Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Liaoning Institute for Drug Control, No. 7, Chongshan West Road, Shenyang 110016, China.
Int J Pharm. 2023 Apr 5;636:122793. doi: 10.1016/j.ijpharm.2023.122793. Epub 2023 Mar 2.
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, T, and AUC 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.
塞来昔布（CXB）对术后急性疼痛具有良好的镇痛效果，但由于频繁给药，其临床依从性受到影响。因此，开发用于长效镇痛作用的注射用塞来昔布纳米混悬剂（CXB-NS）是非常需要的。然而，粒径如何影响 CXB-NS 的体内行为尚不清楚。本文采用湿磨法制备了不同粒径的 CXB-NS。在大鼠（50mg/kg）肌肉注射后，所有 CXB-NS 均实现了持续的全身暴露和长效镇痛作用。更重要的是，CXB-NS 表现出粒径依赖性的药代动力学特征和镇痛效果，最小的 CXB-NS（约 0.5μm）具有最高的 C、T 和 AUC，对切口疼痛的镇痛效果最强。因此，通过肌肉注射，较小的粒径更有利于长效作用，本研究开发的 CXB-NS 是治疗术后急性疼痛的替代制剂。
