# US 10,117,936 B2 · Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,117,936 B2 - Document ID: US10117936B2 - Status: Granted - Kind: B2 - Application number: 14/776,624 - Filed: 2014-03-14 - Published: 2016-02-04 - Granted: 2018-11-06 - Earliest claimed: 2013-03-15 - Assignees: Tonix Pharma Holdings Limited - Applicants: Tonix Pharma Holdings Limited - Inventors: Marino Nebuloni; Patrizia Colombo - Web page: https://patentgrep.com/patent/US10117936B2 ## CPC - A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)} - A61K 9/145: {with organic compounds} - A61K 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules} - A61K 9/1688: {resulting in pure drug agglomerate optionally containing up to 5% of excipient} - A61K 9/1694: {resulting in granules or microspheres of the matrix type containing more than 5% of excipient} - A61K 31/047: having two or more hydroxy groups, e.g. sorbitol - A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} - A61K 47/02: Inorganic compounds - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 21/00: Drugs for disorders of the muscular or neuromuscular system - A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/08: Antiepileptics; Anticonvulsants - A61P 25/20: Hypnotics; Sedatives - A61P 25/22: Anxiolytics - A61P 25/24: Antidepressants - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 37/02: Immunomodulators - A61P 39/00: General protective or antinoxious agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole - 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 pharmaceutical compositions and methods of manufacturing the same, comprising a eutectic of Cyclobenzaprine HCl and mannitol or Amitriptyline HCl and mannitol. ## Claims ### Claim 1 A pharmaceutical composition comprising a eutectic of 25%±2% mannitol and 75%±2% Cyclobenzaprine HCl by weight, wherein the mannitol is β-mannitol or δ-mannitol. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1, wherein the Cyclobenzaprine HCl is micronized Cyclobenzaprine HCl. ### Claim 3 (depends on 1) The pharmaceutical composition of claim 1, further comprising a basifying agent. ### Claim 4 (depends on 3) The pharmaceutical composition of claim 3, wherein the basifying agent is K2HPO4. ### Claim 5 (depends on 3) The pharmaceutical composition of claim 3, wherein the basifying agent is Na2HPO4. ### Claim 6 (depends on 3) The pharmaceutical composition of claim 3, wherein the basifying agent is anhydrous trisodium citrate. ### Claim 7 (depends on 1) A method of manufacturing a pharmaceutical composition of claim 1, comprising mixing the Cyclobenzaprine HCl and the mannitol or milling the Cyclobenzaprine HCl and the mannitol. ### Claim 8 (depends on 7) The method of claim 7, comprising milling the Cyclobenzaprine HCl and the mannitol. ### Claim 9 (depends on 8) The method of claim 8, wherein, the Cyclobenzaprine HCl and the mannitol are milled in a high shear granulator. ### Claim 10 (depends on 7) The method of claim 7, comprising mixing the Cyclobenzaprine HCl and the mannitol. ### Claim 11 (depends on 10) The method of claim 10, wherein the Cyclobenzaprine HCl and the mannitol are mixed via compression. ### Claim 12 (depends on 11) The method of claim 11, wherein the Cyclobenzaprine HCl and the mannitol are compressed via roller compaction. ### Claim 13 (depends on 1) A method of manufacturing a pharmaceutical composition of claim 1, comprising spray drying a mixture of the Cyclobenzaprine HCl and the mannitol. ### Claim 14 (depends on 7) The method of claim 7, wherein the Cyclobenzaprine HCl is micronized Cyclobenzaprine HCl. ### Claim 15 (depends on 7) The method of claim 7, wherein the pharmaceutical composition further comprises a basifying agent. ### Claim 16 (depends on 15) The method of claim 15, wherein the basifying agent is K2HPO4. ### Claim 17 (depends on 15) The method of claim 15, wherein the basifying agent is Na2HPO4. ### Claim 18 (depends on 15) The method of claim 15, wherein the basifying agent is anhydrous trisodium citrate. ### Claim 19 (depends on 1) The pharmaceutical composition of claim 1, wherein the mannitol in the eutectic is β mannitol. ### Claim 20 (depends on 19) The pharmaceutical composition of claim 19, wherein the eutectic melts at 143.6±3° C. ### Claim 21 (depends on 1) The pharmaceutical composition of claim 1, wherein the mannitol in the eutectic is δ mannitol. ### Claim 22 (depends on 21) The pharmaceutical composition of claim 21, wherein the eutectic melts at 134° C±3° C. ### Claim 23 (depends on 7) The method of claim 7, wherein the mannitol in the eutectic is β mannitol. ### Claim 24 (depends on 23) The method of claim 23, wherein the eutectic melts at 143.6±3° C. ### Claim 25 (depends on 7) The method of claim 7, wherein the mannitol in the eutectic is δ mannitol. ### Claim 26 (depends on 25) The method of claim 25, wherein the eutectic melts at 134° C±3° C. ### Claim 27 (depends on 13) The method of claim 13, wherein the pharmaceutical composition further comprises a basifying agent. ### Claim 28 (depends on 27) The method of claim 27, wherein the basifying agent is K2HPO4. ### Claim 29 (depends on 27) The method of claim 27, wherein the basifying agent is Na2HPO4. ### Claim 30 (depends on 27) The method of claim 27, wherein the basifying agent is anhydrous trisodium citrate. ### Claim 31 (depends on 13) The method of claim 13, wherein the mannitol in the eutectic is δ mannitol. ### Claim 32 (depends on 31) The method of claim 31, wherein the eutectic melts at 134° C±3° C. ### Claim 33 (depends on 13) The method of claim 13, wherein the mannitol is β-mannitol. ### Claim 34 (depends on 13) The method of claim 13, wherein the spray drying converts the β-mannitol into δ-mannitol.