FORMULATIONS OF BRINCIDOFOVIR
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 lyophilized powder comprising:
about 13-19% by weight brincidofovir;
about 48%-65% by weight mannitol; and
about 22-33% by weight arginine.
2 . The lyophilized powder of claim 1 , comprising:
about 13% by weight brincidofovir;
about 65% by weight mannitol; and
about 22% by weight arginine.
3 . The lyophilized powder of claim 1 , comprising:
about 19% by weight brincidofovir;
about 48% by weight mannitol; and
about 33% by weight arginine.
4 . The lyophilized powder of claim 1 , comprising:
about 10 mg brincidofovir;
about 50 mg mannitol; and
about 17.4 mg arginine.
5 . The lyophilized powder of claim 1 , comprising:
about 10 mg brincidofovir;
about 25 mg mannitol; and
about 17.4 mg arginine.
6 . A method of treating a viral infection in a subject in need thereof, the method comprising:
(a) dissolving the lyophilized powder of claim 1 in aqueous media to produce an aqueous pharmaceutical composition; and
(b) administering to the subject an effective amount of the aqueous pharmaceutical composition.
7 . The method of claim 6 , 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.
8 . The method of claim 6 , wherein administration to the subject does not result in hemolysis.
9 . The method of claim 6 , wherein administration to the subject does not result in gastrointestinal toxicity.
10 . The method of claim 6 , wherein the aqueous media is a sugar alcohol solution, an aqueous sugar solution, Ringer's solution or an aqueous salt solution.
11 . The method of claim 10 , wherein the aqueous media is an aqueous sugar solution.
12 . The method of claim 11 , wherein the aqueous sugar solution is about 5% dextrose by weight.
13 . The method of claim 11 , wherein the lyophilized powder is dissolved in about 100 mL of aqueous sugar solution.
14 . The method of claim 11 , wherein the lyophilized powder is dissolved in about 200 mL of aqueous sugar solution.
15 . The method of claim 6 , wherein the aqueous pharmaceutical composition comprises:
brincidofovir at a concentration of about 1.0 mg/mL;
mannitol at a concentration of about 2.5 mg/mL to about 5 mg/mL;
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.
16 . The method of claim 6 , wherein the aqueous pharmaceutical composition comprises:
brincidofovir at a concentration of about 1.78 mM;
mannitol at a concentration of about 13.75 mM to about 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.
17 . The method of claim 6 , wherein the aqueous pharmaceutical composition comprises:
brincidofovir at a concentration of about 0.5 mg/mL;
mannitol at a concentration of about 1.25 mg/mL to about 2.5 mg/mL;
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.
18 . The method of claim 6 , wherein the aqueous pharmaceutical composition comprises:
brincidofovir at a concentration of about 0.89 mM;
mannitol at a concentration of about 6.85 mM to about 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.
19 . The method of claim 6 , wherein the aqueous pharmaceutical composition comprises:
about 100 mg brincidofovir;
about 250 mg to about 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.
20 . The method of claim 6 , wherein the aqueous pharmaceutical composition comprises:
about 200 mg brincidofovir;
about 500 mg to about 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.
21 . The method of claim 6 , wherein the aqueous pharmaceutical composition comprises:
about 50 mg brincidofovir;
about 125 mg to about 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.
22 . The method of claim 6 , wherein the aqueous pharmaceutical composition comprises:
about 100 mg brincidofovir;
about 250 mg to about 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.
23 . The method of claim 6 , wherein the aqueous pharmaceutical composition is suitable for intravenous administration.
24 . The pharmaceutical composition of claim 23 , wherein the aqueous pharmaceutical composition is sterile.
25 . A method of preparing the lyophilized powder of claim 1 , comprising
(a) preparing an aqueous solution comprising brincidofovir at a concentration of about 10 mg/mL; mannitol at a concentration of about 25-50 mg/mL; and L-arginine at a concentration of about 17.4 mg/mL; wherein the pH of the composition is about 8.0; and
(b) lyophilizing the aqueous solution.