Polymorphs and uses thereof
The present invention relates to new polymorphs of LXRβ agonists which exhibit improved physical properties. The invention also relates to pharmaceutical compositions including a pharmaceutically effective amount of an LXRβ agonist, as well as methods of treating cancer including administration of a formulation including an LXRβ agonist to a subject in need thereof.
1. A crystalline ansolvate of the hydrochloride salt of a compound having the structure:
wherein the crystalline ansolvate has peaks at diffraction angle 2θ (°) of 9.7°±0.5, 11.4°±0.5, 15.0°±0.5, 17.3°±0.5, 18.8°±0.5, and 19.3°±0.5 as measured by X-ray diffractometry or calculated from X-ray diffractometry.
2. The crystalline ansolvate of claim 1 , wherein the crystalline ansolvate is substantially free of a solvated polymorph of the compound.
3. The crystalline ansolvate of claim 2 having a loss of weight from 25° C. to 140° C. of less than 1% as measured by thermal gravimetric analysis.
4. The crystalline ansolvate of claim 2 having an endothermic onset at about 90° C. in differential scanning calorimetry (DSC) profile.
5. A method of producing a pharmaceutical composition comprising a compound having the structure:
or a pharmaceutically acceptable salt thereof, the method comprising mixing (i) a lipophilic vehicle, comprising a lipid excipient, and (ii) the crystalline ansolvate of claim 1 , wherein the lipophilic excipient is selected from fatty acids, glycerol fatty acid esters, and surfactants.
6. A pharmaceutical composition produced by the method of claim 5 , and a pharmaceutically acceptable excipient.
7. A method of modulating LXRβ activity, the method comprising administering an effective amount of the pharmaceutical composition of claim 6 , or the crystalline ansolvate of claim 1 .
8. The method of claim 7 , wherein LXRβ activity is modulated in a subject having cancer, and wherein the cancer is breast cancer, colon cancer, renal cell cancer, lung cancer, hepatocellular carcinoma, gastric cancer, ovarian cancer, pancreatic cancer, esophageal cancer, prostate cancer, sarcoma, bladder cancer, head and neck cancer, glioblastoma, diffuse large B-cell lymphoma, leukemia, or melanoma.
9. The method of claim 8 , wherein the cancer is metastatic cancer.