Distillation Method for the Purification of Sevoflurane and the Maintenance of Certain Equipment that May be Used in the Distillation Process

Abstract

Processes for preparing commercial quantities of a stable, pharmaceutically acceptable sevoflurane substantially free of impurities are claimed. In another embodiment, a process for removing reactive metal salts from the surface of metallic equipment used in the distillation of sevoflurane and rendering a non-inert metallic surface of the metallic equipment inert.

1 - 37 . (canceled) 
     
     
         38 . A process for obtaining commercial quantities of substantially pure sevoflurane comprising:
 i) providing a crude sevoflurane product;   ii) passivating liquid- and gas-contacting surfaces of distillation equipment capable of providing commercial quantities of sevoflurane;   iii) distilling the crude sevoflurane product in the distillation equipment; and   iv) recovering substantially pure sevoflurane.   
     
     
         39 . The process according to  claim 38 , wherein sevoflurane decomposition suppression agents are not added to the sevoflurane during the distillation. 
     
     
         40 . The process according to  claim 38 , further composing storing the substantially pure sevoflurane up to two years. 
     
     
         41 . The process according to  claim 39 , wherein the substantially pure sevoflurane product is stored in glass containers. 
     
     
         42 . The process according to  claim 41 , wherein the glass containers are made of Type III glass. 
     
     
         43 . The process according to  claim 41 , wherein sevoflurane decomposition suppression agents are not added to sevoflurane during storage. 
     
     
         44 . The process according to  claim 38 , wherein the distillation equipment is metallic. 
     
     
         45 . The process according to  claim 44 , wherein step ii) comprises:
 a) washing the metallic equipment one or more times with water, and if the pH of the discharged wash is initially less than 6, continuing washing until the pH of the discharged wash is at least 6;   b) contacting the surfaces of the equipment that are to be treated with an aqueous solution of a passivation agent;   c) removing the aqueous passivation agent; and   d) rinsing the equipment with water, and if the pH of the discharged wash is initially less than 6, continuing washing until the pH of the discharged water is at least 6.   
     
     
         46 . A process according to  claim 38 , wherein the passivation agent is citric acid, nitric acid, and a mixture of nitric acid and sodium dichromate. 
     
     
         47 . A process according to  claim 38 , wherein the passivation agent is nitric acid. 
     
     
         48 . A process for removing reactive metal salts from the sevoflurane-contacting surfaces of metallic equipment used in the distillation of sevoflurane and rendering the surfaces inert, the process comprising:
 i) washing the metallic equipment one or more times with wafer, and if the pH of the discharged wash is initially less than 6, continuing washing until the pH of the discharged wash is at least 6;   ii) contacting the surfaces of the equipment that are to be treated with an aqueous solution of a passivation agent;   iii) removing the aqueous passivation agent; and   iv) rinsing the equipment with water, and if the pH of the discharged wash is initially less than 6, continuing washing until the pH of the discharged water is at least 6.   
     
     
         49 . A process according to  claim 48 , wherein the concentration of the passivation agent is a minimum of about 1% by weight of the aqueous passivation solution. 
     
     
         50 . A process according to  claim 48 , wherein the concentration of the passivation agent is a minimum of about 10% by weight of the aqueous passivation solution. 
     
     
         51 . A process according to  claim 48 , wherein the concentration of the passivation agent is a maximum of about 90% by weight of the aqueous passivation solution. 
     
     
         52 . A process according to  claim 48 , wherein the concentration of the passivation agent is a maximum of about 50% by weight of the aqueous passivation solution. 
     
     
         53 . A process according to  claim 48 , wherein the metallic equipment is in contact with the aqueous passivation solution for a minimum total time period of about 0.25 hours. 
     
     
         54 . A process according to  claim 48 , wherein the metallic equipment is in contact with the aqueous passivation solution for a minimum total time period of about 0.30 hours. 
     
     
         55 . A process according to  claim 48 , wherein the metallic equipment is in contact with the aqueous passivation solution for a maximum total time period of about 48 hours. 
     
     
         56 . A process according to  claim 48 , wherein the metallic equipment is in contact with the aqueous passivation solution for a maximum total time period of about 24 hours. 
     
     
         57 . A process according to  claim 48 , wherein the passivation agent is citric acid, nitric acid, or mixtures of nitric acid and sodium dichromate. 
     
     
         58 . A process according to  claim 57 , wherein the passivation agent is nitric acid. 
     
     
         59 . A process according to  claim 48 , wherein the metallic equipment comprises stainless steel. 
     
     
         60 . A process according to  claim 48 , wherein the contact temperature when the metallic equipment is in contact with the aqueous passivation solution is a minimum of about 20° C. 
     
     
         61 . A process according to  claim 48 , wherein the contact temperature when the metallic equipment is in contact with the aqueous passivation solution is a minimum of about 35° C. 
     
     
         62 . A process according to  claim 48 , wherein the contact temperature when the metallic equipment is in contact with the aqueous passivation solution is a minimum of about 50° C. 
     
     
         63 . A process according to  claim 48 , wherein the contact temperature when the metallic equipment is in contact with the aqueous passivation solution is a maximum of about 60° C. 
     
     
         64 . A process according to  claim 48 , wherein the contact temperature when the metallic equipment is in contact with the aqueous passivation solution is a maximum of about 70° C. 
     
     
         65 . A process according to  claim 48 , wherein the contact temperature when the metallic equipment Is in contact with the aqueous passivation solution is a maximum of about 80° C.