Calibration Free Supersaturation For Crystallization

The quantitative use of in situ ATR-FTIR for real time supersaturation assessment has been extremely well defined within the literature. However, these now well structured and understood methodologies have yet to be incorporated into the standard pharmaceutical crystallization development due to time and calibration/statistical analysis experience.

In this webinar, a method will be presented which facilitates the calibration free use of in situ ATR-FTIR spectra for the production and control of qualitative supersaturation trajectories.

Development and scale-up experiments are performed in a 100ml and 1L scale laboratory reactors. These lab reactor platforms, used in conjunction with Process Analytical Technologies (PAT), are used to develop and optimize the crystallization of both an Active Pharmaceutical Ingredient (API) and benzoic acid. The use of this methodology for assessing and solving laboratory based tech transfers and scale-up issues is also demonstrated.

The use of a commercially available software package is shown to implement an open loop feedback control strategy, used in conjunction with ATR-FTIR peak height values. The presented strategy demonstrates how qualitative supersaturation trajectories can be controlled to a specific set point and in turn ensure particle dimension and quality are not jeopardized in the tech transfer and scale-up of these processes.

The knowledge gained when coupled with in situ particle dimension information significantly increase process understanding and as a result minimal experimentation is required to output a desirable crystallization process.