Taxane formulations

Abstract

The present invention is directed to various formulations of taxanes having improved solubility as compared to paclitaxel, particularly formulations of such taxane derivatives for oral or parenteral administration to a patient.

1 . A method of treating a patient afflicted with a neoplastic cancer, the method comprising oral administration of a pharmaceutical composition to the patient, the pharmaceutical composition consisting essentially of 
 (a) a taxane;    (b) a solvent capable of dissolving the taxane;    (c) polyoxyethylated castor oil;    (d) a diluent; and    (e) optionally, a flavoring;    wherein the taxane has a solubility in ethanol nat room temperature of atleast 200 mg/ml.    
     
     
         2 . The method of  claim 1  wherein the composition contains a flavoring.  
     
     
         3 . The method of  claim 1  wherein the solvent capable of dissolving the taxane is ethanol.  
     
     
         4 . The method of  claim 1  wherein the diluent is water, saline, dextrose or an electrolyte solution.  
     
     
         5 . The method of  claim 1  wherein the solvent capable of dissolving the taxane is ethanol and the diluent is saline.  
     
     
         6 . The method of  claim 5  wherein the ethanol and polyoxyethylated castor oil are present in a volumetric ratio of about 1 to 1.  
     
     
         7 . The method of  claim 1  wherein the taxane has an ID 50  value determined relative to the HCT116 cell line that is at least 4 times less than that of paclitaxel.  
     
     
         8 . The method of  claim 1  wherein the taxane has an ID50 value determined relative to the HCT116 cell line that is at least 7 times less than that of paclitaxel.  
     
     
         9 . The method of  claim 1  wherein the taxane has an ID50 value determined relative to the HCT116 cell line that is at least 10 times less than that of paclitaxel.  
     
     
         10 . The method of  claim 1  wherein the taxane has a solubility in ethanol at room temperature of at least 500 mg/ml.  
     
     
         11 . The method of  claim 1  wherein the taxane has a solubility in ethanol at room temperature of at least 800 mg/ml.  
     
     
         12 . The method of  claim 10  wherein the taxane has an ID 50  value determined relative to the HCT116 cell line that is at least 4 times less than that of paclitaxel.  
     
     
         13 . The method of  claim 10  wherein the taxane has an ID 50  value determined relative to the HCT116 cell line that is at least 7 times less than that of paclitaxel.  
     
     
         14 . The method of  claim 10  wherein the taxane has an ID 50  value determined relative to the HCT116 cell line that is at least 10 times less than that of paclitaxel.  
     
     
         15 . The method of  claim 11  wherein the taxane has an ID50 value determined relative to the HCT116 cell line that is at least 4 times less than that of paclitaxel.  
     
     
         16 . The method of  claim 11  wherein the taxane has an ID50 value determined relative to the HCT116 cell line that is at least 7 times less than that of paclitaxel.  
     
     
         17 . The method of  claim 11  wherein the taxane has an ID50 value determined relative to the HCT116 cell line that is at least 10 times less than that of paclitaxel.