Pharmaceutical applications of layered double hydroxides

The principle aims of this thesis are to investigate the synthesis of layered double hydroxides (LDHs) for use as drug delivery systems, and to explore the potential of these compounds to provide solutions to typical pharmaceutical problems. In Chapter 1, background information on pharmaceutics and drug delivery is given. LDHs are introduced and their structure, synthesis and general applications described. The biomedical and pharmaceutical applications of LDHs are reviewed. Chapter 2 presents the intercalation of the GABAergic drugs gabapentin and pregabalin into an LDH using the coassembly method. The optimum conditions for the restacking process are investigated, an improved method of anhydrous restacking in ethanol at reduced temperatures is described, and a mechanism is suggested. The stabilising effect of LDH intercalation on the drug ions is measured. Chapter 3 explores the potential for LDHs to stabilise and deliver catecholamine drugs levodopa, carbidopa and methyldopa. The ability of a range of LDHs to intercalate and stabilise these drugs against racemisation and oxidative decomposition across a variety of conditions is reported. In Chapter 4, the potential for LDHs to deliver neutral hydrophobic and cationic drugs through the intercalation of cyclodextrinâdrug inclusion complexes is investi- gated. A range of partially substituted anionic cyclodextrins are synthesised and intercalated into an LDH. Cyclodextrinâdrug inclusion complexes are intercalated, their interlayer orientation is suggested and drug release measured. In Chapter 5, the potential of polymerâLDH composites for drug delivery is explored. A selection of drug intercalated LDHs from Chapters 2 and 3 are encapsulated in several enteric polymers typically used for drug delivery. The release profiles and stabilising effects of the composites are measured. Chapter 6 details the experimental procedures and analytical instruments used throughout this thesis. The Appendices contain supplementary characterisation and analytical data that are referred to in the main text.