Systematic Retrofitting Methodology for Recrystallization of Thermally Unstable Active Pharmaceutical Ingredients

Abstract

Process optimization has become an increasingly important issue in the pharmaceutical industry in recent years. Due to the high competition, companies are obliged to make quick decisions, with sometimes ending up in sub-optimal solutions. In this paper, we propose a systematic retrofitting methodology for process optimization as method for the optimization of post-design pharmaceutical processes. The use of the combination of measurements, process modeling and computer-aided simulation provides a structured procedure for understanding and quantifying the improvement potential of the plant. The methodology consists of five tasks: gain process understanding (I), create process model (II), recognize constraints and optimization parameters (III) optimize the process model (IV). These tasks are supported by an interpretation/verification/validation step (X). The primary target of this methodology is the recrystallizatoin of thermally unstable Active Pharmaceutical Ingredients (APIs) The secondary target is to elucidate the many features contained in the modeling process. As a case study, the method was demonstrated in an actual plant with dissolution, filtration and crystallization (DFC) units. After performing the five steps, we could identify a better temperature and flow rate of the process with a 0.9% improvement of API yield.