Controlled release hydrocodone formulations
A solid oral controlled-release oral dosage form of hydrocodone is disclosed. The dosage form comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof, and a sufficient amount of a controlled release material to render the dosage form suitable for twice-a-day administration to a human patient, the dosage form providing a C 12 /C max ratio of 0.55 to 0.85, said dosage form providing a therapeutic effect for at least about 12 hours.
1. An oral dosage form comprising a or a pharmaceutically acceptable salt thereof the dosage form releasing the hydrocodone or pharmaceutically acceptable salt thereof at such a rate that plasma concentrations of hydrocodone are maintained within the therapeutic range but below toxic concentrations for about 12 hours or longer,
wherein the hydrocodone or pharmaceutically acceptable salt thereof is the only drug in the dosage form,
the dosage form provides a hydrocodone plasma concentration of at least about 8 ng/ml at about 8 hours after oral administration,
a hydrocodone plasma concentration of about 5 ng/ml or greater at 12 hours after oral administration, and
the dosage form is a tablet or a capsule.
2. The dosage form of claim 1 , wherein the dosage form provides controlled release of hydrocodone or a pharmaceutically acceptable salt thereof for about 24 hours.
3. The dosage form of claim 2 , wherein the dosage form is a tablet.
4. The dosage form of claim 3 , wherein the dosage form provides a hydrocodone plasma concentration of at least about 8 ng/ml at about 2 hours after oral administration.
5. The dosage form of claim of claim 4 , wherein the tablet comprises a pharmaceutically acceptable polymer.
6. The dosage form of claim 5 , wherein the pharmaceutically acceptable polymer comprises between 1% and 80% of the tablet by weight.
7. The dosage form of claim 5 , wherein the dosage form comprises an excipient having a melting point of from 30 to about 200° C.
8. The dosage form of claim 5 , wherein the pharmaceutically acceptable polymer is a hydroxyalkylcellulose.
9. The dosage form of claim 8 , wherein the hydroxyalkylcellulose is a hydroxypropylcellulose or a hydroxypropylmethylcellulose.
10. The dosage form of claim 9 , wherein the hydroxyalkylcellulose is the hydroxypropylmethylcellulose.
11. The dosage form of claim 7 , wherein the excipient is a polyalkylene glycol.
12. The dosage form of claim 1 , wherein hydrocodone C max that increases linearly from one dosage strength to another.
13. The dosage form of claim 3 , wherein the dosage form provides a plasma concentration profile of hydrocodone with a C 12 /C max hydrocodone ratio of 0.55 to 0.85.
14. The dosage form of claim 3 , wherein the dosage form provides a plasma concentration profile of hydrocodone with a C 12 /C max hydrocodone ratio of 0.55 to 0.65.
15. The dosage form of claim 3 , wherein the dosage form provides a plasma concentration profile of hydrocodone with a C 12 /C max hydrocodone ratio of 0.65 to 0.85.
16. The dosage form of claim 14 , wherein said C 12 /C max hydrocodone ratio is calculated from hydrocodone plasma concentrations from first oral administration of the dosage form to a population of fasted humans.
17. The dosage form of claim 15 , wherein said C 12 /C max hydrocodone ratio is calculated from hydrocodone plasma concentrations from first oral administration of the dosage form to a population of fasted humans.
18. The dosage form of claim 14 , wherein a portion of the plasma concentration profile of hydrocodone is relatively flat.
19. The dosage form of claim 14 , wherein said C 12 /C max hydrocodone ratio is calculated from hydrocodone plasma concentrations from first oral administration of the dosage form to a fed human.
20. The dosage form of claim 15 , wherein said C 12 /C max hydrocodone ratio is calculated from hydrocodone plasma concentrations from first oral administration of the dosage form to a fed human.
21. The dosage form of claim 13 , wherein said C 12 /C max hydrocodone ratio is calculated from hydrocodone plasma concentrations from first oral administration of the dosage form to a population of fed human.
22. The dosage form of claim 1 , wherein said hydrocodone plasma concentrations are hydrocodone plasma concentrations from first oral administration of the dosage form to a fasted human.
23. The dosage form of claim 1 , wherein said hydrocodone plasma concentrations are hydrocodone plasma concentrations from first oral administration of the dosage form to a fed human.
24. An oral dosage form comprising from or a pharmaceutically acceptable salt thereof and an excipient, the excipient comprising from 1% to 80% of the dosage form by weight, wherein
hydrocodone or a pharmaceutically acceptable salt thereof is the only drug in the dosage form, and
the dosage form provides
a controlled release of hydrocodone or a pharmaceutically acceptable salt thereof over about 8 to about 24 hours,
a hydrocodone plasma concentration of at least about 8 ng/ml from at about 8 hours after oral administration, and
a hydrocodone plasma concentration of about 5 ng/ml or greater at 12 hours after oral administration.
25. The dosage form of claim 24 , wherein the dosage form is a tablet.
26. The dosage form of claim 24 , wherein the dosage form provides a hydrocodone plasma concentration of at least about 8 ng/ml at about 2 hours after oral administration.
27. The dosage form of claim 24 , wherein the dosage form provides a plasma concentration profile of hydrocodone with a C 12 /C max hydrocodone ratio of 0.55 to 0.85.
28. The dosage form of claim 27 , wherein a portion of the plasma concentration profile of hydrocodone is relatively flat.
29. The dosage form of claim 27 , wherein said C 12 /C max hydrocodone ratio is calculated from hydrocodone plasma concentrations from first oral administration of the dosage form to a fasted human.
30. The dosage form of claim 24 , wherein said hydrocodone plasma concentrations are hydrocodone plasma concentrations from first oral administration of the dosage form to a fed human.
31. An oral dosage form comprising a or a pharmaceutically acceptable salt thereof the dosage form releasing the hydrocodone or a pharmaceutically acceptable salt thereof at such a rate that plasma concentrations of hydrocodone are maintained within the therapeutic range but below toxic concentrations for about 12 hours or longer,
wherein the hydrocodone or a pharmaceutically acceptable salt thereof is the only drug in the dosage form,
the dosage form provides a hydrocodone plasma concentration of at least about 8 ng/ml at about 8 hours after oral administration,
a hydrocodone plasma concentration of 3.93 ng/ml or greater at 12 hours after oral administration, and
the dosage form is a tablet or a capsule.
32. The dosage form of claim 31 , wherein the dosage form comprises 15 mg of hydrocodone bitartrate.