Pharmaceutical composition

Abstract

The present invention provides a pharmaceutical composition or a solid preparation containing a stabilized pharmaceutically active ingredient and a stabilizing method thereof. According to the present invention, a pharmaceutical composition can be stabilized by containing a nonpeptidic pharmaceutically active ingredient having a primary or secondary amino group, an excipient and an acidic compound. In addition, a solid preparation containing a pharmaceutically active ingredient, titanium oxide, a plasticizer and a chain organic acid can enhance the stability of the pharmaceutically active ingredient during light irradiation.

1 . A method of stabilizing a pharmaceutical composition comprising a nonpeptidic pharmaceutically active ingredient having a primary or secondary amino group and an excipient, comprising adding an acidic compound to the pharmaceutical composition. 
     
     
         2 . A solid preparation improved in the stability during light irradiation, comprising a pharmaceutically active ingredient, titanium oxide, a plasticizer and a chain organic acid. 
     
     
         3 . The solid preparation of  claim 2 , wherein the plasticizer is represented by the formula:
   HOCH 2 (CH 2 OCH 2 ) n CH 2 OH   
       (n=an integer of 2-870). 
     
     
         4 . The solid preparation of  claim 2 , wherein the plasticizer is polyethylene glycol (PEG). 
     
     
         5 . The solid preparation of  claim 2 , wherein the chain organic acid has pH 6.0 or below when dissolved or dispersed in water. 
     
     
         6 . The solid preparation of  claim 2 , wherein the chain organic acid has an acid dissociation constant (pKa) of a proton complex of 4.0 or below when dissolved or dispersed in water. 
     
     
         7 . The solid preparation of  claim 2 , wherein the chain organic acid is any one kind or more selected from the group consisting of adipic acid, oleic acid, succinic acid, acetic acid, tartaric acid, sorbic acid, fumaric acid, lactic acid, maleic acid, malonic acid, citric acid and malic acid. 
     
     
         8 . The solid preparation of  claim 2 , wherein the content (%) of the chain organic acid is 0.01-50 wt %. 
     
     
         9 . The solid preparation of  claim 2 , wherein the pharmaceutically active ingredient is a compound represented by the formula: 
       
         
           
           
               
               
           
         
       
       wherein X and Y are the same or different and each is a bond or a spacer having 1 to 20 atoms in the main chain, R 4  is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, R 2 , R 3  and R 4  are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, and R 5  is a hydrogen atom or an optionally substituted hydrocarbon group, or a salt thereof. 
     
     
         10 . The solid preparation of  claim 2 , wherein the pharmaceutically active ingredient is 1-{5-(2-fluorophenyl)-1-[(6-methylpyridin-3-yl)sulfonyl]-1H-pyrrol-3-yl}-N-methylmethanamine or a salt thereof, 1-[4-fluoro-5-phenyl-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine or a salt thereof, N-methyl-1-[5-(4-methyl-3-thienyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methanamine or a salt thereof, 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine or a salt thereof, N-methyl-1-[5-(2-methylphenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methanamine or a salt thereof, or 1-[4-fluoro-5-(2-fluoropyridin-3-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine or a salt thereof. 
     
     
         11 . A method of stabilizing a solid preparation comprising a pharmaceutically active ingredient, titanium oxide, and a plasticizer during light irradiation, comprising adding a chain organic acid to the solid preparation.