# US 11,026,898 B2 · Eutectic formulations of cyclobenzaprine hydrochloride

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- Number: US 11,026,898 B2
- Document ID: US11026898B2
- Status: Granted
- Kind: B2
- Application number: 16/518,338
- Filed: 2019-07-22
- Published: 2019-11-07
- Granted: 2021-06-08
- Earliest claimed: 2014-09-18
- Assignees: Tonix Pharma Holdings Limited
- Applicants: Tonix Pharma Holdings Limited
- Inventors: Seth Lederman; Marino Nebuloni
- Web page: https://patentgrep.com/patent/US11026898B2

## CPC

- A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)}
- A61K 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- 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 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- 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.

## Claims

### Claim 1

A pharmaceutical composition comprising a eutectic of δ-mannitol and Cyclobenzaprine HCl, wherein the eutectic comprises 65%±2% Cyclobenzaprine HCl and 35%±2% δ-mannitol by weight.

### 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, Na2HPO4, or anhydrous trisodium citrate.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, wherein said composition comprises granules.

### Claim 6 (depends on 5)

The pharmaceutical composition of claim 5, wherein said granules comprise Cyclobenzaprine HCl and δ mannitol.

### Claim 7 (depends on 1)

A method of manufacturing the pharmaceutical composition of claim 1, comprising mixing Cyclobenzaprine HCl and mannitol in the presence of a solvent.

### Claim 8 (depends on 7)

The method of claim 7, wherein the mannitol is β mannitol or δ mannitol.

### Claim 9 (depends on 7)

The method of claim 7, wherein said mixing is wet granulation mixing.

### Claim 10 (depends on 7)

The method of claim 7, wherein the solvent is water, an alcohol or a mixture thereof.

### Claim 11 (depends on 10)

The method of claim 10, wherein said alcohol is methanol or ethanol.

### Claim 12 (depends on 9)

The method of claim 9, further comprising drying the mixture after said wet granulation.

### Claim 13 (depends on 12)

The method of claim 12, wherein said wet granulation and drying are repeated one or more times.

### Claim 14 (depends on 9)

The method of claim 9, further comprising crystallizing the Cyclobenzaprine HCl-mannitol mixture after said wet granulation.

### Claim 15 (depends on 14)

The method of claim 14, wherein said wet granulation and crystallization are repeated one or more times.

### Claim 16 (depends on 1)

A method of manufacturing the pharmaceutical composition of claim 1 comprising fluid bed drying a mixture of Cyclobenzaprine HCl, mannitol, and a solvent.

### Claim 17 (depends on 16)

The method of claim 16, wherein the mannitol is β mannitol or δ mannitol.

### Claim 18 (depends on 16)

The method of claim 16, wherein the solvent is water, an alcohol or a mixture thereof.

### Claim 19 (depends on 18)

The method of claim 18, wherein the alcohol is methanol or ethanol.

### Claim 20 (depends on 16)

The method of claim 16, wherein the Cyclobenzaprine HCl is dissolved in the solvent and sprayed onto β mannitol particles inside a fluid bed dryer.

### Claim 21 (depends on 1)

The pharmaceutical composition of claim 1, wherein the δ-mannitol eutectic melts at 134° C.±3° C.

### Claim 22 (depends on 7)

The method of claim 7, wherein Cyclobenzaprine HCl is mixed with β mannitol.

### Claim 23 (depends on 22)

The method of claim 22, wherein the β mannitol converts to δ mannitol.