36 research outputs found
Technoeconomic Evaluation of Multiple Mixed Suspension-Mixed Product Removal (MSMPR) Crystallizer Configurations for Continuous Cyclosporine Crystallization
Continuous crystallization using
Mixed Suspension-Mixed Product Removal (MSMPR) crystallizers has been
demonstrated as a feasible method for implementing continuous separations
in pharmaceutical manufacturing processes. This work conducts a steady-state
process modeling and simulation study of the continuous cooling crystallization
of cyclosporine, comparing processes with and without solids recycle
for their technoeconomic viability. The model describes population
balance equations, crystallization kinetics, and process mass balances
to compare attainable crystallization and plantwide yields of different
process configurations. Total cost components using an established
economic analysis methodology are compared for varying numbers of
crystallizers, operating temperatures, total crystallizer cascade
residence times and API feed concentrations. Economic analyses and
the calculation of normalized cost components with respect to total
crystallizer volumes identify the process without recycle as the most
economically viable option, achieving the lowest total costs and low <i>E</i>-factors for pharmaceutical processes. The sensitivity
of total costs to the selected total residence times for economic
analyses highlights the need for rigorous comparison methodologies.
This work identifies the need for technoeconomic optimization studies
of continuous crystallization processes to establish the optimal design
of manufacturing campaigns prior to further development