Particles containing an opioid receptor antagonist and methods of use

Abstract

Particles comprising an opioid receptor antagonist as well as methods of their use and methods of their preparation are provided herein. Such particles may be used for treating and preventing opioid-induced side effects in patients, and may be provided to chronic opioid users as well.

1 . An enterically-coated particle comprising at least one opioid receptor antagonist, at least one hydrophilic additive that is negatively charged at acidic and neutral pH, and at least one hydrophilic additive is positively charged at acidic and neutral pH. 
     
     
         2 . The enterically-coated particle of  claim 1 , wherein the positively-charged opioid receptor antagonist is a peripheral opioid antagonist. 
     
     
         3 . The enterically-coated particle of  claim 2 , wherein the peripheral opioid receptor antagonist is a quaternary morphinan derivative, a carboxy-normorphinan derivative, or a quaternary benzomorphan derivative. 
     
     
         4 . The enterically-coated particle of  claim 3 , wherein the quaternary morphinan is a quaternary salt of N-methylnaltrexone, N-methylnaloxone, N-methylnalorphine, N-diallylnormorphine, N-allyllevellorphan, or N-methylnalmefene. 
     
     
         5 . The enterically-coated particle of  claim 3 , wherein the quaternary benzomorphan derivative is selected from the group consisting of 2′-hydroxy-5,9-dimethyl-2,2-diallyl-6,7-benzomorphanium bromide; 2′-hydroxy-5,9-dimethyl-2-n-propyl-2-allyl-6,7-benzomorphanium bromide; 2′-hydroxy-5,9-dimethyl-2-n-propyl-2-propargyl-6,7-benzomorphanium bromide; and
 2′-acetoxy-5,9-dimethyl-2-n-propyl-2-allyl-6,7-benzomorphanium bromide. 
 
     
     
         6 . The enterically-coated particle of  claim 1 , wherein the particle comprises two or more opioid receptor antagonists. 
     
     
         7 . The enterically-coated particle of  claim 1 , wherein the hydrophilic additive that is negatively charged at acidic and neutral pH is pentasodium tripolyphosphate (TPP). 
     
     
         8 . The enterically-coated particle of  claim 1 , wherein the at least one hydrophilic additive is positively charged at acidic and neutral pH is a polymer. 
     
     
         9 . The enterically-coated particle of  claim 1 , wherein the at least one hydrophilic additive is positively charged at acidic and neutral pH is chitosan. 
     
     
         10 . The enterically-coated particle of  claim 1 , wherein a diameter of the enterically-coated particle is between about 30-1000 nm. 
     
     
         11 . The enterically-coated particle of  claim 1 , wherein a weight percentage of total opioid receptor antagonist in the enterically-coated particle ranges from about 8-35. 
     
     
         12 . The enterically-coated particle of  claim 1 , wherein the enteric coating comprises both a polymethacrylate and a distilled acetylated monoglyceride. 
     
     
         13 . The enterically-coated particle of  claim 1 , further defined as a time release composition, wherein the time release composition is formulated to release the opioid receptor antagonist over time.