Controlled release hydrocodone formulations
First Claim
1. A solid oral twice-a-day controlled-release dosage form, whereinthe dosage form is a tablet consisting of(i) a plurality of individually coated multiparticulates consisting of matrices individually coated with a coating consisting of ethylcellulose and a wax, the matrices collectively consisting of from about 5 mg to about 60 mg hydrocodone or an equivalent amount of a pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose and ethylcellulose,(ii) hydroxypropylmethyl cellulose,(iii) lactose,(iv) a metal stearate, and(v) a colorant,the individually coated multiparticulates compressed along with hydroxypropylmethyl cellulose, lactose, the metal stearate and the colorant into the tablet,said dosage form, after a first administration to a human patient, providesa 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 C12/Cmax ratio of 0.55 to 0.85, anda therapeutic effect for at least 12 hours,wherein the hydrocodone or pharmaceutically acceptable salt thereof is the only active agent in the dosage form,the metal stearate is magnesium stearate, andthe wax is selected from the group consisting of beeswax, glycowax, castor wax, carnauba wax, and glyceryl behenate.
1 Assignment
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Accused Products
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/Cmax ratio of 0.55 to 0.85, said dosage form providing a therapeutic effect for at least about 12 hours.
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Citations
36 Claims
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1. A solid oral twice-a-day controlled-release dosage form, wherein
the dosage form is a tablet consisting of (i) a plurality of individually coated multiparticulates consisting of matrices individually coated with a coating consisting of ethylcellulose and a wax, the matrices collectively consisting of from about 5 mg to about 60 mg hydrocodone or an equivalent amount of a pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose and ethylcellulose, (ii) hydroxypropylmethyl cellulose, (iii) lactose, (iv) a metal stearate, and (v) a colorant, the individually coated multiparticulates compressed along with hydroxypropylmethyl cellulose, lactose, the metal stearate and the colorant into the tablet, said dosage form, after a first administration to a human patient, provides 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 C12/Cmax ratio of 0.55 to 0.85, and a therapeutic effect for at least 12 hours, wherein the hydrocodone or pharmaceutically acceptable salt thereof is the only active agent in the dosage form, the metal stearate is magnesium stearate, and the wax is selected from the group consisting of beeswax, glycowax, castor wax, carnauba wax, and glyceryl behenate.
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22. A solid oral twice-a-day controlled-release dosage form, wherein
the dosage form is a tablet consisting of (i) a plurality of individually coated multiparticulates consisting of matrices individually coated with a coating consisting of ethylcellulose and a wax, the matrices collectively consisting of from about 5 mg to about 60 mg hydrocodone or an equivalent amount of a pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose and ethylcellulose, (ii) hydroxypropylmethyl cellulose, (iii) lactose, (iv) a metal stearate, and (v) a colorant, the individually coated multiparticulates compressed along with hydroxypropylmethyl cellulose, lactose, the metal stearate and the colorant into the tablet, said dosage form, after a first administration to a patient population, provides 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/Cmax ratio of 0.55 to 0.85, and a therapeutic effect for about 12 hours, wherein the hydrocodone or the pharmaceutically acceptable salt thereof is the only active agent in the dosage form, the metal stearate is magnesium stearate, and the wax is selected from the group consisting of beeswax, glycowax, castor wax, carnauba wax, and glyceryl behenate.
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25. A solid oral twice-a-day controlled-release dosage form, wherein the dosage form is a tablet consisting of
(i) a plurality of individually coated multiparticulates consisting of matrices individually coated with a coating consisting of ethylcellulose and a wax, the matrices consisting of hydrocodone or a pharmaceutically acceptable salt thereof, ethylcellulose, hydroxypropylmethyl cellulose and glyceryl behanate, (ii) hydroxypropylmethyl cellulose, (iii) lactose, (iv) a metal stearate, and (v) a colorant, the individually coated multiparticulates compressed along with hydroxypropylmethyl cellulose, lactose, the metal stearate, and the colorant into the tablet, said dosage form, after a first administration to a human patient, provides 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 C12/Cmax ratio of 0.55 to 0.85, and a therapeutic effect for at least 12 hours, wherein the hydrocodone or pharmaceutically acceptable salt thereof is the only active agent in the dosage form, the metal stearate is magnesium stearate, and the wax is selected from the group consisting of beeswax, glycowax, castor wax, carnauba wax, and glyceryl behenate.
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31. A solid oral twice-a-day controlled-release dosage form, wherein the dosage form is a tablet consisting of
(i) a plurality of individually coated multiparticulates consisting of matrices individually coated with a coating consisting of ethylcellulose and a wax, the matrices consisting of hydrocodone or a pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose and ethylcellulose, (ii) an additional amount of hydrocodone or pharmaceutically acceptable salt thereof, (iii) hydroxypropylmethyl cellulose, (iv) lactose, (v) a metal stearate, and (vi) a colorant, the individually coated multiparticulates compressed along with the additional amount of hydrocodone or pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose, lactose, the metal stearate and colorant into the tablet, said dosage form, after a first administration to a human patient, provides 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 C12/Cmax ratio of 0.55 to 0.85, and a therapeutic effect for at least 12 hours, wherein the hydrocodone or pharmaceutically acceptable salt thereof is the only active agent in the dosage form, the amount of the hydrocodone in the dosage form is from about 5 mg to about 60 mg, the metal stearate is magnesium stearate, and the wax is selected from the group consisting of beeswax, glycowax, castor wax, carnauba wax, and glyceryl behenate.
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32. A solid oral twice-a-day controlled-release dosage form, wherein the dosage form is a tablet consisting of
(i) a plurality of individually coated multiparticulates consisting of matrices individually coated with a coating consisting of ethylcellulose and a wax, the matrices collectively consisting of hydrocodone or a pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose and ethylcellulose, (ii) an additional amount of hydrocodone or pharmaceutically acceptable salt thereof, (iii) hydroxypropylmethyl cellulose, (iv) lactose, (v) a metal stearate, and (vi) a colorant, the individually coated multiparticulates compressed along with the additional amount of hydrocodone or pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose, lactose, the metal stearate and the colorant into the tablet, said dosage form, after a first administration to a patient population, provides a plasma concentration of hydrocodone of at least 8 ng/ml at from about 2 to about 8hours 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/Cmax ratio of 0.55 to 0.85, and a therapeutic effect for about 12 hours, wherein the hydrocodone or the pharmaceutically acceptable salt thereof is the only active agent in the dosage form, the amount of the hydrocodone in the dosage form is from about 5 mg to about 60 mg, the metal stearate is magnesium stearate, and the wax is selected from the group consisting of beeswax, glycowax, castor wax, carnauba wax, and glyceryl behenate.
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33. A solid oral twice-a-day controlled-release dosage form, the dosage form is a film coated tablet, the tablet consisting of
(i) a plurality of individually coated multiparticulates consisting of matrices individually coated with a coating consisting of ethylcellulose and a wax, the matrices consisting of hydrocodone or a pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose and ethylcellulose, (ii) an additional amount of hydrocodone or pharmaceutically acceptable salt thereof, (iii) hydroxypropylmethyl cellulose, (iv) lactose, (v) a metal stearate, and (vi) a colorant, the individually coated multiparticulates compressed along with the additional amount of hydrocodone or pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose, lactose, the metal stearate and the colorant into the tablet, the tablet coated with the film, said dosage form, after a first administration to a human patient, provides 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 C12/Cmax ratio of 0.55 to 0.85, and a therapeutic effect for at least 12 hours, wherein the hydrocodone or pharmaceutically acceptable salt thereof is the only active agent in the dosage form, the amount of the hydrocodone in the dosage form is from about 5 mg to about 60 mg, the metal stearate is magnesium stearate, and the wax is selected from the group consisting of beeswax, glycowax, castor wax, carnauba wax, and glyceryl behenate.
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34. A solid oral twice-a-day controlled-release dosage form, wherein the dosage form is a film coated tablet consisting of
(i) a plurality of individually coated multiparticulates consisting of matrices individually coated with a coating consisting of ethylcellulose and a wax, the matrices collectively consisting of hydrocodone or a pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose and ethylcellulose, (ii) an additional amount of hydrocodone or pharmaceutically acceptable salt thereof, (iii) hydroxypropylmethyl cellulose, (iv) lactose, (v) a metal stearate, and (vi) a colorant, the individually coated multiparticulates compressed along with the additional amount of hydrocodone or pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose, lactose, the metal stearate and the colorant into a tablet, the tablet coated with the film, said dosage form, after a first administration to a patient population, provides 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/Cmax ratio of 0.55 to 0.85, and a therapeutic effect for about 12 hours, wherein the hydrocodone or the pharmaceutically acceptable salt thereof is the only active agent in the dosage form, the amount of the hydrocodone in the dosage form is from about 5 mg to about 60 mg, the metal stearate is magnesium stearate, and the wax is selected from the group consisting of beeswax, glycowax, castor wax, carnauba wax, and glyceryl behenate.
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35. A solid oral twice-a-day controlled-release dosage form, wherein the dosage form is a film coated tablet, the tablet consisting of
(i) a plurality of individually coated multiparticulates consisting of matrices individually coated with a coating consisting of ethylcellulose and a wax, the matrices collectively consisting of from about 5 mg to about 60 mg hydrocodone or an equivalent amount of a pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose and ethylcellulose, (ii) hydroxypropylmethyl cellulose, (iii) lactose, (iv) a metal stearate, and (v) a colorant, the individually coated multiparticulates compressed along with hydroxypropylmethyl cellulose, lactose, the metal stearate and the colorant into the tablet, the tablet coated with the film, said dosage form, after a first administration to a human patient, provides 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 C12/Cmax ratio of 0.55 to 0.85, and a therapeutic effect for at least 12 hours, wherein the hydrocodone or pharmaceutically acceptable salt thereof is the only active agent in the dosage form, the metal stearate is magnesium stearate, and the wax is selected from the group consisting of beeswax, glycowax, castor wax, carnauba wax, and glyceryl behenate.
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36. A solid oral twice-a-day controlled-release dosage form, wherein the the dosage form is a film coated tablet, the tablet consisting of
(i) a plurality of individually coated multiparticulates consisting of matrices individually coated with a coating consisting of ethylcellulose and a wax, the matrices collectively consisting of from about 5 mg to about 60 mg hydrocodone or an equivalent amount of a pharmaceutically acceptable salt thereof, hydroxypropylmethyl cellulose and ethylcellulose, (ii) hydroxypropylmethyl cellulose, (iii) lactose, (iv) a metal stearate, and (v) a colorant, the individually coated multiparticulates compressed along with hydroxypropylmethyl cellulose, lactose, the metal stearate and the colorant into the tablet, the tablet coated with the film, said dosage form, after a first administration to a patient population, provides 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/Cmax ratio of 0.55 to 0.85, and a therapeutic effect for about 12 hours, wherein the hydrocodone or the pharmaceutically acceptable salt thereof is the only active agent in the dosage form, and the metal stearate is magnesium stearate, and the wax is selected from the group consisting of beeswax, glycowax, castor wax, carnauba wax, and glyceryl behenate.
Specification