Computer-aided tool for solvent selection in pharmaceutical processes: Solvent swap

In the pharmaceutical processes, solvents have a multipurpose role since different solvents can be used in different stages (such as chemical reactions, separations and purification) in the multistage active pharmaceutical ingredients (APIs) production process. The solvent swap and selection tasks are important factors in API production. The solvent swap problem is defined as the process where a swap solvent is added to the original solvent solution and the original solvent finally is removed by distillation or liquid-liquid extraction. The selection of an appropriate solvent for each process step is usually based on experience where knowledge-based methods could be employed. However, because of economical, safety and environmental concerns, the use of solvent selection guides together with model-based verification is a better option. Gani et al. (2006) have proposed a computeraided framework where the solvent selection problem can be solved considering all the concerns mentioned above. The solvent swap problem can be treated as a special solvent selection (Gani et al., 2006) problem together with additional criteria consideration, involving VLE (vapour–liquid equilibria) and LLE (liquid-liquid equilibria). The application of the developed model-based framework is highlighted through several cases studies published in the literature. In the current state, the framework is suitable for problems where the original solvent is exchanged by distillation. A solvent selection guide for fast of suitable swap solvents is developed and is used to retrieve information for the most commonly used solvent candidates typically found in the pharmaceutical industry. The selection is verified by simulation. The framework for the solvent selection and solvent swap is part of an integrated computer-aided framework with the objective to assist the pharmaceutical industry in gaining better process understanding. A software interface to improve the usability of the tool has been created also.