# US 10,441,544 B2 · Extended release pharmaceutical formulation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,441,544 B2 - Document ID: US10441544B2 - Status: Granted - Kind: B2 - Application number: 15/728,695 - Filed: 2017-10-10 - Published: 2019-04-11 - Granted: 2019-10-15 - Earliest claimed: 2017-10-10 - Assignees: Douglas Pharmaceuticals Limited - Applicants: Douglas Pharmaceuticals Ltd. - Inventors: Paul William Glue; Natalie June Medlicott; Peter William Surman - Web page: https://patentgrep.com/patent/US10441544B2 ## CPC - A61K 9/28: Dragees; Coated pills or tablets {, e.g. with film or compression coating (A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209)} - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/2031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers} - A61K 9/2813: {Inorganic compounds} - A61K 9/2853: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)} - A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - 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 invention provides an oral extended release formulation for the treatment of treatment-resistant depression and treatment-resistant anxiety. ## Claims ### Claim 1 A solid, oral, extended release pharmaceutical tablet comprising: (A) a core comprising: i) a therapeutically effective amount of an active agent selected from the group consisting of ketamine, pharmaceutically acceptable salts thereof, and combinations thereof, wherein the active agent is present at a concentration of at least about 12% ketamine base w/w of the core; ii) at least one high molecular weight polyethylene oxide (PEO) that is cured, wherein said high molecular weight PEO has an approximate molecular weight of about 7 million, based upon rheological measurements, and is present in an amount of at least 75% (by weight) of the core; and iii) magnesium stearate is present at a concentration of about 1% to about 3% by weight; (B) a coating on said core, wherein said tablet is crush resistant and has a breaking strength of at least about 200 N; and wherein said tablet provides a pharmacokinetic parameter selected from the group consisting of: a mean ketamine Cmax of about 10 ng/mL after administration of a single dose of 60 mg to a patient; a mean ketamine Cmax of about 16 ng/mL after administration of a single dose of 120 mg to a patient; a mean ketamine Cmax of about 38 ng/mL after administration of a single dose of 240 mg; a mean ketamine AUC0-∞ of about 79 ng·h/mL after administration of a single dose of 60 mg; a mean ketamine AUC0-∞ of about 197 ng·h/mL after administration of a single dose of 120 mg to a patient; a mean ketamine AUC0-∞ of about 385 ng·h/mL after administration of a single dose of 240 mg. ### Claim 2 (depends on 1) The tablet of claim 1 wherein the dosage amount of active agent is selected from the group consisting of about 30 mg, about 60 mg, about 120 mg, and about 240 mg. ### Claim 3 (depends on 1) The tablet of claim 1 wherein the tablet is cured at a temperature of about 70° C. to about 75° C. ### Claim 4 (depends on 1) The tablet of claim 1 wherein the coating comprises: i) hydroxypropylmethylcellulose; ii) titanium dioxide; and iii) polyethylene glycol. ### Claim 5 (depends on 1) The tablet of claim 1 wherein the tablet is suitable for once daily administration or twice-daily administration to a subject. ### Claim 6 (depends on 1) The tablet of claim 1 wherein the tablet has no or minimal dissociative side effects upon administration to a patient. ### Claim 7 A solid, oral, extended release pharmaceutical tablet comprising: (A) a core comprising: i) a therapeutically effective amount of an active agent selected from the group consisting of ketamine, pharmaceutically acceptable salts thereof, and combinations thereof, wherein the active agent is present at a concentration of at least about 12% ketamine base w/w of the core; ii) at least one high molecular weight polyethylene oxide (PEO) that is cured, wherein said high molecular weight PEO has an approximate molecular weight of about 7 million, based upon rheological measurements, and is present in an amount of at least 75% (by weight) of the core; and iii) magnesium stearate is present at a concentration of about 1% to about 3% by weight; (B) a coating on said core, wherein said tablet is crush resistant and has a breaking strength of at least about 200 N; and wherein said tablet provides a pharmacokinetic parameter selected from the group consisting of: a mean ketamine Cmax of about 12 ng/mL after administration of 5 doses of 60 mg administered every 12 hours to a patient; a mean ketamine Cmax of about 21 ng/mL after administration of 5 doses of 120 mg administered every 12 hours to a patient; a mean ketamine Cmax of about 42 ng/mL after administration of 5 doses of 240 mg administered every 12 hours to a patient; a mean ketamine AUC0-12 of about 74 ng·h/mL after administration of 5 doses of 60 mg administered every 12 hours to a patient; a mean ketamine AUC0-12 of about 133 ng·h/mL after administration of 5 doses of 120 mg administered every 12 hours to a patient; a mean ketamine AUC0-12 of about 217 ng·h/mL after administration of 5 doses of 240 mg administered every 12 hours to a patient. ### Claim 8 (depends on 7) The tablet of claim 7 wherein the tablet is cured at a temperature of about 70° C. to about 75° C. ### Claim 9 (depends on 7) The tablet of claim 7 wherein the coating comprises: i) hydroxypropylmethylcellulose; ii) titanium dioxide; and iii) polyethylene glycol. ### Claim 10 (depends on 7) The tablet of claim 7 wherein the tablet is suitable for once daily administration or twice-daily administration to a subject. ### Claim 11 (depends on 7) The tablet of claim 7 wherein the tablet has no or minimal dissociative side effects upon administration to a patient.