Preclinical studies of ropivacaine extended-release from a temperature responsive hydrogel for prolonged relief of pain at the surgical wound

• Published in: International journal of pharmaceutics 2019-03, Vol.558, p.225-230
• Main Authors: Oh, Keun Sang, Hwang, Changsoon, Lee, Ha-Yeon, Song, Jin Sook, Park, Hyun-Ji, Lee, Chul-Kyu, Song, InO, Lim, Tae-Hong
• Format: Article
• Language: English
• Subjects: Drug-delivery; Hydrogel; Ropivacaine; Surgical wound pain control; Sustained release
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2019.01.011

[Display omitted] Postoperative pain is a common form of acute pain that has been treated commonly by local anesthetics through regional nerve blocking. In this study, a series of experiments were conducted using rats to investigate the pharmacokinetic, distribution, and efficacy of a temperature responsive hydrogel-based drug delivery device (PF-72) containing ropivacaine (0.75%) for extended relief of postoperative pain by allowing the prolonged release of ropivacaine. When the ropivacaine was administered using PF-72, its concentration-time curve (AUClast) and peak concentration (Cmax) were 577.0 h*ng/mL and 271.9 ng/mL, respectively. In contrast when the ropivacaine solution was administered using saline solution, its AUClast and Cmax were 982.8 h*ng/mL and 423.6 ng/mL, respectively. In the tissue distribution study, the peak concentration and mean area under the curve of the ropivacaine in injection area (target tissue) were found about 2-fold higher in the case of PF-72 compared with the case of conventional ropivacaine solution. These results clearly demonstrate the capability of PF-72 hydrogel to retain the ropivacaine at the injection site for an extended period. Effective extended (at least 24 h) pain relief of ropivacaine administered using PF-72 was found in the pharmacodynamic study of prolonged analgesic effect. The results of this study indicated that local drug delivery by PF-72 hydrogel formulation may be an effective method to achieve extended relief of pain. Other advantages of ropivacaine administration using PF-72 include reduced systemic side effects and high localization of a drug in target tissues.