# US 2014/0194510 A1 · Dispersions of rasagiline citrate

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- Number: US 2014/0194510 A1
- Document ID: US20140194510A1
- Status: Published application
- Kind: A1
- Application number: 14/203,209
- Filed: 2014-03-10
- Published: 2014-07-10
- Earliest claimed: 2010-07-27
- Assignees: Teva Pharmaceutical Industries Ltd.
- Inventors: Keith Lorimer; David Engers
- Web page: https://patentgrep.com/patent/US20140194510A1

## CPC

- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 9/1635: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)}
- A61K 31/205: Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
- A61P 25/16: Anti-Parkinson drugs
- 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 subject invention provides a solid dispersion of rasagiline citrate, a composition and a process for the manufacture thereof.

## Claims

### Claim 1

A solid dispersion of at least one polymeric pharmaceutical excipient and rasagiline or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The solid dispersion of claim 1, wherein the at least one polymeric pharmaceutical excipient is a water soluble polymeric pharmaceutical excipient.

### Claim 3 (depends on 1, 2)

The solid dispersion of claim 1 or 2, wherein the pharmaceutically acceptable salt of rasagiline is rasagiline citrate.

### Claim 4 (depends on 3)

The solid dispersion of claim 3, wherein the rasagiline citrate is mono-rasagiline citrate.

### Claim 5 (depends on 1, 2, 3, 4)

The solid dispersion of any one of claims 1-4, wherein the at least one polymeric pharmaceutical excipient is polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose acetate succinate, or hydroxypropyl methylcellulose phthalate.

### Claim 6 (depends on 1, 2, 3, 4)

The solid dispersion of any one of claims 1-4, wherein the at least one polymeric pharmaceutical excipient is a co-polymer.

### Claim 7 (depends on 6)

The solid dispersion of claim 6, wherein the co-polymer is polyvinylpyrrolidone-vinyl acetate or methacrylic acid-ethyl acrylate.

### Claim 8 (depends on 7)

The solid dispersion of claim 7, wherein the co-polymer is methacrylic acid-ethyl acrylate.

### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

The solid dispersion of any one of claims 1-8, wherein Tg of the solid dispersion is at least 20° C. higher than that of rasagiline or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

A pharmaceutical composition comprising the solid dispersion of any one of claims 1-9.

### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

A process for making the solid dispersion of any one of claims 1-9, comprising:
a) combining a mixture of rasagiline free base and the at least one polymeric pharmaceutical excipient in a solvent to form a solution;
b) adding citric acid to the solution; and
c) removing the solvent from the solution.

### Claim 12 (depends on 11)

The process of claim 11, wherein the solvent is methanol, ethanol, acetone, dichloromethane, dioxane and water, or a mixture of at least two thereof.

### Claim 13 (depends on 11, 13)

The process of claim 11 or 13, wherein step c) is performed at a temperature of between about 55° C. and 80° C. by rotary evaporation.

### Claim 14 (depends on 11, 12)

The process of claim 11 or 12, wherein in step b) the solvent is removed by lyophilization.

### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

A process for making the solid dispersion of any one of claims 1-9, comprising:
a) dissolving a mixture of rasagiline or the pharmaceutically acceptable salt thereof, and the at least one polymeric pharmaceutical excipient in a solvent to form a solution; and
b) removing the solvent from the solution.

### Claim 16 (depends on 15)

The process of claim 15, wherein the pharmaceutically acceptable salt of rasagiline is rasagiline citrate.

### Claim 17 (depends on 16)

The process of claim 16, wherein the rasagiline citrate is mono-rasagiline citrate.

### Claim 18 (depends on 15, 16, 17)

The process of any one of claims 15-17, wherein the solvent is methanol, ethanol, acetone, dichloromethane, dioxane and water, or a mixture of at least two thereof.

### Claim 19 (depends on 15, 16, 17, 18)

The process of any one of claims 15-18, wherein step b) is performed at a temperature of between about 55° C. and 80° C. by rotary evaporation.

### Claim 20 (depends on 15, 16, 17, 18)

The process of any one of claims 15-18, wherein in step b) the solvent is removed by lyophilization.

### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

A process for making the solid dispersion of any one claims 1-9, comprising:
a) combining a mixture of rasagiline free base, the at least one polymeric pharmaceutical excipient, and citric acid; and
b) grinding the mixture.

### Claim 22 (depends on 21)

The process of claim 21, wherein step b) is performed by dry milling the mixture.

### Claim 23 (depends on 21)

The process of claim 21, wherein step b) is performed by wet milling the mixture with a solvent.

### Claim 24 (depends on 23)

The process of claim 23, wherein the solvent is methanol or acetone.

### Claim 25 (depends on 21)

The process of claim 21, wherein step b) is performed at a temperature below −100° C.

### Claim 26 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

A process for making the solid dispersion of any one of claims 1-9, comprising:
a) obtaining a solid mixture of rasagiline or the pharmaceutically acceptable salt thereof, and the at least one polymeric pharmaceutical excipient; and
b) grinding the mixture.

### Claim 27 (depends on 26)

The process of claim 26, wherein the pharmaceutically acceptable salt of rasagiline is rasagiline citrate.

### Claim 28 (depends on 27)

The process of claim 27, wherein the rasagiline citrate is mono-rasagiline citrate.

### Claim 29 (depends on 26, 27, 28)

The process of any one of claims 26-28, wherein step b) is performed by dry milling the mixture.

### Claim 30 (depends on 26, 27, 28)

The process of claim any one of claims 26-28, wherein step b) is performed by wet milling the mixture with a solvent.

### Claim 31 (depends on 30)

The process of claim 30, wherein the solvent is methanol or acetone.

### Claim 32 (depends on 26, 27, 28)

The process of claim any one of claims 26-28, wherein step b) is performed at a temperature below −100° C.

### Claim 33 (depends on 10)

A method of treating a human subject afflicted with Parkinson's disease comprising administering to the human subject an amount of the pharmaceutical composition of claim 10, effective to treat the human subject.