Novel lidocaine containing intraperitoneal implants for the improved control of post-surgical pain

  • Abreu Passos

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

The objective of this thesis was to explore alternative ways for sustainable intraperitoneal administration of lidocaine (LID) for pain relief following an abdominal surgery. Thus, pre-formulations of eutectic mixtures (EMs) of LID with lipids (mono and di-carboxylic fatty acids or fatty alcohols) prepared in chapter 3 were further applied in three different platforms in order to improve the physical stability of drug and prolong the therapeutic effect of LID.The LID-lipids were characterised using DSC, PXRD, HSM and FTIR for EMs screening. LID-monocarboxylic FAs and LID-fatty alcohols formed EMs whereas LID-dicarboxylic FAs did not; via HSM studies, only LID-dicarboxylic FAs showed multiple eutectic interface zones in Koffler contact method. Moreover, LID-short chain monocarboxylic FAs systems were the only binary systems which interface zones did not crystallise even at temperatures lower as -90 oC for the systems were low crystallisation tendency. Thus, LID-monocarboxylic FAs and LID-fatty alcohols binary mixtures were carried forward to design novel delivery systems. First, selected EMs were incorporated into (1), oil-in-water emulsions (chapter 4), (2), solid dispersions (SDs) with polyethylene oxide (PEO), (water soluble polymer) (chapter 6) and (3) in solid dispersions with poly(ethylene vinyl acetate) (EVA) (insoluble polymer) (chapter 7).In chapter 5 a relationship of LID and other 3 LAs namely, prilocaine (PRL), ropivacaine (ROP) and mepivacaine (MPV) was investigated by screening their potential to form eutectic mixtures with same series of lipids used in chapter 3. In vitro drug release studies from Pluronic F-127 based o/w formulations, showed drug release for maximum two days before adding NaCl into formulation: however, the LID release prolonged for about 7 days after addition of NaCl. LID-lipids/PEO ternary solid implants prolonged drug release for maximum 7 days whereas LID-lipids/EVA controlled the drug release for even longer period.

Thesis embargoed until 31 December 2025.
Date of AwardDec 2022
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SponsorsThe Angolan Ministry of Higher Education, Sciences and Technology
SupervisorDavid Jones (Supervisor) & Shu Li (Supervisor)

Keywords

  • Eutectic mixtures
  • solid dispersion
  • post-surgical pain
  • local anaesthetics
  • lidocaine
  • intraperitoneal
  • rolonged release
  • deep eutectic mixtures
  • phase diagram
  • EVA
  • pluronic F127
  • amorphous products
  • fatty acids
  • fatty alcohols
  • hot-melt extrusion
  • PEO

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