Stable Granulates Containing S-adenosylmethionine and Process for Preparation Thereof

Abstract

A fluid bed granulation process for manufacturing non-hygroscopic, stable granulates containing a water-soluble salt of S-adenosylmethionine is described. Said process comprises: a) the simultaneous, sequential or alternate dispersion of at least a solution of a water-soluble salt of SAMe (A) and of a solution of a coating agent (B), on a fluid bed granulation carrier (C) and b) the fluid bed granulation of the mixture. Granulates obtainable by said process and solid oral pharmaceutical forms obtainable by said granulates are disclosed.

1 . A process for manufacturing granulates containing a water-soluble salt of S-adenosylmethionine characterized by comprising:
 a) the simultaneous, sequential or alternate dispersion of at least a solution of a water-soluble salt of SAMe (A) and of a solution of a coating agent (B), on a fluid bed granulation carrier (C) and   b) the fluid bed granulation of the mixture so obtained at a temperature not above 62° C.   
     
     
         2 . A process according to  claim 1  wherein said fluid bed granulation is performed at a temperature from 48 and 52° C. 
     
     
         3 . A process according to  claim 1  wherein the water-soluble salt of SAMe (A) is a salt of SAMe, simple or mixed, selected among sulfate, tosylate and 1,4-butandisulfonate. 
     
     
         4 . A process according to  claim 3  wherein said salt is SAMe disulfate tosylate. 
     
     
         5 . A process according to  claim 1  wherein said solutions are aqueous solutions. 
     
     
         6 . A process according to  claim 1  wherein the solution of the water-soluble salt of SAMe (A) has a concentration from 10 to 25% by weight, preferably from 15 to 20% by weight. 
     
     
         7 . A process according to  claim 1  wherein the coating agent (B) is selected from the group comprising chitins, carragenins, cellulose and chemically modified celluloses, gum or xanthane. 
     
     
         8 . A process according to  claim 7  wherein the coating agent (B) is a hydroxypropylmethylcellulose. 
     
     
         9 . A process according to  claim 1  wherein the solution of the coating agent (B) has a concentration from 5 to 15% by weight, preferably from 7 to 10% by weight. 
     
     
         10 . A process according to  claim 1  wherein the fluid bed granulation carrier (C) is selected among starch, cellulose and maltodextrin, preferably said carrier is microcrystalline cellulose. 
     
     
         11 . A process according to  claim 1  wherein the fluid bed granulation carrier (C) is characterized by a granulometry from 50 to 500μ, preferably from 100 to 200μ. 
     
     
         12 . A process according to  claim 1  characterized by comprising an additional coating step with a gastro-resistant coating agent. 
     
     
         13 . A granulate obtainable according to the process of  claim 1 . 
     
     
         14 . A granulate, according to  claim 13 , comprising up to 60% by weight, preferably from 48 and 55% by weight, of a water-soluble salt of SAMe (A), 5-15% by weight of a coating agent (B) and 25-45% by weight of carrier (C). 
     
     
         15 . Oral pharmaceutical compositions containing a granulate according to  claim 13 .