Claims for Patent: 10,946,015

Summary for Patent: 10,946,015

Title:	Stable pharmaceutical compositions comprising a pyrimidine-sulfamide
Abstract:	The invention relates to stable pharmaceutical compositions comprising the compound of the below formula, or pharmaceutically acceptable salts, solvates, hydrates or morphological forms thereof. ##STR00001##
Inventor(s):	Adesuyi; Charles Tokunbo (Swindon, GB), Lithgow; Bruce Hamilton (Bath, GB), Lambert; Olivier (Spechbach-le-Haut, FR), Holman; Lovelace (Arlesheim, CH)
Assignee:	ACTELION PHARMACEUTICALS LTD (Allschwil, CH)
Application Number:	15/900,586
Patent Claims:	1. A pharmaceutical composition comprising: a) the compound of the formula I as drawn below ##STR00004## or a pharmaceutically acceptable salt, solvate, hydrate or morphological form thereof, in a total amount of 1 to 50% in weight based on the total weight of the pharmaceutical composition, b) filler, in an amount of 10 to 95% in weight based on the total weight of the pharmaceutical composition, c) disintegrant, in an amount of 1 to 20% in weight based on the total weight of the pharmaceutical composition, d) surfactant, in an amount from 0.1 to 1% in weight based on the total weight of the pharmaceutical composition, wherein the surfactant comprises a polysorbate, and e) lubricant, in an amount from 0.05 to 10% in weight based on the total weight of the pharmaceutical composition. 2. The pharmaceutical composition of claim 1, wherein the filler comprises one or more from lactose, maize starch, pregelatinized starch, dibasic calcium phosphate dihydrate (CaHPO.sub.4.2H.sub.2O), microcrystalline cellulose, maltodextrin and mannitol. 3. The pharmaceutical composition of claim 1, wherein the filler comprises lactose. 4. The pharmaceutical composition of claim 1, wherein the filler comprises microcrystalline cellulose. 5. The pharmaceutical composition of claim 1, wherein the filler comprises lactose and microcrystalline cellulose. 6. The pharmaceutical composition of claim 1, wherein the filler comprises maize starch. 7. The pharmaceutical composition of claim 1, wherein the filler comprises pregelatinized starch. 8. The pharmaceutical composition of claim 1, wherein the filler comprises dibasic calcium phosphate dihydrate (CaHPO.sub.4.2H.sub.2O). 9. The pharmaceutical composition of claim 1, wherein the filler comprises mannitol. 10. The pharmaceutical composition of claim 1, wherein the disintegrant comprises one or more from croscarmellose sodium, sodium starch glycolate, calcium carboxymethylcellulose, sodium carboxymethylcellulose, cross-linked polyvinylpyrrolidone, polyvinylpyrrolidone, alginic acid, sodium alginate, pregelatinized starch, guar gum, clays and ion exchange resins. 11. The pharmaceutical composition of claim 10, wherein the disintegrant comprises croscarmellose sodium. 12. The pharmaceutical composition of claim 10, wherein the disintegrant comprises sodium starch glycolate. 13. The pharmaceutical composition of claim 10, wherein the disintegrant comprises cross-linked polyvinylpyrrolidone. 14. The pharmaceutical composition of claim 10, wherein the disintegrant comprises polyvinylpyrrolidone. 15. The pharmaceutical composition of claim 10, wherein the disintegrant comprises pregelatinized starch. 16. The pharmaceutical composition of claim 1, wherein the polysorbate is polysorbate 80. 17. The pharmaceutical composition of claim 1, wherein the lubricant comprises one or more from magnesium stearate, aluminium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, sodium benzoate, a glyceryl mono fatty acid, glyceryl dibehenate, glyceryl palmito-stearic ester, polyethylene glycol, hydrogenated cotton seed oil, castor seed oil and sucrose esters. 18. The pharmaceutical composition of claim 17, wherein the lubricant comprises magnesium stearate. 19. The pharmaceutical composition of claim 17, wherein the lubricant comprises aluminium stearate. 20. The pharmaceutical composition of claim 17, wherein the lubricant comprises calcium stearate. 21. The pharmaceutical composition of claim 17, wherein the lubricant comprises stearic acid. 22. The pharmaceutical composition of claim 1, which is in the form of a tablet. 23. The pharmaceutical composition of claim 10, which is in the form of a tablet. 24. The pharmaceutical composition of claim 16, which is in the form of a tablet. 25. The pharmaceutical composition of claim 17, which is in the form of a tablet. 26. A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 1 to a patient in need thereof. 27. A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 10 to a patient in need thereof. 28. A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 16 to a patient in need thereof. 29. A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 17 to a patient in need thereof. 30. A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 22 to a patient in need thereof. 31. A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 23 to a patient in need thereof. 32. A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 24 to a patient in need thereof. 33. A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 25 to a patient in need thereof. 34. A pharmaceutical composition comprising: a) the compound of the formula I as drawn below ##STR00005## or a pharmaceutically acceptable salt, solvate, hydrate or morphological form thereof, in a total amount of 1 to 50% in weight based on the total weight of the pharmaceutical composition, b) filler, in an amount of 10 to 95% in weight based on the total weight of the pharmaceutical composition, wherein the filler comprises one or more from lactose, maize starch, pregelatinized starch, dibasic calcium phosphate dihydrate (CaHPO.sub.4.2H.sub.2O), microcrystalline cellulose, maltodextrin and mannitol, c) disintegrant, in an amount of 1 to 20% in weight based on the total weight of the pharmaceutical composition, wherein the disintegrant comprises one or more from croscarmellose sodium, sodium starch glycolate, calcium carboxymethylcellulose, sodium carboxymethylcellulose, cross-linked polyvinylpyrrolidone, polyvinylpyrrolidone, alginic acid, sodium alginate, pregelatinized starch, guar gum, clays and ion exchange resins, d) surfactant, in an amount from 0.1 to 1% in weight based on the total weight of the pharmaceutical composition, wherein the surfactant comprises a polysorbate, and e) lubricant, in an amount from 0.05 to 10% in weight based on the total weight of the pharmaceutical composition, wherein the lubricant comprises one or more from magnesium stearate, aluminium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, sodium benzoate, a glyceryl mono fatty acid, glyceryl dibehenate, glyceryl palmito-stearic ester, polyethylene glycol, hydrogenated cotton seed oil, castor seed oil and sucrose esters. 35. The pharmaceutical composition of claim 34, wherein the disintegrant is sodium starch glycolate or a combination of sodium starch glycolate and polyvinylpyrrolidone. 36. The pharmaceutical composition of claim 34, wherein the surfactant is polysorbate 80. 37. The pharmaceutical composition of claim 34, wherein the lubricant comprises magnesium stearate. 38. The pharmaceutical composition of claim 34, which is in the form of a tablet. 39. The pharmaceutical composition of claim 36, which is in the form of a tablet. 40. A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 34 to a patient in need thereof. 41. A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 38 to a patient in need thereof. 42. A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 39 to a patient in need thereof.