# US 9,517,236 B2 · Controlled release hydrocodone formulations

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- Number: US 9,517,236 B2
- Document ID: US9517236B2
- Status: Granted
- Kind: B2
- Application number: 15/019,695
- Filed: 2016-02-09
- Published: 2016-06-09
- Granted: 2016-12-13
- Earliest claimed: 2000-10-30
- Assignees: Purdue Pharma L.P.
- Applicants: Purdue Pharma L.P.
- Inventors: Benjamin Oshlack; Hua-Pin Huang; John K. Masselink; Alfred Tonelli
- Web page: https://patentgrep.com/patent/US9517236B2

## CPC

- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61K 9/0004: {Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/141: {Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers ((co) spray-dried products A61K9/16, (co) lyophilised products A61K9/19; the carrier being chemically bound to the active ingredient A61K47/50)}
- 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 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- 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)}
- 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 31/194: having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
- A61K 31/46: 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
- 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]
- 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

A solid oral controlled-release dosage form of hydrocodone is disclosed, the dosage form comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof, and controlled release material.

## Claims

### Claim 1

A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a matrix comprising hydrocodone or a pharmaceutically acceptable salt thereof and a controlled release material comprising a material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, shellac, oils, and mixtures thereof,
the dosage form providing a ratio of a plasma concentration of hydrocodone at the end of a dosing interval to a maximum plasma concentration of hydrocodone during the dosing interval of from 0.55 to 1 and effective pain relief over a period of time of about 12 hours or longer after administration to a human patient, wherein
the dosage form is a compressed tablet, and
the hydrocodone or pharmaceutically acceptable salt thereof is the only active agent in the dosage form.

### Claim 2 (depends on 1)

The dosage form of claim 1, wherein the effective pain relief is provided for about 12 hours.

### Claim 3 (depends on 2)

The dosage form of claim 2, wherein said administration is first administration.

### Claim 4 (depends on 3)

The dosage form of claim 3, wherein the controlled release material comprises a cellulose ether.

### Claim 5

A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a matrix comprising hydrocodone or a pharmaceutically acceptable salt thereof, a controlled release material comprising a material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, shellac, oils, and mixtures thereof,
the dosage form providing a W50 of hydrocodone of between 4 and 22 hours and a plasma concentration of hydrocodone within a therapeutic range over a period of time of about 12 hours or longer after administration to a human patient, wherein
the dosage form is a compressed tablet, and
the hydrocodone or pharmaceutically acceptable salt thereof is the only active agent in the dosage form.

### Claim 6 (depends on 5)

The dosage form of claim 5, wherein the dosage form provides the plasma concentration of hydrocodone within the therapeutic range over a period of time of about 12 hours after administration to the human patient.

### Claim 7 (depends on 6)

The dosage form of claim 6, wherein said administration is first administration.

### Claim 8 (depends on 5)

The dosage form of claim 5, wherein said administration is first administration.

### Claim 9 (depends on 5)

The dosage form of claim 5, wherein the controlled release material comprises a cellulose ether.

### Claim 10 (depends on 7)

The dosage form of claim 7, wherein the dosage form provides a C24/Cmax hydrocodone ratio of from 0.55 to 1 after said administration and a therapeutic effect for about 24 hours.

### Claim 11

A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a matrix comprising hydrocodone or a pharmaceutically acceptable salt thereof, a controlled release material comprising a material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, shellac, oils, and mixtures thereof,
the dosage form providing a Tmax hydrocodone of from about 4 to about 14 hours and a plasma concentration of hydrocodone within a therapeutic range over a period of time of about 12 hours or longer after administration to a human patient, wherein
the dosage form is a compressed tablet, and
the hydrocodone or a pharmaceutically acceptable salt thereof is the only active agent in the dosage form.

### Claim 12 (depends on 11)

The dosage form of claim 11, wherein the dosage form provides the plasma concentration of hydrocodone within the therapeutic range over a period of time of about 12 hours after administration to the human patient.

### Claim 13 (depends on 12)

The dosage form of claim 12, wherein said administration is first administration.

### Claim 14 (depends on 11)

The dosage form of claim 11, wherein said administration is first administration.

### Claim 15 (depends on 1)

The dosage form of claim 1, wherein the dosage form provides a mean C24/Cmax hydrocodone ratio of from 0.55 to 1 and a therapeutic effect for about 24 hours after administration to a patient population and the dosing interval is 24 hours.

### Claim 16 (depends on 1)

The dosage form of claim 1, wherein the dosage form provides a C24/Cmax hydrocodone ratio of from 0.55 to 1 and a therapeutic effect for about 24 hours after administration to the human patient and the dosing interval is 24 hours.

### Claim 17 (depends on 11)

The dosage form of claim 11, wherein the controlled release material comprises a cellulose ether.

### Claim 18

A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a matrix comprising hydrocodone bitartrate, a controlled release material comprising a material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, shellac, oils, and mixtures thereof,
the dosage form providing a plasma concentration of hydrocodone within a therapeutic range over a period of time of about 12 hours or longer after administration to a human patient, wherein
the dosage form is a compressed tablet, and
the hydrocodone bitartrate is the only active agent in the dosage form.

### Claim 19 (depends on 18)

The dosage form of claim 18, wherein the controlled release material comprises a cellulose ether.

### Claim 20 (depends on 18)

The dosage form of claim 18, wherein the controlled release material comprises ethylcellulose.

### Claim 21 (depends on 18)

The dosage form of claim 18, wherein the dosage form provides a mean C24/Cmax hydrocodone ratio of from 0.55 to 1 and a therapeutic effect for about 24 hours after administration to a patient population.

### Claim 22 (depends on 1)

The dosage form of claim 1, wherein the controlled release material comprises ethylcellulose.

### Claim 23 (depends on 18)

The dosage form of claim 18, wherein the controlled release material is included in an effective amount such that the dosage form provides an in-vitro release of hydrocodone when measured by the USP Basket method at 100 rpm in 700 ml aqueous buffer at a pH of 1.2 at 37° C. of from 10% to about 45% by weight hydrocodone released at 1 hour.

### Claim 24 (depends on 18)

The dosage form of claim 18, wherein the dosage form provides the plasma concentration of hydrocodone within the therapeutic range over a period of time of about 12 hours after administration to the human patient.

### Claim 25 (depends on 24)

The dosage form of claim 24, wherein said administration is first administration.

### Claim 26 (depends on 18)

The dosage form of claim 18, wherein said administration is first administration.

### Claim 27 (depends on 1)

The dosage form of claim 1, wherein the matrix comprises a hydroxyalkylcellulose.

### Claim 28 (depends on 3)

The dosage form of claim 3, wherein the dosage form provides a mean ratio of mean plasma concentrations of hydrocodone at the end of a dosing interval to mean maximum plasma concentrations of hydrocodone during the dosing interval of 0.55 to 1 after administration to a patient population.

### Claim 29 (depends on 28)

The dosage form of claim 28, which provides a C24/Cmax hydrocodone ratio of from 0.55 to 1 and a therapeutic effect for about 24 hours after said administration and the dosing interval is 24 hours.

### Claim 30 (depends on 18)

The dosage form of claim 18, wherein the matrix comprises a hydroxyalkylcellulose.