Oral formulations and uses thereof
Provided herein are compounds, salts, crystalline forms, and pharmaceutical compositions that are related to Selective Estrogen Receptor Degraders, as well as methods of preparing the same. Also provided herein are methods of using the compounds, salts, crystalline forms, and pharmaceutical compositions for the treatment of diseases or disorders, such as breast cancer.
1 . A pharmaceutical composition comprising a meglumine salt of Compound FA represented by the structure below:
wherein the meglumine salt of Compound FA is in a crystalline Form I characterized by an X-ray powder diffraction (XRPD) pattern having the following peaks: 4.7, 9.1, 10.0, 17.6, 18.2, 19.0, 21.5, and 23.7 degrees 2 theta, ±0.2°, wherein the meglumine salt of Compound FA is in an amount equivalent to about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, or about 500 mg of Compound FA.
2 . The pharmaceutical composition of claim 1 , which is in a unit dosage form.
3 . A tablet comprising:
a) a meglumine salt of Compound FA in an amount of about 10% to about 80% by weight;
b) a surfactant in an amount of about 0.1% to about 10% by weight,
c) a diluent in an amount of about 15% to about 70% by weight,
d) a binder in an amount of about 0.1% to about 10% by weight,
e) a disintegrant in an amount of about 0.1% to about 10% by weight, and
f) a lubricant in an amount of about 0.1% to about 5% by weight,
wherein the meglumine salt of Compound FA is represented by the structure below:
and wherein the meglumine salt of Compound FA is in a crystalline Form I characterized by an X-ray powder diffraction (XRPD) pattern having the following peaks: 4.7, 9.1, 10.0, 17.6, 18.2, 19.0, 21.5, and 23.7 degrees 2 theta, ±0.2°.
4 . The tablet of claim 3 , wherein the surfactant comprises sodium lauryl sulfate.
5 . The tablet of claim 3 , wherein the diluent comprises microcrystalline cellulose.
6 . The tablet of claim 3 , wherein the diluent comprises mannitol.
7 . The tablet of claim 3 , wherein the binder comprises a povidone.
8 . The tablet of claim 3 , wherein the disintegrant comprises crospovidone.
9 . The tablet of claim 3 , wherein the tablet further comprises a coating.
10 . The tablet of claim 9 , wherein the coating comprises polyvinyl alcohol.
11 . The tablet of claim 9 , wherein the coating weight gain is about 1% to about 5%.
12 . A granule comprising
a) a meglumine salt of Compound FA in an amount of about 10% to about 80% by weight;
b) a surfactant in an amount of about 0.1% to about 10% by weight,
c) a diluent in an amount of about 15% to about 70% by weight,
d) a binder in an amount of about 0.1% to about 10% by weight, and
e) a disintegrant in an amount of about 0.1% to about 10% by weight,
wherein the meglumine salt of Compound FA is represented by the structure below:
and wherein the meglumine salt of Compound FA is in a crystalline Form I characterized by an X-ray powder diffraction (XRPD) pattern having the following peaks: 4.7, 9.1, 10.0, 17.6, 18.2, 19.0, 21.5, and 23.7 degrees 2 theta, ±0.2°.
13 . A process comprising:
a) wet granulating a mixture of a meglumine salt of Compound FA, surfactant, diluent, binder, and disintegrant to form wet granules;
b) optionally drying the wet granules to form dried granules; and
c) optionally dry milling the dried granules to form dry milled granules,
wherein the meglumine salt of Compound FA is represented by the structure below:
and wherein the meglumine salt of Compound FA in a crystalline Form I characterized by an X-ray powder diffraction (XRPD) pattern having the following peaks: 4.7, 9.1, 10.0, 17.6, 18.2, 19.0, 21.5, and 23.7 degrees 2 theta, ±0.2°.
14 . The process of claim 13 , further comprising blending the dry milled granules with an extra-granular disintegrant and a lubricant to form lubricated granules.
15 . The process of claim 14 , further comprising compressing the lubricated granules into a tablet core.
16 . The process of claim 15 , further comprising film coating the tablet core to form a coated tablet.
17 . The process of claim 13 , wherein the meglumine of Compound FA in the mixture is micronized and has a D90 of less than 500 μm.
18 . The process of claim 17 , wherein the meglumine of Compound FA in the mixture is micronized and has a D90 of less than 200 μm.
19 . The process of claim 17 , wherein the meglumine of Compound FA in the mixture is micronized and has a D90 of less than 20 μm.
20 . A method of treating breast cancer, the method comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of claim 1 .