Formulations for administration of eflornithine

Abstract

Eflornithine is an agent that can be used to treat glioma, especially glioma of WHO Grade II or Grade III such as anaplastic glioma. Eflornithine can suppress or prevent mutations in glioma which can cause the glioma to progress to a higher grade. The present invention describes pharmaceutical compositions that contain eflornithine or a derivative, analog, or prodrug thereof. The pharmaceutical compositions can be prepared in a number of dosage forms and may contain another therapeutically active agent or an agent that enhances the therapeutic activity of the eflornithine or the derivative, analog, or prodrug thereof. The present invention also describes a kit that includes dosage forms of pharmaceutical compositions according to the present invention.

1 .- 158 . (canceled) 
     
     
         159 . A pharmaceutical composition that is in the physical form of a solution for oral administration, comprising from about 16.2 wt % to about 19.8 wt % of eflornithine or a pharmaceutically acceptable salt thereof, water, and one or more pharmaceutically acceptable excipients. 
     
     
         160 . The pharmaceutical composition of  claim 159 , wherein the solution comprises about 18% eflornithine or a pharmaceutically acceptable salt thereof. 
     
     
         161 . The pharmaceutical composition of  claim 159 , comprising:
 (a) from about 16.2 wt % to about 19.8 wt % of eflornithine or a pharmaceutically acceptable salt thereof;   (b) from about 0.135 wt % to about 0.165 wt % of preservative;   (c) from about 0.135 wt % to about 0.165 wt % of sweetening agent;   (d) from about 2.7 wt % to about 3.3 wt % of a first thickening agent;   (e) from about 4.5 wt % to about 5.5 wt % of a second thickening agent; and   (f) purified water to 100 wt %.   
     
     
         162 . The pharmaceutical composition of  claim 160 , wherein the preservative is sodium benzoate. 
     
     
         163 . The pharmaceutical composition of  claim 160 , wherein the sweetening agent is saccharin sodium dihydrate. 
     
     
         164 . The pharmaceutical composition of  claim 160 , wherein the first thickening agent is glycerol. 
     
     
         165 . The pharmaceutical composition of  claim 160 , wherein the second thickening agent is propylene glycol. 
     
     
         166 . The pharmaceutical composition of  claim 160 , wherein the composition comprises:
 (a) about 18 wt % of eflornithine or a pharmaceutically acceptable salt thereof;   (b) about 0.15 wt % of sodium benzoate;   (c) about 0.15 wt % of saccharin sodium dihydrate;   (d) about 3.0 wt % of glycerol;   (e) about 5.0 wt % of propylene glycol; and   (f) purified water to 100 wt %.   
     
     
         167 . A kit comprising: a pouch of solid eflornithine or a pharmaceutically acceptable salt thereof, wherein the pouch comprises an individual dosage of eflornithine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient; and
 instructions to prepare an oral solution of eflornithine or a pharmaceutically acceptable salt thereof.   
     
     
         168 . The kit of  claim 167 , wherein the instructions describe preparing an oral solution of eflornithine or a pharmaceutically acceptable salt thereof with a concentration of about 13.5 wt % to about 22.5 wt % in water. 
     
     
         169 . The kit of  claim 167 , wherein the instructions describe preparing an oral solution with a concentration of eflornithine or a pharmaceutically acceptable salt thereof of about 16.2 wt % to about 19.8 wt % in water. 
     
     
         170 . The kit of  claim 167 , wherein the solid eflornithine or pharmaceutically acceptable salt thereof is in the form of a powder. 
     
     
         171 . The kit of  claim 167 , wherein the solid eflornithine or pharmaceutically acceptable salt thereof is in the form of a tablet. 
     
     
         172 . The kit of  claim 167 , wherein the one or more pouches further comprise a sweetening agent. 
     
     
         173 . The kit of  claim 167 , wherein the one or more pouches comprise less than 1 wt % of the sweetening agent. 
     
     
         174 . The kit of  claim 173 , wherein the sweetening agent is selected from the group consisting of an aspartame, dextran, dextrose, fructose, glycerol, mannitol, saccharin, calcium saccharin, sodium saccharin, sorbitol, sucrose, compressible sugar, confectioner's sugar, and syrup. 
     
     
         175 . The kit of  claim 174 , wherein the sweetening agent is saccharin sodium dihydrate. 
     
     
         176 . The kit of  claim 167 , wherein the pharmaceutically acceptable excipient is selected from the group consisting of maize starch, wheat starch, rice starch, potato starch, gelatin, gum, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, or polyvinylpyrrolidone (PVP). 
     
     
         177 . The kit of  claim 176 , wherein the pharmaceutically acceptable excipient is hydroxypropylmethyl-cellulose or polyvinylpyrrolidone. 
     
     
         178 . The kit of  claim 167 , further comprising one or more additional pouches of solid eflornithine or a pharmaceutically acceptable salt thereof wherein each additional pouch comprises an individual dosage of eflornithine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.