This study aims at tackling some of the problems often encountered in photostability testing and liquid formulation development. Three anti-cancer drugs will be employed as models; Dacarbazine (DBZ) has well established photostability issues, Axitinib (AXI) and Sunitinib (SUT) are two new drugs only commercially available in solid dosage forms. In ethanol, the photokinetics of these drugs were well described by the newly proposed Φ-order kinetic mathematical model. This has confirmed the photoreversible character of AXI and SUT’s and unimolecular photoreaction of DBZ’s photodegradations. Also, the Φ-order kinetics is proven to describe them better than the usually used classic thermal reaction orders. In aqueous solution, the drugs were found to undergo thermal and photochemical complex degradations, involving at least 3 photoproducts. A new photokinetic approach has been proposed in this work to solving and unravelling the attributes of such complex mechanisms. For the first time, the quantum yields (QY) of the three drugs were determined and found to increase with irradiation wavelength. SUT’s QY were comparable in ethanol and water (QY460 = 0.02), DBZ was found to be more photoefficient in water (QY330 = 0.04 and 0.1, respectively) and AXI in water (QY330 = 0.06 and 0.03). Φ-order kinetics’ potential for the development of reliable actinometers of the three drugs, without prior knowledge of unknown reaction parameters, has also been established. A general equation to describe the isotherm of a (Gn:Hm) guest-host multicomponent complex was proposed in this work to palliate the lack of a strategy for characterising nanosponge-drug complexes. It provides information on both stiochiometry and association constant of the complex. The results indicate that hydrophobic AXI forms a 1:0.8 complex, indicating the possibility of multiple association sites and/or different types of binding. The newly developed AXI/nanosponge liquid formulation has significantly increased solubility (5000-fold) and thermal stability. Furthermore, the photostability of DBZ and SUT were considerably improved by using a strategy based on light-absorption competitors. Their initial velocities reduced from 10 and 3 s-1 (respectively) to 1 and 0.13 s-1. The successful application of these methods to the model anti-cancer drugs has set out new approaches that might be found useful for future treatments of photodegradation data, development of drug-actinometers and liquid formulations of drugs.

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.