Photochemistry of Desonide, a Non-fluorinated Steroidal Anti-inflammatory Drug

Abstract

Polyfunctional molecules in which different photochemically reactive chromophores are connected by rigid hydrocarbon framework are a subject of fascinating photochemistry.1-3) The intramolecular energy transfer (both singletsinglet and triplet-triplet) may occur from an 'antenna' group to other chromophore leading to chemistry different from that observed by direct excitation of that chromophore. [4][5][6][7] In the photochemistry of such multichromophoric molecules the evaluation of interaction between the chromophores, the mode and extent of local reaction at any chromophore after electronic excitation and possible role of energy transfer is of high mechanistic significance.Morrison established, through a series of elegant papers, [4][5][6][7] that intramolecular energy transfer (both singlet-singlet and triplet-triplet) occurred from the phenyl 'antenna' to C 17 keto group in the steroids by the way of through-bond mechanism. This lead to a different photochemistry observed by the direct excitation of ketone chromophore. Albini et al. 8,9) have demonstrated non-communicating reaction paths in some pregna-1,4-diene-3,20-dione. Since many steroidal drugs are commonly used and several reports on their phototoxic effects have been reported, [10][11][12][13] it was of interest to extensively study the aspect of competition between chemical reactions of the separated excited moieties incorporated in the rigid skeleton of the steroids. It was expected that such photochemical mechanisms might have some relevance for the mechanism of phototoxicity.Glucocorticosteroids are natural hormones with a steroidal structure derived from 5a-pregnane. These steroidal hormones with powerful anti-inflammatory effects are secreted by the cortex of adrenal gland. Semisynthetic derivatives of these hormones are widely used as drugs to treat inflammatory illness, including arthritis and asthma, and many of them are effective by topical use in dermatoses and other dermatological disease.Desonide (De,1) is a synthetic nonfluorinated corticosteroid for topical dermatological use. It is used to treat inflammation caused by a number of conditions such as allergic reactions, asthma and psoriasis.14,15) Desonide is very interesting from photochemical point of view because it bear two spatially separated chromophores i.e. cross conjugated dienone moiety in ring A and an isolated ketone at C 20 . A number of photochemical studies have been carried out on these steroidal ketones, both in solution and in solid state. [16][17][18][19][20][21][22] The photochemistry of cross-conjugated cyclohexadienone has been intensively studied because of their facile and fascinatingly complex photochemical reactions. Williams et al. 23) carried out photolysis of prednisolone, a molecule structurally related to De, at 254 nm and observed that only photoprocess occurring in dioxane solution was the "lumiketone" rearrangement of the cyclohexadienone moiety. With this interest, herein we have investigated the photochemistry of desonide under different combination...

Estimation and characterisation of budesonide tablets impurities

“…An oxidative process is the common synthetic pathway for compound 6, 9 and 11: the aldehyde 6 is oxidized to the 17-carboxylic acid 9 in agreement with reported data about the corticosteroid side chain degradation [18]. Finally, the loss of C-20, followed by a rearrangement of 16␣,17␣-acetal leads to butanoate 11 [16].…”

“…Its presence in the budesonide sample can be explained through an oxidative degradation of side chain, involving also the 16␣,17␣-acetal. A similar reaction was reported in literature in the case of an analogue compound bearing a 16␣,17␣-dimethylketal [16].…”

Investigation of the Stabilizing Effects of Antioxidants and Benzophenone-3 on Desonide Photostability

“…BP-3 is an organic filter capable of absorbing both UVA and UVB radiation (22). As shown in Studies on the photostability of desonide have shown that although the UV absorption spectrum of the drug is limited to the UVC range, the drug is unstable to UVB radiation (8) and UVA (11,23), similar to what we observed in this study. Pregna-1,4-diene-3,20-diones, such as desonide, present two separated chromophore groups: the cross-conjugated dienone in ring A and the ketone at C 20 .…”

“…Regarding the photostability of desonide, Iqbal and co-workers reported the photoinstability of desonide solubilized in organic solvents after exposure to UVB and UVC radiation. They verified the lumiketone rearrangement on the cross-conjugated ketone after exposure to UVC radiation and the photocleavage of the C17-C20 bond followed by hydrogen atom abstraction when the drug was exposed to UVB radiation (8).…”

Development and Physicochemical Characterization of Desonide-Loaded Nanocapsule Suspensions

“…Desonide is a synthetic nonfluorinated corticosteroid and has been widely used as a topical treatment of inflammation caused by a number of conditions such as allergic reactions and psoriasis for more than 30 years [1,2]. Topical corticosteroids were introduced in medicine for 50 years and represent a landmark in dermatologic therapy, have fast action, and are the most effective anti-inflammatory drugs available, by promoting systematic improvement of clinical manifestations [3,4].…”