# US 8,465,776 B2 · Granule and orally disintegrating tablet comprising oxycodone > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,465,776 B2 - Document ID: US8465776B2 - Status: Granted - Kind: B2 - Application number: 12/376,060 - Filed: 2007-07-31 - Published: 2009-12-10 - Granted: 2013-06-18 - Earliest claimed: 2006-08-04 - Assignees: Ethypharm - Applicants: Didier Hoarau - Inventors: Didier Hoarau - Web page: https://patentgrep.com/patent/US8465776B2 ## CPC - A61K 9/0056: {Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals} - A61K 9/167: {with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface (with further drug-free outer coating A61K9/5073)} - A61K 9/2081: {with microcapsules or coated microparticles according to A61K9/50} - A61P 25/04: Centrally acting analgesics, e.g. opioids - A61K 9/5078: {with drug-free core} - 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 present invention relates to granules comprising oxycodone, as well as to orally disintegrating tablets including same and optionally acetaminophen. ## Claims ### Claim 1 A granule consisting essentially of a neutral core coated by: (a) oxycodone or a pharmaceutically acceptable salt of oxycodone, and (b) at least a binding agent, said oxycodone coating being further coated by a subcoat consisting of a compound soluble in gastric fluids and optionally an antistatic agent, wherein said subcoat is further coated by a taste-masking coating consisting of a polymer or copolymer with dialkylaminoalkyl(meth)acrylate units, which is insoluble at a pH above 5.5 but is soluble in gastric juice, and optionally an antistatic agent or a pore-forming agent, wherein the subcoat is adapted to avoid direct contact between the oxycodone or the pharmaceutically acceptable salt of oxycodone and the taste-masking coating such that degradation of oxycodone is inhibited. ### Claim 2 (depends on 1) The granule according to claim 1, wherein the oxycodone comprises oxycodone hydrochloride. ### Claim 3 (depends on 1) The granule according to claim 1, wherein the compound soluble in gastric fluid and the binder are independently selected from the group consisting of: cellulose-based polymers; polyvinyl alcohols; alginic acid; sodium alginate; starch; pregelatinized starch; sucroses; sucrose derivatives; guar gum; polyethylene glycols; and mixtures and copolymers thereof. ### Claim 4 (depends on 3) The granule according to claim 3, wherein the compound soluble in gastric fluid is a cellulose-based polymer selected from the group consisting of hydroxypropylmethylcellulose polymer, hydroxypropylcellulose polymer and hydroxyethylcellulose acrylic polymer. ### Claim 5 (depends on 1) The granule according to claim 1, wherein the polymer or copolymer with dialkylaminoalkyl(meth)acrylate units is a copolymer of dimethylaminoethyl methacrylate, methylmethacrylate and n-butyl methacrylate. ### Claim 6 (depends on 1) The granule according to claim 1, wherein the pore-forming agent is hydroxypropylmethylcellulose. ### Claim 7 (depends on 1) A process for the manufacture of granules according to claim 1, wherein a suspension of oxycodone in a hydroalcoholic medium is sprayed onto neutral cores. ### Claim 8 An orally disintegrating tablet comprising: (a) granules consisting essentially of a neutral core coated by: (a) oxycodone or a pharmaceutically acceptable salt of oxycodone, and (b) at least a binder, said oxycodone coating being further coated by a subcoat consisting of a compound soluble in gastric fluid and optionally an antistatic agent; wherein said subcoat is further coated by a taste-masking coating consisting of a polymer or copolymer with dialkylaminoalkyl(meth)acrylate units, which is insoluble at a pH above 5.5 but is soluble in gastric juice, and optionally an antistatic or a pore-forming agent, wherein the subcoat is adapted to avoid direct contact between the oxycodone or the pharmaceutically acceptable salt of oxycodone and the taste-masking coating such that degradation of oxycodone is inhibited and (b) at least one disintegrant and at least one diluent, wherein said disintegrant comprises crospovidone. ### Claim 9 (depends on 8) The orally disintegrating tablet according to claim 8, further comprising an anti-oxidant agent. ### Claim 10 (depends on 9) The orally disintegrating tablet according to claim 9, wherein the anti-oxidant agent is ascorbyl palmitate. ### Claim 11 An orally disintegrating tablet comprising: (a) granules consisting essentially of a neutral core coated by: (i) oxycodone or a pharmaceutically acceptable salt of oxycodone, and (ii) at least one binding agent, said oxycodone coating being further coated by a subcoat consisting of a compound soluble in gastric fluid and optionally an antistatic agent; wherein said subcoat is further coated by a taste-masking coating consisting of a polymer or copolymer with dialkylaminoalkyl(meth)acrylate units, which is insoluble at a pH above 5.5 but is soluble in gastric juice, and optionally an antistatic or a pore-forming agent, wherein the subcoat is adapted to avoid direct contact between the oxycodone or the pharmaceutically acceptable salt of oxycodone and the taste-masking coating such that degradation of oxycodone is inhibited (b) acetaminophen which is not included within said granules, and (c) at least one disintegrant and at least one soluble diluent agent, wherein said disintegrant comprises crospovidone. ### Claim 12 (depends on 11) The orally disintegrating tablet according to claim 11, wherein the compound soluble in gastric fluids is selected from the group consisting of: cellulose-based polymers; polyvinyl alcohols; alginic acid; sodium alginate; starch; pregelatinized starch; sucroses; sucrose derivatives; guar gum; polyethylene glycols, and mixtures and copolymers thereof. ### Claim 13 (depends on 12) The orally disintegrating tablet according to claim 12, wherein the compound soluble in gastric fluid is hydroxypropylmethylcellulose polymer, hydroxypropylcellulose polymer or hydroxyethylcellulose acrylic polymer. ### Claim 14 (depends on 11) The orally disintegrating tablet according to claim 11, further comprising an anti-oxidant agent. ### Claim 15 (depends on 14) The orally disintegrating tablet according to claim 14, wherein the anti-oxidant agent is ascorbyl palmitate. ### Claim 16 (depends on 11) The orally disintegrating tablet according to claim 11, wherein the pore-forming agent is hydroxypropylmethylcellulose. ### Claim 17 (depends on 11) The orally disintegrating tablet according to claim 11, comprising from 2.5 to 10 mg oxycodone and from 80 to 750 mg acetaminophen. ### Claim 18 (depends on 1) A method for reducing pain in a patient, comprising oral administration to said patient of granules according to claim 1. ### Claim 19 (depends on 8) The method for reducing pain in a patient, comprising oral administration to said patient of a tablet according to claim 8. ### Claim 20 (depends on 8) A process for manufacturing an orally disintegrating tablet according to claim 8, comprising the steps of: (a) spraying onto neutral cores a suspension in a solvent comprising: (i) oxycodone or a pharmaceutically acceptable salt of oxycodone, and (ii) at least one binding agent, so as to obtain pellets, (b) applying the subcoat onto said pellets to obtain coated pellets, (c) optionally drying said coated pellets, (d) applying onto said coated pellets the taste-masking coating to obtain granules, (e) optionally applying an antistatic coating onto said granules, (f) mixing acetaminophen with said granules, at least one disintegrant comprising crospovidone and at least one diluent agent, so as to obtain a mixture, and (g) tableting said mixture, wherein the solvent used in at least one of steps (a) and (b) is a hydroalcoholic solvent. ### Claim 21 (depends on 11) The orally disintegrating tablet according to claim 11 comprising acetaminophen and oxycodone as the only active ingredients, said tablet having an oxycodone content, after dry storage at 80° C. for 14 days of at least 90% of the initial oxycodone content before storage. ### Claim 22 A granule consisting essentially of a neutral core coated by: (a) oxycodone or a pharmaceutically acceptable salt of oxycodone, and (b) at least a binding agent, said oxycodone coating being further coated by a subcoat consisting of a compound soluble in gastric fluids and optionally an antistatic agent, wherein said subcoat is further coated by a taste-masking coating consisting of a polymer or copolymer with dialkylaminoalkyl(meth)acrylate units which is insoluble at a pH above 5.5 but is soluble in gastric juice, and optionally an antistatic agent or a pore-forming agent, wherein the subcoat is adapted to avoid direct contact between the oxycodone or the pharmaceutically acceptable salt of oxycodone and the taste-masking coating such that at least 90% of oxycodone or pharmaceutically acceptable salt of oxycodone remains after storage for 14 days at 80° C. dry heat. ### Claim 23 An orally disintegrating tablet comprising: (a) granules consisting essentially of a neutral core coated by: (i) oxycodone or a pharmaceutically acceptable salt of oxycodone, and (ii) at least a binder, said oxycodone coating being further coated by a subcoat consisting of a compound soluble in gastric fluid and optionally an antistatic agent; wherein said subcoat is further coated by a taste-masking coating consisting of a polymer or copolymer with dialkylaminoalkyl(meth)acrylate units which is insoluble at a pH above 5.5 but is soluble in gastric juice and optionally an antistatic or a pore-forming agent, wherein the subcoat is adapted to avoid direct contact between the oxycodone or the pharmaceutically acceptable salt of oxycodone and the taste-masking coating such that at least 90% of oxycodone or pharmaceutically acceptable salt of oxycodone remains after storage for 14 days at 80° C. dry heat and (b) at least one disintegrant and at least one diluent, wherein said disintegrant comprises crospovidone. ### Claim 24 An orally disintegrating tablet comprising: (a) granules consisting essentially of a neutral core coated by: (i) oxycodone or a pharmaceutically acceptable salt of oxycodone, and (ii) at least one binding agent, said oxycodone coating being further coated by a subcoat consisting of a compound soluble in gastric fluid and optionally an antistatic agent; wherein said subcoat is further coated by a taste-masking coating consisting of a polymer or copolymer with dialkylaminoalkyl(meth)acrylate units, which is insoluble at a pH above 5.5 but is soluble in gastric juice, and optionally an antistatic or a pore-forming agent, wherein the subcoat is adapted to avoid direct contact between the oxycodone or the pharmaceutically acceptable salt of oxycodone and the taste-masking coating such that at least 90% of oxycodone or pharmaceutically acceptable salt of oxycodone remains after storage for 14 days at 80° C. dry heat; (b) acetaminophen which is not included within said granules; and (c) at least one disintegrant and at least one diluent agent, wherein said disintegrant comprises crospovidone.