Solvent-based sterilisation of pharmaceuticals

Abstract

A sterile composition of a pharmaceutical compound is prepared by combining solvent with a non-sterile pharmaceutical compound to form a solution and filtering to yield a sterile pharmaceutical compound, optionally removing all or part of the solvent, and under sterile conditions combining the compound with a pharmaceutically acceptable carrier.

1 - 76 . (canceled) 
   
   
       77 . A method for preparing sterile budesonide comprising:
 (i) dissolving non-sterile budesonide in a solvent to form a non-sterile budesonide solution;   (ii) filtering the non-sterile budesonide solution with a sterile filter to produce a sterile budesonide solution; and   (iii) removing the solvent from the sterile budesonide solution to produce a sterile budesonide powder.   
   
   
       78 . The method as defined in  claim 77  wherein the sterile filter has a pore size of 0.2 μm or less. 
   
   
       79 . The method of  claim 77  further comprising the step of reducing the particle size of the sterile budesonide powder to a mass mean diameter of less than 10 μm. 
   
   
       80 . The method of  claim 79  wherein the particle size of the sterile budesonide powder is reduced to a mass mean diameter of 1-5μm. 
   
   
       81 . The method of  claim 80  wherein the particle size of the sterile budesonide powder is reduced to a mass mean diameter of 2-3μm. 
   
   
       82 . The method of  claim 77  wherein the steps of the method are conducted under low oxygen conditions. 
   
   
       83 . The method of  claim 77  wherein the steps of the method are conducted under vacuum conditions. 
   
   
       84 . The method of  claim 77  wherein the steps of the method are conducted under nitrogen conditions. 
   
   
       85 . The method of  claim 77  wherein the steps of the method are protected from light. 
   
   
       86 . The method of  claim 77  further comprising the step of packaging the sterile budesonide powder. 
   
   
       87 . The method of  claim 86  wherein the step of packaging the sterile budesonide powder is performed under sterile conditions. 
   
   
       88 . The method of  claim 77  wherein step (i) is conducted at room temperature. 
   
   
       89 . The method of  claim 77  further comprising the step of heating the solvent to 30-50° C. prior to dissolving the non-sterile budesonide. 
   
   
       90 . The method of  claim 77  wherein the solvent is removed under reduced pressure. 
   
   
       91 . The method of  claim 77  wherein the solvent is removed under vacuum conditions. 
   
   
       92 . The method of  claim 77  wherein the solvent is removed at a temperature of 40° C. or less. 
   
   
       93 . The method of  claim 77  further comprising the step of combining the sterile budesonide powder with a pharmaceutically acceptable carrier. 
   
   
       94 . The method of  claim 93  wherein the pharmaceutically acceptable carrier is sterile water. 
   
   
       95 . The method of  claim 77  wherein the solvent is a Class 2 solvent selected from the group consisting of acetonitrile, chlorobenzene, chloroform, cyclohexane, 1,2-dichloroethane, dichloromethane, 1,2-dimethoxyethane, 1,4-dioxane, 2-ethoxyethanol, ethyleneglycol, formamide, hexane, methanol, 2-methoxyethanol, methylbutyl ketone, methylcyclohexane, N-methylpyrrolidone, nitromethane, tetrahydrofuran, toluene, 1,2-trichloroethene and xylene. 
   
   
       96 . The method of  claim 77  wherein the solvent is a Class 3 solvent selected from the group consisting of acetone, anisole, 1-butanol, 2-butanol, butyl acetate, tert-butylmethyl ether, cumene, ethanol, ethyl acetate, ethyl ether, heptane, isobutyl acetate, isopropyl acetate, methyl acetate, 3-methyl-1-butanol, methylethyl ketone, methylisobutyl ketone, 2-methyl-1-propanol, pentane, 1-pentanol, 2-pentanol, 2-propanol, and propyl acetate. 
   
   
       97 . The method of  claim 77  wherein the solvent comprises an alcohol. 
   
   
       98 . The method of  claim 97  wherein the alcohol is ethyl alcohol, methyl alcohol or isopropyl alcohol.