Study On Crystallization Process Of 16α,17α-epoxy-11α-hydroxyprogesterone And 16α,17α-epoxyprogesterone

As a kind of steroid, 16α,17α-epoxy-11α-hydroxyprogesterone is an important intermediate for many hormone pharmaceuticals, such as hydrocortisone, prednisone and cortinsone. It can be prepared from 16α,17α-epoxyprogesterone through microbial fermentation by Rhizopus nigricans with conversion percent about 44%. The above two steroids form solid solution which is hard to separate. So recrystallization is used to separate and purify the product, but this process has many disadvantages such as low yield, high cost. Hence, the separation process was systematically studied, especially with antisolvent crystallization. The molecular structures of 16α,17α-epoxy-11α-hydroxyprogesterone and 16α,17α-epoxyprogesterone were studied through IR and XRD data. The parameters of unit cell were obtained through X-ray single crystal diffraction and they were analyzed by the software Cerius2 to predict the crystal habit. Thermal property was studied to optimize the crystallization process. The gravimetrical method, an equilibrium method, was used to measure the solubility of 16α,17α-epoxy-11α-hydroxyprogesterone and 16α,17α-epoxyprogesterone in several solvents at different temperature. At the same time, the metastable zone was measured by laser mornitoring method. The other thermal property of 16α,17α-epoxy-11α-hydroxyprogesterone and 16α,17α-epoxyprogesterone was also studied. The induction time of antisolvent crystallization was measured by laser. The nucleation mechanism of 16α,17α-epoxy-11α-hydroxyprogesterone in chloroform -toluene system was studied by analyzing the relationship between the induction time and supersaturation. And the crystallization kinetic models of 16α,17α-epoxy-11α-hydroxyprogesterone in the antisolvent crystallization were estabilished. The mixture was mainly separated and purified by antisolvent crystallization in chloroform-toluene system. The effects of the crystallization process variables were experimentally studied such as temperature, agitation speed, concentration of solution, adding rate of toluene, crystal seed. The optimal conditions of crystallization were established. The paper supplied the basis for the further study in the future and for industrial production. No similar research has been published yet.