Technoeconomic Evaluation of Multiple Mixed Suspension-Mixed Product Removal (MSMPR) Crystallizer Configurations for Continuous Cyclosporine Crystallization

Samir Diab, Dimitrios I. Gerogiorgis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 E-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.

Original languageEnglish
Pages (from-to)1571-1587
Number of pages17
JournalOrganic Process Research and Development
Volume21
Issue number10
Early online date13 Sep 2017
DOIs
Publication statusE-pub ahead of print - 13 Sep 2017

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