Controlled release hydrocodone formulations

• US 8,951,555 B1
• Filed: 10/21/2014
• Issued: 02/10/2015
• 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:
  US14/520,032
• Publication Number:
  US 20150037409A1
• Time in Patent Office: 112 Days
• Field of Search: 424/451
• US Class Current: 424/451
• 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 an amount of a hydrocodone bitartrate salt equivalent to from about 5 mg to about 60 mg of hydrocodone,

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,

the dosage form is a capsule comprising

a first portion of said amount of the hydrocodone bitartrate salt in an immediate release form and

the remaining portion of said amount of the hydrocodone bitartrate salt and a controlled release material in an extended release form, 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 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 controlled release material 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,

a W₅₀ of hydrocodone of between 4 and 22 hours, 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,

the dosage form is a capsule comprising

a first portion of said amount of the hydrocodone bitartrate salt in an immediate release form and

the remaining portion of said amount of the hydrocodone bitartrate salt and the controlled release material in an extended release form, 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 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 controlled release material 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, and

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,

the dosage form is a capsule comprising

a first portion of said amount of the hydrocodone bitartrate salt in an immediate release form and

the remaining portion of said amount of the hydrocodone bitartrate salt and the controlled release material in an extended release form, 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 each coated substrate comprises a pharmaceutically acceptable bead coated with the hydrocodone bitartrate salt and an acrylic resin.

16. The dosage form of claim 11, wherein the acrylic resin comprises an ammonio methacrylate copolymer.

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.

28. The dosage form of claim 16, wherein the ammonio methacrylate copolymer is a copolymer of acrylic and methacrylic ester with a molar ratio of ammonium groups to neutral (meth)acrylic esters of 1:

40.

18. A solid oral controlled-release dosage form of hydrocodone, the dosage form 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 controlled release material 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,

the dosage form is a capsule comprising

a first portion of said amount of the hydrocodone bitartrate salt in an immediate release form and

the remaining portion of said amount of the hydrocodone bitartrate salt and a controlled release material in an extended release form, wherein

said hydrocodone bitartrate salt 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 extended release form comprises a plurality of coated substrates.

21. The dosage form of claim 20, wherein each coated substrate comprises a pharmaceutically acceptable bead coated with the hydrocodone bitartrate salt and an acrylic resin.

22. The dosage form of claim 21, wherein the acrylic resin comprises an ammonio methacrylate copolymer.

23. The dosage form of claim 22, wherein 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 or a population of patients.

24. The dosage form of claim 23, 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.

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.

27. The dosage form of claim 22, wherein the ammonio methacrylate copolymer is a copolymer of acrylic and methacrylic ester with a molar ratio of ammonium groups to neutral (meth)acrylic esters of 1:

40.