Development of systematic procedures for the evaluation of solvent selection at an early stage in pharmaceutical processes

Three levels of evaluation for the selection of solvents have been developed, taking account the lack of information as one of the main characteristics of the problem. Tools to aided the evaluations and able to be applied early in design were identified. The first level is based on system properties analysis. A second level considers the impact of the potential streams to be formed on the system. A third level exploits process simulation in order to evaluate industrial scale issues of the solvents on the system. A case study based on the synthesis of P ropranolol is presented, where in a typical manufacturing process solvents such as water, isopropylamine, diethyl ether and cyclohexane are used for different operations. The evaluations revealed that solvents such as isopropylamine and diethyl ether gave high costs as implications of their management and containment. On the other hand, some of their characteristics are necessary for the successful performance of operations such as reaction and extraction. Through the analysis future implications related with the use of a group of solvents are explored with the aim of providing decision-support information. By this means, the efforts at early stage can be aimed towars a more sustainable process.