Controlled release hydrocodone formulations

• US 9,320,717 B2
• Filed: 03/30/2015
• Issued: 04/26/2016
• Est. Priority Date: 10/29/1999
• 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, Tonelli, Alfred P.
• Primary Examiner(s): BASQUILL, SEAN M
• Application Number:
  US14/672,894
• Publication Number:
  US 20150216809A1
• Time in Patent Office: 393 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0087 Galenical forms not covered by A61K9/02 - A61K9/7023
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• 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 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/282 Organic compounds, e.g. fats
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61K 9/50 Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids

Abstract

A solid oral controlled-release oral dosage form of hydrocodone is disclosed. The dosage form comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof, and a sufficient amount of a controlled release material to render the dosage form suitable for twice-a-day administration to a human patient, the dosage form providing a C₁₂/C_max ratio of 0.55 to 0.85, said dosage form providing a therapeutic effect for at least about 12 hours.

Claims

1. A twice-a-day solid oral controlled-release dosage form of a pharmaceutically acceptable salt of hydrocodone, the dosage form comprising:

a therapeutically effective amount of a pharmaceutically acceptable salt of hydrocodone, and

two different types of multiparticulates in the form of granules, spheroids, or pellets,

a first type of said multiparticulates comprising a first portion of the pharmaceutically acceptable salt of hydrocodone and providing an immediate release of hydrocodone,

a second type of said multiparticulates comprising a remaining portion of the pharmaceutically acceptable salt of hydrocodone and at least one pharmaceutically acceptable excipient and providing a controlled release of hydrocodone,

the dosage form providing an in-vitro release of from at least 18% to about 42.5% by weight of hydrocodone from the dosage form at one hour when measured by the USP Basket Method at 100 rpm in 700 ml of Simulated Gastric Fluid (SGF) for 55 minutes at 37°

C. and thereafter switching to 900 ml of Simulated Intestinal Fluid (SIF) at 37°

C., and

after a first administration to a human, providing a plasma concentration of hydrocodone of at least 8 ng/ml at from about 2 to about 8 hours after administration and a plasma concentration of hydrocodone of at least 6 ng/ml at about 12 hours after administration, based on oral administration of a dosage form containing 15 mg hydrocodone bitartrate,

a C₁₂/C_max hydrocodone ratio of 0.55 to 0.85 and

a T_max of hydrocodone at from about 2 to about 8 hours, wherein

the therapeutically effective amount of the pharmaceutically acceptable salt of hydrocodone is from about 5 mg to about 60 mg, and

the salt of hydrocodone is an inorganic salt of hydrocodone or a bitartrate salt of hydrocodone.

2. The dosage form of claim 1, which is a capsule.

3. The dosage form of claim 1, which provides a C₁₂/C_max hydrocodone ratio of 0.65 to 0.75 after said first administration.

10. The dosage form of claim 1, which provides a C₁₂/C_max hydrocodone ratio of 0.65 to 0.75 after said first administration.

11. The dosage form of claim 1, which is a capsule comprising from about 5 mg to about 60 mg of hydrocodone bitartrate.

12. The dosage form of claim 1, wherein the pharmaceutically acceptable salt of hydrocodone is hydrocodone bitartrate.

4. A twice-a-day solid oral controlled-release dosage form comprising multiparticulates collectively comprising an amount of a pharmaceutically acceptable salt of hydrocodone equivalent to from about 0.5 mg to about 1250 mg of hydrocodone,

the dosage form providing an in-vitro release of from 18% to about 42.5% by weight of hydrocodone from the dosage form at one hour when measured by the USP Basket Method at 100 rpm in 700 ml of Simulated Gastric Fluid (SGF) for 55 minutes at 37°

C. and thereafter switching to 900 ml of Simulated Intestinal Fluid (SIF) at 37°

C., and,

after a first administration to a human population, providing a mean plasma concentration of hydrocodone of at least 8 ng/ml at from about 2 to about 8 hours after administration and a plasma concentration of hydrocodone of at least 6 ng/ml at about 12 hours after administration, based on oral administration of a dosage form containing 15 mg hydrocodone bitartrate,

a mean C₁₂/C_max hydrocodone ratio of 0.55 to 0.85,

a mean T_max of hydrocodone of from about 2 to about 8 hours, and

a therapeutic effect for about 12 hours, wherein

at least one multiparticulate comprises a gum, and

the pharmaceutically acceptable salt of hydrocodone is selected from the group consisting of bitartrate salts of hydrocodone, hydrocodone hydrochloride, hydrocodone p-toluenesulfonate, hydrocodone phosphate, hydrocodone thiosemicarbazone, hydrocodone sulfate, hydrocodone trifluoroacetate, hydrocodone hemipentahydrate, hydrocodone pentafluoropropionate, hydrocodone p-nitrophenylhydrazone, hydrocodone o-methyloxime, hydrocodone semicarbazone, hydrocodone hydrobromide, hydrocodone mucate, hydrocodone oleate, hydrocodone phosphate dibasic, hydrocodone phosphate monobasic, hydrocodone oleate, trihydrate, hydrocodone bis(heptafuorobutyrate), hydrocodone bis(methylcarbamate), hydrocodone bis(pentafluoropropionate), hydrocodone bis(pyridine carboxylate), hydrocodone bis(trifluoroacetate), hydrocodone chlorhydrate, and hydrocodone sulfate pentahydrate.

5. The dosage form of claim 4, which is a capsule.

6. The dosage form of claim 4, which is a tablet.

7. The dosage form of claim 4, which provides a C₁₂/C_max hydrocodone ratio of 0.65 to 0.75 after said first administration.

8. The dosage form of claim 4, which is a capsule comprising from about 5 mg to about 60 mg of hydrocodone bitartrate.

9. The dosage form of claim 4, wherein each multiparticulate has a diameter of between 0.1 mm and 2.5 mm.

13. The dosage form of claim 4, wherein the pharmaceutically acceptable salt of hydrocodone is hydrocodone bitartrate.