# US 10,117,838 B2 · Pharmaceutical composition for the prolonged release of trimetazidine > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,117,838 B2 - Document ID: US10117838B2 - Status: Granted - Kind: B2 - Application number: 13/753,313 - Filed: 2013-01-29 - Published: 2013-08-08 - Granted: 2018-11-06 - Earliest claimed: 2012-02-03 - Assignees: Les Laboratoires Servier - Applicants: Les Laboratoires Servier - Inventors: Patrick Genty; Christophe Hermelin; Jean-Manuel Pean - Web page: https://patentgrep.com/patent/US10117838B2 ## CPC - A61K 9/5047: {Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose} - A61K 9/5078: {with drug-free core} - A61K 31/495: having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) - A61K 47/02: Inorganic compounds - A61P 1/08: for nausea, cinetosis or vertigo; Antiemetics - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/08: Vasodilators for multiple indications - 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 27/02: Ophthalmic agents - A61P 27/16: Otologicals - 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 Composition for the prolonged release of trimetazidine wherein the inner phase comprises trimetazidine and the outer layer comprises a retardant and an anti-agglomerant. ## Claims ### Claim 1 A pharmaceutical composition for prolonged release of trimetazidine, comprising: an inner phase which comprises trimetazidine, or a pharmaceutically acceptable salt thereof, coated onto a neutral core; and an outer layer consisting of a retardant, an anti-agglomerant, and a plasticiser, wherein the percentage of retardant is from 5.5% to 8% of the total weight of the inner phase; and the percentage of anti-agglomerant is from 100% to 200% of the weight of the retardant. ### Claim 2 (depends on 1) The composition according to claim 1, wherein the retardant is selected from the group consisting of ethylcellulose, cellulose acetate, cellulose acetate butyrate, cellulose acetate propionate, cellulose acetate phthalate, hydroxypropyl methylcellulose acetate succinate and polymethacrylates. ### Claim 3 (depends on 1) The composition according to claim 1, wherein the anti-agglomerant is selected from the group consisting of talc, colloidal silicon dioxide, magnesium stearate, stearic acid and sodium fumaryl stearate. ### Claim 4 (depends on 1) The composition according to claim 1, wherein the plasticiser is selected from the group consisting of acetyl tributyl citrate, glycerol triacetate, acetyl triethyl citrate, acetyl ethyl citrate, diethyl sebacate, dibutyl sebacate, ethyl and dibutyl phthalate, polyethylene glycol, glycerol and propylene glycol. ### Claim 5 (depends on 1) The composition according to claim 1, wherein the percentage of plasticiser is between 5% and 50% inclusive of the weight of the retardant. ### Claim 6 (depends on 1) The composition according to claim 1, wherein the inner phase further comprises a binder. ### Claim 7 (depends on 6) The composition according to claim 6, wherein the binder is selected from the group consisting of hydroxypropyl methylcellulose, hydroxypropylcellulose, maltodextrin, polyvinylpyrrolidone and microcrystalline cellulose. ### Claim 8 (depends on 6) The composition according to claim 6, wherein the binder is hydroxypropyl methylcellulose. ### Claim 9 (depends on 1) The composition according to claim 1, wherein the neutral core comprises sucrose, sucrose and starch, or microcrystalline cellulose. ### Claim 10 (depends on 1) The composition according to claim 1, wherein the trimetazidine is in the form of the dihydrochloride. ### Claim 11 (depends on 1) The composition according to claim 1, wherein the composition contains 80 mg of trimetazidine dihydrochloride as the pharmaceutically acceptable salt of trimetazidine. ### Claim 12 (depends on 1) The composition according to claim 1, wherein the retardant is ethylcellulose; the anti-agglomerant is talc; and the plasticiser is acetyl tributyl citrate and wherein: the acetyl tributyl citrate is present in an amount of from 5% to 30% relative to the weight of the retardant; the ethylcellulose is present in an amount of from 5.5% to 8% relative to the total weight of the inner phase; and the talc is present in an amount from 100% to 200% relative to the weight of the retardant. ### Claim 13 (depends on 8) The composition according to claim 8, wherein the inner phase comprises: from 15% to 40% of neutral core relative to the total weight of the composition; from 35% to 70% of trimetazidine relative to the total weight of the composition; from 1% to 15% of hydroxypropyl methylcellulose relative to the total weight of the composition. ### Claim 14 (depends on 13) The composition according to claim 13, wherein the neutral core comprises minigranules, and wherein the outer layer consists of ethylcellulose as the retardant, talc as the anti-agglomerant, and acetyl tributyl citrate as the plasticiser. ### Claim 15 (depends on 1) The composition according to claim 1, wherein the level of in vitro dissolution of the composition is from 8% to 28% of the trimetazidine released by 4 hours and from 37% to 57% of the trimetazidine released by 8 hours and more than 75% of the trimetazidine released by 24 hours and is selected so that the therapeutically efficacious plasma concentration of trimetazidine obtained in vivo is prolonged over 24 hours following administration of the composition. ### Claim 16 (depends on 14) The composition according to claim 14, wherein the neutral core comprises 80 mg of trimetazidine dihydrochloride, as the pharmaceutically acceptable salt of trimetazidine, 36.677 mg of neutral minigranules, and 6.40 mg of hydroxypropyl methylcellulose, and the outer layer consists of 1.2 mg of acetyl tributyl citrate, 8 mg of ethylcellulose, and 12 mg of talc.