We Claim,
1. A pharmaceutical composition for inhalation comprising salbutamol or
enantiomer or salt or ester thereof, a pharmaceutically acceptable green
propellant HFA-152a and/or HFO-1234ze(E), ethanol and oleic acid.
2. The pharmaceutical composition of claim 1; wherein the oleic acid is present
in a concentration between about 0.001 % to about 0.5% by weight of
composition.
3. The pharmaceutical composition of claim 2; wherein the oleic acid is present
in the concentration of about 0.03 % by weight of composition.
4. The pharmaceutical composition of claim 1; wherein the ethanol is present
in the concentration between 1% to 15% by weight of composition.
5. The pharmaceutical composition of claim 4; wherein the ethanol is present
in the concentration of about 15% by weight of composition.
6. The pharmaceutical composition of claim 1, wherein the composition is
administered using a pressurized metered dose inhaler or a breath actuated
inhaler or a nebulizer.
7. The pharmaceutical composition of claim 1, wherein the composition is in
the form of a suspension or a solution.
8. The pharmaceutical composition of claim 1, wherein salbutamol or
enantiomer or salt or ester thereof is salbutamol base, salbutamol sulphate,
levosalbutamol base, or levosalbutamol tartrate or levosalbutamol
hydrochloride.
9. The pharmaceutical composition of claim 8, wherein the salbutamol base or
salbutamol sulphate is present in the concentration ranging from 0.05% w/w
to 1% w/w or preferably between 0.1% w/w to 0.5%w/w or more preferably
between 0.2%w/w to 0.4%w/w of the composition.
10. The pharmaceutical composition of claim 8, wherein the levosalbutamol or
levalbuterol sulphate or levalbuterol tartrate or levalbuterol hydrochloride is
present in the concentration ranging from 0.05% w/w to 1% w/w or
77
preferably between 0.1% w/w to 0.5%w/w or more preferably between
0.2%w/w to 0.4%w/w of the composition.
11. The pharmaceutical composition of claim 1, wherein the pharmaceutically
acceptable green propellant HFA-152a.
12. The pharmaceutical composition of claim 11, wherein HFA-152a is present
in a concentration of at least 30% or 40% or 50% or 60% or 70% or 80% or
90% or 99% in the composition.
13. The pharmaceutical composition of claim 12, wherein HFA-152a is present
in a concentration of at least 90% in the composition.
14. The pharmaceutical composition of claim 11, wherein the composition
contains less than 1000 ppm of water based on the total weight of the
pharmaceutical composition.
15. The pharmaceutical composition of claim 14, wherein the composition
contains less than 0.5 ppm of water based on the total weight of the
pharmaceutical composition.
16. The pharmaceutical composition of claim 11, wherein the composition
contains less than 400 ppm of oxygen based on the total weight of the
pharmaceutical composition.
17. The pharmaceutical composition of claim 16, wherein the composition
contains less than 1 ppm of oxygen based on the total weight of the
pharmaceutical composition.
18. The pharmaceutical composition of claim 11, wherein the composition
contains less than 0.5 ppm of oxygen based on the total weight of the
pharmaceutical composition.
19. The pharmaceutical composition of claim 11, wherein the propellant HFA-
152a is more than 90% or 95% or 99% or 99.5% or 99.99% pure and does
not have any substantial impurities or free from any impurities.
20. The pharmaceutical composition of claim 11, wherein the HFA-152a is sole
propellant in the composition.
21. The pharmaceutical composition of claim 1, wherein the pharmaceutically
acceptable green propellant HFO-1234ze(E).
78
22. The pharmaceutical composition of claim 21, wherein the HFO-1234ze(E)
is present in the concentration of at least 30% or 40% or 50% or 60% or
70% or 80% or 90% or 99% in the composition.
23. The pharmaceutical composition of claim 22, wherein the HFO-1234ze(E)
is present in the concentration of at least 90% in the composition.
24. The pharmaceutical composition of claim 21, wherein the composition
contains less than 400 ppm of water based on the total weight of the
pharmaceutical composition.
25. The pharmaceutical composition of claim 24, wherein the composition
contains less than 0.5 ppm of water based on the total weight of the
pharmaceutical composition.
26. The pharmaceutical composition of claim 21, wherein the composition
contains less than 1000 ppm of oxygen based on the total weight of the
pharmaceutical composition.
27. The pharmaceutical composition of claim 26, wherein the composition
contains less than 1 ppm of oxygen based on the total weight of the
pharmaceutical composition.
28. The pharmaceutical composition of claim 21, wherein the composition
contains less than 0.5 ppm of oxygen based on the total weight of the
pharmaceutical composition.
29. The pharmaceutical composition of claim 21, wherein the propellant HFO-
1234ze(E) is more than 90% or 95% or 99% or 99.5% or 99.99% pure and
does not have any substantial impurities or free from any impurities.
30. The pharmaceutical composition of claim 29, wherein the propellant HFO-
1234ze(E) contains less than 0.5 to 10 ppm of unsaturated impurities or less
than 0.25ppm of unsaturated impurities.
31. The pharmaceutical composition of claim 29, wherein the propellant HFO-
1234ze(E) contains less than 10ppm of HFO-1234ze(Z).
32. The pharmaceutical composition of claim 231, wherein the propellant HFO-
1234ze(E) contains less than 5ppm of HFO-1234ze(Z).
79
33. The pharmaceutical composition of claim 11, wherein the composition
when administered using the metered dose inhaler produces a fine particle
mass of the salbutamol or enantiomer or salt or ester thereof with less
variability having relative standard deviation of less than 6% over shelf life
as compared to the composition comprising salbutamol or enantiomer or salt
or ester thereof and a propellant HFA-134a or HFA-227ea.
34. The pharmaceutical composition of claim 21, wherein the composition
when administered using the metered dose inhaler produces a fine particle
mass of the salbutamol or enantiomer or salt or ester thereof with less
variability having relative standard deviation of less than 6.5% over shelf
life as compared to the composition comprising salbutamol or enantiomer
or salt or ester thereof and a propellant HFA-134a or HFA-227ea.
35. A pharmaceutical composition for inhalation comprising salbutamol
sulphate or levosalbutamol tartrate or levosalbutamol hydrochloride, a
pharmaceutically acceptable green propellant HFA-152a and HFO-
1234ze(E) and oleic acid; wherein oleic acid is present in concentration of
about 0.03 % by weight of composition.
36. The pharmaceutical composition of claim 35, wherein (a) HFA-152a is
present in about 50% by weight of composition and HFO-1234ze(E) is
present in about 50% by weight of composition or (b) HFA-152a is present
in about 30% by weight of composition and HFO-1234ze(E) is present in
about 70% by weight of composition, or (c) HFA-152a is present in about
70% by weight of composition and HFO-1234ze(E) is present in about 30%
by weight of composition.
37. The pharmaceutical composition of claim 35, wherein the composition
further comprises ethanol and is present in the concentration between 1% to
15% by weight of composition.
38. The pharmaceutical composition of claim 37; wherein the ethanol is present
in the concentration of about 15% by weight of composition.
39. A pharmaceutical composition for inhalation comprising salbutamol
sulphate or levosalbutamol tartrate or levosalbutamol hydrochloride, a
80
pharmaceutically acceptable green propellant HFA-152a and HFO-
1234ze(E), ethanol and oleic acid; wherein oleic acid is present in
concentration of about 0.03 % and ethanol is present in concentration of
about 15% by weight of composition.
40. The pharmaceutical composition of claim 39, wherein (a) HFA-152a is
present in about 50% by weight of composition and HFO-1234ze(E) is
present in about 50% by weight of composition, or (b) HFA-152a is present
in about 30% by weight of composition and HFO-1234ze(E) is present in
about 70% by weight of composition, or (c) HFA-152a is present in about
70% by weight of composition and HFO-1234ze(E) is present in about 30%
by weight of composition.