Abuse resistant opioid drug-ion exchange resin complexes having hybrid coatings

Abstract

A sustained release formulation for opioid drugs is described. The formulation contains an opioid-ion exchange resin complex having a hybrid coating. The hybrid coating contains a cured polyvinylacetate polymer and a pH-dependent enteric coating layer mixed therein. Also provided are methods of making and using same.

1 . A coated modified release opioid-ion exchange resin complex comprising:
 a pharmaceutically effective amount of an opioid bound to a pharmaceutically acceptable ion exchange resin complex;   a hybrid modified release coating layer over the resin complex, said hybrid coating comprising:
 a pH-independent, high tensile strength, water permeable, water insoluble, diffusion barrier coating forming component comprising polyinylacetate (PVA) and a plasticizer and 
 an enteric coating forming component having pH-dependent solubility in an aqueous system which is non-reactive with barrier coating component. 
   
     
     
         2 . The opioid-ion exchange resin matrix according to  claim 1 , wherein the opioid drug is selected from the group consisting of opioid analgesics drugs selected from the group consisting of hydrocodone, morphine, hydromorphone, oxycodone, codeine, levorphanol, meperidine, methadone, oxymorphone, buprenorphine, fentanyl and derivatives thereof, dipipanone, tramadol, etorphine, dihydroetorphine, butorphanol, levorphanol, or salts thereof or mixtures thereof. 
     
     
         3 . The opioid-ion exchange resin matrix according to  claim 1 , wherein the opioid is morphine or morphine sulfate. 
     
     
         4 . The coated opioid-ion exchange resin complex according to  claim 1 , wherein the enteric polymer forming component comprises polyvinyl acetate phthalate and at least one plasticizer. 
     
     
         5 . The coated opioid-ion exchange resin complex according to  claim 1 , wherein the barrier coating forming component and enteric polymer forming component are present in a ratio of about 20:1 to about 3:1 wt/wt. 
     
     
         6 . The coated opioid drug-ion exchange resin complex according to  claim 5 , wherein the barrier coating forming component and enteric polymer forming component are present in a ratio of about 6:1 to 4:1 wt/wt. 
     
     
         7 . The coated opioid drug-ion exchange resin complex according to  claim 2 , wherein the enteric coating forming component comprises a polyinylacetate phthalate, at least one plasticizer, and one or more selected from the group consisting of a detackifier, a lubricant, an alkalizing agent, a viscosity modifier, and an anti-caking agent. 
     
     
         8 . The coated opioid drug-ion exchange resin complex according to  claim 7 , wherein the enteric coating forming component comprises a liquid plasticizer and a solid plasticizer. 
     
     
         9 . The coated opioid drug-ion exchange resin complex according to  claim 9 , wherein the liquid plasticizer is citroflex triethylcitrate. 
     
     
         10 . The coated opioid drug-ion exchange resin complex according to  claim 9 , wherein the solid plasticizer is polyethylene glycol 3350. 
     
     
         11 . The coated opioid drug-ion exchange resin complex according to  claim 7 , wherein the enteric coating forming component comprises titanized polyvinylacetate phthalate. 
     
     
         12 . The coated opioid drug-ion exchange resin complex according to  claim 1 , wherein the barrier coating forming component comprises about 70% to about 95% w/w polyvinyl acetate. 
     
     
         13 . The coated opioid drug-ion exchange resin complex according to  claim 12 , wherein the barrier coating forming component comprises PVA, a stabilizer, a surfactant and a plasticizer. 
     
     
         14 . The coated opioid drug-ion exchange resin complex according to  claim 13 , wherein the plasticizer comprises about 3 to about 10% w/w of solids in the barrier coating forming component. 
     
     
         15 . The coated opioid drug-ion exchange resin complex according to  claim 13 , wherein the plasticizer in the barrier coating forming component is selected from the group consisting of dibutyl sebacate, propylene glycol, polyethylene glycol, polyvinyl alcohol, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, tributyl citrate, triacetin, Soluphor P, and mixtures thereof. 
     
     
         16 . The coated opioid drug-ion exchange resin complex according to  claim 15 , wherein the plasticizer is triacetin. 
     
     
         17 . The coated opioid drug-ion exchange resin complex according to  claim 13 , wherein the stabilizer is a polyvinylpyrrolidone. 
     
     
         18 . The coated opioid drug-ion exchange resin complex according to  claim 17 , wherein the polyvinyl pyrrolidone comprises about 5 to about 10% w/w of the barrier coating forming component. 
     
     
         19 . The coated opioid drug-ion exchange resin complex according to  claim 13 , wherein the surfactant is sodium lauryl sulfate. 
     
     
         20 . The opioid-ion exchange resin complex according to  claim 1 , wherein the hybrid coating comprises 25% to 50% by weight of the coated complex. 
     
     
         21 . The opioid-ion exchange resin complex according to  claim 20 , wherein the hybrid coating comprises 30% to 45% by weight of the coated complex. 
     
     
         22 . A solid dose comprising the coated opioid drug-ion exchange resin complex according to  claim 1  and pharmaceutically acceptable excipients, wherein the opioid-ion exchange resin complex is in a matrix with at least one polymer to form an opioid-drug ion exchange resin complex-matrix. 
     
     
         23 . The solid dose according to  claim 22 , wherein the at least one polymer is selected from the group consisting of a polyvinyl acetate polymer, polyvinylpyrrolidone, ethyl cellulose, cellulose acetate, acrylic based polymers or copolymers, cellulose phthalate, and mixtures thereof. 
     
     
         24 . A solid dose modified release morphine formulation comprising:
 a pharmaceutically effective amount of morphine bound to a pharmaceutically acceptable cationic exchange resin complex;   a cured hybrid modified release coating layer over the resin complex, said hybrid coating comprising a single layer comprising a barrier forming component comprising polyinylacetate (PVA) and a plasticizer and an enteric coating component comprising PVA-phthalate and at least one plasticizer.   
     
     
         25 . The solid dose modified release morphine formulation according to  claim 24 , wherein the barrier forming component further comprises polyvinyl pyrrolidone and sodium laurel sulfate. 
     
     
         26 . The solid dose modified release morphine formulation according to  claim 24 , wherein the enteric coating component further comprises a liquid plasticizer, a solid plasticizer, and at least one or more of a detackifier, a lubricant, an alkalizing agent, a viscosity modifier, and an anti-caking agent. 
     
     
         27 . The solid dose modified morphine formulation according to  claim 26 , wherein the enteric coating component further comprises citroflex triethylcitrate, talc, sodium bicarbonate, polyethylene glycol 3350, stearic acid, sodium alginate, and silica. 
     
     
         28 . The solid dose modified release morphine formulation according to  claim 24 , wherein the cured hybrid coating comprises in about of 20:1 by weight to about 6:1 by weight barrier coating component to enteric coating component. 
     
     
         29 . The solid dose modified release morphine formulation according to  claim 24 , wherein the hybrid coating comprises about 30% by weight of the uncoated complex. 
     
     
         30 . The solid dose modified release morphine formulation according to  claim 24 , further comprising a solvating agent. 
     
     
         31 . The solid dose modified release morphine formulation according to  claim 24 , wherein said solid dose is a tablet. 
     
     
         32 . The solid dose modified release morphine formulation according to  claim 24 , further comprising a non-functional coating on the cured hybrid coating layer. 
     
     
         33 . The solid dose modified release morphine formulation according to  claim 32 , wherein the non-functional coating comprises about 2% by weight of the tablet. 
     
     
         34 . The solid dose modified release morphine formulation according to  claim 24 , wherein the tablet comprises a morphine-cation exchange resin complex, at least one filler, at least one lubricant, and at least one diluent. 
     
     
         35 . The solid dose modified release morphine formulation according to  claim 34 , wherein the filler comprises about 1 to 70% by weight of the tablet. 
     
     
         36 . The solid dose modified release morphine formulation according to  claim 34 , wherein the filler is selected from the group consisting of calcium silicate, microcrystalline cellulose, lactose and combinations thereof. 
     
     
         37 . The solid dose modified release morphine formulation according to  claim 34 , wherein the lubricant comprises about 0.01% to about 5% w/w of the tablet. 
     
     
         38 . The solid dose modified release morphine formulation according to  claim 34 , wherein the lubricant is selected from the group consisting of amorphous silica, talc, magnesium stearate, or combinations thereof. 
     
     
         39 . The solid dose modified release morphine formulation according to  claim 34 , further comprising a disintegrant comprising about 1 to about 20% w/w of the tablet. 
     
     
         40 . The solid dose modified morphine formulation according to  claim 39 , wherein the disintegrant is crospovidone. 
     
     
         41 . A method of delivering a sustained release of morphine over a period of at least 12 to 24 hours comprising orally administering to a subject a solid dose modified release morphine formulation according to  claim 34 .