Tamper resistant dosage forms

Patent metadata

Field	Value
Publication number	US-9492389-B2
Application number	US-201514729565-A
Country	US
Kind code	B2
Filing date	Jun 3, 2015
Priority date	Aug 25, 2006
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

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 cured shaped pharmaceutical tablet comprising:
(1) at least a first compression shaped and then air cured matrix, wherein said curing is without compression, by heated air having a temperature of at least about 62° C. for a duration of at least about 5 minutes, said matrix comprising an opioid or a pharmaceutically acceptable salt thereof in combination with at least one high molecular weight polyethylene oxide having, based on rheological measurements, an approximate molecular weight selected from the group consisting of 4,000,000, 7,000,000, and a combination thereof, and optionally further comprising at least one low molecular weight polyethylene oxide having, based on rheological measurements, an approximate molecular weight of less than 1,000,000;
(2) optionally a second air cured matrix comprising an opioid or a pharmaceutically acceptable salt thereof in combination with at least one low molecular weight polyethylene oxide having, based on rheological measurements, an approximate molecular weight of less than 1,000,000; and
(3) optionally a coating,

wherein, in said tablet:
said high molecular weight polyethylene oxide is at least 54% by weight of the total weight of said uncoated tablet;
low molecular weight polyethylene oxide, if present, is at least 10% by weight of the total weight of said uncoated tablet; and
said tablet provides a once-daily or twice-daily extended release of said opioid or pharmaceutically acceptable salt thereof from said tablet.

2. A cured shaped tablet as defined in claim 1 , wherein said opioid or pharmaceutical salt thereof comprises at least 2.4% by weight, based upon the total weight of said uncoated tablet, and is selected from oxycodone, hydrocodone, morphine, hydromorphone, and oxymorphone.

3. A cured shaped tablet as defined in claim 1 , wherein each shaped and cured matrix has been cured by heated air having a temperature of about 62° C. to about 90° C. for a duration of about 15 minutes to about 10 hours, and then is subsequently cooled.

4. A cured shaped tablet as defined in claim 3 , wherein said heated air temperature is from about 65° C. to about 90° C., said duration is from about 15 minutes to about 8 hours, and said cooling comprises exposure to an air temperature of less than about 62° C.

5. A cured shaped tablet as defined in claim 2 , wherein said pharmaceutically acceptable salt is selected from hydrochloride, hydrobromide, sulfate, phosphate, formate, acetate, trifluoroacetate, maleate, and tartrate.

6. A cured shaped tablet as defined in claim 4 , wherein one or both of said first matrix and second matrix further comprise a coating.

7. A cured shaped tablet as defined in claim 1 , wherein, said second matrix is present and said low molecular weight polyethylene oxide comprises at least about 20% by weight of the total weight of said uncoated tablet.

8. A cured shaped tablet as defined in claim 6 , wherein, said second matrix is present and said low molecular weight polyethylene oxide comprises at least about 20% by weight of the total weight of said uncoated tablet.

9. A cured shaped tablet as defined in claim 7 , wherein said low molecular weight polyethylene oxide is at least 22% by weight based upon the total weight of said uncoated tablet and said opioid or pharmaceutically acceptable salt is at least 2.4% by weight based upon the total weight of said uncoated tablet.

10. A cured shaped tablet as defined in claim 6 , wherein the total combined weight of said high and low molecular weight polyethylene oxide is at least 60% by weight, based upon the total weight of said uncoated tablet.

11. A cured shaped tablet as defined in claim 6 , wherein the total combined weight of said high and low molecular weight polyethylene oxide is at least 65% by weight, based upon the total weight of said uncoated tablet.

12. A cured shaped tablet as defined in claim 6 , wherein the total combined weight of said high and low molecular weight polyethylene oxide is at least 80% by weight, based upon the total weight of said uncoated tablet.

13. A cured shaped tablet as defined in claim 6 , wherein the total combined weight of said high and low molecular weight polyethylene oxide is at least 85% by weight, based upon the total weight of said uncoated tablet.

14. A cured shaped tablet as defined in claim 6 , wherein the total combined weight of said high and low molecular weight polyethylene oxide is at least 90% by weight, based upon the total weight of said uncoated tablet.

15. A cured shaped tablet as defined in claim 6 , wherein said tablet further comprises magnesium stearate.

16. A cured shaped tablet as defined in claim 15 , wherein said tablet further comprises butylated hydroxytoluene.

17. A cured shaped tablet as defined in claim 15 , wherein said tablet further comprises at least one of lactose, microcrystalline cellulose and hydroxypropyl cellulose.

18. A cured shaped tablet as defined in claim 1 , wherein said tablet, when subjected to an indentation test, has at least one of (i) a cracking force of at least 110 N; and (ii) a penetration depth to crack distance of at least 1.0 mm.

19. A cured shaped tablet as defined in claim 1 , wherein said tablet can be flattened to a thickness that is no more than about 60% of the initial tablet thickness without breaking; and said flattened tablet swells upon exposure to water or ethanol.

20. A cured shaped tablet according to claim 1 , wherein, after a plurality of at least 100 of the same tablets are stored at 40° C. and 75% relative humidity for at least 3 months, a set of at least ten of said stored tablets, on average, when measured in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37° C., in the absence of an added stabilizer, release an amount of said opioid or pharmaceutical salt thereof, after 1 hour, 4 hours, and 12 hours, that deviates from an initial dosage amount of said opioid or pharmaceutically acceptable salt thereof by no more than about 10% points.

21. A cured shaped tablet as defined in claim 3 , wherein said air temperature during curing exhibits a plateau profile.

22. A cured shaped tablet as defined in claim 4 , wherein said air temperature during curing exhibits a plateau profile.

23. A cured shaped tablet as defined in claim 3 , wherein said air temperature during curing exhibits a parabolic or triangular profile.

24. A cured shaped tablet as defined in claim 4 , wherein said air temperature during curing exhibits a parabolic or triangular profile.

25. A cured shaped tablet as defined in claim 3 , wherein curing is by convection and said air temperature is measured as a mean exhaust temperature of a convection curing device.

26. A cured shaped tablet as defined in claim 3 , wherein curing is by convection at atmospheric pressure and said air temperature is measured as a mean exhaust temperature of a convection curing device.

27. A cured shaped tablet as defined in claim 4 , wherein curing is by convection at atmospheric pressure and said air temperature is measured as a mean exhaust temperature of a convection curing device.

28. A cured shaped tablet as defined in claim 19 , wherein said tablet, when subjected to an indentation test, has at least one of (i) a cracking force of at least 110 N; and (ii) a penetration depth to crack distance of at least 1.0 mm.

Assignees

• Purdue Pharma Lp
• Purdue Pharmaceuticals LP

Inventors

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

Classifications

• A61P25/04

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

• 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

• B29L2031/753

  Medical equipment; Accessories therefor (bloodbags, medical bags B29L2031/7148; artificial eyes B29L2011/0008) · CPC title