Combined Use of N-Palmitoyl-Glycine-Histidine Gel and Several Penetration Enhancers on the Skin Permeation and Concentration of Metronidazole.

Sabrina Dahlizar,Hiroaki Todo,Chihiro Yatomi,Akie Okada,Kenji Sugibayashi,Mika Futaki

doi:10.3390/pharmaceutics10040163

Sabrina Dahlizar, Hiroaki Todo + Show 4 more

Open Access

https://doi.org/10.3390/pharmaceutics10040163

Copy DOI

Abstract

N-Palmitoyl-Glycine-Histidine (Pal-GH) is a novel low molecular weight gelator. In our previous report, ivermectin, a lipophilic drug, was effectively delivered to skin tissue after topical application with Pal-GH as a spray gel formulation, and a much higher skin concentration was confirmed than with the administration of a conventional oral formulation. The objective of this study was to increase the skin permeation of metronidazole (MTZ), a hydrophilic drug, after the topical application of Pal-GH gel. An evaluation of the combined effect of chemical penetration enhancers (CPEs), such as isopropyl myristate (IPM), propylene glycol (PG), ethanol, diethylene glycol monoethyl ether, and dimethyl sulfoxide (DMSO), on skin permeation was also conducted. We found that a 5% Pal-GH gel containing 1% MTZ (F5MTZ) exhibited a 2.7-fold higher MTZ permeation through excised hairless rat skin than its solution. Furthermore, F5PG-MTZ and F5IPM-MTZ further increased the skin permeation of MTZ when compared to F5MTZ. Interestingly, F5PG-MTZ enhanced the skin penetration of MTZ, although no enhancement effect was observed for an MTZ solution containing PG. Thus, a Pal-GH formulation containing PG and IPM may enhance the skin permeation of MTZ.

Highlights

Low molecular weight gelators have been considered attractive novel soft materials over the past two decades
We reported on the usefulness of Pal-GH gel as a spray gel topical formulation base for the application of ivermectin [1]
Hairless rat skin has been used as a good alternative membrane for human skin to evaluate skin permeation profiles and the permeability coefficients of drugs [2,3,4,5]

Summary

Introduction

Low molecular weight gelators have been considered attractive novel soft materials over the past two decades. One such material, N-Palmitoyl-Glycine-Histidine (Pal-GH) was developed by Nissan Chemical Industries (Tokyo, Japan) and exhibits thixotropic behavior and high dissolving properties for a wide range of hydrophilic to lipophilic drugs. The Pal-GH spray gel showed high spreadability and low flowability on the applied skin site, suggesting that it may be a good formulation base for transdermal drug delivery. Skin is broadly utilized as an application site for many drugs with expected topical and systemic pharmacological effects, the uppermost skin layer, the stratum corneum, has a high barrier property against skin permeation by drugs. It is a formidable challenge to enhance the skin permeation of poorly skin-penetrating drugs such as water-soluble drugs [6,7]

Objectives

Methods

Results