Serotonin reuptake inhibitor formulations

Abstract

A process for preparing amorphous paroxetine hydrochloride or sertraline hydrochloride is provided, which comprises preparing a solution in which paroxetine hydrochloride or sertraline hydrochloride and a water-soluble polymer are dissolved in a co-solvent of a volatile organic solvent and water. Said solution is dried to obtain a composition comprising amorphous paroxetine hydrochloride or sertraline hydrochloride and the water-soluble matrix.

1 - 33 . (canceled)  
     
     
         34 : A process for preparing amorphous paroxetine hydrochloride, comprising: 
 (a) preparing a solution of paroxetine hydrochloride and a water-soluble carrier in a co-solvent of a volatile organic solvent and water, the ratio of said paroxetine hydrochloride and said water-soluble polymer being about 1:1 to about 1:4, by weight; and    (b) drying said solution to produce a composition comprising amorphous paroxetine hydrochloride and the water-soluble polymer.    
     
     
         35 : The process of  claim 34 , wherein the composition of step (b) is a solid dispersion comprising the amorphous paroxetine hydrochloride dispersed in the water-soluble polymer.  
     
     
         36 : The process of  claim 34 , wherein the preparation of the solution of step (a) does not require elevation of temperature.  
     
     
         37 : The process of  claim 34 , wherein the preparation of the solution of step (a) comprises: dissolving paroxetine free base in methanol to form a solution of paroxetine free base; adding hydrochloric acid dissolved in water to said paroxetine free base solution, said hydrochloric acid being in the amount that is sufficient to ensure conversion of said paroxetine free base to paroxetine hydrochloride, to form a solution of paroxetine hydrochloride in a co-solvent of methanol and water; and adding the water-soluble polymer into the paroxetine hydrochloride solution to form the solution of the water- soluble polymer and paroxetine hydrochloride in the co-solvent.  
     
     
         38 : The process of  claim 34 , wherein the preparation of the solution of step (a) comprises dissolving paroxetine hydrochloride in a co-solvent of methanol and water to obtain a paroxetine hydrochloride solution; and adding to the paroxetine hydrochloride solution the water-soluble polymer to form the solution of the paroxetine hydrochloride and the water-soluble polymer in the co-solvent.  
     
     
         39 : The process of  claim 34 , wherein the volatile organic solvent is methanol, and the water-soluble polymer is selected from the group consisting of polyvinylpyrrolidone, hydroxypropylmethylcellulose, polyethylene glycol and mixtures thereof, the ratio of the paroxetine hydrochloride and the water-soluble polymer being about 1:1 to about 1:2, by weight.  
     
     
         40 : The process of  claim 39 , wherein the water-soluble polymer comprises Povidone K-30, the ratio of the paroxetine hydrochloride to Povidone K-30 being about 1:2, by weight, and wherein the ratio of methanol to water in the co-solvent being about 80:20 to about 70:30.  
     
     
         41 : The process of  claim 34 , wherein the weight ratio of the paroxetine hydrochloride and the water-soluble polymer is about 1:1 to about 1:2.  
     
     
         42 : The process of  claim 34 , wherein concentration the paroxetine hydrochloride in the solution of step (a) is about 5% to 25%, by weight.  
     
     
         43 : The process of  claim 34 , wherein the water soluble polymer is selected from the group consisting of polyvinylpyrrolidone, hydroxypropylmethylcellulose, polyethylene glycol and mixtures thereof, the water-soluble polymer comprising about 20% of the solution of step (a) by weight.  
     
     
         44 : The process of claim of 43, wherein the water-soluble polymer is selected from the group consisting of Povidone K-25, Povidone K-30, Povidone K-90, Methocel E5.  
     
     
         45 : The process of  claim 44 , wherein the water-soluble polymer is Povidone K-30.  
     
     
         46 : The process of  claim 34 , wherein the volatile organic solvent is selected from the group consisting of isopropyl alcohol, methanol, ethanol and mixtures thereof.  
     
     
         47 : The process of  claim 34 , wherein the co-solvent is methanol:water.  
     
     
         48 : The process of  claim 34 , wherein the weight ratio of the volatile organic solvent to water in the solution of step (a) is about 95:5 to about 60:40.  
     
     
         49 : The process of  claim 34 , wherein the weight ratio of the volatile organic solvent to water in the solution of step (a) is about 80:20 to about 70:30.  
     
     
         50 : The process of  claim 34 , wherein the drying of step (b) involves spray-drying the solution onto a pharmaceutically acceptable carrier to produce granules comprising the amorphous paroxetine hydrochloride, the water-soluble carrier and the pharmaceutically acceptable carrier.  
     
     
         51 : The process of  claim 50 , wherein the solution of step a) is spray-dried onto the pharmaceutically acceptable carrier to a weight gain of from about 5% to about 500%.  
     
     
         52 : The process of  claim 50 , wherein the solution of step a) is sprayed onto the pharmaceutically acceptable carrier to a weight gain of from 50% to about 300%.  
     
     
         53 : The process of  claim 50 , in which one or more pharmaceutical excipient is added to the solution of the paroxetine hydrochloride and water-soluble polymer, and spray-drying said mixture onto the pharmaceutically acceptable carrier.  
     
     
         54 : The process of  claim 50 , further comprising admixing to the granules sufficient quantities of at least one pharmaceutically necessary tableting excipient and compressing said mixture into tablets suitable form oral administration.  
     
     
         55 : The process of  claim 54 , further comprising the step of overcoating said tablets with a pharmaceutically acceptable film-coating.  
     
     
         56 : The process of  claim 50 , wherein the pharmaceutically necessary tableting excipient is selected from the group consisting of a lubricant, an inert filler, a glidant, a disintegrant and mixtures thereof.  
     
     
         57  (canceled)  
     
     
         58 : The product obtained by the process of  claim 34 .  
     
     
         59 : The product obtained by the process of  claim 39 .  
     
     
         60 : The product obtained by the process of  claim 40 .  
     
     
         61 - 74  (canceled)