Microneedle-mediated transdermal delivery of naloxone hydrochloride for treatment of opioid overdose.
Int J Pharm
; 604: 120739, 2021 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-34048932
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sobredosis de Opiáceos
/
Agujas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Pharm
Año:
2021
Tipo del documento:
Article
Pais de publicación:
Países Bajos