Abuse-resistant pharmaceutical compositions

Abstract

An abuse-resistant controlled release pharmaceutical composition comprising a pharmaceutically effective amount of discrete particles of an active capable of abuse, wherein surfaces of said particles are wetted with a water insoluble coating material, and preferably wherein said composition comprises a matrix, in which said particles are distributed, and which renders the abuse-capable compound within the matrix difficult to separate from the matrix; and a method for the preparation of a controlled release pharmaceutical composition having a reduced potential for abuse, comprising applying a pressure force to a mixture comprising a water insoluble material, and particles of a pharmaceutically active compound capable of inducing in a subject a reaction that is physiologically or psychologically detrimental if administered in an immediate release dosage form, thereby resulting in surface coated particles, and incorporating said surface coated particles into a pharmaceutical composition

1 - 11 . (canceled) 
     
     
         12 . A method for the preparation of an sustained release pharmaceutical composition having a reduced potential for abuse, comprising: (a) providing a pharmaceutically active compound capable of inducing in a subject a reaction that is physiologically or psychologically addictive if administered in an immediate release dosage form; (b) applying a pressure force to a mixture comprising particles of said compound and a water insoluble material thereby resulting in surface coated particles; and (c) incorporating said surface coated particles into a pharmaceutical composition that when subjected to stress does not increase substantially the immediate release of said compound in an aqueous environment. 
     
     
         13 . A method according to  claim 12  wherein said force is applied to a dispersion of said particles in a flowable medium comprising said material. 
     
     
         14 . A method according to  claim 13  wherein said force is an abrupt pressure force. 
     
     
         15 . A method according to  claim 13  wherein said force is an ultrasonic force. 
     
     
         16 . A method according to  claim 13  wherein said force is piston generated shock wave. 
     
     
         17 . A method according to  claim 13  wherein said particles are micronized. 
     
     
         18 . A method according to  claim 17  wherein said particles have a mean particle size of less than about ten microns. 
     
     
         19 . A method according to  claim 13  wherein said material comprises a polymorphic wax 
     
     
         20 . A method according to  claim 19  wherein said wax comprises a hydrogenated vegetable wax, a tri-, di- or mono-glyceride, or a mixture thereof 
     
     
         21 . A method according to  claim 20  wherein said material comprises a polymeric material that is water insoluble, and erodable in the intestinal tract at pH greater than about 6. 
     
     
         22 . A method according to  claim 13  further comprising solidifying said dispersion into microspheres. 
     
     
         23 . A method according to  claim 12  wherein the application of mechanical stress to said composition modifies the aqueous dissolution of said compound by an increase of less than about 15% of said pharmaceutically effective amount in the first hour, and does not substantially modify the dissolution rate of said composition thereafter. 
     
     
         24 . (canceled) 
     
     
         25 . An abuse resistant pharmaceutical composition comprising:
 a hard gelatin capsule encapsulating:
 (i) a plurality of immediate release microspheres of a hydrophobic polymer matrix having dispersed therein, an active ingredient capable of abuse in an amount sufficient to provide a T max  of from 2 to 4 hours; and 
 (ii) a plurality of controlled release microspheres of a water insoluble matrix of organic material resistant to dissolution or acidic degradation at pH less than 4, having a size in the range from 50 to 800 microns, having dispersed therein, an active ingredient capable of abuse, which is the same or different from the active ingredient in the immediate release microspheres, and having a surface coating material comprising methylmethacrylate or ethylcellulose on the surface of the microspheres, 
   wherein the pharmaceutical composition releases the active ingredient at a rate that blood plasma concentrations are maintained within a therapeutic range over a period of time from 8 to 24 hours, and further wherein the composition does not include an antagonist of the water soluble compound capable of abuse.   
     
     
         26 . The abuse-resistant composition according to  claim 25 , wherein said matrix material is non-erodable at pH less than about 6. 
     
     
         27 . The abuse-resistant composition according to  claim 25  wherein said matrix material is erodable in the presence of bile salts and lipase. 
     
     
         28 . The abuse-resistant composition of  claim 25 , wherein the water insoluble matrix of organic material is selected from the group consisting of ethylcellulose, cellulose acetate, vinyl acetate/vinyl chloride copolymers, acrylate/methacrylate copolymers, polyethylene oxide, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, triglycerides, hydrogenated vegetable oils, triglyceride polyalkoxyalkylesters, fats, waxes, water insoluble partially-degraded proteins and mixtures thereof. 
     
     
         29 . The abuse-resistant composition according to  claim 25  wherein said compound is an analgesic opiate narcotic. 
     
     
         30 . The abuse-resistant composition to according to  claim 29  wherein said narcotic is selected from the group consisting of hydromorphone, oxycodone, hydroxycodone, propoxyphene, methadone, tilidine, butorphanol, buprenorphine, levorphanol, codeine, oxymorphone, meperidine, dihydrocodeinone. 
     
     
         31 . An abuse resistant pharmaceutical composition comprising:
 (a) a polymeric matrix composition consisting essentially of a polymeric moiety and from about 1 to about 50% of an aliphatic alcohol having from 8 to 20 carbon atoms, based on the weight the total matrix composition,   (b) particles of an active ingredient capable of abuse having a water insoluble controlled release surface coating thereon, the particles being chemically bonded to the polymeric matrix, whereby the active ingredient capable of abuse is substantially incapable of immediate release from the polymeric matrix, and further wherein the composition does not include an antagonist of the water soluble compound capable of abuse.   
     
     
         32 . The abuse-resistant composition according to  claim 31 , wherein said aliphatic alcohol is fatty alcohol. 
     
     
         33 . The abuse-resistant composition according to  claim 32 , wherein said fatty alcohol is selected from the group consisting of cetyl alcohol, stearyl alcohol and a combination thereof. 
     
     
         34 . The abuse-resistant composition according to  claim 33  wherein said matrix material is erodable in the presence of bile salts and lipase. 
     
     
         35 . The abuse-resistant composition according to  claim 32  wherein said compound is an analgesic opiate narcotic. 
     
     
         36 . The abuse-resistant composition to according to  claim 32  wherein said narcotic is selected from the group consisting of hydromorphone, oxycodone, hydroxycodone, propoxyphene, methadone, tilidine, butorphanol, buprenorphine, levorphanol, codeine, oxymorphone, meperidine, dihydrocodeinone. 
     
     
         37 . The abuse-resistant composition of  claim 32 , wherein the polymeric moiety is a polymer selected from the group consisting of ethylcellulose, cellulose acetate, vinyl acetate/vinyl chloride copolymers, acrylate/methacrylate copolymers, polyethylene oxide, hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, triglycerides, hydrogenated vegetable oils, triglyceride polyalkoxyalkylesters, fats, a hydrogenated cottonseed oil wax, a partially hydrogenated soybean oil, carnuba wax, water insoluble partially-degraded proteins and mixtures thereof.