(606e) Conversion of FBRM® CLD Data to Psd Data: Application to a Needle-Shaped Industrial Case, for the Estimation of Crystallization Kinetics

Focused Beam Reflectance Measurement (FBRM^®) is a commonly employed Process Analytical Technology (PAT) for tracking the evolution of crystallization processes. FBRM^® data can utilised to indicate the onset of nucleation, and the relative rates of other crystallization mechanisms, such as secondary nucleation, crystal growth and/or agglomeration. However, the FBRM^® technique does not provide a measure of the in-situ Particle Size Distribution (PSD), but merely the Chord Length Distribution (CLD) of the particles present in the measurement volume of the FBRM^® probe. In order to utilise FBRM^® data to quantitatively track crystallization processes, a conversion method between FBRM^® measurements and PSD data, typically measured via laser diffraction, is necessary. Conversion of CLD to PSD data is not trivial, as numerous process variables, such slurry concentration, crystal shape, refractive indices of the solution and the crystal can significantly affect the measured FBRM^®CLD data. This work concerns the application of two conversion methods to an industrial case, which exhibits needle-like crystals. This type of crystal shape represents the most difficult of the application cases for CLD to PSD conversion techniques. Indeed, to the authors’ knowledge, all of the published literature on the topic concerns the application of these conversion methods to the more simplistic case of block-like or spherical shaped crystals. 

In this work, two conversion methods were applied to the sample industrial case. The first method correlates certain statistics of the measured FBRM^® CLD data to an attribute of the corresponding PSD, measured via laser diffraction. This method accounts for the average aspect ratio of the crystals present. In this way, this method accounts for the effect of different crystal shapes on the measured FBRM^® data. The second approach utilised in this work, involved the use of the moments (zeroth to sixth), determined from the FBRM^® CLD data. These FBRM^® based moments were then normalised with respect to the solution concentration and the initial PSD for the seed crystals. This method was previously employed for the simultaneous estimation of the kinetic parameters for secondary nucleation, crystal growth and agglomeration for a paracetamol, methanol and water anti-solvent crystallization process[1]. Both of these techniques were found to provide reasonably accurate (±10% on laser diffraction measurements), indications of certain attributes of the PSD. Finally, the successful application of these conversion techniques allowed the FBRM^® data to be quantitatively employed in the estimation of crystallization kinetics for the sample industrial case.