Photochemistry and Phototoxicity of Fluocinolone 16,17‐Acetonide^¶

Abstract

Fluocinolone 16,17‐acetonide is a corticosteroid used topically to treat various inflammatory skin diseases. Its photoreactivity was studied under UV‐A and UV‐B light in aqueous buffer in the presence of oxygen. This drug is photolabile under UV‐B light and, to a lesser extent, under UV‐A light, which is absorbed far less. In phosphate buffer, approximately 80% of fluocinolone acetonide decomposes after 5 J/cm2 of UV‐B irradiation, whereas under 30 J/cm2 of UV‐A light approximately only 20% decomposes. Both the drug and its photoproducts have been evaluated through a battery of in vitro studies and found to cause photohemolysis and induce photodamage to proteins (erythrocyte ghosts, bovine serum albumin) and linoleic acid. In addition, one of the photoproducts (the 17‐hydroperoxy derivative) is highly toxic in the dark. Therefore, both loss of therapeutic activity and light‐induced adverse effects may be expected when patients expose themselves to sunlight after drug administration. A major mechanism for phototoxicity involves radicals forming from drug breakdown, at least under UV‐B, although reactive oxygen species may play a role, particularly under UV‐A.

Photodegradation of prednisolone under UVB solar irradiation. Role of photogenerated ROS in the degradation mechanism

“…Other authors [46,47] have done a comprehensive investigation for other corticoids, flumethasone and fluocinoloneacetonide. They found that these substrates generate O 2 ( 1 ∆ g )…”

Development of fluocinolone acetonide microemulsion mouthwash

“…FA is quite photolabile, particularly when exposed to UV-B. Therefore exposure to sunlight or fluorescent lamps can cause degradation and loss of therapeutic activity due to chemical modification of the FA molecule (Miolo et al, 2005).…”

“…Although all formulations were filled in amber glass vials, wavelengths affecting to FA are both UV-A (320-400 nm) and UV-B (290-320 nm) some wavelengths may pass through the vials. (Miolo et al, 2005) nanoemulsions; therefore, encapsulation of the drug can improve chemical stability.…”

“…Degradation pathways of FA are oxidation, hydrolysis with pH dependence and photolysis. Degradation of FA is catalyze by hydrogen ion, hydroxide ion and trace metal ions (Kenley et al, 1987;Miolo et al, 2005). FA has been prepared in cream, gel, solution, and ointment dosage forms for topical use.…”