Oral pharmaceutical compositions containing taxanes and methods of treatment employing the same

Abstract

Pharmaceutical compositions for oral administration to mammalian subjects comprise a taxane or taxane derivative (e.g., paclitaxel or docetaxel) as active ingredient and a vehicle comprising at least 30% by weight of a carrier for the taxane, said carrier having an HLB value of at least about 10. The compositions may also comprise 0-70% of a viscosity-reducing co-solubilizer. The compositions may be incorporated into conventional oral pharmaceutical dosage forms, or can be in the form of a two-part medicament wherein the first part includes the taxane in a solubilizing vehicle and the second part comprises a carrier for the taxane to promote oral absorption. Methods of treatment of taxane-responsive disease conditions employing the novel compositions are also disclosed, whereby the compositions can be administered alone or in association with an oral bioavailability enhancing agent.

1 . A two-part medicament for oral administration to a mammalian subject, the first part of said medicament comprising a taxane or taxane derivative as active ingredient in a solubilizing vehicle for said taxane, and the second part of said medicament comprising at least 30% by weight of a carrier for the taxane, said carrier having an HLB value at least about 10.  
   
   
       2 . A two-part medicament according to  claim 1  wherein the solubilizing vehicle is capable of solubilizing at least about 25 mg/ml of the taxane at about 20-25° C.  
   
   
       3 . A two-part medicament according to  claim 1  wherein the solubilizing vehicle comprises water, ethanol or a polyoxyethylated or hydrogenated castor oil.  
   
   
       4 . A two-part medicament according to  claim 1  wherein the solubilizing vehicle comprises sweetening, flavoring or coloring agents.  
   
   
       5 . A two-part medicament according to  claim 1  wherein the solubilizing vehicle contains about 2-500 mg/ml or mg/g of the taxane.  
   
   
       6 . A two-part medicament according to  claim 5  wherein the solubilizing vehicle contains about 2-50 mg/ml or mg/g of the taxane.  
   
   
       7 . A two-part medicament according to  claim 1  wherein the carrier includes at least one non-ionic surfactant or emulsifier.  
   
   
       8 . A two-part medicament according to  claim 7  wherein the carrier includes at least one surfactant or emulsifier selected from the group consisting of Vitamin E TPGS, saturated polyglycolyzed glycerides, modified castor oils, polyoxyethylated stearate esters, polyoxyethylated sorbitan esters, polyoxyethylated fatty ethers, modified almond and corn oil glycerides sorbitan diisostearate esters, polyoxyethylated hydroxystearates, and β-cyclodextrin.  
   
   
       9 . A two-part medicament according to  claim 1  wherein the second part of the medicament comprises about 30-240 ml of fluid.  
   
   
       10 . A two-part medicament according to  claim 1  wherein the taxane is paclitaxel or docetaxel.  
   
   
       11 . A two-part medicament according to  claim 10  wherein the taxane is paclitaxel.  
   
   
       12 . A method of treating a mammalian subject suffering from a taxane-responsive disease condition comprising the oral administration to the subject of a two-derivative as active ingredient in a solubilizing vehicle for said taxane and the second part of said medicament comprising at least 30% by weight of a carrier for the taxane, said carrier having an HLB value at least about 10.  
   
   
       13 . A method according to  claim 12  wherein the solubilizing vehicle is capable of solubilizing at least about 25 mg/ml of the taxane at about 20-25° C.  
   
   
       14 . A method according to  claim 12  wherein the solubilizing vehicle comprises water, ethanol or a polyoxyethylated or hydrogenated castor oil.  
   
   
       15 . A method according to  claim 12  wherein the solubilizing vehicle comprises sweetening, flavoring or coloring agents.  
   
   
       16 . A method according to  claim 12  wherein the solubilizing vehicle contains about 2-500 mg/ml or mg/g of the taxane.  
   
   
       17 . A method according to  claim 12  wherein the solubilizing vehicle contains about 2-50 mg/ml or mg/g of the taxane.  
   
   
       18 . A method according to  claim 12  wherein the carrier includes at least one non-ionic surfactant or emulsifier.  
   
   
       19 . A method according to  claim 12  wherein the carrier includes at least one surfactant or emulsifier selected from the group consisting of Vitamin E TPGS, saturated polyglycolyzed glycerides, modified castor oils, polyoxyethylated stearate esters, polyoxyethylated sorbitan esters, polyoxyethylated fatty ethers, modified almond and corn oil glycerides sorbitan diisostearate esters, polyoxyethylated hydroxystearates, and β-cyclodextrin.  
   
   
       20 . A method according to  claim 12  wherein the second part of the composition comprises about 30-240 ml of fluid.  
   
   
       21 . A method according to  claim 12  wherein the taxane is paclitaxel or docetaxel  
   
   
       22 . A method according to  claim 21  wherein the taxane is paclitaxel.