Towards the development of a multi-drug eutectic containing implantable device for enhanced post-operative recovery after peritoneal surgery

Abstract

Postoperative pain management is a critical aspect of healthcare, inadequate control of postoperative pain not only diminishes the quality of life and functional recovery but also poses the risk of persistent pain and long-term dependency on opioids. The evident side effects and potential for abuse associated with opioids underscore the necessity for alternative strategies.

Traditional analgesic approaches, whether centred around opioids or nonsteroidal anti-inflammatory drugs (NSAIDs), often fall short of delivering effective pain relief without introducing undesirable side effects such as nausea or vomiting. Multimodal analgesia (MMA) offers a promising solution by concurrently employing various analgesics with distinct mechanisms, such as opioids, NSAIDs, and local anesthetics. This approach seeks to achieve additive and synergistic analgesia, allowing for reduced doses and mitigated side effects. The development of MMA implants becomes imperative for advancing recovery.

This thesis concentrates on pre-formulation studies aimed at facilitating the design of a device intended for implantation within the peritoneal cavity to enhance the control of pain and inflammation. When combined lidocaine (LID) and ibuprofen (IBU) formed a stable eutectic system. These were characterized across various component molar ratios using differential scanning calorimetry, Fourier-transform infrared spectroscopy, and high-performance liquid chromatography (to quantify the two components).

The stability of the eutectic within a model polymer system (polyethylene oxide) was examined under controlled storage conditions, with advanced statistical analyses providing insights into its shelf-life. The study further examined the effects of polymer molecular weight and the interaction of the eutectic systems with other polymers, emphasizing the importance of inhibiting spontaneous LID-IBU interactions. The investigation extended to X-ray diffraction (XRD) analysis to study crystal components and assess stability.

In conclusion, this research has highlighted the potential of LID/IBU eutectic systems (for MMA) as therapeutic components of implants designed for postoperative administration into the peritoneal cavity.

Date of Award	Jul 2024
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	David Jones (Supervisor) & Shu Li (Supervisor)