Claims for Patent: 10,646,481

Summary for Patent: 10,646,481

Title:	Pharmaceutical composition and administrations thereof
Abstract:	The present invention relates to pharmaceutical compositions comprising a solid dispersion of N-[2,4-Bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline- -3-carboxamide, methods of manufacturing pharmaceutical compositions of the present invention, and methods of administering pharmaceutical compositions of the present invention.
Inventor(s):	Rowe; William (Medford, MA), Hurter; Patricia (Harvard, MA), Young; Christopher (Waltham, MA), Dinehart; Kirk (Holliston, MA), Verwijs; Marinus Jacobus (Framingham, MA), Overhoff; Kirk (Waltham, MA), Grootenhuis; Peter D. J. (San Diego, CA), Botfield; Martyn (Concord, MA), Grossi; Alfredo (Somerville, MA)
Assignee:	Vertex Pharmaceuticals Incorporated (Boston, MA)
Application Number:	15/253,636
Patent Claims:	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-ox- oquinoline-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.