Crystallization research plays an important role in the drug development process as majority of the therapeutic drugs exhibits in multiple polymorph forms and technically each polymorph possess different physical properties. Differences in physical properties (e.g. solubility, hygroscopicity, melting point) would then affect other important properties such as product bioavailability and stability. Pharmaceutical companies worldwide are now trying to gain their competitiveness by stepping in the crystallization research much earlier in the drug development cycle, thus to avoid unexpected crystal form related issues and delays at later stages. This also means crystal form information required during patent application could be obtained much earlier and eventually product launch could also be accelerated.
At the moment, the biggest bottleneck for crystallization research lies in the complex experimental matrix involved and the limited sample quantity. To tackle these issues, Technobis provides three innovative solutions and each of them can effectively perform polymorph screening, solubility and metastable zone width(MSZW) study and crystallization process research. Also, it comes with different features which can fulfil researchers’ needs such as throughput and processing volume at different development stages, and therefore effectively speeding up the entire crystallization research cycle.
As the first step in crystallization research, polymorph screening typically involves screening of various salts, hydrates / solvates and co-crystals. In order to screen out all possible polymorphs and to identify the optimum crystal form for further investigations, it is necessary to perform screening with different solvent systems, counter-ions and co-compounds via different crystallization methods such as cooling, evaporation and slurry. This screening process is tedious and involves very diverse experimental conditions, researchers are advised to use the guide in Table 1 to select the most appropriate crystallizer.
|Reactor volume(mL)||0.05 – 0.2||0.25 – 1.5||1 – 5|
|Individual temperature control module||8||4||8|
|Operating range(℃)||-15 to 150||-15 to 150||-25 to 180|
The polymorph screening workflow is illustrated by Technobis CrystalBreeder as an example. Please mouse over to the workflow to view the corresponding steps.
Fig 1. Crystallization modes of Technobis Crystalbreeder.
Technobis offers three compact-designed parallel crystallizers which are capable to perform comprehensive studies on polymorph screening and crystallization process optimization by effectively utilizing a limited amount of sample. It also rapidly transforms experimental data into valuable information and enhances research efficiency, thus becoming the ideal solutions for high throughput crystallization research.