Effect of binary and ternary polyethyleneglycol and/or (beta)-cyclodextrin complexes on the photochemical and photosensitizing properties of Naproxen

The effect of the polyethylene glycol and/or (beta)-cyclodextrin on the photolability of aqueous solutions of the antiinflammatory drug Naproxen was studied. In all systems studied, the photodegradation process followed zero-order kinetics, leading to the same photoproducts as in the absence of these additives. Kinetic studies revealed that the presence of polyethylene glycol (PEG) reduced drug photodegradation ((phi)=0.11 in water and (phi)=0.045 in the presence of 1% of PEG). By contrast, the binary inclusion complex, Naproxen:(beta)-CD, did not protect the drug from degradation, (phi)=0.11. However, the ternary complex, Naproxen:(beta)-CD:PEG, reduced the efficiency of the photodegradative process to a considerable extent, with (phi)=0.022 in this system. In all cases the presence of the different additives elicited a change in the photomixture composition, the alcoholic derivative being the major photoproduct formed. Nevertheless, the change in the efficiency of the process and the amount of the photoproducts formed in the different systems were not related with the biodamage produced by the drug. In this sense, the presence of free Naproxen clearly sensitized the photoperoxidation of linoleic acid. The photosensitizing effect decreased as the PEG concentration increased and was completely abolished by both the binary (Naproxen:(beta)-CD) and ternary (Naproxen:(beta)CD:PEG) complexes. In light of these observations, it is possible to speculate that in these systems the prevention of biodamage would be due to a decrease in the contact between the short-lived species generated during Naproxen photodegradation and biological structures, rather than to the nature or amount of the photoproducts.