Green Aspects of Scale-Up Synthesis of Some APIs, Drug Candidates Under Development or Their Critical Intermediates

Abstract

The ultimate goal of a process chemist is to achieve robust synthetic processes for active pharmaceutical ingredients (API), drug candidates under development or their critical intermediates. The process developed should be economical, safe and at the same time using green chemistry concepts with minimal impurity formations and achieving higher yields. While doing so, it is prudent on the part of a chemist to review all the available literature, study the various routes of synthesis and chose the one that can be commensurate with the above laid down goals with a view on commercial viability and scaling up to higher levels. It is also one of the goals of the synthetic organic chemist to identify and limit the formation of impurities and degradation products, if any, at each step in the synthesis that helps in achieving higher yields. One of the principal parts of the documentation of the API is a description of impurities or degradation products formed during the process. The identified main impurities and degradation products crossing the threshold levels need to be isolated or synthesized independently by the process chemist for quantification of their levels in API and documentation purposes.

With these concepts in the background, the chemist explores each step in a chemical process preferring usage of relatively greener solvents, commercially viable reagents and the necessary equipment that can be easily procured and installed for achieving the objective with minimal levels of maintenance. In this review article, scale-up processes for some of the APIs, drug candidates under development or their critical intermediates, reported in recent literature, highlighting the greener aspects of such commercially viable processes and achieving the synthesis with the minimal number of steps and higher yields will be reviewed to grab the interest of the researchers.