Triamcinolone acetonide ester

Research teams at Glaxo then undertook the synthesis of derivatives of betamethasone that might afford superior local anti-inflammatory and anti-allergic effectiveness. Using McKenzie and Stoughton s [21] new human-based pharmacologic test that could identify with ease the relative topical potency of steroid inflammatory compounds, a series of 17-esters of betamethasone prepared by Elks [22] was evaluated. This resulted in compounds with new standards of topical potency such as triamcinolone acetonide and fluocinolone acetonide. It was then discovered, that potency peaked with betamethasone-17-valerate and betamethasone-17,21-dipropionate, which were between four- and ten-fold more potent than the standard. 

Another example for the importance of the solubility of the drug is corticosteroids. The different photosensitivities of three marketed hydrocortisone oil-in-water creams as shown in Figure 19, is due to the drug concentration as well as the composition of the preparation. Similar degradation rates were found for creams with triamcinolone-acetonid and betamethasone esters (47). 

In order to increase their Upid solubility, corticosteroids have been esterified with monocarboxylic (fatty) acids. Examples include hydrocortisone acetate, beclomethasone dipropionate and betamethasone isovalerate. For triamcinolone, the following method has been developed to make the substance lipophilic the hydroxyl groups at the C16 and C17-position of triamcinolone are used to form a cyclic acetal (Fig. 18.4). Although the formed substance, triamcinolone acetonide, is not a fatty acid ester, with regard to lipid solubility it behaves as such. 

Dermatology is another important field where fatty acid esters of corticosteroids are applied. Examples are creams with hydrocortisone acetate and triamcinolone acetonide, respectively. These fat-soluble derivatives are used because they show better penetration into the lipophilic stratum comeum of the skin. 

The esters of monovalent fatty acids (triamcinolone acetonide) are usually used in cutaneous preparations. Free corticosteroids can usually be administered orally. When a solution in water is needed the esters of a multivalent acid in the salt form (-disodium phosphate, disodium succinate) should be used. This also applies to processing corticosteroids in a lipid based suppository. 

Triamcinolone is reported to have a half-life in plasma of about 2 h to over 5 h. It is bound to plasma albumin to a much smaller extent than hydrocortisone. The acetonide, diacetate, and hexacetonide esters of triamcinolone are only very slowly absorbed from injection sites. 

---