Controlled release hydrocodone formulations
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 solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a plurality of multiparticulates comprising an amount of a hydrocodone bitartrate salt equivalent to from about 5 mg to about 60 mg of hydrocodone and a controlled release material,
the plurality of multiparticulates compressed into a tablet,
the dosage form providing
a ratio of a plasma concentration of hydrocodone at the end of a dosing interval to a maximum plasma concentration of hydrocodone during the dosing interval of about 0.55 to about 1, and an effective pain relief over a period of time of about 12 hours or longer after administration to a human patient or a population of patients,
an in-vitro release of hydrocodone when measured by the USP Basket method at 100 rpm in 700 ml aqueous buffer at a pH of 1.2 at 37° C. of from 10% to about 45% by weight hydrocodone released at 1 hour,
wherein said hydrocodone bitartrate salt is the only active agent in the dosage form.
2. The dosage form of claim 1 , wherein the effective pain relief is provided for about 12 hours.
3. The dosage form of claim 2 , wherein said administration is first administration.
4. The dosage form of claim 3 , wherein the controlled release material comprises a material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, shellac and oils.
5. A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a plurality of multiparticulates comprising an amount of a hydrocodone bitartrate salt equivalent to from about 5 mg to about 60 mg of hydrocodone and a controlled release material, the multiparticulates individually coated with a controlled-release coating and compressed into a tablet,
the controlled release material included in an effective amount such that the dosage form provides a W 50 of hydrocodone of between 4 and 22 hours and a plasma concentration of hydrocodone within a therapeutic range but below toxic concentrations over a period of time of about 12 hours or longer after administration to a human patient or a population of patients,
wherein said hydrocodone bitartrate salt is the only active agent in the dosage form.
6. The dosage form of claim 5 , wherein the dosage form provides the plasma concentration of hydrocodone within the therapeutic range but below toxic concentrations over a period of time of about 12 hours after administration to the human patient or the population of patients.
7. The dosage form of claim 6 , wherein said administration is first administration.
8. The dosage form of claim 5 , wherein said administration is first administration.
9. The dosage form of claim 5 , wherein the controlled release material comprises a material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, shellac and oils.
10. The dosage form of claim 9 , wherein the acrylic resins are selected from the group consisting of ammonio methacrylate copolymers.
11. A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a plurality of pharmaceutically acceptable matrices comprising an amount of a hydrocodone bitartrate salt equivalent to from about 5 mg to about 60 mg of hydrocodone and a controlled release material, the pharmaceutically acceptable matrices individually coated with a controlled-release coating and compressed into a tablet,
the dosage form providing a T max of hydrocodone of from about 4 to about 10 hours and a plasma concentration of hydrocodone within a therapeutic range but below toxic concentrations over a period of time of about 12 hours or longer after administration to a human patient or a population of patients,
wherein said hydrocodone bitartrate salt is the only active agent in the dosage form.
12. The dosage form of claim 11 , wherein the dosage form provides the plasma concentration of hydrocodone within the therapeutic range but below toxic concentrations over a period of time of about 12 hours after administration to the human patient or the population of patients.
13. The dosage form of claim 12 , wherein said administration is first administration.
14. The dosage form of claim 11 , wherein said administration is first administration.
15. The dosage form of claim 12 , wherein the pharmaceutically acceptable matrices further comprise hydroxypropylmethylcellulose.
16. The dosage form of claim 11 , wherein the controlled release material comprises a material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, shellac and oils.
17. A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a plurality of pharmaceutically acceptable matrices comprising an amount of a hydrocodone bitartrate salt equivalent to from about 5 mg to about 60 mg of hydrocodone and a controlled release material,
the pharmaceutically acceptable matrices compressed into a tablet,
the controlled release material included in an effective amount such that the dosage form provides a T max of hydrocodone of from about 4 to about 10 hours and a plasma concentration of hydrocodone within a therapeutic range but below toxic concentrations over a period of time of about 12 hours or longer after administration to a human patient or a population of patients,
wherein said hydrocodone bitartrate salt is the only active agent in the dosage form.
18. The dosage form of claim 17 , wherein the controlled release material comprises a material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, shellac and oils.
19. The dosage form of claim 18 , wherein the material comprises ethylcellulose.
20. The dosage form of claim 19 , wherein the pharmaceutically acceptable matrices further comprise hydroxypropylmethylcellulose.
21. The dosage form of claim 15 , wherein the controlled release material comprises ethylcellulose.
22. The dosage form of claim 17 , wherein the controlled release material is included in an effective amount such that the dosage form provides an in-vitro release of hydrocodone when measured by the USP Basket method at 100 rpm in 700 ml aqueous buffer at a pH of 1.2 at 37° C. of from 10% to about 45% by weight hydrocodone released at 1 hour.
23. The dosage form of claim 17 , wherein the dosage form provides the plasma concentration of hydrocodone within the therapeutic range but below toxic concentrations over a period of time of about 12 hours after administration to the human patient or the population of patients.
24. The dosage form of claim 23 , wherein said administration is first administration.
25. The dosage form of claim 17 , wherein said administration is first administration.
26. The dosage form of claim 4 , wherein the controlled release material comprises ethylcellulose.
27. The dosage form of claim 26 , wherein the multiparticulates further comprise hydroxypropylmethylcellulose.
28. The dosage form of claim 17 , which provides a W 50 of hydrocodone of between 4 and 22 hours.
29. The dosage form of claim 5 , which provides a T max of hydrocodone of from about 4 to about 10 hours.
30. The dosage form of claim 16 , wherein the acrylic resin comprises an ammonio methacrylate copolymer.