Granted Patent B2

US 10,646,481 · App. 15/253,636 · Granted May 12, 2020

Inventors: William Rowe (Medford, MA); Patricia Hurter (Harvard, MA); Christopher Young (Waltham, MA); Kirk Dinehart (Holliston, MA); Marinus Jacobus Verwijs (Framingham, MA); Kirk Overhoff (Waltham, MA); Peter D. J. Grootenhuis (San Diego, CA); Martyn Botfield (Concord, MA); Alfredo Grossi (Somerville, MA)

Assignee: Vertex Pharmaceuticals Incorporated

A61K31/47A61K9/0053A61K9/1635A61K9/1652A61K9/2009A61K9/2013A61K9/2018A61K9/2027A61K9/2054A61K9/28A61K9/282A61K9/284A61K31/44

Abstract

Claims (59)

1. A pharmaceutical composition comprising a solid dispersion, wherein the solid dispersion comprises:

a) 80% of amorphous or substantially amorphous N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) by weight of the dispersion, wherein substantially amorphous Compound 1 comprises less than 15% crystalline Compound 1,

b) 19.5% of hydroxypropylmethylcellulose acetate succinate (HPMCAS) by weight of the dispersion, and

c) 0.5% of sodium lauryl sulfate (SLS) by weight of the dispersion.

2. The pharmaceutical composition of claim 1 , wherein the composition further comprises 30.5% of microcrystalline cellulose by weight of the composition.

3. The pharmaceutical composition of claim 1 , wherein the composition further comprises 30.4% of lactose by weight of the composition.

4. The pharmaceutical composition of claim 1 , wherein the composition further comprises 3% of sodium croscarmellose by weight of the composition.

5. The pharmaceutical composition of claim 1 , wherein the composition further comprises 0.5% of SLS by weight of the composition.

6. The pharmaceutical composition of claim 1 , wherein the composition further comprises 0.5% of colloidal silicon dioxide by weight of the composition.

7. The pharmaceutical composition of claim 1 , wherein the composition further comprises 1.0% of magnesium stearate by weight of the composition.

8. The pharmaceutical composition of claim 1 , wherein the composition further comprises a coating.

9. The pharmaceutical composition of claim 1 , wherein the composition has a hardness of 98 N (10 kp)±20 percent.

10. The pharmaceutical composition of claim 1 , wherein the composition contains 150 mg of Compound 1.

11. The pharmaceutical composition of claim 1 , wherein the composition contains 100 mg of Compound 1.

12. The pharmaceutical composition of claim 1 , comprising 34.1% of the solid dispersion by weight of the composition.

13. The pharmaceutical composition of claim 1 , wherein substantially amorphous Compound 1 comprises less than 5% crystalline Compound 1.

14. A pharmaceutical table comprising:

a. a solid dispersion in an amount ranging from 30% to 50% by weight of the tablet, wherein the dispersion comprises:

i) 80% of amorphous or substantially amorphous N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1) by weight of the dispersion, wherein substantially amorphous Compound 1 comprises less than 15% crystalline Compound 1,

ii) 19.5% of hydroxypropylmethyl cellulose acetate succinate (HPMCAS) by weight of the dispersion, and

iii) 0.5% of sodium lauryl sulfate (SLS) by weight of the dispersion;

b. a filler, in an amount ranging from 25% to 50% by weight of the tablet;

c. a disintegrant, in an amount ranging from 1% to 10% by weight of the tablet;

d. a surfactant, in an amount ranging from 0.3% to 2% by weight of the tablet;

e. a binder, in an amount ranging from 20% to 45% by weight of the tablet;

f. a glidant, in an amount ranging from 0.09% to 1.0% by weight of the tablet; and

g. a lubricant, in an amount ranging from 0.1% to 2% by weight of the tablet.

15. The pharmaceutical tablet of claim 14 , wherein substantially amorphous Compound 1 comprises less than 5% crystalline Compound 1.

16. The pharmaceutical composition of claim 1 , comprising:

a. 34.1 wt % of a solid dispersion comprising:

i) 80% of amorphous or substantially amorphous Compound 1 by weight of the dispersion, wherein substantially amorphous Compound 1 comprises less than 15% crystalline Compound 1,

ii) 19.5% of HPMCAS by weight of the dispersion, and

iii) 0.5% of SLS by weight of the dispersion;

b. 30.5% of microcrystalline cellulose by weight of the composition;

c. 30.4% of lactose by weight of the composition;

d. 3% of sodium croscarmellose by weight of the composition;

e. 0.5% of SLS by weight of the composition;

f. 0.5% of colloidal silicon dioxide by weight of the composition; and

g. 1.0% of magnesium stearate by weight of the composition.

17. The pharmaceutical composition of claim 16 , wherein substantially amorphous Compound 1 comprises less than 5% crystalline Compound 1.

18. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated as a tablet.

19. The tablet of claim 18 , wherein the tablet further comprises 30.5% of microcrystalline cellulose by weight of the tablet.

20. The tablet of claim 18 , wherein the tablet further comprises 30.4% of lactose by weight of the tablet.

21. The tablet of claim 18 , wherein the tablet further comprises 3% of sodium croscarmellose by weight of the tablet.

22. The tablet of claim 18 , wherein the tablet further comprises 0.5% of SLS by weight of the tablet.

23. The tablet of claim 18 , wherein the tablet further comprises 0.5% of colloidal silicon dioxide by weight of the tablet.

24. The tablet of claim 18 , wherein the tablet further comprises 1.0% of magnesium stearate by weight of the tablet.

25. The tablet of claim 18 , comprising 34.1% of the solid dispersion by weight of the tablet.

26. The tablet of claim 18 , comprising:

a. 34.1 wt % of a solid dispersion comprising:

i) 80% of amorphous or substantially amorphous Compound 1 by weight of the dispersion, wherein substantially amorphous Compound 1 comprises less than 15% crystalline Compound 1,

ii) 19.5% of HPMCAS by weight of the dispersion, and

iii) 0.5% of SLS by weight of the dispersion;

b. 30.5% of microcrystalline cellulose by weight of the tablet;

c. 30.4% of lactose by weight of the tablet;

d. 3% of sodium croscarmellose by weight of the tablet;

e. 0.5% of SLS by weight of the tablet;

f. 0.5% of colloidal silicon dioxide by weight of the tablet; and

g. 1.0% of magnesium stearate by weight of the tablet.

Assignments (2)

Continuity (9)

Cited By (6)

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