Compositions and uses thereof

Patent metadata

Field	Value
Publication number	US-9447089-B2
Application number	US-75203510-A
Country	US
Kind code	B2
Filing date	Mar 31, 2010
Priority date	Apr 3, 2009
Publication date	Sep 20, 2016
Grant date	Sep 20, 2016

Abstract

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.

First claim

That which is claimed is:

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.

Assignees

• Desai Dipen
• Diodone Ralph
• Go Zenaida
• Ibrahim Prabha N
• Iyer Raman
• Mair Hans-Juergen
• Sandhu Harpreet K
• Shah Navnit H
• Visor Gary
• Wyttenbach Nicole
• Lauper Stephan
• Pudewell Johannes
• Wierschem Frank
• Plexxikon Inc
• Hoffman-La Roche Inc

Inventors

• Desai Dipen
• Diodone Ralph
• Go Zenaida
• Ibrahim Prabha N
• Iyer Raman
• Mair Hans-Juergen
• Sandhu Harpreet K
• Shah Navnit H
• Visor Gary
• Wyttenbach Nicole
• Lauper Stephan
• Pudewell Johannes
• Wierschem Frank

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title