(231d) Wet Milling with in-Line Fines Dissolution | AIChE

(231d) Wet Milling with in-Line Fines Dissolution


Boukerche, M., Abbvie
Gaertner, J. G., AbbVie Inc.
Pohlman, D., Abbvie Inc.
Kelkar, M., Abbvie
Singh, M., University of Illinois At Chicago
Nere, N., AbbVie Inc.
Solid-state properties, such as particle size distribution (PSD) and morphology, affect downstream processing steps as well as critical quality attributes (CQAs) of the drug substance. Several post-processing techniques exist for the size reduction and impacting the PSD. Two of the most commonly used approaches for crystal breakage are milling and sonication.

In this study, a wet mill is coupled with a heat exchanger in a closed-loop system to dissolve generated fines from the wet mill and to obtain the desired particle size distribution. Coupling the dissolution step with the breakage step minimizes the time and cost of post-processing, yet it requires a detailed understanding of the system. In addition to the heat exchanger, frictional forces between the crystals and the wet mill also increase the slurry temperature. The heat exchanger design is optimized for the desired PSD using a mathematical model for simultaneous breakage and dissolution using gPROMS from gFormulated products. Initially, breakage and dissolution are studied separately to understand each of these mechanisms and evaluate the necessary coefficients for breakage kernel and dissolution rate constants. A series of milling and dissolution experiments are performed on Carbamazepine (CBZ), and the final PSDs are imported into the model to validate the model parameters. Lastly, the obtained kernels are used to construct a coupled wet mill and heat exchanger model and the model is evaluated against experimental datasets. This model would be used to optimize the heat exchanger design to obtain desired PSD from a given wet milling process.

MK, MB, DP, JG NN are employees or a retiree of AbbVie and may own AbbVie stock. PC was an AbbVie intern and is currently a doctoral student at UIC with no additional conflicts to disclose. MS is a Professor at UIC with no additional conflicts to disclose. AbbVie sponsored and funded the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication.