Rapid conversion of API hydrates to anhydrous forms in aqueous media.
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.
Petrova
Rositza I
RI
Merck & Co., Inc, RY818-B112, P.O. Box 2000, Rahway, New Jersey 07065, USA. rositza_petrova@merck.com
Peresypkin
Andrey
A
Mortko
Christopher J
CJ
McKeown
Arlene E
AE
Lee
Jaemoon
J
Williams
J Michael
JM
D000081:Acetamides / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D004356:Drug Storage; D006813:Humidity; D007700:Kinetics; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D044367:Phase Transition; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics; D013818:Thermogravimetry; D013997:Time Factors; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
D000081:Acetamides; D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water