SUSTAINED RELEASE FORMULATIONS OF OPIOID AND NONOPIOID ANALGESICS

• US 20070281018A1
• Filed: 04/20/2007
• Published: 12/06/2007
• Est. Priority Date: 09/24/2004
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbott Laboratories
• Inventors: KLEIN, Cheri, Qiu, Yihong
• Granted Patent: US 8,541,026 B2
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077

Abstract

The present invention relates to SRSR solid dosage forms for administering pharmaceutical agents, particularly Hydrocodone and acetaminophen, methods for preparing said dosage forms, and methods for providing therapeutic agents to patients in need of treatment.

Claims

1. A pharmaceutical composition comprising at least two sustained release subunits:

a first sustained release subunit that comprises acetaminophen and hydrocodone or an equivalent amount of another acceptable salt or free base of hydrocodone thereof;

a second sustained release subunit that comprises acetaminophen and hydrocodone or an equivalent amount of another acceptable salt or free base of hydrocodone thereof;

wherein said pharmaceutical composition is suitable for twice daily oral dosing to a human, and

further wherein said pharmaceutical composition, when administered to a population of healthy human volunteers is capable of providing analgesia for at least about 12 hours and produces;

a mean AUC for hydrocodone from about 11.3 to about 18.7 ng*hr/mL per mg of hydrocodone bitartrate and a mean AUC for acetaminophen from about 28.7 to about 53.5 ng*hr/mL per mg of acetaminophen after a single dose, and

a plasma profile characterized by;

a Cmax for hydrocodone of between about 0.6 ng/mL per mg of hydrocodone bitartrate to about 1.4 ng/mL per mg of hydrocodone bitartrate, and

a Cmax for acetaminophen of between about 2.8 ng/mL per mg of acetaminophen and 7.9 ng/mL/mg of acetaminophen after a single dose.

2. The pharmaceutical composition of claim 1, wherein the composition contains between about 20 and about 40 times by weight of hydrocodone bitartrate or an equivalent amount of another acceptable salt or free base of hydrocodone thereof.

3. The pharmaceutical composition of claim 1, wherein the first subunit and the second subunit each contain a single rate controlling mechanism.

4. The pharmaceutical composition of claim 3, wherein the single rate controlling mechanism comprises at least one pharmaceutically acceptable hydrophobic rate controlling material, a pharmaceutically acceptable hydrophilic rate controlling material, a non-polymer rate controlling material or any combinations thereof.

5. The pharmaceutical composition of claim 1, wherein the first and second subunit each comprise a monoeximic dosage form.

6. The pharmaceutical composition of claim 5, wherein said monoeximic dosage forms are the same type of dosage forms or different types of dosage forms.

7. The pharmaceutical composition of claim 6, wherein each of the monoeximic dosage forms comprises a matrix system.

8. The pharmaceutical composition of claim 6, wherein each of the monoeximic dosage forms comprises an osmotic system.

9. The pharmaceutical composition of claim 6, wherein each of the monoeximic dosage forms comprises a reservoir system.

10. The pharmaceutical composition of claim 6, wherein one of the monoeximic dosage forms comprises a matrix system and the other monoeximic dosage forms comprises an osmotic system.

11. The pharmaceutical composition of claim 6, wherein one of the monoeximic dosage forms comprises a matrix system and the other monoeximic dosage forms comprises an reservoir system.

12. The pharmaceutical composition of claim 6, wherein one of the monoeximic dosage forms comprises a reservoir system and the other monoeximic dosage forms comprises an osmotic system.

13. The pharmaceutical composition of claim 1, wherein the composition is capable of reducing pain intensity in a patient within about 1 hour.

14. The pharmaceutical composition of claim 13, wherein the composition releases at least 90% of the hydrocodone and acetaminophen in vitro within 12 hours.

15. The pharmaceutical composition of claim 13, wherein the composition releases at least 90% of the hydrocodone and acetaminophen in vitro within about 8 hours.

16. The pharmaceutical composition of claim 1, wherein the composition is adapted to release about 19% to 49% of the hydrocodone and acetaminophen in vitro within 0.75 hours.

17. The pharmaceutical composition of claim 16, wherein the composition releases at least 90% of the hydrocodone and acetaminophen within 12 hours.

18. The pharmaceutical composition of claim 16, wherein the composition releases at least 90% of the hydrocodone and acetaminophen within about 8 hours.

19. The pharmaceutical composition of claim 1, wherein the healthy volunteer is a resident of North America.

20. The pharmaceutical composition of claim 1, wherein the composition comprises about 500 mg of acetaminophen and about 15 mg of hydrocodone bitartrate.

21. The pharmaceutical composition of claim 1,

wherein the human in which the AUC and Cmax for both hydrocodone and acetaminophen is measured is a non-poor CYP2D6 metabolizer, and

wherein the dosage form produces a Cmax for hydromorphone in the human of between about 0.12 ng/ml and about 0.35 ng/ml after a single dose of 30 mg of hydrocodone bitartrate.

22. The pharmaceutical composition of claim 1, wherein the plasma concentration for hydrocodone 12 hours after a single 30 mg dose of hydrocodone bitartrate is between about 11.0 ng/ml and about 27.4 ng/ml.

23. The pharmaceutical composition of claim 1, wherein when a single 1000 mg dose of acetaminophen is administered to the human, the plasma concentration for acetaminophen 12 hours after administration is between about 0.7 μ

g/ml and about 2.5 μ

g/ml.

24. The pharmaceutical composition of claim 1, wherein when a single 1000 mg dose of acetaminophen is administered to the human, the plasma concentration for acetaminophen 12 hours after administration is between about 0.7 μ

g/ml and about 2.5 μ

g/ml.

25. The pharmaceutical composition of claim 2, wherein after a single dose of 30 mg of hydrocodone bitartrate, the plasma concentration profile exhibits a width at half height for hydrocodone of between about 6.4 hours and about 19.6 hours.

26. The pharmaceutical composition of claim 1, wherein after a single dose of 30 mg of hydrocodone bitartrate, the plasma concentration profile exhibits a width at half height for hydrocodone of between about 8.4 hours and about 19.6 hours.

27. The pharmaceutical composition of claim 1, wherein after a single dose of 1000 mg of acetaminophen, the plasma concentration profile exhibits a width at half height for acetaminophen of between about 0.8 hours and about 12.3 hours.