Paroxetine compositions and processes for making the same

Abstract

Paroxetine salt compositions having improved stability are formed by controlling the pH to 6.5 or less. The compositions can be made with the aide of water without significant coloration problems. The paroxetine salts include paroxetine hydrochloride salts but preferably use paroxetine sulfonate salts such as paroxetine methane sulfonate.

We claim:  
     
         1 . A solid paroxetine composition comprising a paroxetine salt and an excipient wherein said composition has a pH of 6.5 or less.  
     
     
         2 . The composition according to  claim 1 , wherein said pH is within the range of about 4.5 to 6.5.  
     
     
         3 . The composition according to  claim 1 , wherein said paroxetine salt is a paroxetine sulfonate salt or a paroxetine hydrochloride salt.  
     
     
         4 . The composition according to  claim 3 , wherein said pH is less than 6.0.  
     
     
         5 . The composition according to  claim 3 , wherein said pH is within the range of about 4.5 to 6.5.  
     
     
         6 . The composition according to  claim 5 , wherein said paroxetine salt is paroxetine methane sulfonate or paroxetine hydrochloride.  
     
     
         7 . The composition according to  claim 6 , wherein said paroxetine salt is paroxetine methane sulfonate.  
     
     
         8 . The composition according to  claim 1 , wherein the excipient is acidic calcium phosphate.  
     
     
         9 . The composition according to  claim 1 , wherein said composition is a tablet and said paroxetine salt is contained in a pharmaceutically effective amount and is selected from paroxetine sulfonate salts and paroxetine hydrochloride salts.  
     
     
         10 . The composition according to  claim 9 , wherein said excipient is selected from the group consisting of a diluent, a binder, a disintegrant, a lubricant, a colorant, or a combination of two or more thereof.  
     
     
         11 . The composition according to  claim 10 , which does not contain a hydrosoluble or hydrophilic diluent.  
     
     
         12 . The composition according to  claim 11 , which does not contain a taste masking coating.  
     
     
         13 . The composition according to  claim 11 , which comprises calcium phosphate, a lubricant and a disintegrant.  
     
     
         14 . The composition according to  claim 13 , wherein said paroxetine salt is paroxetine methane sulfonate salt.  
     
     
         15 . A paroxetine solid dosage form comprising a paroxetine sulfonate salt and having been made with the aid of water.  
     
     
         16 . The dosage form according to  claim 15 , wherein said dosage form is a tablet or a capsule.  
     
     
         17 . The dosage form according to  claim 16 , wherein said paroxetine sulfonate salt is paroxetine methane sulfonate.  
     
     
         18 . The dosage form according to  claim 15 , wherein said paroxetine sulfonate salt was combined as an aqueous solution with at least one excipient in preparing said dosage form.  
     
     
         19 . The dosage form according to  claim 18 , wherein said dosage form has a pH of 6.5 or less.  
     
     
         20 . A granulate formed by mixing water, paroxetine sulfonate, and at least one excipient and drying the resulting mixture.  
     
     
         21 . The granulate according to  claim 20 , wherein said mixing was accomplished by adding together an aqueous solution of said paroxetine sulfonate salt with said at least one excipient.  
     
     
         22 . The granulate according to  claim 21 , wherein said aqueous solution of paroxetine sulfonate salt is a concentrated solution having at least about a 10 wt % concentration of paroxetine sulfonate.  
     
     
         23 . The granulate according to  claim 22 , wherein said aqueous solution has a paroxetine sulfonate salt concentration of at least about 30 wt %.  
     
     
         24 . The granulate according to  claim 20 , wherein said mixing and said drying are carried out simultaneously.  
     
     
         25 . The granulate according to  claim 21 , wherein said aqueous solution of paroxetine sulfonate was added to a powdered or granulated blend of said at least one excipient.  
     
     
         26 . The granulate according to  claim 20 , wherein said granulate has an average remaining added water content of about 2.0 wt % or less.  
     
     
         27 . The granulate according to  claim 26 , wherein said granulate has an average remaining added water content of about 1.0 wt % or less.  
     
     
         28 . The granulate according to  claim 27 , wherein said granulate has an average remaining added water content of about 0.8 wt % or less.  
     
     
         29 . The granulate according to  claim 20 , wherein said granulate composition exhibits a pH value of 6.5 or less.  
     
     
         30 . The granulate according to  claim 29 , wherein said granulate has a pH of about 6.0 or less.  
     
     
         31 . The granulate according to  claim 29 , wherein said granulate has a pH within the range of 4.5 to 6.5.  
     
     
         32 . The granulate according to  claim 20 , wherein said paroxetine sulfonate salt is paroxetine methane sulfonate.  
     
     
         33 . A process, which comprises: 
 mixing an aqueous solution containing at least 10 wt % of a paroxetine sulfonate with at least one solid excipient; and    drying to form a granulate.    
     
     
         34 . The process according to  claim 33 , wherein said drying step produces a granulate having a remaining added water content of about 2.0 wt % or less.  
     
     
         35 . The process according to  claim 34 , wherein said drying step produces a granulate having a remaining added water content of about 1.3 wt % or less.  
     
     
         36 . The process according to  claim 35 , wherein said drying step produces a granulate having a remaining added water content of about 1.0 wt % or less.  
     
     
         37 . The process according to  claim 36 , wherein said drying step produces a granulate having a remaining added water content of about 0.8 wt % or less.  
     
     
         38 . The process according to  claim 33 , wherein said aqueous solution concentration of said paroxetine sulfonate is at least 30 wt %.  
     
     
         39 . The process according to  claim 38 , wherein said aqueous solution concentration of said paroxetine sulfonate is at least 40 wt %.  
     
     
         40 . The process according to  claim 33 , wherein said mixing and drying steps are performed concurrently.  
     
     
         41 . The process according to  claim 33 , wherein said solid excipient is a granulate.  
     
     
         42 . The process according to  claim 33 , which further comprises optionally mixing additional excipients with said granulate and pressing said granulate composition into a tablet.  
     
     
         43 . The process according to  claim 42 , which further comprises film coating said tablet.  
     
     
         44 . The process according to  claim 33 , which further comprises filling said granulate into a capsule or sachet.  
     
     
         45 . The process according to  claim 33 , which further comprises processing said granulate into effervescent tablets, sublingual tablets, controlled release tablets or delayed release tablets.  
     
     
         46 . The process according to  claim 33  wherein the excipients comprise at least one ingredient selected from the group consisting of binders, disintegrants, and fillers.  
     
     
         47 . The process according to  claim 46 , wherein said granulate exhibits a pH value of 6.5 or less.  
     
     
         48 . The process according to  claim 47 , wherein said granulate has a pH of about 6.0 or less.  
     
     
         49 . The process according to  claim 47 , wherein said granulate has a pH of about 5.5 or less.  
     
     
         50 . The process according to  claim 33 , wherein said paroxetine sulfonate is paroxetine methane sulfonate.