Dry powder inhaler

Abstract

The present invention provides a dry powder inhalation device comprising a cassette which holds two or more inhalers, each inhaler comprising: a container containing powdered medication for inhalation; an opening mechanism; and an outlet, such as a mouthpiece or a nose piece, that is covered when the inhaler is located in the cassette When an inhaler is removed from the cassette, its outlet is exposed and the corresponding opening mechanism is actuated so that the container is opened and the powder is accessible for inhalation.

Description

[0001] Dry powder inhaler

[0002] Technical Field of the invention

[0003] The present invention relates to a dry powder inhaler for oral or nasal delivery of medicament in powdered form, more specifically to an inhaler that is designed to deliver large doses of medicament.

[0004] Background to the invention

[0005] Some medical conditions that can be treated by administering a pharmaceutically active ingredient via an inhaler may have an acute onset, for example an asthma exacerbation, a myocardial infarction, or a cerebrovascular accident. Thus, it is important that the inhaler is simple to use and can quickly and effectively deliver the pharmaceutically active ingredient to the patient. Even where a medical condition does not have an acute onset, it is important that the inhaler is easy to use, because this may make it more likely that a patient persists with their treatment.

[0006] Some drugs must be taken in large quantities to achieve the desired therapeutic effect. However, there is a limit to the amount of powder (the “payload”) that can be delivered in a single inhalation, because the efficiency of aerosolization of the powder decreases as the payload increases. Consequently, if the payload is very large, not all of the powder will be aerosolized as fine particles. Moreover, for some drugs (e.g. acidic powders), if the amount of powder exceeds about 50mg, the patient may experience an involuntary cough reflex. As a result, only a partial dose of the powder is inhaled, and furthermore, the cough reflex is unpleasant for the patient. This could be addressed by the patient inhaling from several separate devices in succession, each containing a smaller dose. However, this is inconvenient, because it requires the patient to carry multiple devices. Multidose dry powder inhalers that contain a blister strip with e.g. 30 or 60 doses for daily use are well-known. However, they typically provide relatively small payloads, so multiple actuations and inhalations would be needed, which is again inconvenient for the patient.

[0007] Alternatively, the device could be designed so that the powder is released over two or more inhalations from a single container. This avoids the need for multiple devices or multiple actuations. For example, W02013 / 008040 discloses a high payload inhaler with a reservoir for the powder that moves orbitally and rotationally within a chamber when the patient inhales. The inhaler restricts the emission of powder from the reservoir, such that powder is emitted from the container steadily as it moves. This is advantageous over inhalers in which the entire powder dose is dispensed as soon as the patient starts to inhale, because steady powder emission results in better aerosolization and is less likely to induce a cough response. As a result, a greater quantity of powder can be delivered in each inhalation. Administration of a full 400mg dose requires a number of successive inhalations by the patient, typically between five and eight. However, the amount of powder released in each successive inhalation decreases, since there is less powder in the container at the start of each inhalation.

[0008] It would be desirable to have a single device which can deliver a large dose of medication consistently over a number of separate inhalations without requiring lots of user steps, such as opening and closing a mouthpiece cover to actuate the device.

[0009] Brief Description of the invention

[0010] The present inventors have found that some or all of these drawbacks can be addressed by providing a single device that contains a number of separate inhalers, each of which contains a partial dose of powdered medicament for inhalation. This ensures good aerosolization, avoids the coughing reflex and provides a consistent amount of powder on each inhalation, without the user (the patient) having to carry a number of devices. The inhalers are automatically actuated when they are removed from the device, so that no further user steps are required to prepare the inhaler for use. In this way, large amounts of powder can be delivered from a single device.

[0011] Accordingly, the present invention provides a dry powder inhalation device comprising a cassette which holds two or more inhalers, each inhaler comprising:

[0012] • a container containing powdered medication for inhalation;

[0013] • an opening mechanism; and

[0014] • an outlet that is covered when the inhaler is located in the cassette; wherein, when each inhaler is removed from the cassette, the outlet is exposed, and the corresponding opening mechanism is actuated so that the container in the inhaler is opened and the powder is accessible for inhalation. The outlet may be a mouthpiece or a nose piece. The cassette may cover the outlet when the inhaler is located in the cassette.

[0015] The direction of motion of the inhaler as it is removed from the cassette may be generally perpendicular to the longitudinal axis of the outlet (i.e. the direction of flow of the aerosolized powder through the outlet).

[0016] In one embodiment, the inhalation device has two inhalers.

[0017] Each inhaler may have grips to facilitate removal of the inhaler from the cassette. Similarly, the cassette may have grips. In one embodiment, each inhaler has a pair of grips and the cassette has a corresponding pair of grips for each inhaler.

[0018] In one embodiment, the containers are blisters comprising a base and a lid, and the opening mechanisms each comprise a piercer for piercing the lid of the respective blister.

[0019] Each inhaler may comprise a first housing part comprising the outlet and the piercer, and a second housing part comprising the blister, wherein the first and second housing parts are movable relative to each other. The first and second housing parts may be pushed together when the inhaler is removed from the cassette, causing the piercer to pierce the lid of the blister.

[0020] Each inhaler may comprise two cam surfaces, one in each side of the second housing part and the cassette may comprise corresponding pairs of cams which interact with the cam surfaces. The cams may be angled (in other words sloped) with respect to the direction of motion of the inhaler as it is removed from the cassette. Part of each cam surface at the end at which the corresponding cam is initially located (the first end), may be parallel to the direction of motion of the inhaler as it is removed from the cassette.

[0021] The device may have detent mechanisms for retaining each inhaler in the cassette before use. The device may have further detent mechanisms that prevent the second housing parts from returning to the initial position and / or prevent the inhalers from being put back into the cassette. Each inhaler may comprise a deagglomeration mechanism, such as a vortex chamber and / or a mixing element.

[0022] In another embodiment, the containers are capsules and the opening mechanisms each comprise a pair of needles for piercing the respective capsule.

[0023] The amount of the powdered medication in each container may be 5-300 mg, preferably 20- 200 mg, more preferably 30-150 mg, even more preferably 40-100 mg.

[0024] The powdered medication may contain a non-steroidal anti-inflammatory drug (NSAID), preferably, a salicylate, most preferably acetylsalicylic acid or a pharmaceutically acceptable salt thereof. Alternatively, the powdered medication may contain a bronchodilator; adrenaline and / or atropine; glucose and / or glucagon; benzodiazepine, phenytoin or anti-seizure medications; dihydroergotamine; naloxone; insulin; or a vaccine.

[0025] Brief Description of the Figures

[0026] Figure 1 shows a device according to the invention which has two inhalers.

[0027] Figures 2A and 2B show the first and second inhalers being removed from the cassette.

[0028] Figure 3 A is an expanded view showing the components of the device, and Figure 3B shows a cross-section through the device.

[0029] Figures 4A - 4E show cut away views through an inhaler as it is being removed from the cassette.

[0030] Detailed Description of the invention

[0031] Figure 1 shows a first embodiment of a device according to the invention. The device 1 has a cassette 2 that contains two individual inhalers 3 A, 3B, each having a mouthpiece 4. The device provides a full dose of powder for inhalation. A pre-metered amount of powdered medication, corresponding to half of the full dose, is contained in a blister in each of the inhalers. The cassette 2 holds and protects the inhalers. In particular, the cassette has an extension 7 at each end that extends over the respective mouthpiece 4, thereby preventing foreign material from entering the mouthpieces before use. Each inhaler has a pair of grips 5 A, 5B located on either side of the housing. The cassette has two pairs of grips 6 A, 6B located adjacent to the grips on each inhaler. In order to use the device, the user holds the grips 5A of one of the inhalers 3A between the finger and thumb of one hand, and the corresponding pair of grips 6A on the cassette 2 between the finger and thumb of their other hand. The inhaler 3A is then pulled out of the cassette, as indicated by the arrow in Figure 2A. This action causes the blister to be pierced by a mechanism which is described below. Removal of the inhaler from the cassette both uncovers the mouthpiece and opens the blister, thereby avoiding the need for any further user steps (such as pressing a button or opening a cover to expose the mouthpiece and cause piercing) before use. The user inhales on the mouthpiece to receive the first blister of medication. Then the user removes the second inhaler 3B in the same manner, as indicated by the arrow in Figure 2B, and inhales to receive the second blister of medication.

[0032] The longitudinal axis of the mouthpiece 4 (i.e. the general direction of flow of the aerosolized powder through the mouthpiece during inhalation) is perpendicular to the direction of motion of the inhaler as it is removed from the cassette 2. This configuration means that the mouthpiece 4 of each inhaler can be covered in a very simple manner by means of the extension 7, without hindering removal of the inhaler. In contrast, if the longitudinal axis of the mouthpiece were parallel to the direction of removal of the inhaler (for example as in the disposable, single dose, dry-powder inhalation device disclosed in WO2020 / 214593), then it would be necessary first to remove or open a cover to expose the mouthpiece before removing the inhaler from the cassette. This would require an additional user step.

[0033] Figure 3A is an expanded view of the device, showing the inhalers 3A, 3B and the cassette 2 in more detail. Figure 3B shows a cross-section through the device. Each inhaler has a first housing part 10 with the mouthpiece 4, a central part 30, a mixing element 35, a blister 40 and a second housing part 20.

[0034] The central part 30 is fixed (e.g. clipped or welded) in the first housing part 10. The central part 30 has two pairs of piercing elements 31 (for example of the type described in WO 2014 / 114916) on the side facing the blister. The opposite side of the central part 30 and the internal surface of the first housing part together define an airway that fluidically connects the blister (once it has been pierced) to the mouthpiece 4 via a passage 32 and a deagglomeration chamber 33. The mixing element 35 is located inside the deagglomeration chamber 33. An opening with a mesh 12 is formed in the first housing part; this connects the deagglomeration chamber 33 to the mouthpiece 4.

[0035] The blister 40 has a lid 41 and a base 42 with a rim 43 which fits into slots 21 on either side of the second housing part 20, thereby holding the blister in place in the second housing part.

[0036] The first 10 and second 20 housing parts are movable relative to each other. In the cassette, the first and second housing parts are held in an initial position in which the piercing elements 31 are held spaced apart from the lid 41 of the blister 40. The cassette prevents the first and second housing parts from accidentally being pushed together before use. When an inhaler is removed from the cassette, the cassette 2 interacts with the first 10 and second 20 housing parts, so that they are pushed together into an actuated position, in which the piercing elements 31 pierce the lid 41 and enter the blister 40. One pair of piercing elements creates an air entry opening in the lid of the blister, and the other pair creates an exit opening.

[0037] The mechanism for this consists of two pairs of cams 8A, 8B in the form of pegs on the inside of the cassette and sloping cam surfaces 22 in each side of the second housing part 20 of each inhaler. Figures 4A - 4E show cut away views of an inhaler as it is being removed from the cassette. For simplicity, only one inhaler and only part of the cassette are shown. Figure 4A shows the initial position when the inhaler 3 A is in stored inside the cassette 2. Each cam 8A sits at the first end 23 of the respective cam surface 22. As the inhaler 3 A is removed from the cassette 2, the cams 8 A slide along the cam surfaces 22, as shown in Figure 4B. Since the cam surfaces 22 are angled with respect to the direction of motion of the inhaler, the movement of the cam surfaces 22 past the cams 8A pushes the second housing part 20 to the left, into the first housing part 10. As a result, the blister (not shown in Figures 4A to 4E, so that the other components are clearly visible) is moved towards the piercer 31. When the cam is part way along the cam surface at the position shown in Figure 4C, the piercer pierces the lid of the blister. Figure 4D shows the point where the cams have reached the second end 24 of the cam surface and the piercer 31 has completely entered the blister. Thereafter, the cams 8 move along the base 25 of the second housing part 20 as shown in Figure 4E, until the inhaler completely disengages from the cassette. The cam surfaces 22 have a short section that is not angled at their first ends 23. This allows a small amount of reversible motion of the inhaler relative to the cassette before the first 10 and second 20 housing portions start to move together.

[0038] The device may have a detent mechanism, for example formed by a clip on the inside of the cassette (not visible in Figure 3) and a protrusion 14 on the first housing part, that provides a small force that holds the inhalers in the cassette. This force is easily overcome when the inhaler is pulled out of the cassette by the user but is sufficient to hold the inhaler in the cassette against gravity if it is turned upside down, and also to prevent accidental actuation before use, for example during transport from the manufacturer.

[0039] The inhaler may have a further detent mechanism, such as a clip, that prevents the second housing part from returning to its initial position and / or prevents the user from re-inserting the inhaler into the cassette, since the inhaler is pre-loaded with a blister and intended for single use only.

[0040] Once the inhaler has been removed from the cassette, the user inhales on the mouthpiece 4. This creates an air flow into the blister through the entry opening which aerosolizes the powder, and then carries it out through the exit opening into the passage 32 and then into the deagglomeration chamber 33. The chamber may have one or more inlets for external (i.e. powder-free) air, for example a tangential inlet that creates a vortex in the chamber. This, in combination with the mixing element, deagglomerates the powder into fine particles. The aerosolized fine powder then leaves the deagglomeration chamber 33 via the mesh and flows out through the mouthpiece to the user’s lungs. The mesh 12 prevents any large lumps of powder from leaving the deagglomeration chamber.

[0041] The embodiment shown in Figures 1, 2 and 3 has two inhalers in the cassette. These may be labelled (e.g. “1” and “2”) or coloured to indicate to the user that both inhalers are to be used, or to indicate the order in which the inhalers are to be used, for example if they contain different medications. The cassette may contain any number of inhalers, for example three, four, or five inhalers, or even up to ten inhalers or more.

[0042] The inhalers described above have a blister that contains the dry powder medication, which is pierced by the piercing elements. However, the invention also encompasses other containers, such as a capsule, and other opening mechanisms, such as peeling a lid off a blister, pulling two halves of a capsule apart or piercing a capsule by means of needles, as in WO2020 / 257845 for example. Regardless of which type of opening mechanism is used, the inhaler is automatically actuated by the action of removing it from the cassette.

[0043] The blister, capsule or other container contains a dry powder medication for inhalation. The medication comprises a pharmaceutically active ingredient and may also comprise one or more pharmaceutically acceptable excipients. The amount of the powdered medication in the blister or capsule may be 5-300 mg, preferably 20-200 mg, more preferably 30-150 mg, even more preferably 40-100 mg. For example, there may be about 50, 60, 70, 80 or 90 mg of powder in the blister or capsule. The contents of each inhaler may be delivered from the inhaler in a single inhalation or in two or more inhalations.

[0044] The medication may be capable of treating or preventing a thromboembolic event. The pharmaceutically active ingredient in the medication may be an antiplatelet drug. For example, the pharmaceutically active ingredient may be a non-steroidal anti-inflammatory drug (NSAID). Preferably, the pharmaceutically active ingredient is a salicylate (a salt or ester of salicylic acid), most preferably acetylsalicylic acid or a pharmaceutically acceptable salt thereof. The pharmaceutically active ingredient may be another type of NSAID. For example, the pharmaceutically active ingredient may be Celecoxib (Celebrex), Dexdetoprofen (Keral), Diclofenac (Voltaren, Cataflam, Voltaren-XR), Diflunisal (Dolobid), Etodolac (Lodine, Lodine XL), Etoricoxib (Algix), Fenoprofen (Fenopron, Nalfron), Firocoxib (Equioxx, Previcox), Flurbiprofen (Urbifen, Ansaid, Flurwood, Proben), Ibuprofen (Advil, Brufen, Motrin, Nurofen, Medipren, Nuprin), Indomethacin (Indocin, Indocin SR, Indocin IV), Ketoprofen (Actron, Orudis, Oruvail, Ketoflam), Ketorolac (Toradol, Sprix, Toradol IV / IM, Toradol IM), Licofelone (under development), Lorn oxicam (Xefo), Loxoprofen (Loxonin, Loxomac, O%er|o), Lumiracoxib (Prexige), Meclofenamic acid (Meclomen), Mefenamic acid (Ponstel), Meloxicam (Movalis, Mel ox, Recoxa, Mobic), Nabumetone (Relafen), Naproxen (Aleve, Anaprox, Midol Extended Relief, Naprosyn, Naprelan), Nimesulide (Sulide, Nimalox, Mesulid), Oxaporozin (Daypro, Dayrun, Duraprox), Parecoxib (Dynastat), Piroxicam (Feldene), Rofecoxib (Vioxx, Ceoxx, Ceeoxx), Salsalate (Mono-Gesic, Salflex, Disalcid, Salsitab), Sulindac (Clinoril), Tenoxicam (Mobi flex), Tolfenamic acid (Clotam Rapid, Tufnil), or Valdecoxib (Bextra). The pharmaceutically active ingredient may be an alternative to an NSAID. Such alternatives include P2Y12 inhibitors. Examples of P2Y12 inhibitors include Plavix (clopidogrel), ticlopidine, ticagrelor, prasugrel, and cangrelor. Other pharmaceutically active ingredients may include COX-2 inhibitors, and Nattokinase (an enzyme EC 3.4.21.62, extracted and purified from a Japanese food called natto). The medication may comprise both acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, and a P2Y12 inhibitor.

[0045] The term “pharmaceutically active ingredient” does not include nicotine or nicotine salts. Thus the medication does not contain nicotine or nicotine salts.

[0046] The pharmaceutically active ingredient may alternatively be a bronchodilator, such as a beta-2 agonist or anticholinergic for the treatment of an asthma exacerbation; adrenaline and / or atropine for the treatment of cardiac failure, cardiac dysfunction, cardiac arrest, anaphylaxis, drug overdose or the like; glucose and / or glucagon for the treatment of hypoglycaemia, diabetes induced coma or the like; benzodiazepine, phenytoin or anti-seizure medications for the treatment of seizure; dihydroergotamine for the treatment of migraine; naloxone for treating an opioid overdose; insulin for managing blood sugar level or the like.

[0047] The medication may include one or more agents for inducing an immune response, e.g. a vaccine, such as a measles vaccine, a Hepatitis B vaccine, or an influenza vaccine.

Claims

Claims1. A dry powder inhalation device comprising a cassette which holds two or more inhalers, each inhaler comprising:• a container containing powdered medication for inhalation;• an opening mechanism; and• an outlet that is covered when the inhaler is located in the cassette; wherein, when each inhaler is removed from the cassette the outlet is exposed and the corresponding opening mechanism is actuated so that its container is opened.

2. A dry powder inhalation device according to claim 1, wherein the longitudinal axis of the outlet is perpendicular to the direction of motion of the inhaler as it is removed from the cassette.

3. A dry powder inhalation device according to claim 1 or claim 2, which has two inhalers.

4. A dry powder inhalation device according to any of claims 1 to 3, wherein each inhaler has a pair of grips and the cassette has a corresponding pair of grips for each inhaler to facilitate removal of each inhaler from the cassette.

5. A dry powder inhalation device according to any of claims 1 to 4, wherein the containers are blisters comprising a base and a lid, and the opening mechanisms each comprise a piercer for piercing the lid of the respective blister.

6. A dry powder inhalation device according to claim 5, wherein each inhaler comprises a first housing part comprising the outlet and the piercer, and a second housing part comprising the blister, wherein the first and second housing parts are movable relative to each other.

7. A dry powder inhalation device according to claim 6, wherein the first and second housing parts are pushed together when the inhaler is removed from the cassette, causing the piercer to pierce the lid of the blister.

8. A dry powder inhalation device according to claim 7, wherein each inhaler comprises two cam surfaces, one in each side of the second housing part and the cassette comprises corresponding pairs of cams which interact with the cam surfaces.

9. A dry powder inhalation device according to claim 8, wherein the cam surfaces are angled with respect to the direction of motion of the inhaler as it is removed from the cassette.

10. A dry powder inhalation device according to claim 9, wherein each cam surface has a first end at which the corresponding cam is initially located, and wherein a part of each cam surface at the first end is parallel to the direction of motion of the inhaler as it is removed from the cassette.

11. A dry powder inhalation device according to any of claims 1 to 10, wherein the device has detent mechanisms for retaining each inhaler in the cassette before use.

12. A dry powder inhalation device according to any of claims 1 to 11, wherein the device has detent mechanisms that prevent the second housing parts from returning to the initial position and / or prevent the inhalers from being put back into the cassette.

13. A dry powder inhalation device according to any of claims 1 to 12, wherein each inhaler comprises a deagglomeration mechanism, such as a vortex chamber and / or a mixing element.

14. A dry powder inhaler according to any of claims 1 to 13, wherein the medication comprises a non-steroidal anti-inflammatory drug; a bronchodilator; adrenaline and / or atropine; glucose and / or glucagon; benzodiazepine, phenytoin or anti-seizure medications; dihydroergotamine; naloxone; insulin; or a vaccine.

15. A dry powder inhaler according to any of claims 1 to 14, wherein the amount of the powdered medication in each container is from 5 to 300mg.

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