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Title: ATR-FTIR spectroscopic imaging to study drug release and tablet dissolution
Author: Ewing, Andrew
ISNI:       0000 0004 6423 4578
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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The active pharmaceutical ingredient (API) and excipients are vital for determining the behaviour of drug release from tablet compacts. Macro attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic imaging can be employed for in situ studies of dissolving tablets. This thesis describes new developments that applied macro ATR-FTIR spectroscopic imaging to investigate the stability and dissolution of amorphous APIs, the effect of carriers for improving drug release, the stability of ionised drug candidates and the behaviour of multiple formulations in microfluidic devices. Solid dispersions containing an amorphous drug formulated with different polymers were investigated using ATR-FTIR spectroscopy and spectroscopic imaging. Crystallisation of the amorphous drug was detected during stability and tablet dissolution experiments. The implications of this form change inhibited dissolution of the drug into solution. ATR-FTIR spectroscopic imaging was also used in combination with ultraviolet detection to study the release of a drug formulated with selected carriers. Hydrogen bonded interactions between the drug and carrier were characterised and resulted in an increased rate of drug release. When these interactions were not present in the tablet, a slower rate of dissolution was observed. Disproportionation of an ionised drug was investigated by ATR-FTIR spectroscopic imaging and Raman mapping. During dissolution experiments in acidic solution, chemical changes of the ionised API were detected in real time that resulted in the formation of the less soluble form of the drug. Exciting results were obtained by simultaneously screening the behaviour of multiple formulations in microfluidic channels using macro ATR-FTIR spectroscopic imaging. Moreover, the precipitation of a dissolved drug that crystallised upon contact with an acidic solution was investigated. Overall, the research in this thesis has demonstrated that macro ATR-FTIR spectroscopic imaging can address the challenges of studying a range of innovative delivery systems that can ultimately lead to the development of more efficient pharmaceutical formulations.
Supervisor: Kazarian, Sergei Sponsor: Engineering and Physical Sciences Research Council ; Bristol-Myers Squibb Company
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral