# US 9,872,836 B2 · Pharmaceutical formulation containing gelling agent

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- Number: US 9,872,836 B2
- Document ID: US9872836B2
- Status: Granted
- Kind: B2
- Application number: 15/015,735
- Filed: 2016-02-04
- Published: 2016-06-02
- Granted: 2018-01-23
- Earliest claimed: 2001-08-06
- Assignees: Purdue Pharma L.P.; The P.F. Laboratories, Inc.; Purdue Pharmaceuticals L.P.
- Applicants: Purdue Pharma L.P.
- Inventors: Curtis Wright; Benjamin Oshlack; Christopher Breder
- Web page: https://patentgrep.com/patent/US9872836B2

## CPC

- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61J 3/10: into the form of compressed tablets (tablet presses B30B11/00)
- A61K 8/731: {Cellulose; Quaternized cellulose derivatives}
- 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 9/006: {Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays}
- A61K 9/0095: {Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006)}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/1635: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/1641: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers}
- 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 9/20: Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)}
- A61K 9/2009: {Inorganic compounds}
- 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 9/205: {Polysaccharides, e.g. alginate, gums; Cyclodextrin}
- A61K 9/2095: {Tabletting processes}
- 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)}
- A61K 9/2806: {Coating materials}
- A61K 9/2813: {Inorganic compounds}
- A61K 9/284: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone}
- A61K 9/2846: {Poly(meth)acrylates}
- 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 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)}
- A61K 9/4808: {characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release (capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084)}
- A61K 9/4833: {Encapsulating processes; Filling of capsules (mechanical aspects A61J3/07)}
- A61K 9/485: {Inorganic compounds}
- A61K 9/4858: {Organic compounds}
- A61K 9/4866: {Organic macromolecular compounds}
- A61K 9/4875: {Compounds of unknown constitution, e.g. material from plants or animals (oils, fats, waxes, shellac A61K9/4858)}
- A61K 9/4891: {Coated capsules; Multilayered drug free capsule shells (with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004)}
- A61K 9/5047: {Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose}
- A61K 9/5078: {with drug-free core}
- A61K 9/5089: {Processes}
- A61K 9/70: Web, sheet or filament bases {; Films; Fibres of the matrix type containing drug (hollow drug-filled fibres A61K9/0092)}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
- A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)}
- A61K 31/439: the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46)
- A61K 31/4458: only substituted in position 2, e.g. methylphenidate
- A61K 31/48: Ergoline derivatives, e.g. lysergic acid, ergotamine
- 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 47/02: Inorganic compounds
- A61K 47/08: containing oxygen, {e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides}
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/14: Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- 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 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)
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 47/38: Cellulose; Derivatives thereof
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/36: Opioid-abuse
- 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

## Abstract

Disclosed in certain embodiments is a controlled release oral dosage form comprising a therapeutically effective amount of a drug susceptible to abuse together with one or more pharmaceutically acceptable excipients; the dosage form further including a gelling agent in an effective amount to impart a viscosity unsuitable for administration selected from the group consisting of parenteral and nasal administration to a solubilized mixture formed when the dosage form is crushed and mixed with from about 0.5 to about 10 ml of an aqueous liquid; the dosage form providing a therapeutic effect for at least about 12 hours when orally administered to a human patient.

## Claims

### Claim 1

A method of preparing an abuse deterrent controlled release dosage form comprising:
preparing a mixture comprising an opioid agonist and a gelling agent comprising polyethylene oxide, polyethylene glycol and hydroxypropylmethylcellulose;
heating the mixture to a temperature to at least soften the mixture;
extruding the heated mixture to form an extrudate;
formulating the extrudate into a tablet; and
coating the tablet with a coating comprising polyvinyl alcohol polyethylene glycol and talc,
wherein the opioid agonist is the sole active agent in the dosage form; and wherein the dosage form forms a gel when subjected to tampering comprising dissolution in from about 0.5 ml to about 10 ml of an aqueous liquid;
the dosage form having a ratio of gelling agent to opioid agonist from about 8:1 to about 1:8;
the dosage form providing a therapeutic effect for about 12 hours or longer when orally administered to a human patient.

### Claim 2 (depends on 1)

The method of claim 1, wherein the mixture further comprises alpha-tocopherol.

### Claim 3 (depends on 2)

The method of claim 2, wherein the dosage form subjected to tampering is unsuitable for injection with an insulin syringe.

### Claim 4 (depends on 2)

The method of claim 2, wherein the dosage form subjected to tampering is difficult to pull into an insulin syringe.

### Claim 5 (depends on 2)

The method of claim 2, wherein the dosage form subjected to tampering cannot be filled into an insulin syringe without picking up pockets of air.

### Claim 6 (depends on 2)

The method of claim 2, wherein the dosage form subjected to tampering has a milk like color.

### Claim 7 (depends on 2)

The method of claim 2, wherein the aqueous liquid is water.

### Claim 8 (depends on 2)

The method of claim 2, wherein the gel is formed when the dosage form is subjected to tampering comprising dissolution in about 1 ml to about 3 ml of aqueous liquid.

### Claim 9 (depends on 2)

The method of claim 2, wherein the gel is formed when the dosage form is subjected to tampering comprising crushing and dissolution in the aqueous liquid.

### Claim 10 (depends on 2)

The method of claim 2, wherein the gel is formed when the dosage form is subjected to tampering comprising dissolution in the aqueous liquid at ambient temperature.

### Claim 11 (depends on 2)

The method of claim 2, wherein the gel is formed when the dosage form is subjected to tampering comprising dissolution in the aqueous liquid with heating greater than 45° C.

### Claim 12 (depends on 2)

The method of claim 2, wherein the gelling agent is in an effective amount to impart a viscosity of about 10 cP or more to the gel.

### Claim 13 (depends on 2)

The method of claim 2, wherein the gelling agent is in an effective amount to impart a viscosity of about 60 cP or more to the gel.

### Claim 14 (depends on 2)

The method of claim 2, wherein the gelling agent is in an effective amount to impart a viscosity of about 120 cP or more to the gel.

### Claim 15 (depends on 1)

The method of claim 1, wherein the gelling agent is in an effective amount to impart a viscosity from about 120 cP to about 5,000 cP to the gel.

### Claim 16 (depends on 1)

The method of claim 1, wherein the polyethylene oxide has a weight average molecular weight from about 100,000 daltons to about 1,000,000 daltons.

### Claim 17 (depends on 1)

The method of claim 1, wherein the polyethylene oxide has a weight average molecular weight from about 1,000,000 daltons to about 10,000,000 daltons.

### Claim 18

A method of preparing an abuse deterrent controlled release dosage form comprising:
preparing a mixture comprising an opioid agonist and a gelling agent comprising polyethylene oxide, hydroxypropylmethylcellulose and polyethylene glycol; and
heating the mixture to a temperature to at least soften the mixture;
extruding the heated mixture to form an extrudate;
formulating the extrudate into a tablet; and
coating the tablet with a coating comprising polyvinyl alcohol, polyethylene glycol and talc,
wherein the opioid agonist is the sole active agent in the dosage form; and wherein the dosage form forms a gel when subjected to tampering comprising dissolution in from about 0.5 ml to about 10 ml of an aqueous liquid;
the dosage form having a ratio of gelling agent to opioid agonist from about 8:1 to about 1:1;
the dosage form providing a therapeutic effect for about 12 hours or longer when orally administered to a human patient.

### Claim 19 (depends on 1)

The method of claim 1, wherein the ratio of gelling agent to opioid agonist is from about 3:1 to about 1:1.

### Claim 20 (depends on 18)

The method of claim 18, wherein the mixture further comprises alpha-tocopherol.

### Claim 21 (depends on 18)

The method of claim 18, wherein the aqueous liquid is water.

### Claim 22 (depends on 21)

The method of claim 21, wherein the gel is formed when the dosage form is subjected to tampering comprising crushing and dissolution in the water.

### Claim 23 (depends on 21)

The method of claim 21, wherein the gel is formed when the dosage form is subjected to tampering comprising dissolution in the water with heating greater than 45° C.

### Claim 24 (depends on 21)

The method of claim 21, wherein the gelling agent is in an effective amount to impart a viscosity of about 10 cP or more to the gel.