Design and development of lipid-based in situ forming long-acting injectables for drug delivery

Ajulo, Damilola (2025) Design and development of lipid-based in situ forming long-acting injectables for drug delivery. Doctoral thesis, University of East Anglia.

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Abstract

In recent years, long acting injectables (LAIs) have become a pivotal area of research as a delivery system for the treatment of chronic conditions in the pharmaceutical world with growing emphasis on improving patient compliance and quality of life. This class of formulations offers many advantages including reduced dosing frequency, elimination of painful surgical procedures and the ability to maintain drug concentrations within the therapeutic range. However, a profound understanding of the psychochemical properties of the lipid depot systems and their impact on release kinetics is still being explored and needed, and although various research efforts have demonstrated the potential of lipid-based depots as a vehicle for varying drugs, there continues to remain a need to understand what truly makes a formulation ‘long-acting’.

This project focuses on the design and development of lipid-based in situ forming LAIs as a promising approach for the controlled release of hydrophilic and hydrophobic active pharmaceutical ingredients (APIs). In this study, the use of lipid excipients such as glycerides and phospholipids were investigated to create an in situ depot system that would maintain injectability until the point of injection, where aqueous fluids transform the formulation into a depot with increased viscosity based on a change in body temperature. The key formulation parameters including lipid composition, solvent selection and content, and drug loading were systematically studied to understand their influence on the microstructure of the depot formed, physical and mechanical properties, and the release kinetics of the drug.

A comprehensive psychochemical characterisation of the blank (BLK) and drug loaded (DL) formulations pre and post-injection was conducted using some analytical techniques including confocal Raman microscopy, powder X-ray diffraction (PXRD), small angle X-ray scattering (SAXS), proton nuclear magnetic resonance (NMR), rheological and texture analyser as well as the imaging techniques cryogenic field emission scanning electron microscopy (Cryo-FESEM) and cross polarized light microscopy (CPLM). In vitro release studies were also performed to evaluate the drug release profile. The results demonstrated the complex structures of the gels, due to the various lyotropic liquid crystalline (LLC) phases formed and showed the potential for these ordered structures to release hydrophilic and hydrophobic drug molecules. The formulated systems demonstrated sufficient injectability and upon contact with aqueous fluids portrayed immediate gelation with increased viscosity of the depot system. The microstructure of the liquid crystalline gels formed, enabled the release profile of the hydrophilic model drugs to be controlled and the findings in this project present new ideas for optimising in vitro release profile of hydrophilic drugs

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
Depositing User:	Chris White
Date Deposited:	24 Nov 2025 11:46
Last Modified:	24 Nov 2025 11:46
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101088
DOI:

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