# US 10,864,164 B2 · Tamper-resistant tablet providing immediate drug release > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,864,164 B2 - Document ID: US10864164B2 - Status: Granted - Kind: B2 - Application number: 16/225,418 - Filed: 2018-12-19 - Published: 2019-05-02 - Granted: 2020-12-15 - Earliest claimed: 2011-07-29 - Assignees: GrüNenthal GmbH - Applicants: Grünenthal GmbH - Inventors: Sebastian Schwier; Marcel Haupts; Lutz Barnscheid; Jana Pätz - Web page: https://patentgrep.com/patent/US10864164B2 ## CPC - A61K 9/2081: {with microcapsules or coated microparticles according to A61K9/50} - A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)} - A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} - A61K 31/138: Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377) - A61P 25/04: Centrally acting analgesics, e.g. opioids - 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 invention relates to a tamper-resistant tablet comprising (i) a matrix material in an amount of more than one third of the total weight of the tablet; and (ii) a plurality of coated particulates in an amount of less than two thirds of the total weight of the tablet; wherein said particulates comprise a pharmacologically active compound and a physiologically acceptable polymer, preferably a polyalkylene oxide; and form a discontinuous phase within the matrix material; which preferably provides under in vitro conditions immediate release of the pharmacologically active compound in accordance with Ph. Eur.; and method of using said tablet to treat pain and other conditions. ## Claims ### Claim 1 A tamper-resistant tablet comprising: (i) a matrix material in an amount of at least 40 wt.-% based on a total weight of the tablet; and (ii) a plurality of coated particulates in an amount of less than or equal to 60 wt.-% based on the total weight of the tablet; wherein said coated particulates comprise (a) a pharmacologically active compound selected from the group consisting of stimulants and (b) a physiologically acceptable polymer; wherein the physiologically acceptable polymer is a polyalkylene oxide having a weight average molecular weight of at least 500,000 g/mol; wherein the physiologically acceptable polymer is present in said coated particulates in an amount of at least 25 wt.-% based on a total weight of coated particulates; wherein the coated particulates comprise a coating comprising a coating material comprising a water-soluble polymer selected from the group consisting of cellulose esters, cellulose ethers, poly(meth)acrylates, vinyl polymers, and natural film formers; wherein said coated particulates form a discontinuous phase within the matrix material; wherein said coated particulates do not comprise a disintegrant; and wherein said coated particulates have a breaking strength of at least 300 N; said tablet providing under in vitro conditions immediate release of the pharmacologically active compound in accordance with European Pharmacopoeia (Ph. Eur.). ### Claim 2 (depends on 1) The tablet according to claim 1, which has under in vitro conditions a disintegration time measured in accordance with Ph. Eur. of at most 3 minutes. ### Claim 3 (depends on 1) The tablet according to claim 1, wherein the coated particulates have an average diameter of about 1000±250 μm and/or an average length of about 750±250 μm. ### Claim 4 (depends on 1) The tablet according to claim 1, wherein the content of the polymer is at least 25 wt.-%, based on the total weight of coated particulates. ### Claim 5 (depends on 1) The tablet according to claim 1, wherein the content of the pharmacologically active compound is at least 25 wt.-%, based on the total weight of coated particulates. ### Claim 6 (depends on 1) The tablet according to claim 1, which has a total weight of 500±200 mg and contains (i) 50±10 wt.-% coated particulates having an average particle size of 800±200 μm, wherein the coated particulates comprise 23±10 wt.-% pharmacologically active compound, 22±8 wt.-% physiologically acceptable polymer, optionally, 4.0±2.5 wt.-% plasticizer, and optionally, 0.05±0.03 wt.-% further excipients; and (ii) 49±9 wt.-% matrix material, wherein the matrix material comprises 43±6 wt.-% filler and/or binder, optionally, 5±3 wt.-% disintegrant and optionally, 0.15±0.13 wt.-% lubricant; all wt.-% being expressed relative to the total weight of the tablet. ### Claim 7 (depends on 1) The tablet according to claim 1, wherein the coated particulates are prepared by a process comprising hot melt-extrusion. ### Claim 8 (depends on 1) The tablet according to claim 1, wherein the matrix material is also present in particulate form. ### Claim 9 (depends on 1) The tablet according to claim 1, wherein the matrix material comprises binder, filler, disintegrant and/or lubricant. ### Claim 10 (depends on 1) A method of treating a condition in a patient in need thereof by administering to a patient in need of such treating a tablet comprising an effective amount therefor of a pharmacologically active compound, wherein the tablet is a tablet according to claim 1. ### Claim 11 (depends on 1) The tablet according to claim 1, which, under physiological conditions, releases at least 86% of the pharmacologically active compound originally contained in the tablet within 30 minutes. ### Claim 12 (depends on 1) The tablet according to claim 1, which, under physiological conditions, releases at least 82% of the pharmacologically active compound originally contained in the tablet within 10 minutes. ### Claim 13 (depends on 1) The tablet according to claim 1, wherein the coated particulates comprise a water-soluble coating. ### Claim 14 (depends on 1) The tablet according to claim 1, wherein the coated particulates cannot be pulverized with a hammer or with the assistance of a mortar and pestle. ### Claim 15 A tamper-resistant tablet comprising: (i) a matrix material in an amount of at least 40 wt.-% based on a total weight of the tablet; and (ii) a plurality of coated particulates in an amount of less than or equal to 60 wt.-% based the total weight of the tablet; wherein said coated particulates comprise a pharmacologically active compound and a physiologically acceptable polymer; wherein said pharmacologically active compound is selected from the group consisting of stimulants; wherein the physiologically acceptable polymer is a polyalkylene oxide having a weight average molecular weight of at least 500,000 g/mol; wherein the physiologically acceptable polymer is present in said coated particulates in an amount of at least 25 wt.-% based on a total weight of coated particulates; wherein the coated particulates comprise a coating comprising a coating material comprising a water-soluble polymer selected from the group consisting of cellulose esters, cellulose ethers, poly(meth)acrylates, vinyl polymers, and natural film formers; wherein said coated particulates form a discontinuous phase within the matrix material; wherein said coated particulates do not comprise a disintegrant; and wherein said coated particulates have a breaking strength of at least 300 N; said plurality of coated particulates releasing within 15 minutes at least 60% by weight of the plurality of coated particulates of pharmacologically active compound as monitored in 900 mL 0.1 HCL at 37° C., using a paddle apparatus at 50 rpm; and said tablet providing under in vitro conditions immediate release of the pharmacologically active compound in accordance with European Pharmacopoeia (Ph. Eur.).