Process of making and using pharmaceutical formulations of antineoplastic agents

Abstract

In its several embodiments, this invention discloses a pharmaceutical formulation comprising at least one antineoplastic agent or a pharmaceutically acceptable salt thereof, and at least one dissolution enhancing agent sufficient to substantially dissolve said at least one antineoplastic agent in at least one aqueous diluent, wherein said dissolution enhancing agent is urea, L-histidine, L-threonine, L-asparagine, L-serine, L-glutamine or mixtures thereof; a lyophilized powder comprising said pharmaceutical formulation, and articles of manufacture thereof.

What is claimed is: 
     
         1 . A process of making a pharmaceutical formulation comprising the steps of:
 (i) dissolving at least one dissolution enhancing agent in at least one aqueous diluent wherein said dissolution enhancing agent is selected from the group consisting of urea, L-histidine, L-threonine, L-asparagine, L-serine, and L-glutamine; and   (ii) adding at least one antineoplastic agent or a pharmaceutically acceptable salt thereof.   
     
     
         2 . The process according to  claim 1  further comprising:
 a) adding at least one bulking agent; 
 b) adding at least one buffer; 
 c) adding at least one pH adjuster to form a solution; and 
 d) filtering said solution. 
 
     
     
         3 . The process according to  claim 2 , further comprising lyophilizing said solution from step (d) to form a lyophilized powder. 
     
     
         4 . The lyophilized powder, produced by the process of  claim 3 . 
     
     
         5 . An article of manufacture comprising a container containing the lyophilized powder of  claim 4 . 
     
     
         6 . The article of manufacture according to  claim 5 , wherein said container is a syringe or vial. 
     
     
         7 . The article of manufacture according to  claim 5 , further comprising a volume of at least one aqueous diluent suitable for reconstitution of said lyophilized powder. 
     
     
         8 . A pharmaceutical formulation suitable for administration to a patient, said formulation prepared by reconstituting the lyophilized powder of  claim 4  in a volume of at least one aqueous diluent. 
     
     
         9 . A process for treating or preventing disease in a patient comprising administering a therapeutically effective amount of the pharmaceutical formulation comprising Temozolomide or a pharmaceutically acceptable salt thereof, at least one aqueous diluent, and at least one dissolution enhancing agent sufficient to substantially dissolve said Temozolomide, wherein said dissolution enhancing agent is selected from the group consisting of urea, L-histidine, L-threonine, L-asparagine, L-serine, and L-glutamine, to a patient in need thereof. 
     
     
         10 . The process for treating or preventing disease according to  claim 9 , wherein said disease is carcinoma, sarcoma, melanoma, glioma, glioblastoma, brain cancer, lung cancer, thyroid follicular cancer, pancreatic cancer, breast cancer, bladder cancer, myelodysplasia, prostate cancer, testicular cancer, anaplastic astrocytoma, colon and rectal cancer, lymphoma, leukemia, or mycosis fungoides. 
     
     
         11 . The process for treating or preventing disease according to  claim 9 , wherein said patient is an animal. 
     
     
         12 . The process for treating or preventing disease according to  claim 9 , wherein said patient is a mammal. 
     
     
         13 . The process for treating or preventing disease according to  claim 9 , wherein said patient is a human. 
     
     
         14 . A process for treating or preventing disease in a patient comprising administering a therapeutically effective amount of the pharmaceutical formulation of  claim 8  to a patient in need thereof. 
     
     
         15 . The process for treating or preventing disease according to  claim 14 , wherein said disease is carcinoma, sarcoma, melanoma, glioma, glioblastoma, brain cancer, lung cancer, thyroid follicular cancer, pancreatic cancer, breast cancer, bladder cancer, myelodysplasia, prostate cancer, testicular cancer, anaplastic astrocytoma, colon and rectal cancer, lymphoma, leukemia, or mycosis fungoides. 
     
     
         16 . The process for treating or preventing disease according to  claim 14 , wherein said patient is an animal. 
     
     
         17 . The process for treating or preventing disease according to  claim 14 , wherein said patient is a mammal. 
     
     
         18 . The process for treating or preventing disease according to  claim 14 , wherein said patient is a human.