1. Rapid conversion of API hydrates to anhydrous forms in aqueous media.
- Author
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Petrova RI, Peresypkin A, Mortko CJ, McKeown AE, Lee J, and Williams JM
- Subjects
- Calorimetry, Differential Scanning, Chemistry, Pharmaceutical, Crystallization, Drug Stability, Drug Storage, Humidity, Kinetics, Molecular Structure, Phase Transition, Solubility, Solvents chemistry, Temperature, Thermodynamics, Thermogravimetry, Time Factors, Water chemistry, X-Ray Diffraction, Acetamides chemistry, Pharmaceutical Preparations chemistry
- Abstract
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., ((c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association)
- Published
- 2009
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