Schering Corporation

Richard E Youngstrom

John S Chiu

Paul E McNamara

Charles G Eckhart

John K Jenkins

Stanley Rosenhouse

A novel, stable, crystalline sodium (5R,6S,8R)-6-(1-hydroxyethyl)-2-(2-carbamoyloxyethylthio)-penem-3-carboxyl ate (designated as Form II) is prepared by forming a homogenous solution of sodium (5R,6S,8R)-6-(1-hydroxyethyl)-2-(2-carbamoyloxyethylthio)-penem-3-carboxyl ate combined with stirring the homogenous solution for a time and at a temperature sufficient to produce Form II and recovering Form II. Form II may also be prepared by contacting a first solution obtained by dissolving (5R,6S,8R)-6-(1-hydroxyethyl)-2-(2-carbamoyloxyethylthio)-penem-3-carboxyl ic acid in dimethylacetamide with a second solution obtained by dissolving a sodium salt of an organic acid having a pKa of up to about 5, e.g., sodium 2-ethylhexanoate in acetone, in the presence of at least 5 volume percent water while stirring the reaction mixture so formed at a temperature and for a time sufficient to produce Form II followed by recovering Form II. Form II exhibits a greater physical stability and increased solid state chemical stability and reduced hygroscopicity over that of the amorphous form (e.g., Form I) which renders Form II greatly superior to Form I as a clinically suitable antibacterial agent.

Growing community of inventors

Cedar Grove, NJ, United States of America

Richard E Youngstrom