Ramalho De Almeida E Sousa, LF; (2013) Photocalorimetry for pharmaceutical photostability assessment. Doctoral thesis (PhD), UCL (University College London).

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Abstract

There is a requirement to demonstrate photostability of medicines early in development but a lack of clear methodologies for doing so. While the International Conference on Harmonization (ICH) has a guideline on photostability testing (ICH, 1996), it does not specify a universal method for the analysis of samples after irradiation. Moreover, the current methods used in photostability testing separate irradiation of samples from analysis, rendering sample preparation critical in the whole process. In this context, photocalorimetry (the measurement of heat changes when a sample is irradiated) offers an alternative method which addresses most of the issues in current photostability testing. Some of the advantages of this technique include the real-time collection of data, the universal character of heat as a measure of change and the “in situ” analysis of photodegradation processes. Two different photocalorimetric designs were developed in the School of Pharmacy, University of London, to study the photodegradation of pharmaceuticals in any physical form. These instruments used light-emitting diodes (LEDs), as the light source, adapted to an isothermal heat conduction microcalorimeter (TAM 227), in one case, and a Multi-Cell Differential Scanning Calorimeter (MCDSC), in the other. To test the instruments’ ability to detect photoreaction heat outputs, known photolabile pharmaceutical formulations were tested in different physical states. Solution phase studies were performed on samples of nifedipine in ethanol and the calorimetric outputs were quantitatively analysed. Solid nifedipine was also tested with the two photocalorimeters, although, data was only analysed qualitatively. Other solid drugs were tested with the photo-MCDSC; some of them are known photolabile compounds (2-nitrobenzaldehyde, benzoquinone, carbamazepine, chloramphenicol, dipyridamole and furosemide) while others are considered stable to light (paracetamol and aspirin). Parallel to the photocalorimetric studies, important progress was made regarding the analysis of calorimetric data for solid state processes and zero-order kinetics in solution.

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