Injectable melphalan compositions comprising a cyclodextrin derivative and methods of preparing and using them

摘要

A diluted pharmaceutical composition for use in a method of treating a subject suffering from a neoplastic disorder, by administering the diluted pharmaceutical composition by injection to the subject in need, wherein the diluted pharmaceutical composition is prepared by diluting a composition with a aqueous diluent to provide a dilute pharmaceutical composition comprising from 25 mg to 125 mg of melphalan and a cyclodextrin derivative of formula I: ** Formula ** where n is 4, 5 or 6; wherein R1, R2, R3, R4, R5, R6, R7, R8, and R9 are independently a straight or branched chain C1-C8- (alkylene) -SO3- group having an average degree of substitution of about 6.5 by cyclodextrin derivative, and the remaining substituents are -H; wherein the diluted pharmaceutical composition has a pH of 4 to 6; wherein the cyclodextrin derivative is present in a concentration of at least 50: 1 (w / w) relative to melphalan; wherein melphalan in the diluted pharmaceutical composition degrades by 2% or less at 25 ° C within 5 hours of dilution.