Controlled release hydrocodone formulations

A solid oral controlled-release dosage form suitable for 24 hour dosing in a human patient comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof, and controlled release material selected from the group consisting of hydrophobic polymers, hydrophilic polymers, gums, protein derived materials, waxes, shellac, oils and mixtures thereof, said dosage form after oral administration, providing a rate of absorption during the time period from Tmax to about 24 hours after oral adminstration of the dosage form which is from about 45% to about 85% of the rate of elimination during the same time period, said dosage form providing a therapeutic effect for at least about 24 hours.

A method of providing analgesia in a human patient for at least about 24 hours comprising orally administering a dosage form comprising a pharmaceutically acceptable matrix comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof and controlled release material selected from the group consisting of hydrophobic polymers, hydrophilic polymers, gums, proteins derived materials, waxes, shellac, oils and mixtures thereof, said dosage form after administration to a human patient, providing a C24/Cmax ratio of 0.55 to about 0.85 and a therapeutic effect for at least about 24 hours.

A process for the preparation of a solid oral controlled-release dosage form, comprising incorporating an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof into a controlled release material selected from the group consisting of hydrophobic polymers, hydrophilic polymers, gums, proteins derived materials, waxes, shellac, oils and mixtures thereof, forming a controlled release matrix formulation, said dosage form after administration to a human patient, providing a C24/Cmax ratio of 0.55 to about 0.85 and a therapeutic effect for at least about 24 hours.

A solid oral controlled-release dosage form suitable for 24 hour dosing in a human patient comprising a plurality of pharmaceutically acceptable beads coated with an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof and overcoated with a pH-independent hydrophobic material, said dosage form providing, 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;

• the in-vitro release rate being substantially independent of pH in that a difference, at any given time, between an amount of opioid released at one pH and an amount released at any other pH, when measured in-vitro using the USP Paddle Method of U.S. Pharmacopeia XXII (1990) at 100 rpm in 900 ml aqueous buffer, is no greater than 10%;
• said dosage form providing a C24/Cmax ratio of 0.55 to about 0.85;
• and a therapeutic effect for at least 24 hours, after oral administration to a human patient.