Transdermal Delivery of Gabapentin: Effect of Cosolvent and Microemulsion on Permeation through the Rat Skin

• 作者: Charles O. Nnadi Chika J. Mbah
• 来源期刊: 药理与制药(英文)
• 学科: 化学
• 关键词: TRANSDERMAL Delivery COSOLVENT System MICROEMULSION GABAPENTIN
• 年，卷（期）: 2014,（5）
• 页码范围: 471-478
• 页数: 8页
• 分类号: O6

摘要

The objective of the present study was to examine the influence of cosolvent system and micro-emulsion formulation on in-vitro skin permeation of gabapentin, furthermore, to characterize the physicochemical properties of drug-loaded oil-in-water (o/w) and water-in-oil (w/o) cremophor 40-based microemulsions in comparison to the blank counterparts. The cosolvent system prepared by homogenous mixing is composed of ethanol-water and propylene glycol-water mixture (90:10, 80:20, 70:30 v/v) respectively. The microemulsion consisted of coconut oil, water and mixture of cremophor 40 (surfactant) and ethanol (cosurfactant) and was prepared by aqueous phase titration method. Physicochemical properties of microemulsions were determined using reported procedures. Transdermal flux for gabapentin was studied in-vitro using modified Franz diffusion cells. The physicochemical properties of drug-loaded microemulsions and their blank counterparts were generally alike, however, slight variation in pH and viscosity was observed probably due to the intrinsic properties of the drug. The ethanol-water system (70:30 v/v) gave higher flux for gabapentin when compared to propylene glycol-water system (70:30 v/v). The w/o microemulsion formulations resulted in, higher flux for gabapentin when compared to o/w formulations. FTIR spectra of the untreated stratum corneum, when compared to cosolvent system and microemulsion treated stratum corneum, suggest the mechanism of permeation to be disruption of lipid bilayers and keratin denaturation of the stratum corneum. The results show that incorporation of gabapentin into microemulsions did not change the microemulsion type. The in vitro permeation data obtained from experimental work suggest that the cosolvent system (ethanol-water 70:30 v/v) and w/o microemulsion formulations respectively, can be successfully used as potential vehicles in developing transdermal therapeutic systems for gabapentin.