Canadian Patents Database

Claims page

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Patent Document Number: 2468958

(54) English Title: PULMONARY DELIVERY OF AMINOGLYCOSIDES

(54) French Title: ADMINISTRATION PULMONAIRE D'AMINOGLYCOSIDES

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Claims:

Note: Claims are shown in the official language in which they were submitted.




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WHAT IS CLAIMED IS


1. A dispersible dry powder composition for localized delivery to the lungs of
a
human patient for the treatment or prevention of respiratory infections, said
composition
comprising particles comprising an aminoglycoside or a pharmaceutically
acceptable salt
thereof and a phospholipid, wherein
- the particles have a geometric diameter from 0.5 - 5 microns,
- the particles have a mass median aerodynamic diameter of less than 5
microns,
- the composition has a bulk density of greater than 0.08 g/cm3,
- wherein the aminoglycoside or the pharmaceutically acceptable salt thereof
is
present in an amount of at least 50% by weight
- the composition is provided in the form of unit doses and the fill mass of
the
composition in one unit dose is at least 20 mg,
- the composition provides an emitted dose of at least 70% per unit dose, and
- less than 6 of said unit doses containing the composition deliver a
therapeutically effective amount of aminoglycoside to the lungs of said
patient
when administered by a dry powder inhalation device.


2. A composition according to claim 1 wherein the aminoglycoside or a
pharmaceutically acceptable salt thereof is present in an amount of at least
60% by
weight.


3. A composition according to claim 6 wherein the aminoglycoside or a
pharmaceutically acceptable salt thereof is present in an amount from about
80% to 95%
by weight.


4. A composition according to claim 1 wherein the aminoglycoside is selected
from
the group consisting of gentamicin, netilmicin, paramecin, tobramycin,
amikacin,
kanamycin, neomycin, azithromycin, streptomycin and their pharmaceutically
acceptable
salts.


5. A composition according to claim 1 having a residual moisture content of
less
than 15 % by weight.




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6. A composition according to claim 5 wherein the residual moisture content is
less
than 8 % by weight.


7. A composition according to claim 1, wherein the fill mass of the
composition in
one unit dose is at from 20 mg to 50 mg.


8. A composition according to claim 1 wherein the particles have a mass median

aerodynamic diameter of less than 4.0 microns.


9. A composition according to claim 1 wherein the emitted dose is at least
80%.


10. A composition according to claim 1 wherein the aminoglycoside is
tobramycin or
a pharmaceutically acceptable salt thereof.


11. A composition according to claim 10 comprising at least 75% w/w tobramycin
or
a pharmaceutically acceptable salt thereof.


12. A composition according to claim 11 comprising at least 85% w/w tobramycin
or
a pharmaceutically acceptable salt thereof.


13. A composition according to claim 11 comprising up to 20% w/w of a
phospholipid.


14. A composition according to claim 1 comprising at least 75% by weight of
tobramycin or a pharmaceutically acceptable salt thereof, 2-25% w/w of the
phospholipid, and 0-5% w/w of calcium chloride,


15. A composition according to claim 14, wherein the phospholipid is DSPC.


16. A composition according to claim 14 comprising a bulk density of greater
than
0.10 g/cm3.


17. A composition according to claim 16 comprising a bulk density of greater
than
0.12 g/cm3.


18. A composition according to claim 1, wherein one unit dose of said
composition is




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provided as a capsule comprising a volume corresponding to a size #00 capsule,
a size #0
capsule, a size #1 capsule, a size #2 capsule or a size #3 capsule.


19. A composition according to claim 18, wherein one unit dose of said
composition
is provided as a capsule comprising a volume corresponding to a size #2
capsule.


20. A composition according to claim 1, wherein the particles have a hollow
and
porous morphology.


21. A composition according to claim 11 comprising a tobramycin potency of
greater
than 60%.


22. A composition according to any one of claims 1-21, wherein the particles
are
prepared by spray-drying.


23. A composition according to claim 22 wherein the particles are prepared
using an
emulsification - spray-drying process.


24. A use of the composition defined in any one of claims 1-23, for delivery
of the
aminoglycoside to the lungs of a human patient by inhalation wherein the
composition is
in aerosolized form.


25. The use according to claim 24, wherein the composition is for
administration by
means of a dry powder inhaler.


26. The use according to claim 24 or 25, wherein the composition is for
dispersal into
a gas stream to form a dry powder aerosol from a dry powder inhalation device
from less
than 6 unit doses; and the dry powder is for pulmonary delivery to a patient
at an emitted
dose of at least 70%.


27. The use according to claim 26, wherein said dry powder composition is
provided
in unit doses that each comprise 10 - 60 mg of aminoglycoside.


28. The use according to claim 27, wherein less than 6 unit doses provide a
therapeutically effective amount of aminoglycoside throughout a 24 hour
period.




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29. The use according to claim 28, wherein less than 4 unit doses provide a
therapeutically effective amount of aminoglycoside throughout a 24 hour
period.