Spray device for inhaler

Abstract

The present disclosure relates to an atomizing device (2) for an inhaler (100), said atomizing device (2) comprising an aperture plate (6) having a fluid side (7) to which a fluid (110) is supplied and an atomizing side (9) from which said fluid is atomized, said aperture plate (6) comprising a single layer (5) of a single material, a plurality of recesses (10) formed in said single layer (5), each of said recesses (10) having an opening (11) facing said fluid side (7) and a bottom (12) facing said atomizing side (9), and a plurality of apertures (20) formed in said bottom (12) of each of said recesses (20).

Description

[Technical field]

[0001] The present disclosure relates to a nebulizer device for an inhaler, in particular to an aperture plate thereof. The present disclosure also relates to a method for manufacturing such an aperture plate. [Background technology]

[0002] US Pat. No. 5,399,433 describes a method for producing an aperture plate from a single layer of a single material, in particular stainless steel. In such a method, a number of apertures, each penetrating the single layer, are formed by laser drilling. For example, three laser drilling stages are used to form each aperture, the fluence of the laser decreasing from the first to the third laser drilling stage. In this context, fluence is defined as the time integral of the flux of a certain radiation or particle flow. In particular, the fluence F of a (single) laser pulse is the optical energy delivered per unit area. Its most common unit is J / cm. 2 This process causes the cross-sectional area of ​​each aperture to decrease from the fluid (liquid) side of the aperture plate to the spray side of the aperture plate, thus creating a tapered hole.

[0003] Although this method works reasonably well, it does have some drawbacks. First, known methods are embodied as short-pulse lasers (such as nanosecond lasers). As a result, burrs form around the opening of the apertures on the fluid side of the aperture plate, necessitating a finishing step (such as, for example, electropolishing as described in US Pat. No. 5,399,363). Such a finishing step, however, tends to enlarge the opening of the apertures on the fluid side of the aperture plate and may possibly modify other parameters of the apertures (especially those of the so-called "nozzle portion" that is formed in the last (e.g., third) stage of the laser drilling process). The enlargement of the openings and the modification of the parameters are difficult to control. Thus, the diameter of the openings may vary from aperture to aperture, raising issues regarding the reproducibility of the aperture plate.

[0004] Additionally, in-process monitoring allows only limited conclusions to be drawn regarding the actual characteristics of the aperture (length and diameter at each laser drilling step). In one example, optical transmission inspection may be used, as described in more detail in "Laser Drilling and Laser Drilling Tests: A Laser Drilling System for Laser Drilling in a Micromachined ...

[0005] The aperture characteristics, especially the diameter of the exit opening of the "nozzle portion", greatly influence the Mass Median Diameter (MMD, in μm) and Geometric Standard Deviation (GSD) of the aerosol generated by the inhaler, and therefore lung deposition. Furthermore, the Total Output Rate (TOR, in μg / min) of the inhaler is affected by the aperture characteristics, especially the length and diameter of the nozzle portion, and as a result the duration of treatment (single dose / inhalation regimen).

[0006] To determine the exact characteristics of the aperture plate, a polished cut image of the aperture plate must be produced, which destroys the aperture plate. The apertures must then be measured by using a scanning electron microscope, which is time-consuming and expensive. Hence, the method is not suitable for in-process control. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] European Patent No. 2717951 [Patent Document 2] European Patent No. 1429888 [Non-patent literature]

[0008] [Non-Patent Document 1] Ross HM Hatley, Lucy EA Hardaker, Joseph Zarins-Tutt, Filippo Quadrelli, Brendan Hogan, Ronan Mac Loughlin, John N. Pritchard, “Investigation of Optical Density for the Characterization of Nebulizer Meshes”, Respiratory Drug Delivery 2016 Summary of the Invention [Problem to be solved by the invention]

[0009] In view of the above, it was an object to provide a nebulizer device for an inhaler, in particular an aperture plate thereof, and a method for manufacturing such an aperture plate, which is capable of addressing one or more of the above mentioned drawbacks.

[0010] One object is to provide an inhaler nebulizer device, in particular an aperture plate thereof, and a method for manufacturing such an aperture plate, which makes it easier to determine, preferably measure, the characteristics of the aperture, and more particularly the characteristics of the nozzle portion. In a preferred form, this is possible as an in-process monitoring and / or without the need to destroy the aperture plate.

[0011] Another object is to provide a nebulizer device for an inhaler (particularly an aperture plate thereof) and a manufacturing method for such an aperture plate, which improves manufacturing precision and / or ease of manufacturing and / or reduces manufacturing costs.

[0012] However, the advantages of the known nebulizer device for an inhaler (particularly its aperture plate) in terms of its structural stability and / or its vibration characteristics are maintained. [Means for solving the problem]

[0013] According to one aspect of the present disclosure, a nebulizer for an inhaler is proposed, which comprises an aperture plate having a fluid side (first side or liquid side) to which a fluid (liquid) can be supplied and an atomization side (second side or aerosol side) to which the fluid (liquid) is atomized upon vibration of the aperture plate and / or the fluid.

[0014] The aperture plate comprises a single (one single) layer of a single material. A single layer of a single material does not have clear boundaries, interfaces, or confinement layers, etc. in a polished cut image of the single layer. Thus, an example of a single layer is a piece of polycrystalline material. An aperture plate produced by electroforming is therefore excluded, since some layers formed by electroforming, even if made of the same material, show interfaces or confinement layers between layers in a polished cut image. The aperture plate may, in one embodiment, comprise further layers attached to the single layer. In other embodiments, the aperture plate may consist of only a single layer.

[0015] A plurality of recesses are formed in the single layer. The recesses have an opening facing the fluid side or, in the case where the aperture plate is made of a single layer, each has an opening on the fluid side of the aperture plate. The recesses each have a bottom facing the opening (i.e., on the side facing the spray side, i.e., on the spray side of the aperture plate). The recesses may also be referred to as blind holes introduced from one side of the single layer (the fluid side (first side) of the aperture plate). In one embodiment, two or more recesses are provided. In another embodiment, three or more recesses are provided. Furthermore, the number of recesses may be preferably, but not limited to, less than 3,000, less than 1,000, or less than 500. Alternatively, less than 50 or less than 20 recesses may be provided. A relatively large number of smaller recesses (such as between 500 and 3,000, or between 500 and 1,000) may be beneficial to achieve high stability of the aperture plate. The more recesses are provided in the aperture plate, the higher the remaining reinforcement between the recesses, which provides the overall thickness of the single material layer and therefore the stability. Conversely, fewer and larger recesses (such as between 2 and 50, or between 2 and 20) may be beneficial to achieve a larger effective area for spraying with less dead area. In this context, a "dead area" is an area of ​​the aperture plate that does not have an aperture through it and therefore does not participate in the spraying process. That is, in these areas, the fluid cannot pass through the aperture plate to be sprayed on the fluid side. In addition, the manufacturing process may be simplified when using fewer recesses. The area of ​​the recesses relative to the total area of ​​the aperture plate does not exceed 50% in one example.

[0016] Furthermore, a plurality of apertures are formed at the bottom of each recess. The plurality of apertures may each have an entrance opening formed at the bottom of the respective recess and an exit opening facing or formed at the spray side of the aperture plate. The apertures may be cylindrical. Alternatively, the apertures may be cone- or funnel-shaped (see below), especially if only one laser drilling stage (one single laser fluence stage) is used to form the apertures. Alternatively, the apertures may have a first curved portion (such as a hemispherical portion) at the bottom side of the recess and a second cone- or funnel-shaped portion at the spray side (second side) forming the nozzle portion. The smaller opening of the cone- or funnel-shaped aperture or part thereof may be positioned as the exit opening at the spray side (second side). In this example, the apertures may be formed by laser drilling into the bottom of a previously formed recess (see below). Alternatively, the smaller opening of the cone- or funnel-shaped aperture or part thereof may be positioned as an inlet opening at the bottom of the recess. In this case, the aperture or at least the nozzle part may be formed by laser drilling into the spray side (second side) of the single layer. Positioning the smaller opening at the bottom side of the recess may provide the advantage that a lower threshold pressure is required on the fluid side to spray the fluid. In addition to this, lower shear forces may act on the fluid during spraying, reducing heating of the fluid due to friction. Thus, such a configuration may provide the advantage that more sensitive fluids, such as pharmaceutical compositions (including proteins whose protein chains tend to be damaged by heat or shear forces), may be sprayed with less protein damage.

[0017] According to one embodiment, there are no additional apertures formed in the aperture plate other than the apertures formed in the bottom of the recesses, and according to another embodiment, there are at least no additional apertures formed in the single layer between the recesses that are blind holes.

[0018] Furthermore, the dimensions of the apertures and / or recesses may be controlled only by the single layer. Thus, coatings on the inner surfaces of the recesses and / or apertures are excluded. In other words, no coating is applied to the single layer that would enter the recesses and / or apertures and thus modify the inner dimensions of the recesses and / or apertures compared to the inner dimensions of and provided by the single layer itself. Thus, the inner dimensions may be controlled only by machining the single layer (such as ablating material from the single layer), for example by the described laser drilling and / or milling processes.

[0019] The spray device may further comprise a vibrator (such as a piezoelectric element) configured to vibrate the aperture plate. The vibrator may be attached to a surface portion of the aperture plate or to a support member supporting the aperture plate, either directly, such as by adhesive, or indirectly through another layer or coating (the aperture plate may be fixed to the support member, such as by welding). Thus, the vibration of the vibrator is directly transmitted to the aperture plate or the support member, so that the aperture plate, or the support member as well as the aperture plate, vibrate together with the vibrator. This configuration may be considered as direct excitation of the aperture plate by the vibrator. Indirect excitation via the fluid to be sprayed differs from such direct excitation in this respect.

[0020] Fluid on the fluid side of the aperture plate passes through the recesses and apertures upon vibration of the aperture plate and / or the fluid and is atomized while exiting the aperture through an exit opening on the atomization side of the aperture plate, and thus an aerosol is formed on the atomization side of the aperture plate for inhalation by the patient.

[0021] Due to the opening of the recess having a relatively large area, a relatively small aspect ratio can be achieved. More precisely, state-of-the-art three-dimensional microscopes can only be used to inspect the geometric shape under suitable illumination conditions. These conditions can be met if the aspect ratio (i.e. the depth of the recess relative to the smallest dimension of the opening of the recess (e.g. the diameter when considering a circular recess)) is low enough (aspect ratio = depth / smallest dimension (e.g. the diameter when considering a circular recess)). The aspect ratio can be, for example, 2 or less, 1.5 or less, 1 or less, or 0.6 or less.

[0022] It is therefore possible to realise in-process inspection through the apertures, so that the characteristics of the recesses as well as the characteristics of the entrance openings of the apertures formed at the bottom of the recesses can be measured using state-of-the-art 3D microscopes without the need to destroy the aperture plate.

[0023] By using a single layer of a single material, the structural stability of the aperture plate as well as its vibration characteristics may nevertheless be maintained. In addition, because the entrance opening of the apertures can be relatively small, the density of the apertures can be increased compared to that of prior art three-stage laser-drilled apertures, thus increasing the TOR.

[0024] Furthermore, as detailed above, the TOR and MMD are strongly dependent on the geometry of the nozzle part, i.e., the geometry of the aperture (especially the length and diameter). By forming the recess, a small and relatively uniform or constant thickness of the bottom of the recess is achieved. Thus, the length of the aperture is very clearly determined. In addition, the formation of a relatively short aperture is much more accurate in terms of the diameter at the inlet side (corresponding to the fluid side) and the outlet side (corresponding to the spray side). As a result, much more consistent aperture geometries with respect to each other can be achieved, thereby reducing the GSD. Thus, the aperture plate can be manufactured with improved repeatability in terms of the aperture geometry, and thus the TOR, MMD, and GSD. Thus, the properties of the aerosol (the sprayed fluid) are more consistent when compared to different aperture plates obtained from the same manufacturing process.

[0025] The recesses and apertures may be produced by means of etching processes also used in the semiconductor industry (e.g. as disclosed in Oskar Z. Olszewskia, Ronan MacLoughlinb, Alan Blakea, Mike O'Neillc, Alan Mathewsona, Nathan Jackson, "A silicon-based MEMS vibrating mesh nebulizer for inhaled drug delivery", 30th Eurosensors Conference, EUROSENSORS 2016). Suitable methods are wet etching, plasma etching, reactive ion etching, deep reactive ion etching, etc.

[0026] Alternatively, electron beam machining may be used, electron beam drilling may be used to drill the apertures, and electron beam milling may be used to form the recesses. The electron beam may also be replaced by an ion beam.

[0027] The recesses and / or apertures may also be formed by a mechanical punching process (Byung-Yun Joo, Sung-Han Rhim, Soo-Ik Oh, "Micro-hole fabrication by mechanical punching process", Journal of Materials Processing Technology, 2005, Vol. 170, p. 593-601).

[0028] In one embodiment, however, the recesses are laser milled and / or the apertures are laser drilled. "Laser milling" involves the application of laser energy to remove material by ablation in a layer by layer manner. "Laser drilling" is a process of creating through holes (here apertures) by repeatedly pulsing focused laser energy onto a material (here a single layer). The use of a laser milling process to form the recesses is also beneficial in terms of achieving a relatively uniform and constant remaining material thickness in the bottom region of the recesses. Hence, even more precise formation of the apertures in terms of diameter and length can be achieved with the above-mentioned benefits of constant aerosol property reproducibility.

[0029] In a particular example, an ultrashort pulse laser is used for laser milling. Ultrashort pulse lasers are defined as lasers using laser pulses of less than 10 picoseconds. Ultrashort pulse lasers have the advantage of being more accurate, potentially even improving on the benefits of repeatability of consistent aerosol properties mentioned above.

[0030] The aperture may still be formed by using a short pulse laser (e.g., a nanosecond laser), or an ultrashort pulse laser, where a short pulse laser is defined as a laser that uses laser pulses longer than 10 picoseconds and shorter than 500 nanoseconds.

[0031] When using a laser to manufacture the recesses and / or apertures, the formation of burrs at the opening of the recesses and / or the entrance opening of the apertures can be minimized or even avoided. This is especially true when an ultrashort pulsed laser is used to manufacture the recesses (which is an athermal process). In any case, it is possible to dispense with finishing steps (e.g. polishing) that are usually required, simplifying the manufacturing process. In addition to this, the risk of widening of the openings due to the polishing process is avoided.

[0032] As indicated above, it is advantageous to use an ultrashort pulsed laser. Therefore, the surface roughness of the recess and / or aperture surface (wall and / or bottom) may be relatively low so that finishing steps including polishing are unnecessary. Therefore, the arithmetic mean roughness (Ra) of the recess and / or aperture surface is 0.4 μm or less. When dealing with roughness profiles, the arithmetic mean height is referred to as the arithmetic mean roughness Ra. The arithmetic mean height indicates the average of absolute values ​​along the sampling length.

[0033] The aperture plate may be domed after formation of the recesses and apertures, particularly in the areas containing the recesses. Alternatively, the aperture plate may remain flat. Experiments have shown that the TOR can be increased by positioning the apertures in correspondence with the amplitude of the oscillation of the aperture plate during the oscillation of the aperture plate. On the other hand, the positioning of the apertures and / or recesses and their shapes also affect the vibration characteristics of the aperture plate and thereby the position of the oscillation amplitude.

[0034] Taking the above into account, at least some of the recesses are, according to one example, located in the region of the amplitude of oscillation of the aperture plate during vibration of the aperture plate, so that it is possible to increase the TOR without increasing the number of apertures, thus maintaining or even increasing the stability of the aperture plate.

[0035] In one embodiment, the spray device further comprises an annular piezoelectric element (vibrator) for vibrating the aperture plate, such that the aperture plate is excited to vibrate in an annular manner. In this respect, the recesses may be arranged in a single layer or in a rotationally symmetric pattern as viewed from the fluid side of the aperture plate, which has been found to be advantageous in order to match the vibration amplitude of the aperture plate with the recesses and at the same time achieve the required stability of the aperture plate.

[0036] Furthermore, the shape of the recess in the top view of the opening of the recess or the cross section perpendicular to the direction from the fluid side to the spray side of the aperture plate may be of any type. These shapes include, but are not limited to, rectangular, square, trapezoidal, parallelogram, triangular, linear, lattice, circular, annular, annular sector, circular sector, circular segment, or combinations thereof. Using appropriate shapes and positions of the recess, the stability and vibration characteristics of the aperture plate may be adjusted as needed. However, shapes with few or no edges or corners are preferred to avoid the formation of cracks during use.

[0037] Advantageously, the recesses comprise one or more annular recesses and / or one or more circular recesses. Again, the use of annular and / or circular recesses has been found to be advantageous for matching the recesses to the vibration amplitude of the aperture plate and at the same time achieving the required stability of the aperture plate, as well as avoiding or minimizing the risk of crack formation during use.

[0038] As shown above, forming a larger recess followed by forming a number of smaller apertures at the bottom of the recess provides the advantage that the size of the aperture entrance opening is relatively small (compared to the entrance opening of a three-stage laser drilled aperture), allowing the apertures to be placed closer together. Thus, the apertures at the bottom of the recess may be placed at a pitch between 5 μm and 90 μm, or between 5 μm and 50 μm. In this context, the pitch is measured from the center of one aperture to the center of an adjacent aperture. As a result, it is possible to increase the TOR without having to increase the size of the aperture plate.

[0039] In one embodiment, the density of the apertures at the bottom of the recess is 200 / mm 2 and 40,000 pieces / 1mm 2 Between or 400 pieces / 1mm 2 and 20,000 pieces / 1mm 2 Between 1 and 1,000 pieces / 1mm 2 and 10,000 pieces / 1mm 2 As a result, multiple apertures can be formed in a relatively small area, thereby allowing the size of the aperture plate to be minimized and still achieving a relatively high TOR.

[0040] The recesses have a peripheral sidewall that extends between an opening facing the fluid side of the aperture plate and a bottom of each recess. In one embodiment, the peripheral sidewall of the recess is stepped towards the bottom.

[0041] This configuration makes it possible to avoid possible adverse effects at the edge / perimeter sidewall of the recess. In addition, such a configuration has the advantage that the fluid is guided towards the bottom of the recess and thus towards the inlet opening of the aperture. This is due to the tapering of the opposing (facing) peripheral sidewall or opposing (facing) parts of the peripheral sidewall. This advantage may be particularly true for relatively small recesses (e.g. diameters of 40 μm to 70 μm (see below)), but may also be valid for larger recesses depending on the properties (e.g. viscosity) of the fluid to be sprayed.

[0042] In one aspect, the peripheral sidewall has an inclined shape such that opposing peripheral sidewalls, or opposing portions of the peripheral sidewalls, taper toward one another in the direction toward the bottom of the recess. "Inclined" means inclined with respect to the direction from the fluid side to the spray side of the aperture plate.

[0043] From the perspective of the simplest configuration to enable the characteristics of the recess to be measured, a straight peripheral sidewall may be preferred, in this context straight means parallel to the direction from the fluid side to the spray side of the aperture plate (perpendicular to the bottom of the recess).

[0044] Finally, the peripheral side wall may have a concave or convex shape (i.e. a curved shape) relative to the direction from the fluid side to the spray side of the aperture plate. The stiffness and vibration characteristics of the aperture plate may thus be optimized. In addition to this, as mentioned above, the fluid guidance towards the bottom of the recess and thus the inlet opening of the aperture is improved. In addition to this, potential edges or corners may be avoided, thus minimizing the risk of crack formation during use.

[0045] In one embodiment, the minimum dimension of the opening of the recess facing the fluid side is between 40 μm and 500 μm (preferably between 70 μm and 400 μm), and most preferably between 90 μm and 300 μm. If the shape of the opening is circular, the minimum dimension is the diameter. In the case of an annular opening, the minimum dimension is the width of the ring. In the case of a rectangular shape, the minimum dimension is the dimension of the smaller edge (leg) of the rectangular shape, etc. By selecting a minimum dimension in the above range, a relatively small aspect ratio is possible. More precisely, state-of-the-art three-dimensional microscopes may only be used to inspect the geometric shapes under suitable lighting conditions. These conditions can be met if the aspect ratio (i.e. the depth of the recess relative to the minimum dimension of the opening of the recess (e.g. the diameter when considering a circular recess)) is sufficiently low (aspect ratio = depth / minimum dimension, e.g. the diameter when considering a circular recess). The aspect ratio may be, for example, 2 or less, 1.5 or less, 1 or less, or 0.6 or less. Thus, during manufacture, visual inspection of the properties of the respective recesses and / or the apertures formed in the respective recesses (in particular their entrance openings) is possible. It is therefore possible to enable in-process monitoring / inspection. In this context, the minimum dimension is selected to be large enough to obtain a relatively small aspect ratio. The above definition of the minimum dimension of the recess openings therefore enables in-process monitoring / measurement, but at the same time is small enough to maintain the required stability of the aperture plate.

[0046] The size of the exit opening of the aperture has a large effect on the MMD. Depending on the type of fluid to be sprayed, the MMD is linearly larger than the diameter of the exit opening, and is therefore directly proportional. Thus, the aperture may be circular with a diameter (the diameter of the exit opening) facing the spray side, which may be between 1 μm and 7 μm, preferably between 1.5 μm and 5 μm, and most preferably between 1.5 μm and 3 μm.

[0047] In this context, it should be emphasized that the inner dimensions of the apertures and / or recesses may be controlled only by the single layer. In other words, no coating is applied to the single layer that would enter the recesses and / or apertures and thus modify the inner dimensions of the recesses and / or apertures compared to the inner dimensions of and provided by the single layer itself. The inner dimensions may therefore be controlled only by machining the single layer (such as by ablating material from the single layer), for example by the described laser drilling and / or milling process.

[0048] The length of the apertures in the single layer (which may also be referred to as height or depth) may be between 3 μm and 50 μm. In another example, the length of the apertures in the single layer may be between 5 μm and 20 μm. In a possibly further example, the length of the apertures in the single layer may be between 10 μm and 20 μm. Other ranges may be 5 μm to 15 μm, 5 μm to 12 μm, or 10 μm to 15 μm.

[0049] In one example, the single layer has a thickness in the direction from the fluid side to the spray side. The single layer may have a uniform thickness, although it is also contemplated that the single layer has different thicknesses in different regions.

[0050] The recesses may have a depth (which may also be referred to as length or height) of 50% or more of the thickness of the monolayer. In another example, the depth of the recesses may be between 70% and 95% of the thickness of the layer, or between 80% and 95% thereof. If the thickness of the monolayer varies locally according to the area of ​​the monolayer, the percentages relate to the thickness of the regions where the recesses are provided. In this context, the thickness of the monolayer in the regions where the recesses are provided is integral. The recesses may all have the same depth or may have different depths.

[0051] Since the length of the aperture (see above) is controlled by the depth of the recess, the length of the aperture is the same within a recess but may vary between recesses. If the recesses all have the same depth, the length of the aperture is also the same as long as the single layer has a unitary thickness.

[0052] Each recess may have 2 or more, 5 or more, 20 or more, 50 or more, or 100 or more apertures formed in its base. Up to a maximum each recess may have 5,000 or 10,000 apertures.

[0053] The single material may generally be any type of material. The main criteria for the material are durability, machinability (depending on the process for forming the recesses and / or apertures as described above), and / or biocompatibility. Possible materials include, but are not limited to, ceramics, plastic materials, semiconductor materials and metals. However, it has been found that biocompatible metals such as titanium or stainless steel, which have high stiffness and elasticity for efficient vibration excitation, are advantageous. In one particular example, the single material of the single layer may therefore be a metal, in particular stainless steel. In this context, it has already been found that stainless steel provides a relatively high stiffness and meets the requirements for efficient vibration excitation and biocompatibility. However, when forming recesses and / or holes by short-pulse lasers using a relatively high fluence, there is a risk of burrs being formed on the entrance side of the laser into the single material. This may, however, be avoided by providing recesses and forming apertures only at the bottom of the recesses. This problem may be further mitigated when using the ultrashort-pulse lasers described above. It is therefore possible to omit the subsequent electropolishing process.

[0054] Apart from the above nebulizer device, the present disclosure also relates to a method for manufacturing an aperture plate (e.g., as described above) of a nebulizer device for an inhaler. Thus, any of the above-mentioned aspects and embodiments and related features may also be embodied in the method described below.

[0055] The method includes providing a single layer of a single material having a first side and a second side opposite the first side, the first side facing or optionally being the fluid side of the aperture plate, and the second side facing or optionally being the spray side of the aperture plate as described above.

[0056] The method further includes forming a plurality of recesses on a first side of the single layer, the recesses having an opening on the first side and a bottom facing the second side, and forming a plurality of apertures, the plurality of apertures extending from the bottom of the recesses to the second side and having an opening on the second side of the single layer.

[0057] Thus, easier and improved process monitoring and control can be achieved, as described above with respect to the aperture plate. In addition, the geometric characteristics of the apertures and / or recesses are highly reproducible and can be obtained without the need to destroy the aperture plate.

[0058] The recesses and / or apertures may be formed by removing material from a single layer. When removing material from a single layer rather than displacing material, greater flexibility regarding the shape, location, and precision of the recesses and / or apertures can be achieved.

[0059] In addition to the different processes mentioned above for forming recesses and / or apertures, which may be embodied in the method, the recesses may be laser milled and / or the apertures may be laser drilled. The use of laser technology is beneficial because laser processing allows easy reconfiguration by reprogramming the integrated laser scanner to obtain different geometries (shapes and / or positions) of the recesses / apertures. Laser processing does not require complex tools (e.g. masks, punches, etc.) that must be newly generated when changing the geometry. Also, in material growing processes such as electroforming, changing the geometry is cumbersome.

[0060] In a particular example, an ultrashort pulsed laser is used for laser milling. The aperture may nevertheless be formed by using a short pulsed laser or may be generated as well by using an ultrashort pulsed laser. In some cases, when using a laser to manufacture the recesses and / or apertures, it is possible to minimize or even avoid the formation of burrs at the opening of the recesses and / or the entrance opening of the apertures. This is especially true when using an ultrashort pulsed laser to form the recesses, which is an athermal process. In any case, it is possible to do away with the finishing steps (e.g. polishing) that are usually required, simplifying the manufacturing process. In addition, the risk of widening of the openings due to the polishing process is avoided. As mentioned above, an ultrashort pulsed laser may be used for laser milling of the recesses and / or laser drilling of the apertures. In addition, if stainless steel is used as a single material, it is possible to avoid the formation of burrs at the first side and / or the bottom and / or the second side (the side of incidence of the laser beam). It is therefore possible to do away with the step of electrolytic polishing.

[0061] The aperture may be laser drilled using the same fluence. Thus, only one laser stage is required to form the aperture at the bottom of the recess. Since the aperture only needs to penetrate the bottom of the recess (the remaining thickness of the single layer), a relatively low fluence is sufficient to form the aperture. Thus, the formation of burrs can be effectively avoided. Alternatively, the aperture at the bottom of the recess may also be drilled using two laser stages with different fluences. For example, a first laser drilling stage with a first fluence may be used to form a first part of the aperture at the bottom of the recess, and a second laser drilling stage with a second fluence lower than the first fluence may be used to finish the aperture (i.e., to completely penetrate the bottom and thus form the nozzle part). When using two laser drilling stages, the part of the aperture formed in the first laser drilling stage may have a curved inner periphery, ideally a hemispherical inner periphery. The propagation of the laser beam is a nonlinear function. Thus, the curved shape of the aperture is possible by adjusting / displacing the focus of the laser beam away / relative to the surface where the aperture is formed. To form a curved inner periphery of the portion of the aperture formed in the first laser drilling stage, the focus of the laser beam may be positioned at a distance to the second side of the monolayer, for example at a distance away from the bottom of the recess to the spray side. The portion of the aperture formed in the second laser drilling stage may be cone- or funnel-shaped with a smaller opening on the second side (e.g. the spray side). Compared to only one laser drilling stage, the remaining thickness of the monolayer between the bottom of the recess and the second side may be larger, which may improve the vibration characteristics and stability of the aperture plate.

[0062] The recesses have a peripheral sidewall that extends between an opening facing the fluid side of the aperture plate and a bottom of the respective recess. In one aspect, the peripheral sidewall of the recess is stepped toward the bottom.

[0063] This configuration makes it possible to avoid possible adverse effects at the edge / perimeter sidewall of the recess. In addition, such a configuration has the advantage that the fluid is guided towards the bottom of the recess and thus towards the inlet opening of the aperture. This is due to the tapering of the opposing (facing) peripheral sidewall or opposing (facing) parts of the peripheral sidewall. This advantage may be particularly true for relatively small recesses (e.g. diameters of 40 μm to 70 μm (see below)), but also for larger recesses depending on the properties (e.g. viscosity) of the fluid to be sprayed.

[0064] This advantage may also be achieved when the peripheral sidewall has an inclined shape, with the opposing (facing) peripheral sidewalls, or opposing (facing) portions of the peripheral sidewalls, tapering towards each other in the direction towards the bottom of the recess. "Inclined" means inclined with respect to the direction from the fluid side to the spray side of the aperture plate.

[0065] From the perspective of the simplest configuration to enable the characteristics of the recess to be measured, a straight peripheral sidewall may be preferred, in this context straight meaning parallel to the direction from the fluid side to the spray side of the aperture plate.

[0066] The aperture plate may be domed after formation of the recesses and apertures, particularly in the areas comprising the recesses, or alternatively, the aperture plate may remain flat.

[0067] In one embodiment, the minimum dimension of the opening of the recess facing the fluid side is between 40 μm and 500 μm (preferably between 70 μm and 400 μm), most preferably between 90 μm and 300 μm. If the shape of the opening is circular, the minimum dimension is the diameter. In the case of an annular opening, the minimum dimension is the width of the ring. In the case of a rectangular shape, the minimum dimension is the dimension of the smaller edge (leg) of the rectangular shape, etc. By selecting a minimum dimension in the above range, a relatively small aspect ratio is possible. More precisely, state-of-the-art three-dimensional microscopes may only be used to inspect the geometric shape under suitable lighting conditions. These conditions can be met if the aspect ratio (i.e. the depth of the recess relative to the minimum dimension of the opening of the recess (e.g. the diameter when considering a circular recess)) is sufficiently low (aspect ratio = depth / minimum dimension, e.g. the diameter when considering a circular recess). The aspect ratio may be, for example, 2 or less, 1.5 or less, 1 or less, or 0.6 or less. The above definition of the minimum dimension of the recess opening therefore allows visual inspection of the properties of the respective recess and / or the apertures formed in the respective recess (in particular their entrance openings) during production. In-process monitoring / inspection can therefore be made possible. In this context, the minimum dimension is selected to be large enough to obtain a relatively small aspect ratio. The above definition of the minimum dimension of the recess opening therefore allows in-process monitoring / measurement, but at the same time is small enough to maintain the required stability of the aperture plate.

[0068] By forming a larger recess and then forming a number of smaller apertures at the bottom of the recess, the advantage is provided that the size of the entrance opening of the apertures is relatively small and the apertures can be arranged closer to each other without overlapping. Thus, the apertures at the bottom of the recess may be arranged with a pitch between 5 μm and 90 μm, or between 5 μm and 50 μm. In this context, the pitch is measured from the center of one aperture to the center of the adjacent aperture. As a result, it is possible to increase the TOR without having to increase the size of the aperture plate.

[0069] The recesses may have a depth (which may also be referred to as length or height) of 50% or more of the thickness of the layer. In another example, the depth of the recesses may be between 70% and 95% of the thickness of the layer, or between 80% and 95% thereof. If the thickness of the monolayer varies according to the area of ​​the monolayer, the percentages relate to the thickness of the area in which the recesses are provided. In this context, the thickness of the monolayer in the area in which the recesses are provided is integral. The recesses may all have the same depth or may have different depths.

[0070] Since the length of the aperture (see above) is controlled by the depth of the recess, the length of the aperture may be the same within one recess but different between multiple recesses. If the recesses all have the same depth, the length of the aperture is also the same as long as the single layer has a unitary thickness. In particular, the recess is adapted so that the remaining thickness of the single layer corresponding to the bottom is thick enough to maintain stability and stable vibration characteristics, but thin enough to allow one-stage laser drilling at a constant fluence to finally drill the aperture. In order to increase the accuracy of the geometry of the aperture (i.e., the nozzle part), only one drilling stage for forming the aperture is preferred. As mentioned above, the TOR and MMD strongly depend on the geometry of the nozzle part (i.e., the geometry of the aperture (especially the length and diameter)). The formation of a relatively short aperture is much more accurate in terms of diameter at the inlet side (corresponding to the fluid side) and the outlet side (corresponding to the spray side). This is especially true when using only one laser drilling step (multiple laser pulses at a constant laser fluence) to form each of the apertures at the bottom of the recess. As a result, much more consistent aperture geometries with respect to each other can be achieved. As a result, aperture plates can be manufactured with improved repeatability in terms of aperture geometries and thus TOR, MMD and GSD. Thus, the properties of the aerosol (atomized fluid) are more consistent between different aperture plates obtained from the same manufacturing process.

[0071] In another embodiment, the aperture at the bottom of the recess may also be drilled using two laser drilling steps with different fluences. For example, a first laser drilling step with a first fluence may be used to form a first part of the aperture at the bottom of the recess, and a second laser drilling step with a second fluence lower than the first fluence may be used to finish the aperture (i.e., completely through the bottom). In this example, the nozzle portion may be determined only by the second laser drilling step. Thus, the bottom may remain thicker (lower recess depth) when using more than one laser drilling step to form the aperture. This may provide greater mechanical rigidity of the aperture plate.

[0072] The single material may generally be any type of material. The main criteria for the material are durability, machinability (depending on the process for forming the recesses and / or apertures as described above), and / or biocompatibility. Possible materials include, but are not limited to, ceramics, plastic materials, semiconductor materials and metals. However, it has been found that biocompatible metals such as titanium or stainless steel, which have high stiffness and elasticity for efficient vibration excitation, are advantageous. In one example, the single material of the single layer may therefore be a metal, in particular stainless steel. In this context, stainless steel has already been found to provide a relatively high stiffness and to meet the requirements of efficient vibration excitation and biocompatibility. However, when forming recesses and / or holes by a short-pulse laser using a relatively high fluence, there is a risk of burr formation at the entrance side of the laser into the single material. This may however be avoided by providing a recess. Due to the recess, the thickness of the remaining material of the single layer (thickness at the bottom of the recess) is relatively small. Thus, the aperture can be formed at the bottom of the recess using a relatively low fluence. Thus, the risk of burr formation at the entrance side of the laser into the single material is reduced. This problem may be further mitigated when using the ultrashort pulsed laser mentioned above, so that the subsequent electropolishing process can be omitted. [Brief description of the drawings]

[0073] [Figure 1] 1 is a longitudinal cross-sectional view of an inhaler comprising a nebulizer device of the present disclosure; [Diagram 2] FIG. 2 shows a top view of the spray side of the aperture plate of the spray device shown in FIG. 1 prior to dome formation. [Diagram 3] FIG. 3 is a cross-sectional view taken along line 3-3 in FIG. 2. [Figure 4A] FIG. 4 shows an enlarged portion of the cross-sectional view of FIG. 3. [Figure 4B] FIG. 4B shows an alternative form of aperture in the same cross section as FIG. 4A. [Figure 4C] FIG. 4B shows an alternative form of aperture in the same cross section as FIG. 4A. [Figure 4D] FIG. 4B shows an alternative form of aperture in the same cross section as FIG. 4A. [Figure 5A] 1A-1C show plan views of the fluid side of an aperture plate illustrating different geometric shapes of the recesses. [Figure 5B] 1A-1C show plan views of the fluid side of an aperture plate illustrating different geometric shapes of the recesses. [Figure 5C] 1A-1C show plan views of the fluid side of an aperture plate illustrating different geometric shapes of the recesses. [Figure 5D] 1A-1C show plan views of the fluid side of an aperture plate illustrating different geometric shapes of the recesses. [Figure 5E] 1A-1C show plan views of the fluid side of an aperture plate illustrating different geometric shapes of the recesses. [Figure 5F] 1A-1C show plan views of the fluid side of an aperture plate illustrating different geometric shapes of the recesses. [Figure 5G] 1A-1C show plan views of the fluid side of an aperture plate illustrating different geometric shapes of the recesses. [Figure 5H] 1A-1C show plan views of the fluid side of an aperture plate illustrating different geometric shapes of the recesses. [Figure 5I]1A-1C show plan views of the fluid side of an aperture plate illustrating different geometric shapes of the recesses. [Figure 6A] 11A-11C are cross-sectional views of different configurations of the peripheral sidewall of the recess. [Figure 6B] 11A-11C are cross-sectional views of different configurations of the peripheral sidewall of the recess. [Figure 6C] 11A-11C are cross-sectional views of different configurations of the peripheral sidewall of the recess. [Figure 6D] 11A-11C are cross-sectional views of different configurations of the peripheral sidewall of the recess. [Figure 6E] 11A-11C are cross-sectional views of different configurations of the peripheral sidewall of the recess. [Figure 6F] 11A-11C are cross-sectional views of different configurations of the peripheral sidewall of the recess. [Figure 6G] 11A-11C are cross-sectional views of different configurations of the peripheral sidewall of the recess. [Figure 7] FIG. 1 illustrates the vibration of an aperture plate during one vibration cycle. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0074] FIG. 1 shows a schematic longitudinal cross-section of an inhaler 100 comprising a nebulizer device 2 . The inhaler 100 comprises a first housing portion 102 and a second housing portion 108 that are joined together at a connecting portion 118. The first housing portion 102 has an aerosol chamber 104 and a mouthpiece 106. The second housing portion 108 forms a fluid chamber for receiving the fluid 110 to be aerosolized / nebulized.

[0075] The atomizing device 2 is received in a recess 114 formed in the second housing part 108 and a recess 116 formed in the first housing part 102. The aerosol generator 2 comprises an annular housing 3 and a vibratable head 1, which is partially housed in the housing 3. The vibratable head 1 comprises an annular support member 4 and a circular vibrating membrane (aperture plate) 6 supported by the support member 4. The aperture plate 6 may be integrally formed with the support member 4 or may be manufactured separately and attached to the support member 4. The aperture plate 6 and the support member 4 are made of a metal, such as stainless steel. The aperture plate 6 has a number of recesses and apertures not visible in FIG. 1, as will be described in more detail below.

[0076] The vibrable head 1 further comprises a vibrator 8 configured to vibrate the aperture plate 6. The vibrator 8 is attached to a surface portion of the support member 4 by adhesive. The vibrator 8 is a ceramic annular piezoelectric element.

[0077] In the following, the operation of the inhaler 100 for the generation and delivery of an aerosol may be described. A fluid 110 to be aerosolized / nebulized, for example a fluid containing an active compound (such as a drug substance or drug), is loaded into a fluid reservoir formed by the second housing portion 108 .

[0078] Fluid 110 received in the fluid reservoir abuts the fluid side 7 of the aperture plate 6 of the vibratable head 1 . A controller (not shown) is operated to provide an activation signal to the vibrator 8 via electrical contacts (not shown) of the vibrator 8, activating the vibrator 8 and thereby vibrating the aperture plate 6. The electrical contacts of the vibrator 8 may be provided in the form of one or more conductors (e.g. one or more flexible strip conductors, e.g. printed circuit board tracks or striplines). The one or more conductors may be attached to one or more surface portions of the vibrator 8, for example by adhesive.

[0079] Fluid 110 abutting against the fluid side 7 of the aperture plate 6 is conveyed through recesses and apertures in the aperture plate 6, described below, and thereby aerosolized / atomized into the aerosol chamber 104 at the atomization side 9 of the aperture plate 6. The aerosol 112 thus provided in the aerosol chamber 104 is inhaled by the patient or user through a mouthpiece 106, which is disposed in fluid communication with the aerosol chamber 104.

[0080] As can be seen from FIG. 1, the aperture plate 6 may be dome-shaped (ie convex towards the aerosol chamber 104 or concave towards the fluid 110) in the region of the recess 10 / aperture 20.

[0081] Figure 2 shows a plan view of the aperture plate 6 as seen from the fluid side 7 of the aperture plate 6, prior to dome formation. Figure 3 shows a cross-sectional view along line 3-3 in Figure 2.

[0082] In one example, the aperture plate 6 is circular and may be attached to or integrally formed with the support member 4 . The aperture plate 6 in this example consists of a single layer 5 of stainless steel. However, in other embodiments, the aperture plate 6 may comprise further layers attached to the fluid side 7 (first side) and / or the spray side 9 (second side). In addition to this, other biocompatible metals may be used instead of stainless steel. Referring to the summary section above, other materials may also be used when manufacturing the single layer 5 of the aperture plate 6.

[0083] The exemplary aperture plate 6 comprises a plurality of recesses 10 (three in one example). The recesses 10 comprise two annular recesses 101 and 102 and a central circular recess 103. The annular recesses 101 and 102 are concentric with the center of the circular recess 103. Thus, the recesses 10 are shaped and positioned to be rotationally symmetric about the center of the aperture plate 6, which coincides with the center of the circular recess 103.

[0084] The recess 10 has an opening 11 facing the fluid side 7, or in one example has an opening 11 at the fluid side 7 of the aperture plate 6. The recess is formed as a blind hole with a bottom 12 facing the opening 11. The shape shown in plan view in Figures 2 and 5 is controlled by the opening 11 of the recess.

[0085] Alternative geometries and arrangements of recesses 20 are shown in Figures 5A-5I. From a plan view, it can be seen that the shapes of those recesses 20, i.e. the openings 21, may vary. The shapes may include circular shapes (as in Figs. 5A, 5C, 5D, 5G and 5I), annular shapes (as in Figs. 5D and 5I), square shapes (as in Fig. 5B), rectangular shapes (as in Figs. 5B and 5E), line and grid shapes (as in Figs. 5E and 5H), triangular shapes (as in Fig. 5G), annular sections (as in Fig. 5F), circular sections (as in Fig. 5F), etc. These shapes may be combined as desired. By selecting the shape and pattern of the recesses 20, the resonant frequency of the aperture plate 6 may be adjusted. In addition to this, the natural modes of vibration (natural frequencies / resonant modes) may be influenced by the selected pattern.

[0086] In one example, an annular piezoelectric element 8 is used to vibrate the aperture plate 6, so that the excitation of the aperture plate is rotationally symmetric. As a result, it has been found to be advantageous to use rotationally symmetric patterns such as those shown in Figures 5A, 5C, 5D, 5F, 5G, and 5I. Note that Figure 5C is not perfectly rotationally symmetric, but is still close enough to be considered rotationally symmetric.

[0087] Furthermore, the structure is divided into relatively small sections, thereby minimizing the risk of stress fracture. Furthermore, edges are avoided to reduce the risk of stress in the cutouts. Finally, a central recess with a relatively large area has been found to be advantageous with regard to stability during the dome formation process (i.e. bending / curving of the aperture plate 6 after formation of the recesses 10 and apertures 20).

[0088] When the aperture plate 6 is excited by an annular piezoelectric element 8, the vibration amplitude during one vibration period may be located at a center (301) and in concentric rings (302) around the center (see FIG. 7). By positioning the recesses 10, or at least some of the recesses 10, corresponding to the vibration amplitude, it is possible to further increase the TOR without having to provide a large number of apertures 20.

[0089] Taking the foregoing into consideration, shapes and patterns such as those shown in Figures 5A, 5C, 5D, and 5I promise the best results. The pattern in Figure 5A comprises a number of equally dimensioned circular recesses 10. A central recess 101 and a number of recesses 102 (six in this example) are arranged with their centres on rings concentric with the central recess 101.

[0090] The pattern in FIG. 5C comprises a plurality of recesses formed in a circular area, which are preferably equally spaced apart and arranged with their centers on concentric rings and / or radial lines.

[0091] The pattern in Figure 5D corresponds to the pattern shown in Figure 2. The pattern in Figure 5I differs from the pattern in Figure 5D in that only one annular recess 10 is provided instead of two as in Figure 5D.

[0092] The recess 10 has a peripheral side wall 13. In the case of the circular recess 103, the peripheral side wall 13 corresponds to a cylindrical covering. Moreover, in the cross-sections in Figures 3 and 4, parts of the peripheral side wall are opposite (facing) each other. In the case of the circular recesses 101 and 102, two peripheral side walls 13 are provided which are positioned opposite each other, i.e. facing each other.

[0093] 6, the peripheral sidewall 13 may assume various shapes (geometry). As shown in Figures 6A and 6B, opposing portions of the peripheral sidewall, i.e., the facing peripheral sidewall, may taper towards the bottom 12. Thus, the fluid 110 may be directed towards the inlet opening 21 of the aperture 20, which will be described later.

[0094] In the example shown in Figure 6A, the peripheral sidewall is stepped, with a number of steps 14. Such a configuration has been found to be advantageous when manufacturing recesses according to their size for directing fluid towards the entrance opening 21 of the aperture by laser milling using an ultrashort pulsed laser.

[0095] A similar effect may also be achieved when the peripheral side wall 13 is inclined relative to the direction from the fluid side 7 to the spray side 9. In this example, however, the peripheral side wall 13 is straight rather than stepped.

[0096] The peripheral side wall 13 may instead have a concave or convex shape (i.e. a curved shape) relative to the direction from the fluid side 7 to the spray side 9 of the aperture plate. Hence, the fluid guidance towards or retention at the bottom 12 of the recess 10 and thus the opening 21 of the aperture 20 is improved for relatively small recesses with a minimum dimension of less than 70 μm. In addition, potential edges or corners are avoided, thus minimizing the risk of crack formation during use. A concave shape is shown in FIG. 6D. A convex shape is shown in FIG. 6E, and a funnel shape is shown in FIG. 6F. A funnel shape may be beneficial to avoid stress peaks. The same applies to the "S" shaped peripheral side wall 13 in FIG. 6G.

[0097] From the perspective of the simplest configuration to enable measurements of the properties of the recess 10, a straight shaped peripheral sidewall 13 may be preferred. In this context, straight means parallel to the direction from the fluid side 7 to the spray side 9 of the aperture plate 6. Thus, opposing peripheral sidewalls 13 or opposing parts of one peripheral sidewall 30 may extend parallel to each other. Such a configuration is shown in Figure 6C as well as in Figures 3 and 4.

[0098] As indicated above, the recesses 10 may be formed in the single layer 5 by using an ultrashort pulsed laser. In this context, the recesses 10 are preferably produced by laser milling, moving the single layer 5 of the laser beam and / or the aperture plate 6 relative to each other, whereby material of the single layer 5 is gradually removed.

[0099] Minimum dimension D of the recess 10 R may be 300 μm for the central recess 103 and 250 μm for the annular recesses 101 and 102. However, other dimensions are also conceivable. For example, the smallest dimension D of the opening 11 of the recess 10 facing the fluid side 7 R may be between 40 μm and 500 μm, between 70 μm and 400 μm, or between 90 μm and 300 μm.

[0100] In this context, the minimum dimension D for the circular central recess 103 R corresponds to the diameter of the circle. R Regarding the minimum dimension D R corresponds to the width of the annular ring (see Figure 2).

[0101] The thickness T of the single layer 5 may be 100 μm. Depth or length L of recess 10 R may be selected between 80% and 95% of the thickness T of the single layer 5. Thus, the depth L of the recess 10 R may be between 80 μm and 95 μm.

[0102] However, the thickness T of the monolayer 5 may be in the range between 50 μm and 200 μm. R may be chosen to be equal to or greater than 50% of the thickness T of the single layer 5.

[0103] Each recess 10 has a plurality of apertures 20 formed in the base 12 and extending from the base 12 to the spray side 9 (second side) of the single layer 5 . Each recess 10 may have 2 or more, 20 or more, or 50 or more, 100 or more apertures 20 formed in the base 12. At most each recess may have 5,000 or 10,000 apertures 20.

[0104] Each aperture 20 has an inlet opening 21 at the bottom 12 and an outlet opening 22 at the spray side (second side) 9 of the monolayer 5. The apertures 20 may be substantially cylindrical (straight sidewalls 23 as shown in FIG. 4A) or conical (sloping sidewalls 23 as shown in FIG. 4B) with the smaller opening (hence the outlet opening 22) located at the spray side 9. However, the geometry is not limited thereto and other geometries are also contemplated. For example, a cone-shaped or funnel-shaped aperture may be oriented such that the smaller opening is on the fluid side (bottom 12 of the recess 10) as shown in FIG. 4C. In this case, the inlet opening 21 of the aperture 10 may be circular and have a diameter D at the bottom 12 of the recess 10. E The diameter D of the inlet opening 21 may be between 1 μm and 7 μm, preferably between 1.5 μm and 5 μm, and most preferably between 1.5 μm and 3 μm. A The diameter (of the exit opening 22) may be between 2 and 12 μm, preferably between 2.5 and 10 μm, and most preferably between 3 and 8 μm.

[0105] The size of the exit opening 22 of the aperture 20 has a significant effect on the MMD. Depending on the fluid, the MMD can be determined by the diameter D of the exit opening 22. A 4A, 4B, and 4D have a diameter D A (diameter of exit opening) may be between 1 μm and 7 μm, preferably between 1.5 μm and 5 μm, and most preferably between 1.5 μm and 3 μm.

[0106] Length L of aperture 20 in single layer 5 A In another example, the length L of the aperture in the single layer 5 (which may also be referred to as the height or depth) may be between 3 μm and 50 μm. AIn a further example, the length L of the aperture in the single layer may be between 5 μm and 20 μm. A The thickness may be between 10 μm and 20 μm. Other ranges may be 5 μm to 15 μm, 5 μm to 12 μm, or 10 μm to 15 μm.

[0107] Furthermore, as detailed above, the TOR and MMD are strongly dependent on the geometry of the nozzle part, i.e., the geometry of its apertures (especially the length and diameter). By forming the recesses, a small and relatively uniform or constant thickness of the bottom of the recesses is achieved. Thus, the length of the apertures may be very clearly determined. In addition, the formation of relatively short apertures is much more accurate in terms of the diameters at the inlet side (corresponding to the fluid side) and the outlet side (corresponding to the spray side). As a result, a much more consistent geometry of the apertures relative to each other may be achieved and the GSD may be reduced. As a result, the aperture plate can be manufactured with improved repeatability in terms of the geometry of the apertures and thus the TOR, MMD, and GSD. Thus, the properties of the aerosol (the sprayed fluid) are more consistent between different aperture plates obtained from the same manufacturing process.

[0108] The aperture 20 may be formed by the same ultrashort pulse laser used to form the recess 10. However, a short pulse laser, as used in the prior art, may also be used to form the aperture 20.

[0109] In any case, the formation of the aperture 20 is preferably performed in one laser drilling step at a substantially constant laser fluence. In order to increase the accuracy of the geometric shape of the aperture (i.e., the nozzle part), only one drilling step for forming the aperture is preferred. When using only one laser drilling step, the diameters at the inlet side (corresponding to the fluid side) and outlet side (corresponding to the spray side) can be very clearly determined with the above benefits.

[0110] In another embodiment, the aperture at the bottom of the recess may also be drilled using two laser drilling stages with different fluences. For example, a first laser drilling stage with a first fluence may be used to form a first portion of the aperture at the bottom of the recess, and a second laser drilling stage with a second fluence lower than the first fluence may be used to finish the aperture (i.e., completely penetrate the bottom). In this example, the nozzle portion may be determined only by the second laser drilling stage. Thus, the bottom may remain thicker (lower recess depth) when using more than one laser drilling stage to form the aperture. This may provide greater mechanical rigidity of the aperture plate. When using two laser drilling stages, the portion 20a of the aperture 20 formed in the first laser drilling stage may have a curved inner periphery, ideally a hemispherical inner periphery, as shown in FIG. 4D. The propagation of the laser beam is a nonlinear function. Thus, a curved shape of the aperture 20 is possible by adjusting / displacing the focus of the laser beam away / with respect to the surface where the aperture 20 is formed. To form a curved inner circumferential surface of the portion 20a of the aperture 20 formed in the first laser drilling step, the focus of the laser beam may be positioned at a distance away from the bottom 12 of the recess 10 to the sprayed side 9 of the single layer 5. The portion 20b of the aperture 20 formed in the second laser drilling step may be cone- or funnel-shaped with a smaller opening at the sprayed side 9 or cylindrical as in FIG. 4A. Compared to only one laser drilling step, the remaining thickness L of the single layer 5 between the bottom 12 of the recess 10 and the sprayed side 9 is 100% smaller than the remaining thickness L of the single layer 5 between the bottom 12 of the recess 10 and the sprayed side 9. A may be larger, which improves the vibration characteristics and stability of the aperture plate 6.

[0111] The manufacturing method may comprise, as a first step, the formation of a recess 10 from a first side (fluid side 7) of the single layer 5. In a second, subsequent step, the apertures 20 are formed in the bottom 12 of the recess 10 from the first side of the single layer 5. Alternatively, the apertures 20 may be formed in the bottom 12 of the recess 10 from the second side (i.e. the spray side 9) of the single layer 5. This is especially the case when aiming for apertures 20 with a cone or funnel shape with the larger opening at the spray side 9, as shown in Figure 4C.

[0112] The aperture plate 6 and / or the single layer 5 may then be domed as previously described. Reference List 1 Vibrating Head 2 Spray device 3. Housing 4 Support member 5 Single layer 6 Aperture Plate 7 Fluid side (first side) 8 Vibrator 9 Spray side (second side) 10 Recess 11 Aperture 12 bottom 13 Periphery side wall 20 Aperture 20a Curved section 20b Funnel shaped part 21 Entrance opening 22 Exit opening 23 Side wall 30 Vibration Amplitude 100 inhalers 102 first housing part 104 Aerosol Chamber 106 Mouthpiece 108 Second housing part 110 Fluid 112 Aerosol 114 Recess in second housing part 116 Recess in first housing part 118 Connection

Claims

1. A nebulizer (2) for an inhaler (100), said nebulizer (2) comprising: an aperture plate (6) having a fluid side (7) to which a fluid (110) is supplied and a spray side (9) to which the fluid is sprayed; The spray device, wherein the aperture plate (6) comprises a single layer (5) of a single material, a plurality of recesses (10) are formed in the single layer (5), each recess (10) having an opening (11) facing the fluid side (7) and a bottom (12) facing the spray side (9), and a plurality of apertures (20) are formed in the bottom (12) of each of the recesses (10).

2. 2. The spray device of claim 1, wherein the recess (10) is laser cut, the aperture (20) is laser drilled, or both.

3. The spray device according to claim 1, wherein the arithmetic mean roughness (Ra) of the surface of the recess (10) is 0.4 μm or less.

4. 2. The spray device according to claim 1, wherein at least some of the recesses (10) are arranged in a region of an amplitude (30) of oscillation of the aperture plate (6) when the aperture plate (6) vibrates.

5. 2. The spray device according to claim 1, further comprising a vibrator configured to vibrate the aperture plate, the vibrator being attached to a surface portion of the aperture plate or to a support member supporting the aperture plate so as to directly excite the aperture plate.

6. 6. A spray device according to claim 5, wherein the vibrator is an annular piezoelectric element (8) and the recesses (10) are arranged in the single layer in a rotationally symmetrical pattern.

7. The spray device of claim 1 , wherein the recess (10) comprises one or more annular recesses, one or more circular recesses, or both.

8. A spray device as described in claim 1, wherein the apertures (20) at the bottom (12) of the recess (10) are arranged at a pitch between 5 μm and 90 μm, or between 5 μm and 50 μm.

9. The density of the apertures (20) at the bottom (12) of the recess (10) is 200 pieces / 1 mm ２ and 40,000 pieces / 1mm ２ The spray device of claim 1 , wherein

10. 2. The spray device of claim 1, wherein the recess (10) has a peripheral side wall (13), the peripheral side wall (13) being stepped, inclined, curved or straight.

11. The smallest dimension (D Ｒ 2. The spray device according to claim 1, wherein the diameter of the nozzle is between 40 and 500 μm (preferably between 70 and 400 μm), most preferably between 90 and 300 μm.

12. The aperture (20) has a diameter (D Ａ 2. The spray device according to claim 1, wherein the nozzle is circular with a diameter between 1 and 7 μm, preferably between 1.5 and 5 μm, and most preferably between 1.5 and 3 μm.

13. The length (L) of the aperture (20) in the single layer (5) Ａ 2. The spray device of claim 1, wherein the particle diameter is between 3 and 50 μm (preferably between 5 and 20 μm), most preferably between 10 and 20 μm.

14. The monolayer (5) has a thickness (T) in the direction from the fluid side (7) to the spray side (9), and the recess (10) has a depth (L) that is 50% or more of the thickness of the monolayer (5). Ｒ ), preferably a depth (L Ｒ 2. The spray device of claim 1 , further comprising:

15. 2. The spray device of claim 1, wherein each recess (10) has 2 or more, 20 or more, 50 or more, or 100 or more of said apertures (20) formed in its bottom (12).

16. Atomization device according to claim 1, characterized in that the single material of the single layer (5) is metal, preferably stainless steel.

17. 2. The spray device of claim 1, wherein the aperture (20) is cone-shaped or funnel-shaped.

18. A spray device according to claim 17, wherein the smaller opening of the aperture faces the spray side (9) or is located at the bottom (12) of the recess (10).

19. 2. A spraying device according to claim 1, wherein the aperture (20) comprises a first part (20a) having a curved or hemispherical shape and a second part (20b) having a conical or funnel-shaped shape, with a smaller opening facing the spray side (9).

20. Atomization device according to any one of the preceding claims, wherein the inner dimensions of the aperture (20), the inner dimensions of the recess (10), or both, are controlled solely by the single layer (5).

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