Abuse Resistant Drug Formulation

Abstract

A pharmaceutical composition may include a granulate which may include at least one active pharmaceutical ingredient susceptible to abuse by an individual mixed with at least two materials, a first material that is substantially water insoluble and at least partially alcohol soluble and a second material that is substantially alcohol insoluble and at least partially water soluble, wherein the active pharmaceutical ingredient and the two materials are granulated in the presence of water and alcohol. The composition may also include a coating on the granulate exhibiting crush resistance which may have a material that is deposited on the granulate using an alcohol based solvent. The composition further comprises a second particle comprising a fat/wax. The present invention also includes a coated granulate, various dosage forms of the composition, as well as methods of production and tableting.

1 . A coated granulate, comprising:
 a granulate comprising at least one active pharmaceutical ingredient susceptible to abuse by an individual in an amount between about 0.1 to about 90 percent by weight of the granulate mixed with an at least two materials, said at least two materials comprise a first material that is substantially water insoluble and at least partially alcohol soluble and is present in an amount between about 1 to about 90 percent by weight of the granulate and a second material that is substantially alcohol insoluble and at least partially water soluble and is present in an amount between about 1 and about 90 percent by weight of the granulate, wherein the active pharmaceutical ingredient and the two materials are granulated in the presence of water and alcohol; and   a coating on said granulate provided in an amount of between about 20 and about 75 percent by weight of the coated granulate exhibiting crush resistance, wherein the coating comprises a material selected from the group consisting of cellulose polymers, methacrylate ester copolymers, methacrylic acid copolymers and shellac, said material deposited on said granulate using an alcohol based solvent.   
     
     
         2 . The coated granulate of  claim 1  wherein the first material comprises natural and synthetic starches, natural and synthetic celluloses, acrylics, vinylics, resins, methacrylates or shellac. 
     
     
         3 . The coated granulate of  claim 2  wherein the first material is ethylcellulose. 
     
     
         4 . The coated granulate of  claim 1  wherein the second material is natural and synthetic starches, natural and synthetic celluloses, acrylates, or polyalkylene oxides. 
     
     
         5 . The coated granulate of  claim 4  wherein the second material is selected from the group consisting of hydroxypropylmethylcellulose, methylcellulose, hydroxyethylmethylcellulose, sodium carboxy methylcellulose, hydroxyethylcellulose and polyethylene oxide. 
     
     
         6 . The coated granulate of  claim 5  wherein the second material is hydroxypropylmethylcellulose. 
     
     
         7 . The coated granulate of  claim 1  wherein the coating comprises ethylcellulose. 
     
     
         8 . A pharmaceutical composition, comprising:
 a granulate comprising at least one active pharmaceutical ingredient susceptible to abuse by an individual in an amount between about 0.1 to about 90 percent by weight of the granulate mixed with an at least two materials, said at least two materials comprise a first material that is substantially water insoluble and at least partially alcohol soluble and is present in an amount between about 1 to about 90 percent by weight of the granulate and a second material that is substantially alcohol insoluble and at least partially water soluble and is present in an amount between about 1 and about 90 percent by weight of the granulate, wherein the active pharmaceutical ingredient and the two materials are granulated in the presence of water and alcohol; and   a coating on said granulate provided in an amount of between about 20 and about 75 percent by weight of the coated granulate exhibiting crush resistance, wherein the coating comprises a material selected from the group consisting of cellulose polymers, methacrylate ester copolymers, methacrylic acid copolymers and shellac, said material deposited on said granulate using an alcohol based solvent; and   a fat/wax present in an amount between about 1 to about 50 percent by weight of the pharmaceutical composition.   
     
     
         9 . The pharmaceutical composition of  claim 8  wherein the first material comprises natural and synthetic starches, natural and synthetic celluloses, acrylics, vinylics, resins, methacrylates, or shellac. 
     
     
         10 . The pharmaceutical composition of  claim 9  wherein the first material is ethylcellulose. 
     
     
         11 . The pharmaceutical composition of  claim 8  wherein the second material is natural and synthetic starches, natural and synthetic celluloses, acrylates, or polyalkylene oxides. 
     
     
         12 . The pharmaceutical composition of  claim 11  wherein the second material is selected from the group consisting of hydroxypropylmethylcellulose, methylcellulose, hydroxyethylmethylcellulose, sodium carboxy methylcellulose, hydroxyethylcellulose and polyethylene oxide. 
     
     
         13 . The pharmaceutical composition of  claim 12  wherein the second material is hydroxypropylmethylcellulose. 
     
     
         14 . The pharmaceutical composition of  claim 8  wherein the coating comprises ethylcellulose. 
     
     
         15 . The pharmaceutical composition of  claim 8  wherein the fat/wax comprises glycerol fatty esters, fatty glyceride derivatives, waxes, or fatty alcohols. 
     
     
         16 . The pharmaceutical composition of  claim 15  wherein the fat/wax is selected from the group consisting of glycerol behenate, glycerol palmitostearate, stearoyl macroglycerides, carnauba wax, bees wax, microcrystalline wax, and cetyl alcohol. 
     
     
         17 . A pharmaceutical dosage form, comprising:
 a granulate comprising an opiate in an amount between about 0.1 to about 90 percent by weight of the granulate mixed with an at least two materials, wherein said at least two materials comprise a first material comprising ethylcellulose present in an amount between about 10 to about 40 percent by weight of the granulate and a second material comprising hydroxypropylmethylcellulose present in an amount between about 20 and about 50 percent by weight of the granulate, wherein the active pharmaceutical ingredient and the two materials are granulated in the presence of water and alcohol, said granulate present in an amount sufficient to provide an effective amount of said opiate;   a coating on said granulate provided in an amount of between about 40 and about 60 percent by weight of the coated granulate exhibiting crush resistance, wherein the coating comprises a material selected from the group consisting of cellulose polymers, methacrylate ester copolymers, methacrylic acid copolymers and shellac, said material deposited on said granulate using an alcohol based solvent;   a fat/wax present in an amount between about 5 to about 25 percent by weight of the final dosage form; and   at least one excipient.   
     
     
         18 . The pharmaceutical dosage form of  claim 17  wherein the fat/wax comprises glycerol fatty esters, fatty glyceride derivatives, waxes, or fatty alcohols. 
     
     
         19 . The pharmaceutical dosage form of  claim 18  wherein the fat/wax is selected from the group consisting of glycerol behenate, glycerol palmitostearate, stearoyl macroglycerides, carnauba wax, bees wax, microcrystalline wax, and cetyl alcohol. 
     
     
         20 . The pharmaceutical dosage form of  claim 17  wherein said excipient comprises other APIs, taste masking agents, binders, fillers, sugars, artificial sweeteners, polymers, flavoring agents, coloring agents, lubricants, glidants, bio- or muco-adhesives, viscosity modifiers, surfactants, buffers, or disintegrants. 
     
     
         21 . The pharmaceutical dosage form of  claim 17  further comprising barrier beads. 
     
     
         22 . The pharmaceutical dosage form of  claim 17  wherein the coating comprises ethylcellulose. 
     
     
         23 . A method of making a coated granulate, comprising:
 combining an at least one active pharmaceutical ingredient susceptible to abuse by an individual in an amount between about 0.1 to about 90 percent by weight of the granulate mixed with an at least two materials, said at least two materials comprise a first material that is substantially water insoluble and at least partially alcohol soluble and is present in an amount between about 1 to about 90 percent by weight of the granulate and a second material that is substantially alcohol insoluble and at least partially water soluble and is present in an amount between about 1 and about 90 percent by weight of the granulate, wherein the active pharmaceutical ingredient and the two materials are granulated in the presence of water and alcohol, forming a wet granulate;   milling and drying the wet granulate to form a granulate comprising an average particle size of about 50 to about 700 um;   depositing a coating on said granulate provided in an amount of between about 20 and about 75 percent by weight of the coated granulate exhibiting crush resistance, wherein the coating comprises a material selected from the group consisting of cellulose polymers, methacrylate ester copolymers, methacrylic acid copolymers and shellac, said material deposited on said granulate using an alcohol based solvent; and   allowing coating to dry.   
     
     
         24 . A method of treating a patient having pain, comprising administering a pharmaceutical dosage form as found in  claim 17 .