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 . A pharmaceutical composition comprising an aqueous solution of water for injection, an ibuprofen solubilizing agent comprising sodium hydroxide, 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 4 mg/mL without turning hazy and/or precipitating, said aqueous solution being suitable for parenteral administration. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the molar ratio of sodium hydroxide to ibuprofen is about 1.05:1 or greater. 
     
     
         3 . The pharmaceutical composition of  claim 1 , which shows no detectable chemical degradation after incubation for one month at 40° C. 
     
     
         4 . The pharmaceutical composition of  claim 1 , which is sterile filtered or terminally sterilized. 
     
     
         5 . The pharmaceutical composition of  claim 1 , which can be stored at ambient conditions in prefilled polyolefin bags and remains clear and colorless for at least about 12 weeks. 
     
     
         6 . The pharmaceutical composition of  claim 1 , which can be stored in a bag made from a pharmaceutically acceptable polymer for at least about 12 weeks at 4° C. 
     
     
         7 . The pharmaceutical composition of  claim 1 , which can be stored in a bag made from a pharmaceutically acceptable polymer for at least about 12 weeks at 25° C. 
     
     
         8 . The pharmaceutical composition of  claim 1 , which remains clear and colorless when stored in a bag made from a pharmaceutically acceptable polymer and exposed to a freeze-thaw cycle. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the pH of the aqueous solution of ibuprofen is from about 6.8 to about 7.8. 
     
     
         10 . The pharmaceutical composition of  claim 1 , which is contained in a bag made of a pharmaceutically acceptable polymeric material. 
     
     
         11 - 44 . (canceled) 
     
     
         45 . The pharmaceutical composition of  claim 1 , wherein the ibuprofen is in a concentration of about 4 mg/mL to about 15 mg/ml. 
     
     
         46 . The pharmaceutical composition of  claim 10 , wherein the aqueous solution contained in the bag has an ibuprofen concentration from about 4 mg/mL to about 15 mg/mL and a volume selected from about 40 mL, about 50 ml, about 80 ml and about 100 mL. 
     
     
         47 . A pharmaceutical composition, comprising a pre-filled bag for intravenous use containing from about 40 to about 100 ml of an aqueous solution of water for injection, an effective dose of ibuprofen together with an ibuprofen solubilizing agent comprising sodium hydroxide, and the concentration of ibuprofen in the aqueous solution being from about 4 mg/mL to about 15 mg/mL. 
     
     
         48 . The pharmaceutical composition of  claim 47 , wherein the ibuprofen is at a concentration of 10 mg/mL and is contained in the bag at a volume of 80 mL or 40 mL. 
     
     
         49 . The pharmaceutical composition of  claim 47 , wherein the ibuprofen is at a concentration of 8 mg/mL and is contained in the bag at a volume of 100 mL or 50 mL. 
     
     
         50 . The pharmaceutical composition of  claim 47 , wherein the pH of the aqueous solution of ibuprofen is from about 6.8 to about 7.8. 
     
     
         51 . The pharmaceutical composition of  claim 47 , wherein the aqueous solution of ibuprofen contained in the bag is physically and chemically stable. 
     
     
         52 . The pharmaceutical composition of  claim 47 , which further comprises about 0.9% sodium chloride for injection. 
     
     
         53 . The pharmaceutical composition of  claim 47 , wherein the ibuprofen is present in an amount from about 400 mg to about 800 mg ibuprofen, and the ibuprofen is solubilized in the aqueous solution such that the solution is clear and colorless, without precipitate, and suitable for injection. 
     
     
         54 . The aqueous solution of  claim 53 , which is contained in a bag, a glass vial, a plastic vial, or a bottle. 
     
     
         55 . The aqueous solution of  claim 47 , wherein the concentration of ibuprofen in the aqueous solution is about 4 mg/mL. 
     
     
         56 . The aqueous solution of  claim 47 , wherein the molar ratio of sodium hydroxide to ibuprofen is about 1.05:1 or greater. 
     
     
         56 . The aqueous solution of  claim 47 , wherein the pH of the aqueous solution is adjusted to a pH from about 6.8 to about 7.8. 
     
     
         57 . A single-dose vial containing an ibuprofen solution suitable for injection, comprising from about 400 mg to about 800 mg ibuprofen, and an ibuprofen solubilizing agent comprising sodium hydroxide, the concentration of ibuprofen in the aqueous solution from about 70 mg/ml to about 100 mg/ml, wherein the ibuprofen is solubilized in the aqueous solution such that the solution is clear and colorless, without precipitate, and suitable for injection. 
     
     
         58 . The single-dose vial of  claim 57 , wherein the sodium hydroxide is in a molar ratio to ibuprofen from about 1.05:1 or greater.