Physicochemical and Biopharmaceutical Characterization of Celecoxib Nanoparticle: Avoidance of Delayed Oral Absorption Caused by Impaired Gastric Motility

Publication date: Available online 22 September 2018Source: International Journal of PharmaceuticsAuthor(s): Keisuke Yakushiji, Mizuki Ogino, Hiroki Suzuki, Yoshiki Seto, Hideyuki Sato, Satomi OnoueAbstractThe present study aimed to develop a celecoxib (CEL) nanoparticle with improved dissolution/dispersion and consistent absorption even in the presence of impaired gastric motility. CEL was pulverized by a wet-milling with hydroxypropyl cellulose (HPC), and the prepared nanoparticles were physicochemically characterized after freeze-drying. CEL nanoparticle with HPC-SSL (NP/CEL) exhibited better dissolution/dispersion behavior in pH1.2 solution compared with CEL nanoparticles with other polymers, as evidenced by a 21.8-fold higher initial dissolution/dispersion rate than crystalline CEL. The mean particle diameter of water suspended-NP/CEL was 250 nm, and the CEL nanoparticle existed in an amorphous state. Even after storage at 40°C for 4 weeks, there were no significant changes in the dissolution/dispersion behavior. Oral absorption of CEL samples (5 mg-CEL/kg) was evaluated in normal and propantheline (PPT)-treated rats with simulated gastric motility impairment. In PPT-treated rats, oral crystalline CEL led to a decrease in oral absorption by 12% of the AUC0–4 compared with that in normal rats, whereas NP/CEL suppressed the pharmacokinetic transition of CEL by 40% of the AUC0–4 due to the improved dissolution/dispersion behavior of CEL. The NP/CEL system might be prom...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research