Drug delivery system

Abstract

A drug delivery system for the controlled release of a pharmaceutically-active compound by oral route comprises an intercalate of a layered double hydroxide having, before intercalation, layers of metal hydroxides, and having intercalated therein a pharmaceutically-active compound having at least one anionic group. A preferred layered double hydroxide is one that has layers which comprise [LiAl 2 (OH) 6 ] + . The drug delivery system has use in the delivery of drugs such as 4-biphenylacetic acid, Diclofenac, Gemfibrozil, Ibuprofen, Naproxen, 2-Propylpentanoic acid and Tolfenamic acid.

1 . A drug delivery system comprising an intercalate of a layered double hydroxide having, before intercalation, layers of metal hydroxides, and having intercalated therein a pharmaceutically-active compound having at least one anionic group.  
     
     
         2 . The system according to  claim 1  wherein the layered double hydroxide, before intercalation, is represented by the general formula 
       [M (1−x)   II M x   III (OH) 2 ] x+ [A x/n   n− ] 
       in which M II  is a divalent metal cation; 
 M III  is a trivalent metal cation;  
 A is a displaceable anion;  
 n is an integer; and  
 x is a number less than 1, which compound is optionally hydrated with a stoichiometric amount or a non-stoichiometric amount of water.  
 
     
     
         3 . The system according to  claim 2 , wherein M II  is Mg or Ca and M III  is Al.  
     
     
         4 . The system according to  claim 2  or  claim 3 , wherein A is selected from OH, F, Cl, Br, I, SO 4  and NO 3 .  
     
     
         5 . The system according to  claim 1 , wherein the layered double hydroxide, before intercalation, is represented by the general formula 
       [M I M 2   III (OH) 6 ] + [A 1/n   n− ] 
       in which M I  is a monovalent metal cation; 
 M III  is a trivalent metal cation;  
 A is a displaceable anion; and  
 n is an integer, which compound is optionally hydrated with a stoichiometric or non-stoichiometric amount of water.  
 
     
     
         6 . The system according to  claim 5 , wherein M I  is Li and M III  is Al.  
     
     
         7 . The system according to  claim 5  or  claim 6 , wherein A is selected from OH, F, Cl, Br, I, SO 4  and NO 3 .  
     
     
         8 . The system according to  claim 7 , wherein the layered double hydroxide is [LiAl 2 (OH) 6 ]Cl.H 2 O.  
     
     
         9 . The system according to any one of  claims 1  to  8 , wherein the pharmaceutically-active compound having at least one anionic group is a pharmaceutically-active compound containing at least one carboxylic acid group or a non-toxic salt thereof.  
     
     
         10 . The system according to any one of  claims 1  to  9 , which additionally comprises a non-toxic compound having an anion which is capable of displacing the pharmaceutically-active compound from the intercalate.  
     
     
         11 . The system according to  claim 10 , wherein the non-toxic compound is selected from magnesium carbonate, magnesium hydrogen carbonate, calcium carbonate or calcium hydrogen carbonate.  
     
     
         12 . The system according to any one of  claims 1  to  11 , wherein the pharmaceutically-active compound is selected from 4-biphenylacetic acid, Diclofenac, Gemfibrozil, Ibuprofen, Naproxen, 2-propylpentanoic acid and Tolfenamic acid.  
     
     
         13 . A method of making an intercalate of a layered double hydroxide having, intercalated therein, a pharmaceutically-active compound having at least one anionic group which comprises treating an aqueous solution of the pharmaceutically-active compound, optionally in the form of a non-toxic salt thereof, with the layered double hydroxide and separating the intercalate of the layered double hydroxide.  
     
     
         14 . The method according to  claim 13 , wherein the layered double hydroxide, before intercalation, is represented by the general formula 
       [M (1−x)   II M x   III (OH) 2 ] x+ [A x/n   n− ] 
       in which M II  is a divalent metal cation; 
 M III  is a trivalent metal cation;  
 A is a displaceable anion;  
 n is an integer; and  
 x is a number less than 1, which compound is optionally hydrated with a stoichiometric amount or a non-stoichiometric amount of water.  
 
     
     
         15 . A method according to  claim 14 , wherein M II  is Mg and M III  is Al.  
     
     
         16 . The method according to either  claim 14  or  claim 15 , wherein A is selected from OH, F, Cl, Br, I, SO 4  and NO 3 .  
     
     
         17 . The method according to  claim 13 , wherein the layered double hydroxide, before intercalation, is represented by the general formula 
       [M I M 2   III (OH) 6 ] + [A 1/n   n− ] 
       in which M I  is a monovalent metal cation; 
 M III  is a trivalent metal cation;  
 A is a displaceable anion; and  
 n is an integer, which compound is optionally hydrated with a stoichiometric amount or a non-stoichiometric amount of water.  
 
     
     
         18 . The method according to  claim 17 , wherein M I  is Li and M III  is Al.  
     
     
         19 . The method according to either  claim 17  or  claim 18 , wherein A is selected from OH, F, Cl, Br, I, SO 4  and NO 3 .  
     
     
         20 . The method according to  claim 19 , wherein the layered double hydroxide is [LiAl 2 (OH) 6 ]Cl.H 2 O.  
     
     
         21 . The method according to any one of  claims 13  to  20 , wherein the pharmaceutically-active compound having at least one anionic group is a pharmaceutically-active compound containing at least one carboxylic acid group or a non-toxic salt thereof.  
     
     
         22 . The method according to  claim 21  wherein the pharmaceutically-active compound is selected from 4-biphenylacetic acid, Diclofenac, Gemfibrozil, Ibuprofen, Naproxen, 2-propylpentanoic acid and Tolfenamic acid.