(223a) Green Chemistry in the Redesign of the Celecoxib Manufacturing Process

The celecoxib manufacturing process was redesigned with Green Chemistry objectives as part of the project's primary goals and resulted in dramatic environmental and worker safety improvements in the manufacture of the active ingredient in the medicine Celebrex®. These improvements followed the elucidation of two unprecedented reaction mechanisms responsible for the formation of an isomeric impurity whose presence required a subsequent recrystallization with its concomitant yield loss and resource expenditure. Application of this new mechanistic/kinetic understanding provided a significant increase in the process efficiency with respect to raw materials, solvents, energy and waste. For example, waste was reduced by 69 percent (greater than 5000 metric tons per year at current production levels.) The regulatory challenges of developing and implementing a pharmaceutical manufacturing process that isolates the final active pharmaceutical ingredient directly from a reaction mixture will be discussed.