Tamper resistant dosage forms

Patent metadata

Field	Value
Publication number	US-9775811-B2
Application number	US-201715413554-A
Country	US
Kind code	B2
Filing date	Jan 24, 2017
Priority date	Aug 25, 2006
Publication date	Oct 3, 2017
Grant date	Oct 3, 2017

Abstract

The present invention relates to pharmaceutical dosage forms, for example to a tamper resistant dosage form including an opioid analgesic, and processes of manufacture, uses, and methods of treatment thereof.

First claim

The invention claimed is:

1. A method of producing a plurality of extended release pharmaceutical dosage forms comprising the steps of:
mixing an active agent comprising oxycodone or a pharmaceutically acceptable salt thereof and at least one high molecular weight polyethylene oxide (PEO), having an approximate molecular weight of from 1 million to 8 million, to provide a PEO composition;
compressing the PEO composition to provide a plurality of shaped matrix compositions;
curing the shaped matrix compositions by exposure to heated air at a curing temperature that is at least about 60° C. for a curing time of at least about 10 minutes, to provide a plurality of cured matrix compositions;
cooling the cured matrix compositions;
combining any of the matrix compositions with at least one additive, before or after curing; and
optionally providing the cured matrix compositions with at least one film coating, after curing and cooling; wherein
(a) the molecular weight of each PEO is based on rheological measurements;
(b) the high molecular weight PEO comprises at least about 30% (by weight) of each dosage form;
(c) the total weight of each dosage form is calculated by excluding the combined weight of any film coatings;
(d) the active agent comprises at least about 2.4% (by weight) of each dosage form; and
(e) each cured matrix composition comprises a solid oral pharmaceutical dosage form that provides an extended release of at least one active agent.

2. A method according to claim 1 , wherein the curing temperature does not exceed about 90° C.

3. A method according to claim 2 , wherein the curing time does not exceed about 10 hours.

4. A method according to claim 3 , wherein the film coating is present.

5. A method according to claim 3 , wherein the additive comprises at least one of an anti-tacking agent, an antioxidant, an immediate release component, and a retardant.

6. A method according to claim 5 , wherein the additive comprises at least one of butylated hydroxytoluene (BHT), magnesium stearate, talc, silica, fumed silica, colloidal silica dioxide, calcium stearate, carnauba wax, stearic acid, stearyl alcohol, mineral oil, paraffin, micro crystalline cellulose, glycerin, propylene glycol, polyethylene glycol, lactose, povidone, triacetin, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and copolymers comprising methyl methacrylate.

7. A method according to claim 5 , wherein the additive comprises at least one of magnesium stearate, talc, silica, fumed silica, colloidal silica dioxide, calcium stearate, carnauba wax, stearic acid, stearyl alcohol, mineral oil, paraffin, micro crystalline cellulose, glycerin, propylene glycol, polyethylene glycol, lactose, povidone, triacetin, and hydroxypropyl cellulose.

8. A method according to claim 5 , wherein the high molecular weight PEO has a molecular weight that is selected from at least one of 1 million, 2 million, 4 million, 5 million, 7 million, and 8 million.

9. A method according to claim 8 , wherein the active agent is oxycodone hydrochloride in a dosage amount selected from 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, and 80 mg; and the high molecular weight PEO comprises at least about 50% (by weight) of each dosage form.

10. A method according to claim 9 , wherein the high molecular weight PEO has a molecular weight that is selected from at least one of 4 million and 7 million; the film coating is present; and at least one additive is an anti-tacking agent.

11. A method of producing a plurality of solid oral extended release pharmaceutical tablets comprising the steps of:
mixing an active agent comprising oxycodone or a pharmaceutically acceptable salt thereof, and at least one high molecular weight polyethylene oxide (PEO), having an approximate molecular weight of from 1 million to 8 million, to provide a PEO composition;
compressing the PEO composition to provide a plurality of tablet shaped matrix compositions;
curing the shaped matrix compositions by exposure to heated air at a curing temperature that is at least about 60° C. for a curing time of at least about 10 minutes, to provide a plurality of cured matrix compositions;
cooling the cured matrix compositions;
combining the matrix compositions with at least one additive, before or after curing; and
optionally providing the cured matrix compositions with at least one film coating, after curing and cooling;

wherein
(a) the molecular weight of each PEO is based on rheological measurements;
(b) the high molecular weight PEO comprises at least about 50% (by weight) of each tablet;
(c) the active agent comprises more than about 5% (by weight) of each tablet;
(d) the total weight of each tablet is calculated by excluding the combined weight of said film coating; and
(e) each cured matrix composition comprises a solid oral pharmaceutical tablet that provides an extended release of at least one active agent.

12. A method according to claim 11 , wherein
at least one additive comprises an anti-tacking agent;
the curing and cooling steps are conducted in a convection curing device comprising a bed of free flowing tablets;
the heated air comprises inlet air and exhaust air entering and leaving the convection curing device;
the curing temperature does not exceed about 90° C.;
the curing time does not exceed about 10 hours;
the cooling temperature is below about 50° C.; and
each of the curing temperature and the cooling temperature is one of (a) the temperature of the inlet air, (b) the temperature of the exhaust air; and (c) the temperature inside the convection curing device.

13. A method according to claim 12 , wherein the combining step comprises at least one of blending, compressing, layering, spraying, and coating.

14. A method according to claim 12 , wherein each of the curing temperature and the cooling temperature is the temperature of the exhaust air.

15. A method according to claim 14 , wherein the high molecular weight PEO has an approximate molecular weight that is selected from at least one of 1 million, 2 million, 4 million, 5 million, 7 million, and 8 million.

16. A method according to claim 14 , wherein the high molecular weight PEO has an approximate molecular weight that is selected from 1 million, 2 million, 4 million, and 7 million.

17. A method according to claim 16 , wherein the low molecular weight PEO comprises at least about 20% (by weight) of each tablet.

18. A method according to claim 16 , further comprising the step of combining the matrix composition with a low molecular weight PEO having an approximate molecular weight of from 100,000 to 900,000, wherein the low molecular weight PEO comprises at least about 10% (by weight) of each tablet.

19. A method according to claim 18 , wherein the low molecular weight PEO has an approximate molecular weight selected from 100,000and 900,000.

20. A method according to claim 14 , wherein the high molecular weight PEO has an approximate molecular weight selected from 4 million and 7 million.

21. A method according to claim 20 , wherein
the step of compressing the PEO composition comprises tableting by direct compression;
the convection curing device comprises a coating pan;
the curing temperature optionally has a plateau-like profile;
the film coating is present and is combined with the matrix composition, in the coating pan; and
the coating pan has a rotation speed selected for each of the curing, cooling, and film coating steps.

22. A method according to claim

Assignees

• Purdue Pharma Lp
• Purdue Pharmaceuticals LP

Inventors

• Mckenna William H
• Mannion Richard O
• O'Donnell Edward P
• Huang Haiyong H

Classifications

• A61P29/02

  without antiinflammatory effect · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61K9/2013

  Organic compounds, e.g. phospholipids, fats · CPC title