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

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.

Ionic Liquid-In-Oil Microemulsions Prepared with Biocompatible Choline Carboxylic Acids for Improving the Transdermal Delivery of a Sparingly Soluble Drug

“…ME6 was prepared to compare the surface activity, drug loading capacity, permeability, and toxicity of [Ch][Ole] and Tween-80. 3 ) compared with Span-20 (1.032 g/cm 3 ), but the differences were not significant among them. The viscosity of the MEs varied significantly with the S/Co ratio and increased with increasing [Ch][Ole] content in the S/Co mix , whereas the viscosity did not depend on the ILs, Table S1.…”

“…The transdermal drug delivery system (TDDS), a safe, non-invasive, easy, and effective drug delivery system, has attracted much attention in recent research because of its numerous prospective advantages, including improved patient compliance, avoidance of the first-pass metabolism, persistent and controlled delivery, and reduction of undesirable adverse effects [1,2]. However, the widespread use of this system is restricted to a few drugs only, because of the impermeable nature of the stratum corneum (SC), the outermost layer of the skin [3,4]. To overcome these limitations, many micro-structured fluid systems, including microemulsions, nanoparticles, and permeation enhancers containing other vesicles have been investigated to improve drug delivery efficiency via disrupting and modifying the regular arrangement of the corneocytes of the SC [5,6].…”

Pengaruh Karbopol dan Propilen Glikol terhadap Laju Penetrasi Sediaan Emulgel Xanthone Rich Fraction dari Kulit Buah Manggis (Garcinia mangostana L.)

“…Viskositas sediaan dapat berkaitan dengan laju penetrasi dimana nilai viskositas berbanding terbalik dengan laju penetrasi. Semakin tinggi viskositas sediaan maka semakin sulit zat aktif terlepas dari pembawanya [25]. Oleh karena itu, jumlah αmangostin dan persentase α-mangostin F3 lebih rendah daripada F4.…”

Current Status of Amino Acid-Based Permeation Enhancers in Transdermal Drug Delivery

“…This approach may be used to increase skin concentration of otherwise non-absorbed drugs from topical formulations. The same authors described the use of a gelator made up of the same alkylpeptide Pal-GH, to increase the skin permeation of metronidazole (MTZ), a hydrophilic drug with low skin permeability [ 82 ]. Formulations of Pal-GH with MTZ alone and in the presence of several CPEs were prepared.…”