Development and Evaluation of Topical Gabapentin Formulations.

Christopher J Martin,James C Birchall,Sarah Hiom,Natalie Alcock

doi:10.3390/pharmaceutics9030031

Christopher J Martin, James C Birchall + Show 2 more

Open Access

https://doi.org/10.3390/pharmaceutics9030031

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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.

Highlights

Gabapentin is an anti-epileptic drug (AED) currently licensed for the treatment of partial epileptic seizures [1] and peripheral neuropathic pain (NP) conditions, such as vulvodynia, post-herpetic neuralgia and painful diabetic peripheral neuropathy [2]
The aim of the current study is to develop and optimise stable topical gabapentin formulations and to investigate their delivery capabilities using a human epidermal membrane model, which can be considered to have a close correlation to the human skin barrier found in vivo
The oil-in-water (o/w) formulations consisted of macroscopic emulsions that presented with a white to off-white colour

Summary

Introduction

Gabapentin is an anti-epileptic drug (AED) currently licensed for the treatment of partial epileptic seizures [1] and peripheral neuropathic pain (NP) conditions, such as vulvodynia, post-herpetic neuralgia and painful diabetic peripheral neuropathy [2]. Whilst gabapentin is considered to be better tolerated with fewer side effects than other AEDs, treatment of NP with oral gabapentin is still often limited by adverse effects [3], such as dizziness, somnolence [4], ataxia and fatigue [1]. Topical or localised drug delivery has been shown to limit the adverse effects of systemically delivered medications for NP whilst providing high concentrations of active at the site of administration [5]. A recent in vivo study has shown topically applied gabapentin to be efficacious in a diabetic rodent model of both allodynia and vulvodynia [6]. The product is available as a “pharmaceutical special” with reported efficacy when used as a treatment for peripheral NP [3,7]

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