A twice-a-day solid oral controlled-release dosage form of a bitartrate salt of hydrocodone consisting ofna pharmaceutically acceptable capsule,immediate release multiparticulates consisting of a first portion of pharmaceutically acceptable inert beads, a first portion of the bitartrate salt of hydrocodone, hydroxypropylmethylcellulose, glidant(s), and optional plasticizer(s), andcontrolled release multiparticulates consisting of the remaining portion of the pharmaceutically acceptable inert beads, the remaining portion of the bitartrate salt of hydrocodone, an ammonio methacrylate copolymer, glidant(s), and optional plasticizer(s),wherein the total amount of the bitartrate salt of hydrocodone in the dosage form is from about 5 mg to about 60 mg,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., andafter a first administration to a human patient, providing a C12/Cmax hydrocodone ratio of 0.55 to 0.85, a Tmax of hydrocodone at from about 2 to 8 hours and a therapeutic effect for about 12 hours.
›2.↳ 1The dosage form of claim 1, which provides a C12/Cmax ratio of 0.65 to 0.75 after said first administration.d2
The dosage form of claim 1, which provides a C12/Cmax ratio of 0.65 to 0.75 after said first administration.
›3.↳ 1The dosage form of claim 1, which provides a dissolution rate in-vitro of the hydrocodone from the dosage form when measured by the USP Basket method …d2
The dosage form of claim 1, which provides a dissolution rate in-vitro of the hydrocodone from the dosage form when measured by the USP Basket method at 100 rpm in 900 ml aqueous buffer at a pH of 1.2 at 37° C. from about 25 to about 65% by weight hydrocodone released after 2 hours, from about 45 to about 85% by weight hydrocodone released after 4 hours, and greater than about 60% by weight hydrocodone released after 8 hours.
›4.↳ 1The dosage form of claim 1, which provides a dissolution rate in-vitro of the hydrocodone from the dosage form when measured by the USP Basket method …d2
The dosage form of claim 1, which provides a dissolution rate in-vitro of the hydrocodone from the dosage form when measured by the USP Basket method at 100 rpm in 900 ml aqueous buffer at a pH of 7.5 at 37° C. from about 25 to about 65% by weight hydrocodone released after 2 hours, from about 45 to about 85% by weight hydrocodone released after 4 hours, and greater than about 60% by weight hydrocodone released after 8 hours.
›5.↳ 1The dosage form of claim 1, which provides a Tmax of hydrocodone in said patient at from about 3 to about 7 hours after said first administration of t…d2
The dosage form of claim 1, which provides a Tmax of hydrocodone in said patient at from about 3 to about 7 hours after said first administration of the dosage form.
›6.↳ 1The dosage form of claim 1, which provides a Tmax of hydrocodone in said patient at from about 4 to about 6 hours after said first administration of t…d2
The dosage form of claim 1, which provides a Tmax of hydrocodone in said patient at from about 4 to about 6 hours after said first administration of the dosage form.
›7.↳ 1The dosage form of claim 1, which provides a plasma concentration of hydrocodone of at least 8 ng/ml at from about 2 to about 8 hours after said first…d2+1
The dosage form of claim 1, which provides a plasma concentration of hydrocodone of at least 8 ng/ml at from about 2 to about 8 hours after said first administration and provides a plasma concentration of hydrocodone of at least 6 ng/ml at about 12 hours after said first administration, based on oral administration of a dosage form containing 15 mg hydrocodone bitartrate.
›8.↳ 7The dosage form of claim 7, which provides a plasma concentration of hydrocodone of at least 8 ng/ml at from about 3 to about 7 hours after said first…d3
The dosage form of claim 7, which provides a plasma concentration of hydrocodone of at least 8 ng/ml at from about 3 to about 7 hours after said first administration.
›9.↳ 1The dosage form of claim 1, which maintains a plasma concentration of hydrocodone within 80% of Cmax for about 1 to about 9 hours during the 12 hour d…d2
The dosage form of claim 1, which maintains a plasma concentration of hydrocodone within 80% of Cmax for about 1 to about 9 hours during the 12 hour dosing interval.
›10.↳ 1The dosage form of claim 1, which maintains a plasma concentration of hydrocodone within 80% of Cmax for about 4 to about 8 hours during the 12 hour d…d2
The dosage form of claim 1, which maintains a plasma concentration of hydrocodone within 80% of Cmax for about 4 to about 8 hours during the 12 hour dosing interval.
›11.↳ 1The dosage form of claim 1, which maintains a plasma concentration of hydrocodone within 90% of Cmax for about 1 to about 6.5 hours during the 12 hour…d2
The dosage form of claim 1, which maintains a plasma concentration of hydrocodone within 90% of Cmax for about 1 to about 6.5 hours during the 12 hour dosing interval.
›12.↳ 1The dosage form of claim 1, which maintains a plasma concentration of hydrocodone within 90% of Cmax for about 2 to about 5 hours during the 12 hour d…d2
The dosage form of claim 1, which maintains a plasma concentration of hydrocodone within 90% of Cmax for about 2 to about 5 hours during the 12 hour dosing interval.
›16.↳ 1The dosage form of claim 1, wherein the remaining portion of the pharmaceutically acceptable inert beads is coated with the remaining portion of the b…d2
The dosage form of claim 1, wherein the remaining portion of the pharmaceutically acceptable inert beads is coated with the remaining portion of the bitartrate salt of hydrocodone, the ammonio methacrylate copolymer and glidant(s).
›17.↳ 1The dosage form of claim 1, wherein the multiparticulates are in the form of spheroids.d2+2
The dosage form of claim 1, wherein the multiparticulates are in the form of spheroids.
›18.↳ 17The dosage form of claim 17, wherein the spheroids are in a form of spherical granules having a diameter of between 0.1 mm and 2.5 mm.d3+1
The dosage form of claim 17, wherein the spheroids are in a form of spherical granules having a diameter of between 0.1 mm and 2.5 mm.
›19.↳ 18The dosage form of claim 18, wherein the spherical granules have a diameter of between 0.5 mm and 2 mm.d4
The dosage form of claim 18, wherein the spherical granules have a diameter of between 0.5 mm and 2 mm.
›20.↳ 1The dosage form of claim 1, wherein the multiparticulates are in the form of granules.d2
The dosage form of claim 1, wherein the multiparticulates are in the form of granules.
›21.↳ 1The dosage form of claim 1, wherein at least one of the glidants is talc.d2
The dosage form of claim 1, wherein at least one of the glidants is talc.
›22.↳ 1The dosage form of claim 1, wherein the ammonio methacrylate copolymer is a copolymer of acrylic and methacrylic ester with a molar ratio of ammonium …d2
The dosage form of claim 1, wherein the ammonio methacrylate copolymer is a copolymer of acrylic and methacrylic ester with a molar ratio of ammonium groups to neutral (meth)acrylic esters of 1:40.
