# US 9,872,835 B2 · Multiparticles safeguarded against ethanolic dose-dumping

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- Number: US 9,872,835 B2
- Document ID: US9872835B2
- Status: Granted
- Kind: B2
- Application number: 14/719,351
- Filed: 2015-05-22
- Published: 2015-11-26
- Granted: 2018-01-23
- Earliest claimed: 2014-05-26
- Assignees: GrüNenthal GmbH
- Applicants: GrüNenthal GmbH
- Inventors: Lutz Barnscheid; Klaus Wening; Jana Pätz; Anja Geissler
- Web page: https://patentgrep.com/patent/US9872835B2

## CPC

- A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)}
- A61K 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules}
- A61K 9/1682: {Processes}
- A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)}
- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- 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 9/4866: {Organic macromolecular compounds}
- 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

The invention relates to an oral pharmaceutical dosage form providing resistance against dose dumping in aqueous ethanol and comprising a pharmacologically active ingredient embedded in a matrix material, wherein the matrix material comprises an alkyl cellulose and a heteropolysaccharide; and wherein the relative weight ratio of heteropolysaccharide to alkyl cellulose is within the range of from 1:20 to 20:1; and wherein the total content of alkyl cellulose and heteropolysaccharide is at least 35 wt.-%, relative to the total weight of the dosage form. A process of producing the dosage form and methods of using the dosage form, for example to treat pain, are also disclosed.

## Claims

### Claim 1

An oral pharmaceutical dosage form comprising a pharmacologically active ingredient embedded in a matrix material, wherein:
the pharmacologically active ingredient is one selected from pharmacologically active ingredients classified in Anatomical Therapeutic Chemical Classification System (ATC), class Nervous System;
the matrix material comprises a mixture of an alkyl cellulose and a heteropolysaccharide;
the alkyl cellulose is present in the dosage form in an amount of at least 50 wt.-% relative to the total weight of the dosage form;
the heteropolysaccharide is present in the dosage form in an amount of below 50 wt.-% relative to the total weight of the dosage form;
the total content of alkyl cellulose and heteropolysaccharide is at least 60 wt.-% relative to the total weight of the dosage form;
the pharmaceutical dosage form releases by 60 minutes more than 60% of the pharmacologically active ingredient when release of the pharmacologically active ingredient from the pharmaceutical dosage form is measured with a paddle apparatus at 50 rpm, at 37±5° C., in 900 mL 0.1 M HCl (pH 1.0) or simulated intestinal fluid at pH 6.8 (phosphate buffer) or pH 4.5; and
the pharmaceutical dosage form provides resistance against dose dumping in aqueous ethanol.

### Claim 2 (depends on 1)

The dosage form according to claim 1, wherein
the alkyl cellulose is ethyl cellulose; and/or
the heteropolysaccharide is xanthan gum.

### Claim 3 (depends on 1)

The dosage form according to claim 1, which provides prolonged release of the pharmacologically active ingredient.

### Claim 4 (depends on 1)

The dosage form according to claim 1, wherein the content of the heteropolysaccharide is below 45 wt.-%, relative to the total weight of the dosage form.

### Claim 5 (depends on 4)

The dosage form according to claim 4, wherein the content of the heteropolysaccharide is below 30 wt.-%, relative to the total weight of the dosage form.

### Claim 6 (depends on 1)

The dosage form according to claim 1, wherein the total content of alkyl cellulose and heteropolysaccharide is at least 70 wt.-%, relative to the total weight of the dosage form.

### Claim 7 (depends on 1)

The dosage form according to claim 1, wherein the alkyl cellulose is ethyl cellulose having an ethoxyl content of from 40 wt.-% to 60 wt.-%.

### Claim 8 (depends on 1)

The dosage form according to claim 1, wherein the alkyl cellulose is ethyl cellulose having a solution viscosity within the range of from 70 mPa·s to 130 mPa·s, measured in a 5 wt.-% solution of 80 wt.-% toluene and 20 wt.-% ethanol at 25° C. in an Ubbelohde viscosimeter.

### Claim 9 (depends on 1)

The dosage form according to claim 1, wherein the pharmacologically active ingredient is an opioid.

### Claim 10 (depends on 9)

The dosage form according to claim 9, wherein the pharmacologically active ingredient is selected from the group consisting of oxycodone, oxymorphone, hydrocodone, hydromorphone, tramadol, tapentadol, morphine, buprenorphine, and the physiologically acceptable salts thereof.

### Claim 11 (depends on 1)

The dosage form according to claim 1, which is particulate.

### Claim 12 (depends on 1)

The dosage form according to claim 1, which is a filled capsule or a tablet.

### Claim 13 (depends on 1)

The dosage form according to claim 1, which is particulate and in form of a filled capsule, wherein
the pharmacologically active ingredient is selected from the group consisting of oxycodone, oxymorphone, hydrocodone, hydromorphone, tramadol, tapentadol, morphine, buprenorphine, and the physiologically acceptable salts thereof; and
the alkyl cellulose is ethyl cellulose; and
the heteropolysaccharide is xanthan gum; and
the relative weight ratio of xanthan gum to ethyl cellulose is within the range of from 1:18 to 1:1.

### Claim 14 (depends on 1)

A method for treating pain in a patient in need thereof, said method comprising administering to said patient an effective amount therefor of a dosage form according to claim 1.

### Claim 15 (depends on 1)

The dosage form according to claim 1, wherein the content of the alkyl cellulose is at least 63 wt.-%, relative to the total weight of the dosage form.

### Claim 16 (depends on 1)

The dosage form according to claim 1, which releases by 3 hours at least 90% of the pharmacologically active ingredient.