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Preclinical Studies of Ropivacaine Extended-Release from a Temperature Responsive Hydrogel for Prolonged Relief of Pain at Surgical Wound.
International Journal of Pharmaceutics 2019 January 15
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 prolonged release of ropivacaine. When the ropivacaine was administered using PF-72, its concentration-time curve (AUClast ) and peak concentration (Cmax ) were 577.0 hr*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 hr*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 hours) 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. Another advantages of ropivacaine administration using PF-72 include reduced systemic side effects and high localization of a drug in target tissues.
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