Controlled release hydrocodone formulations

• US 8,361,499 B2
• Filed: 06/28/2012
• Issued: 01/29/2013
• 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 P.
• Primary Examiner(s): Sasan, Aradhana
• Application Number:
  US13/535,996
• Publication Number:
  US 20120263788A1
• Time in Patent Office: 215 Days
• Field of Search: 424/451, 424/484, 424/464, 514/282, 514/161
• 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 comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof and a controlled release material selected from the group consisting of hydrophobic polymers, hydrophilic polymers, gums, protein derived materials, waxes, shellac, oils and mixtures thereof, the dosage form providing

a 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 or a pharmaceutically acceptable salt thereof, 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 and after the maximum plasma concentration of the hydrocodone is reached, providing a relatively flat serum plasma profile of the hydrocodone meaning that the plasma level of the hydrocodone provides a C₂₄/C_max ratio of about 0.55 to about 1.0.

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

3. The dosage form of claim 1, which provides a therapeutic plasma concentration of the hydrocodone for a period of time of about 12 hours or longer and a W₅₀ for the hydrocodone of between 4 and 22 hours.

4. The dosage form of claim 1, which provides a C₂₄/C_max ratio of 0.55 to 0.75.

5. The dosage form of claim 1, wherein the controlled release material is incorporated into a matrix along with the hydrocodone or the pharmaceutically acceptable salt thereof, or the controlled release material is applied as a sustained release coating over a substrate comprising the hydrocodone or the pharmaceutically acceptable salt thereof.

6. The dosage form of claim 5, wherein the controlled release material is incorporated into the matrix along with the hydrocodone or the pharmaceutically acceptable salt thereof.

7. The dosage form of claim 6, wherein the matrix comprises an alkylcellulose, a hydroxyalkylcellulose, or mixtures thereof.

8. The dosage form of claim 7, wherein the matrix further comprises a hydrophobic material having a melting point from about 30 to about 200°

C.

9. The dosage form of claim 7, wherein the matrix further comprises a fatty acid, a fatty alcohol, a glyceryl ester of fatty acid, a wax, a polyalkylene glycol, or a mixture of any of the foregoing materials.

10. The dosage form of claim 9, wherein the matrix comprises the glyceryl ester of a fatty acid.

11. The dosage form of claim 9, wherein the matrix is coated with a coating comprising (i) an alkylcellulose, (ii) an acrylic polymer, or (iii) a mixture of the alkylcellulose and the acrylic polymer.

12. The dosage form of claim 6, wherein said matrix comprises a granule comprising a water soluble hydroxyalkyl cellulose and the hydrocodone or the pharmaceutically acceptable salt thereof.

13. The dosage form of claim 12, wherein the granule is coated with a coating comprising (i) an alkylcellulose, (ii) an acrylic polymer, or (iii) or a mixture of the alkylcellulose and the acrylic polymer.

14. The dosage form of claim 13, wherein the coating further comprises a water insoluble material.

15. The dosage form of claim 14, wherein the water insoluble material is a wax.

16. The dosage form of claim 1 which is provided as a multiparticulate formulation.

17. The dosage form of claim 1 which is provided as spheroids.

18. The dosage form of claim 1 which is provided as an osmotic dosage form.

19. The dosage form of claim 18 which comprises a single layer or bilayer core comprising the hydrocodone or the pharmaceutically acceptable salt thereof;

an expandable polymer;

a semipermeable membrane surrounding the core; and

a passageway disposed in the semipermeable membrane for sustained release of the hydrocodone or the pharmaceutically acceptable salt thereof.

20. The dosage form of claim 17, wherein the spheroids have a diameter of between 0.1 mm and 2.5 mm.

21. The dosage form of claim 17, wherein a portion of the spheroids provides a controlled release of the hydrocodone or the pharmaceutically acceptable salt thereof and a portion of the spheorids provides an immediate release of the hydrocodone or the pharmaceutically acceptable salt thereof.

22. The dosage form of claim 21, wherein the spheroids providing the controlled release of the hydrocodone comprise hydrocodone or the pharmaceutically acceptable salt thereof coated with the coating comprising the controlled release material.

23. The dosage form of claim 22, wherein the controlled release material in the coating comprises an acrylic resin.

24. The dosage form of claim 23, wherein the coating further comprises one or more release-modifying agents.

25. The dosage form of claim 23, wherein the coating further comprises an erosion-promoting agent.

26. The dosage form of claim 25, wherein the erosion-promotion agent is starch.

27. The dosage form of claim 22 further comprising talc.

28. The dosage form of claim 22 further comprising a surfactant.

29. The dosage form of claim 16 further comprising povidone.

30. The dosage form of claim 21, comprising a capsule comprising the spheroids providing the controlled release of the hydrocodone or the pharmaceutically acceptable salt thereof and the spheroids providing the immediate release of the hydrocodone or the pharmaceutically acceptable salt thereof.