Rapid conversion of API hydrates to anhydrous forms in aqueous media

✍ Scribed by Rositza I. Petrova; Andrey Peresypkin; Christopher J. Mortko; Arlene E. McKeown; Jaemoon Lee; J. Michael Williams

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 235 KB
• Volume: 98
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.21703

✦ Synopsis

Three anhydrous polymorphs, a monohydrate and a dihydrate of an active pharmaceutical ingredient, N-{[(5S)-3-(4-{6-[(1R,5S)-6-cyano-3-oxabicyclo[3.1.0]hex-6-yl]pyridin-3-yl}phenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide (Compound 1), have been crystallized and characterized. Slurry experiments and thermal data have been used to determine their relative thermodynamic stability. The hydrates of Compound 1 were found to be less stable than the most stable anhydrous Form I and converted into Form I in water within 15 min. The rate of conversion in a dry state was found to depend on the relative humidity (RH) and was highest at the two RH extremes examined, 5% and 97.5% RH.