Crystalline forms of plasma kallikrein inhibitors
Pure crystalline forms of 1-benzyl-N-(4-carbamimidoylbenzyl)-1H-pyrazole-4-carboxamide acetate, and an amorphous form, pharmaceutical compositions thereof, and methods for making the same, are disclosed.
1. Crystalline Form I of anhydrous 1-benzyl-N-(4-carbamimidoylbenzyl)-1H-pyrazole-4-carboxamide acetate characterized by an X-ray powder diffraction (XRPD) pattern that comprises peaks at 10.0, 18.1, 18.6, 20.1, and 23.9 degrees, ±0.5 degrees, 2θ, wherein said XRPD is made using Cu Kα radiation, and Crystalline Form I is substantially free of other polymorphic forms of 1-benzyl-N-(4-carbamimidoylbenzyl)-1H-pyrazole-4-carboxamide acetate.
2. The crystalline form of claim 1 , further characterized by a melting point of about 253° C., and an aqueous solubility of about 8.3 mg/mL at 25° C.
3. The crystalline form of claim 1 , wherein the XRPD pattern further comprises a peak at 20.5 degrees, ±0.5 degrees, 2θ.
4. The crystalline form of claim 1 , wherein the XRPD pattern is substantially similar to the pattern of FIG. 1 .
5. A pharmaceutical composition comprising crystalline Form I according to claim 1 , and a pharmaceutically acceptable carrier.
6. A pharmaceutical composition comprising crystalline Form I according to claim 4 , and a pharmaceutically acceptable carrier.