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

Abstract

The present investigation was carried out to formulate a terpene-based hydroxypropyl cellulose (HPC) gel drug reservoir system for its optimal transdermal permeation of ondansetron hydrochloride. The HPC gel formulations containing ondansetron hydrochloride (3% w/w) and selected concentrations of either nerodilol (0% w/w, 1% w/w, 2% w/w, 3% w/w, and 4% w/w), carvone (0% w/w, 2% w/w, 4% w/w, 8% w/w, and 10% w/w), or limonene (0% w/w, 2% w/w, 3% w/w, and 4% w/w) were prepared and subjected to in vitro permeation of the drug across rat epidermis. All the 3 terpene enhancers increased the transdermal permeation of ondansetron hydrochloride. The optimal transdermal permeation was observed with 3% w/w of nerodilol (175.3 ± 3.1 μg/ cm 2. h), 8% w/w of carvone (87.4 ± 1.6 μg/cm 2. h), or 3% w/w of limonene (181.9 ± 0.9 μg/cm 2. h). The enhancement ratio (ER) in drug permeability with 3% w/w nerodilol, 8% w/w carvone, and 3% w/w limonene were 21.6, 10.8, and 22.5, respectively, when compared with that obtained without a terpene enhancer (control). However, there was 1.04-, 2.09-, and 2.17-fold increase in the optimal drug flux obtained with carvone, nerodilol, and limonene, respectively, when compared with the desired drug flux (84 μg/cm 2. h). It was concluded that the HPC gel drug reservoir systems containing either 3% w/w nerodilol or 3% w/w limonene act as optimal formulations for use in the design of membrane-controlled transdermal therapeutic system (TTS) of ondansetron hydrochloride.

Biopolymer-Based Transdermal Films of Donepezil as an Alternative Delivery Approach in Alzheimer’s Disease Treatment

“…A similar, negative effect of enhancer concentration on permeation profile of valsartan was also reported previously by Rizwan et al (26). Krishnaiah et al also studied the transdermal permeation of ondansetron in the presence and absence of different terpenes (13). They also indicated that there was no significant difference on the penetration enhancing effect of limonene depending on increasing its concentration, due to plateau effect on the drug permeation across skin above 3%.…”

“…The mechanism of permeation enhancing activity of terpenes have been attributed to increment of the drug partition into the stratum corneum and creating perturbation on the intercellular packing of the stratum corneum lipids (10,11). Limonene is a lipophilic hydrocarbon terpene (logP: 4.58), obtained from the lemon peel of Citrus lemon (12,13).…”

Anti-Inflammatory Activity of Spearmint (Mentha spicata) Essential Oil in Human Dermal Fibroblasts

“…Studies have also shown evidence that carvone and limonene act as transdermal permeation enhancers [29]. Limonene has been found to promote skin repair and inhibit skin tumorigenesis [30,28].…”

Optimization of Biopolymer Based Transdermal Films of Metoclopramide as an Alternative Delivery Approach

“…Terpenes are derived from plant essential oils, have been shown to increase the percutaneous absorption of both hydrophilic and lipophilic drugs [12,15,18,19]. It was reported that terpenes enhance the permeation of drug across the skin mainly by disrupting the highly ordered intercellular chain packing of stratum corneum lipids and thereby increasing drug diffusivity [20,21].…”

“…However, transdermal transport of drugs is limited due to low permeability of the uppermost layer of the skin, stratum corneum. In order to overcome that barrier and to enhance the permeability of the drugs across the skin, permeation enhancers and co-solvents, which reversibly perturb the permeability of stratum corneum or increase partition of drug to stratum corneum are included in the transdermal formulation [12][13][14].…”