Browsing by Author "Lee, Lok Yan"

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    Actinometric and Φ-order photodegradation properties of anti-cancer Sunitinib.
    (Elsevier, 2015-02-24) Maafi, Mounir; Lee, Lok Yan
    The photodegradation reaction of Sunitinib (SUT), occurring via Z–E photoisomerization, has been evaluated in this study using the recently developed –order kinetics. In ethanol, the forward (Z E) photoreaction of SUT was invariant with irradiation (its quantum yield, 0.019) in contrast to the E Z isomerisation whose undergoes a 30‐fold, sigmoid–shaped, increase with increasing irradiation wavelength. This situation limited usefully the extent of Z– SUT photodegradation at the photostationary state to a maximum of c.a. 30 % of the initial concentration. Nevertheless, these results support a strong recommendation for a complete protection of SUT from light at all stages. Furthermore, a SUT‐actinometer was developed and was proven to be useful for the 320–480 nm spectral range. The latter wavelength interval defined as well SUT photodegradation causative range. The formalism of –order kinetics, proves to be a useful investigative tool for drugs’ photodegradation studies.
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    Determination of Dacarbazine Φ‐Order Photokinetics, Quantum Yields, and Potential for Actinometry.
    (Elsevier, 2016-01-08) Maafi, Mounir; Lee, Lok Yan
    The characterization of drugs’ Photodegradation kinetics is more accurately achieved by means of the recently developed –order kinetics than by the 0th–, 1st– and/or 2nd–order classical treatments. The photodegradation of anti–cancer Dacarbazine (DBZ) in ethanol has been investigated and found to obey –order kinetics when subjected to continuous and monochromatic irradiation of various wavelengths. Its photochemical efficiency was proven to be wavelength–dependent in the 220‐350 nm range, undergoing a 50–fold increase. Albeit this variation was well defined by a sigmoid pattern, the overall photoreactivity of DBZ was proven to depend also on the contributions of reactants’ and experimental attributes. The usefulness of DBZ to serve as a drug–actinometer has been investigated using the mathematical framework of –order kinetics. It has been shown that DBZ in ethanol can represent a good candidate for reliable actinometry in the range 270–350 nm. A detailed and easy–to–implement procedure has been proposed for DBZ–actinometry. This procedure could advantageously be implemented prior to the determination of the photodegradation quantum yields. This approach might be found useful for the development of many drug–actinometers as alternatives to quinine hydrochloride.
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    Study Of The Photodegradation And Photostability Of Anti-Cancer Drugs In Different Media Towards The Development Of Both New Actinometers And Liquid Formulations
    (De Montfort University, 2016-05) Lee, Lok Yan
    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.