Inhalable pharmaceutical compositions

Patent metadata

Field	Value
Publication number	US-10973763-B2
Application number	US-201213526333-A
Country	US
Kind code	B2
Filing date	Jun 18, 2012
Priority date	Jun 17, 2011
Publication date	Apr 13, 2021
Grant date	Apr 13, 2021

Abstract

Inhalable pharmaceutical compositions can include an aqueous dispersion of particles including a hydrophobic bioactive agent (e.g., CoQ10) suitable for continuous aerosolization. Due to their chemical composition and methods of manufacture, the pharmaceutical compositions exhibit distinctive physicochemical properties that provide advantageous aerosol transmission and output.

First claim

The invention claimed is:

1. An inhalable pharmaceutical composition comprising a dispersion of particles suitable for continuous aerosolization, the composition comprising:
a dispersion of particles having an average diameter between about 30 and 200 nm, each particle comprising Coenzyme Q10 (CoQ10), DPPC, and an aqueous dispersion vehicle,
wherein the CoQ10 is about 4% w/w of the composition, the phospholipid is about 2.5% w/w of the composition, and the particles are dispersed within the aqueous dispersion vehicle, and
wherein, upon administration to a subject, the composition is characterized by continuous aerosolization sufficient to provide a therapeutic dose of CoQ10 to the subject.

2. An inhalable pharmaceutical composition comprising a dispersion of particles suitable for continuous aerosolization, the composition comprising:
a dispersion of particles having an average diameter between about 30 and 200 nm, each particle comprising Coenzyme Q10 (CoQ10), DSPC, and an aqueous dispersion vehicle,
wherein the CoQ10 is about 4% w/w of the composition, the phospholipid is about 2.5% w/w of the composition, and the particles are dispersed within the aqueous dispersion vehicle, and
wherein, upon administration to a subject, the composition is characterized by continuous aerosolization sufficient to provide a therapeutic dose of CoQ10 to the subject.

3. An inhalable pharmaceutical composition comprising a dispersion of particles suitable for continuous aerosolization, the composition comprising:
a dispersion of particles having an average diameter between about 30 and 200 nm, each particle comprising Coenzyme Q10 (CoQ10), DMPC, and an aqueous dispersion vehicle,
wherein the CoQ10 is about 4% w/w of the composition, the phospholipid is about 2.5% w/w of the composition, and the particles are dispersed within the aqueous dispersion vehicle, and
wherein, upon administration to a subject, the composition is characterized by continuous aerosolization sufficient to provide a therapeutic dose of CoQ10 to the subject.

4. An inhalable pharmaceutical composition comprising a dispersion of particles suitable for continuous aerosolization, the composition comprising:
a dispersion of particles having an average diameter between about 30 and 200 nm, each particle comprising CoQ10, a phospholipid, and an aqueous dispersion vehicle,
wherein the CoQ10 is about 4% w/w of the composition, the phospholipid is about 2.5% w/w of the composition, and the particles are dispersed within the aqueous dispersion vehicle,
wherein the phospholipid is DPPC, DSPC, DMPC, or a combination thereof, and
wherein, upon continuous aerosolization, the composition is capable of achieving a CoQ10 concentration of at least about 500 μg/g wet lung tissue.

5. The inhalable pharmaceutical composition of claim 1 , wherein the aqueous dispersion vehicle comprises water or an aqueous salt solution.

6. The inhalable pharmaceutical composition of claim 1 , wherein the dispersion of particles is in the form of a continuous respirable aerosol comprising a plurality of aqueous droplets containing a dispersion of particles and having a mass median aerodynamic diameter (MMAD) between about 1 and 5 μm.

7. The inhalable pharmaceutical composition of claim 1 , wherein the composition has a polydispersivity index (PDI) of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, or 0.7.

8. The inhalable pharmaceutical composition of claim 1 , wherein the composition has a total aerosol output (TAO) of at least about 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100%.

9. The inhalable pharmaceutical composition of claim 1 , further comprising sodium chloride in an amount less than about 1.0% w/v of the composition.

10. The inhalable pharmaceutical composition of claim 1 , further comprising a salt in an amount making the composition essentially isosmotic with the human lung.

11. The inhalable pharmaceutical composition of claim 1 , wherein the dispersion is a suspension or an emulsion.

12. The inhalable pharmaceutical composition of claim 1 , wherein the continuous aerosolization has a duration of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 50, or 60 minutes.

13. The inhalable pharmaceutical composition of claim 1 , further comprising a polyoxypropylene-poloxyethylene block polymer at 0.001-5% by weight of the total composition.

14. The inhalable pharmaceutical composition of claim 1 , wherein the dispersion is a nano-suspension or microemulsion.

15. The inhalable pharmaceutical composition of claim 2 , wherein the aqueous dispersion vehicle comprises water or an aqueous salt solution.

16. The inhalable pharmaceutical composition of claim 2 , wherein the dispersion of particles is in the form of a continuous respirable aerosol comprising a plurality of aqueous droplets containing a dispersion of particles and having a mass median aerodynamic diameter (MMAD) between about 1 and 5 μm.

17. The inhalable pharmaceutical composition of claim 2 , wherein the composition has a polydispersivity index (PDI) of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, or 0.7.

18. The inhalable pharmaceutical composition of claim 2 , wherein the composition has a total aerosol output (TAO) of at least about 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100%.

19. The inhalable pharmaceutical composition of claim 2 , further comprising sodium chloride in an amount less than about 1.0% w/v of the composition.

20. The inhalable pharmaceutical composition of claim 2 , further comprising a salt in an amount making the composition essentially isosmotic with the human lung.

21. The inhalable pharmaceutical composition of claim 2 , wherein the dispersion is a suspension or an emulsion.

22. The inhalable pharmaceutical composition of claim 2 , wherein the continuous aerosolization has a duration of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 50, or 60 minutes.

23. The inhalable pharmaceutical composition of claim 2 , further comprising a polyoxypropylene-poloxyethylene block polymer at 0.001-5% by weight of the total composition.

24. The inhalable pharmaceutical composition of claim 3 , wherein the aqueous dispersion vehicle comprises water or an aqueous salt solution.

25. The inhalable pharmaceutical composition of claim 3 , wherein the dispersion of particles is in the form of a continuous respirable aerosol comprising a plurality of aqueous droplets containing a dispersion of particles and having a mass median aerodynamic diameter (MMAD) between about 1 and 5 μm.

26. The inhalable pharmaceutical composition of claim 3 , wherein the composition has a polydispersivity index (PDI) of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, or 0.7.

27. The inhalable pharmaceutical composition of claim 3 , wherein the composition has a total aerosol output (TAO) of at least about 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100%.

28. The inhalable pharmaceutical composition of claim 3 , further comprising sodium chloride in an amount less than about 1.0% w/v of the composition.

29. The inhalable pharmaceutical composition of claim 3 , further comprising a salt in an amount making the composition essentially isosmotic with the human lung.

30. The inhalable pharmaceutical composition of claim 3 , wherein the dispersion is a suspension or an emulsion.

31. The in

Assignees

• Narain Niven Rajin
• Mccook John Patrick
• Berg Llc

Inventors

• Narain Niven Rajin
• Mccook John Patrick

Classifications

• A61K9/0078 Primary

  for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions · CPC title

• G01N15/0205

  by optical means · CPC title

• A61K9/127 Primary

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K31/122

  having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin · CPC title

• G01N2015/0038

  Investigating nanoparticles · CPC title