PHARMACEUTICAL FORMULATION CONTAINING GLYCOPYRROLATE AND INDACATEROL MALEATE

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

(a) glycopyrrolate and indacaterol maleate;

(b) a solvent;

(c) a pharmacologically acceptable solubilizing agent; and

(d) a pharmacologically acceptable preservative,

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 glycopyrrolate is present in an amount ranging from about 0.2 mg/100 ml to about 550 mg/100 ml.

3 . The pharmaceutical formulation according to claim 1 , wherein the indacaterol maleate is present in an amount ranging from about 0.34 mg/100 ml to about 1000 mg/100 ml.

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

5 . The pharmaceutical formulation according to claim 1 , wherein the solubilizing agent is selected from the group consisting of tween-80, poloxamer, polyoxyethylated castor oil, polyethylene glycol, solutol HS 15, polyvinylpyrrolidone, cyclodextrin derivatives, sulfobutylether β-cyclodextrin, and combinations thereof.

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

7 . The pharmaceutical formulation according to claim 1 , wherein the pharmacologically acceptable preservative is selected from the group consisting of benzalkonium chloride, benzoic acid, sodium benzoate, and combinations thereof.

8 . The pharmaceutical formulation according to claim 7 , wherein the preservative is present in an amount ranging from about 2 mg/100 ml to about 300 mg/100 ml.

9 . The pharmaceutical formulation according to claim 1 , wherein the stabilizer is selected from the group consisting of edetic acid, edetate disodium dehydrate, edetate disodium, citric acid, and combinations thereof.

10 . The pharmaceutical formulation according to claim 9 , wherein the stabilizer is present in an amount ranging from about 1 mg/100 ml to about 500 mg/100 ml.

11 . The pharmaceutical formulation according to claim 1 , wherein the pharmaceutical formulation comprises a pharmacologically acceptable additive.

12 . The pharmaceutical formulation according to claim 11 , wherein pharmacologically acceptable additive is an antioxidant.

13 . A method for administering the pharmaceutical formulation according to claim 1 , comprising nebulizing the pharmaceutical formulation using an inhaler depicted in FIG. 1 .

14 . 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.

15 . The method according to claim 14 , wherein the defined amount of the pharmaceutical formulation ranges from about 5 microliters to about 30 microliters.

16 . The method according to claim 14 , wherein aerosol has an MMAD of less than about 10 μm.

17 . The method according to claim 14 , wherein aerosol has a D50 of less than about 10 μm.

18 . The method according to claim 13 , wherein the inhaler further comprises a block function and a counter.

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

20 . The method of claim 19 , wherein the pharmaceutical formulation is administered at a therapeutically effective dose of glycopyrronium bromide ranging from about 1 μg to about 142 μg and a therapeutically effective dose of indacaterol maleate ranging from about 5 μg to about 500 μg.

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

an aqueous solution of:

(a) glycopyrrolate in an amount of about 0.2 mg/100 mL to about 550 mg/mL,

(b) indacaterol maleate in an amount of about 0.3 mg/100 mL to about 1000 mg/100 mL,

(c) sulfobutylether β-cyclodextrin (SBECD) in an amount of about 1 g/100 mL to about 40 g/mL,

(d) 50% benzalkonium chloride aqueous solution in an amount of about 2 mg/100 mL to about 300 mg/mL, and

(e) edetate disodium dihydrate in an amount of about 1 mg/100 mL to about 500 mg/mL,

wherein the pharmaceutical preparation has a pH ranging from about 3.0 to about 4.0.

22 . A method for preparing a pharmaceutical formulation comprising a solution of indacaterol maleate in water comprising: (i) adding about 3.4 mg to about 10 g of indacaterol maleate to about 100 g of water substantially free of other solvents to provide a suspension and (ii) heating the suspension at a temperature of at least about 50° C. to about 90° C. with stirring until the indacaterol dissolves.

23 . The method of claim 22 comprising:

(i) combining about 10 g to about 400 g of sulfobutylether β-cyclodextrin (SBECD), about 10 mg to about 5000 mg of EDTA, about 20 mg to about 3000 mg of 50% benzalkonium chloride aqueous solution, and about 50 g of water to provide a first solution;

(ii) adding about 3.4 mg to about 10 g of indacaterol maleate to about 50 g of water to provide a first suspension;

(iii) combining the first suspension with the first solution to provide a second suspension;

(iv) heating the second suspension at a temperature of about 50° C. to about 90° C. with stirring until the indacaterol maleate dissolves to provide a second solution;

(v) adding about 20 mg to about 3000 mg of glycopyrronium bromide to the second solution to provide a mixture and stirring the mixture until the glycopyrronium bromide dissolves.