Soft mist inhaler

Abstract

An aerosol dispensing system for a liquid medication (8) for inhalation is provided. The system comprises: - a first container (1) for a gas (4), having a first movable wall (5); - a heating element (3) for heating the gas in the first container; - a second container (2) for the liquid medication having an outlet (9) with one or more apertures and a second movable wall (7); and - a shaft (6) that connects the first and second movable walls. When the gas in the first container is heated, the gas expands against the first movable wall thereby displacing the shaft and hence the second movable wall, to force the liquid medication out through the outlet to form an aerosol for inhalation.

Description

[0001] Soft Mist Inhaler

[0002] Technical Field of the Invention

[0003] The present invention relates to a soft mist inhaler containing an active substance for inhalation. In particular, the invention relates to an inhaler that is easy for a patient to use and that produces a consistent aerosol droplet size.

[0004] Background to the Invention

[0005] A soft mist inhaler (for example, the Respimat® inhaler marketed by Boehringer Ingleheim) is a respiratory medical device that delivers liquid medication as a fine mist. Benefits of soft mist inhalers include a propellant-free drug formulation, less demand from patients to coordinate actuation and inhalation, and an increase in drug deposition deeper into the lungs because the mist comes out more slowly and lasts longer in the air compared to pressurized metered dose inhalers (pMDIs).

[0006] Many soft mist inhalers have a spring that is primed by the patient through twisting the device causing the spring to compress. The spring in its compressed state has potential energy which can be used to aerosolize the drug. When the patient is ready, they press a dose release button which allows the spring to expand back to its original state while driving a piston that forces the liquid medication through a fine nozzle. The resulting droplets come out of the inhaler slowly as a mist. In the Respimat® inhaler, the mist is created by a block which splits the liquid medication into two streams that form converging jets. These jets collide at a specific angle at the outlet, atomizing the drug into a mist.

[0007] A disadvantage of soft mist inhalers is that the patient has to prime the inhaler before use, which may be difficult for patients who have manual dexterity issues or cognitive impairment, e.g. elderly persons. Furthermore, the droplet size may depend on the force applied by spring, and thus may change during the course of an actuation. For example, the droplets may be larger towards the end of the actuation, as the force applied by the spring reduces. Thus, there remains a need for soft mist inhalers that are easier for patients to use, and that provide a more uniform droplet size. Brief description of the invention

[0008] The present invention provides an aerosol dispensing system for a liquid medication for inhalation comprising:

[0009] • a first container for a gas having a first movable wall;

[0010] • a heating element for heating the gas in the first container;

[0011] • a second container for the liquid medication having an outlet with one or more apertures and a second movable wall;

[0012] • a shaft that connects the first and second movable walls; so that when the gas in the first container is heated, the gas expands against the first movable wall, thereby displacing the shaft and hence the second movable wall, to force the liquid medication out through the outlet to form an aerosol for inhalation.

[0013] The heating element may be powered by a battery that is rechargeable and / or replaceable. The heating element may be a resistive, inductive, or dielectric heating element.

[0014] The first container may be insulated.

[0015] The aerosol dispensing system may have a sensor to detect the temperature or pressure of the gas within the first container and a controller to control the power supplied to the heating element.

[0016] The first container may further contain a liquid that has a boiling point in the range of about 25-60°C.

[0017] The first and second containers may be cylindrical and the diameter of the first container may be larger than the diameter of the second container. For example, the diameter of the first container may be from 20 to 80mm, preferably 40 to 60 mm and the diameter of the second container may be from 3 to 10mm, preferably 4 to 8 mm.

[0018] The apertures may be from 0.5 to 25 pm in diameter, preferably from 1 to 10 pm, more preferably from 2 to 8 pm. In one embodiment, the outlet has at least 10, preferably at least 100 apertures and may be in the form of a mesh or perforated membrane. In another embodiment, the outlet has two or more apertures that create impinging jets to form the aerosol. In a further embodiment, the outlet has one or more channels that create an oscillating jet to form the aerosol.

[0019] Brief Description of the Figures

[0020] The invention will now be further described with reference to Figure 1, which is a schematic diagram of a soft mist inhaler according to the invention.

[0021] Detailed Description of the Invention

[0022] Figure 1 shows an inhalation device according to the invention having two compartments: an insulated gas container 1 and a liquid medication container 2, each having a cylindrical shape with differing dimensions. An electric heating element 3 is located in the insulated gas container 1. It is powered by a battery (not shown) that provides the current for activation. The battery is preferably rechargeable and / or replaceable. The insulated gas container 1 and the liquid medication container 2 have movable walls 5,7 respectively. The movable walls 5,7 are connected by a shaft 6.

[0023] Upon activation, the heating element increases the temperature and pressure of the gas 4 (which may be air or may comprise air) inside the insulated gas container 1. The pressurized gas exerts force against the movable wall 5, thereby displacing the shaft 6 and hence the other movable wall 7. Motion of the wall 7 forces the liquid medication 8 through an outlet 9 which has one or more fine apertures to form an aerosol mist 10. The device has a patient interface, such as a mouthpiece, nose piece or face mask (not shown) which delivers the aerosol mist to the patient’s airways.

[0024] The apertures may be provided by a fine mesh or a perforated membrane. The apertures may be small channels that create impinging microjets. Alternatively, a fluidic oscillator mechanism may be used to create the mist. This mechanism can generate an oscillating jet spray without any moving parts by directing the liquid medication through an aperture with a feedback channel on either side. The Coanda effect causes the jet to attach to one side of the channel. The feedback channel on that side directs a portion of the liquid back to the aperture, creating a vortex. As the vortex grows bigger, it pushes the jet to the other side of the channel, where the process repeats, so that the jet oscillates from side to side.

[0025] The gas container 1 is insulated to prevent the liquid medication from heating up, because active pharmaceutical ingredient(s) (APIs) in the liquid medication are often degraded by heat. Effective insulation not only preserves the integrity of the APIs but also mitigates heat loss, thereby enhancing the overall efficiency of the system.

[0026] Efficient mist formation can be achieved without excessive heating of the gas 4 by creating a mechanical advantage. This is achieved by making the area of the movable wall 5 of the insulated gas container greater than that of the movable wall 7 of the liquid medication container 2 to ensure that the temperature of the gas remains within manageable limits. The smaller diameter of the liquid medication container 2 creates a higher pressure for a given applied force, while the larger diameter of the insulated gas container 1 requires a lower pressure to achieve an equivalent force. As a result, a lower gas temperature is required to create the aerosol mist than if the areas of the movable walls were equal.

[0027] The initial (Pi, Vi, Ti) and subsequent (P2, V2, T2) pressure, volume and temperature of the gas 4 in the insulated gas container 1 are related by the ideal gas law, Equation 1 :

[0028] Typically, a pressure drop (AP) of about 10 atmospheres across a fine mesh is required to create the aerosol mist. If the movable wall 7 of the liquid medication container 2 has a cross-sectional area a, the force (F) that needs to be applied to the movable wall 7 to create the aerosol mist is given by Equation 2:

[0029] F

[0030] - = AP a

[0031] The pressure in the insulated gas container 1 to create this force is given by Equation 3: = (P2- Po) x A where A is the cross-sectional area of moveable wall 5 and Po is the external atmospheric pressure (which acts against the internal pressure).

[0032] The volume of liquid that is aerosolized in each actuation of the device is quite small (for example from 1 to 500 pL, such as 15 to 250 pL or from 25 to 150 pL, typically < 100 pL) so the movable walls do not move very far. Consequently, the change in the volume of the insulated gas container is very small, so V2 can be approximated as being equal to Vi. If the initial pressure in the insulated gas container (Pi) is atmospheric pressure (Po), the final temperature of the gas can be estimated by combining Equations 1, 2 and 3 into Equation 4:

[0033] For movable walls 5, 7 with diameters of 5mm and 50mm respectively, the final temperature (T2) of the gas 4 is calculated to be approximately 50°C. Increasing the ratio (A / a) of the areas of the movable walls 5, 7 reduces the final temperature, and vice versa.

[0034] The mechanical advantage can be chosen according to the viscosity and volume of the liquid that is aerosolized. Liquids with relatively high viscosity typically require a greater pressure drop across the aperture(s) for aerosolization, so a larger mechanical advantage is required. On the other hand, a smaller mechanical advantage is preferable if a very large volume of liquid is to be aerosolized.

[0035] The insulated gas container may contain (in addition to the gas) a liquid that has a boiling point in the range of about 25-60°C, such as acetone or ether. When the liquid is heated, it evaporates due to its low boiling point. This rapidly increases the pressure inside the insulated gas container because of the sudden increase in volume when the liquid changes its state to a gas.

[0036] The shaft may be retractable after the liquid medication has been forced out through the outlet and the second container may be refillable with liquid medication after use.

[0037] The key feature of the invention is that it uses gas pressure to provide the force that is required to create the aerosol mist instead of a compressed spring, as in known soft mist inhalers. This means that the user does not need to prime the inhaler for use, because the necessary energy is stored in a battery. The patient only needs to press a button to activate the heater, rather than, for example, twisting the inhaler to compress a spring.

[0038] Moreover, the force, and hence the rate of aerosol generation, can be easily controlled by heating the gas in the insulated gas container to a preset temperature / time profile. A sensor for detecting the temperature or pressure of the gas within the first container may provide feedback to a controller in order to control the power supplied to the heating element by the battery. An approximately constant pressure can thereby be maintained throughout the actuation of the inhalation device so that the aerosol is generated at a steady rate and has a constant droplet size. In contrast, in a typical soft mist inhaler, the pressure created by the spring decreases towards the end of the actuation so the droplet size may increase and / or the rate of aerosol generation may decrease.

[0039] A breath-actuated mechanism may be added to the device so that as the patient inhales on the mouthpiece, the heating element is automatically turned on to pressurize the gas and generate the aerosol. This could be achieved by using a pressure sensor in the patient interface (e.g. a mouthpiece), so that power is supplied to the heating element when the pressure drops below a predetermined threshold value as the patient starts to inhale.

Claims

Claims1 . An aerosol dispensing system for a liquid medication for inhalation comprising:• a first container for a gas, having a first movable wall;• a heating element for heating the gas in the first container;• a second container for the liquid medication having an outlet with one or more apertures and a second movable wall; and• a shaft that connects the first and second movable walls; so that when the gas in the first container is heated, the gas expands against the first movable wall thereby displacing the shaft and hence the second movable wall to force the liquid medication out through the outlet to form an aerosol for inhalation.

2. The aerosol dispensing system according to claim 1, wherein the first container is insulated.

3. The aerosol dispensing system according to claim 1 or claim 2, wherein the heating element is powered by a battery that is rechargeable and / or replaceable.

4. The aerosol dispensing system according to any of claims 1 to 3, wherein the heating element is a resistive, inductive, or dielectric heating element.

5. The aerosol dispensing system according to any of claims 1 to 4, which has a sensor to detect the temperature or pressure of the gas within the first container and a controller to control power supplied to the heating element.

6. The aerosol dispensing system according to any of claims 1 to 5, wherein the first container contains a liquid which has a boiling point in the range of about 25-60°C.

7. The aerosol dispensing system according to any of claims 1 to 6, wherein the first and second containers are cylindrical and wherein the diameter of the first container is larger than the diameter of the second container.

8. The aerosol dispensing system according to claim 7, wherein the diameter of the first container is from 20 - 80mm and the diameter of the second container is from 3 - 10 mm.

9. The aerosol dispensing system according to claim 8, wherein the diameter of the first container is from 40 - 60 mm.

10. The aerosol dispensing system according to claim 9, wherein the diameter of the second container is from 4 - 8 mm.1 1 . The aerosol dispensing system according to any of claims 1 to 10, wherein the apertures are from 0.5 to 25 pm in diameter.

12. The aerosol dispensing system according to claim 11, wherein the apertures are from 1 to 10 pm in diameter.

13. The aerosol dispensing system according to any of claims 1 to 12, wherein the outlet has at least 10 apertures, such at least 100 apertures, and is in the form of a mesh or perforated membrane.

14. The aerosol dispensing system according to any of claims 1 to 12, wherein the outlet has two or more apertures that create impinging jets to form the aerosol.

15. The aerosol dispensing system according to any of claims 1 to 12, wherein the outlet has one or more apertures that create an oscillating jet spray to form the aerosol.

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