in this area is scarce, particularly regarding the exploration of the injection process and outcomes at the intramuscular depth. We developed solution and nanosuspension formulations of the poorly water-soluble drug midazolam and assessing their effectiveness following NFIT and needle injection administration. Our systematic evaluations encompass the velocity of needle-free injection, the establishment of a gel model for visualizing distribution, and documentation of the needle-free injection process, distribution range, impact of needle-free injection on nanocrystals’ size and tissue injury, as well as a comprehensive pharmacokinetic study. Our systematic evaluation confirmed that the nanocrystals retained their physicochemical properties following needle-free injection, ensuring consistent therapeutic efficacy. A significant finding was the faster time to maximum concentration (Tmax) observed with the NFIT-administered nanosuspension (11.67 ± 5.16 min) compared to both the needle injection of nanosuspension (32.50 ± 22.08 min) and the NFIT-administered solution (32.50 ± 14.75 min). Additionally, the needle-free method extended the residence time of the nanosuspension formulation. This research enhanced our understanding of NFIT and underscored its synergistic potential when combined with nanosuspensions for intramuscular drug delivery. Our findings present NFIT as a viable, less injury and rapidly effective alternative to traditional needle injections, especially offering a promising approach for the administration of midazolam nanosuspension.

Keywords: Needle-free, Jet injection, Nanosuspension, Nanocrystal, Midazolam