Misuse preventative, controlled release formulation

Abstract

Disclosed is a misuse preventative, controlled release composition in the form of a multilayered oral dosage form. A first layer contains a plurality of controlled release microparticles having a pharmaceutically active agent (for example, an opioid analgesic) disposed therein. The second layer, which can be adjacent the first layer comprises a pharmaceutically active agent that can be the same or different from the pharmaceutically active agent in the microparticles in the first layer. The composition further comprises a superabsorbent material (for example, polycarbophil) disposed within the first layer, the second layer, or both the first layer and the second layer. When intact, the pharmaceutically active agent is released from the second layer faster than the pharmaceutically active agent in the first layer. When crushed, either intentionally or accidentally, and exposed to an aqueous medium, the superabsorbent material present swells to encapsulate the microparticles, which remain substantially intact thereby retarding the release of the pharmaceutically active agent from the composition. Also disclosed is a method of using the misuse preventative, controlled release composition to deliver at least one pharmaceutically active agent to a mammal, for example, a human, in need thereof.

1 . A solid composition for oral administration of at least one pharmaceutically active agent, comprising:
 (a) a first layer comprising a first population of controlled release microparticles having a pharmaceutically active agent disposed therein;   (b) a second layer comprising a pharmaceutically active agent disposed therein; and   (c) a superabsorbent material disposed within the first layer, the second layer, or both the first layer and the second layer, wherein the composition,
 (i) when intact and exposed to an aqueous environment, the pharmaceutically active agent disposed in the second layer is initially released at a faster rate than the pharmaceutically active agent disposed in the first layer, and 
 (ii) when crushed and exposed to an aqueous environment, the superabsorbent material swells to create a hard gel that traps the microparticles, whereupon the hard gel, the microparticles or both the hard gel and microparticles provide controlled release of at least the pharmaceutically active agent disposed within the microparticles. 
   
     
     
         2 . The composition of  claim 1 , wherein the superabsorbent material is disposed within the first layer. 
     
     
         3 . The composition of  claim 1 , wherein the superabsorbent material is disposed within the second layer. 
     
     
         4 . A solid composition for oral administration of at least one pharmaceutically active agent, comprising:
 (a) a first layer comprising a superabsorbent material and first population of controlled release microparticles having a pharmaceutically active agent disposed therein;   (b) a second layer comprising a pharmaceutically active agent disposed therein, wherein the composition,
 (i) when intact and exposed to an aqueous environment, the pharmaceutically active agent disposed in the second layer is initially released at a faster rate than the pharmaceutically active agent disposed in the first layer, and 
 (ii) when crushed and exposed to an aqueous environment, the superabsorbent material swells to create a hard gel that traps the microparticles, whereupon the hard gel, the microparticles or both the hard gel and microparticles provide controlled release of at least the pharmaceutically active agent disposed within the microparticles. 
   
     
     
         5 . The composition of  claim 1 , wherein the pharmaceutically active agent disposed in the second layer is present in a second population of controlled release microparticles. 
     
     
         6 . The composition of  claim 1 , wherein the pharmaceutically active agent present in the first layer and the pharmaceutically active agent present in the second layer are the same. 
     
     
         7 . The composition of  claim 1 , wherein the pharmaceutically active agent present in first layer and the pharmaceutically active agent present in the second layer are different. 
     
     
         8 . The composition of  claim 1 , wherein the first layer is adjacent the second layer. 
     
     
         9 . The composition of  claim 8 , wherein the composition is a bilayer. 
     
     
         10 . The composition of  claim 1 , wherein a third layer is disposed between the first layer and the second layer. 
     
     
         11 . The composition of  claim 1 , wherein the pharmaceutically active agent present in the first layer is released over a period of at least 6 hours. 
     
     
         12 . The composition of  claim 1 , wherein the pharmaceutically active agent present in the first layer is released over a period of at least 12 hours. 
     
     
         13 . The composition of  claim 12 , wherein the pharmaceutically active agent present in the first layer is released over a period of at least 24 hours. 
     
     
         14 . The composition of  claim 1 , wherein the superabsorbent material is a polysaccharide derivative selected from the group consisting of a starch graft copolymer, a cross-linked carboxymethylcellulose derivative, a cross-linked hydroxypropyl distarch phosphate, a hydrolyzed starch-acrylonitrile graft copolymer and a neutralized starch-acrylic acid graft copolymer. 
     
     
         15 . The composition of  claim 1 , wherein the superabsorbent material is a polymer selected from the group consisting of polyacrylic acid, polyacrylamido methylpropane sulfonic acid, polyvinyl acetic acid, polyvinyl phosphonic acid, polyvinyl sulfonic acid, isobutylene-maleic anhydride copolymer, carboxymethyl cellulose, alginic acid, carrageenan, polyaspartic acid, polyglutamic acid, polyvinyl amine, polydiallyl dimethyl ammonium hydroxide, polyacrylamidopropyl trimethyl ammonium hydroxide, polyamino propanol vinyl ether, polyallylamine, chitosan, polylysine, polyglutamine, polycarbophil, polycarbophilic calcium, polymethacrylic acid, polyacrylic acid, and mixtures thereof. 
     
     
         16 . The composition of  claim 1 , wherein the superabsorbent material constitutes from about 1% to about 70% (w/w) of the first layer or the second layer. 
     
     
         17 . The composition of  claim 16 , wherein the superabsorbent material constitutes from about 2% to about 50% (w/w) of the first layer or the second layer. 
     
     
         18 . The composition of  claim 1 , wherein the first layer, the second layer, or both the first and second layers further comprise a controlled release agent. 
     
     
         19 . The composition of  claim 18 , wherein the controlled release agent is selected from the group consisting of acetate succinate, a polyvinyl derivative, polyethylene oxide, polyacrylic acid, modified starch, cross-linked high amylose starch, hydroxypropyl starch, hydroxypropyl methylcellulose phthalate, cellulose, microcrystalline cellulose, carboxymethylethyl cellulose, cellulose acetate, methylcellulose, ethylcellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, cellulose phthalate, cellulose acetate, cellulose acetate phthalate, cellulose acetate propionate, cellulose acetate succinate, cellulose acetate butyrate, cellulose acetate trimellitate, poloxamer, povidone, alginic acid, sodium alginate, polyethylene glycol, polyethylene glycol alginate, gums, polymethacrylate, a copolymer of methacrylic acid and ethyl acrylate, a copolymer of polymethyl vinyl ether and malonic acid anhydride, a copolymer of polymethyl vinyl ether and malonic acid or the ethyl-, isopropyl-, n-butylesters thereof, zein, and mixtures of any of the foregoing. 
     
     
         20 . The composition of  claim 1 , wherein the first layer, the second layer or both the first and second layers further comprise a diluent, a lubricant, a glidant, or a mixture thereof. 
     
     
         21 - 66 . (canceled)