PROPELLANTS FOR ANTICHOLINERGIC AGENTS IN PRESSURIZED METERED DOSE INHALERS
A composition comprising a solution comprising an active pharmaceutical ingredient comprising an anticholinergic agent, such as ipratropium bromide, and a propellant comprising HFA-152a, HFO-1234ze(E), or both. A metered dose inhaler comprising a metering valve a canister; and an actuator comprising an actuator nozzle; wherein the canister comprises said composition.
1 . A composition comprising:
a solution comprising:
an active pharmaceutical ingredient comprising an anticholinergic agent; and
a propellant comprising HFA-152a, HFO-1234ze(E), or both.
2 . The composition of claim 1 , wherein the anticholinergic agent comprises a long-acting muscarinic antagonist.
3 . The composition of claim 1 , wherein the anticholinergic agent is selected from ipratropium, tiotropium, aclidinium, umeclidinium, glycopyrronium, a pharmaceutically acceptable salt or ester of any of the listed drugs, or a mixture of any of the listed drugs, their pharmaceutically acceptable salts or their pharmaceutically acceptable esters.
4 . The composition of claim 1 , wherein the anticholinergic agent comprises a quaternary ammonium salt.
5 . The composition of claim 1 , wherein the anticholinergic agent is selected from ipratropium, tiotropium, glycopyrronium, and a pharmaceutically acceptable salt or ester of any of the listed drugs.
6 . A composition comprising:
a solution comprising:
ipratropium bromide; and
HFA-152a, HFO-1234ze(E), or both.
7 . The composition of claim 1 , wherein the active pharmaceutical ingredient consists essentially of ipratropium bromide.
8 . The composition of claim 1 , the solution further comprising ethanol.
9 . The composition of claim 8 , wherein ethanol is present at 5 wt-% to 22.5 wt-% of the total composition.
10 . The composition of claim 1 , the solution further comprising an acid.
11 . The composition of claim 1 , the solution further comprising water.
12 . The composition of claim 10 , wherein the acid is present at a concentration of 0.001 wt-% to 5 wt-% of the total composition.
13 . The composition of claim 11 , wherein water is present at 0.1 wt-% to 1 wt-% of the total composition.
14 . The composition of claim 1 , wherein HFA-152a, HFO-1234ze(E), or a combination thereof makes up 75 wt-% to 95 wt-% of the total composition.
15 . The composition of claim 1 , wherein the active pharmaceutical ingredient is present at 0.02 wt-% to 0.06 wt-% of the total composition.
16 . A composition comprising:
a solution comprising:
ipratropium bromide;
HFA-152a, HFO-1234ze(E), or both;
an acid;
water; and
ethanol.
17 . A metered dose inhaler comprising:
a metering valve;
a canister; and
an actuator comprising an actuator nozzle;
wherein the canister comprises the composition of claim 1 .
18 . The metered dose inhaler of claim 17 , wherein the metering valve comprises a metering chamber having a size between 25 microliters and 200 microliters.
19 . The metered dose inhaler of claim 17 , wherein the actuator has an exit orifice diameter between 0.12 mm and 0.4 mm.
20 . The metered dose inhaler of claim 17 , wherein the canister comprises from about 1 mL to about 30 mL of the composition.