Method and system for producing high purity vancomycin hydrochloride

Abstract

A method is provided for preparing spray dried powder containing vancomycin hydrochloride. The method comprises providing a vancomycin hydrochloride solution with a chromatographic purity of at least 95%, adding an excipient to the vancomycin hydrochloride solution to form a mixture solution of the vancomycin hydrochloride solution and the excipient, concentrating the mixed solution of the vancomycin hydrochloride solution and the excipient to form a 20% to 30% vancomycin concentrate, filtering the vancomycin concentrate to form a final filtrate and spray crying the final filtrate to form a spray dried vancomycin hydrochloride powder with EP impurity B level of not more than 1.5%.

1 - 21 . (canceled) 
     
     
         22 . Spray dried powder of vancomycin hydrochloride, comprising an EP impurity B level of not more than 1.5%. 
     
     
         23 . The spray dried powder of  claim 22  further comprising trehalose. 
     
     
         24 . The spray dried powder of  claim 22  in a sealed vial. 
     
     
         25 . The spray dried powder of  claim 24  wherein the vial is sealed under vacuum and nitrogen gas. 
     
     
         26 . The spray dried powder of  claim 22  wherein the powder is sterile. 
     
     
         27 . The spray dried powder of  claim 24  wherein the vial comprises a dose selected from the group consisting of about 0.25 g, about 0.5 g, about 0.75 g, about 1.0 g, about 2 g, about 5 g, about 10 g and about 20 g. 
     
     
         28 . The spray dried powder of  claim 22 , wherein the water content is below 3%. 
     
     
         29 . A spray dried powder of vancomycin hydrochloride comprising an EP impurity B level of not more than 1.5% prepared using a mixture comprising a vancomycin hydrochloride solution and at least one of a stabilizer and a solubilizer, wherein:
 (a) the vancomycin hydrochloride solution has a chromatographic purity of at least 95%;   (b) the stabilizer is selected from the group consisting of saccharides and polyols, wherein the saccharides are present in an amount of about 5-35% by weight of dry vancomycin hydrochloride, and the polyols are present in an amount of about 10-50% by weight of dry vancomycin hydrochloride;   (c) the solubilizer is selected from the group consisting of PEG-400 and a surfactant, wherein if PEG-400 is present, it is in an amount of about 10-50% by weight of dry vancomycin hydrochloride, and the surfactant is present in an amount of about 0.005-0.05% by weight of dry vancomycin hydrochloride; and   (d) the mixture is concentrated to form from about 20% to about 30% vancomycin concentrate.   
     
     
         30 . The spray dried powder of vancomycin hydrochloride of  claim 29 , wherein:
 (a) the saccharides are selected from the group consisting of trehalose, fructose, sorbose, lactose and glucose; and   (b) the polyol is mannitol.   
     
     
         31 . The spray dried powder of vancomycin hydrochloride of  claim 29 , wherein the saccharide is trehalose. 
     
     
         32 . The spray dried powder of vancomycin hydrochloride of  claim 29 , wherein the trehalose is present in an amount of about 25% by weight of dry vancomycin hydrochloride. 
     
     
         33 . The spray dried powder of vancomycin hydrochloride of  claim 29 , wherein the surfactant is selected from the group consisting of polyoxyethylene sorbitan monooleat (tween 80), poloxamer 188, polyethylene glycol (35), castor oil hydrogenated (RH-35), polyethylene glycol (40), castor oil hydrogenated (RH-40), and polyglycol 12 hydroxystearate. 
     
     
         34 . The spray dried powder of vancomycin hydrochloride of  claim 29 , wherein the surfactant is polyoxyethylene sorbitan monooleat (tween 80). 
     
     
         35 . The spray dried powder of vancomycin hydrochloride of  claim 29 , wherein the polyoxyethylene sorbitan monooleat (tween 80) is present in an amount of about 0.01% by weight of dry vancomycin hydrochloride. 
     
     
         36 . The spray dried powder of vancomycin hydrochloride of  claim 29 , wherein:
 (a) the vancomycin concentrate is filtered by passing it through at least one of a reverse osmosis membrane and a 200-800 Da nano-filtration membrane; and   (b) the filtration is done under a controlled temperature not exceeding 20° C.   
     
     
         37 . The spray dried powder of vancomycin hydrochloride of  claim 29 , wherein the vancomycin concentrate has a pH of about 2.0 to 4.0 and stored at a temperature of about 2 to 8° C. for not more than about 120 hours. 
     
     
         38 . The spray dried powder of  claim 29 , wherein the powder is sterile. 
     
     
         39 . The spray dried powder of  claim 29  packaged in a vial at a dose selected from the group consisting of about 0.25 g, about 0.5 g, about 0.75 g, about 1.0 g, about 2 g, about 5 g, about 10 g and about 20 g. 
     
     
         40 . The spray dried powder of  claim 29 , wherein the water content is below 3%. 
     
     
         41 . A spray dried powder of vancomycin hydrochloride having an EP impurity B level of not more than 1.5% prepared using a mixture comprising:
 (a) a vancomycin hydrochloride solution has a chromatographic purity of at least 95%;   (b) trehalose present in an amount of about 5-35% by weight of dry vancomycin hydrochloride; and   (c) polyoxyethylene sorbitan monooleat (tween 80) present in an amount of about 0.005-0.05% by weight of dry vancomycin hydrochloride,   wherein the mixture is concentrated to form from about 20% to about 30% vancomycin concentrate.   
     
     
         42 . The spray dried powder of vancomycin hydrochloride of  claim 41 , wherein the trehalose is present in an amount of about 25% by weight of dry vancomycin hydrochloride. 
     
     
         43 . The spray dried powder of vancomycin hydrochloride of  claim 41 , wherein the polyoxyethylene sorbitan monooleat (tween 80) is present in an amount of about 0.01% by weight of dry vancomycin hydrochloride. 
     
     
         44 . The spray dried powder of vancomycin hydrochloride of  claim 41 , wherein the trehalose is present in an amount of about 25% by weight of dry vancomycin hydrochloride and the polyoxyethylene sorbitan monooleat (tween 80) is present in an amount of about 0.01% by weight of dry vancomycin hydrochloride. 
     
     
         45 . The spray dried powder of vancomycin hydrochloride of  claim 41 , wherein:
 (a) the vancomycin concentrate is filtered by passing it through at least one of a reverse osmosis membrane and a 200-800 Da nano-filtration membrane; and   (b) the filtration is done under a controlled temperature not exceeding 20° C.   
     
     
         46 . The spray dried powder of vancomycin hydrochloride of  claim 41 , wherein the vancomycin concentrate has a pH of about 2.0 to 4.0 and stored at a temperature of about 2 to 8° C. for not more than about 120 hours. 
     
     
         47 . The spray dried powder of vancomycin hydrochloride of  claim 41 , wherein the spray dried powder is sterile and is administered orally or intravenously. 
     
     
         48 . The spray dried powder of vancomycin hydrochloride of  claim 41  prepared by a method of spray drying comprising:
 (a) turning on a spray dryer, including a heating device; 
 (b) controlling an inlet temperature and an outlet temperature; 
 (c) turning on a feeding switch; 
 (d) maintaining the spray dryer in a positive pressure; and 
 (e) using above 95% nitrogen as a heating gas, wherein 
 
       the inlet temperature is controlled from about 160° C. to about 240° C. and the outlet temperature is controlled from about 80° C. to about 120° C. 
     
     
         49 . A spray dried powder of vancomycin hydrochloride having an EP impurity B level of not more than 1.5% prepared using a mixture comprising:
 (a) vancomycin hydrochloride solution has a chromatographic purity of at least 95%;   (b) mannitol present in an amount of about 10-50% by weight of dry vancomycin hydrochloride; and   (c) PEG-400 present in an amount of about 10-50% by weight of dry vancomycin hydrochloride,   wherein the mixture is concentrated to form from about 20% to about 30% vancomycin concentrate.   
     
     
         50 . The spray dried powder of vancomycin hydrochloride of  claim 49 , wherein the mannitol is present in an amount of about 20% by weight of dry vancomycin hydrochloride. 
     
     
         51 . The spray dried powder of vancomycin hydrochloride of  claim 49 , wherein PEG-400 present in an amount of about 20% by weight of dry vancomycin hydrochloride. 
     
     
         52 . The spray dried powder of vancomycin hydrochloride of  claim 49 , wherein the mannitol is present in an amount of about 20% by weight of dry vancomycin hydrochloride and PEG-400 present in an amount of about 20% by weight of dry vancomycin hydrochloride. 
     
     
         53 . The spray dried powder of vancomycin hydrochloride of  claim 49 , wherein:
 (a) the vancomycin concentrate is filtered by passing it through at least one of a reverse osmosis membrane and a 200-800 Da nano-filtration membrane; and   (b) the filtration is done under a controlled temperature not exceeding 20° C.   
     
     
         54 . The spray dried powder of vancomycin hydrochloride of  claim 49 , wherein the vancomycin concentrate has a pH of about 2.0 to 4.0 and stored at a temperature of about 2 to 8° C. for not more than about 120 hours. 
     
     
         55 . A spray dried powder of vancomycin hydrochloride prepared by steps comprising:
 (a) turning on a spray dryer, including a heating device;   (b) controlling an inlet temperature and an outlet temperature;   (c) turning on a feeding switch;   (d) maintaining the spray dryer in a positive pressure; and   (e) using above 95% nitrogen as a heating gas,   
       wherein the inlet temperature is controlled from about 160° C. to about 240° C. and the outlet temperature is controlled from about 80° C. to about 120° C. 
     
     
         56 . The spray dried powder of  claim 55  wherein the steps further comprise:
 (f) filling the spray dried vancomycin hydrochloride powder in a dosage form; and 
 (g) sealing the dosage while vacuuminzing and injecting nitrogen gas into the vial to provide a sealed dosage form.