# US 10,946,010 B2 · Abuse-resistant pharmaceutical composition for the treatment of opioid dependence > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,946,010 B2 - Document ID: US10946010B2 - Status: Granted - Kind: B2 - Application number: 17/009,702 - Filed: 2020-09-01 - Published: 2020-12-24 - Granted: 2021-03-16 - Earliest claimed: 2011-09-19 - Assignees: Orexo AB - Applicants: Orexo AB - Inventors: Andreas Fischer - Web page: https://patentgrep.com/patent/US10946010B2 ## CPC - A61K 31/485: Morphinan derivatives, e.g. morphine, codeine - 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 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays} - A61K 9/14: Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)} - A61K 9/20: Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)} - A61K 9/2013: {Organic compounds, e.g. phospholipids, fats} - A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates} - A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets} - A61K 9/2095: {Tabletting processes} - A61K 31/4748: forming part of bridged ring systems (strychnine A61K31/475; morphinan derivatives A61K31/485) - A61P 25/04: Centrally acting analgesics, e.g. opioids - A61P 25/30: for treating abuse or dependence - A61P 25/36: Opioid-abuse - 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 There is provided pharmaceutical compositions for the treatment of e.g. opioid dependency comprising microparticles of a pharmacologically-effective amount of buprenorphine, or a pharmaceutically-acceptable salt thereof, in associative admixture with particles comprising a weak acid, or particles comprising weakly-acidic buffer forming materials. The composition may further comprise a disintegrant and/or particles of a pharmacologically-effective amount of naloxone, or a pharmaceutically-acceptable salt thereof. The compositions are useful in the treatment of opioid dependency/addiction and/or pain. ## Claims ### Claim 1 A pharmaceutical composition in the form of a tablet suitable for sublingual administration, which comprises: buprenorphine or a pharmaceutically acceptable salt thereof provided in the form of microparticles, particles comprising a weakly acidic material, which weakly acidic material is citric acid, or particles comprising weakly-acidic buffer-forming materials, which weakly-acidic buffer-forming materials are citric acid and sodium citrate, which microparticles of buprenorphine or salt thereof are, at least in part, in contact with the particles comprising citric acid and/or sodium citrate, naloxone or a pharmaceutically acceptable salt thereof, and a disintegrant, wherein the dose ratio of buprenorphine to naloxone (calculated as the free bases) is about 4:1. ### Claim 2 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the particles comprising citric acid and sodium citrate are separate particles. ### Claim 3 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the naloxone or salt thereof is provided in the form of particles. ### Claim 4 (depends on 3) The pharmaceutical composition as claimed in claim 3, wherein the particles of naloxone or salt thereof are microparticles. ### Claim 5 (depends on 4) The pharmaceutical composition as claimed in claim 4, wherein the microparticles of naloxone or salt thereof and the microparticles of buprenorphine or salt thereof each have a weight based mean diameter of between about 0.5 μm and about 15 μm. ### Claim 6 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the microparticles of buprenorphine or salt thereof have a weight based mean diameter of between about 0.5 μm and about 15 μm. ### Claim 7 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the particles comprising citric acid are of a size that is in the range of about 1 μm to about 1000 μm. ### Claim 8 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the particles comprising sodium citrate are of a size that is in the range of about 1 μm to about 1000 μm. ### Claim 9 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the disintegrant is selected from the group croscarmellose sodium, sodium starch glycolate, crosslinked polyvinylpyrrolidone, and mixtures thereof. ### Claim 10 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the disintegrant is in particulate form, having a weight based mean diameter of between about 0.1 μm and about 100 μm. ### Claim 11 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the disintegrant is present in an amount of about 0.5% to about 15% by weight, based upon the total weight of the composition. ### Claim 12 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the per tablet dosage of buprenorphine is about 0.1 mg to about 15 mg (calculated as free base). ### Claim 13 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the per tablet dosage of buprenorphine (calculated as the free base) is 11.4 mg, 8.6 mg, 5.7 mg, 2.9 mg, or 1.4 mg. ### Claim 14 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the microparticles of buprenorphine or salt thereof are present in an amount of about 0.1% to about 10% by weight, based upon the total weight of the composition. ### Claim 15 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the naloxone or salt thereof are present in an amount of about 0.125% to about 5% by weight, based upon the total weight of the composition. ### Claim 16 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the particles comprising citric acid are present in an amount of about 1% to about 10% by weight, based upon the total weight of the composition. ### Claim 17 (depends on 1) The pharmaceutical composition as claimed in claim 1, wherein the particles comprising sodium citrate are present in an amount of about 1% to about 15% by weight, based upon the total weight of the composition. ### Claim 18 (depends on 1) The pharmaceutical composition as claimed in claim 1, further comprising a binder, carrier particles, or both. ### Claim 19 (depends on 18) The pharmaceutical composition as claimed in claim 18, wherein the binder is present in an amount of about 0.5 to about 20% by weight, based upon the total weight of the composition. ### Claim 20 (depends on 19) The pharmaceutical composition as claimed in claim 19, wherein the binder is a cellulose gum or microcrystalline cellulose. ### Claim 21 (depends on 1) The pharmaceutical composition as claimed in claim 1, further comprising one or more of a lubricant, a flavoring, a sweetener, an antioxidant, a gliding agent, and a preservative.