# US 10,946,015 B2 · Stable pharmaceutical compositions comprising a pyrimidine-sulfamide > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,946,015 B2 - Document ID: US10946015B2 - Status: Granted - Kind: B2 - Application number: 15/900,586 - Filed: 2018-02-20 - Published: 2018-09-20 - Granted: 2021-03-16 - Earliest claimed: 2005-09-12 - Assignees: Actelion Pharmaceuticals Ltd. - Applicants: Actelion Pharmaceuticals Ltd. - Inventors: Charles Tokunbo Adesuyi; Bruce Hamilton Lithgow; Olivier Lambert; Lovelace Holman - Web page: https://patentgrep.com/patent/US10946015B2 ## CPC - A61K 31/506: not condensed and containing further heterocyclic rings - A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)} - A61K 9/205: {Polysaccharides, e.g. alginate, gums; Cyclodextrin} - A61K 9/2059: {Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin} - A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets} - A61K 9/2846: {Poly(meth)acrylates} - A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 9/12: Antihypertensives - A61P 11/00: Drugs for disorders of the respiratory system - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## 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. ## Claims ### Claim 1 A pharmaceutical composition comprising: a) the compound of the formula I as drawn below 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. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1, wherein the filler comprises one or more from lactose, maize starch, pregelatinized starch, dibasic calcium phosphate dihydrate (CaHPO4.2H2O), microcrystalline cellulose, maltodextrin and mannitol. ### Claim 3 (depends on 1) The pharmaceutical composition of claim 1, wherein the filler comprises lactose. ### Claim 4 (depends on 1) The pharmaceutical composition of claim 1, wherein the filler comprises microcrystalline cellulose. ### Claim 5 (depends on 1) The pharmaceutical composition of claim 1, wherein the filler comprises lactose and microcrystalline cellulose. ### Claim 6 (depends on 1) The pharmaceutical composition of claim 1, wherein the filler comprises maize starch. ### Claim 7 (depends on 1) The pharmaceutical composition of claim 1, wherein the filler comprises pregelatinized starch. ### Claim 8 (depends on 1) The pharmaceutical composition of claim 1, wherein the filler comprises dibasic calcium phosphate dihydrate (CaHPO4.2H2O). ### Claim 9 (depends on 1) The pharmaceutical composition of claim 1, wherein the filler comprises mannitol. ### Claim 10 (depends on 1) 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. ### Claim 11 (depends on 10) The pharmaceutical composition of claim 10, wherein the disintegrant comprises croscarmellose sodium. ### Claim 12 (depends on 10) The pharmaceutical composition of claim 10, wherein the disintegrant comprises sodium starch glycolate. ### Claim 13 (depends on 10) The pharmaceutical composition of claim 10, wherein the disintegrant comprises cross-linked polyvinylpyrrolidone. ### Claim 14 (depends on 10) The pharmaceutical composition of claim 10, wherein the disintegrant comprises polyvinylpyrrolidone. ### Claim 15 (depends on 10) The pharmaceutical composition of claim 10, wherein the disintegrant comprises pregelatinized starch. ### Claim 16 (depends on 1) The pharmaceutical composition of claim 1, wherein the polysorbate is polysorbate 80. ### Claim 17 (depends on 1) 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. ### Claim 18 (depends on 17) The pharmaceutical composition of claim 17, wherein the lubricant comprises magnesium stearate. ### Claim 19 (depends on 17) The pharmaceutical composition of claim 17, wherein the lubricant comprises aluminium stearate. ### Claim 20 (depends on 17) The pharmaceutical composition of claim 17, wherein the lubricant comprises calcium stearate. ### Claim 21 (depends on 17) The pharmaceutical composition of claim 17, wherein the lubricant comprises stearic acid. ### Claim 22 (depends on 1) The pharmaceutical composition of claim 1, which is in the form of a tablet. ### Claim 23 (depends on 10) The pharmaceutical composition of claim 10, which is in the form of a tablet. ### Claim 24 (depends on 16) The pharmaceutical composition of claim 16, which is in the form of a tablet. ### Claim 25 (depends on 17) The pharmaceutical composition of claim 17, which is in the form of a tablet. ### Claim 26 (depends on 1) A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 1 to a patient in need thereof. ### Claim 27 (depends on 10) A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 10 to a patient in need thereof. ### Claim 28 (depends on 16) A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 16 to a patient in need thereof. ### Claim 29 (depends on 17) A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 17 to a patient in need thereof. ### Claim 30 (depends on 22) A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 22 to a patient in need thereof. ### Claim 31 (depends on 23) A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 23 to a patient in need thereof. ### Claim 32 (depends on 24) A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 24 to a patient in need thereof. ### Claim 33 (depends on 25) A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 25 to a patient in need thereof. ### Claim 34 A pharmaceutical composition comprising: a) the compound of the formula I as drawn below 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 (CaHPO4.2H2O), 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. ### Claim 35 (depends on 34) The pharmaceutical composition of claim 34, wherein the disintegrant is sodium starch glycolate or a combination of sodium starch glycolate and polyvinylpyrrolidone. ### Claim 36 (depends on 34) The pharmaceutical composition of claim 34, wherein the surfactant is polysorbate 80. ### Claim 37 (depends on 34) The pharmaceutical composition of claim 34, wherein the lubricant comprises magnesium stearate. ### Claim 38 (depends on 34) The pharmaceutical composition of claim 34, which is in the form of a tablet. ### Claim 39 (depends on 36) The pharmaceutical composition of claim 36, which is in the form of a tablet. ### Claim 40 (depends on 34) A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 34 to a patient in need thereof. ### Claim 41 (depends on 38) A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 38 to a patient in need thereof. ### Claim 42 (depends on 39) A method of treating pulmonary arterial hypertension comprising the administration of a pharmaceutical composition according to claim 39 to a patient in need thereof.