Formation of Mixed Crystals in Crystallization of 11(alpha)-Hydroxy-16(alpha),17(alpha)-epoxyprogesterone and 16(alpha),17(alpha)Epoxyprogesterone

In the present study, the crystallization of two isomorphic steroid pharmaceutical intermediates 11(alpha)-hydroxy-16(alpha),17(alpha)epoxyprogesterone (abbreviated as HEP) and 17(alpha)-epoxyprogesterone (abbreviated as EP) were studied. Formation of solid solution type mixed crystal system of two steroids in the crystallization process of corresponding mixture from solution was postulated and further confirmed. The experimental results indicate that forming mixed HEP/EP crystal takes place in a wide interval of HEP/EP ratios with the use of the powder X-ray diffraction, differential scanning calorimetry, and high-performance liquid chromatography techniques. Meanwhile, some thermal data (the melting point and enthalpy of melt) of HEP, EP, and their mixed crystals were determined. This discovery will helps us understand the distribution of EP in HEP crystals in the purification process of HEP by crystallization in more depth and will be very beneficial to develop and design the separation process of two steroids.