Tiotropium dry powders
The present invention relates to respirable dry powder comprising respirable dry particles that comprise sodium chloride, leucine, and tiotropium bromide, wherein the sodium chloride is about 60% to about 90%, the leucine is about 10% to about 40%, the tiotropium bromide is about 0.01% to about 0.5%, and optionally one or more additional therapeutic agents up to about 20%, wherein all percentages are weight percentages on a dry basis and all the components of the respirable dry particles amount to 100%. The invention also relates to respirable dry powders that contain respirable dry particles that comprise sodium chloride, leucine, and tiotropium bromide, wherein the sodium chloride is 67% to 84%, the leucine is 12% to 28%, the tiotropium bromide is about 0.01% to about 0.5%, and optionally one or more additional therapeutic agents up to about 20%, wherein all percentages are weight percentages on a dry basis and all the components of the respirable dry particles amount to 100%. The invention also relates to respirable dry powders that contain respirable dry particles that comprise about 79.5% to about 80.5% (w/w) sodium chloride, about 19.5% to about 20.5% (w/w) leucine, and about 0.01% to about 0.5% (w/w) tiotropium bromide, and methods for treating a subject using the respirable dry powders.
1. A receptacle comprising a respirable dry powder consisting of homogenous respirable dry particles that comprise sodium chloride, leucine, and tiotropium bromide, wherein the sodium chloride is 67% to 84% by weight, the leucine is 12% to 28% by weight, the tiotropium bromide is about 0.01% to about 0.5% by weight, and optionally one or more additional therapeutic agents up to about 20% by weight, wherein all percentages are weight percentages on a dry basis and all the components of the respirable dry particles amount to 100%, wherein the receptacle contains a nominal dose of tiotropium between about 1.5 to about 12 micrograms.
2. The receptacle of claim 1 , wherein the receptacle is a capsule or a blister, and wherein the receptacle contains about 15 mg of dry powder or less.
3. The receptacle of claim 1 , wherein the receptacle contains a nominal dose of tiotropium between about 3 to about 12 micrograms.
4. The receptacle of claim 1 , wherein the receptacle contains a nominal dose of tiotropium between about 3 to about 9 micrograms.
5. The receptacle of claim 1 , wherein the receptacle contains a nominal dose of tiotropium between about 3 to about 6 micrograms.
6. The receptacle of claim 1 , wherein the respirable dry powder has a fine particle dose less than 5.0 microns of between about 1 microgram and about 5 micrograms of tiotropium.
7. The receptacle of claim 1 , wherein the respirable dry powder has a fine particle dose less than 4.4 microns of between about 1 microgram and about 4 micrograms of tiotropium.
8. The receptacle of claim 1 , wherein the respirable dry powder has a fine particle dose less than 4.4 microns of between about 1.5 micrograms and about 3.5 micrograms of tiotropium.
9. The receptacle of claim 1 , wherein the receptacle is a capsule, and wherein the capsule contains less than 6 mg of dry powder.
10. The receptacle of claim 1 , wherein the sodium chloride is about 79.5% to about 80.5% by weight and the leucine is about 19.5% to about 20.5% by weight.
11. The receptacle of claim 1 , wherein the respirable dry particles have a volume median geometric diameter (VMGD) of about 5 micrometers or less.
12. The receptacle of claim 1 , wherein the respirable dry powder has a mass median aerodynamic diameter (MMAD) of between about 1 micron and about 5 microns.
13. The receptacle of claim 1 , wherein the respirable dry particles have a 1/4 bar dispersibility ratio (1/4 bar) of less than 1.5 as measured by laser diffraction.
14. The receptacle of claim 1 , wherein the respirable dry particles have a tap density greater than 0.4 g/cc to about 1.2 g/cm 3 .
15. The receptacle of claim 1 , wherein the one or more additional therapeutic agent is one or more corticosteroids.
16. A receptacle comprising a respirable dry powder consisting of homogenous respirable dry particles that comprise sodium chloride, leucine, and tiotropium bromide, wherein the sodium chloride is 67% to 84% by weight, the leucine is 12% to 28% by weight, the tiotropium bromide is about 0.01% to about 0.5% by weight, and optionally one or more additional therapeutic agents up to about 20% by weight, wherein all percentages are weight percentages on a dry basis and all the components of the respirable dry particles amount to 100%, wherein the receptacle contains a nominal dose of tiotropium between about 0.5 to about 6 micrograms.
17. The receptacle of claim 16 , wherein the receptacle contains a nominal dose of tiotropium between about 0.5 microgram to about 3 micrograms.
18. The receptacle of claim 16 , wherein the respirable dry powder has a fine particle dose less than 5.0 microns of between about 1 microgram and about 5 micrograms of tiotropium.
19. The receptacle of claim 1 , wherein the respirable dry powder has a fine particle dose less than 4.4 microns of between about 1.5 micrograms and about 3.5 micrograms of tiotropium.
20. A method for treating a respiratory disease selected from the group consisting of COPD, chronic bronchitis, emphysema, asthma, cystic fibrosis, or non-cystic fibrosis bronchiectasis, comprising administering to the respiratory tract of a patient in need thereof an effective amount of a respirable dry powder of claim 1 .
21. A method for treating or reducing the incidence or severity of an acute exacerbation of a respiratory disease selected from the group consisting of COPD, chronic bronchitis, emphysema, asthma, cystic fibrosis, or non-cystic fibrosis bronchiectasis, comprising administering to the respiratory tract of a patient in need thereof an effective amount of a respirable dry powder of claim 1 .
22. The method of claim 20 , wherein the respiratory disease is COPD.
23. A dry powder inhaler that contains the receptacle of claim 1 , wherein the dry powder inhaler is a capsule-based dry powder inhaler or a blister-based dry powder inhaler.