Consequences of Excited State Processes to Drug Stability in Vitro

10 CONSEQUENCES OF EXCITED STATE PROCESSES TO DRUG STABILITY IN VITRO 

Two case studies, naproxen and sulfamethoxazole, will be described briefly to illustrate how information concerning the excited state assists in elucidation of the mechanism of photodegradation. Their spectroscopic properties are detailed in Table 2.1, together with several other drugs given for comparative purposes. The state of ionization of the molecule can be a factor in the photochemistry, so it is relevant to show the information for neutral and anionic sulfamethoxazole (pKa 5.6). Ionization of naproxen (pKa 4.2) has no significant effect on its spectroscopic properties because the carboxyl group is distant from the naphthalene chromophore. 

Note nd means not determined DF is 2,5-dimethylfuran. a Phosphorescence measured in an ethanol glass at 77 K (drug in neutral form). 

Sources diclofenac data from Moore, D.E. et al., Photochem. Photobiol., 52 685-690, 1990 data for chlorpromazine and frusemide from Moore, D.E. and Burt, C.D., Photochem. Photobiol., 34 431-439, 1981 naproxen data from Moore, D.E. and Chappuis, P.P., Photochem. Photobiol., 47 173-181, 1988. 

Both molecules have the capacity to emit fluorescence and phosphorescence, the latter suggesting an appreciable population and lifetime of their respective triplet states. The first photochemical tests involve using spectrophotometry and liquid chromatography to analyze the reaction mixtures after irradiation for varying times. It is important to follow the reaction from the very early stages to ensure that the products seen are those formed from the very beginning of the reaction. Some primary products may decompose in secondary thermal and/or photochemical reactions. 

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