Tamper resistant dosage forms
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.
1. A pharmaceutical composition comprising:
morphine or a pharmaceutically acceptable salt thereof, and at least one high molecular weight polyethylene oxide (PEO), in a solid oral extended release dosage form that is compression shaped, cured, cooled and hardened;
optionally at least one additive;
optionally at least one film coating; and
optionally at least one low molecular weight PEO having an approximate molecular weight of less than 1,000,000; wherein
the high molecular weight PEO has an approximate molecular weight of from 1,000,000 to 15,000,000;
the high and low molecular weight PEO together comprise at least about 50% (by weight) of the dosage form;
the molecular weight of each PEO is based on rheological measurements; and
the total weight of the dosage form excludes the combined weight of any film coatings.
2. A pharmaceutical composition according to claim 1 , wherein the high molecular weight PEO is at least partially melted upon curing.
3. A pharmaceutical composition according to claim 2 , wherein the dosage form comprises a tablet or multi particulates.
4. A pharmaceutical composition according to claim 3 , wherein curing comprises exposure to heated air, without compression, at a curing temperature of at least the softening temperature of the high molecular weight PEO, for a curing time of at least 5 minutes.
5. A pharmaceutical composition according to claim 4 , wherein the dosage form is cured by exposure to heated air within a convection curing device; the heated air comprises inlet air and exhaust air that enters and leaves the convection curing device; the curing temperature is the temperature of the exhaust air and is at least about 60° C.; and the curing time is at least about 10 minutes.
6. A pharmaceutical composition according to claim 5 , wherein the curing temperature does not exceed about 90° C. and the curing time does not exceed about 24 hours.
7. A pharmaceutical composition according to claim 6 , wherein the active agent comprises at least about 5% of the dosage form and the dosage form comprises a tablet.
8. A pharmaceutical composition according to claim 7 , wherein the dosage form is expanded upon curing and provides a hardness of at least about 438 N.
9. A pharmaceutical composition according to claim 8 , wherein the low molecular weight PEO is not present.
10. A pharmaceutical composition according to claim 9 , wherein at least one of the additive and the film coating is present and is selected from 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, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and copolymers comprising methyl methacrylate.
11. A pharmaceutical composition comprising:
morphine or a pharmaceutically acceptable salt thereof, and at least one high molecular weight polyethylene oxide (PEO), in a solid oral extended release tablet that is compression shaped, convection cured, cooled and hardened;
at least one of an additive and a film coating; and
optionally at least one low molecular weight PEO having an approximate molecular weight of less than 1,000,000; wherein
each high molecular weight PEO has an approximate molecular weight that is selected from 1 million, 2 million, 4 million, 5 million, 7 million, and 8 million;
the high and low molecular weight PEO together comprise at least about 50% (by weight) of the tablet;
the tablet is cured for at least 10 minutes by exposure to heated air 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 is the temperature of the exhaust air and is at least about 60° C.;
the molecular weight of each PEO is based on rheological measurements; and
the total weight of the tablet excludes the combined weight of any film coatings.
12. A pharmaceutical composition according to claim 11 , wherein morphine or its pharmaceutically acceptable salt comprises at least about 5% (by weight) of the tablet, and the tablet is expanded upon curing.
13. A pharmaceutical composition according to claim 12 , wherein the pharmaceutically acceptable salt is morphine sulfate, which comprises at least about 10% (by weight) of each tablet.
14. A pharmaceutical composition according to claims 13 , wherein at least one of the additive and the film coating is present and is selected from 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, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and copolymers comprising methyl methacrylate.
15. A pharmaceutical composition according to claim 13 , wherein at least one additive is present and is selected from magnesium stearate and colloidal silica dioxide.
16. A pharmaceutical composition according to claim 13 , wherein at least one additive is present and is an anti-tacking agent.
17. A pharmaceutical composition according to claim 16 , wherein the high molecular weight PEO comprises at least about 60% (by weight) of the tablet.
18. A pharmaceutical composition according to claim 17 , wherein the low molecular weight PEO is not present.
19. A pharmaceutical composition according to claim 18 , wherein the high molecular weight PEO has an approximate molecular weight that is selected from 1 million and 2 million.
20. A pharmaceutical composition according to claim 19 , wherein the curing temperature does not exceed about 90° C.
21. A pharmaceutical composition according to claim 19 , wherein the curing time does not exceed about 24 hours.
22. A pharmaceutical composition according to claim 19 , wherein the curing time does not exceed about 10 hours.
23. A pharmaceutical composition according to claim 19 , wherein the curing temperature is from about 68° C. to about 90° C.
24. A pharmaceutical composition according to claim 19 , wherein at least one additive or anti-tacking agent is magnesium stearate.
25. A pharmaceutical composition according to claim 19 , wherein at least one film coating is present and comprises at least one of talc and polyethylene glycol.
26. A pharmaceutical composition according to claim 19 , wherein the curing temperature is from about 68° C. to about 90° C. and the curing time does not exceed about 10 hours.
27. A pharmaceutical composition according to claim 26 , wherein at least one additive or anti-tacking agent is magnesium stearate.
28. A pharmaceutical composition according to claim 26 , wherein at least one film coating is present and comprises at least one of talc and polyethylene glycol.
29. A pharmaceutical composition according to claim 26 , wherein at least one additive or anti-tacking agent is magnesium stearate and at least one film coating is present and comprises at least one of talc and polyethylene glycol.
30. A pharmaceutical composition according to claim 29 , wherein cooling comprises a reduced air temperature of below about 50° C.
31. A pharmaceutical composition according to claim 30 , wherein the tablet is expanded upon curing, as measured by a decrease in tablet density of at least about 1%.
32. A pharmaceutical composition according to claim 31 , wherein the tablet provides a hardness of at least about 438 N.
33. A pharmaceutical composition according to claim 26 , wherein cooling comprises a reduced air temperature of below about 50° C.
34. A pharmaceutical composition according to claim 33 , wherein the tablet is expanded upon curing, as measured by a decrease in tablet density of at least about 1%.
35. A pharmaceutical composition according to claim 34 , wherein the tablet provides a hardness of at least about 438 N.
36. A pharmaceutical composition according to claim 19 , wherein at least one additive or anti-tacking agent is magnesium stearate and at least one film coating is present and comprises at least one of talc and polyethylene glycol.
37. A pharmaceutical composition according to claim 36 , wherein cooling comprises a reduced air temperature of below about 50° C.
38. A pharmaceutical composition according to claim 37 , wherein the tablet is expanded upon curing, as measured by a decrease in tablet density of at least about 1%.
39. A pharmaceutical composition according to claim 38 , wherein the tablet provides a hardness of at least about 438 N.
40. A pharmaceutical composition according to claim 19 , wherein cooling comprises a reduced air temperature of below about 50° C.
41. A pharmaceutical composition according to claim 40 , wherein the tablet is expanded upon curing, as measured by a decrease in tablet density of at least about 1%.
42. A pharmaceutical composition according to claim 41 , wherein the tablet provides a hardness of at least about 438 N.
43. A pharmaceutical composition according to any of claims 32 - 40 , wherein the high molecular weight PEO comprises at least about 65% (by weight) of the tablet.
44. A pharmaceutical composition according to any of claims 32 - 40 , wherein the high molecular weight PEO comprises at least about 80% (by weight) of the tablet.