Simulation-optimization framework for the digital design of pharmaceutical processes using Pyomo and PharmaPy

The problem of performing model-based process design and optimization in the pharmaceutical industry is an important and challenging one both computationally and in choice of solution implementation. In this work, a framework is presented to directly utilize a process simulator via callbacks during derivative-based optimization. The framework allows users with little experience in translating mechanistic ODEs and PDEs to robust, fully discretized algebraic formulations, required for executing simultaneous equation-oriented optimization, to obtain mathematically guaranteed optima at a competitive solution time when compared with existing derivative-free and derivative-based frameworks. The effectiveness of the framework in accuracy of optimal solution as well as computational efficiency is analyzed on on two case studies: (i) an integrated 2-unit reaction synthesis train used for the synthesis of an anti-cancer active pharmaceutical ingredient, and (ii) a more complex flowsheet representing a common synthesis-purification-isolation train of a pharmaceutical manufacturing processes.