Tiotropium Inhalation Solution for Nebulization

1 . A pharmaceutical composition comprising

i) tiotropium or its pharmaceutically acceptable salts thereof;

ii) water; and

iii) optionally a complexing agent,

wherein said composition is free of preservative.

2 . A therapeutically effective unit dose of sterile nebulization solution, comprising:

i) a total tiotropium content of at least 3 mcg tiotropium; and

ii) a total water content of no more than 1.0 mL water.

3 . The therapeutically effective unit dose of claim 2 , wherein the unit dose is therapeutically effective for the treatment of chronic obstructive pulmonary disease.

4 . The therapeutically effective unit dose of claim 2 , wherein the nebulization solution is preservative-free.

5 . The therapeutically effective unit dose of claim 2 , wherein the nebulization solution is benzalkonium chloride-free.

6 . The therapeutically effective unit dose of claim 2 , wherein the nebulization solution is complexing agent-free.

7 . The therapeutically effective unit dose of claim 2 , wherein the nebulization solution is ethylenediaminetetraacetic acid-free and disodium edetate-free.

8 . The therapeutically effective unit dose of claim 2 , wherein the nebulization solution is preservative-free and complexing agent-free.

9 . The therapeutically effective unit dose of claim 2 , wherein the tiotropium is amorphous and anhydrous.

10 . A method of treating, preventing, or ameliorating one or more symptoms of a bronchoconstriction-related disease or disorder, comprising: nebulizing, by a nebulizer, the therapeutically effective unit dose of of claim 2 .

11 . The method of claim 10 , wherein the nebulizer is a hand-held, battery powered nebulizer.

12 . A method of increasing patient compliance with a therapeutic dosage regimen, comprising: nebulizing, by a vibrating mesh nebulizer, the therapeutically effective unit dose of sterile nebulization solution of claim 2 in less than 10 minutes.

13 . The method of claim 12 , wherein the total tiotropium content is 5 mcg.

14 . The pharmaceutical composition of claim 1 , comprising:

i) 0.2-0.6 wt. % sodium citrate;

ii) 0.06-0.1 wt. % citric acid; and

iii) at least 97 wt. % water,

wherein the pharmaceutical composition—

a) is complexing agent-free and has a pH in the range of 2.8-3.0; and

b) has a total volume of 1 mL or less and comprises a total tiotropium content of no more than 5 mcg tiotropium.

15 . A blow-fill-seal plastic ampoule containing a sterile, preservative-free, complexing agent-free pharmaceutical composition, the pharmaceutical composition comprising:

i) 0.0008-0.001 wt. % tiotropium;

ii) at least 0.004 wt. % sodium citrate;

iii) citric acid; and

iv) at least 97 wt. % water.

16 . A process to make a sterile tiotropium nebulization product, comprising:

i) dissolving a quantity of tiotropium in a quantity of water to form a tiotropium solution; followed by

ii) adjusting the pH and/or osmolality of the tiotropium solution;

iii) sterilizing the tiotropium solution;

iv) injecting a therapeutically effective unit dose of the sterilized tiotropium solution into a sterile blow-fill-seal container; and

v) sealing the sterile blow-fill-seal container,

the process exclusive of heat sterilization following the sealing.

17 . The process of claim 16 , wherein the process is exclusive of sterilization following the sealing.

18 . The process of claim 16 , wherein the sterilizing is exclusive of heat sterilization prior to the injecting.

19 . The process of claim 16 , wherein the sterilizing comprises passing the tiotropium nebulization solution through a filter prior to the injecting.

20 . The process of claim 16 , wherein the tiotropium solution is further or redundantly sterilized by heat transfer from the sterile blow-fill-seal container.