PHARMACEUTICAL FORMULATION CONTAINING ACTIVE METABOLITES OF REMDESIVIR OR ITS ANALOG FOR INHALATION

1 . A liquid, propellant-free pharmaceutical formulation comprising:

(a) one or more active ingredients selected from the group consisting of (i) an active metabolite of remdesiver or a pharmaceutically acceptable salt or solvate thereof and (ii) GS-441524 or a pharmaceutically acceptable salt or solvate thereof;

(b) a solvent;

(c) a pharmacologically acceptable solubilizing agent;

(d) a pharmacologically acceptable preservative; and

(e) a pharmacologically acceptable stabilizer.

2 . The pharmaceutical formulation of claim 1 , wherein the concentration of the one or more active ingredients ranges from about 0.1 g/100 ml to about 50 g/100 ml.

3 . The pharmaceutical formulation of claim 1 , wherein the concentration of the one or more active ingredients ranges from about 1 mg/100 ml to about 20 g/100 ml.

3 . The pharmaceutical formulation of claim 1 , wherein the solvent is water.

4 . The pharmaceutical formulation of claim 1 , wherein the solvent comprises water.

5 . The pharmaceutical formulation of claim 1 , wherein the pH of the formulation ranges from about 3.0 to about 5.0.

6 . The pharmaceutical formulation of claim 1 , wherein the pharmacologically acceptable solubilizing agent is selected from the group consisting of Tween 80 and cyclodextrin derivative or a salt thereof.

7 . The pharmaceutical formulation of claim 6 , wherein the pharmacologically acceptable solubilizing agent is present in an amount ranging from about 1 mg/100 ml to about 40 g/100 ml.

8 . The pharmaceutical formulation of claim 6 , wherein the pharmacologically acceptable solubilizing agent is a cyclodextrin derivative or a salt thereof.

9 . The pharmaceutical formulation of claim 7 , wherein the pharmacologically acceptable solubilizing agent is sulfobutylether-β-cyclodextrin or a salt thereof.

10 . The pharmaceutical formulation of claim 1 , wherein the preservative is selected from the group consisting of benzalkonium chloride, benzoic acid, and sodium benzoate.

11 . The pharmaceutical formulation of claim 1 , wherein the preservative is present in an amount ranging from about 2 mg/100 ml to about 300 mg/100 ml.

12 . The pharmaceutical formulation of claim 1 , wherein the preservative is benzalkonium chloride in an amount of about 10 mg/100 ml.

13 . The pharmaceutical formulation of claim 1 , wherein the stabilizer is selected from the group consisting of edetic acid (EDTA), disodium edetate, edetate disodium dihydrate, and citric acid.

14 . The pharmaceutical formulation of claim 1 , wherein the stabilizer is present in an amount ranging from about 1 mg/100 ml to about 500 mg/100 ml.

15 . The pharmaceutical formulation of claim 13 , wherein stabilizer is edetate disodium dihydrate in a concentration of about 10 mg/100 ml.

16 . A method for administering the pharmaceutical formulation of claim 1 comprising nebulizing a defined amount of the pharmaceutical formulation with an inhaler by using pressure to force the pharmaceutical preparation through a nozzle to form an inhalable aerosol.

17 . The method of claim 16 , wherein the defined amount of the pharmaceutical formulation is less than about 70 microliters.

18 . The method of claim 16 , wherein the average particle size of the aerosol is less than about 15 microns.

19 . The method of claim 16 , wherein the aerosol has a mass median aerodynamic diameter ranging from about 1 micron to about 5 microns.

20 . The method of claim 16 , wherein the pharmaceutical formulation is administered using an inhaler as depicted in FIG. 1 .

21 . A method of treating asthma or COPD in a patient, comprising administering to the patient the pharmaceutical formulation of claim 1 by inhalation.

22 . A liquid, propellant-free pharmaceutical formulation selected from the group consisting of:

(I) an aqueous solution comprising:

(a) nucleoside triphosphate in an amount ranging from about 2,000 mg/100 mL of solution to about 10,000 mg/100 mL of solution; and

(b) sodium chloride in an amount ranging from about 300 mg/100 mL of solution to about 900 mg/100 mL of solution wherein the pH of the formulation ranges from about 3.0 to about 4.0;

(II) an aqueous solution comprising:

(a) nucleoside triphosphate in an amount ranging from about 10,000 mg/100 mL of solution to about 20,000 mg/100 mL of solution;

(b) edetate disodium dihydrate in an amount ranging from about 10 mg/100 mL of solution to about 20 mg/100 mL of solution; and

(c) 50% benzalkonium chloride aqueous solution in an amount ranging from about 20 mg/100 mL of solution to about 40 mg/100 mL of solution;

wherein the pH of the formulation ranges from about 3.0 to about 4.0;

(III) an aqueous solution comprising:

(a) alanine metabolite in an amount ranging from about 5,000 mg/100 mL of solution to about 10,000 mg/100 mL of solution; and

(b) sodium chloride in an amount ranging from about 0 mg/100 mL of solution to about 300 mg/100 mL of solution;

wherein the pH of the formulation ranges from about 3.0 to about 4.0;

(IV) an aqueous solution comprising:

(a) alanine metabolite in an amount ranging from about 2,000 mg/100 mL of solution to about 3,000 mg/100 mL of solution;

(b) edetate disodium dihydrate in an amount ranging from about 10 mg/100 mL of solution to about 20 mg/100 mL of solution; and

(c) 50% benzalkonium chloride aqueous solution in an amount ranging from about 20 mg/100 mL of solution to about 40 mg/100 mL of solution;

wherein the pH of the formulation ranges from about 3.0 to about 4.0;

(V) an aqueous solution comprising:

(a) GS-441524 in an amount ranging from about 500 mg/100 mL of solution to about 1,000 mg/100 mL of solution;

(b) sulfobutylether-β-cyclodextrin in an amount ranging from about 5,000 mg/100 mL of solution to about 10,000 mg/100 mL of solution; and

(c) sodium chloride in an amount ranging from about 0 mg/100 mL of solution to about 300 mg/100 mL of solution;

wherein the pH of the formulation ranges from about 3.0 to about 4.0; and

(VI) an aqueous solution comprising:

(a) GS-441524 in an amount ranging from about 2,000 mg/100 mL of solution to about 3,000 mg/100 mL of solution;

(b) sulfobutylether-β-cyclodextrin in an amount ranging from about 5,000 mg/100 mL of solution to about 10,000 mg/100 mL of solution;

(c) edetate disodium dihydrate in an amount ranging from about 10 mg/100 mL of solution to about 20 mg/100 mL of solution; and

(d) 50% benzalkonium chloride aqueous solution in an amount ranging from about 20 mg/100 mL of solution to about 40 mg/100 mL of solution;

wherein the pH of the formulation ranges from about 3.0 to about 4.0.