METERED DOSE INHALERS AND SOLUTION COMPOSITIONS

1 . A metered dose inhaler comprising:

a metering valve;

a canister; and

an actuator comprising an actuator nozzle;

wherein the canister comprises a formulation, the formulation comprising greater than 70% by weight of propellant HFO-1234ze(E), and at least one active pharmaceutical ingredient dissolved in the formulation to form a solution.

2 . The inhaler of claim 1 , wherein the active pharmaceutical ingredient is selected from beta agonists, corticosteroids, anticholinergic agents, TYK inhibitors, and combinations thereof.

3 . The inhaler of claim 2 , wherein the corticosteroid is selected from beclomethasone and ciclesonide.

4 . The inhaler of claim 2 , wherein the anticholinergic agent is selected from ipratropium, tiotropium, aclidinium, umeclidinium, and glycopyrronium.

5 . The inhaler of claim 2 , wherein the beta agonist is selected from formoterol, indacaterol, olodaterol, vilanterol, and abediterol.

6 . The inhaler of claim 1 , wherein the formulation comprises at least two active pharmaceutical ingredients in solution.

7 . The inhaler of claim 6 , wherein one active pharmaceutical ingredient is a short- or long-acting beta agonist and one active pharmaceutical ingredient is a corticosteroid in solution.

8 . The inhaler of claim 7 , wherein the formulation further comprises an anticholinergic agent in solution.

9 . A metered dose inhaler comprising:

a metering valve;

a canister; and

an actuator comprising an actuator nozzle;

wherein the canister comprises a formulation, the formulation comprising a propellant comprising HFO-1234ze(E), and an active pharmaceutical ingredient comprising:

beclomethasone or a pharmaceutically acceptable salt or ester thereof, wherein the beclomethasone or pharmaceutically acceptable salt or ester thereof is dissolved in the formulation to form a solution; and/or

formoterol or a pharmaceutically acceptable salt or ester thereof, wherein the formoterol or pharmaceutically acceptable salt or ester thereof is dissolved in the formulation to form a solution.

10 . (canceled)

11 . (canceled)

12 . A metered dose inhaler comprising:

a metering valve;

a canister; and

an actuator comprising an actuator nozzle;

wherein the canister comprises a formulation, the formulation comprising a propellant comprising HFO-1234ze(E), and an active pharmaceutical ingredient comprising tiotropium or a pharmaceutically acceptable salt or ester thereof, wherein the tiotropium or pharmaceutically acceptable salt or ester thereof is dissolved in the formulation to form a solution.

13 . The inhaler of claim 1 , wherein HFO-1234ze(E) is the sole propellant.

14 . The inhaler of claim 1 , wherein the formulation further comprises ethanol.

15 . The inhaler of claim 14 , wherein the amount of ethanol by weight of the total formulation is between 5% and 20%.

16 . The inhaler of claim 1 , wherein the formulation further comprises an organic acid, an inorganic acid, or a combination thereof.

17 . The inhaler of claim 16 , wherein the formulation comprises 0.04% to 0.4% acid by weight of the total formulation.

18 . The inhaler of claim 1 , wherein the metering valve comprises a metering chamber having a size between 25 microliters and 200 microliters.

19 . The inhaler of claim 1 , which does not comprise coated internal components.

20 . The inhaler of claim 1 , wherein the actuator nozzle comprises an exit orifice effective diameter of 0.12 mm to 0.3 mm.

21 . The inhaler of claim 16 , wherein the formulation comprises citric acid.

22 . The inhaler of claim 9 , wherein the amount of HFO-1234ze(E) by weight of the total propellant in the formulation is at least 90%.