Compositions and uses thereof
Provided are solid dispersions, solid molecular complexes, salts and crystalline polymorphs involving propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide.
1. A solid dispersion comprising Compound I having the formula:
wherein Compound I is molecularly dispersed within a polymer matrix formed by hydroxypropylmethyl cellulose acetate succinate (HPMCAS) in its solid state, and wherein Compound I is substantially amorphous.
2. The solid dispersion according to claim 1 , wherein Compound I is present in a nanoparticulate size range.
3. The solid dispersion according to claim 1 , wherein Compound I is present in the solid dispersion in an amount of from about 20% to about 60% by weight of the solid dispersion.
4. The solid dispersion according to claim 1 , wherein Compound I is present in the solid dispersion in an amount of from about 20% to about 40% by weight of the solid dispersion.
5. The solid dispersion according to claim 1 , wherein at least 98% of Compound I is in amorphous form.
6. The solid dispersion according to claim 1 , wherein the ratio of an amount by weight of Compound I within the solid dispersion to an amount by weight of HPMCAS is from about 1:9 to about 1:1.
7. The solid dispersion according to claim 1 , wherein the ratio of an amount by weight of Compound I within the solid dispersion to an amount by weight of HPMCAS is from about 2:8 to about 4:6.
8. The solid dispersion according to claim 1 , wherein the ratio of an amount by weight of Compound I within the solid dispersion to an amount by weight of HPMCAS is about 3:7.
9. The solid dispersion according to claim 1 , wherein HPMCAS is selected from the group consisting of AS-LF, AS-MF, AS-HF, AS-LG, AS-MG, and AS-HG.
10. The solid dispersion according to claim 1 , wherein HPMCAS is present in an amount of not less than about 20% by weight of the solid dispersion.
11. The solid dispersion according to claim 1 , HPMCAS is present in an amount greater than about 50% by weight of the solid dispersion.
12. The solid dispersion according to claim 1 , wherein HPMCAS is present in an amount of about 20% to about 70% by weight of the solid dispersion.
13. A formulation comprising the solid dispersion according to claim 5 .
14. The formulation according to claim 13 , wherein the formulation is a tablet.
15. The formulation according to claim 13 , wherein the formulation is a coated tablet.
16. The formulation according to claim 15 , further comprising colloidal silicon dioxide.
17. The formulation according to claim 16 , wherein the colloidal silicon dioxide is present in an amount of at least 0.5% by weight of the formulation.
18. The formulation according to claim 15 , further comprising 2% by weight hydroxypropylcellulose.
19. A composition comprising a solid dispersion according to claim 5 and a pharmaceutically-acceptable carrier.
20. A tablet comprising a solid dispersion, wherein the solid dispersion comprises Compound I having the formula:
wherein Compound I is molecularly dispersed within a polymer matrix formed by hydroxypropylmethyl cellulose acetate succinate (HPMCAS) in its solid state, Compound I is substantially amorphous, and the ratio of an amount by weight of Compound I within the solid dispersion to an amount by weight of HPMCAS is about 3:7.
21. The tablet according to claim 20 , wherein the tablet is coated.
22. The tablet according to claim 21 , wherein Compound I is stable.
23. The tablet according to claim 22 , wherein Compound I is stable for at least 2 months at 40° C. and 75% relative humidity.
24. The tablet according to claim 23 , wherein Compound I is stable for at least 3 months at 40° C. and 75% relative humidity.
25. The tablet according to claim 23 or 24 , wherein the compound is stable if at least 95% remains in amorphous form at the end of the time period.
26. The tablet according to claim 23 or 24 , wherein the compound is stable if at least 98% remains in amorphous form at the end of the time period.
27. The tablet according to claim 23 or 24 , wherein the stability of compound I is evaluated using powder X-ray diffraction.
28. The tablet according to claim 27 , wherein Compound I is stable if it does not form any detectable crystalline peaks.
29. The tablet according to claim 22 , 23 , or 24 , wherein compound I stability is evaluated using dissolution testing.