The Development of Thermal and Spectroscopic Characterisation Techniques for the Study of Amorphous Pharmaceutical Materials

• Main Author: Grisedale, Louise Clare
• Published: University of East Anglia 2009
• Subjects: 615.19
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.514322

In recent years there has been an increased interest in the use of amorphous materials in the pharmaceutical industry because of their enhanced thermodynamic properties owing to their greater molecular mobility. Pharmaceutically, formulating with an amorphous material can improve the dissolution and bioavailability of a drug. It can also be used in the stabilisation of another formulation component. However, any potential benefits of an amorphous pharmaceutical are counterbalanced by their metastable nature and tendency to recrystallise spontaneously to their, more stable, crystalline state. The work presented here details the development of thermal and spectroscopic characterisation techniques to study pharmaceutical materials in partially and fully amorphous states. This thesis focuses on the characterisation of a single pharmaceutical material, salbutamol sulphate, nevertheless the experimental research involved highlights the complexities of a "real" amorphous material. Throughout this work numerous difficulties were encountered in characterising the amorphous phase. Specifically the close proximity of the decomposition temperature of amorphous salbutamol sulphate to its glass transition temperature proved eventful and differences seen in both the recrystallisation kinetics and physical stability associated with the preparation method were intriguing. In general, the interaction of water with the amorphous phase further complicates its behaviour. Progress was made towards understanding this relationship and this work has identified and detailed several questions and possible future areas of research. Of the newly developed techniques to study amorphous materials, photothermal microspectroscopy was identified as having the potential to differentiate morphological, chemical and physical differences spatially between the amorphous and crystalline forms. Thermally stimulated current spectroscopy was, however, found to be less reliable at determining the relaxation behaviour of the amorphous sample. To conclude, the research carried out and detailed within this thesis used existing and newly developed thermal and spectroscopic characterisation techniques to further our understanding of amorphous materials and their associated complexities.