Stable Formulation for Parenteral Administration of Tapentadol

Abstract

The invention relates to an aqueous pharmaceutical composition for parenteral administration comprising Tapentadol or a physiologically acceptable salt thereof, wherein the concentration of Tapentadol is within the range of from 0.10 to 8.00 mg/mL, based on the weight of Tapentadol free base and based on the total volume of the composition; and wherein the pH value of the composition is buffered and within the range of from 4.0 to 6.0. The invention also relates to a container comprising the pharmaceutical composition and a process for the preparation thereof. The invention also relates to a kit comprising the contained according to the invention in a packaging. The pharmaceutical composition according to the invention is particularly useful for treating pain, especially acute pain, preferably in pediatric patients.

1 .- 61 . (canceled) 
     
     
         62 . An aqueous pharmaceutical composition for parenteral administration comprising Tapentadol or a physiologically acceptable salt thereof, wherein the concentration of Tapentadol is within the range of from 0.10 to 8.00 mg/mL, based on the weight of Tapentadol free base and based on the total volume of the composition; and wherein the pH value of the composition is buffered and within the range of from 4.0 to 6.0. 
     
     
         63 . The composition according to  claim 62 , which is stable upon autoclaving and preferably exhibits an unaltered pH value upon autoclaving. 
     
     
         64 . The composition according to  claim 63 , which is stable upon autoclaving for 20 minutes at 121° C. and 2 bar and preferably exhibits an unaltered pH value upon autoclaving under these conditions. 
     
     
         65 . The composition according to  claim 62 , wherein the content of molecular oxygen in the composition is not more than 9.0 mg/L, based on the total volume of the composition. 
     
     
         66 . The composition according to  claim 62 , wherein the content of molecular oxygen in the composition is not more than 0.2 mg/L, based on the total volume of the composition. 
     
     
         67 . The composition according to  claim 62 , wherein the pH value is within the range of from 4.5 to 5.5, in particular before and after autoclaving. 
     
     
         68 . The composition according to  claim 62 , which comprises a buffer comprising one or more conjugate bases and one or more conjugate acids selected from the group consisting of citrate, hydrogencitrate, dihydrogencitrate and citric acid. 
     
     
         69 . The composition according to  claim 62 , which comprises a buffer comprising one or more conjugate bases and one or more conjugate acids and having a concentration of at least 0.5 mmol/L, based on the total content of the one or more conjugate bases and the one or more conjugate acids and based on the total volume of the composition. 
     
     
         70 . The composition according to  claim 62 , which comprises a buffer comprising one or more conjugate bases and one or more conjugate acids and having a concentration of not more than 1.5 mmol/L, based on the total content of the one or more conjugate bases and the one or more conjugate acids and based on the total volume of the composition. 
     
     
         71 . The composition according to  claim 62 , which comprises a buffer comprising one or more conjugate bases and one or more conjugate acids and having a concentration within the range of from 0.5 to 1.5 mmol/L, based on the total content of the one or more conjugate bases and the one or more conjugate acids and based on the total volume of the composition. 
     
     
         72 . The composition according to  claim 62 , wherein Tapentadol is present as Tapentadol hydrochloride. 
     
     
         73 . The composition according to  claim 62 , wherein the concentration of Tapentadol is within the range of 1.0±0.5 mg/mL, based on the weight of Tapentadol free base and based on the total volume of the composition. 
     
     
         74 . The composition according to  claim 62 , which comprises an isotonizing agent. 
     
     
         75 . The composition according to  claim 74 , wherein the isotonizing agent is sodium chloride. 
     
     
         76 . The composition according to  claim 62 , which has a titration acidity of not more than 1.8 mmol/L. 
     
     
         77 . The composition according to  claim 62 , which does not contain any antioxidant and/or chelating agent. 
     
     
         78 . The composition according to  claim 62 , which does not contain any preservative. 
     
     
         79 . A container comprising the pharmaceutical composition according to  claim 62 . 
     
     
         80 . The container according to  claim 79 , which is a glass ampoule. 
     
     
         81 . The container according to  claim 79 , which comprises from 1.0 to 3.0 mL of the composition. 
     
     
         82 . The container according to  claim 79 , which comprises the composition as a liquid phase and a gaseous phase in a headspace above the liquid phase, wherein the gaseous phase has a content of molecular oxygen of not more than 2.5% Vbar.