Abuse-deterrent pharmaceutical compositions of opioids and other drugs

Abstract

An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opiods. In the preferred embodiment, a drug is modified to increase its lipophilicity. In preferred embodiments the modified drug is homogeneously dispersed within microparticles composed of a material that is either slowly soluble or not soluble in water. In some embodiments the drug containing microparticles or drug particles are coated with one or more coating layers, where at least one coating is water insoluble and preferably organic solvent insoluble, but enzymatically degradable by enzymes present in the human gastrointestinal tract. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is broken down or dissolved gradually within the GI tract by a combination of enzymatic degradation, surfactant action of bile acids, and mechanical erosion.

1 - 32 . (canceled) 
     
     
         33 . A method of preparing an abuse-deterrent pharmaceutical composition comprising
 (a) dispersing a lipophilic drug or lipophilic derivative of a drug prone to abuse or lipophilic derivative of a drug prone to abuse in one or more carrier materials selected from the group consisting of fats, fatty substances, waxes, wax-like substances and mixtures thereof,   (b) forming microparticles from the material obtained in step (a), and   (c) optionally coating the microparticles obtained in step (b).   
     
     
         34 . A method of preparing an abuse-deterrent pharmaceutical composition comprising
 (a) dispersing a lipophilic derivative of a drug prone to abuse in one or more carrier materials which are either slowly soluble in water or insoluble in water,   (b) forming microparticles from the material obtained in step (a), and   (c) optionally coating the microparticles obtained in step (b).   
     
     
         35 . The method of  claim 33  or  34  wherein the one or more carrier materials are heated above their melting temperatures and the lipophilic drug or lipophilic derivative of the drug is dispersed in the resulting molten liquid. 
     
     
         36 . The method of  claim 35  wherein the drug or drug derivative is dissolved in the molten carrier materials. 
     
     
         37 . The method of  claim 35  wherein the drug or drug derivative is partially dissolved in the molten carrier materials. 
     
     
         38 . The method of  claim 35  wherein the drug or drug derivative is dispersed, but not dissolved, in the molten carrier materials. 
     
     
         39 . The method of  claim 33  or  34  wherein the one or more carrier material are dissolved in a solvent and the lipophilic drug or lipophilic derivative of a drug is co-dissolved in the solvent. 
     
     
         40 . The method of  claim 35  wherein microparticles are formed by solidifying the molten mixture of carrier materials and drug or drug derivative under constant stirring as the mixture cools. 
     
     
         41 . The method of  claim 35  wherein microparticles are formed by
 (d) extruding the molten mixture, and   (e) optionally spheronizing the resulting pellets to form beads.   
     
     
         42 . The method of  claim 35  wherein the microparticles are formed by congealing. 
     
     
         43 . The method of  claim 35  wherein the microparticles are formed by spray chilling. 
     
     
         44 . The method of  claim 35  wherein the microparticles are formed by dispersing the molten mixture into water under stirring. 
     
     
         45 . The method of  claim 33  or  34  wherein the microparticles are coated in a wet granulation process. 
     
     
         46 . The method of  claim 33  or  34  wherein the microparticles are coated in spray process. 
     
     
         47 . The method of  claim 33  or  34  wherein the microparticles are coated via a coacervation process.