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.
Jarring
K
K
Analytical Development, Pharmaceutical & Analytical R&D, AstraZeneca R&D Lund, S-221 87 Lund, Sweden.
Larsson
T
T
Stensland
B
B
Ymén
I
I
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