# US 8,541,026 B2 · Sustained release formulations of opioid and nonopioid analgesics > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,541,026 B2 - Document ID: US8541026B2 - Status: Granted - Kind: B2 - Application number: 11/737,914 - Filed: 2007-04-20 - Published: 2007-12-06 - Granted: 2013-09-24 - Earliest claimed: 2004-09-24 - Assignees: AbbVie Inc. - Applicants: Yihong Qiu; Cheri E Klein - Inventors: Yihong Qiu; Cheri E Klein - Web page: https://patentgrep.com/patent/US8541026B2 ## CPC - A61K 9/209: {containing drug in at least two layers or in the core and in at least one outer layer} - A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets} - A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 9/4808: {characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release (capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084)} - A61K 9/5084: {Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs (tablets containing such a mixture A61K9/2077)} - A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol - A61K 31/485: Morphinan derivatives, e.g. morphine, codeine - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - 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 SRSR solid dosage forms for administering pharmaceutical agents, particularly Hydrocodone and acetaminophen, methods for preparing the dosage forms, and methods for providing therapeutic agents to patients in need of treatment. ## Claims ### Claim 1 A pharmaceutical composition comprising at least two sustained release subunits: a first sustained release subunit that comprises acetaminophen and hydrocodone or an equivalent amount of another acceptable salt or free base of hydrocodone thereof; a second sustained release subunit that comprises acetaminophen and hydrocodone or an equivalent amount of another acceptable salt or free base of hydrocodone thereof; wherein each of the sustained release subunits are in a monoeximic dosage form selected from the group consisting of an osmotic system and a matrix system, wherein each monoexemic osmotic system contains only one membrane to control the rate of drug release, and wherein the sustained release subunits release the drugs contained therein over a period of longer than two hours. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1, wherein the composition contains acetaminophen between about 20 and about 100 times by weight of hydrocodone bitartrate or an equivalent amount of another acceptable salt or free base of hydrocodone thereof. ### Claim 3 (depends on 1) The pharmaceutical composition of claim 1, wherein the first subunit and the second subunit each contain a single rate controlling mechanism. ### Claim 4 (depends on 3) The pharmaceutical composition of claim 3, wherein the single rate controlling mechanism comprises at least one pharmaceutically acceptable hydrophobic rate controlling material, a pharmaceutically acceptable hydrophilic rate controlling material, a non-polymer rate controlling material or any combinations thereof. ### Claim 5 (depends on 1) The pharmaceutical composition of claim 1, wherein the first and second subunit each comprise a monoeximic dosage form. ### Claim 6 (depends on 5) The pharmaceutical composition of claim 5, wherein the first and second subunits comprise the same type of monoeximic dosage forms or different types of monoeximic dosage forms. ### Claim 7 (depends on 6) The pharmaceutical composition of claim 6, wherein each of the monoeximic dosage forms comprises a matrix system. ### Claim 8 (depends on 6) The pharmaceutical composition of claim 6, wherein each of the monoeximic dosage forms comprises an osmotic system. ### Claim 9 (depends on 6) The pharmaceutical composition of claim 6, wherein one of the monoeximic dosage forms comprises a matrix system and the other monoeximic dosage forms comprises an osmotic system. ### Claim 10 (depends on 1) The pharmaceutical composition of claim 1, wherein the composition is capable of reducing pain intensity in a patient within about 1 hour. ### Claim 11 (depends on 10) The pharmaceutical composition of claim 10, wherein the composition releases at least 90% of the hydrocodone and acetaminophen in vitro within 12 hours. ### Claim 12 (depends on 10) The pharmaceutical composition of claim 10, wherein the composition releases at least 90% of the hydrocodone and acetaminophen in vitro within about 8 hours. ### Claim 13 (depends on 1) The pharmaceutical composition of claim 1, wherein the dosage form is adapted to release about 19% to 49% of the hydrocodone and acetaminophen in vitro within 0.75 hours. ### Claim 14 (depends on 13) The pharmaceutical composition of claim 13, wherein the dosage form releases at least 90% of the hydrocodone and acetaminophen within 12 hours. ### Claim 15 (depends on 13) The pharmaceutical composition of claim 13, wherein the dosage releases at least 90% of the hydrocodone and acetaminophen within about 8 hours. ### Claim 16 (depends on 1) The pharmaceutical composition of claim 1, wherein the dosage form comprises about 500 mg of acetaminophen and about 15 mg of hydrocodone bitartrate. ### Claim 17 (depends on 1) The pharmaceutical composition of claim 1, wherein the human in which the AUC and Cmax for both hydrocodone and acetaminophen is measured is a non-poor CYP2D6 metabolizer, and wherein the dosage form produces a Cmax for hydromorphone in the human of between about 0.12 ng/ml and about 0.35 ng/ml after a single dose of 30 mg of hydrocodone bitartrate. ### Claim 18 (depends on 1) The pharmaceutical composition of claim 1, wherein the plasma concentration for hydrocodone 12 hours after a single 30 mg dose of hydrocodone bitartrate is between about 11.0 ng/ml and about 27.4 ng/ml. ### Claim 19 (depends on 1) The pharmaceutical composition of claim 1, wherein when a single 1000 mg dose of acetaminophen is administered to the human, the plasma concentration for acetaminophen 12 hours after administration is between about 0.7 μg/ml and about 2.5 μg/ml. ### Claim 20 (depends on 1) The pharmaceutical composition of claim 1, wherein when a single 1000 mg dose of acetaminophen is administered to the human, the plasma concentration for acetaminophen 12 hours after administration is between about 0.7 μg/ml and about 2.5 μg/ml. ### Claim 21 (depends on 1) The pharmaceutical composition of claim 1, wherein after a single dose of 30 mg of hydrocodone bitartrate, the plasma concentration profile exhibits a width at half height for hydrocodone of between about 6.4 hours and about 19.6 hours. ### Claim 22 (depends on 1) The pharmaceutical composition of claim 1, wherein after a single dose of 30 mg of hydrocodone bitartrate, the plasma concentration profile exhibits a width at half height for hydrocodone of between about 8.4 hours and about 19.6 hours. ### Claim 23 (depends on 1) The sustained pharmaceutical composition of claim 1, wherein after a single does of 1000 mg of acetaminophen, the plasma concentration profile exhibits a width at half height for acetaminophen of between about 0.8 hours and about 12.3 hours.