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渗透促进剂对拉莫三嗪从Eudragit RS100聚合物基质型药物贴剂中的体外释放及经皮递送的影响。

Effect of permeation enhancers on in vitro release and transdermal delivery of lamotrigine from EudragitRS100 polymer matrix-type drug in adhesive patches.

作者信息

Jafri Ifrah, Shoaib Muhammad Harris, Yousuf Rabia Ismail, Ali Fatima Ramzan

机构信息

Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan.

出版信息

Prog Biomater. 2019 Jun;8(2):91-100. doi: 10.1007/s40204-019-0114-9. Epub 2019 May 8.

Abstract

The drug-in-adhesive (DIA)-type matrix patches of lamotrigine are developed using variable permeation enhancers (oleic acid, PG, lemon oil and aloe vera), and drug in vitro release and its permeation are evaluated. Lamotrigine has been long used as an anti-epileptic, mood stabilizer, to treat bipolar disorder in adults and off label as an antidepressant. lamotrigine matrix patches comprising of EudragitRS100 (rate-controlling polymer) and DuroTak 387-2510 (adhesive) were prepared by pouring the solution on backing membrane (3M-9720). The thickness of 120 µm was adjusted through micrometer film applicator. USP Apparatus V was used for the evaluation of release profile, which was fitted into various mathematical models. Quality characteristics of patches were determined through weight variation, moisture content, moisture uptake and drug content evaluation. FTIR studies were performed for drug-excipient compatibility; Franz diffusion cell was employed for studying in vitro permeation parameters such as flux, lag time, and ER. Skin sensitivity study of optimized patch was also performed. The release from patches comprising of PG and oleic acid was maximum, i.e., 96.24 ± 1.15% and 91.12 ± 1.11%, respectively. Formulations (A1-A5) exhibited Makoid-Banakar release profile. Formulation A3 consisting of oleic acid was optimized due to enhanced permeation of drug across skin compared to other enhancers with enhancement ratio of 3.55. Skin sensitivity study revealed patch as safe and non-allergenic. The study demonstrates that oleic acid can be used as a suitable permeation enhancer for transdermal delivery of lamotrigine from matrix-type patches.

摘要

采用不同的渗透促进剂(油酸、丙二醇、柠檬油和芦荟)研制了拉莫三嗪的药物黏附型(DIA)基质贴片,并对药物的体外释放及其渗透情况进行了评估。拉莫三嗪长期以来一直用作抗癫痫药、情绪稳定剂,用于治疗成人双相情感障碍,也可作为抗抑郁药用于未标明的适应症。通过将溶液浇铸在背衬膜(3M - 9720)上制备了由丙烯酸树脂RS100(控释聚合物)和DuroTak 387 - 2510(黏合剂)组成的拉莫三嗪基质贴片。通过微米薄膜涂布器将厚度调整为120μm。使用美国药典装置V评估释放曲线,并将其拟合到各种数学模型中。通过重量差异、水分含量、吸湿量和药物含量评估来确定贴片的质量特性。进行了傅里叶变换红外光谱(FTIR)研究以考察药物 - 辅料相容性;采用弗兰兹扩散池研究体外渗透参数,如通量、滞后时间和渗透比。还对优化后的贴片进行了皮肤敏感性研究。含丙二醇和油酸的贴片释放量最大,分别为96.24±1.15%和91.12±1.11%。制剂(A1 - A5)呈现出马科伊德 - 巴纳卡尔释放曲线。与其他促进剂相比,含油酸的制剂A3因药物经皮渗透增强而被优化,增强比为3.55。皮肤敏感性研究表明该贴片安全且无致敏性。该研究表明油酸可作为一种合适的渗透促进剂,用于从基质型贴片中经皮递送拉莫三嗪。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48c6/6556165/87317b556334/40204_2019_114_Fig1_HTML.jpg

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