Modelling and elucidation of photoreaction kinetics - Applications and actinometry using nifedipine, nisoldipine, montelukast, fluvoxamine and riboflavin.
The kinetics of drugs photodegradation have traditionally been treated using thermal kinetic analysis methods consisting most commonly in zero and first order kinetics. These treatment strategies were shown to lack specificity and present a number of limitations when applied to photoreactions kinetics. Nevertheless, these methods have widely been used due to a lack of integrated rate-laws for the majority of photoreactions types, in turn, due to the presence of a variable time-dependent factor in most photoreactions rate-laws that prevents their mathematical integration. To address these limitations, a new methodology for the development and validation of semi-empirical integrated rate-laws that faithfully describe photoreactions kinetics and photoreactions simulated cases generated by numerical integration methods (NIMs), is hereby presented. Using this methodology, a new kinetic order was ascribed to photoreactions namely the Φ-order kinetics. Semi-empirical integrated rate-laws were, thus, developed for three photoreaction types namely, unimolecular, AB(1Φ), photoreversible ,AB(2Φ), and consecutive, AB4(4Φ), photoreactions. The proposed models were further tested experimentally on drugs following these photodegradation mechanisms using; nifedipine and nisoldipine for unimolecular photoreactions; montelukast and fluvoxamine for photoreversible reactions; and riboflavin for consecutive photoreactions. The developed models not only accurately described the photoreaction kinetics of these drugs but also allowed the determination of all the kinetic parameters that characterise them. Furthermore, the above studied drugs were shown to act as precise and simple actinometers when analytically treated with the Φ-order kinetic methods, hereby presented. A universal standard method for the precise and worldwide reproducible study of drugs stability and compounds photoreactions, based on monochromatic irradiation and Φ-kinetics data analysis, is also detailed and adopted throughout the thesis. Finally, two new kinetic parameters namely, the pseudo-rate-constant and pseudo-initial velocity have been identified and shown to be more reliable and accurate in the description and universal comparison of photoreactions kinetics.
- PhD