Comparison of two self-nanoemulsifying drug delivery systems using different solidification techniques for enhanced solubility and oral bioavailability of poorly water-soluble celecoxib

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.

Highlights

• Celecoxib-loaded liquid SNEDDS was prepared with Captex, Tween 80 and TPGS.
• S-SNEDDS and S-SNEGS were developed using two different solidification methods.
• Both systems converted celecoxib from crystalline to amorphous form.
• S-SNEGS showed improved flowability and enhanced oral bioavailability in rats.

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.

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Materials

Celecoxib, polyethylene glycol 4000 and Ca-silicate were acquired from Hanmi Pharm. Co. (Suwon, South Korea). Castor oil, corn oil, cottonseed oil, peanut oil, sesame oil, soybean oil, Span 20 and Tween 80 were bought from Daejung Chem. Co. (Siheung, South Korea). Poloxamer 188, Solutol HS15 and Cremophor® EL were purchased from BASF (Ludwigshafen, Germany). TPGS (D-α-Tocopherol polyethylene glycol 1000 succinate) was acquired from Sigma Aldrich (St. Louis, MO, USA). Capryol® 90 from Gattefosse.

Mi Ran Woo, Sanghyun Woo, Young-Woo Bak, Seunghyun Cheon, Jung Suk Kim, Sang Hun Ji, Seonghyeon Park, Jong Oh Kim, Sung Giu Jin, Han-Gon Choi, Comparison of two self-nanoemulsifying drug delivery systems using different solidification techniques for enhanced solubility and oral bioavailability of poorly water-soluble celecoxib,
Colloids and Surfaces B: Biointerfaces, 2024, 114044, ISSN 0927-7765, https://doi.org/10.1016/j.colsurfb.2024.114044.

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