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

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 241; p. 114044
• Main Authors: Woo, Mi Ran, Woo, Sanghyun, Bak, Young-Woo, Cheon, Seunghyun, Kim, Jung Suk, Ji, Sang Hun, Park, Seonghyeon, Kim, Jong Oh, Jin, Sung Giu, Choi, Han-Gon
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2024
• Subjects: Administration, Oral; Animals; Biological Availability; Celecoxib; Celecoxib - administration & dosage; Celecoxib - chemistry; Celecoxib - pharmacokinetics; Drug Delivery Systems; Emulsions - chemistry; Flow properties; Male; Nanoparticles - chemistry; Oral bioavailability; Particle Size; Polysorbates - chemistry; Rats; Rats, Sprague-Dawley; Solid self-nanoemulsifying drug delivery system; Solid self-nanoemulsifying granule system; Solubility; Surface-Active Agents - chemistry; Water - chemistry; Solid self-nanoemulsifying granule system; Solid self-nanoemulsifying drug delivery system; Flow properties; Oral bioavailability; Celecoxib; Solubility
• DOI: 10.1016/j.colsurfb.2024.114044
• ISSN: 0927-7765; 1873-4367

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. [Display omitted] •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.