Study On Crystal Morphology And Crystallization Process Optimization Of Hydrocortisone

Hydrocortisone is an important glucocorticoid,which can be used for many diseases such as rheumatoid arthritis,rheumatism and so on.Hydrocortisone have a variety of crystal type and solvent compounds.Hydrocortisone form I is a stable polymorph,which is the most widely used in clinically.Nowadays,there still exist some problems such as low purity as well as yield,poor color and the lack of equivalent quality of product in the production process of hydrocortisone for domestic enterprises.In this paper,the crystal morphology and crystallization process of hydrocortisone was studied systematically from the following aspects to solve these problems.The hydrocortisone I crystal transformation process was studied by online Raman technology in methanol solvent and the factors effect on the crystal transformation was studied.The kinetics and mechanisms of desovation were also systematically researched at different temperatures.Through the crystal transformation and solvent thermodynamics research,it can provide corresponding theoretical guidance for subsequent crystallization process such as solvent system selection and the desolvation of the product.The solubility of hydrocortisone form I were determined in common pure solvent and mixture solvents under 278.15K~323.15 K by dynamic method.And the calculation of dissolution thermodynamic functions according to modified van't Hoff equation provided basis for process optimization.The metastable zone of hydrocortisone in methanol was determined by online focused beam reflection instrument FBRM.Furthermore the different cooling rate effect on the metastable zone of hydrocortisone was discussed in methanol solvent.Through research of crystallization thermodynamics,crystallization kinetics,crystal transformation and desolvation of hydrocortisone,the optimization of crystallization process of hydrocortisone were been found and the effects of numerous factors related to the purity or properties of product were studied and analyzed,such as solvents,the amount of activated carbon,decolorization time,stirring rate,cooling rate and drying conditions.The products obtained have high purity,high yield,good color and uniform size under the optimization of crystallization process.It can provide theoretical guidance for industrial production.