Separation of hydrocortisone and epi-hydrocortisone by solvent extraction

Abstract

Solvent extraction, instead of traditional crystallization, is suggested as a new method for separation of hydrocortisone and its optical isomer, epi-hydrocortisone. The extraction behavior of alcohols, ketones, esters, ethers and chlorinated hydrocarbons was studied experimentally. For the industrial separation process it was found that the best solvents are n-butyl acetate or chloroform. The distribution coefficients of hydrocortisone and epi-hydrocortisone in an n-butyl acetate/water system at 17°C were found to be 9·98 and 2·62, respectively, and 5·57 and 1·93, respectively, in a chloroform/water system at 17°C. When n-butyl acetate or chloroform solution of crude hydrocortisone (the mixture of hydrocortisone, epi-hydrocortisone and other steroid impurities) was scrubbed by deionized water in a nine-stage cross-current at 25°C, the organic phase hydrocortisone purity increased from 78·10% to 98·22% (wt%) for the n-butyl acetate case and from 78·10% to 98·02% (wt%) for the chloroform case. The medicinal standard for hydrocortisone was attained. The effects of alcohol concentration, temperature, salting-out and pH on extraction are also discussed. ©1997 SCI