Gamma-hydroxybutyric acid granules

Abstract

A granule including a solid core on which is supported an active ingredient, said active ingredient being selected from gamma-hydroxybutric acid or one of its pharmaceutically acceptable salts, said granule further including, supported on said solid core, one or more compounds which may generate gas evolvement, one or more diluents, said granule being in that it is coated with a membrane, and in that the solid core represents from 15% to 25% by weight based on the total weight of the granule.

1 . A coated granule composed of a solid core on which is supported:
 an active ingredient, the active ingredient being selected from gamma hydroxybutric acid or one of its pharmaceutically acceptable salts,   a gas generator,   a diluent,   a binder, and   a coating membrane, where
 the coating membrane is a layer surrounding the active ingredient, the gas generator, the diluent, and the binder, and the layer has a surface that is an outermost surface of the coated granule; wherein 
 the coated granule comprises the following, by weight based on the total weight of the granule:
 15-25% of the solid core, 
 50-60% of the active ingredient, 
 5-15% of the gas generator, 
 2-18% of the diluent, 
 3-10% of the binder, and 
 3-6% of the coating membrane, 
 
 the gas generator is sodium bicarbonate; 
 the diluent is magnesium aluminometasilicate; and 
 the hinder is shellac. 
   
     
     
         2 . The coated granule according to  claim 1 , wherein the solid core is one or more member selected from the group consisting of polyols, gums, derivatives of silica, calcium derivatives, potassium derivatives, mineral compounds, dicalcium phosphates, tricalcium phosphates, calcium carbonates, saccharose, cellulose derivatives, microcrystalline cellulose, ethyl cellulose, hydroxypropylmethylcellulose, and starch. 
     
     
         3 . The coated granule according to  claim 1 , wherein the coating membrane consists of coating excipients for immediate release. 
     
     
         4 . The coated granule according to  claim 1 , wherein the coating membrane consists of coating excipients for sustained release. 
     
     
         5 . The coated granule according to  claim 1 , wherein the coated granule further comprises a coloring agent. 
     
     
         6 . The coated granule according to  claim 1 , wherein the coloring agent is soluble in an aqueous solvent. 
     
     
         7 . The coated granule according to  claim 1 , wherein the coloring agent is soluble in an alcoholic solvent. 
     
     
         8 . The coated granule according to  claim 5 , wherein
 the coated granule is formed by mixing the active ingredient, the gas generator, the diluent, and the coloring agent to form a mixture that is applied on the solid core, the application of which to the solid core being carried out concomitantly with spraying of a binder in the form of a solution, where the obtained granule is surrounded by the application of the coating membrane.   
     
     
         9 . The coated granule according to  claim 1 , wherein the coated granule further comprises a metal pigment. 
     
     
         10 . The coated granule according to  claim 5 , wherein
 the coated granule further comprises a metal pigment, and   the coated granule is formed by mixing the active ingredient, the gas generator, the diluent, the coloring agent, and the metal pigment to form a mixture that is applied on the solid core, the application of which to the solid core being carried out concomitantly with spraying of a binder in the form of a solution, where the obtained granule is surrounded by the application of the coating membrane.   
     
     
         11 . The coated granule according to  claim 9 , wherein the metal pigment is present in the layer having the surface that is the outermost surface of the coated granule. 
     
     
         12 . The coated granule according to  claim 1 , wherein the coated granule farther comprises one or more member selected from the group consisting of a sweetener, a flavoring agent, bitterness agent and a lubricant. 
     
     
         13 . A pharmaceutical composition comprising a mixture of the coated granules according to  claim 1 , wherein said mixture comprises at least two groups of coated granules, the at least two groups of coated granules having different kinetics for releasing the active ingredient. 
     
     
         14 . A method for treating a pathology requiring at least very fast in vivo availability of GHB, the method comprising administering an effective amount of a composition comprising the coated granule of  claim 1  to a patient to treat the pathology. 
     
     
         15 . The method according to  claim 14 , wherein the pathology is narcolepsy. 
     
     
         16 . The method according to  claim 14 , wherein the pathology is alcoholic withdrawal. 
     
     
         17 . A coated granule composed of a solid core on which is supported:
 an active ingredient, the active ingredient being selected from gamma hydroxybutric acid or one of its pharmaceutically acceptable salts,   a gas generator,   a diluent,   a binder,   one or more optional ingredients selected from the group consisting of a coloring agent, a metal pigment, a lubricant, a bitterness agent, a sweetener, and a flavoring agent, and   a coating membrane, where
 the coating membrane is a layer surrounding the active ingredient, the gas generator, the diluent, the one or more optional ingredients, and the binder, and the layer has a surface that is an outermost surface of the coated granule; wherein 
 the coated granule consisting essentially of the following, by weight based on the total weight of the granule:
 15-25% of the solid core, 
 50-60% of the active ingredient, 
 5-15% of the gas generator, 
 2-18% of the diluent. 
 3-10% of the binder, 
 3-6% of the coating membrane, and 
 optionally, the balance being the one or more optional ingredients; 
 
 the gas generator is sodium bicarbonate; 
 the diluent is magnesium aluminometasilicate; and 
 the binder is shellac. 
   
     
     
         18 . A coated granule consisting of a solid core on which is supported:
 an active ingredient, the active ingredient being selected from gamma hydroxybutric acid or one of its pharmaceutically acceptable salts,   a gas generator,   a diluent,   a binder,   one or more optional ingredients selected from the group consisting of a coloring agent, a metal pigment, a lubricant, a bitterness agent, a sweetener, and a flavoring agent, and   a coating membrane, where
 the coating membrane is a layer surrounding the active ingredient, the gas generator, the diluent, the one or more optional ingredients, and the binder, and the layer has a surface that is an outermost surface of the coated granule; wherein 
 the coated granule consisting of the following, by weight based on the total weight of the granule:
 15-25% of the solid core, 
 50-60% of the active ingredient, 
 5-15% of the gas generator, 
 2-18% of the diluent, 
 3-10% of the binder, 
 3-6% of the coating membrane, and 
 optionally, the balance being the one or more optional ingredients; 
 
 the gas generator is sodium bicarbonate; 
 the diluent is magnesium aluminometasilicate; and 
 the binder is shellac.