Methods of providing analgesia
A solid oral controlled-release dosage form of hydrocodone is disclosed, the dosage form comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof, and controlled release material.
1. A method of providing analgesia in a human comprising:
orally administering once daily to the human a formulation comprising a bitartrate salt of hydrocodone and a pharmaceutically acceptable polymer,
wherein the pharmaceutically acceptable polymer comprises between 1% and 80% of the formulation by weight,
hydrocodone is the only drug in the formulation, and
the formulation provides an in-vitro release rate of hydrocodone, when measured by the USP Basket Method at 100 rpm in 900 ml aqueous buffer at a pH of between 1.6 and 7.2 at 37° C., of from 0% to about 35% at 1 hour, from about 10% to about 70% at 4 hours, from about 20% to about 75% at 8 hours, from about 30% to about 80% at 12 hours, from about 40% to about 90% at 18 hours, and greater than about 60% at 24 hours, and a plasma concentration profile of hydrocodone comprising a C max of hydrocodone and a C 24 of hydrocodone,
wherein the ratio of said C 24 to said C max is from 0.55 to 0.85.
2. The method of claim 1 , wherein the formulation is a capsule or a tablet.
3. The method of claim 2 , wherein the pharmaceutically acceptable polymer is polyethylene oxide.
4. The method of claim 3 , wherein the formulation further comprises a hydroxyalkylcellulose.
5. The method of claim 4 , wherein the hydroxyalkylcellulose is a hydroxypropylcellulose or a hydroxypropylmethylcellulose.
6. The method of claim 5 , wherein the hydroxyalkylcellulose is the hydroxypropylcellulose.
7. The method of claim 1 , wherein said formulation provides therapeutically effective plasma concentrations of hydrocodone for about 24 hours after said administration.
8. The method of claim 1 , wherein a portion of the plasma concentration profile of hydrocodone is relatively flat.
9. The method of claim 7 , wherein said ratio is from 0.55 to 0.7.
10. The method of claim 7 , wherein said ratio is from 0.55 to 0.6.
11. The method of claim 1 , wherein the ratio is calculated from hydrocodone plasma concentration from first administration of the formulation to the human.
12. The method of claim 10 , wherein the ratio is calculated from hydrocodone plasma concentration from first administration of the formulation to the human.
13. A method of providing analgesia in a human comprising:
orally administering once daily to the human a formulation comprising a bitartrate salt of hydrocodone and a pharmaceutically acceptable polymer,
wherein the formulation is a capsule or a tablet,
hydrocodone is the only drug in the formulation,
the pharmaceutically acceptable polymer comprises between 1% and 80% of the formulation by weight,
the formulation provides an in-vitro release rate of hydrocodone, when measured by the USP Basket Method at 100 rpm in 900 ml aqueous buffer at a pH of between 1.6 and 7.2 at 37° C., of from 0% to about 35% at 1 hour, from about 10% to about 70% at 4 hours, from about 20% to about 75% at 8 hours, from about 30% to about 80% at 12 hours, from about 40% to about 90% at 18 hours, and greater than about 60% at 24 hours, and
maintains plasma concentrations of hydrocodone within the therapeutic range over 12 hours or longer after administration to the human,
wherein the formulation provides a hydrocodone plasma concentration profile with a ratio of the plasma concentration of hydrocodone at 24 hours after administration to the highest concentration of hydrocodone during the 24 hours of from 0.55 to 1.0.
14. The method of claim 13 , wherein the formulation provides a C max that increases linearly from one dosage strength to another.
15. The method of claim 13 , wherein the formulation provides an AUC that increases linearly from one dosage strength to another.
16. The method of claim 13 , wherein the pharmaceutically acceptable polymer is polyethylene oxide.
17. The method of claim 16 , wherein the formulation further comprises a hydroxyalkylcellulose.
18. The method of claim 17 , wherein the hydroxyalkylcellulose is a hydroxypropylcellulose or a hydroxypropylmethylcellulose.
19. The method of claim 18 , wherein the hydroxyalkylcellulose is the hydroxypropylcellulose.
20. The method of claim 13 , wherein the formulation maintains therapeutically effective plasma concentrations of hydrocodone for about 24 hours after administration to the human.
21. The method of claim 13 , wherein the formulation comprises a material having a melting point from about 30 to about 200° C.
22. The method of claim 20 , wherein the formulation provides a hydrocodone plasma concentration profile with a ratio of the plasma concentration of hydrocodone at 24 hours after administration to the highest concentration of hydrocodone during the 24 hours of from 0.55 to 0.75.
23. The method of claim 20 , wherein the formulation provides a hydrocodone plasma concentration profile with a ratio of the plasma concentration of hydrocodone at 24 hours after administration to the highest concentration of hydrocodone during the 24 hours of from 0.55 to 0.7.
24. The method of claim 20 , wherein the formulation provides a hydrocodone plasma concentration profile with a ratio of the plasma concentration of hydrocodone at 24 hours after administration to the highest concentration of hydrocodone during the 24 hours of from 0.55 to 0.6.
25. The method of claim 21 , wherein the ratio is calculated from hydrocodone plasma concentration from first administration of the formulation to the human.
26. The method of claim 24 , wherein the ratio is calculated from hydrocodone plasma concentration from first administration of the formulation to the human.
27. The method of claim 13 , wherein the material is polyethylene oxide.