Controlled release hydrocodone formulations

• US 9,056,052 B1
• Filed: 02/03/2015
• Issued: 06/16/2015
• Est. Priority Date: 10/30/2000
• Status: Expired due to Fees

• 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:
  US14/612,483
• Publication Number:
  US 20150148367A1
• Time in Patent Office: 133 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 form of hydrocodone, the dosage form comprising a matrix comprising hydrocodone or a pharmaceutically acceptable salt thereof, a controlled release material and hydroxypropylcellulose or hydroxypropylmethylcellulose, such that the dosage form provides 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, 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 hydrocodone or pharmaceutically acceptable salt thereof 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.

15. The dosage form of claim 1, wherein the dosage form provides a mean C₂₄/C_max hydrocodone ratio of from about 0.55 to about 1 after administration to a patient population.

22. The dosage form of claim 1, wherein the controlled release material comprises ethylcellulose.

27. The dosage form of claim 1, wherein the matrix comprises a granulation comprising the hydrocodone or pharmaceutically acceptable salt thereof and the hydroxypropylcellulose or hydroxypropylmethylcellulose.

28. The dosage form of claim 1, wherein the dosage form provides a mean ratio of mean plasma concentrations of hydrocodone at the end of a dosing interval to mean maximum plasma concentrations of hydrocodone during the dosing interval of about 0.55 to about 1 after administration to a patient population.

5. A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a matrix comprising hydrocodone or a pharmaceutically acceptable salt thereof, a controlled release material and hydroxypropylcellulose or hydroxypropylmethylcellulose, such that the dosage form provides a W₅₀ 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, 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 hydrocodone or pharmaceutically acceptable salt thereof 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.

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

11. A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a matrix comprising hydrocodone or a pharmaceutically acceptable salt thereof, a controlled release material and hydroxypropylcellulose or hydroxypropylmethylcellulose, such that the dosage form provides a T_max of hydrocodone of from about 4 to about 14 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, 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 hydrocodone or a pharmaceutically acceptable salt thereof 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.

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.

16. The dosage form of claim 11, wherein the dosage form provides a C₂₄/C_max hydrocodone ratio of from about 0.55 to about 1 after administration to the human patient.

17. 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.

18. A solid oral controlled-release dosage form of hydrocodone, the dosage form comprising a matrix comprising hydrocodone bitartrate, a controlled release material and hydroxypropylcellulose or hydroxypropylmethylcellulose, such that the dosage form provides 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, wherein

the dosage form is a compressed tablet,

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

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

19. The dosage form of claim 18, wherein the controlled release material comprises a material selected from the group consisting of gums, cellulose ethers, acrylic resins, waxes, shellac, and oils.

20. The dosage form of claim 18, wherein the controlled release material comprises ethylcellulose.

21. The dosage form of claim 18, wherein the dosage form provides a mean C₂₄/C_max hydrocodone ratio of from about 0.55 to about 1 after administration to a patient population.

23. The dosage form of claim 18, 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.

24. The dosage form of claim 18, 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.

25. The dosage form of claim 24, wherein said administration is first administration.

26. The dosage form of claim 18, wherein said administration is first administration.

29. The dosage form of claim 18, which provides a C₂₄/C_max hydrocodone ratio of from about 0.55 to about 1 after said administration.

30. The dosage form of claim 18, wherein the matrix comprises a granulation comprising the hydrocodone or pharmaceutically acceptable salt thereof and the hydroxypropylcellulose or hydroxypropylmethylcellulose.