Controlled release hydrocodone formulations

• US 9,669,023 B2
• Filed: 12/13/2016
• Issued: 06/06/2017
• Est. Priority Date: 10/30/2000
• Status: Expired due to Term

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P.
• Inventors: Huang, Hua-Pin, Tonelli, Alfred, Masselink, John K, Oshlack, Benjamin
• Primary Examiner(s): Sasan, Aradhana
• Application Number:
  US15/376,745
• Publication Number:
  US 20170087151A1
• Time in Patent Office: 175 Days
• Field of Search: None
• 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 hydrocodone formulation comprising:

hydrocodone or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable polymer,

the pharmaceutically acceptable polymer comprising between 1% and 80% of the formulation by weight,

the formulation providing 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,

wherein the formulation provides a plasma concentration profile of hydrocodone with a ratio of the plasma concentration of hydrocodone at 24 hours after administration to the highest concentration of hydrocodone during the 24 hours of from 0.55 to 1.0,

maintains the plasma concentrations of hydrocodone within the therapeutic range over 12 hours or longer after administration to a human and is administrable on a once a day basis.

2. The formulation of claim 1, wherein the formulation is a capsule or a tablet.

3. The formulation of claim 2, wherein the pharmaceutically acceptable polymer is polyethylene oxide.

4. The formulation of claim 3, wherein the formulation further comprises a hydroxyalkylcellulose.

5. The formulation of claim 4, wherein the hydroxyalkylcellulose is a hydroxypropylcellulose or a hydroxypropylmethylcellulose.

6. The formulation of claim 5, wherein the hydroxyalkylcellulose is the hydroxypropylcellulose.

7. The formulation of claim 1, wherein the formulation maintains therapeutically effective plasma concentrations of hydrocodone for about 24 hours after administration.

8. The formulation of claim 1, wherein a portion of the plasma concentration profile of hydrocodone is relatively flat.

9. The formulation of claim 1, wherein the formulation provides a plasma concentration profile of hydrocodone with a ratio of the plasma concentration of hydrocodone at 24 hours after administration to the highest concentration of hydrocodone during the 24 hours of 0.55 to 0.85.

10. The formulation of claim 1, wherein the formulation provides a plasma concentration profile of hydrocodone with a ratio of the plasma concentration of hydrocodone at 24 hours after administration to the highest concentration of hydrocodone during the 24 hours of 0.55 to 0.7.

11. The formulation of claim 1, wherein the formulation provides a plasma concentration profile of hydrocodone with a ratio of the plasma concentration of hydrocodone at 24 hours after administration to the highest concentration of hydrocodone during the 24 hours of 0.55 to 0.6.

12. The formulation of claim 1, wherein the ratio is calculated from hydrocodone plasma concentrations from first administration of the formulation to a human.

13. The formulation of claim 1, wherein the ratio is calculated from hydrocodone plasma concentrations from first administration of the formulation to a human population.

14. A hydrocodone formulation comprising:

hydrocodone or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable polymer,

the pharmaceutically acceptable polymer comprising between 1% and 80% of the formulation by weight,

the formulation providing

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 first administration to a human, a plasma concentration profile of hydrocodone comprising a C_max of hydrocodone and a C₂₄ of hydrocodone sufficient to render the formulation administrable on a once a day basis,

wherein the C_max of hydrocodone increases linearly from one formulation strength to another.

15. The formulation of claim 14, wherein the pharmaceutically acceptable polymer is polyethylene oxide.

16. The formulation of claim 15, wherein the formulation further comprises a hydroxyalkylcellulose.

17. The formulation of claim 16, wherein the hydroxyalkylcellulose is a hydroxypropylcellulose or a hydroxypropylmethylcellulose.

18. The formulation of claim 17, wherein the hydroxyalkylcellulose is the hydroxypropylcellulose.

19. The formulation of claim 14, wherein the ratio of said C₂₄ to said C_max is from 0.55 to 1.0.

20. The formulation of claim 19, wherein a portion of the plasma concentration profile of hydrocodone is relatively flat.

21. The formulation of claim 14, wherein the ratio of said C₂₄ to said C_max is 0.55 to 0.75.

22. The formulation of claim 14, wherein the ratio of said C₂₄ to said C_max is 0.55 to 0.7.

23. The formulation of claim 14, wherein the ratio of said C₂₄ to said C_max is 0.55 to 0.6.

24. The formulation of claim 19, wherein the ratio is calculated from hydrocodone plasma concentrations from first administration of the formulation to the human.

25. The formulation of claim 19, wherein the ratio is calculated from hydrocodone plasma concentrations from first administration of the formulation to the human population.

26. The formulation of claim 14, wherein the formulation comprises a bitartrate salt of hydrocodone and a material having a melting point of from about 30 to about 200°

C.

27. The formulation of claim 26, wherein the melting point is from about 30 to about 100°

C.

28. The formulation of claim 27, wherein the material is polyethylene oxide.