# US 8,771,732 B2 · Sustained release formulations of nalbuphine

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- Number: US 8,771,732 B2
- Document ID: US8771732B2
- Status: Granted
- Kind: B2
- Application number: 11/509,347
- Filed: 2006-08-24
- Published: 2007-03-01
- Granted: 2014-07-08
- Earliest claimed: 2005-08-24
- Assignees: Endo Pharmaceuticals Inc.
- Applicants: Anand R. Baichwal; Philip A. Goliber; Anthony E. Carpanzano; Thomas Sciascia; Donald Diehl, II; Brian Vogler
- Inventors: Anand R. Baichwal; Philip A. Goliber; Anthony E. Carpanzano; Thomas Sciascia; Donald Diehl, II; Brian Vogler
- Web page: https://patentgrep.com/patent/US8771732B2

## CPC

- A61K 9/205: {Polysaccharides, e.g. alginate, gums; Cyclodextrin}
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/209: {containing drug in at least two layers or in the core and in at least one outer layer}
- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- 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

Sustained release formulations of nalbuphine or pharmaceutically acceptable salts thereof; methods for making the sustained release formulations of nalbuphine or pharmaceutically acceptable salts thereof; and methods for using the sustained release formulations of nalbuphine or pharmaceutically acceptable salts thereof to treat patients suffering from pain are provided.

## Claims

### Claim 1

An oral sustained release formulation of nalbuphine comprising nalbuphine compound or a pharmaceutically acceptable salt thereof homogeneously dispersed within a hydrophilic gel matrix, wherein the hydrophilic gel matrix comprises xanthan gum, a hydrophilic cellulose ether or both, wherein the formulation provides an analgesic effect for at least about 8 hours.

### Claim 2 (depends on 1)

The sustained release formulation of claim 1, wherein the nalbuphine or pharmaceutically acceptable salt thereof is present in an amount of about 1 mg to about 200 mg in the formulation.

### Claim 3 (depends on 1)

The sustained release formulation of claim 1, wherein the nalbuphine or pharmaceutically acceptable salt thereof is present in an amount of about 60 mg in the formulation.

### Claim 4 (depends on 1)

The sustained release formulation of claim 1, wherein the formulation provides an analgesic effect for at least about 12 hours.

### Claim 5 (depends on 1)

The sustained release formulation of claim 1, wherein the hydrophilic gel matrix comprises xanthan gum and a hydrophilic cellulose ether.

### Claim 6 (depends on 1)

The sustained release formulation of claim 1, wherein the hydrophilic cellulose ether is hydroxypropylcellulose.

### Claim 7 (depends on 1)

The sustained release formulation of claim 1, wherein the hydrophilic cellulose ether is hydroxypropylmethylcellulose.

### Claim 8 (depends on 1)

The sustained release formulation of claim 1, wherein the hydrophilic gel matrix further comprises a cross-linking agent.

### Claim 9 (depends on 1)

The sustained release formulation of claim 1, wherein the hydrophilic gel matrix further comprises a pharmaceutical diluent.

### Claim 10 (depends on 1)

The sustained release formulation of claim 1, wherein the hydrophilic gel matrix further comprises a cationic cross-linking agent.

### Claim 11 (depends on 1)

The sustained release formulation of claim 1, wherein the hydrophilic gel matrix further comprises a lubricant.

### Claim 12 (depends on 5)

The sustained release formulation of claim 5, wherein the hydrophilic gel matrix further comprises a cross-linking agent, a cationic cross-linking agent, a pharmaceutical diluent, and a lubricant.

### Claim 13 (depends on 12)

The sustained release formulation of claim 12, wherein the hydrophilic cellulose ether is hydroxypropylcellulose, the cross-linking agent is locust bean gum, the pharmaceutical diluent is mannitol, the cationic cross-linking agent is calcium sulfate dihydrate, and the lubricant is magnesium stearate.

### Claim 14 (depends on 5)

The sustained release formulation of claim 5, wherein the hydrophilic gel matrix further comprises a pharmaceutical diluent and a lubricant.

### Claim 15 (depends on 14)

The sustained release formulation of claim 14, wherein the pharmaceutical diluent comprises lactose, microcrystalline cellulose or both.

### Claim 16 (depends on 11)

The sustained release formulation of claim 11, wherein the hydrophilic cellulose ether is hydroxypropylmethylcellulose.

### Claim 17 (depends on 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A solid dosage form comprising the formulation of any one of claims 1-2, 4 and 5-16.

### Claim 18 (depends on 17)

The solid dosage form of claim 17, wherein the formulation is a tablet.

### Claim 19 (depends on 17)

The solid dosage form of claim 17, wherein the formulation is a powder.

### Claim 20 (depends on 17)

The solid dosage form of claim 17, wherein the formulation is a capsule.

### Claim 21 (depends on 17)

The solid dosage form of claim 17, wherein the oral dosage form provides a blood serum level of nalbuphine or a pharmaceutically acceptable salt thereof characterized by one or more peaks followed by plateau region.

### Claim 22 (depends on 21)

The solid dosage form of claim 21, wherein the plateau region has a duration of at least about 1 hour.

### Claim 23 (depends on 21)

The solid dosage form of claim 21, wherein the blood serum level of nalbuphine or a pharmaceutically acceptable salt thereof at each time point in the plateau region ranges from about 75% to about 125% of the mean blood serum level in the plateau region.

### Claim 24 (depends on 21)

The solid dosage form of claim 21, wherein 75%-100% of the nalbuphine or a pharmaceutically acceptable salt thereof is released after about 12 hours as determined using USP Apparatus III at 15 dpm in a pH 6.8 buffer at 37° C.