TOWARDS EFFECTIVE CRYSTALLIZATION WITH THE CRYSTALBREEDER

An example of a medium-throughput crystallization screen on the CrystalBreeder™

Every year, hundreds of active ingredients are produced within the pharmaceutical, food, personal care, dye and agrochemical industries. Understanding the solid state of your active ingredient will lead you to full properties acquirement. Polymorphs, as well as solvates or hydrates of your active ingredient may differ in key properties such as solubility, dissolution rate, stability, and particle habit. Finding the optimal form with the best characteristics for development is critical. When the compound reaches the batch-production stage, reproducibility of the desired polymorphic or salt form is of key importance in the development of the compound. In order to be able to select the optimal form, knowledge of as many as possible forms is needed.
Crystallization is the experimental technique used to perform solid form screens. The crystallization methods discussed here are applicable to all organic molecules.

Challenges in solid form screening

There are several challenges that one can face while screening for solid forms. Do you want to be able to perform a crystallization screen with as little amount of compound as 200 mg? Would you like to be able to reproduce all crystallization parameters without any doubt? Do you see the need of performing crystallization experiments in parallel in order to gain time for other challenges that might appear later on during development or formulation? How do you make sure you maximize the chance of finding a developable solid form? Which crystallization techniques do you employ for that? What solvents or mixtures should you use? How can you minimize the number of experiments you should do, while still having full confidence about the results?

The CrystalBreeder system comes as a tool to aid in your crystallization screen and helps to overcome many of these challenges. Automating the execution of crystallization experiments means more experiments can be carried out in the same timeframe, but also, the results are much more reproducible and controllable, which is essential for good science and answering the requirements put forward by the regulatory authorities. One CrystalBreeder can run up to 32 experiments in parallel.

General considerations when designing your crystallization screen

When designing a crystallization screen there are several experimental parameters to consider, such as: crystallization method, solvents and solvent mixtures, concentration, cooling rates, ageing time, etc. Below you may find some general guidelines to consider while designing your crystallization screen.

 

Example of crystallization screening

Here is an example of medium-throughput crystallization screen on theCrystalBreeder that can be easily integrated in any workflow. The screen was performed on yellow isoxazolone dye which was known to have only 2 polymorphic forms: form I (needles) and form II (blocks). The present screen revealed the existence of a third polymorphic form.

 
Additionally, the CrystalBreeder also enables you to perform crystallization techniques such as anti-solvent and hot-filtration.

McCrone and polymorphism

Last but not least, according to W.C. McCrone, "the number of forms known for a given compound is proportional to the time and money spent in research on that compound". In hope that time and money spent in your laboratories can be reduced, the CrystalBreeder instrument comes as a tool to aid in your crystallization screen.

For further information on the CrystalBreeder™ instrument or crystal form screening, please visit www.crystallizationsystems.com or contact Technobis Crystallization Systems on +31 72 3020040/ info@crystallizationsystems.com


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