Development and Evaluation of Topical Gabapentin Formulations

Abstract

Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w) gabapentin 0.75% (w/w) Carbopol® hydrogels containing 5% (w/w) DMSO or 70% (w/w) ethanol and a compounded 10% (w/w) gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations.

A pilot study of transdermal gabapentin in cats

“…[27][28][29][30] Lipoderm was chosen as our drug delivery vehicle based on published human and veterinary medical literature for its stability and consistency. 3,18,29,[31][32][33][34] Based on our results, gabapentin does permeate both the feline ear pinna and cervical skin in vitro.…”

“…Each sample then was mounted on a diffusion cell with 10 mL sterile PBS in its receptor chamber and placed in a warm water bath at 39 C as described in experiments evaluating topical gabapentin formulations. 3 Transdermal gabapentin (10% or 20% in a Lipoderm base) was applied using a gloved finger to the mounted cadaver skin at 0 and 12 hours. Samples were collected from the receptor chamber of the diffusion cell (100 μL) at 0, 2, 4, 12, and 24 hours after initial transdermal application and immediately frozen at À80 C. An equivalent volume of PBS was not added to the receptor chamber after each sample collection.…”

“…[13][14][15] Transdermal delivery in veterinary medicine is challenging because of species differences in skin structure, barrier properties of skin, surface area required for optimal drug absorption, and lipid solubility of the medications used. [16][17][18] Transdermal administration of gabapentin recently was evaluated in humans, 3 buttransdermal absorption studies evaluating its use in cats are limited. 19 Our aim was to evaluate if gabapentin in a proprietary base (Lipoderm) permeates feline skin in vitro and in vivo and to determine if validated pain scores improve after its administration.…”

The Neuromodulatory Effect of Antipruritic Treatment of Chronic Prurigo

“…However, it is recommended as a treatment option [43]. Because of the common side effects of gabapentinoids, such as fatigue, drowsiness, dizziness, blurred vision, peripheral edema, weight gain and sexual dysfunction, a topical formula for the treatment of neuropathic pain is currently under development [44]. If this topical preparation is successful, it may also attract interest for the treatment of CNPG.…”

Penetration Enhancement of Topical Formulations

“…One study by Martin et al [8], which is reported in this special issue, exemplifies a chemical penetration enhancement strategy that is being deployed to improve topical drug delivery. They compounded and evaluated a range of topical gabapentin formulations, including hydrogels and creams, for the relief of neuropathic pain.…”