Formulations of brincidofovir

Abstract

Disclosed are formulations comprising brincidofovir. The formulations can be intravenous formulations. The formulations can be used in cases where a subject experiences gastrointestinal issues in response to oral administration of brincidofovir. The formulations can also be used in cases where oral administration of drug is not possible due to underlying conditions or concern around inadequate oral absorption.

1 . A pharmaceutical composition, comprising:
 brincidofovir;   a bulking agent;   a buffer; and   water; wherein the pH of the composition is about 8.0.   
     
     
         2 - 15 . (canceled) 
     
     
         16 . A lyophilized powder comprising:
 about 13-19% by weight brincidofovir;   about 48%-65% by weight mannitol; and   about 22-33% by weight arginine.   
     
     
         17 . (canceled) 
     
     
         18 . An aqueous pharmaceutical composition, comprising:
 brincidofovir;   a bulking agent;   a buffer; and   an aqueous sugar alcohol solution, an aqueous sugar solution, Ringer's solution or a sodium chloride solution.   
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the aqueous sugar solution is a solution comprising about 5% dextrose by weight. 
     
     
         20 . The pharmaceutical composition of  claim 18 , wherein the sodium chloride solution is 0.9% sodium chloride by weight. 
     
     
         21 . The aqueous pharmaceutical composition of  claim 18 , comprising:
 brincidofovir at a concentration of about 1.0 mg/mL;   mannitol at a concentration of about 2.5-5 mg/mL; and   L-arginine at a concentration of about 1.74 mg/mL; and   dextrose at a concentration of about 50 mg/mL;   wherein the pH of the composition is about 8.0.   
     
     
         22 . The aqueous pharmaceutical composition of  claim 18 , comprising:
 brincidofovir at a concentration of about 1.78 mM;   mannitol at a concentration of about 13.75-27.5 mM;   L-arginine at a concentration of about 10 mM; and   dextrose at a concentration of about 287 mM;   wherein the pH of the composition is about 8.0.   
     
     
         23 . The aqueous pharmaceutical composition of  claim 18 , comprising:
 brincidofovir at a concentration of about 0.5 mg/mL;   mannitol at a concentration of about 1.25-2.5 mg/mL; and   L-arginine at a concentration of about 0.87 mg/mL; and   dextrose at a concentration of about 50 mg/mL;   wherein the pH of the composition is about 8.0.   
     
     
         24 . The aqueous pharmaceutical composition of  claim 18 , comprising:
 brincidofovir at a concentration of about 0.89 mM;   mannitol at a concentration of about 6.85-13.7 mM;   L-arginine at a concentration of about 5 mM; and   dextrose at a concentration of about 287 mM;   wherein the pH of the composition is about 8.0.   
     
     
         25 . The pharmaceutical composition of  claim 18 , wherein the volume of the aqueous sugar alcohol solution, aqueous sugar solution, Ringer's solution, or aqueous sodium chloride solution is about 100 or 200 mL. 
     
     
         26 . The aqueous pharmaceutical composition of  claim 18 , comprising:
 about 100 mg brincidofovir;   about 250-500 mg mannitol;   about 174 mg arginine;   about 5 g dextrose; and   about 100 mL water;   wherein the pH of the solution is about 8.0.   
     
     
         27 . The aqueous pharmaceutical composition of  claim 18 , comprising:
 about 200 mg brincidofovir;   about 500-1000 mg mannitol;   about 348 mg arginine;   about 10 g dextrose; and   about 200 mL water;   wherein the pH of the solution is about 8.0.   
     
     
         28 . The aqueous pharmaceutical composition of  claim 18 , comprising:
 about 50 mg brincidofovir;   about 125-250 mg mannitol;   about 87 mg arginine;   about 5 g dextrose; and   about 100 mL water;   wherein the pH of the solution is about 8.0.   
     
     
         29 . The aqueous pharmaceutical composition of  claim 18 , comprising:
 about 100 mg brincidofovir;   about 250-500 mg mannitol;   about 174 mg arginine;   about 10 g dextrose; and   about 200 mL water;   wherein the pH of the solution is about 8.0.   
     
     
         30 . The pharmaceutical composition of  claim 18 , wherein the brincidofovir, the bulking agent, and the buffer have previously been lyophilized. 
     
     
         31 . The pharmaceutical composition of  claim 18 , wherein the composition is suitable for intravenous administration. 
     
     
         32 . The pharmaceutical composition of  claim 18 , wherein the composition is sterile. 
     
     
         33 . An aqueous pharmaceutical composition for intravenous administration, comprising:
 brincidofovir at a concentration of between about 0.5 mg/mL and about 1.0 mg/mL;   a bulking agent at a concentration of between about 2.5 mg/mL and about 5 mg/mL;   a buffer at a concentration of between about 0.87 mg/mL and about 1.74 mg/mL; and   dextrose at a concentration of about 50 mg/mL;   wherein the pH of the composition is about 8.0.   
     
     
         34 . A method of treatment of a subject with a viral infection, comprising administering to the subject in need thereof an effective amount of the aqueous pharmaceutical composition of  claim 18 . 
     
     
         35 . The method of  claim 34 , wherein the viral infection is selected from polyomavirus, papillomavirus, herpes virus, adenovirus, Epstein-Barr virus, cytomegalovirus, Hepatitis B virus, Hepatitis C virus, varicella zoster virus, adenovirus, poxvirus, or a combination thereof. 
     
     
         36 . The method of  claim 34 , wherein administration to the subject does not result in hemolysis. 
     
     
         37 . The method of  claim 34 , wherein administration to the subject does not result in gastrointestinal toxicity. 
     
     
         38 . A method of treating a subject with a viral infection, the method comprising:
 administering to the subject an intravenous pharmaceutical composition comprising brincidofovir at a concentration of between about 0.5 mg/mL and about 1.0 mg/mL;   a bulking agent at a concentration of between about 2.5 mg/mL and about 5 mg/mL;   a buffer at a concentration of between about 0.87 mg/mL and about 1.74 mg/mL; and   dextrose at a concentration of about 50 mg/mL %;   wherein the pH of the composition is about 8.0.   
     
     
         39 - 41 . (canceled)