# US 10,864,176 B2 · Eutectic formulations of cyclobenzaprine hydrochloride and amitriptyline hydrochloride

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- Number: US 10,864,176 B2
- Document ID: US10864176B2
- Status: Granted
- Kind: B2
- Application number: 16/140,105
- Filed: 2018-09-24
- Published: 2019-01-24
- Granted: 2020-12-15
- 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/US10864176B2

## 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 of comprising a eutectic of Amitriptyline HCl and mannitol, wherein the pharmaceutical composition comprises amounts of Amitriptyline HCl and mannitol selected from: 40%±2% Amitriptyline HCl and 60%±2% mannitol, 45%±2% Amitriptyline HCl and 55%±2% mannitol, 50%±2% Amitriptyline HCl and 50%±2% mannitol, 55%±2% Amitriptyline HCl and 45%±2% mannitol, 60%±2% Amitriptyline HCl and 40%±2% mannitol, 65%±2% Amitriptyline HCl and 35%±2% mannitol, 70%±2% Amitriptyline HCl and 30%±2% mannitol, 80%±2% Amitriptyline HCl and 20%±2% mannitol, 85%±2% Amitriptyline HCl and 15%±2% mannitol, and 90%±2% Amitriptyline HCl and 10%±2% mannitol by weight.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises 60%-90% Amitriptyline HCl and 40%-10% mannitol by weight.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, comprising 50%±2% Amitriptyline HCl and 50%±2% mannitol by weight.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein the Amitriptyline HCl is micronized Amitriptyline HCl.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, further comprising a basifying agent.

### Claim 6 (depends on 5)

The pharmaceutical composition of claim 5, wherein the basifying agent is K2HPO4, Na2HPO4 or anhydrous trisodium citrate.

### Claim 7 (depends on 1)

The pharmaceutical composition of claim 1, wherein the mannitol in the eutectic is β mannitol.

### Claim 8 (depends on 1)

The pharmaceutical composition of claim 1, wherein the mannitol in the eutectic is δ mannitol.

### Claim 9 (depends on 7, 8)

The pharmaceutical composition of claim 7 or 8, wherein the Amitriptyline HCl is micronized Amitriptyline HCl.

### Claim 10 (depends on 7, 8)

The pharmaceutical composition of claim 7 or 8, further comprising a basifying agent.

### Claim 11 (depends on 10)

The pharmaceutical composition of claim 10, wherein the basifying agent is K2HPO4, Na2HPO4 or anhydrous trisodium citrate.