ABUSE RESISTANT FORMS OF IMMEDIATE RELEASE HYDROCODONE, METHOD OF USE AND METHOD OF MAKING
An abuse resistant oral pharmaceutical composition, comprising: a barrier layer, comprising a first polymer; a diffusion layer, comprising a second polymer, substantially covering the barrier layer, wherein the diffusion layer is bonded to the barrier layer and comprises a drug that is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the gastrointestinal (GI) tract; and optionally an expansion layer comprising an expandable polymer, wherein the expansion layer is substantially covered by the barrier layer. Methods of making the same and methods of using the same are also provided.
1 . A method of treating pain in a patient in need thereof, comprising
orally administering to the patient an abuse resistant pharmaceutical composition comprising
an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer,
a barrier layer that substantially covers the expansion layer and comprises a first polymer that does not substantially dissolve in the gastrointestinal (GI) tract, and
a diffusion layer that substantially covers and is bonded to the barrier layer and comprises hydrocodone or pharmaceutically acceptable salt thereof substantially homogeneously distributed within a second polymer selected from the group consisting of ethyl cellulose, quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, synthetic waxes, natural waxes, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose acetate succinate, shellac, cellulose acetate trimellitate, and mixtures thereof, wherein the hydrocodone or pharmaceutically acceptable salt thereof diffuses from the diffusion layer within the GI tract to treat pain,
wherein the pharmaceutical composition is configured such that when the pharmaceutical composition is administered to a subject in an intact form at least 90% of the total amount of hydrocodone or pharmaceutically acceptable salt thereof in the intact form is released after 1 hour,
wherein when the pharmaceutical composition is physically compromised to produce particles having a particle size between 8 mesh and 500 mesh and exposed to a liquid comprising water and/or alcohol, the bond between the diffusion layer and the barrier layer is substantially preserved and the expandable polymer of the expansion layer absorbs at least a portion of the liquid and expands and/or forms a gel, and
wherein when the pharmaceutical composition is physically compromised to produce particles having a particle size between 8 mesh and 500 mesh and administered to a subject no more than 75% of the total amount of hydrocodone or pharmaceutically acceptable salt thereof in the particles is released after 1 hour.
2 . The method of claim 1 , wherein the hydrocodone or pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 400 mg.
3 . The method of claim 1 , wherein the hydrocodone or pharmaceutically acceptable salt thereof comprises hydrocodone bitartrate.
4 . The method of claim 1 , wherein the pharmaceutical composition in the intact form releases at least 80% of the hydrocodone or pharmaceutically acceptable salt thereof in vitro after 1 hour, as determined under the following conditions: USP Apparatus I (basket) at 100 rpm in 900 mL aqueous buffer at pH 1.6 or 7.2 and 37° C.
5 . The method of claim 1 , wherein the pharmaceutical composition is in a form selected from the group consisting of a tablet, a capsule, a micro tablet, granules, pellets, a lozenge, a lollipop, and a coated capsule.
6 . The method of claim 1 , wherein the pharmaceutical composition is in a form of a tablet.
7 . The method of claim 6 , wherein the expansion layer has a thickness of about 5 to 95% of the total thickness of the tablet.
8 . The method of claim 6 , wherein the barrier layer has a thickness of about 5 to 50% of the total thickness of the tablet.
9 . The method of claim 6 , wherein the diffusion layer has a thickness of about 1 to 30% of the total thickness of the tablet.
10 . The method of claim 1 , wherein the first polymer and the second polymer are each independently selected from the group consisting of acrylic polymers, methacrylic polymers, acrylic copolymers and methacrylic copolymers.
11 . The method of claim 1 , wherein the first polymer and the second polymer are independently selected from the group consisting of ethyl acrylate, methyl methacrylate, and copolymers thereof.
12 . A method of treating pain in a patient in need thereof, comprising
orally administering to the patient an abuse resistant pharmaceutical composition comprising
an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer,
a barrier layer that substantially covers the expansion layer and comprises a first polymer that does not substantially dissolve in the gastrointestinal (GI) tract, and
a diffusion layer that substantially covers and is bonded to the barrier layer and comprises hydrocodone or pharmaceutically acceptable salt thereof substantially homogeneously distributed within a second polymer selected from the group consisting of ethyl cellulose, quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, synthetic waxes, natural waxes, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose acetate succinate, shellac, cellulose acetate trimellitate, and mixtures thereof, wherein the hydrocodone or pharmaceutically acceptable salt thereof diffuses from the diffusion layer within the GI tract to treat pain,
wherein the pharmaceutical composition is configured such that when the pharmaceutical composition is physically compromised to produce particles having a particle size between 8 mesh and 500 mesh and exposed to a liquid comprising water and/or alcohol, the bond between the diffusion layer and the barrier layer is substantially preserved and the expandable polymer of the expansion layer absorbs at least a portion of the liquid and expands and/or forms a gel, and
wherein when the pharmaceutical composition is physically compromised to produce particles having a particle size between 8 mesh and 500 mesh and administered to a subject the maximum blood concentration (Cmax) and/or area under the serum concentration curve (AUC) of the hydrocodone or pharmaceutically acceptable salt thereof achieved in the subject after 2 hours is lower than the Cmax and/or AUC achieved in the subject when the pharmaceutical composition is administered in an intact form.
13 . The method of claim 12 , wherein the hydrocodone or pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 400 mg.
14 . The method of claim 12 , wherein the hydrocodone or pharmaceutically acceptable salt thereof comprises hydrocodone bitartrate.
15 . The method of claim 12 , wherein the hydrophilic expandable polymer is present in an amount of 5 to 90% by weight based on the total weight of the dosage form.
16 . The method of claim 12 , wherein the pharmaceutical composition is in a form selected from the group consisting of a tablet, a capsule, a micro tablet, granules, pellets, a lozenge, a lollipop, and a coated capsule.
17 . The method of claim 12 , wherein the pharmaceutical composition is in a form of a tablet.
18 . The method of claim 17 , wherein the expansion layer has a thickness of about 5 to 95% of the total thickness of the tablet.
19 . The method of claim 17 , wherein the barrier layer has a thickness of about 5 to 50% of the total thickness of the tablet.
20 . The method of claim 17 , wherein the diffusion layer has a thickness of about 1 to 30% of the total thickness of the tablet.
21 . The method of claim 12 , wherein the first polymer and the second polymer are each independently selected from the group consisting of acrylic polymers, methacrylic polymers, acrylic copolymers and methacrylic copolymers.
22 . The method of claim 12 , wherein the first polymer and the second polymer are independently selected from the group consisting of ethyl acrylate, methyl methacrylate, and copolymers thereof.
23 . A method of treating pain in a patient in need thereof, comprising
orally administering to the patient an abuse resistant pharmaceutical composition comprising
an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer,
a barrier layer that substantially covers the expansion layer and comprises a first polymer that does not substantially dissolve in the gastrointestinal (GI) tract, and
a diffusion layer that substantially covers and is bonded to the barrier layer and comprises hydrocodone or pharmaceutically acceptable salt thereof substantially homogeneously distributed within a second polymer selected from the group consisting of ethyl cellulose, quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, synthetic waxes, natural waxes, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose acetate succinate, shellac, cellulose acetate trimellitate, and mixtures thereof, wherein the hydrocodone or pharmaceutically acceptable salt thereof diffuses from the diffusion layer within the GI tract to treat pain,
wherein the pharmaceutical composition is configured such that when the pharmaceutical composition is physically compromised to produce particles having a particle size between 8 mesh and 500 mesh and exposed to a liquid comprising water and/or alcohol, the bond between the diffusion layer and the barrier layer is substantially preserved and the expandable polymer of the expansion layer absorbs at least a portion of the liquid and expands and/or forms a gel, and
wherein when the pharmaceutical composition is administered with an alcohol, the rate of release of the hydrocodone or pharmaceutically acceptable salt thereof from the pharmaceutical composition within 2 hours after administration is lower than the rate of release of the hydrocodone or pharmaceutically acceptable salt thereof from the pharmaceutical composition without alcohol.
24 . The method of claim 23 , wherein the hydrocodone or pharmaceutically acceptable salt thereof is present in an amount of about 5 mg to about 400 mg.
25 . The method of claim 23 , wherein the hydrocodone or pharmaceutically acceptable salt thereof comprises hydrocodone bitartrate.
26 . The method of claim 23 , wherein the pharmaceutical composition is in a form selected from the group consisting of a tablet, a capsule, a micro tablet, granules, pellets, a lozenge, a lollipop, and a coated capsule.
27 . The method of claim 23 , wherein the pharmaceutical composition is in a form of a tablet.
28 . The method of claim 23 , wherein the first polymer and the second polymer are each independently selected from the group consisting of acrylic polymers, methacrylic polymers, acrylic copolymers and methacrylic copolymers.
29 . The method of claim 23 , wherein the first polymer and the second polymer are independently selected from the group consisting of ethyl acrylate, methyl methacrylate, and copolymers thereof.
30 . The method of claim 23 , wherein the rate of release is determined by comparing the maximum blood concentration (Cmax) and/or area under the serum concentration curve (AUC) of the hydrocodone or pharmaceutically acceptable salt thereof achieved in a subject after administration of the pharmaceutical composition with alcohol versus administration of the pharmaceutical composition without alcohol.