Tiotropium inhalation solution for nebulization
The present invention relates to a sterile pharmaceutical composition comprising tiotropium or a pharmaceutically acceptable salt thereof, for inhalation via nebulization to a subject (e.g. a human). The invention also relates to a process for preparing the pharmaceutical composition and its use in the treatment of respiratory diseases such as chronic obstructive pulmonary disease (COPD) in a subject.
1. A pharmaceutical composition comprising
(i) about 0.0001% to about 0.03% by weight of tiotropium or a pharmaceutically acceptable salt thereof;
(ii) water;
(iii) a complexing agent, the complexing agent being disodium EDTA and present at a concentration of up to 0.01% by weight,
wherein (a) the composition is free of preservative, (b) the composition is in a solution form for nebulization, (c) the tiotropium or pharmaceutically acceptable salt thereof is the sole active ingredient in the composition, and (d) the osmolality of the composition is 275 mOsm/kg to 325 mOsm/kg.
2. A composition according to claim 1 , wherein tiotropium is present in an amount of about 0.001 mg to about 0.3 mg.
3. A composition according to claim 1 , wherein tiotropium is present in an amount of about 0.005 mg to about 0.2 mg.
4. A composition according to claim 1 , wherein the complexing agent is present in an amount of about 0.01% by weight.
5. A composition according to claim 1 , wherein the composition further comprises sodium chloride.
6. A composition according to claim 5 , wherein the sodium chloride is present in an amount up to about 0.9% by weight.
7. A composition according to claim 1 , wherein the composition is contained in a prefilled container.
8. A composition according to claim 1 , wherein the volume of the composition is between about 0.1 ml to about 5 ml.
9. A composition according to claim 1 , wherein the pH of the composition is between about 2.5 to about 3.5.
10. A composition according to claim 9 , wherein the pH of the composition is about 2.7.
11. A kit comprising a nebulizer, instructions for using a nebulizer and the composition according to claim 1 .
12. A method of relieving bronchospasm associated with chronic obstructive pulmonary disease in a patient comprising administering to said patient the composition according to claim 1 .
13. A process of preparing a pharmaceutical composition comprising about 0.0001% to about 0.03% by weight of tiotropium or a pharmaceutically acceptable salt thereof, water, about 0.01% by weight of a complexing agent, and about 0.9% by weight of sodium chloride, wherein the composition has a pH ranging from about 2.7 to about 2.9 and is free of preservative, the process comprising the steps of:
(a) dissolving sodium chloride in water to form a solution;
(b) adding a complexing agent to the solution of step (a);
(c) adjusting the pH of the solution of step (b) to about 2.7 to about 2.9;
(d) adding tiotropium or a pharmaceutically acceptable salt thereof;
(e) filtering the solution of step (d); and
(f) filling a container with the solution of step (e).
14. A prefilled container containing about 2 mL of an aqueous pharmaceutical composition comprising (i) from about 10 to about 80 μg of tiotropium bromide;
(ii) sodium chloride; and
(iii) about 0.01% by weight of disodium EDTA, wherein the composition is free of preservative, and the composition has a pH of from about 2.7 to about 2.9.
15. The prefilled container of claim 14 , wherein the sodium chloride is present at about 0.9% by weight.
16. The prefilled container of claim 15 , wherein the pH of the pharmaceutical composition is about 2.7.
17. The process of claim 13 , wherein the osmolality of the composition is 275 mOsm/kg to 325 mOsm/kg.
18. The prefilled container of claim 14 , wherein the osmolality of the pharmaceutical composition is 275 mOsm/kg to 325 mOsm/kg.
19. The composition of claim 6 , wherein (a) the complexing agent is present in an amount of about 0.01% by weight, (b) the composition comprises from about 10 to about 80 μg of tiotropium bromide, (c) the volume of the composition is about 2 mL, and (d) the pH of the composition is from about 2.7 to about 2.9.
20. A method of relieving bronchospasm associated with chronic obstructive pulmonary disease in a patient comprising administering to said patient the composition according to claim 19 .