# US 10,478,399 B2 · Modified release tablet composition comprising mirabegron > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,478,399 B2 - Document ID: US10478399B2 - Status: Granted - Kind: B2 - Application number: 15/730,988 - Filed: 2017-10-12 - Published: 2019-04-18 - Granted: 2019-11-19 - Earliest claimed: 2017-10-12 - Assignees: Synthon BV - Applicants: Synthon B.V. - Inventors: Agnes Fernandez Pena; Onne Peter Hilbert Backers; Jose Velada Calzada - Web page: https://patentgrep.com/patent/US10478399B2 ## CPC - A61K 9/2031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers} - A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 9/2086: {Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat (active cores with a complete drug-free outer coat A61K9/28)} - A61K 9/2095: {Tabletting processes} - A61K 31/426: 1,3-Thiazoles - A61K 31/4725: containing further heterocyclic rings - 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) ## Abstract The present invention relates to a pharmaceutical composition, particularly a modified release tablet composition comprising mirabegron or a pharmaceutically acceptable salt thereof and to a process for preparing such a composition. ## Claims ### Claim 1 A modified release tablet composition comprising: a) 5 to 25 wt % with respect to the total weight of the uncoated tablet of a therapeutically effective dose of mirabegron or a pharmaceutically acceptable salt thereof; and b) polyethylene oxide (PEO) having an average molecular weight of approximately 7,000,000 or a viscosity of 7500 to 10000 cps at a 1% aqueous solution at 25° C. and polyethylene glycol (PEG) having an average molecular weight of approximately 6000 to 10000, wherein the weight ratio PEO to PEG ranges from 1:3 to 1:4.5; wherein said tablet exhibits an in vitro dissolution profile that meets the following release criteria: 15%-35% of mirabegron is released within 1 hour, at least 50% of mirabegron is released within 2 hours, and at least 90% of mirabegron is released within 3 hours, wherein said dissolution profile is measured in 250 ml phosphate buffer (pH 6.8) using USP apparatus 3 at 20 dpm and 37° C. ### Claim 2 (depends on 1) The modified release tablet composition according to claim 1, wherein the weight ratio PEO to PEG ranges from 1:3 to 1:4. ### Claim 3 (depends on 1) The modified release tablet composition according to claim 1, further comprising microcrystalline cellulose (MCC). ### Claim 4 (depends on 1) The modified release tablet composition according to claim 1, wherein mirabegron has a particle size distribution of D90 between 10 and 60 μm. ### Claim 5 (depends on 1) The modified release tablet composition according to claim 1, wherein said polyethylene glycol (PEG) has an average molecular weight of approximately 8000. ### Claim 6 (depends on 1) The modified release tablet composition according to claim 1, wherein said tablet is stable such that a dissolution profile obtained after storing a tablet for 6 months at 40° C. and 75% RH meets said release criteria. ### Claim 7 (depends on 1) The modified release tablet composition according to claim 1, wherein the weight ratio PEO to PEG ranges from 1:3.2 to 1:3.8 and said polyethylene glycol (PEG) has an average molecular weight of approximately 8000. ### Claim 8 (depends on 1) The modified release tablet composition according to claim 1, wherein said tablet contains 25 mg or 50 mg of mirabegron. ### Claim 9 (depends on 1) A multilayer tablet comprising the modified release tablet composition according to claim 1. ### Claim 10 (depends on 9) The multilayer tablet according to claim 9, which is a bilayer tablet. ### Claim 11 (depends on 9) The multilayer tablet according to claim 9, further comprising solifenacin. ### Claim 12 A modified release tablet composition comprising the following ingredients: a) a therapeutically effective dose of mirabegron or a pharmaceutically acceptable salt thereof in an amount of from 5 to 25 wt % with respect to the total weight of the uncoated tablet; b) polyethylene oxide (PEO) having an average molecular weight of approximately 7,000,000 or a viscosity of 7500 to 10000 cps at a 1% aqueous solution at 25° C. and polyethylene glycol (PEG) having an average molecular weight of approximately 6000 to 10000, wherein the weight ratio PEO to PEG ranges from 1:3 to 1:4.5; c) a binder in an amount of from 1 to 5 wt % with respect to the total weight of the uncoated tablet; d) a lubricant in an amount from 0.05% to 5 wt % with respect to the total weight of the uncoated tablet; and e) optionally microcrystalline cellulose (MCC); wherein said tablet exhibits an in vitro dissolution profile that meets the following release criteria: 15%-35% of mirabegron is released within 1 hour, at least 50% of mirabegron is released within 2 hours, and at least 90% of mirabegron is released within 3 hours, wherein said dissolution profile is measured in 250 ml phosphate buffer (pH 6.8) using USP apparatus 3 at 20 dpm and 37° C. ### Claim 13 (depends on 12) The modified release tablet composition according to claim 12, prepared by a dry-granulation process, which process comprises: a) mixing mirabegron, polyethylene oxide, polyethylene glycol and one or more further pharmaceutically acceptable excipients to form a mixture; b) compacting the resulting mixture to form a granulate; c) further mixing the obtained granulate with one or more further pharmaceutically acceptable excipients to form a further mixture; d) compressing the mixture obtained in step (c) into a tablet; and e) optionally, coating the tablet. ### Claim 14 (depends on 13) The modified release tablet composition according to claim 13, wherein the compacting step (b) is performed by slugging or by a roller compactor. ### Claim 15 (depends on 13) The modified release tablet composition according to claim 13, wherein the granules have a particle size distribution D90 equal or less than 1 mm. ### Claim 16 (depends on 12) The modified release tablet composition according to claim 12, wherein said polyethylene glycol (PEG) has an average molecular weight of approximately 8000. ### Claim 17 (depends on 12) The modified release tablet composition according to claim 12, wherein said binder is hydroxypropylcellulose. ### Claim 18 (depends on 12) The modified release tablet composition according to claim 12, wherein the weight ratio PEO to PEG ranges from 1:3 to 1:4. ### Claim 19 (depends on 12) The modified release tablet composition according to claim 12, wherein mirabegron has a particle size distribution of D90 between 10 and 60 μm.