# US 2015/0148366 A1 · Particulates

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- Number: US 2015/0148366 A1
- Document ID: US20150148366A1
- Status: Published application
- Kind: A1
- Application number: 14/547,874
- Filed: 2014-11-19
- Published: 2015-05-28
- Earliest claimed: 2004-02-12
- Assignees: Euro-Celtique S.A.
- Applicants: Euro-Celtique S.A.
- Inventors: Geoffrey Gerard Hayes; Hassan Mohammad; Harjit Tamber; Malcolm Walden; Steve Whitelock; Helen Kathleen Danagher; Derek Allan Prater
- Web page: https://patentgrep.com/patent/US20150148366A1

## CPC

- A61K 9/1694: {resulting in granules or microspheres of the matrix type containing more than 5% of excipient}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/16: Agglomerates; Granulates; Microbeadlets {; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction (A61K9/20 takes precedence if the final form is a tablet; microspheres with drug-free outer coating, microcapsules A61K9/50; mixture of different granules, microcapsules, (coated) microparticles A61K9/5084; nanoparticles A61K9/51)}
- 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 9/20: Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets}
- A61K 9/2086: {Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat (active cores with a complete drug-free outer coat A61K9/28)}
- A61K 9/2095: {Tabletting processes}
- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61P 23/00: Anaesthetics
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/24: Antidepressants
- A61P 25/26: Psychostimulants, e.g. nicotine, cocaine
- A61P 25/36: Opioid-abuse
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- B29B 9/06: in the form of filamentary material, e.g. combined with extrusion
- B29K 2033/12: {Polymers of methacrylic acid esters, e.g. PMMA, i.e. polymethylmethacrylate}
- B29K 2105/0085: {Copolymers}
- 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
- B29B: PREPARATION OR PRETREATMENT OF THE MATERIAL TO BE SHAPED; MAKING GRANULES OR PREFORMS; RECOVERY OF PLASTICS OR OTHER CONSTITUENTS OF WASTE MATERIAL CONTAINING PLASTICS
- 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

A neutral poly(ethyl acrylate, methyl methacrylate) copolymer is employed as a carrier in the manufacture of pharmaceutical formulations containing an active ingredient. The formulations are preferably made by melt extrusion, and can have rubbery characteristics and can exhibit tamper resistance.

## Claims

### Claim at position 1

1-130. (canceled)

### Claim 131

A process for preparing multiparticulates comprising melt extruding a granulate comprising a neutral poly(ethyl acrylate, methyl methacrylate) copolymer and an active agent.

### Claim 132 (depends on 131)

The process of claim 131, further comprising granulating a mix comprising a neutral poly(ethyl acrylate, methyl methacrylate) copolymer and an active agent to produce said granulate.

### Claim 133 (depends on 132)

The process of claim 132, wherein said granulating is wet granulating.

### Claim 134 (depends on 133)

The process of claim 133, wherein a dispersion of a neutral poly(ethyl acrylate, methyl methacrylate) copolymer is granulated.

### Claim 135 (depends on 134)

The process of claim 134, wherein during granulating a dispersion of a neutral poly(ethyl acrylate, methyl methacrylate) copolymer is added by spraying or dropwise to a mixture comprising said active agent.

### Claim 136 (depends on 135)

The process of claim 135, wherein said mixture comprising said active agent is a dry mixture.

### Claim 137 (depends on 132)

The process of claim 132, wherein said granulating is in a high shear mixer, a fluid bed granulator or a fluid bed granulator with a rotary insert.

### Claim 138 (depends on 132)

The process of claim 132, further comprising drying said granulate.

### Claim 139 (depends on 132)

The process of claim 132, further comprising extruding said granulate.

### Claim 140 (depends on 139)

The process of claim 139, further comprising drying said extruded granulate.

### Claim 141 (depends on 131)

The process of claim 131, comprising:
(a) granulating a mix comprising a neutral poly(ethyl acrylate, methyl methacrylate) copolymer and an active agent to produce a granulate;
(b) optionally extruding said granulate;
(c) drying said granulate or extruded granulate to produce dried granulate;
(d) optionally screening and/or milling said dried granulate or said dried extruded granulate; and
(e) melt extruding the product from step (c) or (d).

### Claim 142 (depends on 141)

The process of claim 141, wherein said dried granulate or dried extruded granulate contains less than 5% w/w water.

### Claim 143 (depends on 141)

The process of claim 141, wherein the extruded product from step (e) is conveyed to a pelletiser and cut into multiparticulates.

### Claim 144 (depends on 141)

The process of claim 141, wherein a cutter cuts the extruded product from step (e) as it emerges from the extruder.

### Claim 145 (depends on 131)

The process of claim 131, wherein said extrusion provides a rubbery matrix in said multiparticulates.

### Claim 146 (depends on 145)

The process of claim 145, wherein said matrix provides tamper resistance which reduces release of the active agent upon grinding of the formulation and extraction.

### Claim 147 (depends on 146)

The process of claim 146, wherein said multiparticulates show at least one of the following characteristics (a) to (e) when tested by a test method comprising admixing a dosage amount of multiparticulates with 10 ml of the liquid in a glass flask and shaking at 500 to 600 oscillations per minute for 15 minutes using a Stuart Scientific Shaker Model SF1:
(a) 15 minutes shaking in water at room temperature: less than 7.5% release of active agent;
(b) 5 minutes standing in water at 50° C. followed by 15 minutes shaking at the same temperature: less than 15% release of active agent;
(c) 5 minutes standing at 75° C. followed by 15 minutes shaking at the same temperature: less than 20% release of active agent;
(d) 5 minutes standing at 100° C. followed by 15 minutes shaking at the same temperature: less than 25% release of active agent;
(e) 15 minutes shaking in 40% ethanol at room temperature: less than 25% release of active agent.

### Claim 148 (depends on 131)

The process of claim 131, wherein the active agent is selected from the group consisting of an opioid, a stimulant, a barbiturate, an anti-depressant, a dissociative anaesthetic, and a combination thereof.

### Claim 149 (depends on 148)

The process of claim 148, wherein said active agent is oxycodone, or a pharmaceutically acceptable salt thereof.

### Claim 150 (depends on 131)

The process of claim 131, wherein said multiparticulates comprise at least one other polymer to modify release.

### Claim 151 (depends on 150)

The process of claim 150, wherein said other polymer is selected from the group consisting of an alkyl cellulose and a water insoluble ammonium methacrylate copolymer.

### Claim 152 (depends on 151)

The process of claim 151, wherein said other polymer is ethyl cellulose.

### Claim 153 (depends on 148)

The process of claim 148, wherein said multiparticulates comprise an opioid and further comprise an opioid antagonist.

### Claim 154 (depends on 153)

The process of claim 153, wherein the opioid is oxycodone, or a pharmaceutically acceptable salt thereof.

### Claim 155 (depends on 153)

The process of claim 153, wherein the opioid antagonist is naltrexone, or a pharmaceutically acceptable salt thereof.

### Claim 156 (depends on 153)

The process of claim 153, wherein the opioid is oxycodone, or a pharmaceutically acceptable salt thereof, and the opioid antagonist is naltrexone, or a pharmaceutically acceptable salt thereof.

### Claim 157 (depends on 131)

The process of claim 131, wherein said multiparticulates further comprise a plasticiser.

### Claim 158 (depends on 131)

the process of claim 131, wherein said multiparticulates further comprise a lubricant.

### Claim 159 (depends on 131)

The process of claim 131, wherein said multiparticulates comprise 15 to 50%, based on the total weight of ingredients, of a neutral poly(ethyl acrylate, methyl methacrylate) copolymer.

### Claim 160 (depends on 131)

The process of claim 131, wherein said multiparticulates comprise 5 to 55%, based on the total weight of ingredients, of active agent.

### Claim 161 (depends on 131)

A process for preparing a controlled release formulation, wherein said formulation comprises a plurality of melt extruded multiparticulates, comprising preparing multiparticulates by the method of claim 131.