Investigation of the polymorphism of the angiotensin II antagonist agent MK-996.
The polymorphism of the angiotensin II antagonist agent MK-996 was studied, with particular emphasis on crystal form stability, solubility, and reproducible crystallization of the drug. X-ray powder diffraction patterns indicated differences in the crystal forms of early research and development lots. Solubility data for the different crystal forms in water at 25 degrees C are in agreement with the solution calorimetry data and indicated that crystalline form I is the thermodynamically stable polymorph of MK-996 under ambient conditions. In contrast to the other polymorphs, form I is reproducibly prepared on both the laboratory and production scale. This study examines methodology to determine the most suitable polymorph for development.
Jahansouz
H
H
Department of Pharmaceutical Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. Jahansouz@merck.com
Thompson
K C
KC
Brenner
G S
GS
Kaufman
M J
MJ
D057911:Angiotensin Receptor Antagonists; D003460:Crystallization; D004355:Drug Stability; D007093:Imidazoles / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D012995:Solubility; D013816:Thermodynamics
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; C090789:MK 996