Abstract
This paper describes the development of a method to calculate the overall “greenness” of a pharmaceutical process that uses multiple solvents. This calculation is made by taking into account various environmental parameters and determining an overall greenness index. Through this method a scientist or engineer can effectively determine alternative, “greener” solvents or processes based on the use of a solvent database and greenness score. The objective is to develop a means to improve the process of drug development through solvent replacement/reduction. A solvent selection table, using a common spreadsheet software routine, was developed for the purpose of allowing a user to compare the greenness between two different process routes. This table includes over 60 solvents and associated chemicals common in the pharmaceutical and chemical industries. The comparison was made possible by the creation of a user-defined, weighted-solvent, greenness index that is an overall weighted factor taking into consideration solvent type, quantity used, and environmental impact. A given process or solvent receives an index ranking based on a variety of environmental and health parameters. The index values, along with the mass of solvents used in the given process, are used to compute the index, which allows for a quick and easy quantitative environmental comparison between two potential process routes.
Acknowledgments
Support for this project is funded by a grant from the U.S. Environmental Protection Agency, X1 97275805-0. We appreciate the guidance of Bristol-Myers Squibb scientists and engineers Drs. San Kiang, Thomas LaPorte, Lori Spangler, and Stephan Taylor who played key roles in providing feedback on this project. We would like to acknowledge the following Rowan students who worked on this project: Scott Barnes, Nicholas DeSantis, Daniel Fichana, and Thor Farnsworth. We thank Dr. Robert Hesketh for his involvement in the early stages of the project. We thank Dr. Peter Dunn of Pfizer for supplying the solvent usage data on the sildenafil citrate process.
Notes
*Following the implementation of solvent recovery for toluene and ethyl acetate.
**Following implementation of 2-butanone recovery and yield improvements on acylation cyclisation steps
***Following introduction of ethanol/ethoxide process.