Hydrocortisone esters

Armed with the above insight, we can examine the pharmacological ramifications of esterifying hydrocortisone. In Fig. 5 the ability of hydrocortisone esters to suppress inflammation induced by tetra-hydrofurfural alcohol, which acts simultaneously as irritant and vehicle, is shown as a function of the alkyl chain length of the esters [56]. An optimum chain in effect is seen at an alkyl chain length of six (hexanoate),... 

Armed with the above insight, we can examine the pharmacological ramifications of esterifying hydrocortisone. In Figure 6, the ability of hydrocortisone esters to suppress inflammation induced by tetrahydrofurfural alcohol, which acts simultaneously as an... 

Figure 6 Ability of hydrocortisone esters to suppress inflammation.

The cream, ointment, and topical solution contain the topical corticosteroid hydrocortisone butyrate, a nonflu-orinated hydrocortisone ester. It has the chemical name pregn-4-ene-3,20-dione, 11,21 -dihydroxy-17- [(1 -oxobu-tyl)oxy-,(ll(beta))- the molecular formula is C25H3606 and the molecular weight is 432.54. Each gram of cream contains 1 mg hydrocortisone butyrate in a hydrophilic... 

Many functional groups are stable to alkaline hydrogen peroxide. Acetate esters are usually hydrolyzed under the reaction conditions although methods have been developed to prevent hydrolysis.For the preparation of the 4,5-oxiranes of desoxycorticosterone, hydrocortisone, and cortisone, the alkali-sensitive ketol side chains must be protected with a base-resistant group, e.g., the tetrahydropyranyl ether or the ethylene ketal derivative. Sodium carbonate has been used successfully as a base with unprotected ketol side chains, but it should be noted that some ketols are sensitive to sodium carbonate in the absence of hydrogen peroxide. The spiroketal side chain of the sapogenins is stable to the basic reaction conditions. 

Common Name Ester of Bendazac with hydrocortisone Structural Formula ... 

T. A. Hagen, Physicochemical Study of Hydrocortisone and Hydrocortisone n-Alkyl-21-Esters, thesis, University of Michigan, 1979. 

S. Kaur, P. Khanna, S. S. Parmar, B. Ah, Selective Stimulation of Carboxylesterases Metabolising Charged Steroid Esters by Hydrocortisone , Biochem. Pharmacol. 1991, 41, 476-478. 

The first extensively tested RES-specific contrast agent on the basis of iodinated lipids was EOE-13 with its precursors, AG 52-315 and AG 60-99. EOE-13 is an aqueous emulsion of the iodinated ester of poppy seed oil and is able to selectively enhance the normal liver and spleen parenchyma [10-12]. However, severe adverse events such as headache, fever and chills prevented further use of these contrast agents [13-15], although their extent could be decreased by hydrocortisone given prior to contrast injection. 

Pharmacokinetics Hydrocortisone and most of its congeners are readily absorbed from the Gl tract altered onsets and durations are usually achieved with injections of suspensions and esters. Hydrocortisone is metabolized by the liver, which is the rate-limiting step in its clearance. The metabolism and excretion of the synthetic glucocorticoids generally parallel hydrocortisone. Induction of hepatic enzymes will increase the metabolic clearance of hydrocortisone and the synthetic... 

As in the case of hydrocortisone acetate, where hydrocortisone might be expeeted to occur as a result of hydrolysis of the acetate ester, tests for the presenee of known impurities are based on the known manufacturing sequence or on likely degradation pathways. For example, the tests carried out on clotrimazole are based on the last step in its manufacture as shown in Figure 13.8. Unreacted imidazole is an obvious impurity and chlorotritanol would be readily formed from unreacted chlorotrityl bromide by hydrolysis, which would occur when the clotrimazole is extracted from the reaction mixture. 

Hagen, T. A. 1979. Physicochemical study of hydrocortisone and hydrocortisone n-alkyl-21-esters. 94-96. Ph.D. Dissertation, The University of Michigan. 

M. D. Smith, Kinetic study of USP blue tetrazolium assay with methylprednisolone, hydrocortisone, and their hemisuccinate esters by HPLC, J. Pharm. Sci., 69 960 (1980). 

Figure 2. Hydrocortisone release rate at 35°C from a n-hexyl half-ester of a copolymer of methyl vinyl ether and maleic anhydride at pH 6.25 in the absence and presence of external urea. No external urea IC M external urea s10 M external urea. (Reproduced with permission from Ref. 2. Copyright 1979, American Pharmaceutical Association.)...

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