Microneedle-Mediated Transdermal Delivery of Naloxone Hydrochloride for Treatment of Opioid Overdose
Document Type
Article
Publication Date
7-15-2021
Description
Naloxone (NAL) is administered parenterally or intranasally for treating opioid overdose. The short duration of action of NAL calls for frequent re-dosing which may be eliminated by the development of a transdermal system. This study aimed to assess the effect of microneedles on improving the skin permeation of NAL hydrochloride. In vitro permeation of NAL across intact and microneedle-treated (Dr. Pen™ Ultima A6) porcine skin was evaluated. The effect of microneedle length and application duration, and donor concentration on NAL permeation were investigated. In-vitro in-vivo correlation of the permeation results was done to predict the plasma concentration kinetics of NAL in patients. In vitro passive permeation of NAL after 6 h was observed to be 8.25±1.06 µg/cm2. A 56- and 37-fold enhancement was observed with 500 and 250 µm needles applied for 1 min, respectively. Application of 500 µm MNs for 2 min significantly reduced the lag time to ~ 8 min and increasing the donor concentration for the same treatment group doubled the permeation (p < 0.05). Modeling simulations demonstrated the attainment of pharmacokinetic profile of NAL comparable to those obtained with the FDA-approved intramuscular and intranasal devices. Microneedle-mediated transdermal delivery holds potential for rapid and sustained NAL delivery for opioid overdose treatment.
Citation Information
Puri, Ashana; Frempong, Dorcas; Mishra, Dhruv; and Dogra, Prashant. 2021. Microneedle-Mediated Transdermal Delivery of Naloxone Hydrochloride for Treatment of Opioid Overdose. International Journal of Pharmaceutics. Vol.604 https://doi.org/10.1016/j.ijpharm.2021.120739 PMID: 34048932 ISSN: 0378-5173