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基于丁香油的无助表面活性剂氟比洛芬微乳剂:改善溶解度并减轻药物性胃炎

Clove oil based co-surfactant free microemulsion of flurbiprofen: Improved solubility with ameliorated drug-induced gastritis.

作者信息

Tanzeem Muhammad Umair, Asghar Sajid, Khalid Syed Haroon, Asif Muhammad, Ullah Malik Saad, Khan Ikram Ullah, Khalid Ikrima, Faran Syed Ali, Rehman Abdul, Gohar Umar Farooq, Hussain Tanveer

机构信息

Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Pakistan.

Institute of Industrial Biotechnology, Government College University Lahore, Pakistan.

出版信息

Pak J Pharm Sci. 2019 Nov;32(6(Supplementary)):2787-2793.

Abstract

Flurbiprofen, an NSAID, is a water insoluble drug that is also notorious for gastric irritation and inflammation. This study was aimed at using a natural gastrprotective oil as the internal phase to develop flurbiprofen micro emulsion (ME) to improve it solubility and ameliorate its gastric side effects. Upon screening of ME components for drug solubility, clove oil, tween 80 and transcutol were identified as the oil, surfactant and co surfactant, respectively, with higher flurbiprofen solubility. Pseudo-ternary phase diagrams revealed that the ME made with surfactant only and without co-surfactant displayed the similar ME region as made with the mixture of surfactant and co-surfactant. Furthermore, drug loaded oil was also used to draw pseudo-ternary phase diagram and a very little decrease in the ME region was observed. Therefore, co-surfactant free flurbiprofen loaded ME was developed to avoid side effects associated with the use of excessive surfactant quantities. ME were found to possess size in the range of 11-41 nm with PDI <0.5 and a slightly negative charge. Conductivity, pH and refractive indices of the selected MEs were well in the range. Drug release studies indicated maximum drug release from MEs within 5 min. Analysis of the gastric mucosa of rats after oral administration of drug solution and drug loaded ME confirmed that clove oil based ME provided significant protection against the NSAIDs induced gastric damage.

摘要

氟比洛芬是一种非甾体抗炎药,是一种水不溶性药物,也因引起胃刺激和炎症而声名狼藉。本研究旨在使用一种天然的胃保护油作为内相来开发氟比洛芬微乳剂(ME),以提高其溶解度并改善其胃部副作用。在筛选用于药物溶解的微乳剂成分时,分别确定丁香油、吐温80和二乙二醇单乙醚为油相、表面活性剂和助表面活性剂,它们对氟比洛芬的溶解度较高。伪三元相图显示,仅用表面活性剂而不用助表面活性剂制备的微乳剂与用表面活性剂和助表面活性剂混合物制备的微乳剂具有相似的微乳区域。此外,载药油也用于绘制伪三元相图,观察到微乳区域仅有非常小的减小。因此,开发了不含助表面活性剂的载氟比洛芬微乳剂,以避免因使用过量表面活性剂而产生的副作用。发现微乳剂的粒径在11-41nm范围内,多分散指数(PDI)<0.5,且带轻微负电荷。所选微乳剂的电导率、pH值和折射率均在合适范围内。药物释放研究表明,微乳剂在5分钟内药物释放量最大。对大鼠口服药物溶液和载药微乳剂后的胃黏膜进行分析,证实基于丁香油的微乳剂对非甾体抗炎药引起的胃损伤具有显著的保护作用。

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