Patent ID: 6670384
Filing Date: 2003-12-30
Classification: A61K,A61P

Abstract:
A process for formulating, for parenteral administration, an epothilone analog represented by formula I: wherein:Q is selected from the group consisting of: andM is selected from the group consisting of oxygen, sulfur, NR8, and CR9R10; each R1, R2, R3, R4, R5, R7, R11, R12, R13, R14, and R15 is, independently, selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl and heterocyclo, and wherein R1, and R2, are alkyl, they can be joined to form cycloalkyl; R6, is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, heterocyclo and substituted heterocyclo; R8 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, R14, C&boxH;O, R12OC&boxH;O and R13SO2; and each R9 and R10 is, independently, selected from the group consisting of hydrogen, halogen, alkyl, substituted alkyl, aryl, heterocyclo, hydroxy, R14C&boxH;O, and R15OC&boxH;O; and any salts, solvates, or hydrates thereof, comprising the following steps carried out under protection from light: a) dissolving said epothilone analog in a mixture of at least about 50% by volume tertiary-butanol in water to form a solution; b) performing primary drying of said solution at a temperature of from about âˆ’10Â° C. to about âˆ’40Â° C. under high vacuum of from about 50 millitorr to about 300 millitorr for from about 24 hours to about 96 hours to form a dried product; c) performing secondary drying of the resultant dried product at a temperature of from about 10Â° C. to about 30Â° C. under high vacuum of from about 50 millitorr to about 300 millitorr for from 24 hours to about 96 hours to provide a lyophilized product; and d) packaging said lyophilized product in a first vial in combination with a second vial containing a sufficient quantity of an equal mixture by volume of a suitable nonionic surfactant and anhydrous ethanol to effect solution thereof.