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. A twice-a-day solid oral controlled-release tablet comprising
a matrix comprising (i) a controlled release material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, oils, and mixtures of any of the foregoing controlled release materials, and (ii) hydrocodone or a pharmaceutically acceptable salt thereof,
the tablet providing a mean C 12 /C max hydrocodone ratio of 0.55 to 0.85 and a mean T max of hydrocodone from about 2 to about 8 hours after a first administration to human subjects,
further providing a mean plasma concentration of hydrocodone of at least 8 ng/ml at from about 2 to about 8 hours and a mean plasma concentration of hydrocodone of at least 6 ng/ml at about 12 hours, based on administration of a tablet containing 15 mg hydrocodone bitartrate, and
releasing from 18% to about 42.5% by weight of hydrocodone at one hour when measured by the USP Basket Method at 100 rpm in 700 ml of Simulated Gastric Fluid (SGF) for 55 minutes at 37° C. and thereafter switching to 900 ml of Simulated Intestinal Fluid (SIF) at 37° C.
2. The tablet of claim 1 , wherein the tablet comprises from about 5 mg to about 60 mg of a bitartrate salt of hydrocodone.
3. The tablet of claim 1 , wherein the bitartrate salt of hydrocodone is hydrocodone bitartrate.
4. The tablet of claim 1 , which comprises a fatty acid ester.
5. A twice-a-day solid oral controlled-release tablet comprising
a matrix comprising (i) a controlled release material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, oils, and mixtures of any of the foregoing controlled release materials, and (ii) hydrocodone or a pharmaceutically acceptable salt thereof,
the tablet providing a mean C 12 /C max hydrocodone ratio of 0.65 to 0.75 and a mean T max of hydrocodone from about 2 to about 8 hours after a first administration to human subjects,
further providing a mean plasma concentration of hydrocodone of at least 8 ng/ml at from about 2 to about 8 hours and a mean plasma concentration of hydrocodone of at least 6 ng/ml at about 12 hours, based on administration of a tablet containing 15 mg hydrocodone bitartrate, and
releasing from 18% to about 42.5% by weight of hydrocodone at one hour when measured by the USP Basket Method at 100 rpm in 700 ml of Simulated Gastric Fluid (SGF) for 55 minutes at 37° C. and thereafter switching to 900 ml of Simulated Intestinal Fluid (SIF) at 37° C.
6. The tablet of claim 4 , wherein the tablet comprises from about 5 mg to about 60 mg of a bitartrate salt of hydrocodone.
7. The tablet of claim 4 , wherein the bitartrate salt of hydrocodone is hydrocodone bitartrate.
8. The tablet of claim 4 , which comprises a fatty acid ester.
9. A twice-a-day solid oral controlled-release tablet comprising
a matrix comprising (i) a controlled release material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, oils, and mixtures of any of the foregoing controlled release materials, and (ii) hydrocodone or a pharmaceutically acceptable salt thereof,
the tablet providing a mean C 12 /C max hydrocodone ratio of 0.65 to 0.85 and a mean T max of hydrocodone from about 2 to about 8 hours after a first administration to human subjects,
further providing a mean plasma concentration of hydrocodone of at least 8 ng/ml at from about 2 to about 8 hours and a mean plasma concentration of hydrocodone of at least 6 ng/ml at about 12 hours, based on administration of a tablet containing 15 mg hydrocodone bitartrate, and
releasing from 18% to about 42.5% by weight of hydrocodone at one hour when measured by the USP Basket Method at 100 rpm in 700 ml of Simulated Gastric Fluid (SGF) for 55 minutes at 37° C. and thereafter switching to 900 ml of Simulated Intestinal Fluid (SIF) at 37° C.
10. The tablet of claim 9 , wherein the tablet comprises from about 5 mg to about 60 mg of a bitartrate salt of hydrocodone.
11. The tablet of claim 9 , wherein the bitartrate salt of hydrocodone is hydrocodone bitartrate.
12. The tablet of claim 9 , which comprises a fatty acid ester.
13. The tablet of claim 1 , which maintains a plasma concentration of hydrocodone within 90% of C max for about 4 hours.
14. The tablet of claim 1 , which maintains a plasma concentration of hydrocodone within 90% of C max for about 5 hours.
15. The tablet of claim 1 , which maintains a plasma concentration of hydrocodone within 90% of C max for about 6.5 hours.
16. The tablet of claim 5 , which maintains a plasma concentration of hydrocodone within 90% of C max for about 4 hours.
17. The tablet of claim 5 , which maintains a plasma concentration of hydrocodone within 90% of C max for about 5 hours.
18. The tablet of claim 5 , which maintains a plasma concentration of hydrocodone within 90% of C max for about 6.5 hours.
19. The tablet of claim 9 , which maintains a plasma concentration of hydrocodone within 90% of C max for about 4 hours.
20. The tablet of claim 9 , which maintains a plasma concentration of hydrocodone within 90% of C max for about 5 hours or about 6.5 hours.
21. The tablet of claim 1 , which releases 39.7% or less of hydrocodone at one hour when measured by the USP Basket Method at 100 rpm in 700 ml of Simulated Gastric Fluid (SGF) for 55 minutes and thereafter switching to 900 ml of Simulated Intestinal Fluid (SIF) without enzyme.
22. The tablet of claim 21 , which releases at least 23.9% by weight of hydrocodone at one hour when measured by the USP Basket Method at 100 rpm in 700 ml of Simulated Gastric Fluid (SGF) for 55 minutes and thereafter switching to 900 ml of Simulated Intestinal Fluid (SIF) without enzyme.
23. The tablet of claim 5 , which releases 39.7% or less of hydrocodone at one hour when measured by the USP Basket Method at 100 rpm in 700 ml of Simulated Gastric Fluid (SGF) for 55 minutes and thereafter switching to 900 ml of Simulated Intestinal Fluid (SIF) without enzyme.
24. The tablet of claim 23 , which releases at least 23.9% by weight of hydrocodone at one hour when measured by the USP Basket Method at 100 rpm in 700 ml of Simulated Gastric Fluid (SGF) for 55 minutes and thereafter switching to 900 ml of Simulated Intestinal Fluid (SIF) without enzyme.
25. The tablet of claim 9 , which releases 39.7% or less of hydrocodone at one hour when measured by the USP Basket Method at 100 rpm in 700 ml of Simulated Gastric Fluid (SGF) for 55 minutes and thereafter switching to 900 ml of Simulated Intestinal Fluid (SIF) without enzyme.
26. The tablet of claim 25 , which releases at least 23.9% by weight of hydrocodone at one hour when measured by the USP Basket Method at 100 rpm in 700 ml of Simulated Gastric Fluid (SGF) for 55 minutes and thereafter switching to 900 ml of Simulated Intestinal Fluid (SIF) without enzyme.
27. A twice-a-day solid oral controlled-release tablet comprising
a matrix comprising (i) a controlled release material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, oils, and mixtures of any of the foregoing controlled release materials, and (ii) hydrocodone or a pharmaceutically acceptable salt thereof,
the tablet providing a mean C 12 /C max hydrocodone ratio of 0.55 to 0.85 and a mean T max of hydrocodone from about 2 to about 8 hours after a first administration to human subjects,
further providing a mean plasma concentration of hydrocodone of at least 8 ng/ml at from about 2 to about 8 hours and a mean plasma concentration of hydrocodone of at least 6 ng/ml at about 12 hours, based on administration of a tablet containing 15 mg hydrocodone bitartrate, and
releasing at least 12.5% to about 42.5% by weight of hydrocodone at one hour when measured by the USP Paddle Method at 100 rpm in 900 ml of Simulated Gastric Fluid (SGF) at 37° C.
28. The tablet of claim 27 , which provides a mean C 12 /C max hydrocodone ratio of 0.65 to 0.85.
29. The tablet of claim 28 , which provides a mean C 12 /C max hydrocodone ratio of 0.65 to 0.75.