ABUSE RESISTANT FORMS OF EXTENDED RELEASE HYDROMORPHONE, METHOD OF USE AND METHOD OF MAKING

摘要

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.

主权项

1. A method of treating pain in a patient in need thereof, comprising
orally administering to the patient an abuse resistant extended release 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, anda diffusion layer that substantially covers and is bonded to the barrier layer and comprises hydromorphone 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 hydromorphone or pharmaceutically acceptable salt thereof diffuses from the diffusion layer within the GI tract to provide extended release over a period of about 6 to about 24 hours 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, wherein the amount of hydromorphone or pharmaceutically acceptable salt thereof released from the particles within a time period selected from the group consisting of 2 hours, 4 hours, 8 hours and 16 hours, is substantially the same or lower than the amount of hydromorphone or pharmaceutically acceptable salt thereof released from the pharmaceutical composition in intact form, wherein the release is 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.