Crystal forms of LY334370 HCl: isolation, solid-state characterization, and physicochemical properties
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Published on: April 11, 2021
Susan M Reutzel-Edens1, Rita L Kleemann, Peggy L Lewellen
1Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. reutzel-edens_susan_m@lilly.com
Abstract:
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.
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