# US 11,298,322 B2 · Tamper resistant dosage forms

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- Number: US 11,298,322 B2
- Document ID: US11298322B2
- Status: Granted
- Kind: B2
- Application number: 17/027,088
- Filed: 2020-09-21
- Published: 2021-01-07
- Granted: 2022-04-12
- Earliest claimed: 2006-08-25
- Assignees: Purdue Pharma L.P.; Purdue Pharmaceuticals L.P.
- Applicants: Purdue Pharma L.P.; Purdue Pharmaceuticals L.P.
- Inventors: William H. McKenna; Richard O. Mannion; Edward P. O'Donnell; Haiyong H. Huang
- Web page: https://patentgrep.com/patent/US11298322B2

## CPC

- A61K 9/28: Dragees; Coated pills or tablets {, e.g. with film or compression coating (A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209)}
- A61J 3/005: {Coating of tablets or the like (coating of sweetmeats or confectionery A23G3/20; coating of granules in general B01J2/006)}
- A61J 3/06: into the form of pills, lozenges or dragees
- A61J 3/10: into the form of compressed tablets (tablet presses B30B11/00)
- A61K 9/0002: {Galenical forms characterised by the drug release technique; Application systems commanded by energy}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/1641: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/2031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers}
- 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 9/209: {containing drug in at least two layers or in the core and in at least one outer layer}
- A61K 9/2095: {Tabletting processes}
- A61K 9/284: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone}
- A61K 9/2853: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)}
- A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2893: {Tablet coating processes (mechanical aspects A61J3/06)}
- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 29/02: without antiinflammatory effect
- B29B 7/02: non-continuous, with mechanical mixing or kneading devices, i.e. batch type
- B29B 7/88: Adding charges {, i.e. additives}
- B29C 35/045: {using gas or flames}
- B29C 35/16: Cooling {(cooling extruded material B29C48/911; cooling preforms for blow moulding B29C49/6427; cooling blown articles B29C49/66; cooling tyres during post cure inflation B29D30/0643)}
- B29C 37/0025: {Applying surface layers, e.g. coatings, decorative layers, printed layers, to articles during shaping, e.g. in-mould printing (moulding on preformed layers as inserts B29C70/68; applying fluent material to surfaces in general B05)}
- 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 43/52: Heating or cooling
- B29C 71/00: After-treatment of articles without altering their shape; Apparatus therefor (B29C44/56, B29C73/00 take precedence; surface shaping B29C59/00 {; for joined or sealed parts B29C66/03; after-treatment specially adapted for vulcanising tyres B29D30/0633})
- B29C 71/009: {using gases without chemical reaction (C08J7/12 takes precedence; in combination with blow-moulding B29C49/46; surface treatment using plasma B29C59/14, ionised gas B29C59/16)}
- A61K 9/2072: {characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms (A61K9/0004, A61K9/0056, A61K9/0065 take precedence)}
- B29C 2035/046: {dried air}
- B29C 2035/1658: {using gas}
- B29K 2071/02: {Polyalkylene oxides, e.g. PEO, i.e. polyethylene oxide, or derivatives thereof}
- B29K 2105/0035: {Medical or pharmaceutical agents}
- B29K 2105/251: {Particles, powder or granules (expandable particles B29K2105/046)}
- B29K 2995/0088: Molecular weight
- B29L 2031/753: {Medical equipment; Accessories therefor (bloodbags, medical bags B29L2031/7148; artificial eyes B29L2011/0008)}
- 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)
- A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- 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
- 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
- B29L: INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES

## Abstract

The present invention relates to pharmaceutical dosage forms, for example to a tamper resistant dosage form including an opioid analgesic, and processes of manufacture, uses, and methods of treatment thereof.

## Claims

### Claim 1

A process of preparing a solid oral extended release pharmaceutical dosage form, comprising the steps of:
(a) combining (1) at least one polyethylene oxide (PEO) having, based on rheological measurements, an approximate molecular weight of at least 800,000, and (2) at least one opioid analgesic, to form a composition;
(b) shaping the composition to form an extended release matrix formulation;
(c) subsequently heating said extended release matrix formulation by subjecting the extended release matrix formulation to an elevated temperature that is at least the softening temperature of said PEO for a time period of at least about 1 minute; and
(d) cooling the heated extended release matrix formulation.

### Claim 2 (depends on 1)

The process of claim 1, wherein said time period is at least about 15 minutes.

### Claim 3 (depends on 1)

The process of claim 1, wherein said elevated temperature is at least about 55° C.

### Claim 4 (depends on 1)

The process of claim 1, wherein said elevated temperature is at least about 62° C.

### Claim 5 (depends on 1)

The process of claim 1, wherein the total PEO content of the shaped composition is at least about 30% (by weight) of the shaped composition.

### Claim 6 (depends on 1)

The process of claim 1, wherein the total PEO content of the shaped composition is at least about 50% (by weight) of the shaped composition.

### Claim 7 (depends on 1)

The process of claim 1, wherein the extended release matrix is shaped by direct compression to form a tablet.

### Claim 8 (depends on 1)

The process of claim 1, wherein said cooling is at a temperature below 50° C.

### Claim 9 (depends on 1)

The process of claim 1, wherein said time period is at least about 5 minutes and said elevated temperature is at least about 55° C.

### Claim 10 (depends on 1)

The process of claim 1, wherein the extended release matrix is shaped to form a tablet; the heating step takes place in a coating pan; said time period is at least about 5 minutes; and said elevated temperature corresponds to the exhaust temperature of the coating pan and is at least about 60° C.

### Claim 11 (depends on 10)

The process of claim 10, wherein the opioid analgesic is oxycodone or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 10)

The process of claim 10, wherein the opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 1)

The process of claim 1, wherein the total PEO content of the shaped composition is at least about 15% (by weight) of the shaped composition.

### Claim 14 (depends on 13)

The process of claim 13, wherein said time period is at least about 5 minutes and said elevated temperature is at least about 55° C.

### Claim 15 (depends on 14)

The process of claim 14, wherein said PEO has, based on rheological measurements, an approximate molecular weight of at least 1,000,000.

### Claim 16 (depends on 14)

The process of claim 14, wherein said PEO has, based on rheological measurements, an approximate molecular weight of at least 4,000,000.

### Claim 17 (depends on 14)

The process of claim 14, wherein said elevated temperature is at least about 60° C.

### Claim 18 (depends on 14)

The process of claim 14, wherein said elevated temperature is at least about 68° C.

### Claim 19 (depends on 14)

The process of claim 14, wherein said opioid analgesic is oxycodone or a pharmaceutically acceptable salt thereof.

### Claim 20 (depends on 14)

The process of claim 14, wherein said active agent is hydrocodone or a pharmaceutically acceptable salt thereof.

### Claim 21

A process of preparing a solid oral extended release pharmaceutical dosage form, comprising the steps of:
(a) combining (1) at least one polyethylene oxide (PEO) having, based on rheological measurements, an approximate molecular weight of at least 800,000, and (2) at least one opioid analgesic, to form a composition, wherein the total PEO content of the composition is at least about 15% (by weight) of the composition;
(b) shaping the composition to form a plurality of extended release tablets;
(c) subsequently subjecting the tablets to an elevated temperature of at least about 55° C. for a time period of at least about 15 minutes; and
(d) cooling the tablets at a temperature below 50° C.

### Claim 22 (depends on 21)

The process of claim 21, wherein the total PEO content of the composition is at least about 20% (by weight) of the composition.

### Claim 23 (depends on 21)

The process of claim 21, wherein the total PEO content of the composition is at least about 50% (by weight) of the composition.

### Claim 24 (depends on 21)

The process of claim 21, wherein said elevated temperature is at least about 62° C.

### Claim 25 (depends on 21)

The process of claim 21, wherein said opioid analgesic is oxycodone or a pharmaceutically acceptable salt thereof.

### Claim 26 (depends on 21)

The process of claim 21, wherein said opioid analgesic is hydrocodone or a pharmaceutically acceptable salt thereof.

### Claim 27 (depends on 21)

The process of claim 21, wherein said PEO has, based on rheological measurements, an approximate molecular weight of at least 1,000,000.

### Claim 28 (depends on 21)

The process of claim 21, wherein said PEO has, based on rheological measurements, an approximate molecular weight of at least 4,000,000.

### Claim 29 (depends on 21)

The process of claim 21, wherein the dosage form further comprises at least one of a cellulosic additive, magnesium stearate, talc, silica, fumed silica, colloidal silica dioxide, calcium stearate, carnauba wax, stearic acid, stearyl alcohol, mineral oil, paraffin, glycerin, propylene glycol, polyethylene glycol, lactose, povidone, triacetin, and copolymers comprising methyl methacrylate.

### Claim 30 (depends on 29)

The process of claim 29, wherein the cellulosic additive is microcrystalline or hydroxypropylated.