Methods of use of emulsion formulations of aprepitant

Abstract

Disclosed herein are novel pharmaceutical formulations of aprepitant suitable for parenteral administration including intravenous administration. Also included are formulations including both aprepitant and dexamethasone sodium phosphate. The pharmaceutical formulations are stable oil-in-water emulsions for non-oral treatment of emesis and are particularly useful for treatment of subjects undergoing highly emetogenic cancer chemotherapy.

What is claimed is: 
     
         1 . A method for preventing nausea and vomiting in a subject in need thereof, comprising:
 administering to the subject a physically stable pharmaceutical composition comprising
 aprepitant; 
 an emulsifier; 
 an oil; and 
 water; 
   wherein the ratio of the emulsifier to aprepitant (wt %:wt %) ranges from about 18:1 to 22:1,   wherein the ratio of the oil to aprepitant (wt %:wt %) ranges from about 11:1 to 15:1, and   wherein the composition is an emulsion.   
     
     
         2 . The method according to  claim 1 , wherein the nausea and vomiting is chemotherapy induced nausea and vomiting. 
     
     
         3 . The method according to  claim 2 , wherein the chemotherapy induced nausea and vomiting is in response to highly emetic chemotherapy. 
     
     
         4 . The method according to  claim 2 , wherein the chemotherapy induced nausea and vomiting is in response to moderately emetic chemotherapy. 
     
     
         5 . The method according to  claim 1 , wherein the administering is intravenous. 
     
     
         6 . The method according to  claim 1 , wherein the composition comprises 0.4 wt/wt % to 1.0 wt/wt % aprepitant. 
     
     
         7 . The method according to  claim 1 , wherein the composition comprises 11 wt/wt % to 15 wt/wt % emulsifier. 
     
     
         8 . The method according to  claim 7 , wherein the emulsifier is egg yolk lecithin. 
     
     
         9 . The method according to  claim 1 , wherein the composition comprises 9 wt/wt % to 10 wt/wt % oil. 
     
     
         10 . The method according to  claim 9 , wherein the oil is soybean oil. 
     
     
         11 . The method according to  claim 1 , wherein the composition further comprises sodium oleate as a pH modifier. 
     
     
         12 . The method according to  claim 1 , wherein the pH of the composition ranges from 7.5 to 9.0. 
     
     
         13 . The method according to  claim 1 , wherein the composition further comprises 3 wt/wt % to 8 wt/wt % sucrose. 
     
     
         14 . The method according to  claim 1 , wherein the composition further comprises 2 wt/wt % to 6 wt/wt % ethanol. 
     
     
         15 . A method for preventing nausea and vomiting in a subject in need thereof, comprising:
 administering to the subject an injectable emulsion comprising:
 aprepitant; 
 11 wt/wt % to 15 wt/wt % of an emulsifier; 
 an oil; 
 a co-emulsifier which is an alcohol; 
 a tonicity modifier; 
 a pH modifier; and 
 water; 
   wherein the pH of the emulsion ranges from about 7.5 to 9.0.   
     
     
         16 . The method according to  claim 15 , wherein the oil and the aprepitant are in a ratio in the emulsion of between 10:1 to 15:1 (wt/wt %). 
     
     
         17 . The method according to  claim 15 , wherein the emulsifier and the aprepitant are in a ratio in the emulsion of between 15:1 to 30:1 (wt/wt %). 
     
     
         18 . The method according to  claim 15 , wherein the emulsifier and the oil are in a ratio in the emulsion of between 1:1 to 3:1 (wt/wt %). 
     
     
         19 . The method according to  claim 15 , wherein the emulsifier is an egg lecithin. 
     
     
         20 . The method according to  claim 15 , further comprising dexamethasone sodium phosphate, wherein the dexamethasone sodium phosphate is present in an aqueous phase of the emulsion. 
     
     
         21 . The method according to  claim 15 , wherein the pH modifier is sodium oleate. 
     
     
         22 . The method according to  claim 15 , wherein the oil is soybean oil. 
     
     
         23 . The method according to  claim 15 , wherein the alcohol is ethanol. 
     
     
         24 . The method according to  claim 23 , wherein the ethanol is present at less than 10 wt/wt %. 
     
     
         25 . The method according to  claim 15 , wherein the nausea and vomiting is chemotherapy induced nausea and vomiting. 
     
     
         26 . The method according to  claim 25 , wherein the chemotherapy induced nausea and vomiting is in response to highly emetic chemotherapy. 
     
     
         27 . The method according to  claim 25 , wherein the chemotherapy induced nausea and vomiting is in response to moderately emetic chemotherapy. 
     
     
         28 . The method according to  claim 15 , wherein the administering is intravenous.