Comparison of in vivo behaviors of intramuscularly long-acting celecoxib nanosuspensions with different particle sizes for the postoperative pain treatment

Abstract

Celecoxib (CXB) has a good analgesic effect on postoperative acute pain, but clinically its compliance is compromised because of frequent administration. Therefore, the development of injectable celecoxib nanosuspensions (CXB-NS) for long-acting analgesic effects is highly desirable. However, how the particle size affects the in vivo behaviors of CXB-NS remains unclear. Herein, CXB-NS with different sizes were prepared by the wet-milling method. Following intramuscular (i.m.) injection in rats (50 mg/kg), all CXB-NS achieved sustained systemic exposure and long-acting analgesic effects. More importantly, CXB-NS showed size-dependent pharmacokinetic profiles and analgesic effects, and the smallest CXB-NS (about 0.5 μm) had the highest C_max, T_1/2, and AUC_0-240h and the strongest analgesic effects on incision pain. Therefore, small sizes are preferred for long action by i.m. injection, and the CXB-NS developed in this study were alternative formulations for the treatment of postoperative acute pain.

Keywords: Analgesic effects; Celecoxib; Long-acting; Nanosuspensions; Particle size-dependent pharmacokinetics.