Computer‐aided solvent selection and design for the efficient extraction of a pharmaceutical molecule

Abstract

AbstractWe have employed a computer‐aided approach to select and design task‐specific organic solvents for the liquid‐liquid extraction of ephedrine from its aqueous solution. We have identified three solvent performance indicators (SPIs) as the shortlisting criteria for solvents with desirable properties: high ephedrine solubility; low solvent loss; and high partition coefficient. Other properties that were considered include octanol‐water partition coefficient and toxicity, which give a measure of the safety/health/environmental (SHE) impacts, and liquid viscosity, which is an important process design parameter. We have first analyzed the trends in these SPIs for a range of common organic solvents. Toluene (currently employed for the extraction of R‐phenylacetylcarbinol, the precursor to ephedrine) has low solvent loss but relatively poor values of the other SPIs for ephedrine extraction, though with a relatively benign SHE impact. We are unable to identify a solvent (from the list of common organic solvents) that satisfies all the shortlisting criteria for use in the pharmaceutical industry and this provided the motivation for the design of task‐specific solvents. We have designed organic solvents (acyclic aliphatic, aromatic with one side chain attachment, and aromatic with two side chain attachments) with superior values of SPIs than the reference solvent, toluene. We have employed limiting values on the melting and boiling points to ensure the designed solvents are liquids at the operating conditions. Designed aliphatic compounds contain the chloro‐group(s), whereas there are aromatic solvents without the chloro‐groups with better SPIs than toluene. Designed solvents without chloro‐groups may be considered as the starting point for further screening experiments.