Crystallization often serves as a key final and intermediate separation/purification unit operation in pharmaceutical production. More than 90% of small molecule drugs are produced in crystalline form[1]. Operation conditions of crystallization process determine process metrics such as crystal size distribution, yield, space-time yield (STY) and crystal quality attributes like crystal shape, morphology as well as solvates. The crystal product properties affect the efficiency of downstream unit operations such as filtration, drying and formulation. Moreover, in pharmaceutical products the crystal properties affect the stability and efficacy of drugs. Therefore, a comprehensive multi-scale and multi-purpose thermodynamic and kinetic modeling is the main objective of this work in order to understand crystallization mechanism and define optimum operation conditions. Optimization of crystallization operation conditions includes selection of the best solvent or mixture of solvents, cooling rate, anti-solvent flowrate, pH profile, mixing and seeding parameters as well as selection of mode of operation such as batch or continuous. Figure 1 shows a comprehensive multi-scale and multi-purpose modeling framework for in silico designing and optimization of pharmaceutical crystallization process.
Figure 1: A schematic diagram illustrating comprehensive multi-scale and multi-purpose modeling framework for in silico designing and optimization of pharmaceutical crystallization process
The framework will be implemented in Matlab-Simulink environment as a tool to support different engineering tasks from solvent selection to crystallization process design, optimization and control in life science and biopharmaceutical industries.
Acknowledgment: We would like to thank the Danish Council for Independent Research (DFF) for financing the project with grant ID: DFF-6111600077B.
See more of this Group/Topical: Process Development Division