Polymorph Screening and Selection

Polymorph screening is an essential procedure in drug development. For our polymorph screening service, we adopt a variety of crystallization methods, such as solvent evaporation, cooling, agitating slurry, vapor diffusion, rapid precipitation, melt-quench, and amorphous transformation, to conduct the polymorph screening experiments. For a standard screening project, we conduct more than 200 experiments with over 20 solvents. The identified crystal forms are then characterized following scale-up production, and their relative thermodynamic stability is determined by competitive slurry experiments. To enhance the completeness of polymorph screening and mitigate the risk of missing stable forms, when appropriate, we incorporate our CSP technology to locate low-energy structures, which serve as clear targets for the screening experiments. We also compare the experimental results with the computationally generated energy ranking to confirm the relative stability between crystal forms.

Salt Screening and Selection

When a free form API has undesired solubility or stability properties, a common optimization strategy is to screen for possible salt forms and select the optimal form for subsequent R&D. Our systematic salt screening and selection service involves testing of more than 10 of each of acidic and alkaline counterions in salt forming reactions with the free form API. The resulting samples are characterized by a series of methods to confirm the formation of salt form, determine certain parameters such as the ratio of counterions, and assess the thermodynamic properties. For the salt forms with desired properties, we then carry out scaled-up production and systematic characterization studies, such as hygroscopicity, stability and solubility, to select the optimal salt form for the subsequent R&D.
The figure below outlines the major components of solid-state screening and evaluation studies.