Local sustained delivery of bupivacaine HCL from a new castor oil-based nanoemulsion system

Heni Rachmawati* (Corresponding Author), Yang Aryani Arvin, Sukmadjaja Asyarie, Kusnandar Anggadiredja, Raymond Rubianto Tjandrawinata, Gert Storm

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

Bupivacaine HCl (1-butyl-2′,6′-pipecoloxylidide hydrochloride), an amide local anesthetic compound, is a local anesthetic drug utilized for intraoperative local anesthesia, post-operative analgesia and in the treatment of chronic pain. However, its utility is limited by the relative short duration of analgesia after local administration (approximately 9 h after direct injection) and risk for side effects. This work is aimed to develop a nanoemulsion of bupivacaine HCl with sustained local anesthetics release kinetics for improved pain management, by exhibiting extended analgesic action and providing reduced peak levels in the circulation to minimize side effects. Herein, biodegradable oils were evaluated for use in nanoemulsions to enable sustained release kinetics of bupivacaine HCl. Only with castor oil, a clear and stable nanoemulsion was obtained without the occurrence of phase separation over a period of 3 months. High loading of bupivacaine HCl into the castor oil-based nanoemulsion system was achieved with about 98%entrapment efficiency and the resulting formulation showed high stability under stress conditions (accelerated stability test) regarding changes in visual appearance, drug content, and droplet size. We show herein that the in vitro release and in vivo pharmacokinetic profiles as well as pharmacodynamic outcome (pain relief test) after subcutaneous administration in rats correlate well and clearly demonstrate the prolonged release and extended duration of activity of our novel nanoformulation. In addition, the lower Cmax value achieved in the blood compartment suggests the possibility that the risk for systemic side effects is reduced. We conclude that castor oil-based nanomulsion represents an attractive pain treatment possibility to achieve prolonged local action of bupivacaine HCl.

Original languageEnglish
Pages (from-to)515-524
Number of pages10
JournalDrug delivery and translational research
Volume8
Issue number3
Early online date7 Mar 2018
DOIs
Publication statusPublished - Jun 2018

Keywords

  • UT-Hybrid-D
  • Bupivacaine HCl
  • Cardiotoxic
  • Castor oil
  • Local analgesic
  • Nanoemulsion
  • Prolonged release
  • Amide local anesthetic

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