Thermodynamic stability and crystal structures for polymorphs and solvates of formoterol fumarate.
Polymorph screening of formoterol fumarate was performed in 12 solvents, followed by evaluations of thermodynamic stability. Three anhydrates, a dihydrate, a diethanolate, a diisopropanolate, and a dibensylalcoholate were found. The crystal structure of three solvated modifications and of the most stable anhydrate was investigated. This indicated that solvation is needed to get a stable and well packed crystal structure. Thermodynamic testing suggests that five crystal modifications are thermodynamically stable, at different conditions, since they are all reversibly related to each other.
Analytical Development, Pharmaceutical & Analytical R&D, AstraZeneca R&D Lund, S-221 87 Lund, Sweden.
K
K
Jarring
T
T
Larsson
B
B
Stensland
I
I
Ymén
D019840:2-Propanol; D019905:Benzyl Alcohol; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004355:Drug Stability; D000431:Ethanol; D004983:Ethanolamines / Q000737:chemistry*; D000068759:Formoterol Fumarate; D007536:Isomerism; D007700:Kinetics; D008958:Models, Molecular; D012997:Solvents; D013816:Thermodynamics; D013818:Thermogravimetry; D014961:X-Ray Diffraction
D004983:Ethanolamines; D012997:Solvents; D000431:Ethanol; D019905:Benzyl Alcohol; D019840:2-Propanol; D000068759:Formoterol Fumarate