(160f) Technoeconomic and Technosustainability Analysis of Batch and Continuous Pharmaceutical Crystallization Systems

As the scope and range of pharmaceutical manufacturing grows in the modern world, so does the need for more flexible and efficient models of manufacturing in the drug industry. One of the pivotal technologies for this adaptation is the implementation of continuous crystallization unit operations as a means of process intensification [1]. However, despite the necessity, the application of novel technologies to existing systems can be a difficult process. To facilitate this process, technoeconomic cost and sustainability models can be a key tool to aid manufacturers in the decision-making process.

This work illustrated the use of a combined the techno-economic (TEA) and sustainability analysis framework for the comparative evaluation of batch versus continuous purification of a generic pharmaceutical manufacturing process. The chosen active pharmaceutical ingredient (API) for the simulations is paracetamol, a common analgesic drug. Then, the results of purifying the API from a batch crystallizer and a cascading mixed suspension, mixed product removal (MSMPR) continuous crystallizer layout is compared. Thus, through the analysis and comparison of a batch and continuous crystallization simulation, trends and characteristics of these different manufacturing methods can be observed. The simulation of these two different manufacturing methods was created using PharmaPy, a Python-based library developed for pharmaceutical flowsheet analysis [2]. The batch and continuous production simulations were created under the constraint of a varying range of annual production volumes. The cost of the pharmaceutical manufacturing process was assessed on an economic and sustainability basis. The economic efficiency was investigated by observing both the capital expenses (CapEx) and the operational expenses (OpEx) of the layout. The sustainability of the processes was assessed by using the process mass intensity (PMI) metric. Once the simulation framework was established as such, the process was then optimized using a dual annealing algorithm with either the total cost or the total PMI rating as the objective function.

Once the batch and continuous manufacturing processes were established and optimized, analysis of the preliminary results could be conducted. For most annual production volumes, the continuous system proved to be more economically efficient while maintaining a similar PMI score as batch systems. While the cost drivers of each system are complex, the main driver for this is since the batch system required cleaning solvents in between each batch run, thus significantly increasing the material costs for operation. However, as the production volume decreases, we observed that the batch systems proved to be more economically and environmentally efficient, which aligns with current industry understandings. With further analysis, this study can show the characteristics of each system as well as their trends in future industrial practices.

Acknowledgement:

This work was supported by the National Science Foundation (NSF) under Grant No. 2229250.

References:

1. Diab, Samir, and Dimitrios I. Gerogiorgis. "No more than three: technoeconomic mixed integer nonlinear programming optimization of mixed suspension, mixed product removal crystallizer cascades for melitracen, an antidepressant API." Industrial & Engineering Chemistry Research49 (2020): 21458-21475.
2. Casas-Orozco, Daniel, et al. "PharmaPy: An object-oriented tool for the development of hybrid pharmaceutical flowsheets." Computers & Chemical Engineering 153 (2021): 107408.