DEVELOPMENT OF SYSTEMATIC PROCEDURES FOR THE EVALUATION OF SOLVENT SELECTION AT AN EARLY STAGE IN PHARMACEUTICAL PROCESSES
Sustainable process-product development & green chemistry
Selection & Use of Organic Solvents (T1-7)
Keywords: Early stage, solvent selection, system, systematic evaluation, stakeholders
SAMUEL Perez and PAUL Sharratt
School of Chemical Engineering and Analytical Science, The University of Manchester, PO Box 88, Sackville St, Manchester, M60 1QD, UK
Samuel.Perez-vega@postgrad.manchester.ac.uk
paul.sharratt@manchester.ac.uk
Abstract
The production of pharmaceuticals is known for its high consumption of solvents. For selectivity and solubility reasons, the chosen reaction solvent often differs from one step to the next. As a result, synthesis progress includes a great deal of solvent substitution steps. The scaling-up of a new pharmaceuticals from a small laboratory production (grams per batch) into a process (kilograms or more per batch), can represent a challenge due to the differences in conditions that are presented in the synthesis of the drug in the laboratory, from those conditions presented at large scale.
Process simulation, CAMD, optimization models, assessment of key categories, LCA based approaches, property based approaches, and hybrid approaches are some examples of methodologies proposed for the selection of solvents. Nevertheless, some approaches only consider one or two aspects of a whole system at the time of establishing criteria for selecting a solvent. Moreover, some require information which is not available at an early stage. Because of these, solvent selection for a complete system at an early stage should involve the consideration of many aspects such as reaction, separation, VOC, cleaning, availability, cost, waste produced, and safety among others. An important characteristic of systems is that the system optimum is not equal to the sum of the optima of its individual components. Hence, the best solvent option for a single operation in a process would not be the best option for the complete system. As a consequence, there is a need of evaluation tools where the interaction among all the stakeholders involved in the synthesis and development of a drug can interact. As a result, these stakeholders would be able to detect and exchange information for the development of the drug. Also, the efforts can be aimed to real concerns related with the scaling up of the entire process.
This research introduces to the systematic evaluation of solvent selection at early stage. Three levels of evaluation where developed, where the lack of information in one of the main characteristics. Due the complexity of the problem a great number of tools such as process simulation, property and mixture simulation, laboratory experiments, and selectivity analysis among others are employed. In order to introduce a systematic and easier application of the methodology a programming tool was developed with the aim to guide the user (e.g. chemist and chemical engineer) through the evaluations. A case study based on synthesis of a pharmaceutical active material, propanolol is presented to highlight important aspects at each level in evaluation of the performance of the solvents in a system. The aim of these evaluations is to provide decision-making information about the performance of a solvent in the complete system and advice very early in design about the potential implications related with the solvents selected.
See the full pdf manuscript of the abstract.
Presented Tuesday 18, 08:45 to 09:05, in session Selection & Use of Organic Solvents (T1-7).
