Controlled release hydrocodone formulations

• US 9,205,055 B2
• Filed: 06/02/2015
• Issued: 12/08/2015
• 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): HENLEY III, RAYMOND J
• Application Number:
  US14/727,997
• Publication Number:
  US 20150258089A1
• Time in Patent Office: 189 Days
• Field of Search: 514/282, 424/451, 424/464, 424/472, 424/484
• 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 process for preparation of a solid oral controlled-release dosage form of hydrocodone comprising incorporating hydrocodone or a salt thereof into a controlled-release matrix by forming granules and compressing granules into a tablet such that the tablet after administration to a human patient provides a C₂₄/C_max ratio of about 0.55 to about 1.0 and a therapeutic effect for at least about 24 hours.

2. The process of claim 1, wherein the controlled-release material comprises a controlled-release polymer.

3. The process of claim 2, wherein the controlled-release polymer is selected from the group consisting of alkylcelluloses, acrylic and methacrylic acid polymers and copolymers, cellulose ethers, carboxyalkylcelluloses, and mixtures thereof.

4. The process of claim 3, wherein the cellulose ether comprises a hydroxyalkylcellulose.

5. The process of claim 3, wherein the acrylic and methacrylic acid polymers and copolymers are selected from the group consisting of methyl methacrylate, methyl methacrylate copolymers, ethoxyethyl methacrylates, cynaoethyl methacrylate, aminoalkyl methacrylate copolymer, poly(acrylic acid), poly(methacrylic acid), methacrylic acid alkylamine copolymer, poly(methyl methacrylate), polymethacrylate, polyacrylamide, poly(methacrylic acid anhydride), glycidyl methacrylate copolymers, and mixtures thereof.

6. The process of claim 1, wherein the salt is a bitartrate salt of hydrocodone.

7. The process of claim 1, comprising incorporating a gum into the controlled-release matrix.

8. The process of claim 1, comprising incorporating a wax into the controlled release matrix.

9. The process of claim 1, wherein from about 0.5 mg to about 1250 mg of hydrocodone or salt thereof is incorporated into the controlled-release matrix.

10. The process of claim 1, wherein the granules are compressed into the tablet such that the tablet provides an in-vitro release of the 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 or salt thereof released at 1 hour.

20. The process of claim 10, wherein the granules are compressed into the tablet such that the tablet provides an in-vitro release of the 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 or salt thereof released at 1 hour.

11. A process for preparation of a solid oral controlled-release dosage form of hydrocodone comprising incorporating hydrocodone or a salt thereof into a controlled-release matrix by forming granules and compressing granules into a tablet such that the tablet provides controlled release of the hydrocodone or the pharmaceutically acceptable salt thereof for a time period of from 8 to at least about 24 hours,

an in-vitro release rate of hydrocodone, when measured by the USP Basket Method at 100 rpm in 900 ml aqueous buffer at a pH of between 1.6 and 7.2 at 37°

C., of from 0% to about 35% at 1 hour, from about 10% to about 70% at 4 hours, from about 20% to about 75% at 8 hours, from about 30% to about 80% at 12 hours, from about 40% to about 90% at 18 hours, and greater than about 60% at 24 hours, and,

after administration to a human patient or a population of patients a C₂₄/C_max ratio of about 0.55 to about 1.0.

12. The process of claim 11, wherein the controlled-release material comprises a controlled-release polymer.

13. The process of claim 12, wherein the controlled-release polymer is selected from the group consisting of alkylcelluloses, acrylic and methacrylic acid polymers and copolymers, cellulose ethers, carboxyalkylcelluloses, and mixtures thereof.

14. The process of claim 13, wherein the cellulose ether comprises a hydroxyalkylcellulose.

15. The process of claim 13, wherein the acrylic and methacrylic acid polymers and copolymers are selected from the group consisting of methyl methacrylate, methyl methacrylate copolymers, ethoxyethyl methacrylates, cynaoethyl methacrylate, aminoalkyl methacrylate copolymer, poly(acrylic acid), poly(methacrylic acid), methacrylic acid alkylamine copolymer, poly(methyl methacrylate), poly(methacrylic acid)(anhydride), polymethacrylate, polyacrylamide, poly(methacre etherylic acid anhydride), glycidyl methacrylate copolymers, and mixtures thereof.

16. The process of claim 11, wherein the salt is a bitartrate salt of hydrocodone.

17. The process of claim 11, comprising incorporating a gum into the controlled-release matrix.

18. The process of claim 11, comprising incorporating a wax into the controlled release matrix.

19. The process of claim 11, wherein from about 0.5 mg to about 1250 mg of hydrocodone or salt thereof is incorporated into the controlled-release matrix.