Penetration-Enhancing Effect of Ethanolic Solution of Menthol on Transdermal Permeation of Ondansetron Hydrochloride Across Rat Epidermis

Abstract

The aim of this investigation was to study the effect of an ethanolwater solvent system and ehtanolic solution of menthol on the permeation of ondansetron hydrochloride across the rat epidermis in order to select a suitable ethanol-water vehicle and optimal concentration of menthol for the development of a transdermal therapeutic system. The solubility of ondansetron hydrochloride in ethanol, water and selected concenetrtaion of ethanol-water vehicles (20:80 v/v, 40:60 v/v and 60:40 v/v) was determined. The effect of these solvent vehicles, containing 1.5% w/v of ondansetron hydrochloride, on the in vitro permeation of the drug was studied across the rat epidermis. The highest permeation was observed from 60% v/v of ethanol-water vehicle that showed highest solubilty. Hence, the hydroxypropyl cellulose (HPC) (2% w/w) gel formulations containing 1.5% w/w of ondansetron hydrochloride and selected concentrations of menthol (0, 2, 4, 8 and 10% w/w) were prepared using 60% v/v of ethanol-water vehicle, and subjected to in vitro permeation of the drug across rat epidermis. The transdermal permeation of ondansetron hydrochloride was enhanced markedly by the addition of menthol to HPC gel drug reservoir formulations. A maximum flux of ondansetron hydrochloride (77.85 ± 2.85 μg/cm 2. h) was observed with a mean enhancement ratio of 13.06 when menthol was incorporated at a concentration of 8% w/w in HPC gels. However, there was no significant increase in the drug flux with 10% w/w menthol when compared to that obtained with 8% w/w of menthol in HPC gel formulations. The results suggest that 2% w/w HPC gel drug reservoir formulation, prepared with 60% v/v ethanol-water, containing 8% w/w of menthol provides an optimal transdermal permeation of ondansetron hydrochloride.

Formulation and Evaluation of Transdermal Patch of Indomethacin Containing Patchouli Oil as Natural Penetration Enhancer

“…The enhancer ratio was also estimated using the equation: E SS =J SS (enhancer treated)/J ss (control). All the data, hence, found was expressed as a mean ± standard deviation (SD) [24][25][26].…”

Studies on Optimizing In Vitro Transdermal Permeation of Ondansetron Hydrochloride Using Nerodilol, Carvone, and Limonene as Penetration Enhancers

“…[16] However, the flux obtained with 8% w/w menthol (77.9 ± 2.9 μg/cm 2. h) was less than the desired flux (84 μg/cm 2. h) to provide a steady-state permeation of ondansetron hydrochloride in humans. The desired flux (J) was calculated based on the mean pharmacokinetic parameters of ondansetron hydrochloride (clearance, CL = 21,240 ml/h) to obtain a mean steady-state plasma drug concentration (C ss ) of 26.2 ng/ml in humans using the equation: J = [(C ss × CL)/ area of the membrane].…”

Interaction of menthol with mixed-lipid bilayer of stratum corneum: A coarse-grained simulation study

“…As previously reported, menthol can efficiently promote the penetration of both hydrophilic and lipophilic drugs, such as quercetin, ondansetron hydrochloride, salicylate, zidovudine, etc. [9][10][11][12]. Given the "yaofuheyi" characteristic (means that an agent in a preparation not only have the effect of drug but also can be used as an excipient) and good penetration enhancing efficiency of menthol, it turned out to be a representative volatile oil of TCM used as a PE.…”