Aqueous risperidone formulations

Abstract

The present invention is concerned with physicochemically stable aqueous solutions of risperidone for oral and parenteral administration; processes for preparing such formulations.

1. An aqueous solution suitable for oral and parenteral administration comprising water, risperidone or a pharmaceutically acceptable acid addition salt thereof, characterized in that said solution comprises a buffer to maintain the pH in the range of 2 to 6 and is essentially free of sorbitol. 
     
     
       2. A solution according to  claim 1  wherein said pH range is obtained with a tartaric acid/sodium hydroxide buffer. 
     
     
       3. A solution according to  claim 1  wherein the amount of risperidone ranges from 0.01% to 1% by weight based on the total volume of the solution. 
     
     
       4. A solution according to  claim 1  having a pH ranging from 3 to 4 which is suitable for oral administration. 
     
     
       5. A solution according to  claim 4  further comprising benzoic acid as a preservative. 
     
     
       6. A solution according to  claim 5  containing
 (a) 1 mg/ml risperidone;  
 (b) 2 mg/ml benzoic acid;  
 (c) 7.5 mg/ml tartaric acid and sufficient sodium hydroxide to adjust the pH in the range from 3 to 4; and  
 (d) water q.s. ad 1 ml.  
 
     
     
       7. A solution according to  claim 6  further comprising one or more members selected from the group consisting of sweetening agents and flavouring substances. 
     
     
       8. A solution according to  claim 1  having a pH ranging from 5 to 6 which is suitable for parenteral administration. 
     
     
       9. A solution according to  claim 4  further comprising sodium chloride as an isotonizing agent. 
     
     
       10. A solution according to  claim 9  containing
 (a) 1 mg/ml risperidone;  
 (b) 5 mg/ml sodium chloride;  
 (c) 7.5 mg/ml tartaric acid and sufficient sodium hydroxide to adjust the pH in the range from 5 to 6; and  
 (d) water q.s. ad 1 ml.  
 
     
     
       11. A process of preparing a solution according to  claim 1  comprising the steps of
 (a) adding the acid component of the buffer and the active ingredient risperidone to an amount of water,  
 (b) stirring the mixture until complete dissolution and cooling the solution to room temperature,  
 (c) adjusting the pH with the base component of the buffer, and  
 (d) further diluting the solution with water to the required end-volume.  
 
     
     
       12. A process according to  claim 11  for preparing an oral solution as defined in  claim 5  wherein step (a) is preceded by the steps of:
 (a) dissolving the preservative in an amount of heated water, and  
 (b) diluting the solution with about an equal amount of water.  
 
     
     
       13. A process according to  claim 11  for preparing an parenteral solution as defined in  claim 9  wherein step (d) is preceded immediately by the step of rendering the solution about isotonic by the addition of an appropriate amount of isotonizing agent, and is followed by autoclaving.