Crystalline forms of a therapeutic compound and uses thereof
Disclosed herein are certain crystalline forms of Compound 5, N-(5-((2-(4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butanamido)imidazo[1,2-0]pyridazin-6-yl)oxy)-2-methylphenyl)-1,3-dimethyl-1/-/-pyrazole-5-carboxamide, as well as pharmaceutical compositions comprising the crystalline forms. The present disclosure further relates to methods for treating or preventing diseases or disorders using the crystalline forms or pharmaceutical compositions thereof in a subject in need thereof, including diseases or disorders associated with abnormal or pathological angiogenesis and/or aberrant signaling of a growth factor signaling pathway (e.g., vascular endothelial growth factor (VEGF)), such as proliferative diseases and ocular diseases.
1. A crystalline form of Compound 5:
wherein the crystalline form is crystalline Form I, wherein the crystalline Form I has an X-ray powder diffraction (XRPD) pattern with a largest peak at about 4.31±0.2 degrees 2θ and a second largest peak at about 6.30±0.2 degrees 2θ, wherein the X-ray source is a Cu/Kα source.
2. A crystalline form of Compound 5,
wherein the crystalline form is crystalline Form II, wherein the crystalline Form II has an X-ray powder diffraction (XRPD) pattern with a largest peak at about 4.59±0.2 degrees 2θ and a second largest peak at about 3.42±0.2 degrees 2θ, wherein the X-ray source is a Cu/Kα source.
3. A process for preparing a crystalline form of claim 2 , comprising:
mixing crystalline Form I of Compound 5 with a solution of acetonitrile and water;
heating the solution to dissolve Compound 5 and then allowing the solution to cool; and
recovering crystalline Form II of Compound 5 from the solution.
4. The process of claim 3 , wherein the solution comprises a 90:10 acetonitrile:water mixture.
5. A pharmaceutical composition comprising a crystalline form of claim 1 or 2 , and a pharmaceutically acceptable carrier.
6. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is suitable for topical administration, injection, oral administration, inhalation, or delivery to the eye.
7. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition is a liquid that is packaged for delivery in eye drop form.
8. A method of treating an ocular disease associated with aberrant signalling of a Vascular Endothelial Growth Factor (VEGF) signalling pathway, comprising administering to a subject in need thereof a therapeutically effective amount of the crystalline form of claim 1 or 2 or the pharmaceutical composition of claim 5 , wherein the ocular disease is retinopathy, age-related macular degeneration, corneal neovascularization, diabetic macular edema, cystoid macular edema, or retinal vein occlusion.