Field of the invention

The present invention relates to a dosing device comprising a powder hopper and a plate with a surface, wherein said plate is provided with at least one cavity adapted for receiving a particulate material, and filling means being movable along said surface for moving particulate material into said at least one cavity. The present invention also relates to a method for filling a cavity provided in a plate of a dosing device with a quantity of particulate material.

Background of the invention

Today supply and distribution of medicament is accomplished in many different ways. Within health care more and more effort is focused on the possibility to dose and distribute medicaments in the form of powder directly to the lungs of a user by means of a dispensing device, for example an inhalation device, to obtain an efficient and user friendly administration of the specific medicament. In most cases, some form of dosing process is used for preparing the dose to be inhaled. For instance, the doses of medicament may be provided in packs having several cavities for housing a dose of medicament. The cavities filled with a dose are subsequently sealed by a sealing sheet, for example a foil of aluminium. These packs are loaded into a dispensing device, in which the foil above the cavity is penetrated or and the dose of medicament is released for inhalation by the user. By this sealing, the medicament is well protected before inhalation.

There are also other cases where it is suitable to provide doses of medicament in packs having cavities for housing a dose of medicament, which cavities are sealed by a foil. The packs containing the doses of medicament can be in the form of blister packs or injection moulded discs provided with blisters and cavities, respectively, for housing the powdered medicament, the packs can have various shapes, and the cavities can be distributed in various patterns. The method for filling said cavities should provide an accurate and changeable dosing into the cavities, to provide packs containing accurate doses of medicament of different sizes.

It is often desired, in both of the above-mentioned situations, that the cavities are not completely filled with the medicament. Therefore, a dosing process may be used in which cavities of a dosing device are filled with desired dose of medicament, said cavities of the dosing device having a smaller volume than the cavities of the final packs, and thereafter the medicament is transferred to the final pack. By this it is possible to distribute a specified dose of powder having a smaller volume than the volume of the cavity housing the dose, with a satisfactory accuracy. One method and device for filling cavities in a drug disc with a quantity of particulate material is disclosed in WO 06/118526. It discloses a filling element which is provided with a bottom surface comprising several chambers, the amount of which is the same as the amount of cavities in the drug disc. The filling element has scraper means in the form of four rotating scrapers for scrape filling the chambers. When using the filling element, powdered medicament is dispensed on the surface of the filling element and scraped into the chambers by the scraper means. After the particulate material has been filled in the chambers of the filling element, the particulate material is transferred to the drug disc. However, the above-mentioned solution has the drawback that it is not suitable for all forms of particulate material. For example particulate material that has limited free-flowing characteristics may be adhered to lumps, which may cause uneven distribution of the material between different cavities, i.e. some of the cavities may not be filled with the desired amount of medicament.

An object of the present invention is therefore to provide a method and device for filling at least one cavity with a quantity of particulate material (such as powder), which thereafter can distribute an accurate dose of particulate material having a smaller volume than that of the cavity housing the dose, that can handle cohesive particulate material, i.e. particulate material that does not flow freely, and that gives an accurate distribution of the particulate material in each of the cavities.

Summary of the invention The above-mentioned objects are achieved by a dosing device of the kind defined in claim 1. Said dosing device comprises a powder hopper and a plate with a surface, wherein said plate is provided with at least one cavity adapted for receiving a particulate material, and filling means being movable along said surface for moving particulate material into said at least one cavity, wherein said filling means is adapted to exert a compressing force on said particulate material in a direction towards said surface so that said particulate material is forced into said at least one cavity.

Particulate material that has limited free-flowing abilities has a tendency to adhere to each other, causing small lumps of the material. When shovelling material into cavities, as described above for the prior art device, such a lump may be shovelled into a cavity and block e.g. the entry opening of the cavity so that it does not become filled with the desired amount of particulate material. The dosing device according to the present invention will instead press the particulate material into the cavities of the dosing device. This has the advantage that e.g. small lumps formed in the particulate material will be split up by the force exerted onto them. By this, the filling of the cavities will be more reliable, thus ensuring an accurate dose of medicaments in each cavity. However, the device according to the present invention is not only beneficial for packing particulate material when small lumps have been formed in the material. It also gives accurate packing of material that has limited free-flowing characteristics also when no lumps have been formed in it. Furthermore, the device according to the present invention is also suitable for packing free- flowing particulate material. Experiments have shown that doses of approximately 5 mg of particulate material can be packed with a device according to the present invention with a relative standard deviation of only 3 %.

The cavities in the dosing device according to the present invention can be arranged in any desirable shape, and, suitably, so that they correspond to the pattern of a drug dispenser.

Suitably, the cavities of the dosing device have a smaller volume than that of the cavity housing the dose in the final pack. Since the particulate material is pressed down into the cavity of the dosing device, a very accurate dosing is achieved. Hence, when the particulate material later is transferred to the cavity in the final pack, it will provide a very accurate dosing even if the cavity in the final housing has a larger volume. Furthermore, the device provides an uncomplicated filling of particulate material in cavities at a low cost. Advantageously, the cavity of the dosing device is exchangeable to adapt to the size of the dose to be dosed in said cavity.

Materials that can be filled include powder of organic materials with particle sizes in the range of 0.5-1000 μm. For example, powders of lactose monohydrate with particle sizes ranging from 1-50 μm have been successfully filled with the method according to the invention. With particle size is here by meant the mass median diameter, MMD, for example measured by a laser diffraction method.

According to at least one example embodiment, the dosing device further comprises scraper means, wherein said scraper means is movable along said surface of the plate.

When the filling means are moved along the surface of the plate in the dosing device, and exerts a force on the particulate material in the direction towards the plate, some of the particulate material may be compressed on the plate surface located between neighbouring cavities. It is therefore advantageous to have scraper means that is movable along the surface and that can loosen up the compressed material. Suitably, the scraper means has a geometry that is designed to efficiently turn up the particulate material retained on the surface of the plate. The loosened up particulate material may thereafter be moved and pressed into a cavity by the filling means, or be transferred and reused in another dosing device. Alternatively, the loosened up particulate material may be removed and later reused in the same dosing device. The scraper means may also loosen up material that is compressed over the cavities, i.e. on top of the material that has been pressed into the cavities. However, by providing the scraper means movable along the surface, the scraper means is prevented from loosen up or removing material that has been pressed into a cavity. Hence, the scraper means does not negatively affect the accuracy of the dosing.

It is advantageous if said filling means may also move in a direction that is perpendicular to the surface of the plate. The reason for this is that the filling means may then be moved a short distance away from the surface when they come into contact with more compressed particulate material, e.g. small lumps, and thereafter be moved towards the surface, and hence, exert a force on the particulate material in that direction. By that, it acts to split up the lump and compress the particulate material into a cavity.

According to at least one example embodiment, said filling means is biased towards said surface. In order for the filling means to exert a force on the particulate material in the direction towards the plate, it is preferred that said filling means is biased towards the plate. This may e.g. be achieved by the filling means being spring-loaded towards the plate. By this arrangement, the filling means may be movable a short distance away from the surface, in order to "climb" over e.g. lumps as described above, but at the same time strive to return in a direction towards the plate and compress the particulate material.

Suitably, said scraper means is biased towards said surface. The purpose of the scraper means is that it is movable along the surface and that it can loosen up the compressed material. It is therefore advantageous if it is biased towards said surface so that it during movement along the surface remains in close relationship with the surface.

Suitably, said filling means is biased towards said surface with a lower force than the force biasing said scraper means towards said surface. This is advantageous since the scraper means should follow in close relationship with the surface and the filling means should be able to move a short distance away from said surface, in a direction substantially perpendicular to said surface. However, when moved away from the surface, the filling means should strive to move back into close relationship with the surface.

According to at least one example embodiment, said surface has a circular shape and is provided with several cavities, said cavities being arranged in a circular pattern around said surface. Suitably, said filling means and said scraper means are provided at a common boss. Suitably, said common boss is arranged in the centre of said circular pattern of cavities.

A circular plate being provided with several cavities and having a centrally arranged boss, on which said filling means and scraper means are arranged has proven to be a beneficial design for a dosing device. The circular boss, and hence the filling and scraper means, may be arranged for rotation both clockwise and counter-clockwise. Even though the filling means compresses the particulate material towards the surface, and the scraper means loosens up the particulate material, they also move the particulate material along the surface. By providing a circulate plate, the particulate material may be transferred around the surface of the plate without ending up at an end thereof. Furthermore, it is also possible to alternatingly rotate the boss clockwise and counter clockwise in order to transfer the particulate material along the surface in both directions. By this, it is possible to provide and maintain an even distribution of the particulate material on the surface. This is beneficial in terms of obtaining an even distribution of the particulate material in each cavity.

Other alternative designs, such as a rectangular plate, are however also conceivable. According to at least one example embodiment, said filling means is constituted of at least one wheel, said wheel being able to rotate on said surface. By that, an efficient manner in compressing the particulate material into the cavities is achieved. The wheel may be adapted to rotate on said surface of the plate and compress the particulate material into the cavities. With this design the wheel does not have to enter the cavity in order to compress the material and hence, the portion of the wheel compressing particulate material into a specific cavity may have larger dimensions than the cavity. This is advantageous in terms of production tolerances since no exact match of the filling means and the cavity is necessary. Furthermore, a wheel of one size may be used for filling cavities of different sizes.

According to at least one example embodiment, the dosing device comprises a filling arrangement comprising two wheels and two scrapers being arranged at a common boss. The wheels and scrapers are alternatingly arranged around the common boss so after each wheel a scraper is provided. This is advantageous since if a first wheel compresses the particulate material, a scraper will loosen it up before the second wheel reaches that portion of the particulate material. Furthermore, in accordance with the invention it is presented a method for filling a cavity provided in a plate of a dosing device with a quantity of particulate material, comprising the steps of providing particulate material to a powder hopper, moving filling means along a surface of said plate so that said filling means, at the same time as it is being moved along said surface, exerts a compressive force on said particulate material in the direction towards said plate.

As stated above, particulate material that has limited free-flowing abilities has a tendency to adhere to each other, causing lumps in the powdered medicament. With the method described above the particulate material will be pressed into the cavities of the dosing device. This has the advantage that e.g. lumps formed in the particulate material will be split up by a force exerted onto them. By this, the filling of the cavities will be more reliable, thus ensuring an accurate dose of medicaments in each cavity. However, the method according to the present invention is not only beneficial for packing particulate material when small lumps have been formed in the material. It also gives accurate packing of material that has limited free-flowing characteristics also when no lumps have been formed in it. Furthermore, the method according to the present invention is also suitable for packing free-flowing particulate material.

Suitably, the cavities of the dosing device have a smaller volume than that of the cavity housing the dose in the final pack. Since the particulate material is pressed down into the cavity of the dosing device, a very accurate dosing is achieved. Hence, when the particulate material later is transferred to the cavity in the final pack, it still has a very accurate dosing even if the cavity in the final housing has a larger volume. Experiments have shown that doses of approximately 5 mg of particulate material can be packed with a method according to the present invention with a relative standard deviation of only 3 %.

Furthermore, the method provides an uncomplicated filling of particulate material in cavities at a low cost. Advantageously, the cavity of the dosing device is exchangeable to adapt to the size of the dose to be dosed in said cavity. The particulate material handled by the method according to the invention may, for instance, be a powdered medicament in pure form or admixed with a suitable excipient in powder form.

For example, mixtures of micronised medicaments used for asthma treatment, e.g. budesonide and beclomethasone dipropionate (BDP) and lactose monohydrate excipient have been successfully filled with the method according to the invention.

According to at least one example embodiment, the method further comprises the step of loosen up compressed particulate material on said surface by means of scraper means.

According to at least one example embodiment, said particulate material comprises pharmaceutical powder for use in dry powder inhalers.

It should be understood that the above described inventive method encompasses and may be implemented with any embodiments or any features described in connection with the previously discussed inventive dosing device, as long as those embodiments or features are compatible with the method.

Brief description of the drawings The present invention will now be described, for exemplary purposes, in more detail by way of embodiments and with reference to the enclosed drawings, in which: Fig 1 is a schematic perspective view of an embodiment of a dosing device, and an embodiment of the filling and scraper means according to the present invention,

Fig 2 is a schematic cross sectional view of an embodiment of the dosing device, and an embodiment of the filling and scraper means according to the present invention,

Figs 3a - 3c are partial schematic cross sectional side views disclosing a hole structure illustrating the main steps of a dosing and pouring method,

Fig 4 is a schematic perspective view of an alternative cavity structure.

Detailed description of the drawings

Figs 1 and 2 show a dosing device 1 provided with a powder hopper 2 for housing particulate material, such as powdered medicament (not shown). The powder hopper has a funnel shaped interior and the sloping surfaces 12 thereof are intended to guide the powdered medicament (not shown) towards a plate 11 having a surface 3, which can be seen as forming the bottom of the powder hopper 2. The surface 3 is formed as a hole structure 4 with cavities 5 extending into the plate 11. In this embodiment, the cavities are distributed in a circular pattern around the plate 11. In the middle of the circular pattern of cavities 5 a filling arrangement 13 is rotatably arranged.

The filling arrangement 13 comprises two filling means, which in this exemplifying embodiment are two wheels 6, and two scrapers 14. The wheels 6 and scrapers 14 are provided at a common boss 15. A driving axis 16 is connected to the boss 15 so that the boss 15, and hence the wheels 6 and scrapers 14, can be rotated. As can be seen in e.g. fig 1, the wheels 6 and scrapers 14 are evenly distributed, i.e. at approximately 90° intervals, around the boss, with each wheel 6 being followed by a scraper 14. The geometry of the scrapers 14 is designed to turn up compressed particulate material on the surface 3. For instance, regarded in the travelling direction of the scrapers 14, the forwardly facing or leading surface of the scrapers may have its most forwardly located portion substantially in contact with the plate surface 3. Herein, the scrapers 14 are illustrated as having inclined surfaces and having e.g. a triangular cross section. This enables turn up of compressed particulate material for both clockwise and counter clockwise travel.

The boss 15 is axially spring loaded towards the plate 11 and the scrapers 14, being fixedly arranged to the boss 15, are hence also spring loaded towards the plate 11. In the illustrated embodiment, a spring 9 is provided in relation to the driving axis 16 and may be connected to an outer casing (not shown) in order to bias the boss towards the surface 3. The spring load decides the force between the two scrapers 14 and the surface 3 of the plate 11. It is beneficial that the scrapers 14 are arranged in close proximity to the surface 3, the reason for this is described in more detail below. Each wheel 6 is independently moveable in an axial relation, i.e. towards and away from the surface 3 of the plate 11, in relation to the boss 15. Each wheel is also independently spring-loaded towards the surface 3, but with a spring load that is lower than the spring load on the boss 15 towards the surface 3. The reason for this is that the wheels 6 shall be able to move a short distance away from the surface 3 when they encounter e.g. a portion of adhered and/or compressed particulate material, such as a small lump. The wheels 6 may then climb on the lump of compressed material and, due to the spring loading, exert a force on the lump in the direction towards the plate 11 and thus break up the lump. The spring or other means biasing each of the wheels towards the surface may e.g. be provided in the connection between the boss 15 and each of the wheels 6. In fig 3a there is shown a shaft 10, which the wheels 6 is rotatable around. The shaft 10 is arranged to bias the wheels 6 towards the surface 3, at the same time as it allows a certain movement of the wheels 6 in a direction that is substantially perpendicular in relation to the surface 3, as is illustrated by the arrow D in fig 3a.

The spring load on the boss 15 and the wheels 6 can be adjusted so that an accurate dosing of the particulate material in each cavity is achieved.

The wheels 6 are for example made of, or have a surface of, silicone. The reason for this is to avoid that the particulate material adheres to the wheels. However, other materials than silicone may also be used as long as the particulate material does not adhere to it. The dosing device will now be explained in use. First, particulate material is provided to the hopper 2. Suitably, the particulate material is provided in such an amount that it extends from the surface 3 to approximately the centre of the wheels 6, thereby covering the scrapers 14. The filling arrangement 13, i.e. the boss 15, the wheels 6 and the scrapers 14, are thereafter rotated by the driving axis 16, bringing the wheels 6 to rotate on the surface 3. Due to the spring-load biasing the boss 15 towards the surface 3, the scrapers 14 follow in close relation with the surface 3. The wheels 6 and scrapers 14 each pass the cavities 5 one by one during rotation of the filling arrangement 13. When the wheels 6 rotate, they exert a compressing force on the particulate material and when they pass a cavity 5 they press the particulate material into the cavity. This is illustrated in fig 3 a in which the arrow A indicates the movement of the wheel 6 in relation to the surface 3, the arrow B indicates the rotational direction of the wheel 6 and the arrow C illustrates how particulate material 21 is being introduced into a cavity 5 of a hole structure 4. Due to the rotation of the wheel 6 different portions of the wheel will press the particulate material into the cavity 5.

A layer of compressed particulate material retains on the surface 3 between each cavity 5 after the wheel has passed. When the scrapers 14 passes the compressed retained particulate material it turns it up so that the lifted particulate material can be reused.

In order for the cavities 5 to be filled with the desired amount of particulate material, the filling arrangement 13 is rotated one or several turns. The driving axis 16 may also be so arranged that the filling arrangement 13 may rotate both clockwise and counter- clockwise. By this, the filling arrangement may be rotated alternatingly between these two directions in order to fill the cavities with an even amount of particulate material. When all cavities 5 are filled with the desired quantity, the excessive particulate material can be moved to another dosing device for use in that system or be returned to a storage system. When the cavities of the dosing device 1 has been filled with the desired quantity of particulate material, the particulate material is transferred to a drug disc to be used in a dispensing device such as an inhalation device. Several different methods and devices may be used for transferring the particulate material from the dosing device 1 to the drug disc.

One such method and device that may be used in conjunction with the present invention are ejector means. The cavities 5 may then be formed with a retractable bottom. When the cavities are filled with the desired amount of particulate material, the bottom of each of the cavities is removed and the ejector means may be inserted into the cavity and push the material out of the cavity and into a final pack of a drug dispenser.

Another such method and device that may be used in conjunction with the present invention is disclosed in the pending patent application WO 2006/118526 in the name of ASTRA ZENECA AB. In this method the plate 11 of the dosing device 1 is positioned on top of the drug disc, with the cavities 5 positioned opposite corresponding cavities in the drug disc so that the particulate material can be transferred from the cavities 5 of the plate 11 to the cavities of the drug disc. The dosing device may be provided with vibrating means or ultrasonic elements for enabling controlled emptying of the cavities into a corresponding cavity of a drug disc.

Yet another method and device for transferring the quantity of particulate material from the dosing device 1 to a drug disc is disclosed in the pending U.S. Provisional Patent Application No. 60/957822 in the name of ASTRA ZENECA AB. In this application, a plate having holes with moveable wall portions is disclosed. This method and device may suitable be used in combination with the present invention and will be further described with reference to figs. 3a - 3c. In fig. 3a a section of one cavity 5, of a hole structure 4, is outlined schematically. The wall structure of said cavities 5 comprises a plurality of movable wall portions 22, which may be moved in relation to one another. The cavities 5 of the dosing device 1 are in this embodiment formed of holes, which may be closed by a closing arrangement 8. The closing arrangement 8 is conveniently formed as a plate which, in a first position, is positionable so that it will block the holes 5 entry into or out from the hole from that side. The closing arrangement 8 is thus adapted to form a bottom of the holes 5 when in the first position.

The blocking of a hole 5 is in effect during filling of the hole 5 as disclosed in fig. 3a. When a sufficient amount of powder 21 has been introduced into the hole 5 it may be closed. For this purpose the dosing system 3 comprises a lid arrangement 7. The lid arrangement 7 has openings, which, in a first position, is positionable in register with the holes 5 of the hole structure 4. The first position of the lid arrangement openings is disclosed in fig. 3a illustrating an initial step in the powder providing sequence. During this step the powder is introducible into the hole 5, in the manner described above. Now, continuing to fig. 3b an intermediate condition of the dosing operation is disclosed. In said intermediate condition the lid arrangement 7 is provided in a closing state and the closing arrangement 8 as well. The movable wall portions of plates piled upon each other define a closed volume together with the lid and closing arrangement 7, 8. As will be readily appreciated from the cross section of fig. 3b the hole 5 will be completely filled with particulate material 21 in this intermediate operation condition.

Referring further to fig. 3c, in which the emptying operation of the hole 5 is illustrated. Sideways of the hole closing arrangement part, which is adapted to form the bottom of anyone of said holes 5, there exist openings with generally the same dimensions as the hole 5 openings. In a second position the openings of the hole closing arrangement 8 are positioned in register with the holes 5 as seen from the side. When an opening of the hole closing arrangement 8 is in a corresponding position to that of a hole 5 the powder may be discharged from said hole 5. Suitably the lid arrangement 7, when emptying of the powder from any one of the holes 5 is due, is positionable in an offset position so as to block the opening of the holes 5. This is performed in order to prevent additional powder from entering the hole 5 once a metered dose has been accomplished and thus it is assured that a correct dose of powder is delivered further to the system. In order to further improve correct delivery of powder quantity the wall portions 22 of the hole/holes in questions are moved in relation to one another. The relative movement of the wall portions 22 has proven to enable a reliable emptying effect and an accurate further dosing of powder with low retention of powder.

Suitably, the relative movement of wall portions in the exemplified embodiment is accomplished by movement of the plates constituting the hole structure 4. The structure surrounding the hole 5 walls 22 consequently constituting the wall structure for the holes 5. The plates forming said hole structure may be slidable back and forth in a direction substantially perpendicular relative to the main propagation direction of the hole in question, which main propagation direction substantially coincides with intended path for the powder. The movement of each plate 22 is conveniently, but not exclusively, in the range between ± 2 % to ±50 % of the diameter of the hole 5 with reference from the aligned start and stop position. Suitably, the plate movement is between ± 5 % to 25 % of the diameter of the hole, for instance, between ± 7 % to 15 % of the diameter of the hole 5. When referring to the diameter of the hole 5 it is submitted that a hole 5 may be formed differently. Hence, the diameter in accordance with the present application should be interpreted in a broad meaning as representing the longest distance across the hole in question, whether it is squared or has another shape that may have different distances between sides thereof.

The dosing device 1 has been described in relation to an exemplified embodiment. However, several modifications and adaptations are possible within the scope of the present invention as defined in the appended claims. For example, the plate 11 does not need to be circular. Fig 4 shows an embodiment with a rectangular plate 11 ' having the cavities 5 arranged along a straight line of the plate 11 '. In this embodiment, the wheels 6 and scrapers 14 may be provided at a linearly moving means instead of a rotating boss. The wheels and scrapers may thereafter be moved back and forth over the surface 3 ' in order to fill the cavities 5 with particulate material in the same manner as described above for the circular plate. In this rectangular embodiment it may be suitable that the scraper means 14 may be moved away a short distance from the surface 3' of the plate 1 1 '. The reason for this is that the filling means and the scrapers during use may move the particulate material along the surface of the plate. Some of the material will therefore during the filling process become positioned at the end of the plate. It is therefore beneficial to be able to lift the scraper means from the plate, over the particulate material provided thereon, and position the scraper means at the outer end of the plate. The particulate material that has been positioned at an outer end of the plate may thereafter be moved towards the other end of the plate, and be filled in cavities. Another possible modification is that the wheels and scrapers do not need to be provided at a common boss or hub. Instead, the movement of the scrapers and wheels may be provided by different means, which are controlled to move the wheels and scrapers in a desired mutual relationship.

Furthermore, the filling means has in the exemplified embodiment been described as wheels rotating on the surface 3, which compresses the particulate material into the cavities 5 by this rotating movement. However, it is for example also possible to provide the filling means as a substantially planar surface, such as a mat or similar non-rotating means. This non-rotating means may be spring-loaded towards the surface 3 of the plate 11 in order to exert a compressive force on the particulate material when the non-rotating means are moved along the surface 3. As for the wheels, the means with a planar surface may be made of, or have a surface of, silicone in order to prevent particulate material from adhering to it. Filling means having a substantially planar surface may be used both for a circular plate 11 or a plate of any other shape, such as the rectangular plate 11 '. Furthermore, the filling arrangement 13 has in the exemplified embodiment been described as comprising two filling means, in the described embodiment wheels 6, and two scrapers 14. However, other numbers of filling means and scrapers, e.g. one filling means and one scraper, is also conceivable.