Abstract：
In this study, we aimed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) and a solid self-nanoemulsifying granule system (S-SNEGS) to enhance the solubility and oral bioavailability of celecoxib. This process involved the preparation of a liquid SNEDDS (L-SNEDDS) and its subsequent solidification into a S-SNEDDS and a S-SNEGS. The L-SNEDDS consisted of celecoxib (drug), Captex® 355 (Captex; oil), Tween® 80 (Tween 80; surfactant) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS; cosurfactant) in a weight ratio of 3.5:25:60:15 to produce the smallest nanoemulsion droplet size. The S-SNEDDS and S-SNEGS were prepared with L-SNEDDS/Ca-silicate/Avicel PH 101 in a weight ratio of 103.5:50:0 using a spray dryer and 103.5:50:100 using a fluid bed granulator, respectively. We compared the two novel developed systems and celecoxib powder based on their solubility, dissolution rate, physicochemical properties, flow properties and oral bioavailability in rats. S-SNEGS showed a significant improvement in solubility and dissolution rate compared to S-SNEDDS and celecoxib powder. Both systems had been converted from crystalline drug to amorphous form. Furthermore, S-SNEGS exhibited a significantly reduced angle of repose, compressibility index and Hausner ratio than S-SNEDDS, suggesting that S-SNEGS was significantly superior in flow properties. Compared to S-SNEDDS and celecoxib powder, S-SNEGS increased the oral bioavailability (AUC value) in rats by 1.3 and 4.5-fold, respectively. Therefore, S-SNEGS wolud be recommended as a solid self-nanoemulsifying system suitable for poorly water-soluble celecoxib.
摘要：
在这项研究中,我们旨在开发固体自纳米乳化药物递送系统(S-SNEDDS)和固体自纳米乳化颗粒系统(S-SNEGS),以提高塞来昔布的溶解度和口服生物利用度.该过程涉及液体SNEDDS（L-SNEDDS）的制备及其随后固化为S-SNEDDS和S-SNEGS。L-SNEDDS由塞来昔布（药物）组成，Captex®355(Captex;油),Tween®80(Tween80;表面活性剂)和D-α-生育酚聚乙二醇1000琥珀酸酯(TPGS;助表面活性剂)以3.5:25:60:15的重量比产生最小的纳米乳液液滴尺寸。S-SNEDDS和S-SNEGS用L-SNEDDS/Ca-硅酸盐/AvicelPH101以103.5:50:0的重量比使用喷雾干燥器和103.5:50:100的重量比使用流化床造粒机制备,分别。我们比较了两种新开发的体系和塞来昔布粉末的溶解度，溶出度,物理化学性质，大鼠的流动性能和口服生物利用度。与S-SNEDDS和塞来昔布粉末相比，S-SNEGS显示出溶解度和溶解速率的显着改善。两种系统都已从结晶药物转化为无定形形式。此外，S-SNEGS表现出明显减小的静止角，压缩指数和Hausner比S-SNEDDS，这表明S-Snegs在流动性能方面明显优越。与S-SNEDDS和塞来昔布粉相比，S-SNEGS将大鼠的口服生物利用度（AUC值）提高了1.3倍和4.5倍，分别。因此,建议使用S-SNEGSWolud作为固体自纳米乳化系统，适用于水溶性差的塞来昔布。
