Peroxide removal from drug delivery vehicle

Abstract

The present invention is related to methods for lowering peroxide levels in sucrose acetate isobutyrate formulations and to composition used in and formed by such methods.

1 . A method of treating a sucrose acetate isobutyrate formulation to be used as a drug delivery vehicle comprising adding to the formulation an amount of bisulfite salt effective to substantially remove peroxides, the bisulfite salt comprising sodium metabisulfite, potassium metabisulfite, sodium bisulfite, or potassium bisulfite, or a mixture thereof. 
     
     
         2 . The method of  claim 1 , wherein the bisulfite salt is sodium metabisulfite. 
     
     
         3 . The method of  claim 1 , wherein the method removes peroxide to a level that is 10% or less than the level present I the formulation before addition of the bisulfite salt. 
     
     
         4 . The method of  claim 1 , wherein the method removes peroxide to result in a formulation having less than 5 ppm of peroxide. 
     
     
         5 . The method of  claim 1 , wherein the formulation serves as a drug delivery vehicle for use with an osmotically pump-driven implantable device. 
     
     
         6 . The method of  claim 1 , wherein the adding step comprises mixing a solution of bisulfite salt with the sucrose acetate isobutyrate formulation. 
     
     
         7 . The method of  claim 1 , wherein the formulation further comprises a cosolvent comprising hexane, ethyl acetate, ethanol, benzyl benzoate, N-methyl pyrrolidone, or iso-propyl alcohol, or a combination thereof. 
     
     
         8 . The method of  claim 7 , wherein the cosolvent is hexane or ethyl acetate. 
     
     
         9 . The method of  claim 7 , further comprising vacuum treating the formulation to remove the cosolvent. 
     
     
         10 . The method of  claim 1 , further comprising washing the formulation with water to remove the bisulfite salt. 
     
     
         11 . The method of  claim 1 , further comprising washing the formulation with glycerin to remove the bisulfite salt. 
     
     
         12 . The method of  claim 10 , further comprising drying the formulation using magnesium sulfate, calcium chloride anhydrous, calcium sulfate anhydrous, activated silica gel, phosphorous pentoxide, or vacuum, or combinations thereof. 
     
     
         13 . The method of  claim 10 , further comprising drying the formulation using magnesium sulfate. 
     
     
         14 . The method of  claim 10 , wherein the steps of adding a bisulfite salt, washing the formulation, and drying the formulation are repeated at least once. 
     
     
         15 . A drug delivery vehicle for a drug that is to be delivered in vivo comprising sucrose acetate isobutyrate having substantially reduced levels of peroxide, the drug delivery vehicle being treated with an amount of bisulfite salt effective to substantially reduce levels of peroxide in said drug delivery vehicle, the bisulfite salt comprising sodium metabisulfite, potassium metabisulfite, sodium bisulfite, or potassium bisulfite, or a combination thereof. 
     
     
         16 . The drug delivery vehicle of  claim 15 , wherein the bisulfite salt is sodium metabisulfite. 
     
     
         17 . The drug delivery vehicle of  claim 15 , wherein the prolonged stability comprises reduced oxidation, reduced deamidation, or reduced aggregation of the drug. 
     
     
         18 . The drug delivery vehicle of  claim 15 , wherein the prolonged stability is reduced oxidation of the drug. 
     
     
         19 . The drug delivery vehicle of  claim 15 , wherein the substantially reduced levels of peroxide are levels at or below 20 ppm in the drug delivery vehicle. 
     
     
         20 . The drug delivery vehicle of  claim 15 , wherein the substantially reduced levels of peroxide are levels at or below 10 ppm in the drug delivery vehicle. 
     
     
         21 . The drug delivery vehicle of  claim 15 , wherein the substantially reduced levels of peroxide are levels at or below 5 ppm in the drug delivery vehicle. 
     
     
         22 . The drug delivery vehicle of  claim 15 , wherein the treatment with the bisulfate salt comprises removal of the bisulfate salt from the drug delivery vehicle. 
     
     
         23 . The drug delivery vehicle of  claim 15 , wherein the vehicle is adapted to serve as a drug depot. 
     
     
         24 . The drug delivery vehicle of  claim 15 , wherein the vehicle is adapted for delivery from an implantable device. 
     
     
         25 . The drug delivery vehicle of  claim 24 , wherein the implantable device is an osmotically pump-driven implantable device.