Pharmaceutical composition with improved storage stability and method for preparing the same

Abstract

A pharmaceutical composition containing a specific related compound within a specified limit and a method for preparing the same are provided.

1 . A polymeric micelle pharmaceutical composition, comprising:
 a purified amphiphilic block copolymer comprising a hydrophilic block (A) and a hydrophobic block (B), and   one or more poorly water-soluble drugs selected from the group consisting of paclitaxel and docetaxel,   wherein the pharmaceutical composition contains, when stored at 40° C. for 6 months, a related compound represented by the following Formula 1 in an amount of less than 0.58 part by weight, based on 100 parts by weight of the initial amount of the poorly water-soluble drug:   
       
         
           
           
               
               
           
         
         wherein 
         R 1  is H or COCH 3 , and R 2  is phenyl or O(CH 3 ) 3 . 
       
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the compound of Formula 1 includes a compound of the following Formula 1a, a compound of the following Formula 1b, or both of them: 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are the same as defined in  claim 1 . 
       
     
     
         3 . The pharmaceutical composition according to  claim 2 , which contains the compound of Formula 1a in an amount of less than 0.22 part by weight, based on 100 parts by weight of the initial amount of the poorly water-soluble drug. 
     
     
         4 . The pharmaceutical composition according to  claim 2 , which contains the compound of Formula 1b in an amount of less than 0.36 part by weight, based on 100 parts by weight of the initial amount of the poorly water-soluble drug. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein the compound of Formula 1 is the compound of the following Formula 1c: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The pharmaceutical composition according to  claim 5 , wherein the compound of Formula 1c includes the compound of the following Formula 1d, the compound of the following Formula 1e, or both of them: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The pharmaceutical composition according to  claim 1 , which contains the related compound of Formula 1 in an amount of 0.5 part by weight or less, based on 100 parts by weight of the initial amount of the poorly water-soluble drug. 
     
     
         8 . The pharmaceutical composition according to  claim 7 , which contains the related compound of Formula 1 in an amount of 0.2 part by weight or less, based on 100 parts by weight of the initial amount of the poorly water-soluble drug. 
     
     
         9 . The pharmaceutical composition according to  claim 8 , which contains the related compound of Formula 1 in an amount of 0.1 part by weight or less, based on 100 parts by weight of the initial amount of the poorly water-soluble drug. 
     
     
         10 . The pharmaceutical composition according to  claim 1 , which contains, when stored at 80° C. for 3 weeks, the related compound of Formula 1 in an amount of less than 0.45 part by weight, based on 100 parts by weight of the initial amount of the poorly water-soluble drug. 
     
     
         11 . The pharmaceutical composition according to  claim 1 , wherein the hydrophilic block (A) comprises one or more selected from the group consisting of polyethylene glycol or derivatives thereof, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylamide and combinations thereof. 
     
     
         12 . The pharmaceutical composition according to  claim 1 , wherein the hydrophobic block (B) comprises one or more selected from the group consisting of polylactide, polyglycolide, polymandelic acid, polycaprolactone, polydioxan-2-one, polyamino acid, polyorthoester, polyanhydride, polycarbonate and combinations thereof. 
     
     
         13 . The pharmaceutical composition according to  claim 1 , wherein the hydrophilic block (A) is polyethylene glycol or monomethoxypolyethylene glycol, and the hydrophobic block (B) is polylactide. 
     
     
         14 . The pharmaceutical composition according to  claim 1 , wherein the hydrophilic block (A) has a number average molecular weight of 200 to 20,000 Daltons, and the hydrophobic block (B) has a number average molecular weight of 200 to 20,000 Daltons. 
     
     
         15 . The pharmaceutical composition according to  claim 1 , wherein the amphiphilic block copolymer is one purified by sublimation at a temperature of 80° C. or higher and lower than 120° C. and under a pressure of a vacuum degree of 10 torr or less for 10 to 74 hours.