PREPARATION OF A PHARMACEUTICAL COMPOSITION OF OLODATEROL, TIOTROPIUM BROMIDE AND BUDESONIDE

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

(a) budesonide, olodaterol, and tiotropium bromide;

(b) a solvent;

(c) a pharmacologically acceptable solubilizing agent.

wherein the pharmaceutical formulation has a pH ranging from about 2.0 to about 6.0.

2 . The pharmaceutical formulation according to claim 1 , wherein budesonide is present in an amount ranging from about 1 mcg/ml to about 640 mcg/ml; the olodaterol is present in an amount ranging from about 2 mcg/ml to about 500 mcg/ml; and the tiotropium bromide is present in an amount ranging from about 1 mcg/ml to about 200 mcg/ml.

3 . The pharmaceutical formulation according to claim 1 , wherein the solvent is water substantially free of other solvents.

4 . The pharmaceutical formulation according to claim 1 , wherein the solubilizing agent is selected from the group consisting of tween-80, cyclodextrin derivatives or a salt thereof, and combinations thereof.

5 . The pharmaceutical formulation according to claim 4 , wherein the solubilizing agent is present in an amount ranging from about 1 g/100 ml to about 40 g/100 ml.

6 . The pharmaceutical formulation according to claim 5 , wherein the solubilizing agent is sulfobutylether β-cyclodextrin in an amount ranging from about 0.04 g/4 ml to about 1.6 g/4 ml.

7 . The pharmaceutical formulation according to claim 1 , further comprising a pharmacologically acceptable preservative selected from the group consisting of benzalkonium chloride, benzoic acid, and sodium benzoate.

8 . The pharmaceutical formulation according to claim 8 , wherein the pharmacologically acceptable preservative is present in an amount ranging from about 0.08 mg/4 ml to about 12 mg/4 ml.

9 . The pharmaceutical formulation according to claim 7 , wherein the pharmacologically acceptable preservative is benzalkonium chloride in an amount of about 0.4 mg/4 ml.

10 . The pharmaceutical formulation according to claim 1 , further comprising a stabilizer selected from the group consisting of edetic acid (EDTA), edetate disodium, edetate disodium dihydrate, and citric acid.

11 . The pharmaceutical formulation according to claim 10 , wherein the stabilizer is present in an amount ranging from about 0.04 mg/4 ml to about 20 mg/4 ml.

12 . The pharmaceutical formulation according to claim 1 , further comprising sodium chloride in an amount ranging from about 0.1 g/100 ml to about 0.9 g/100 ml.

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

14 . The method according to claim 13 , wherein the defined amount of the pharmaceutical formulation is less than about 8 milliliters of the pharmaceutical formulation.

15 . The method according to claim 13 , wherein the average particle size of the aerosol is less than about 15 micron.

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

17 . The method of claim 16 , wherein the pharmaceutical formulation is administered at a therapeutically effective dose of budesonide ranging from about 1 μg to about 100 μg; a therapeutically effective dose of olodaterol ranging from about 5 μg to about 500 μg; and a therapeutically effective dose of tiotropium bromide ranging from about 1 μg to about 100 μg.

18 . The liquid, propellant-free pharmaceutical formulation of claim 1 comprising:

an aqueous solution comprising

(a) budesonide in an amount of about 2 mg/100 g;

(b) olodaterol in an amount of about 1.8 mg/100 g

(c) tiotropium bromide in an amount of about 50.9 mg/100 g; and

(d) sulfobutylether β-cyclodextrin in an amount of about 9.6 mg/100 g,

wherein the pH is adjusted with citric acid to a value of 4.0.

19 . The liquid, propellant-free pharmaceutical formulation of claim 1 comprising:

an aqueous solution comprising

(a) budesonide in an amount of about 2 mg/100 g;

(b) olodaterol in an amount of about 1.8 mg/100 g

(c) tiotropium bromide in an amount of about 50.9 mg/100 g; and

(d) sulfobutylether β-cyclodextrin in an amount of about 9.6 mg/100 g,

wherein the pH is adjusted with hydrochloric acid to a value of 4.5.

20 . The liquid, propellant-free pharmaceutical formulation of claim 1 comprising:

an aqueous solution comprising

(a) budesonide in an amount of about 1 mcg/ml to about 640 mcg/ml;

(b) olodaterol in an amount of about 2 mcg/ml to about 500 mcg/ml;

(c) tiotropium bromide in an amount of about 1 mcg/ml to about 200 mcg/ml; and

(d) sulfobutylether β-cyclodextrin in an amount of about 1 g/100 ml to about 40 g/100 ml,

wherein the pH is adjusted with citric acid to a value of 4.0.

21 . The liquid, propellant-free pharmaceutical formulation of claim 1 comprising:

an aqueous solution comprising;

(a) budesonide in an amount of about 1 mcg/ml to about 640 mcg/ml;

(b) olodaterol in an amount of about 2 mcg/ml to about 500 mcg/ml;

(c) tiotropium bromide in an amount of about 1 mcg/ml to about 200 mcg/ml; and

(d) sulfobutylether β-cyclodextrin in an amount of about 1 g/100 ml to about 40 g/100 ml,

wherein the pH is adjusted with hydrochloric acid to a value of 4.5.