Betamethasone esters

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... 

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). 

Mckenzie AW, Atkinson RM. Topical activities of betamethasone esters in man. Arch Dermatol 1964 89 741-746. 

C22H2XO3 14135-32-1) see Betamethasone 17a-hydroxy-16P-methyl-5p-pregn-9(ll)-ene-3,20-dione (C22H32O3 13656-78-5) see Betamethasone 21-hydroxy-2 -methyl-5p//-5a-pregn-9(ll)-eno[17,16-d]-oxazole-3,20-dione acetate (ester)... 

E Tertiary alcohol group, neutral, prone to elimination by dehydration at high temperatures. Where the hydroxyl group at E is converted to an ester such as valerate, e.g. betamethasone valerate, thermal elimination of the ester can occur quite readily. Another decomposition reaction of the valerate esters is the... 

Prednisolone 5.43 min Betamethasone Prednisolone and 6.24 min betamethasone and their esters eluted from an ODS column (25 cm X 4.6 mm) with Betamethasone 21 -valerate methanol/water (75 25) as mobile phase, UV 20.60 min detection at 240 nm. ... 

Loo, J.C., et al. 1981. Pharmacokinetic evaluation of betamethasone and its water soluble phosphate ester in humans. Biopharm Drug Dispos 2 265. 

It should be noted that many market names are used for all of the antiinflammatories listed in Table 2, depending on market liaisons, generic competition, derivatives such as esters, and the form of the drug product (e.g., topical, inhaler, nasal spray, etc.). For example, Schering s betamethasone 17,21-dipropionate is marketed as Diprosone, and Glaxo s betamethasone-17-valerate was marketed as Betnovate. 

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. 

For topical application in the treatment of various skin disorders, the dipropionate and valerate esters are extensively used. Betamethasone valerate has also been used by inhalation for the prophylaxis of asthma. 

Anti-inflammatory potencies were measured in mice by a 5-day modification of the Tonelli croton oil ear assay. The most potent topical anti-inflammatory compounds were 17a-heterocyclic esters in the 16a-methyl series where the 21-substit-uent was either chloro or fluoro. Thus, [21-chloro-17-(2 -furoate)] was eight-fold more potent than betamethasone valerate, while [21-fluoro-17-(2 -furoate)], [21-chloro-17-(2 -thenoate)] and 6a-fluoro-21-chloro-17-(2 -furoate)] were three-fold as potent as betamethasone valerate. 

Differentiation between the stereoisomeric dexamethasone and betamethasone (Figure 13.2) has been investigated in detail [47-49]. While De Wasch et al. [47] differentiated from differences in relative abundances, Antignac et al. [48] proposed the use of multivariate statistical techniques, based on principal component analysis. Baseline separation between betamethasone, dexamethasone, and various related esters was reported by Arthur et al. [49] using a Cg column and a step gradient. 

Betamethasone, USP. Betamethasone. 9-fluoro-l Ij3. 17.21 -trihydroxy-16/8-mcthylpregna-1.4-dicnc-3.20-dione. is available us a variety of ester derivatives. 

In the case of ester derivatives the degree of esterification (i.e., mono or diesters) and the size of the esterifying acid helps to determine the extent of lipophilicity of the product. Thus betamethasone 17-valerate (Table 14-1) would be expected to be more soluble in CHC13 (1 2) than the 21 -acetate (1 16), which in turn is more lipid soluble than the alcohol (1 325). Topical antiinflammatory potency parallels such values. 

The declaration of the chemical form of steroids for dermal use has to be clear. Some of the steroids have no effect on the skin, for example triamcinolone or betamethasone, but the esters do. 

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