Formulation and evaluation of multilamellar vesicles ropivacaine in pain management

Abstract

Purpose

The improvement of postoperative pain control plays an important role in recovery outcomes and patient satisfaction. Multilamellar vesicles ropivacaine, MVR, is being developed to sustain the release of ropivacaine in situ while maintaining the local concentration of ropivacaine within the therapeutic window.

Methods

These studies summarized the processes of MVR formulation development and the evaluation of its releasing profile in vitro and the pharmacokinetics and anesthetic effect in vivo.

Results

The MVR demonstrates a sustained-release profile in an in vitro serum environment model after 24 hrs of incubation which translates in the in vivo rat pharmacokinetic profile of ropivacaine as a prolonged half-life that is 10-fold longer in duration than plain ropivacaine solution. The anesthetic effect of single-dose MVR is apparent by providing a prolonged analgesia effect compared to plain ropivacaine solution in an in vivo guinea pig pin-prick wheal model after a single intracutaneous injection. From a safety evaluation, MVR is well tolerated after a subcutaneously injection at a dose level of 20 mg/kg in rats, with no observable changes in clinical observation, body weight, organ weight, hematology and serum chemistry analysis.

Conclusion

These results suggest that single administration of MVR is a promising candidate in postoperative pain management.

Keywords:

• multilamellar vesicles
• postoperative pain management
• ropivacaine
• sustained release

Acknowledgments

Part of the results in this manuscript were presented at the 44th Annual Regional Anesthesiology & Acute Pain Medicine Meeting named “The Pharmacokinetic and Pharmacodynamic Evaluation of Multilamellar Vesicles Formulated Ropivacaine, TLC590, Administered by Local Injection in Rats” as a poster presentation with interim findings.

Disclosure

The authors were supported by TLC Biopharmaceuticals, Inc. (South San Francisco, USA) and Taiwan Liposome Company, Ltd. (Taipei, Taiwan). All authors are employees of TLC Biopharmaceuticals, Inc. The authors report no other conflicts of interest in this work.