An injectable ropivacaine and lornoxicam sustained-release gel regulated by low molecular weight poly(ortho esters)

Persistent postoperative pain is commonly occurred after surgical procedures, while over half of patients suffer from poorly controlled pain, due to the limited therapeutic period of commercial drugs and suboptimal drug delivery strategy. Herein, an injectable sustained-release gel was developed by a combination of ropivacaine (a local anesthetic) and lornoxicam (a nonsteroidal anti-inflammatory drug), which formulated by poly(ortho esters) (POE) to regulate the sustained-release behavior. POE with low molecular weight was synthesized and employed to prepare the ropivacaine and lornoxicam sustained-release gel (RL-SRG) with the rheological characteristics of temperature-sensitivity. <i>In vitro</i> release studies demonstrated that RL-SRG exhibited sustained release for 72 h. The RL-SRG was stable for 3 months at 40 ± 2 °C and a relative humidity of 75 ± 5%. <i>In vivo</i> pharmacokinetic studies in rats indicated that RL-SRG maintained the plasma concentrations of ropivacaine and lornoxicam for 3 days. Compared to commercial products, RL-SRG prolonged the time of peak concentration (<i>T</i>_max), mean residence time (MRT), and elimination half life (<i>t</i>_1/2), as well as possessed similar the area under the plasma concentration-time curve (AUC_0-<i>_t</i>). Therefore, RL-SRG has been validated as a novel sustained release system to the application for the long-term treatment of postoperative pain.