Stable Oral Liquid Formulation of Trimetazidine

Abstract

Disclosed is a stable oral liquid pharmaceutical composition of trimetazidine having a pH of about pH 4 to about pH 8, comprising a therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof, one or more orally acceptable buffers, and one or more orally acceptable preservatives that is effective in said pH range. Also disclosed are methods of treating patients with stable oral liquid pharmaceutical composition. The phamaceutical composition is particularly suitable for treating a patient having a condition treatable by trimetazidine, such as cirrhosis and renal deficiency, and who has a decreased tolerance for acidic or highly basic oral solutions.

What is claimed is: 
     
         1 . A stable oral liquid pharmaceutical composition of trimetazidine having a pH greater than pH 4 and less than pH 8, comprising less than 5% w/v of trimetazidine or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The pharmaceutical composition according to  claim 1  which comprises an orally suitable buffer selected from the group consisting of acetate, carbonate, and phosphate. 
     
     
         3 . The pharmaceutical composition according to  claim 2 , wherein the one or more orally suitable buffers is a phosphate buffer. 
     
     
         4 . The pharmaceutical composition according to  claim 3 , wherein the pH of the composition is from about 5.5 to about 6.5. 
     
     
         5 . The pharmaceutical composition according to  claim 4 , further comprising one or more orally acceptable preservatives. 
     
     
         6 . The pharmaceutical composition according to  claim 5 , wherein the one or more orally acceptable preservatives includes methylparaben or ethylparaben or both. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein the amount of trimetazidine or a pharmaceutically acceptable salt thereof is less than 2% w/v trimetazidine as free base or a pharmaceutically acceptable salt. 
     
     
         8 . The pharmaceutical composition according to  claim 7 , wherein the amount of trimetazidine or a pharmaceutically acceptable salt thereof is from about 0.1% to about 2% w/v trimetazidine as free base or a pharmaceutically acceptable salt. 
     
     
         9 . The pharmaceutical composition according to  claim 8 , wherein the amount of trimetazidine or a pharmaceutically acceptable salt thereof is from about 0.1% to about 1% w/v trimetazidine as free base or a pharmaceutically acceptable salt. 
     
     
         10 . The pharmaceutical composition according to  claim 9 , wherein the amount of trimetazidine or a pharmaceutically acceptable salt thereof is from about 0.1% to about 0.5% trimetazidine as free base or a pharmaceutically acceptable salt, wherein the composition further comprises one or more orally acceptable buffers and the one or more orally acceptable preservatives. 
     
     
         11 . The pharmaceutical composition according to  claim 10 , wherein the wherein the therapeutically effective amount of trimetazidine or a pharmaceutically acceptable salt thereof is from about 0.1% to about 0.3% trimetazidine as free base or a pharmaceutically acceptable salt; the one or more orally acceptable buffers is a phosphate buffer; and the one or more orally acceptable preservatives is one or more parabens. 
     
     
         12 . A method of treating a condition treatable with trimetazidine in a patient having a said condition and who has a decreased tolerance for acidic or highly basic oral solutions, comprising administering to said patient the composition according to  claim 1 . 
     
     
         13 . The method according to  claim 12 , wherein the patient has liver cirrhosis. 
     
     
         14 . The method according to  claim 13 , wherein said patient has renal insufficiency. 
     
     
         15 . The method according to  claim 12 , wherein the composition comprises from about 0.1% to about 1% w/v trimetazidine as free base or a pharmaceutically acceptable salt; and further comprises one or more orally acceptable buffers, and wherein the pH is from about 5.5 to about 6.5. 
     
     
         16 . The method according to  claim 15 , wherein the preservative is a mixture of methylparaben sodium and ethylparaben sodium. 
     
     
         17 . The method according to  claim 16 , wherein the orally suitable buffer is selected from the group consisting of acetate, carbonate, and phosphate.