Modelling nifedipine photodegradation, photostability and actinometric properties

Background: The photodegradation of drugs obeying unimolecular mechanisms such as that of nifedipine (NIF) were usually characterised in the literature by zero-, first- and second-order kinetics. This approach has been met with varying success. This paper addresses this issue and proposes a novel approach for unimolecular photodegradation kinetics. The photodegradation of the cardiovascular drug nifedipine is investigated within this framework. Methods: Experimental kinetic data of nifedipine photodegradation were obtained by continuous monochromatic irradiation and DAD analysis. Fourth-order RungeKutta calculated kinetic data served for the validation of the new semi-empirical integrated rate-law model proposed in this study. Results: A new model equation has been developed and proposed which faithfully describes the kinetic behaviour of NIF in solution for non-isosbestic irradiations at wavelengths where both NIF and its photoproduct absorb. NIF absolute quantum yield values were determined and found to increase with irradiation wavelength according to a defined sigmoid relationship. The effects of increasing NIF or excipients concentrations on NIF kinetics were successfully modelled and found to improve NIF photostability. The potential of NIF for actinometry has been explored and evaluated. A new reaction order (the so-called Phi-order) has been identified and specifically proposed for unimolecular photodegradation reactions. Conclusion: The semi-empirical and integrated rate-law models facilitated reliable kinetic studies of NIF photodegradation as an example of AB(1 Phi) unimolecular reactions. It allowed filling a gap in kinetic studies of drugs since, thus far, thermal first-order or a combination of first- and zero- order kinetic equations were generally applied for drug photoreactions in the literature. Also, a new reaction order, the Phi-order, has been evidenced and proposed as a specific alternative for photodegradation kinetics. (C) 2013 Elsevier B.V. All rights reserved.