Immediate Release Abuse-Deterrent Granulated Dosage Forms

Abstract

Described are oral dosage forms that contain abuse-deterrent features and that contain core-shell polymers that include an active pharmaceutical ingredient, with particular examples including immediate release dosage forms that contain a drug that is commonly susceptible to abuse.

What is claimed is: 
     
         1 . An immediate release abuse deterrent dosage form comprising:
 a) core-shell particles, the core-shell particles comprising:
 i) a core, the core comprising at least one of: a wax, a sugar sphere, a microcrystalline cellulose sphere or a gelling polymer; 
 ii) an active pharmaceutical layer surrounding the core, the active pharmaceutical layer comprising an active pharmaceutical ingredient which is commonly susceptible to abuse, wherein the active pharmaceutical ingredient is selected from: a narcotic analgesic, a sedative-hypnotic, a CNS stimulant, an anxiolytic, an antipsychotic, a dissociative anesthetic, and a muscle relaxant; and 
 iii) at least one film layer surrounding the active pharmaceutical layer, at least one film layer comprising a film forming polymer; and 
   b) a matrix comprising a disintegrant and a gelling polymer.   
     
     
         2 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the core contains less than 5 weight percent of a total amount of the active pharmaceutical ingredient in the core-shell particles. 
     
     
         3 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the active pharmaceutical ingredient is a narcotic analgesic. 
     
     
         4 . The immediate release abuse deterrent dosage form according to  claim 3 , wherein the narcotic analgesic is an opioid. 
     
     
         5 . The immediate release abuse deterrent dosage form according to  claim 4 , wherein the opioid is selected from buprenorphine, codeine, dihydrocodeine, dihydromorphine, hydrocodone, hydromorphone, pseudoephedrine, morphine, oxycodone, oxymorphone, and pharmaceutically acceptable salts thereof. 
     
     
         6 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the active pharmaceutical ingredient is a sedative-hypnotic. 
     
     
         7 . The immediate release abuse deterrent dosage form according to  claim 6 , wherein the sedative-hypnotic is selected from barbiturates, benzodiazepines, phenothiazines, and sleep medications. 
     
     
         8 . The immediate release abuse deterrent dosage form according to  claim 7 , wherein the sedative-hypnotic is a sleep medication selected from zolpidem, zaleplon, eszopiclone and pharmaceutically acceptable salts thereof. 
     
     
         9 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the active pharmaceutical ingredient is a CNS stimulant. 
     
     
         10 . The immediate release abuse deterrent dosage form according to  claim 9 , wherein the CNS stimulant is selected from amphetamines and non-amphetamine psychostimulants. 
     
     
         11 . The immediate release abuse deterrent dosage form according to  claim 9 , wherein the CNS stimulant is an amphetamine selected from dextroamphetamine, levoamphetamine, methamphetamine, pseudoephedrine, Adderall and pharmaceutically acceptable salts thereof. 
     
     
         12 . The immediate release abuse deterrent dosage form according to  claim 9 , wherein the CNS stimulant is a non-amphetamine psychostimulant selected from methylphenidate and pharmaceutically acceptable salts thereof, modafinil and armodafinil. 
     
     
         13 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the active pharmaceutical ingredient is an anxiolytic. 
     
     
         14 . The immediate release abuse deterrent dosage form according to  claim 13 , wherein the anxiolytic is a benzodiazepine selected from diazepam, chlordiazepoxide, estazolam, lorazepam, triazolam, alprazolam, clonazepam, flurazepam and pharmaceutically acceptable salts thereof. 
     
     
         15 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the active pharmaceutical ingredient is an antipsychotic. 
     
     
         16 . The immediate release abuse deterrent dosage form according to  claim 15 , wherein the antipsychotic is selected from phenothiazines, butyrophenones, dibenzoxazepines and atypical antipsychotic agents. 
     
     
         17 . The immediate release abuse deterrent dosage form according to  claim 15 , wherein the antipsychotic is an atypical antipsychotic agent selected from aripiprazole, clozapine, olanzapine, quetiapine, risperidone ziprasidone, paliperidone and remoxipride. 
     
     
         18 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the active pharmaceutical ingredient is a muscle relaxant. 
     
     
         19 . The immediate release abuse deterrent dosage form according to  claim 18 , wherein the muscle relaxant is selected from cyclobenzaprine and pharmaceutically acceptable salts thereof, cannabinols and cannabinoids. 
     
     
         20 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the active pharmaceutical ingredient is a dissociative anesthetic. 
     
     
         21 . The immediate release abuse deterrent dosage form according to  claim 20 , wherein the dissociative anesthetic is selected from Ketamine or Esketamine. 
     
     
         22 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the core comprises a gelling polymer or a wax. 
     
     
         23 . The immediate release abuse deterrent dosage form according to  claim 22 , wherein the core further comprises a binder. 
     
     
         24 . The immediate release abuse deterrent dosage form according to  claim 23 , wherein the binder is selected from: alginic acid, sodium carboxymethylcellulose, microcrystalline cellulose, dextrin, ethylcellulose, gelatin, starch, pregelatinized starch, polyvinyl alcohol, polyethylene oxide, polyvinylpyrrolidone, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropylmethylcellulose, hydroxymethyl cellulose and any combination thereof. 
     
     
         25 . The immediate release abuse deterrent dosage form according to  claim 24 , wherein the core comprises a gelling polymer, a wax and a binder selected from: alginic acid, sodium carboxymethylcellulose, microcrystalline cellulose, dextrin, ethylcellulose, gelatin, starch, pregelatinized starch, polyvinyl alcohol, polyethylene oxide, polyvinylpyrrolidone, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, methylcellulose, hydroxypropyl cellulose, hydroxymethyl cellulose and any combination thereof. 
     
     
         26 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the core comprises a gelling polymer selected from a natural starch, a synthetic starch, a natural cellulose, a synthetic cellulose, an acrylate, a polyalkylene oxide, a poly(acrylic acid), and combinations thereof. 
     
     
         27 . The immediate release abuse deterrent dosage form according to  claim 26 , wherein the gelling polymer in the core is selected from ethylcellulose, cellulose acetate, cellulose acetate propionate, cellulose acetate butyrate, cellulose acetate phthalate, cellulose triacetate, cellulose ether, cellulose ester, cellulose ester ether, cellulose, an acrylic acid and methacrylic acid copolymer, a methyl methacrylate copolymer, an ethoxyethyl methacrylate, a cyanoethyl methacrylate, poly(acrylic acid), poly(methacrylic acid), methacrylic acid alkylamide copolymer, poly(methyl methacrylate), polymethacrylate, poly(methyl methacrylate) copolymer, polyacrylamide, aminoalkyl methacrylate copolymer, poly(methacrylic acid anhydride), glycidyl methacrylate copolymer, agar, acacia, karaya, tragacanth, algin, guar; polyacrylamide; water-swellable indene maleic anhydride polymer, hydroxypropyl methyl cellulose, hydroxy methyl cellulose, methyl cellulose, hydroxyethylmethyl cellulose, sodium carboxymethyl cellulose, a carbomer polymer, polyethylene oxide, polyvinyl alcohol and combinations thereof. 
     
     
         28 . The immediate release abuse deterrent dosage form according to  claim 26 , wherein the gelling polymer in the core is selected from hydroxypropyl methyl cellulose, hydroxy methyl cellulose, methyl cellulose, ethyl cellulose, hydroxyethylmethyl cellulose, sodium carboxymethyl cellulose, a carbomer polymer, polyethylene oxide, polyvinyl alcohol and combinations thereof. 
     
     
         29 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the core comprises a wax. 
     
     
         30 . The immediate release abuse deterrent dosage form according to  claim 29 , wherein the wax comprises a fatty acid ester, a fatty glyceride derivative, or a fatty alcohol. 
     
     
         31 . The immediate release abuse deterrent dosage form according to  claim 30 , wherein the wax is selected from glyceryl behenate, glycerol palmitostearate, a stearoyl macroglyceride, carnauba wax, bees wax, microcrystalline wax, cetyl alcohol, and a combination thereof. 
     
     
         32 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the core comprises a microcrystalline cellulose sphere or a sugar sphere. 
     
     
         33 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the gelling polymer in the matrix is selected from a natural starch, a synthetic starch, a natural cellulose, a synthetic cellulose, an acrylate, a polyalkylene oxide, and combinations thereof. 
     
     
         34 . The immediate release abuse deterrent dosage form according to  claim 33 , wherein the gelling polymer in the matrix is selected from hydroxypropyl methyl cellulose, hydroxy methyl cellulose, methyl cellulose, hydroxyethylmethyl cellulose, sodium carboxymethyl cellulose, a carbomer polymer, and combinations thereof. 
     
     
         35 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the disintegrant in the matrix is selected from corn starch, croscarmellose sodium, crospovidone, sodium starch glycolate, PVP, HPC, pregelatinized starch and a combination thereof. 
     
     
         36 . The immediate release abuse deterrent dosage form according to  claim 35 , wherein the dosage form comprises from 0.5 to 50 weight percent disintegrant based on total weight of the dosage form. 
     
     
         37 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the at least one film layer surrounding the active pharmaceutical layer comprises a pH-sensitive film forming polymer. 
     
     
         38 . The immediate release abuse deterrent dosage form according to  claim 37 , wherein the pH-sensitive film forming polymer is insoluble in water at a pH greater than 5 and is soluble in water at a pH below 5. 
     
     
         39 . The immediate release abuse deterrent dosage form according to  claim 38 , wherein the pH-sensitive film forming polymer is a copolymer of dimethyl aminoethyl methacrylate, butyl methacrylate, and methyl methacrylate monomers. 
     
     
         40 . The immediate release abuse deterrent dosage form according to  claim 1 , wherein the dosage form excludes an emetic, a nasal irritant, and an effervescent. 
     
     
         41 . The immediate release abuse deterrent dosage form according to  claim 4 , wherein the dosage form excludes an opioid antagonist. 
     
     
         42 . The immediate release abuse deterrent dosage form according to  claim 1  wherein the dosage form is in a suppository, capsule, caplet, pill, gel, soft gelatin capsule, or compressed tablet form. 
     
     
         43 . The immediate release abuse deterrent dosage form according to  claim 42  wherein the dosage form is in a compressed tablet form. 
     
     
         44 . A method of preventing, alleviating, or ameliorating a level of pain in a subject, the method comprising administering to the subject a dosage form as recited at  claim 3 .