Controlled release hydrocodone formulations
AssigneePurdue Pharma L.P.
InventorsBenjamin Oshlack, Hua-Pin Huang, John K. Masselink, Alfred P. Tonelli
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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.
Claims42
A solid oral controlled-release dosage form suitable for 24 hour dosing of an active agent in a human patient comprising a pharmaceutically acceptable matrix comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof and controlled release material;
- said dosage form after administration to a human patient, providing a C24/Cmax ratio of 0.55 to about 0.85;
- a therapeutic effect for at least about 24 hours and a dissolution release rate in-vitro of the hydrocodone or salt thereof, when measured by the USP Basket Method at 100 rpm in 700 ml Simulated Gastric Fluid (SGF) at 37° C. for 1 hour and thereafter switching to 900 ml with Phosphate Buffer at a pH of 7.5 at 37° C., wherein at least 20% by weight hydrocodone or salt thereof is released at 4 hours, from about 20% to about 65% by weight hydrocodone or salt thereof is released at 8 hours, from about 45% to about 85% by weight hydrocodone or salt thereof is released at 12 hours, and at least 80% by weight hydrocodone or salt thereof is released at 24 hours.
A solid oral controlled-release dosage form suitable for 24 hour dosing of an active agent 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 comprising an acrylic polymer, 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.
A sustained release oral dosage form comprising:
- (a) a bilayer core comprising:
- (i) a drug layer comprising an analgesically effective amount of an active agent comprising hydrocodone or a pharmaceutically acceptable salt thereof;
- and
- (ii) a displacement layer comprising an osmopolymer;
- and
- (b) a semipermeable wall comprising a hydrophobic material selected from the group consisting of a cellulosic polymer, an acrylic polymer and a combination thereof surrounding the bilayer core and having a passageway disposed therein for the release of said hydrocodone or pharmaceutically acceptable salt thereof;
- said dosage form providing a C24/Cmax ratio of 0.55 to about 0.85;
- a therapeutic effect for at least about 24 hours after oral administration to a human patient and a dissolution release rate in-vitro of the hydrocodone or salt thereof, when measured by the USP Basket Method at 100 rpm in 700 ml Simulated Gastric Fluid (SGF) at 37° C. for 1 hour and thereafter switching to 900 ml with Phosphate Buffer at a pH of 7.5 at 37° C., wherein at least 20% by weight hydrocodone or salt thereof is released at 4 hours, from about 20% to about 65% by weight hydrocodone or salt thereof is released at 8 hours, from about 45% to about 85% by weight hydrocodone or salt thereof is released at 12 hours, and at least 80% by weight hydrocodone or salt thereof is released at 24 hours.
A sustained release oral dosage form comprising:
- (a) a bilayer core comprising:
- (i) a drug layer comprising an active agent comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof;
- and
- (ii) a displacement layer comprising an osmopolymer;
- and
- (b) a semipermeable wall comprising a hydrophobic material selected from the group consisting of a cellulosic polymer, an acrylic polymer and a combination thereof surrounding the bilayer core and having a passageway disposed therein for the release of said hydrocodone or pharmaceutically acceptable salt thereof;
- 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. Pharmacopoeia XXII (1990) at 100 rpm in 900 ml aqueous buffer, is no greater than 10%.
Dependencies are inferred from the claim text.