Cortisone manufacture

Various drugs are known to exist in different polymorphic forms (e.g., cortisone and prednisolone). The rate of conversion from a metastable into the stable form is an important criteria to be considered with respect to the shelf life of a pharmaceutical product. Polymorphic changes have also been observed during the manufacture of steroid suspensions. When steroid powders are subjected to dry heat sterilization, subsequent rehydration of anhydrous steroid in the presence of an aqueous vehicle results in the formation of large, needle-like crystals. A similar effect may be... 

Bile acids were the logical starting point for the manufacture of cortisone in the late 1940s, but steroids from plant sources, and particularly diosgenin ex yams, were gaining credibility as time passed. The chemical synthesis challenges associated with each of these raw materials are outlined in Scheme 7. 

Glaxo was one of several European companies involved in finding a route to cortisone. Initially, Glaxo worked with ergosterol as a starting material but soon switched to hecogenin (XXXIV) found in juices discarded by the manufacturers of sisal fiber in East Africa. 

We used the radical relay process, chlorinating C-9 and then generating the 9(11) double bond, in a synthesis of cortisone 91 [158]. This is a substitute for manufacturing processes in which C-9 or C-ll are hydroxylated by biological fermentation. Also, with templates that directed the chlorination to C-17 of 3a-cholestanol, such as that in 90, we were able to remove the steroid sidechain [159-162]. Using an electrochemical oxidation process, we could direct chlorination by simple chloride ion with an iodo-phenyl template [163]. A general review of the processes with iodophenyl templates has been published [164]. 

It is current good manufacturing practice for a manufacturer to establish and follow written standard operating procedures to clean production equipment in a manner that precludes contamination of current and future batches. This is especially critical where contamination may present direct safety concerns, as with a potent drug such as a steroid (e.g., cortisone, and estrogen), antibiotic, or sulfa drug, where there are hypersensitivity concerns. 

OTHER COMMENTS used as an oxidizing agent used in the manufacture of dyes and hydroquinone can strengthen animal fibers and make gelatin insoluble used in pharmaceutical industry for production of cortisone use in polymer and resins industry use as a tanning agent for leather industry. 

While Merck, beginning in 1949, and Sobering, in 1951, manufactured cortisone from deoxycholic acid, Peterson and Murray, biochemist and microbiolc st, respectively, with the Upjohn Company, chose to attack the problem of the introduction of 11-oxygen by the potentially more direct, microbiological method. They have said (P-723) that they were stimulated to enter this fi d by the successes of the Mamoli school. They were also encouraged, early in their work, by the report of Hechter and collaborators that perfusion of deoxycorticosterone through isolated adrenal glands resulted in the formation of corticosterone by enzymatic 11/3-hydroxylation. 

After the discovery of prednisone and prednisolone through the use of Coryne-bacterium simplex (N-671) with cortisone and hydrocortisone, respectively, many 1-dehydrogenatii cultures were described. Among the most significant of these were Bacillus sphaericus (S-942), Bacterium cyclo-oxydans (K-480),and Septomyxa affinis (M-573), ill of which have been or are being used for the manufacture of antiinflammatory steroids. 

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