# US 2014/0350027 A1 · Pharmaceutical Compositions Comprising Imatinib and a Release Retardant

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2014/0350027 A1
- Document ID: US20140350027A1
- Status: Published application
- Kind: A1
- Application number: 14/300,511
- Filed: 2014-06-10
- Published: 2014-11-27
- Earliest claimed: 2005-05-10
- Assignees: Novartis AG
- Inventors: Madhav Vasanthavada; Jay Parthiban; Wei-Qin Tong; Abu T. M. Serajuddin
- Web page: https://patentgrep.com/patent/US20140350027A1

## CPC

- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2068: {Compounds of unknown constitution, e.g. material from plants or animals (oils, fats, waxes, shellac A61K9/2013)}
- A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets}
- A61K 9/2095: {Tabletting processes}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- B29C 43/003: {characterised by the choice of material}
- B29C 43/02: of articles of definite length, i.e. discrete articles {(B29C35/0227 takes precedence)}
- B29C 48/04: Particle-shaped (making granules B29B9/00)
- B29C 48/05: Filamentary, e.g. strands
- B29C 48/06: Rod-shaped
- B29C 48/40: using two or more parallel screws {or at least two parallel non-intermeshing screws}, e.g. twin screw extruders
- B29C 48/911: {Cooling}
- A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)}
- B29K 2001/08: {Cellulose derivatives}
- B29K 2105/0035: {Medical or pharmaceutical agents}
- B29K 2105/251: {Particles, powder or granules (expandable particles B29K2105/046)}
- B29K 2995/0056: Biocompatible, e.g. biopolymers or bioelastomers
- B29K 2995/006: Bio-degradable, e.g. bioabsorbable, bioresorbable or bioerodible
- 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
- B29C: SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING (making preforms B29B11/00; making laminated products by combining previously unconnected layers which become one product whose layers will remain together B32B37/00 - B32B41/00)
- B29K: INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR {MOULDS, } REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS

## Abstract

Sustained release pharmaceutical compositions that contain imatinib or a pharmaceutically acceptable salt thereof. The pharmaceutical compositions further contain a release retardant, for example a water soluble, a water swellable and/or a water insoluble polymer. The present invention also features a particularly useful process of making such sustained release pharmaceutical compositions by using an extruder.

## Claims

### Claim at position 1

1-25. (canceled)

### Claim 26

A pharmaceutical composition comprising imatinib or any of its salts and a release retardant.

### Claim 27 (depends on 26)

The pharmaceutical composition of claim 26, comprising between about 50% by weight imatinib.

### Claim 28 (depends on 27)

The pharmaceutical composition of claim 27, wherein said composition comprises between about 62% and about 99% by weight of imatinib.

### Claim 29 (depends on 26)

The pharmaceutical composition of claim 26, wherein said composition comprises at least 400 mg of imatinib mesylate.

### Claim 30 (depends on 26)

The pharmaceutical composition of claim 26, wherein said release retardant is a polymer.

### Claim 31 (depends on 30)

The pharmaceutical composition of claim 30, wherein said polymer has a glass transition temperature less than the melting point of imatinib mesylate.

### Claim 32 (depends on 31)

The pharmaceutical composition of claim 31, further comprising a plasticizer.

### Claim 33 (depends on 26)

The pharmaceutical composition of claim 26, wherein said release retardant is a non-polymeric release retardant.

### Claim 34 (depends on 33)

The pharmaceutical composition of claim 33, wherein said non-polymeric release retardant melts at a temperature less than the melting point of imatinib or the imatinib salt employed.

### Claim 35 (depends on 33)

The pharmaceutical composition of claim 33, wherein said non-polymeric release retardant is hydrogenated castor oil.

### Claim 36 (depends on 26)

The pharmaceutical composition of claim 26, wherein the pharmaceutical composition comprises at least one release retardant selected from the group consisting of water soluble, water insoluble and water swellable cellulose polymers, acrylic polymers, polysaccharides and polyols.

### Claim 37 (depends on 26)

The pharmaceutical composition of claim 26, wherein the pharmaceutical composition comprises at least one release retardant selected from the group consisting of hydroxypropyl cellulose, hydroxypropylmethyl cellulose, ethylcellulose and methacrylate polymers.

### Claim 38 (depends on 26)

The pharmaceutical composition according to claim 26, further comprising a release modifier.

### Claim 39

A method of making a modified release pharmaceutical composition comprising the step of granulating imatinib or any of its salts with a release retardant and optionally a release modifier in an extruder while heating to a temperature below the melting temperature of imatinib or its salt, to form melt granules.

### Claim 40 (depends on 39)

The method of claim 39, wherein the melt granules are once again introduced into the extruder, to further granulate with or without release retardant or release modifier or plasticizer, at a temperature less than the melting point of imatinib or the imatinib salt employed.

### Claim 41 (depends on 39)

The method of claim 39, further comprising cooling of said melt granules to a desired temperature, which is less than melt granulation process temperature.

### Claim 42 (depends on 39)

The method of claim 39, further comprising compressing the melt granules into a tablet.

### Claim 43 (depends on 42)

The method of claim 42, wherein melt granules manufactured separately using different release retardants and/or release modifiers and/or plasticizers at different compositions are blended and compressed into a tablet.

### Claim 44 (depends on 39)

The method of claim 39, wherein said extruder is a twin-screw extruder.

### Claim 45 (depends on 40)

The method of claim 40, wherein the release retardant is a polymer.

### Claim 46 (depends on 45)

The method of claim 45, wherein said polymer is hydroxypropyl cellulose.

### Claim 47 (depends on 39)

The method of claim 39, wherein said composition comprises at least 50% imatinib by weight of the composition.

### Claim 48 (depends on 26)

The pharmaceutical composition according to claim 26, where the drug release from the pharmaceutical composition is not greater than 80% at 1 hour, and not less than 80% at 10 hours, when tested using USP I basket apparatus at 50 rpm in 900 mL of 0.1N hydrochloric acid at 37° C.

### Claim 49 (depends on 26)

The pharmaceutical composition according to claim 26, where the drug release from the pharmaceutical composition is not greater than 80% at 2 hours and not less than 80% at 8 hours, when tested using USP I basket apparatus at 50 rpm in 900 mL of 0.1N hydrochloric acid at 37° C.

### Claim 50 (depends on 26)

The pharmaceutical composition according to claim 26, wherein the composition provides, in healthy humans, a mean plasma concentration value not exceeding 3.5 μg Imatinib/mL, when dosed 2 hours after a light breakfast.