Abstract The oral administration of celecoxib (CLX) is a real problem because of its low aqueous solubility that results in high variability in absorption and its severe adverse effect such as cardiotoxic effects and gastrointestinal toxicity. Self-nanoemulsifying drug delivery systems (SNEDDS) can enhance the poor dissolution and erratic absorption of poorly water-soluble drugs such as CLX. This study was conducted to investigate the potential of SNEDDS to enhance the efficacy of CLX on inflamed mucous tissue and reduce systemic adverse effects by increasing its poor dissolution properties. A pseudo-ternary phase diagram was derived from the results of CLX solubility experiments in various excipients. These studies revealed the use of Labrafil M 2515 CS as oil, tween 80 as a surfactant, and polyethylene glycol 400 as a co-surfactant for the optimization of SNEDDS formulations. Eight formulations were formulated and characterized by their particle size, polydispersity index, viscosity, globular shape, drug solubility, self-emulsification efficiency, in vitro drug release, and permeation. The anti-inflammatory effect of CLX-SNEDDS was evaluated by carrageenan-induced cheek oedema in rats. The cheeks were treated with CLX-SNEDDS before oedema induction and then noticed for narrow periods (2 h) followed by histopathological studies to determine the efficacy of treatment. The selected formulations (F3 and F5) showed spherical morphologies under transmission electron microscopy, mean droplet sizes of 116.9 ± 1.78 and 124 ± 1.87 nm, respectively, complete in vitro drug release, and high cumulative amounts of drug permeation in 8 h. They also showed significant remarkable cheek oedema inhibition in comparison with the control groups (p < 0.05). CLX-SNEDDS was found to achieve effective local therapeutic concentration and intended to reduce cheek oedema, congestive capillary, inflammatory cells, and side effects due to lower dose size.

中文翻译：

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塞来昔布自纳米乳化给药系统治疗口腔炎症的制剂开发

摘要 塞来昔布 (CLX) 的口服给药是一个真正的问题，因为它的水溶性低，导致吸收的高度可变性和严重的副作用，如心脏毒性和胃肠道毒性。自纳米乳化给药系统 (SNEDDS) 可以增强难溶性药物（如 CLX）的溶出度差和吸收不稳定。本研究旨在研究 SNEDDS 提高 CLX 对发炎粘液组织的疗效并通过增加其较差的溶解特性来减少全身不良反应的潜力。拟三元相图源自 CLX 在各种赋形剂中的溶解度实验结果。这些研究表明，使用 Labrafil M 2515 CS 作为油，吐温 80 作为表面活性剂，聚乙二醇 400 作为辅助表面活性剂，用于优化 SNEDDS 配方。配制了八种制剂，并通过它们的粒度、多分散指数、粘度、球状、药物溶解性、自乳化效率、体外药物释放和渗透进行表征。通过角叉菜胶诱导的大鼠脸颊水肿评估 CLX-SNEDDS 的抗炎作用。在水肿诱导前用 CLX-SNEDDS 治疗脸颊，然后在很短的时间内（2 小时）观察，然后进行组织病理学研究以确定治疗效果。所选制剂（F3 和 F5）在透射电子显微镜下显示球形形态，平均液滴尺寸分别为 116.9 ± 1.78 和 124 ± 1.87 nm，完全体外药物释放，8 小时内药物渗透累积量高。与对照组相比，它们还显示出显着显着的脸颊水肿抑制（p < 0.05）。发现 CLX-SNEDDS 可达到有效的局部治疗浓度，旨在减少脸颊水肿、充血性毛细血管、炎症细胞和由于较低剂量而产生的副作用。