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 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 hydrocodone 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 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 hydrocodone 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;
said 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 extended release of hydrocodone or pharmaceutically acceptable salt thereof from said tablet.
2. A cured shaped tablet as defined in claim 1 , wherein said hydrocodone or pharmaceutical salt thereof comprises at least 2.4% by weight, based upon the total weight of said uncoated tablet.
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 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 1 , wherein said shaped tablet is coated at least one of before or after being cured.
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 hydrocodone 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 hydrocodone or pharmaceutical salt thereof, after 1 hour, 4 hours, and 12 hours, that deviates from an initial dosage amount of said hydrocodone 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.
29. A cured shaped tablet as defined in claim 1 wherein said cured shaped tablet has a density that is at least about 1% lower than the density of said shaped tablet prior to curing.
30. A cured shaped tablet as defined in claim 4 wherein said cured shaped tablet has a density that is at least about 1% lower than the density of said shaped tablet prior to curing.