Injectable Nitrogen Mustard Compositions Comprising a Cyclodextrin Derivative and Methods of Making and Using the Same

Abstract

The present disclosure is directed to pharmaceutical compositions comprising a nitrogen mustard and a cyclodextrin derivative, and methods of making and using the same.

What is claimed is: 
     
         1 .- 17 . (canceled) 
     
     
         18 . A solid pharmaceutical composition consisting of melphalan and sulfobutyl ether-β-cyclodextrin in a weight ratio of 54:1, wherein when the composition is diluted with a saline solution to 5 mg/mL melphalan, the melphalan in the diluted solution is stable at room temperature for at least one hour, as compared to a cyclodextrin-free reference melphalan standard. 
     
     
         19 . The solid pharmaceutical composition of  claim 18 , wherein after dilution, less than 2% by weight of said melphalan is degraded after 5 hours at room temperature as compared to the amount of melphalan present before holding said formulation at room temperature for 5 hours. 
     
     
         20 . The solid pharmaceutical composition of  claim 18 , wherein after dilution, less than 4% by weight of said melphalan is degraded when said formulation is held at room temperature for 10 hours as compared to the amount of melphalan present before holding said formulation at room temperature for 10 hours. 
     
     
         21 . The solid pharmaceutical composition of  claim 18 , wherein said saline solution comprises 9 mg/mL NaCl. 
     
     
         22 . The solid pharmaceutical composition of  claim 18 , wherein said saline solution is at a pH of between 4 and 6. 
     
     
         23 . A solid pharmaceutical composition consisting of melphalan and sulfobutyl ether-β-cyclodextrin in a weight ratio of 54:1, wherein when the composition is diluted with a saline solution to 0.45 mg/mL melphalan and administered to a patient, the composition provides a melphalan AUC 0-t  in the patient that is at least 20% greater than a melphalan AUC 0-t  provided by a melphalan formulation containing an equivalent dose of melphalan and lacking the cyclodextrin derivative. 
     
     
         24 . The solid pharmaceutical composition of  claim 23 , wherein said saline solution comprises 9 mg/mL NaCl. 
     
     
         25 . The solid pharmaceutical composition of  claim 23 , wherein said saline solution is at a pH of between 4 and 6. 
     
     
         26 . A solid pharmaceutical composition consisting of melphalan and sulfobutyl ether-β-cyclodextrin in a weight ratio of 54:1, wherein when the composition is diluted with a saline solution to 5 mg/mL melphalan and wherein when the said diluted composition is further diluted with a saline solution to prepare a composition having 0.45 mg/mL melphalan concentration and administered to a subject provides a melphalan AUC 0-t  in a the subject that is at least 20% greater than a melphalan AUC 0-t  provided by a melphalan formulation containing an equivalent dose of melphalan and lacking the sulfobutyl ether-β-cyclodextrin. 
     
     
         27 . The solid pharmaceutical composition of  claim 26 , wherein said saline solution comprises 9 mg/mL NaCl. 
     
     
         28 . The solid pharmaceutical composition of  claim 26 , wherein said saline solution is at a pH of between 4 and 6. 
     
     
         29 . A solid pharmaceutical composition consisting of melphalan and sulfobutyl ether-β-cyclodextrin in a weight ratio of 54:1, wherein the composition is diluted with an aqueous diluent to 5 mg/mL melphalan, and wherein said aqueous diluent does not include propylene glycol or ethanol. 
     
     
         30 . The solid pharmaceutical composition of  claim 29 , wherein said aqueous diluent is saline solution comprising 9 mg/mL NaCl. 
     
     
         31 . The solid pharmaceutical composition of  claim 30 , wherein said saline solution is at a pH of between 4 and 6. 
     
     
         32 . A solid pharmaceutical composition consisting of melphalan and sulfobutyl ether-β-cyclodextrin in a weight ratio of 54:1, wherein the composition is diluted with an aqueous diluent to 0.45 mg/mL melphalan, and wherein the said aqueous diluent does not include propylene glycol or ethanol. 
     
     
         33 . The solid pharmaceutical composition of  claim 32 , wherein said aqueous diluent is saline solution comprising 9 mg/mL NaCl. 
     
     
         34 . The solid pharmaceutical composition of  claim 33 , wherein said saline solution is at a pH of between 4 and 6.