Controlled release hydrocodone formulations

• US 10,179,130 B2
• Filed: 03/15/2013
• Issued: 01/15/2019
• 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:
  US13/833,263
• Publication Number:
  US 20140271840A1
• Time in Patent Office: 2,132 Days
• Field of Search: 514282, 424456, 424457, 424468, 424494, 424496, 424497
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/00 Medicinal preparations characterised by special physical form nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12
• 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 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• 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 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

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 comprising a gum and two types of multiparticulates, the multiparticulates collectively comprising from about 5 mg to about 60 mg of a pharmaceutically acceptable organic salt of hydrocodone,

the gum and two types of multiparticulates compressed into a tablet,

a first type of multiparticulates comprising microcrystalline cellulose and a first portion of said 5 mg to 60 mg of the pharmaceutically acceptable organic salt of hydrocodone, each multiparticulate individually coated with a controlled release coating comprising an acrylic polymer,

a second type of multiparticulates in the form of uncoated granules, spheroids, or pellets comprising a remaining portion of said 5 mg to 60 mg of the pharmaceutically acceptable organic salt of hydrocodone,

said 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 patient population, providing a plasma concentration of hydrocodone of at least 8 ng/ml at from about 2 to about 8 hours after said administration and a plasma concentration of hydrocodone of at least 6 ng/ml at about 12 hours after said 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 from about 2 to 8 hours, and a therapeutic effect for about 12 hours.

2. A twice-a-day solid oral controlled-release dosage form consisting essentially of

an amount of a bitartrate salt of hydrocodone equivalent to from about 5 mg to about 60 mg of hydrocodone,

a controlled release material selected from the group consisting of ethylcellulose, hydroxypropylmethylcellulose, and mixtures thereof, and

additional pharmaceutically acceptable excipients selected from the group consisting of lactose, glyceryl behenate, metal stearates, colorants, plasticizers, and mixtures thereof,

the controlled release material and the additional pharmaceutically acceptable excipients being in effective amounts such that the dosage form, after a first administration to a human patient population, provides a mean C₁₂/C_max hydrocodone ratio of 0.55 to 0.85 and a therapeutic effect for about 12 hours, wherein

the dosage form is free from acrylic polymers.

3. The dosage form of claim 2, wherein said human population is a fasted human patient population.

4. The dosage form of claim 3, wherein the dosage form consists of said bitartrate salt of hydrocodone and pharmaceutically acceptable excipients selected from the group consisting of ethylcellulose, hydroxypropylmethylcellulose, lactose, glyceryl behenate, metal stearates, colorants and plasticizers.