Patent Application
20250065059
The present invention relates to a dry powder inhaler, i.e. a device for dispensing a powdered medicament preparation by inhalation. The device is in particular a portable, multiple-dose, breath activated dry powder inhaler without propellant gas, equipped with a metering device which dispenses doses from a medicament container.
Inhalers are hand-held portable devices that deliver medication directly to the lungs. One class of inhalers is passive dry powder inhalers (“DPI”). A passive DPI is a patient driven device wherein the action of breathing in through the device draws the powder formulation into the respiratory tract. DPIs are well recognized as a method of drug delivery to the lung for treatment of pulmonary and systemic diseases. They can generally be divided in: i) single-dose (unit-dose) inhalers, for the administration of an individual dose of the active ingredient/s (in capsule or blister) loaded by the patient immediately before use; ii) pre-metered multi-dose inhalers containing a series of blisters or capsules with the active ingredient/s formulation or iii) reservoir inhalers containing a larger amount of the powder formulation of active ingredient/s, corresponding to multiple doses, which is metered from a storage unit just before inhalation.
Document WO 2004/012801, by the same Applicant, discloses a powder inhaler comprising a casing with a lower shell and an integral cover pivotably coupled to the lower shell. The lower shell delimits a mouthpiece and the integral cover is movable between a closed position in which the mouthpiece is enclosed and hidden by the integral cover and an open position in which the mouthpiece is exposed for use. The lower shell houses a container for storing a powdered medicament, a metering member having a dosing recess to be filled with a dose of the powdered medicament and an inhalation channel in communication with the mouthpiece. The powder inhaler further comprises a protective member which is slidingly moveable on the metering member between a closed position, in which the protective member covers the dosing recess of the metering member if the metering member is in an inhalation position, and an open position, in which the protective member exposes the dosing recess thereby enabling inhalation of the dose of the powdered medicament contained in the dosing recess. The protective member is coupled to an inhalation actuated mechanism in such a manner that the inhalation actuated mechanism moves the protective member from its closed position to its open position if there is an inhalation suction force exerted by a user which exceeds a predetermined level.
Document WO 2016/000983, by the same Applicant, discloses a powder inhaler similar to the one of WO 2004/012801.
Document WO 92/09322 discloses a propellant-free inhalation device with a supply of pulverized medical substance. The device is provided with a mouthpiece for active inhalation and an air channel to distribute a dose discharged from a dosing chamber in the flow of breathing air. The mouthpiece can be closed with a cover which comprises detent noses to engage into air intakes and subsequently close the same and take care of a safe sealing of the device.
Document US 2012/0017902 discloses a nasal delivery device comprising a cap provided for covering a discharge aperture of a discharge member of the device during non-use. A seal protrusion extends from an inner surface of the cap to engage the discharge member.
Document U.S. Pat. No. 8,508,385 discloses a metering device for inhaling a powder substance comprising a closure cap.
Document US 2016/0095990 discloses a deformable mouthpiece cover made from an elastomeric material for a dry powder inhaler.
A formulation for powder inhalers is commonly a powder blend of one or more active ingredients dispersed in a pharmacologically inert bulk solid, comprising a physiologically acceptable diluent, such as lactose, and optional additional excipients such as lubricants. The particle size of inhalable active ingredients should be optimized to deliver the drug deep into the lung to achieve efficacy. This efficacious particle size typically lies between 1-6 μm whereas larger particles, in the range 6-10 μm, tend to be deposited in the upper airways without reaching the site of action in the lower airways.
It is well known that stability of the powder as well as the aerosol performances could be affected by environmental conditions, humidity in particular. Therefore, it is desirable to control the humidity within powder inhalers and in particular in reservoir DPIs. There is the need of more efficacious systems to protect from humidity, in particular but not solely, when the drug-containing powder formulation from reservoir DPIs are intended for being stored and used in sub-tropical and tropical countries.
It is an object of the present invention to eliminate the above drawbacks of hitherto known powder inhalers and to provide a powder inhaler with an improved protection from environmental conditions, like humidity, temperature, light, pressure.
In particular, it is an object of the present invention to provide a powder inhaler which is able to control the humidity inside the inhaler itself.
It is object of the present invention to prevent or at least to limit the entry of atmospheric moisture inside the inhaler and in particular inside the container storing the powdered medicament during distribution and storage at a pharmacy (i.e. before delivering the inhaler to the user) and also after delivering the inhaler to the user, during the time period (e.g. days, months) when the user uses the inhaler.
At least one of the above objects is substantially achieved by a powder inhaler according to one or more of the appended claims and/or of the following aspects.
In accordance with a 1st independent aspect, a powder inhaler, comprises:
The word “more deformable” referred to the sealing element in this description and claims means that, when the sealing element engages the mouthpiece and/or the casing, said sealing element deforms more than the mouthpiece and/or the casing so as to adapt its shape to that of the mouthpiece and/or of the opening of the mouthpiece and/or the casing and copy its/their shape. In other words, the sealing element is more flexible and softer than the mouthpiece and/or the casing in order to mimic the external geometry of the mouthpiece and/or casing, to fill the gaps of the mouthpiece/casing and avoid that humidity could enter through these gaps.
The invention allows to improve the stability of the powder and the aerosol performances (i.e. the capability of delivering the drug deep into the lung to achieve efficacy) by protecting said powder from the environmental conditions, particularly from humidity.
In particular, the invention allows to prevent or at least limit the entry of atmospheric moisture inside the inhaler through the mouthpiece and/or the air channel/s when the cover of the inhaler is closed.
Therefore, the invention allows to protect the powder during the period when the inhaler is in use but is closed and stored in a bag, in a pocket, in the open air, in a drawer or in a furniture or other place between inhalations.
Other aspects of the invention are disclosed in the following.
In a 2nd aspect according to aspect 1, the casing has at least one air inlet in fluid communication with the inhalation channel to allow air intake at least when the user inhales through the mouthpiece; when the cover is engaged with the casing and closes the mouthpiece, an auxiliary portion of the sealing element is coupled to the at least one air inlet to tight close said at least one air inlet; optionally wherein the material of the sealing element is more deformable than a material of the casing.
In a 3rd aspect according to any of the preceding aspects, the sealing element comprises or is made of at least one of the following materials: silicone, thermoplastic elastomer (TPE), in particular TPE for medical—pharmaceutical applications, for instance styrene block copolymers (TPS (TPE-s)), thermoplastic polyolefin elastomers (TPO (TPE-o)), thermoplastic vulcanizates (TPV (TPE-v or TPV)), thermoplastic polyurethanes (TPU), thermoplastic copolyesters (TPC (TPE-E)), thermoplastic polyamides (TPA (TPE-A)), not classified thermoplastic elastomers (TPZ).
In a 4th aspect according to any of the preceding aspects, the sealing element has a hardness between 10 Shore A and 60 Shore A (soft and medium soft materials), optionally between 20 Shore A and 50 Shore A, optionally between 25 Shore A and 35 Shore A, optionally of 30 Shore A.
In a 5th aspect according to any of the preceding aspects, the sealing element has a thickness between about 0.2 mm and 5 mm, preferably between about 1 mm and 2 mm.
In a 6th aspect according to any of the preceding aspects, the sealing element is over-molded to the cover or press-fit in the cover and optionally glued to the cover or mechanically connected to the cover.
In a 7th aspect according to any of the preceding aspects, the main portion of the sealing element has a shape copying a shape of the mouthpiece, optionally at least when the cover is engaged with the casing and closes the mouthpiece.
In an 8th aspect according to any of the preceding aspects, the main portion of the sealing element comprises a convex part.
In a 9th aspect according to the preceding aspect, the convex part is dome shaped.
In a 10th aspect according to the preceding aspect 8 or 9 a top portion of the mouthpiece delimits a concave area and the opening is fashioned in said concave area; the convex part of the sealing element having a shape copying at least in part a shape of the concave area.
In a 11th aspect according to the preceding aspect 10, the concave area has a circular or oval or elliptical outline; optionally the opening has a circular outline.
In a 12th aspect according to the preceding aspect 11, the opening is off-center with respect to the circular or oval or elliptical outline of the concave area.
In a 13th aspect according to the preceding aspect 11 or 12, when the cover is engaged with the casing and closes the mouthpiece, the convex part of the sealing element is centered on the opening.
In a 14th aspect according to any of the preceding aspects 10 to 13, the main portion of the sealing element comprises an annular or elliptical recess surrounding the convex part and accommodating, when the cover is engaged with the casing and closes the mouthpiece, a rim of the top portion of the mouthpiece.
In a 15th aspect according to aspect 2 or to any other aspect when according to aspect 2, the second auxiliary portion of the sealing element has a shape copying a shape of said at least one air inlet.
In a 16th aspect according to aspect 2 or to any other aspect when according to aspect 2, the at least one air inlet is slit shaped and the auxiliary portion of the sealing element comprises at least one rib engageable in the slit shaped air inlet.
In a 17th aspect according to aspect 2 or to any other aspect when according to aspect 2, the casing has a plurality of slit shaped air inlets and the auxiliary portion comprises a plurality of ribs each engageable in one of the slit shaped air inlet (5).
In a 18th aspect according to the preceding aspect 17, the slit shaped air inlets are parallel to each other and the ribs are parallel to each other.
In a 19th aspect according to the preceding aspect 17 or 18, the at least one slit shaped air inlet is fashioned in part on a side of the casing carrying the mouthpiece and in part on one corner of the casing, the at least one rib having a curved design to follow the at least one slit shaped air inlet.
In a 20th aspect according to aspect 2 or to any other aspect when according to aspect 2, the sealing element is made of a single body comprising the main portion and the auxiliary portion.
In a 21st aspect according to aspect 2 or to any other aspect when according to aspect 2, the sealing element has a first surface coupled to an inner surface of the cover and a second surface carrying the main portion and the auxiliary portion.
In a 22nd aspect according to the preceding aspect 21, the first surface has indentations and/or recesses configured to couple with elements of the cover and/or to hold glue connecting the sealing element to said cover.
In a 23rd aspect according to the preceding aspect 21 or 22, the inner surface of the cover is substantially concave and the first surface of the sealing element is substantially convex.
In a 24th aspect according to any of the preceding aspects 21 to 23, when the cover is engaged with the casing and closes the mouthpiece, portions of the second surface of the sealing element other than the main portion and the auxiliary portion are spaced from the casing.
In a 25th aspect according to any of the preceding aspects, the mouthpiece comprises or is made of at least one rigid thermoplastic material, optionally of the following materials: polypropylene (PP), polyethylene (PE), polyvinylchloride (PVC), polycarbonate (PC), polyethylene (PE), polyamide (PA, such as Nylons).
In a 26th aspect according to any of the preceding aspects, the mouthpiece has a hardness greater than 30 Shore D (hard and extra-hard materials), optionally lower than 100 Shore D.
In a 27th aspect according to any of the preceding aspects, the casing comprises or is made of at least one rigid thermoplastic material, optionally of the following materials: PP, PE, PVC, ABS, PC, PET, Nylon.
In a 28th aspect according to any of the preceding aspects, the casing has a hardness greater than 30 Shore D (hard and extra-hard materials), optionally lower than 100 Shore D.
In a 29th aspect according to any of the preceding aspects, the cover comprises or is made of at least one rigid thermoplastic material, optionally of the following materials: PP, PE, PVC, ABS, PC, PET, Nylon.
In a 30th aspect according to any of the preceding aspects, the cover has a hardness greater than 30 Shore D (hard and extra-hard materials), optionally lower than 100 Shore D.
In a 31st aspect according to any of the preceding aspects, the powder inhaler comprises a desiccant chamber placed inside the casing and containing or configured to contain a desiccant, wherein the desiccant comprises molecular sieves.
In a 32nd aspect according to the preceding aspect 31, the desiccant is contained in a bag able of being inserted in the desiccant chamber or the desiccant is in the form of a single tablet able of being inserted in the desiccant chamber.
In a 33rd aspect according to the preceding aspect 31 or 32, the desiccant chamber is part of the container for the powdered medicament.
In a 34th aspect according to the preceding aspect 33, a permeable membrane separates the desiccant chamber from a medicament chamber delimited by the container.
In a 35th aspect according to the preceding aspect 34, a permeability of the permeable membrane is different from, in particular greater than that between either the desiccant or the medicament and the outside environment.
In a 36th aspect according to any of the preceding aspect 31 to 35, the molecular sieves are made of a material with pores of uniform size configured to absorb small molecules, such as molecules of water.
In a 37th aspect according to the preceding aspect 36, the molecular sieves comprise alkaline salts of aluminosilicates, called zeolites, or aluminophosphates or porous glass or active carbon or artificial zeolites.
In a 38th aspect according to any of the preceding aspects 31 to 37, the powder inhaler further comprises the powder medicament and/or the desiccant.
In a 39th aspect according to any of the preceding aspects, the cover is hinged to the casing and is movable between an open position and a closed position in which the cover is engaged with the casing and closes the mouthpiece.
In a 40th aspect according to any of the preceding aspects, the dispensing device comprises a metering device configured to meter suitable amounts of unit doses of the powdered medicament.
In a 41st aspect according to the preceding aspect, the metering device has at least one dosing recess; the metering device being movable, with respect to the container and the inhalation channel, between an idle state, in which the dosing recess is in communication with an opening of the container so as to be filled with a dose of the powdered medicament, and a triggered state, in which the dosing recess is in communication with the inhalation channel for enabling inhalation of the dose of the powdered medicament contained in the dosing recess through the mouthpiece.
In a 42nd aspect according to any of the preceding aspects, the powdered medicament is a pharmaceutical composition comprising a pharmaceutically acceptable salt of formoterol, optionally in combination with a pharmaceutically acceptable salt of glycopyrronium and/or beclometasone dipropionate (BDP).
In a 43rd aspect according to any of the preceding aspects, the powder inhaler comprises a dose counting unit contained into the casing and coupled to an inhalation actuated mechanism and/or to the cover; optionally, the casing comprises a window or an opening for displaying the number of doses taken or the number of doses left in the powder inhaler, said number being counted by the dose counting unit.
With reference to the appended drawings,
The powder inhaler 1 comprises a casing 2 and a cover 3 being pivotably or rotatably coupled to the casing 2. As can be taken from
The casing 2 is a closed shell made of a rigid thermoplastic material (e.g. PP, PE, PVC, ABS, PC, PET, Nylon, etc.) and comprises lateral sides, an upper side and a lower side (upper and lower with respect to the orientation of the powder inhaler 1 of
The concave area 7 and the rim 8 have an oval outline and the opening 6 has a circular outline. In other embodiment, not shown, the shape of the opening 6 and of the top portion of the mouthpiece 4 may be others (e.g. circular or elliptical). As can be seen in
The air inlets 5 are slit shaped and parallel to each other. These slit shaped air inlets 5 are formed partly on the upper side and partly on a corner of the casing 2 connecting the upper side to one of the lateral sides (
The cover 3 is an open shell made of plastic material (e.g. the same material of the casing 2) and having an outer surface and a substantially concave inner surface 9. The inner surface 9 comprises two lateral sides and one bottom side. The cover 3 is hinged to the casing 2 and can be rotated between a closed position, shown in
The powder inhaler 1 comprises a container 10 for storing a powdered medicament, an inhalation channel 11 connected to the opening 6 of the mouthpiece 4 and a dispensing device 12. The inhalation channel 11 has a first opening connected to the mouthpiece 4 and a second opening, opposite with respect to the first opening. As shown in
As is shown in
The container 10, in particular the medicament chamber 13, is filled or is configured to be filled with an amount of powder medicament corresponding to a plurality of doses, e.g. up to 100-200 doses. For instance, the powdered medicament is a pharmaceutical composition comprising a pharmaceutically acceptable salt of formoterol, e.g. in combination with a pharmaceutically acceptable salt of glycopyrronium and/or beclometasone dipropionate (BDP).
The desiccant is contained in a bag able of being inserted in the desiccant chamber 14 or the desiccant is in the form of a single tablet able of being inserted in the desiccant chamber 14. The desiccant is or comprises molecular sieves made of a material with pores of uniform size, for instance alkaline salts of aluminosilicates, called zeolites, or aluminophosphates or porous glass or active carbon or artificial zeolites. The molecular sieves are configured to absorb small molecules such as molecules of water.
The dispensing device 12 comprises a metering device 16 having a dosing recess 17. The metering device 16 shown in
The shuttle is slidingly moveable between a filling position (
The shuttle is mechanically coupled to the cover 3 such that an opening of the cover 3 beyond a range of rotational movement from the closed position causes the shuttle to move from the filling position to the inhalation position. Closing of the cover 3 causes the shuttle to move back from the inhalation position to the filling position.
The protective member 18 is parallel with respect to the shuttle and is slidingly movable on the shuttle between a closed position and an open position. In the closed position, the protective member 18 is shifted backwards towards the second opening of the inhalation channel 11 and towards the container 10. In the closed position, a rear part of the protective member 18 may at least in part close the second opening of the inhalation channel 11. In the open position, the protective member 18 is shifted forward towards a wall of the casing 2. In the open position, a rear part of the protective member 18 leaves the second opening of the inhalation channel 11 open.
The protective member 18 is in the closed position when the shuttle is in the filling position. The protective member 18 may be moved between the closed position and the open position when the shuttle is in the inhalation position. Therefore, the metering device 16 is configured to take the three different states cited above (idle, armed, triggered) and these states are determined by the positions of the shuttle and of the protective member 18. In the idle state, the shuttle is in the filling position and the protective member 18 is in the closed position. The protective member 18 does not cover the dosing recess 17. The dosing recess 17 is communication with the opening of the container 10 to receive the medicament dose. In the armed state, the shuttle is in the inhalation position and the protective member 18 is in the closed position. The protective member 18 covers the dosing recess 17. The protective member 18 prevents the powdered medicament contained in the dosing recess 17 from entering the inhalation channel 11 and being lost in case of rotation or movement of the inhaler in oblique position before the inhalation manoeuvre or if the user blows into the mouthpiece. In the triggered state, the shuttle is in the inhalation position and the protective member 18 is in the open position. The protective member 18 does not cover the dosing recess 17, thereby exposing the dosing recess 17 to the inhalation channel 11 so as to enable a user to inhale the dose of the powdered medicament contained in the dosing recess 17.
The powder inhaler 1 shown in the attached
The flap 20 is coupled to the protective member 18 through the coupling member 21 such that, if there is an inhalation suction force exceeding a predetermined value, the flap 20 is moved from a first position to a second position, thereby causing the protective member 18 to move from the closed position to the open position. The flap 20 is placed inside the casing 2 and close to the air inlets 5.
In the first position (
The flap 20 is hinged to the casing 2 in order to rotate between the first position and the second position around a respective rotation axis which is substantially perpendicular to a main axis Z-Z of the inhalation channel 11. The coupling member 21 is also hinged to the casing 2 in order to rotate between a respective first position and second position around a respective rotation axis Y-Y which is substantially perpendicular to the main axis Z-Z of the inhalation channel 11.
The coupling member 21 comprises an arm, not shown in
The coupling member 21 comprises a prolongation 23 engaging with an opening formed in the protective member 18 in order to move the protective member 18 from the closed position to the open position when the coupling member 21 moves from its respective first position to its respective second position and vice-versa.
The prolongation 23 of the coupling member 21 is also moveably arranged in a longitudinal opening 24 which is formed in the shuttle along its longitudinal direction, such that said prolongation 23 can freely move in the longitudinal opening 24, while a movement of the shuttle from the inhalation position to the filling position causes the prolongation 23 of the coupling member 21 to abut against an edge of the longitudinal opening 24 thereby moving the coupling member 21 back into its initial first position.
The internal mechanisms and functioning of the powder inhaler 1 disclosed here above are substantially the same as disclosed in document WO2021/105440, by the same Applicant.
The powder inhaler 1 may also comprise a dose counting unit, not shown in the embodiment of the attached drawings, contained into the casing 2 and coupled both to the inhalation actuated mechanism 19 and to the closure of the cover 3 after an efficacious inhalation has occurred. The casing 2 may also comprise a window or an opening for displaying the number of doses taken or the number of doses left in the container 10, this number being counted by the dose counting unit. For instance, the dose counting unit is the same or similar to the one disclosed in document WO 2004/012801.
According to the present invention, the powder inhaler 1 further comprises a sealing element 25 housed in the cover 3 (as shown in
The sealing element 25 is coupled to the bottom side of the inner surface 9 of the cover 3 and may be over-molded to the cover 3 or press-fit in the cover and optionally glued to the cover 3 or mechanically connected to the cover 3 in another way. Different views of the standalone sealing element 25 are shown in the attached
The sealing element 25 is made of a material that is softer and more deformable than the material of the mouthpiece 4 and usually of the casing 2. The sealing element 25 is made of a soft or a medium soft material. In some embodiments, the sealing element 25 is made of silicone, e.g. PlatSil® FS-20 mixed with PlatSil® GEL-25. In other embodiments, the sealing element 25 may be of a thermoplastic elastomer (TPE), in particular TPE for medical-pharmaceutical applications, for instance styrene block copolymers (TPS (TPE-s)), thermoplastic polyolefin elastomers (TPO (TPE-o)), thermoplastic vulcanizates (TPV (TPE-v or TPV)), thermoplastic polyurethanes (TPU), thermoplastic copolyesters (TPC (TPE-E)), thermoplastic polyamides (TPA (TPE-A)), not classified thermoplastic elastomers (TPZ). Suitable TPE may be selected from those of medical-pharmaceutical grade belonging to any of the classes listed above. For instance, the sealing element 25 has a hardness between 20 Shore A and 50 Shore A (e.g. 30 Shore A) and the casing 2 together with the mouthpiece 4 and the cover 3 have a hardness greater than 30 Shore D and lower than 100 Shore D (hard and extra-hard materials).
When the cover 3 is engaged with the casing 2 and closes the mouthpiece 4, a main portion 26 of the sealing element 25 is coupled to the opening 6 to tight close said opening 6 and an auxiliary portion 27 of the sealing element 25 is coupled to the air inlets 5 to tight close said air inlets 5. In the embodiment of
The main portion 26 and the auxiliary portion 27 mimic the external geometry of the top portion of the mouthpiece 4 and of the air inlets 5, in order to fill the gaps and avoid that humidity could enter through those gaps. Furthermore, the difference between the hardness of materials is such that, when the sealing element 25 engages the mouthpiece 4 and the casing 2 (closed position), said sealing element 25 deforms more than the mouthpiece 4 and the casing 2 so as to adapt its shape to that of the mouthpiece 4 and the casing 2 and copy their shape.
In the embodiment of the attached Figures, the sealing element 25 is made of a single body having a first substantially convex surface 28 coupled to the concave inner surface 9 of the cover 3 and a second surface 29 carrying the main portion 26 and the auxiliary portion 27. In other embodiments, not shown, the main portion 26 and the auxiliary portion 27 may be two separate parts.
As represented in
As shown in particular in
The main portion 26 of the sealing element 25 has a shape copying a shape of the concave area 7 and of the rim 8 of the mouthpiece 4 and to seal the opening 6 when the cover 3 is engaged with the casing 2 and closes the mouthpiece 4 (closed position of
The auxiliary portion 27 comprises a plurality of ribs 34 parallel to each other and each engageable in one of the slit shaped air inlets 5. The ribs 34 have a curved design to copy the shape of the slit shaped air inlets 5 in order to seal said slit shaped air inlets 5 when the cover 3 is in the closed position. As shown in
A test was performed by comparing a powder inhaler as detailed above with no sealing element with two different powder inhalers provided with the sealing element 25 made of PlatSil® FS-20 mixed with PlatSil® GEL-25.
Two different embodiments of the invention were tested:
Test conditions: 30° C. and 75% RH.
The desiccant was removed from the desiccant chamber 14 and the medicament chamber 13 was filled with 3 g of calcium chloride anhydrous to evaluate the moisture ingress in said medicament chamber 13.
The chart of
After 41 days (984 h), both the embodiments B and C exhibit an improvement in the humidity protection.
The chart of
The press-fit concept shows a saving of 39 mg of water (10%) and the over-molded concept a saving of 30 mg (8%). Both the embodiments B and C show a cumulative effect (the saving of absorbed water increases over time).
The sealing element according to the invention may also be implemented in powder inhalers other than the one illustrated herein by way of example, e.g. with other shapes of the mouthpiece and/or of the cover and/or of the casing and/or with different couplings between the cover and the casing, different dispensing devices, etc. The features of the sealing element of the invention (e.g. shapes, materials, etc.) will be designed/suitable for the respective powder inhaler in order to provide a correct sealing of the mouthpiece and of any air vent.
| Number | Date | Country | Kind |
|---|---|---|---|
| 21216517.9 | Dec 2021 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2022/086690 | 12/19/2022 | WO |
