The Crystal16 and CrystallinePV instruments are the perfect tools for investigating the effect of additives on the crystallization process of an active ingredient. One of the strategies to improve filterability in process crystallization is the use of additives. In order to modify the crystal shape of a polymorphic form, crystallization in presence of additives is a solution. Additives preferentially adsorb onto different growing crystal faces and inhibit/promote crystallization in certain directions.Moreover, additives may directly influence the size of the metastable zone width (MZW).
Supersaturation is the driving force for both the nucleation and the crystal growth step in a crystallization process. Every solution has a maximum supersaturation limit that is defined as metastable zone width (MZW). The knowledge of MZW is very important in terms of designing crystallization processes and obtaining desired crystal sizes, shapes, and purities. For this reason, the supersaturation level should be controlled and the crystallizer has to be operated at an optimum supersaturation level that is approximately half of the width of the metastable zone.
The Crystal16 combines automation with integrated turbidity measurement to determine clear and cloud points resulting in solubility data at an early stage with only a minimal amount of sample. The CrystalClear software assists in identifying clear points and automatically constructs and exports solubility curves.
The Crystal16 can quite simply generate solubility curves for four solvents in short time with less than 100 mg of material. The turbidity measurement allows one to determine cloud and clear points and thus the MSZW. Using MSZW and the solubility curves, our users are able to significantly improve their crystallization processes.
Pictures taken with CrystallinePV instrument
The Crystalline instrument with through the vial analytical capabilities like particle visualization allows you to visualize the crystallization process and the influence of additives on the crystal shape of your active ingredient. Crystal shape engineering has never been easier.
Moreover additives are also used in preferential Crystallization (PC) to separate enantiomers.
References
- Songgu Wu, Kangli Li, Junbo Gong, BIWIC 2014, 21st International Workshop on Industrial Crystallization
- Kongsamai, P., Maneedaeng, A., Flood, C. et al. Eur. Phys. J. Spec. Top. (2017) 226: 823.
- Carlos A. Pons Siepermann and Allan S. Myerson, Cryst. Growth Des. 2018, 18, 6, 3584-3595
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With the Technobis Crystallization Systems Workflow - consisting of CrystalBreeder, Crystal16 and Crystalline products - scientists are now able to perform fully controlled crystallization studies from hit identification and lead optimization up through process scale up.