Hydrocortisone esters activity

Steroid creams will often clear the condition and hydrocortisone can be prescribed under a variety of trade names such as Alphaderm. More powerful are the creams based on betamethasone esters, of which Betnovate is the best known and has been used for more than 40 years. If this does not work then the doctor can prescribe even stronger drugs based on clobetasol propionate, such as Dermovate, or similar active agents. There are several such creams now available and it is rare for eczema not to respond to one of them and be cured - and kept at bay. If the eczema is infected then various antibiotics, antivirals, and anti-fungals can be given to clear up the infection. Very... 

Prednisolone, USP. Prednisolone. J -hydrocortisone. Il/3.l7.2l-trihydroxypregna-l.4-diene-3.20-dione. has less salt-retention activity than hydrocortisone (see Table 23-8), but some patients have more frequently experienced complications such as gastric irritation and peptic ulcers. Because of low mineralocorticoid activity, it cannot be used alone fur adrenal insufficiency. Prednisolone is available in a variety of salts and esters to maximize its therapeutic utility (see Fig. 23-30) ... 

Amin and Jakobs48) dissolve suppositories and ointments, which contain several active ingredients (hydrocortisone or its esters, an antihistaminic, a local anaesthetic and a disinfectant), in chloroform/methanol. They apply the solution directly on a thin-layer plate without freeing it from the suppository or ointment base. After the separation the active ingredients are scanned with variation coefficients of 1.29-3.56%. 

The ethylene ketal derivative of prostaglandin E2 (dinopros-tone) possesses much improved solid-state stability (see Chapter 41). Functionalized spirothiazolidines of hydrocortisone and hydrocortisone 21-acetate (Figure 36.6), prepared with cysteine esters or related 3-aminothiols, have improved topical anti-inflammatory activity. It is specnlated... 

Hydrocortisone (24) (Ri, R, R Xj, X, = H, no A Fig. 15.10) undergoes a variety of oxidative and reductive metabolic conversions (115). Oxidation of its dihydroxyacetone side-chain leads to formation of cortienic acid (25) through a 21-aldehyde (21-dehydrocortisol) and a 21 -acid (cortisolicacid). Cortienic acid is an ideal lead for the inactive metabolite approach because it lacks corticosteroid activity and is a major metabolite excreted in human urine. To obtain active compounds,the important pharmacophores found in the 17a and 17P side-chains had to be restored. Suitable isosteric/isoelectronic substitution of the a-hydroxy and /3-carboxy substituents with esters or other types of functions should restore the original corticosteroid activity and also incorporate hydrolytic features to help avoid accumulation of toxic levels. More than 120 of such soft steroids (24) that resulted from modifications of the 17/3-carboxyl function and the 17o -hydroxy function together with other... 

Figure 14.2 Skin flux, absorption or pharmacodynamic activity as a function of permeant lipophilicity. A Phenols CHinz et al. 1991) B Salicylates CO) and other NSAIDs [ ) [Yano et al. 1986) C Hydrocortisone-21-esters [Flynn 1996).

Adding a 6a-methyl group to prednisolone increases the glucocortiooid activity and effectively abolishes mineralooortiooid aotion. It has fivefold the gluoocorticoid activity of hydrocortisone (prednisolone has fourfold the gluoocorticoid activity) and none of its mineralocorticoid properties. It is used almost exolusively as a systemio product and is available as the free alcohol for oral administration and as various esters (Table 44.7). 

Mouthwashes usually are solutions of active substances in water or aqueous solvents so the water soluble form of the active substance is chosen. For corticosteroids this would mean an aqueous solution of a phosphate ester. When rinsing with such a solution the contact time would be too short to obtain a sufficient therapeutic effect of the corticosteroid [1]. As a viscous suspension sticks to the oral mucosa, the active substance can work for a longer period of time. Therefore a (viscous) suspension is to be preferred. In addition such a suspension has the advantage that the bitter taste of the corticosteroid is less pronounced. An example is a suspensimi with hydrocortisone acetate, lidocaine and dexpanthenol (Table 7.1). 

Hydrocortisone and the acetate and butyrate esters are often used for cutaneous application. In the skin the esters hydrolyse rapidly and the active substance hydrocortisone is formed. Usually the concentration of hydrocortisone acetate in creams is 10 mg/g. The usual concentration of hydrocortisone butyrate is 1 mg/g,... 

Preparations with hydrocortisone acetate are classified in activity class 1, preparations with hydrocortisone butyrate in class 11. Although the active substance in both preparations is the same, the therapeutic effectiveness of the butyrate ester is stronger. This is the consequence of the higher lipophilicity of the butyrate ester that leads to better skin penetration. 

For a good therapeutic effect the choice of the active substance and the choice of the vehicle are important. Physical and chemical factors play an important role. The solubility of the active substance in the vehicle and the concentration, the size of the molecule of the active substance, the partition between vehicle and skin, the particle size (in case of suspensions) and the nature of the vehicle (aqueous or lipid) determine the penetration speed and depth. Hydrocortisone, for example, is more lipid soluble in the ester form (hydrocortisone acetate). The latter will penetrate into the skin faster and more complete. Hydrocarbons, such as soft and liquid paraffin, release lipophilic active substances only very slowly and substances formulated in these bases will penetrate only in limited amounts into the skin. Fatty oils (vegetable oils, triglycerides) are able to pass into the upper layers of the skin. Penetration enhancers (salicylic acid, dimethyl sulfoxide, propylene glycol, urea) increase the penetration of active substances into the skin. 

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