Injectable ibuprofen formulation

Abstract

The present invention provides a pharmaceutical composition comprising an aqueous solution of an ibuprofen solubilizing agent and ibuprofen, the ibuprofen solubilizing agent being in an effective amount such that the ibuprofen in the solution remains soluble at concentrations from 100 mg/mL to 5 mg/mL without undergoing a phase transition. The invention further provides a method of treating a condition chosen from pain, inflammation, fever, and/or patent ductus arteriosis, comprising administering to a patient in need thereof an effective amount of an aqueous solution a ibuprofen solubilizing agent and ibuprofen, the ibuprofen solubilizing agent being in an effective amount such that the ibuprofen in the solution remains soluble at concentrations from 100 mg/mL to 5 mg/mL without undergoing a phase transition, as well as a method for manufacturing the composition.

1 .- 44 . (canceled) 
     
     
         45 . A pharmaceutical composition comprising an aqueous solution of water for injection, ibuprofen and an ibuprofen solubilizing agent selected from
 (i) tribasic sodium phosphate, tribasic potassium phosphate, or a combination of tribasic sodium phosphate and tribasic potassium phosphate, in a molar ratio of ibuprofen solubilizing agent to ibuprofen from 0.65:1 to 0.9:1; or   (ii) dibasic sodium phosphate, dibasic, potassium phosphate, monobasic sodium phosphate, monobasic potassium phosphate, or a combination of any of the foregoing, together with an alkalinizing agent in an amount suitable to provide a solubilized ibuprofen solution when ibuprofen is added to the ibuprofen solubilizing agent/alkalinizing agent mixture in a ratio of ibuprofen solubilizing agent to ibuprofen from 0.8 to 1.1:1, such that the pH of the resultant aqueous ibuprofen solution is from 6.5 to 9;   
       the aqueous solution remains clear and colorless when the ibuprofen is diluted from a concentration of 100 mg/ml to 1 mg/ml. 
     
     
         46 . The pharmaceutical composition of  claim 45 , wherein the ibuprofen solubilizing agent is tribasic sodium phosphate, tribasic potassium phosphate, or a combination of tribasic sodium phosphate and tribasic potassium phosphate, in a molar ratio of ibuprofen solubilizing agent to ibuprofen from 0.7:1 to 0.9:1. 
     
     
         47 . The pharmaceutical composition of  claim 46 , wherein the ibuprofen solubilizing agent is tribasic sodium phosphate. 
     
     
         48 . The pharmaceutical composition of  claim 45 , wherein the ibuprofen solubilizing agent is dibasic sodium phosphate, dibasic potassium phosphate, monobasic sodium phosphate, monobasic potassium phosphate, or a combination of any of the foregoing, together with an alkalinizing agent in an amount suitable to provide a solubilized ibuprofen solution when ibuprofen is added to the ibuprofen solubilizing agent/alkalanizing agent mixture in a ratio of ibuprofen solubilizing agent to ibuprofen from 0.8 to 0.9:1, such that the pH of the resultant aqueous ibuprofen solution is from 6.5 to 9. 
     
     
         49 . The pharmaceutical composition of  claim 48 , wherein the pH of the solution prior to the addition of ibuprofen is from pH 11.5 to 12.5. 
     
     
         50 . The pharmaceutical composition of  claim 48 , wherein the ibuprofen solubilizing agent is dibasic sodium phosphate and the alkalinizing agent is sodium hydroxide. 
     
     
         51 . The pharmaceutical composition of  claim 45 , which is sterile filtered or terminally sterilized. 
     
     
         52 . The pharmaceutical composition of  claim 45 , which remains clear and colorless when stored for at least 12 weeks at 75° C. 
     
     
         53 . The pharmaceutical composition of  claim 45 , wherein the pH of the aqueous solution of ibuprofen is from 7.2 to 9. 
     
     
         54 . The pharmaceutical composition of  claim 45 , wherein the aqueous solution comprises ibuprofen in a concentration of 5 mg to 15 mg/ml. 
     
     
         55 . The pharmaceutical composition of  claim 54 , wherein the aqueous solution contained in the bag is from 40 ml to 100 ml. 
     
     
         56 . The pharmaceutical composition of  claim 54 , wherein the aqueous solution contained in the bag has an ibuprofen concentration of 8 mg/ml to 10 mg/ml and the volume of the aqueous solution is 40 ml, 50 ml, 80 ml or 100 ml. 
     
     
         57 . The pharmaceutical composition of  claim 54 , which is contained in a pharmaceutical container for intravenous use, the pharmaceutical container being a pre-filled bag made of a pharmaceutically acceptable polymeric material, glass bottle, or plastic bottle. 
     
     
         58 . The pharmaceutical composition of  claim 57 , wherein the aqueous solution is contained in a bag made from a material selected from polypropylene, polyolefin and polyvinylchloride. 
     
     
         59 . The pharmaceutical composition of  claim 45 , which comprises a dose of ibuprofen from 400 mg to 800 mg. 
     
     
         60 . The pharmaceutical composition of  claim 45 , wherein the aqueous solution is contained in a bag for intravenous administration at an ibuprofen concentration from 5 mg/ml to 15 mg/ml and an ibuprofen dose from 400 rug to 800 mg. 
     
     
         61 . The pharmaceutical composition of  claim 45 , wherein the alkalinizing agent is selected from alkali or alkaline-earth metal hydroxides, carbonates, bicarbonates and phosphates, sodium borate, and basic salts of organic acids. 
     
     
         62 . The pharmaceutical composition of  claim 61 , wherein the alkalinizing agent is sodium hydr