# US 2014/0155489 A1 · Process for the production of an abuse-proofed solid dosage form

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- Number: US 2014/0155489 A1
- Document ID: US20140155489A1
- Status: Published application
- Kind: A1
- Application number: 14/174,876
- Filed: 2014-02-07
- Published: 2014-06-05
- Earliest claimed: 2004-04-22
- Assignees: GrüNenthal GmbH
- Applicants: GrüNenthal GmbH
- Inventors: Elisabeth ARKENAU-MARIC; Johannes BARTHOLOMÄUS; Heinrich KUGELMANN
- Web page: https://patentgrep.com/patent/US20140155489A1

## CPC

- A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)}
- A61J 3/10: into the form of compressed tablets (tablet presses B30B11/00)
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/2031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers}
- A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets}
- A61K 9/2095: {Tabletting processes}
- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- 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 25/04: Centrally acting analgesics, e.g. opioids
- B29C 43/003: {characterised by the choice of material}
- B29C 43/006: {Pressing and sintering powders, granules or fibres}
- A61J 3/06: into the form of pills, lozenges or dragees
- A61J 2200/20: Extrusion means, e.g. for producing pharmaceutical forms
- B29L 2031/00: Other particular articles
- 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
- 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)
- B29L: INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES

## Abstract

The present invention relates to a process for the production of an abuse-proofed solid dosage form containing at least one active ingredient with potential for abuse and a binder with a breaking strength of ≧500 N, by exposing a mixture comprising the active ingredient and the binder to ultrasound and force.

## Claims

### Claim 1

A process for the production of an abuse-proofed solid dosage form comprising at least one active ingredient with potential for abuse and at least one binder with a breaking strength of ≧500 N, wherein a mixture comprising the active ingredient and the binder is exposed to ultrasound and force.

### Claim 2 (depends on 1)

A process according to claim 1, wherein the dosage form is an oral dosage form.

### Claim 3 (depends on 1)

A process according to claim 1, wherein the at least one active ingredient is at least one active ingredient selected from the group consisting of opioids, opiates, stimulants and further narcotics and the physiologically acceptable derivatives thereof.

### Claim 4 (depends on 3)

A process according to claim 3, wherein the physiologically acceptable derivatives are salts, solvates, esters, ethers or amides.

### Claim 5 (depends on 1)

A process according to claim 1, wherein the active ingredient with potential for abuse which is selected from the group consisting of oxycodone, morphine, hydromorphone, tramadol and the physiologically acceptable salts thereof.

### Claim 6 (depends on 1)

A process according to claim 1, wherein the at least one binder is present in a quantity of at least 20 wt. %, relative to the total weight of the dosage form.

### Claim 7 (depends on 1)

A process according to claim 1, wherein the at least one binder is at least one synthetic or natural polymer and optionally a wax, in each case with a breaking strength of at least 500 N.

### Claim 8 (depends on 7)

A process according to claim 7, wherein the polymer exhibits a viscosity at 25° C. of 4500 to 17600 cP, measured on a 5 wt. % aqueous solution with the assistance of a Brookfield viscosimeter.

### Claim 9 (depends on 7)

A process according to claim 7, wherein the polymer is at least one polymer selected from the group consisting of polyethylene oxides, polyethylenes, polypropylenes, polyvinyl chlorides, polycarbonates, polystyrenes, polyacrylates and the copolymers thereof.

### Claim 10 (depends on 9)

A process according to claim 9, wherein the polymer is polyethylene oxide, and the polyethylene oxide has a molecular weight of at least 1 million.

### Claim 11 (depends on 1)

A process according to claim 1, wherein, apart from the active ingredient with potential for abuse and the binder, the dosage form further comprises conventional auxiliary substances.

### Claim 12 (depends on 11)

A process according to claim 11, wherein the dosage form comprises a plasticiser as the auxiliary substance.

### Claim 13 (depends on 1)

A process according to claim 1, wherein the applied ultrasound has a frequency of 1 kHz to 2 MHz.

### Claim 14 (depends on 1)

A process according to claim 1, wherein there is direct contact between the mixture and the ultrasound source during ultrasonication.

### Claim 15 (depends on 1)

A process according to claim 1, wherein ultrasonication proceeds until the binder has softened.

### Claim 16 (depends on 1)

A process according to claim 1, wherein shaping of the mixture proceeds by compaction during or after ultrasonication or by extrusion with rollers and/or by calendering during or after ultrasonication.

### Claim 17 (depends on 16)

A process according to claim 16, wherein a force is applied for the purpose of compaction.

### Claim 18 (depends on 16)

A process according to claim 16, wherein, for compaction, the mixture is already in the form of powder, pellets, microparticles or granules, which have been produced by conventional processes.

### Claim 19 (depends on 1)

A process according to claim 1, which further comprises shaping the mixture into tablets.

### Claim 20 (depends on 1)

A process according to claim 1, wherein the mixture is shaped into a multiparticulate final shape.