Green solvent free methods for active pharmaceutical ingredient polymorph control

Polymorphism control of pharmaceutical compounds is a fundamental issue in pharmaceutical companies. Solution crystallization is a well-known pharmaceutical process. There are a variety of factors that can influence the crystallization process from solution, such as the effect of solvent on crystal habit. Choice of suitable solvent and solubility problem of some compounds is another problem that solution crystallization causes. Furthermore, polymorphism control using solvents does not always lead to the desired polymorph and it can result in an undesired solvate form. All these issues can be eliminated by using green solvent free methods, such as gas phase crystallization. Almost two third of organic compound have the ability to convert to the gas phase. Despite the general association of sublimation with high energy costs the aim of this study was to develop an optimized method to control the polymorphism of a range of APIs and to investigate the effect of additives and templates on the sublimation process. Milling as a secondary processing technique in pharmaceutical manufacturing is another solvent free method that is used in this study. Milling-induced polymorphic transformations and the formation of supramolecular in the presence of catalytic amounts of solvents are investigated. In this study a variety of examples confirm the wide application and potential of solvent free methods