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局部用加巴喷丁制剂的研发与评价

Development and Evaluation of Topical Gabapentin Formulations.

作者信息

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

机构信息

St Mary's Pharmaceutical Unit, Cardiff and Vale UHB, Cardiff CF14 4HY, UK.

Cardiff School of Pharmacy and Pharmaceutical Sciences, Redwood Building, King Edward VII Avenue, Cardiff University, Cardiff CF10 3NB, UK.

出版信息

Pharmaceutics. 2017 Aug 30;9(3):31. doi: 10.3390/pharmaceutics9030031.

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% (/) gabapentin 0.75% (/) Carbopol hydrogels containing 5% (/) DMSO or 70% (/) ethanol and a compounded 10% (/) 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.

摘要

局部递送加巴喷丁有助于治疗周围神经性疼痛,同时避免全身副作用。迄今为止,体外局部递送加巴喷丁的报道结果不一,且取决于所采用的皮肤模型,主要涉及啮齿动物和猪模型。在本研究中,对多种局部用加巴喷丁制剂进行了研究,包括含有各种渗透促进剂的卡波姆水凝胶,以及一系列专利基质,包括一种复方脂质体配方;此外,微针辅助递送用作阳性对照。关键的是,使用弗兰兹型扩散池评估加巴喷丁在体外透过人表皮膜的情况。随后,在更广泛的文献范围内对这些数据进行了分析。尽管局部递送加巴喷丁的报道结果各异,很大程度上取决于所使用的皮肤模型,但本研究表明,含5%二甲亚砜或70%乙醇的6%(/)加巴喷丁0.75%(/)卡波姆水凝胶以及复方10%(/)加巴喷丁脂质体配方能够促进该分子透过人体皮肤。需要进一步的临床前和临床研究来考察预期制剂的局部递送性能和药效学作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/019b/5620572/e769ae2688b5/pharmaceutics-09-00031-g001.jpg

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