Excipient Mediated Photochemistry

Our first introduction to this topic (see Ref. 6 for a full description of this work) was initiated by pH 6 citrate buffer formulations of drug A (a phenyl ether, shown 

The photosensitivity was unexpected as there is negligible overlap of the drug A absorption spectrum and either the ICH visible or UV lamp outputs (Fig. 3, bottom). Furthermore, the molecular components of the matrix (Table 1) are also nonlight absorbing in the 300 to 700 nm exposure regions. 

We were then left to explore the nature of the photosensitivity of this citrate-based formulation and examine the generality of the experimental observations to a larger class of buffer systems and, in general, to liquid dosage forms. Furthermore, the role of package components was also investigated and will be discussed as well. 

Drug A Citric acid Sodium citrate Sodium chloride 

Throughout the course of these studies, multiple batches of the same formulation were exposed to either full ICH exposure conditions or only the visible component of ICH light. Substantial variation was observed between different preparations of the formulation. One major trend appears to be that older formulation solutions are more photosensitive than recently prepared solutions (vide supra). After ICH visible exposure, a three-month-old solution has about 0.1% levels of phenol and a 13-month-old solution forms 0.4% phenol, whereas a 23-month-old solution forms 1.2% phenol. The large magnitude of the variation in photosensitivity observed for different manufactured batches as well as for bench top preparations (Table 3) argue that the photodegradation is not a function of a component that is intentionally controlled in the formulation. 

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