Formulation of Bioerodible Ketamine Microparticles as an Analgesic Adjuvant Treatment Produced by Supercritical Fluid Polymer Encapsulation

Han, Felicity; Whittaker, Andrew; Howdle, Steven; Naylor, Andrew; Shabir-Ahmed, Anjumn; Zhang, Cheng; Smith, Maree

Abstract

Pain is inadequately relieved by escalating doses of a strong opioid analgesic such as morphine in up to 25% of patients with cancer-related severe pain complicated by a neuropathic (nerve damage) component. Hence, there is an unmet medical need for research on novel painkiller strategies. In the present work, we used supercritical fluid polymer encapsulation to develop sustained-release poly(lactic-co-glycolic acid) (PLGA) biodegradable microparticles containing the analgesic adjuvant drug ketamine, for injection by the intrathecal route. Using this approach with a range of PLGA co-polymers, drug loading was in the range 10–60%, with encapsulation efficiency (EE) of 60–100%. Particles were mainly in the size range 20–45 µm and were produced in the absence of organic solvents and surfactants/emulsifiers. Investigation of the ketamine release profiles from these PLGA-based microparticles in vitro showed that release took place over varying periods in the range 0.5–4.0 weeks. Of the polymers assessed, the ester end-capped PLGA5050DLG-1.5E gave the best-controlled release profile with drug loading at 10%.

Citation

Han, F., Whittaker, A., Howdle, S., Naylor, A., Shabir-Ahmed, A., Zhang, C., & Smith, M. (2018). Formulation of Bioerodible Ketamine Microparticles as an Analgesic Adjuvant Treatment Produced by Supercritical Fluid Polymer Encapsulation. Pharmaceutics, 10(4), Article 264. https://doi.org/10.3390/pharmaceutics10040264

• Journal Article Type: Article
• Acceptance Date: Dec 4, 2018
• Online Publication Date: Dec 6, 2018
• Publication Date: Dec 6, 2018
• Deposit Date: Mar 4, 2019
• Publicly Available Date: Mar 4, 2019
• Journal: Pharmaceutics
• Electronic ISSN: 1999-4923
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 4
• Article Number: 264
• DOI: https://doi.org/10.3390/pharmaceutics10040264
• Keywords: analgesic adjuvant; ketamine; cancer pain; drug delivery; poly(lactic-co-glycolic acid) (PLGA); sustained release
• Public URL: https://nottingham-repository.worktribe.com/output/1603001
• Publisher URL: https://www.mdpi.com/1999-4923/10/4/264
• Contract Date: Mar 4, 2019