Crystal forms of LY334370 HCl: isolation, solid-state characterization, and physicochemical properties.
LY334370 HCl, a 5HT1f agonist investigated for the treatment of migraines, was identified in five crystal forms: three anhydrates (I-III), a dihydrate, and an acetic acid solvate. The identification and characterization of these crystal forms by optical microscopy, differential scanning calorimetry, thermogravimetric and moisture sorption analyses, solid-state NMR spectroscopy, and X-ray crystallography (Form I only) are presented. Physical properties, including hygroscopicity, solubility, and intrinsic dissolution rate, were assessed for Form I and the dihydrate, the two most viable crystal forms for commercial development. Surprisingly, anhydrous Form I was found to be the thermodynamically most stable crystal form in water, dissolving six times slower than the dihydrate, a difference that correlates well with the rank order of aqueous solubility.
Reutzel-Edens
Susan M
SM
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. reutzel-edens_susan_m@lilly.com
Kleemann
Rita L
RL
Lewellen
Peggy L
PL
Borghese
Alfio L
AL
Antoine
Luc J
LJ
D001549:Benzamides / Q000737:chemistry* / Q000302:isolation & purification*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D018360:Crystallography, X-Ray; D004355:Drug Stability; D006813:Humidity; D007211:Indoles / Q000737:chemistry* / Q000302:isolation & purification*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011208:Powders; D017366:Serotonin Receptor Agonists / Q000737:chemistry* / Q000302:isolation & purification*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013997:Time Factors
C108218:4-fluoro-N-(3-(1-methyl-4-piperidinyl)-1H-indol-5-yl)benzamide; D001549:Benzamides; D007211:Indoles; D011208:Powders; D017366:Serotonin Receptor Agonists; D012997:Solvents