Self-Emulsifying Drug Delivery System of Celecoxib for Avoiding Delayed Oral Absorption in Rats with Impaired Gastric Motility.

Abstract

This study aimed to develop a self-emulsifying drug delivery system (SEDDS) of celecoxib (CEL) for suppressed delay in oral absorption under impaired gastric motility. A pseudo-ternary phase diagram was constructed for the determination of the optimal component ratio in SEDDS of CEL (SEDDS/CEL), and the SEDDS/CEL was physicochemically characterized. A pharmacokinetic study on orally dosed CEL samples (5-mg CEL/kg) was carried out in normal and propantheline (PPT)-treated rats to mimic impaired gastric motility. SEDDS/CEL rapidly formed a fine emulsion with a mean size of 147nm in distilled water and significantly improved the dissolution behavior of CEL under pH 1.2 condition with a 20-fold higher dissolved amount than crystalline CEL. In normal rats, orally dosed SEDDS/CEL provided a 4.6-fold higher systemic exposure than that of crystalline CEL, due to the improved dissolution properties of CEL. Crystalline CEL showed delayed and decreased oral absorption of CEL in PPT-treated rats as evidenced by a 6.9-h-delayed mean absorption time and only 12% of the systemic exposure of CEL compared with those in normal rats. In contrast, SEDDS/CEL enhanced the oral absorption of CEL with a 14.6-fold higher systemic exposure with significant suppression of delay in absorption than crystalline CEL even in PPT-treated rats. SEDDS/CEL could be an efficacious option for suppressing delay in CEL absorption even under impairment of gastric motility, possibly leading to rapid and reproducible management of severe acute pain.