Journal Article

Combination with l-Menthol Enhances Transdermal Penetration of Indomethacin Solid Nanoparticles

Fukuoka, Yuya, Otake, Hiroko, Ogata, Fumihiko, Yamaguchi, Mizuki, Nakazawa, Yosuke, Kawasaki, Naohito, Nagai, Noriaki

2019

Overview

This study designed the transdermal formulations containing indomethacin (IMC)—1% IMC was crushed with 0.5% methylcellulose and 5% 2-hydroxypropyl-β-cyclodextrin by the bead mill method, and the milled IMC was gelled with or without 2% l-menthol (a permeation enhancer) by Carbopol® 934 (without menthol, N-IMC gel; with menthol, N-IMC/MT gel). In addition, the drug release, skin penetration and percutaneous absorption of the N-IMC/MT gel were investigated. The particle sizes of N-IMC gel were approximately 50–200 nm, and the combination with l-menthol did not affect the particle characterization of the transdermal formulations. In an in vitro experiment using a Franz diffusion cell, the skin penetration in N-IMC/MT gel was enhanced than the N-IMC gel, and the percutaneous absorption (AUC) from the N-IMC/MT gel was 2-fold higher than the N-IMC gel. On the other hand, the skin penetration from the N-IMC/MT gel was remarkably attenuated at a 4 °C condition, a temperature that inhibits all energy-dependent endocytosis. In conclusion, this study designed transdermal formulations containing IMC solid nanoparticles and l-menthol, and found that the combination with l-menthol enhanced the skin penetration of the IMC solid nanoparticles. In addition, the energy-dependency of the skin penetration of IMC solid nanoparticles was demonstrated. These findings suggest the utility of a transdermal drug delivery system to provide the easy application of solid nanoparticles (SNPs).

• Publisher: MDPI AG,MDPI
• Subject: Administration, Cutaneous / Animals / Anti-Inflammatory Agents, Non-Steroidal - administration & dosage / Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics / Cosmetics industry / Drug Carriers - chemistry / Drug Combinations / Drug Compounding / Drug Delivery Systems / Drugs / Indomethacin - administration & dosage / Indomethacin - chemistry / Indomethacin - pharmacokinetics / Inflammation / Menthol - administration & dosage / Menthol - chemistry / Menthol - pharmacokinetics / Microscopy, Atomic Force / Nanoparticles / Nanoparticles - chemistry / Particle size / Permeability / Rats / Skin / Skin Absorption / Spectrum Analysis / Studies / Transdermal medication