Controlled release hydrocodone formulations

• US 9,289,391 B2
• Filed: 05/07/2015
• Issued: 03/22/2016
• Est. Priority Date: 10/30/2000
• Status: Expired due to Term

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P.
• Inventors: Oshlack, Benjamin, Huang, Hua-Pin, Masselink, John K., Tonelli, Alfred
• Primary Examiner(s): Sasan, Aradhana
• Application Number:
  US14/706,699
• Publication Number:
  US 20150238418A1
• Time in Patent Office: 320 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/141 Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers (co) spray-dried products A61K9/16, (co) lyophilised products A61K9/19; the carrier being chemically bound to the active ingredient A61K47/50
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• 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 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

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.

Claims

1. A solid oral controlled-release dosage comprising hydrocodone or a pharmaceutically acceptable salt thereof and at least one polymer hydrogel, the dosage form, after administration to a human subject, providing a C₂₄/C_max hydrocodone ratio of from about 0.55 to about 1.0, wherein

the dosage form is a tablet,

the amount of hydrocodone in the dosage form is from about 0.5 mg to about 1250 mg, and

the hydrocodone or pharmaceutically acceptable salt thereof is the only active agent in the dosage form.

2. The dosage form of claim 1, which provides a therapeutic effect for about 24 hours.

3. The dosage form of claim 1, wherein said administration is first administration.

4. The dosage form of claim 1, which comprises a 1,000,000 to 10,000,000 weight-average molecular weight poly(alkylene oxide).

5. The dosage form of claim 4, wherein the poly(alkylene oxide) is poly(ethylene oxide).

6. The dosage form of claim 5, wherein the poly(ethylene oxide) has a 7,000,000 average molecular weight.

7. The dosage form of claim 1, which comprises a poly(ethylene oxide) which has an average molecular weight of at least 400,000.

8. The dosage form of claim 1, which provides a C₂₄/C_max hydrocodone ratio of 0.55 to 0.85.

9. The dosage form of claim 8, which provides a C₂₄/C_max hydrocodone ratio of 0.6 to about 0.7.

10. The dosage form of claim 1, which provides a T_max of hydrocodone at about 8 to about 14 hours after administration of the dosage form.

11. The dosage form of claim 1, which comprises an amount of the hydrocodone bitartrate salt which is equivalent to from about 5 mg to about 60 mg of hydrocodone.

12. A solid oral controlled-release dosage form comprising hydrocodone or a pharmaceutically acceptable salt thereof and at least one polymer hydrogel, the dosage form, after administration to human subjects, providing a mean C₂₄/C_max hydrocodone ratio of from about 0.55 to about 1.0, wherein

the dosage form is a tablet,

the amount of hydrocodone in the dosage form is from about 0.5 mg to about 1250 mg, and

the hydrocodone or pharmaceutically acceptable salt thereof is the only active agent in the dosage form.

13. The dosage form of claim 12, which provides a therapeutic effect for about 24 hours.

14. The dosage form of claim 12, wherein said administration is first administration.

15. The dosage form of claim 12, which comprises a 1,000,000 to 10,000,000 weight-average molecular weight poly(alkylene oxide).

16. The dosage form of claim 15, wherein the poly(alkylene oxide) is poly(ethylene oxide).

17. The dosage form of claim 16, wherein the poly(ethylene oxide) has a 7,000,000 average molecular weight.

18. The dosage form of claim 12, which provides a mean C₂₄/C_max hydrocodone ratio of 0.55 to 0.85.

19. The dosage form of claim 18, which provides a mean C₂₄/C_max hydrocodone ratio of 0.6 to about 0.7.

20. The dosage form of claim 12, which provides a mean T_max of hydrocodone at about 8 to about 14 hours after administration of the dosage form.

21. A solid oral controlled-release dosage form comprising a bitartrate salt of hydrocodone and at least one polymer hydrogel, wherein

the dosage form, after administration to a human subject, provides a W₅₀ of hydrocodone of between 4 and 22 hours and a therapeutic effect for about 24 hours,

the dosage form is a compressed tablet,

the amount of hydrocodone in the dosage form is from about 0.5 mg to about 1250 mg, and

the bitartrate salt of hydrocodone is the only active agent in the dosage form.

22. The dosage form of claim 21, wherein said administration is first administration.

23. The dosage form of claim 21, wherein the dosage form provides a C₂₄/C_max hydrocodone ratio of from about 0.55 to about 1 after said administration.

24. The dosage form of claim 23, which provides C₂₄/C_max hydrocodone ratio of from 0.55 to about 0.85.

25. The dosage form of claim 24, which provides a C₂₄/C_max hydrocodone ratio of 0.55 to 0.75.

26. The dosage form of claim 25, which provides a C₂₄/C_max hydrocodone ratio of 0.6 to about 0.7.

27. The dosage form of claim 21, which provides a T_max of hydrocodone at about 8 to about 14 hours after administration of the dosage form.

30. The dosage form of claim 23, which provides a meanC₂₄/C_max hydrocodone ratio of from 0.55 to about 0.85, and a mean a T_max of hydrocodone at about 8 to about 14 hours after administration of the dosage form.

28. A solid oral controlled-release dosage form comprising a bitartrate salt of hydrocodone and at least one polymer hydrogel, wherein

the dosage form, after administration to human subjects, provides a mean W₅₀ of hydrocodone of between 4 and 22 hours and a therapeutic effect for about 24 hours,

wherein

the dosage form is a compressed tablet,

the amount of hydrocodone in the dosage form is from about 0.5 mg to about 1250 mg, and

the bitartrate salt of hydrocodone is the only active agent in the dosage form.

29. The dosage form of claim 28, wherein said administration is first administration.