NL2023033B1

NL2023033B1 - Spray inhaler device

Info

Publication number: NL2023033B1
Application number: NL2023033A
Authority: NL
Inventors: Petrus Johannes De Kruijf Wilhelmus; Johannes Maria Van Rijn Cornelis; Nijdam Wietze; Joseph Van Egmond Henri
Original assignee: Medspray B V
Priority date: 2019-04-30
Filing date: 2019-04-30
Publication date: 2020-11-23

Abstract

A spray inhaler device comprises a container (10) for holding a fluid to be sprayed together with pressurizing means (20) for pressuring said fluid. Spraying means comprises a spray nozzle (30) for releasing a spray of said fluid beyond a threshold pressure of said fluid. An outlet section (40) having a substantially hollow aerosol chamber (35) is open at opposite ends in which said spraying means release said spray along a spray path (Pl). Airflow means are provided for carrying an airflow through said aerosol chamber (35) along an airflow path (P2) that at least partly coincides with said spray path (Pl). Said outlet section (40) is provided with at least one screen member (50,60) having a screen portion (52,61,62) that crosses said airflow path (P2) to deflect at least part of said airflow during operation. Said spray path (Pl) passes said screen portion of said member to allow a passage of at least part of said spray along said spray path in the absence of said airflow.

Description

Spray inhaler device The present invention relates to a spray inhaler device, comprising a reservoir for holding a fluid to be sprayed, pressurizing means for pressuring said fluid, spraying means that comprise a spray nozzle for releasing a spray of said fluid, an outlet section having a substantially hollow aerosol chamber that is open at opposite ends to receive said spray along a spray path, and airflow means for carrying an airflow through said aerosol chamber along an airflow path that at least partly coincides with said spray path.

Such an inhaler device is commonly used for administering a pharmaceutically active compound to the respiratory system of a user. A liquid that contains said compound is being held in the container of said spray inhaler device and is being pressurized by appropriate pressure means, like a pump or a suitable propellant, to deliver said liquid at a pressure above said threshold pressure at an inlet of said spray nozzle unit. The nozzle then generates a fine spray of distributed droplets that is released into said aerosol chamber along a spray path. This spray path coincides with an airflow path of an airflow that is built up and maintained in said aerosol chamber, for instance by the user inhaling ambient air through said aerosol chamber. As a consequence the spray droplets will be carried along with said flow of air to finally enter the respiratory system of the user. Spray inhaler devices of the aforementioned kind are generally referred to as soft mist inhalers {SMI}, metered dose inhalers (MDI) and aerosol inhalers.

It is an object of any of these inhaler devices to deliver as much as possible of the sprayed liquid at the intended target in the respiratory system, notably into {a certain region of) the pulmonary zone, trachea or bronchi of the user and as little as possible into the oral cavity. This not only enhances the dosing efficiency of the active compound, but also avoids irritation and a distasteful taste within the oral cavity due to the relevant liquid. It has been found that, at a certain airflow velocity, a landing spot of a spray droplet is predominantly determined by its size, i.e. mass. Accordingly, the spray droplets that are being generated by said spray nozzle preferably feature a relatively narrow droplet size distribution such that they will predominantly all hit the same target area.

2. The spray inhaler device according to the invention, accordingly, particularly relates to a device for generating a so-called micro-jet spray of very fine droplets, having a controlled pre-defined size, from a pressurized liquid.

Such micro-jet spray may contain many emitting jets, emanating from individual nozzle orifices, in which each jet will initially breakup into a mono disperse primary droplet train according to the so-called Rayleigh breakup mechanism.

As a result,

consecutive primary droplets have a same size and propagate from the nozzle orifice in a same direction, typically the diameter of the primary droplet is 1,85-2,0 times the diameter of the nozzle orifice.

Often the corresponding nozzle orifices are provided in a planar substrate yielding jets that are all directed in a same or varying spraying direction, depending on the specific nozzle configuration.

Due to possible coalescence of mutually interfering droplets the average droplet size within the spray may eventual grow and, likewise, also the droplet size distribution of the spray may spread.

It as an object of the invention to shape the droplet size distribution of the spray that is carried into the respiratory system to within narrower boundaries.

In practice, it turns out often necessary to activate the pressure means before inhaling through the device.

By this, so called, priming of the device a liquid channel between the container and the nozzle device is being filled and the liquid pressure is built up to exceed the threshold pressure.

It is a further object of the invention to allow appropriate priming of the device prior to first use.

In order to achieve said first and further object, a spray inhaler device of the type described in the opening paragraph according to the invention is characterized in that outlet section is provided with at least one screen member that extends into said aerosol chamber and crosses said airflow path to deflect at least part of said airflow during operation, and in that said spray path passes said screen member to allow a passage of at least part of said spray along said spray path in the absence of said airflow.

By deflecting the airflow during operation, said screen forces droplets within said spray into separate trajectories, depending on the mass, hence size,

of the individual droplets.

Larger/heavier droplets may not be able to follow the deflected path that is imposed by said screen on the airflow and, hence, these droplets will be eliminated from the spray that is

3- delivered at the outlet of the aerosol chamber of the device. As the same screen member is configured to allow a passage of said spray along said spray path, the screen member allows said spray to follow said spray path all along its way through the aerosol chamber during priming when there is no or hardly no airflow from the airflow means. As a result the spray inhaler device delivers a narrowed droplet size distribution within the aerosol that it delivers while enabling priming at startup. In a special embodiment, the spray inhaler device according to the invention is characterized in that said at least one screen member crosses said airflow path while having a void at a location of said spray path to allow a substantially free passage of said spray through said void in the absence of said airflow. The screen member, in this case, may cross both the airflow path and the spray path but by having a void at the spray path nonetheless allows at least part of the spray that is generated by the spray nozzle to reach the outlet during priming.

The screen member may be configured in different manners. in a preferred embodiment, the spray inhaler device according to the invention is characterized in that said at least one screen member comprises a pair of mutually opposing baffles, extending from opposite walls of said chamber over part of a distance between said opposite walls of said chamber and being placed at a mutual distance along said airflow path. Said baffles may extend over a full width of the aerosol chamber, said width being defined perpendicular to the length over which the baffles extend between both said walls. What is important that they will allow the spray that is generated by the spray nozzle to reach the outlet during priming of the device, i.e. when there is no or hardly no air flow from the airflow means.

In a further special embodiment, the spray inhaler device according to the invention is characterized in that said baffles cross said airflow path and said spray part and each comprising a void at said spray path. By having a cut out portion at its free edge at the location of the spray path, at least part of the spray that is generated by the spray nozzle is allowed to reach the outlet during priming. During further operation, however, said baffles force the air flow into consecutive curved trajectories and thereby hinder heavier spray droplets to continue to the outlet. Instead the droplets that are unable to fllow said trajectory will bounce against one of the baffles. Particularly good results where obtained by a special embodiment of the spray inhaler device of the invention that is characterized in that said pair of baffles comprises a

4. first baffle at said entrance of said aerosol chamber and a second, opposite baffle at said outlet of said aerosol chamber, particularly at a mutual distance of the order of 10 millimetres. Apart from a baffle that may cross the entire width of the aerosol chamber, the screen member may as well occupy less part of the cross section of the chamber. In that respect a further preferred embodiment of the spray inhaler device according to the invention is characterized in that said aerosol chamber extends between opposing walls, in that said screen member comprises a screen body that is suspended within said aerosol chamber in a spaced relationship with respect to said walls of said aerosol chamber, said screen body crossing said airflow path while allowing a passage of at least part of said spray along said spray path in the absence of said airflow. The screen member in this case is a shield that is freely suspended in the path of the air flow to thereby deflect said alr flow and block the heavier droplets within the spray. By allowing a passage of the spray during priming, i.e. when there is no or hardly no airflow from the airflow means, initial priming of the device in nonetheless facilitated.

In a special embodiment the spray inhaler device according to the invention is characterized in that said screen body crosses said spray path while having a void, particularly an opening, at a location of said spray path to allow a substantially free passage of said spray through said void in the absence of said airflow. In this respect particularly good results where obtained with a further embodiment that is characterized in that said screen body is dome shaped, having a convex curvature facing towards said entrance of said aerosol chamber. A free passage of the spray during priming may be allowed by the screen member by having a void at the location of the spray path or by avoiding the spray path all together. A further special embodiment of the spray inhaler device according to the invention is, in this respect, characterized in that said outlet section is provided with a screen member that extends into said aerosol chamber, and in that said screen member is displaceable between a first position in which said screen member crosses said airflow path for deflecting at least part of said airflow during operation, and a second position away from at least said spray flow path. In this manner the screen member is not fixed but is {re)movable to be out of the way during priming. A particular embodiment of the spray inhaler device is thereby characterized in that said screen member is adjustable within said aerosol chamber of said outlet section between said first position, crossing said airflow path, and said second position, away from at least said spray

5. path, and particularly that said screen member is hingedly suspended in said aerosol chamber. In this configuration the screen member may cross both the airflow path and the spray path during normal operation in the first position, but is (put) in the second position during initial priming of the device.

In a further specific embodiment the spray inhaler device is further characterized in that said screen member is biassed towards said first position. As a result the device is set for normal operation and the screen member has to be released form its first position, for example manually by the user, to enable priming. In a second further embodiment, however, the spray inhaler device according to the invention is further characterized in that said screen member is biassed towards said second position and carried into said first position by said airflow. In this embodiment the device is (pre)set to its second position to enable priming and dragged automatically to the second position to improve and enhance normal operation once the airflow from the airflow means passes.

In a further specific embodiment the spray inhaler device according to the invention is characterized in that said screen member is detachable from said outlet section. By being detachable and simply taking away the screen member from the device, the device is allowed unrestricted priming at startup. Thereafter the screen member is mounted for normal operation of the device, taking out the heavier droplets to thereby restrict the droplet size distribution within the spray. The invention will now be elucidated in further detail with reference to a number of particular embodiments and an accompanying drawing, In the drawing: Fig.1 is a cross sectional view of a first embodiment of a spray inhaler device according to the invention; Fig. 2 is a perspective view of the spray inhaler device of figure 1; Fig. 3 isa front view of the spray inhaler device of the outlet member of the spray inhaler device of figure 1; Fig. 4 is a perspective view of an alternative outlet member of the spray inhaler device of figure 1; Fig. 5 is a front view of a further alternative outlet member for the spray inhaler device of figure 1;

6- Fig. 6 isa cross sectional view of a second embodiment of a spray inhaler device according to the invention; and Fig. 7 is a perspective view of the spray inhaler device of figure 6. It should be noticed that the drawings are drafted purely schematically and not to scale. In particular, certain dimensions may have been exaggerated to a lesser or greater extent for sake of clarity and understanding. Corresponding parts have been identified with same reference numerals throughout the drawing. The spray inhaler device of figure 1 comprises a container {cannister) 10 holding a quantity of a liquid that is to be inhaled. Said container may be a refillable or replaceable cannister of glass, plastic or any other convenient material that is screwed into a bay portion 15 of the spray inhaler device. The device further comprises pressurising means in the form of manually operable pump means 20 within the inhaler device, communicating with an outflow opening of said cannister 10. The cannister 10 is axially displacable, i.e. slidable, within the surrounding bay portion 15 of the device. Pushing the cannister 10 deeper into the inhaler device, energizes the pump means 20 to create a pressure that is typically of the order of between 5 and 20 bar inside the cannister. As a result the fluid is being expelled tunder said pressure o nozzle means 30 that are placed further downstream of the cannister 10.

The nozzle means 30 comprise a nozzle chip encapsulated in a surrounding carrier body of plastic or any other suitable material as described and shown in further detail in European patent application EP3.157.681 by applicant, the content of which is herewith incorporated by reference. The nozzle chip essentially comprises a silicon carrier body having one or more cavities across said body and a perforated silicon nitride membrane layer spanning each such cavity. The fluid is forced under pressure of the pumping means 20 trough one or more perforations in said membrane layer, causing the fluid to breakup in a spray of individual droplets. This, so called Rayleigh breakup, delivers a more or less continuous train of droplets, each having a size within a relative narrow range that is determined by a size of the perforations in the membrane layer. Other mechanisms that might be used within the nozzle means may be based on impinging jets of said fluid that cross each other to create droplets or may involve swirl techniques to create a turbulent liquid flow that will breakup into droplets.

7- The spray that is generated at the surface of the nozzle device 30 will propagate into an aerosol chamber 35 of a baffled outlet member 40 of the device.

Said aerosol chamber 35 is open on both ends to receive said nozzle spray along a spray path P1 at an entrance and to deliver an aerosol of said spray at an outlet 45, opposite said entrance.

The outlet member 40 provides a mouth piece to the user by which said aerosol may be inhaled.

To that end the device is provided with airflow means that comprise an air intake 42 for ambient air upstream of, and communicating with, said aerosol chamber 35. This will create an airstream along an airflow path P2 through the device that at least partly coincides with said spray path P1 within the aerosol chamber 35. As a result, the spray that is created by the nozzie means will be taken up by this air stream P2 to form an aerosol.

The air intake may be placed at any convenient spot and in several ways, such as a local opening through the wall 15 of the housing of the device or a open slit between the cannister and the surrounding wall 15. The outlet member 40 is provided with a screen 50 that may be integral with the walls of the outlet member, as in figures 1-3, or may be a separate piece to be placed over the outlet member, see figure 4. The screen 50 comprises a solid disc-shaped more or less central screen portion 52, having a cross-section of about 5 mm, that crosses said airflow path P2 downstream of said nozzle device 30 to force the joint air/aerosol stream out of a linear trajectory.

This causes the airstream P2 to drag smaller droplets from their initial propagation path P1 with it into the same non-linear, curved trajectory P2, but larger, hence heavier, droplets will continue in a more or less straight line to be intercepted by such solid screen portion 52. As a result, the aerosol emanating at the outlet 45 of the aerosol chamber 35 will comprise lesser relatively large droplets that would also be unable to follow the curved trajectory of the respiratory system.

The central disc-shaped shield portion 52 may either be flat or bow! shaped, either convex or concave as seen from outside.

Moreover the shield portion 52 may be exactly in the middle of the straight spray propagation path P1 or somewhat eccentric out of that path P1. During initial priming of the device, however, in the absence of a major airstream P2 the droplets that are created by the nozzle 30 will remain in their initial spray path P1 that at least partly passes the solid screen portion(s) 52. As a result the screen member 50 still allows for a priming operation of the device that forces the fluid from the container 10 to the nozzle device 30, thereby filling any empty portion of a fluid line in between.

An alternative embodiment of the screen member 50 is depicted in figure 5. This embodiment may replace either that of figures 3 and 4 and comprises a central opening 55 within the screen portion 52 to provide an even better straight passage to the initial spray path P1.

An alternative embodiment of the spray device according to the invention is shown figures 6 and 7. The device is similar to the device depicted in figures 1 and 2, having a cannister 10 with fluid to be sprayed, pump means 20 to pressurize the fluid, a nozzle device 30 to deliver a fluid spray and an outlet member or outlet section 40 with an aerosol chamber 35 inside to form a fine mist of said spray. The spray that is generated at the surface of the nozzle device 30 will propagate into said aerosol chamber 35 along a substantially straight propagation path P1, see figure 7, to the outlet 45 of the outlet member 40 of the device. The baffled outlet member of this example comprises a pair of mutually opposing baffles 61,62 that are in the airflow path P2 of an airstream that is taken in at an open intake 42 once the user inhales. As a result the airstream that is generated, is forced out of a linear trajectory into a curved path by both baffles 61,62 as shown in figure 6. This will also drag the spray out of its initial spray propagation path P1 into this curvature. Heavier, i.e. larger, droplets will not be able to follow this curved path due to their relatively large momentum and will, on the contrary, impinge onto one of the baffles 61,62. The spray that emanates at the outlet 45, as a consequence, will contain substantially fewer large droplets than initially formed downstream of the nozzle device 30 due to coalescence with outer droplets. As at least one of both baffles 61,62 has a central opening 65 in the linear spray propagation path P1, the device still allows for initial priming in the absence of the airstream P2, as shown in figure 7. The spray in this case leaves the device along a substantially straight line through said opening(s).

Below is a table of results of tests that were carried out on the devices of figures 3, 4, 5 and 6 respectively against a reference device that has a completely open aerosol chamber 35, i.e. void of any screen member, The devices are filled with 5 mL of 8.6% CBD solution with EtOH/5% saline, EtOH being an ethanol fast evaporating solvent. The CBD formulation contains TM231.1 CBD powder mixed with ethanol absolute and 5% NaCl. The formulation is prepared according to “FPO01_Formulation protocol CBD placebo v1”. The CBD concentration of 8.6% is based on weight percentage.

9. Each device is primed for 15 actuations using a force control tool at 36 N. Before each use the outlet member was cleaned using an ethanol solution and blown dried. Three consecutive actuations are measured at a flow rate of 15 l/min using a cascade impactor apparatus (NGI) equipped with a universal induction port (UIP) as described in the pharmacopeia that simulates a human throat. The measurements are performed according to a standard test measurement protocol. The goal of these experiments is to find the optimal device that minimizes deposition in the throat area. The devices according to the invention, having a baffled output section, are compared with a same device without such baffled output section. The baffled output is expected to filter/capture larger aerosol droplets from the aerosol cloud that would otherwise hit the throat area. By minimising the deposition in the throat and in the extra-thoracic area irritation to the user may be reduced significantly. The results are as follows: Sample: Emitted Volume Extra Thoracic Dose Thoracic Dose Alveolar Dose per actuation fut] full {nl} full A Reference, no baffle 17.87 3.37 14.17 10.95 is Bl 33 C Figure 6 and 7, d = 15 mm 14.77 3.07 11.44 8.81 E Figure 3 and 4, concave shield 18.57 5.18 13.12 10.09 F Figure 5 15.50 2.54 12.68 9.90 From the table it is clear that all samples B-F according to the invention, that have a baffled output section, outperform the reference sample (sample A} without such an output section. Two samples B,D are found to perform best in terms of minimising deposition in the throat area and maximising the alveolar deposition. Sample D shows the best overall performance. The fraction in the extra-thoracic area is the one of the lowest for all samples and the total lung deposition and the alveolar deposition is the highest amongst all, This embodiment has the highest alveolar deposition of 11.3 ul and one of the lowest throat deposition: 2.1 ul per actuation.

The second sample with a baffled output section (Sample B} has the second lowest fraction in the extra-thoracic area for all samples and the total lung deposition and the alveolar deposition is the one of the highest amongst all. This sample has a lower emitted mass due to the presence of the solid baffles, but it will give rise to the lowest throat irritation as an extra-

10- thoracic deposition of only 1.9 uL was observed per actuation, although also a lower alveolar dose of 7.8 uL per actuation will be introduced.

This sample performed best amongst all regarding its usability during priming.

Although the invention has been described to merely a limited number of embodiments in the preceding, it will be clear that the invention is by no means limited to those embodiments as shown in the drawing.

On the contrary, many variations and alternatives are feasible to a person of ordinary skill without departing from the scope and spirit of the invention as emanating from the following claims.

Claims

11. Claims: 1 Inheletor device for inhaling a mist, comprising: a reservoir for holding a fluid to be nebulized, pumping means for pressurizing the fluid, nebulizing means comprising a nebulizer for delivering a mist of the fluid , an outlet section having a substantially hollow aerosol chamber open at opposite ends for receiving said mist in a spray path, and air flow means for passing an air stream through said aerosol chamber in a fuchs flow path at least partially coinciding with said spray path, with characterized in that said outlet section includes at least one screen element extending into said aerosol chamber and traversing the air flow path to deflect at least a portion of the air flow during operation, and that said screen element is arranged to, in the absence of said air flow, zen passage of at least one to allow part of the aforementioned mist according to the aforementioned spray path,

2. Inhaler device according to claim 1, characterized in that said at least one screen element traverses said air flow path while having a recess at said spray path to allow, in the absence of the air flow, a substantially free passage of said nebula through. said cavity.

3. Inhaler device according to claim 2, characterized in that the at least one screen element comprises a pair of opposed plaques extending from opposite walls of the chamber for part of a distance between the opposite walls of the chamber and which spaced along the airflow path.

4. Inhaler device as claimed in claim 3, characterized in that the baffles traverse the air flow path and the spray path and each comprise a recess at the location of the spray path.

Inhaler device according to claim 3 or 4, characterized in that the pair of baffles comprise a first baffle near the entrance of the aerosol chamber and a second opposed baffle at the outlet of the aerosol chamber, in particular at a mutual distance of on the order of 10-15 millimeters, in particular 10 mm.

S10

An inhaler device according to claim 1, characterized in that the aerosol chamber extends between opposite walls, that the screen element comprises a screen body which is freely suspended in the aerosol chamber at a distance from the walls of the aerosol chamber; wherein the screen body crosses the airflow path while at least a portion of the mist is transmitted along the spray path, in the absence of the airflow.

7. Inheletor device according to claim 8, characterized in that said screen body crosses said spray hood while having a recess at the location of said spray path, in particular an opening, to allow a substantially free passage of said mist through said cavity. stand in the absence of said air flow.

Inhaler device according to claim 5 or 7, characterized in that the shield body is spherical, with a convex curvature directed towards the entrance of the aerosol cup.

An inhaler device according to claim 1, characterized in that the screen element is movable between a first position, in which the screen element crosses the airflow path for deflecting at least part of the airflow during operation, and a second position out of the way. of at least said spray path.

An inhaler device according to claim 9, characterized in that the screen element in the aerosol chamber of the outlet portion is adjustable between the first position, crossing the aerosol path, and the second position away from at least the spray path.

11. Inhaler device according to claim 10, characterized in that the screen element is hingedly suspended in the aerosol chamber.

Inhaler device according to claim 10 or 11, characterized in that the screen element is biased to the first position.

13. An inhaler device according to claim 10 or 11, characterized in that the screen element is biased to said second position and is brought into the first position by the air flow.

-13- 14. Inhaler device according to claim 9, characterized in that the screen element is removable from the ejection portion.