The invention relates to a method for separating and for transferring pellets, in particular cryo-pellets, into a target container, and to a singularization device for carrying out this method.
Numerous pharmaceutical agents are applied as solutions but are unstable in the dissolved state. However, the pharmaceutical agents as freeze-dried formulations can be stored in a stable manner and be dissolved again immediately prior to being used. Examples thereof to be mentioned are biotechnological products, peptides, vaccines, and certain reagents.
More recently, such formulations are also produced in the form of more or less spherical multi-particular preparations as so-called cryo-pellets. To this end, the source solution is brought into a drop form, wherein drops having an accurately defined volume are producible. These drops are frozen, for example in liquid nitrogen, and are then dried by way of sublimation. The dry cryo-pellets that are produced in this way have at least approximately a spherical configuration having a defined mean diameter. If required, the cryo-pellets can again be dissolved in suitable quantities. The target herein is to produce only such a limited quantity of solution as is required for covering the immediate demand, to which end corresponding quantities of cryo-pellets are kept available in suitable packaging units.
The number of cryo-pellets required for preparing a solution is typically very low. Consequently, only a single pellet or just a few pellets are required which is why a volumetric metering in the filling of respective packaging units is precluded. Rather, a filling of the packaging units with a specific suitable number of pellets is targeted, to which end the pellets in this very number have to be separated from a comparatively large supply and then have to be transferred into the target container. However, the prior art does not provide any suitable method for separating and for transferring and also no device suitable for this purpose, which can be traced back to inter alia the following aspects:
It is an object of the invention to provide a method for separating and for transferring pellets into a target container, the method enabling a reliable and economical implementation also in the case of difficult materials such as in the case of cryo-pellets.
This object can, for example, be achieved by a method for separating and transferring pellets into a target container. The method includes the steps of: providing a supply of pellets in a storage space; directing the pellets from the storage space into a metering duct that leads out of the storage space downward and is vertically oriented in such a manner that a column of pellets that lie on top of one another is formed in the metering duct, wherein a lowermost pellet of the column of pellets is located in a connection point, and wherein an outlet duct is connected to the metering duct at the connection point and leads transversely away from the metering duct; impinging a first pressure differential duct, which opens into the metering duct via a first duct mouth above the connection point, with negative pressure, wherein a pellet is suctioned onto the first duct mouth and on account thereof is locationally fixed thereto, and wherein this suctioned pellet acts as a block for the pellets located thereabove; impinging a second pressure differential duct, which opens into the connection point via a second duct mouth, with positive pressure, wherein the pellet that is located in the connection point is pneumatically ejected by way of the outlet duct and supplied to the target container; and, switching off the negative pressure in the first pressure differential duct after the pneumatic ejection of the lowermost pellet such that the pellet that is locationally fixed at the first duct mouth moves on toward the connection point and a new lowermost pellet is located in the connection point.
It is a further object of the invention to provide a singularization device for separating and transferring pellets into a target container.
This object can, for example, be achieved by a singularization device having: a storage space for pellets; a metering duct leading downward from the storage space and being vertically oriented; an outlet duct connected to said metering duct at a connection point and leading transversely away from said metering duct; at least one first pressure differential duct opening into said metering duct above said connection point via a first duct mouth; a second pressure differential duct opening into said connection point via a second duct mouth; said first pressure differential duct being configured to be impinged with negative pressure; said second pressure differential duct being configured to be impinged with positive pressure; a negative pressure source configured to impinge said first pressure differential duct with negative pressure so as to cause a pellet to be suctioned onto said first duct mouth and become locationally fixed thereat so as to act as a block for pellets located thereabove; a positive pressure source configured to impinge said second pressure differential duct with positive pressure so as to pneumatically eject a lowermost pellet located at said connection point via said outlet duct and to supply the pellet to a target container; and, said negative pressure source being configured to cease impinging said first pressure differential duct with negative pressure after the pneumatic ejection of the lowermost pellet so as to cause the pellet locationally fixed at said first duct mouth to move toward said connection point.
Initially a supply of pellets is provided in a storage space. The pellets are then directed in such a manner from the storage space into a metering duct that leads out of the storage space downward and is vertically oriented, that a column of pellets that lie on top of one another is formed in the metering duct. The lowermost pellet of this column of pellets is located in a connection point, wherein an outlet duct is connected to the metering duct at the connection point and leads transversely away from the metering duct. A first pressure differential duct which via a first duct mouth above the connection point opens into the metering duct is impinged with negative pressure, wherein a pellet is suctioned onto the first duct mouth and is consequently locationally fixed thereto. This suctioned pellet herein acts as a block for the pellets that are located thereabove.
Proceeding therefrom, a second pressure differential duct which via a second duct mouth opens into the connection point is impinged with positive pressure, wherein the pellet that is located in the connection point is pneumatically ejected by way of the outlet duct and supplied to the target container. After the pneumatic ejection of the lowermost pellet the holding negative pressure in the first upper pressure differential duct is switched off such that the pellet that is held at the first duct mouth moves on toward the connection point and a new lowermost pellet is located in the connection point.
By way of a method according to the invention that has been described above, and by way of the associated device, one or a plurality of pellets can be separated from the enlarged pellet supply and be supplied to the target container, wherein separating as well as supplying is performed solely by the targeted application of negative pressure and positive pressure. The mechanical action on the pellets is very minor on account of the purely pneumatic handling. Even mechanically critical pellets such as cryo-pellets can be reliably handled without mechanical damage to the pellets, such as abrasion or the like, is to be noted. The density of the pellets that is insufficient for a conveyance by weight, proves to be an advantage because suctioning and fixing the pellets, as well as the transportation by pneumatic ejection, function similarly effectively in the case of the typically very low material densities herein. Friction and other mechanical effects are reduced to a minimum such that electrostatic charging or the possible effects thereof, respectively, are largely avoided or are negligible, respectively.
The first and the second duct mouth are mutually disposed at a height differential. In an advantageous embodiment of the singularization device, the height differential is an integral multiple of a mean diameter of the pellets. It is ensured on account thereof that a defined number of pellets is collected below that pellet that acts as a block, the defined number being precisely blown into the target container. The integral multiple can be two, three, four, or more, and predefines the number of the pellets that are to be in each case pneumatically ejected into one target container. In an advantageous embodiment the integral multiple is one, as a consequence of which exactly one pellet is pneumatically ejected with each work cycle. However, this does not necessarily mean that also exactly only one pellet is supplied to the target container. Rather, a specific number of individual pellets can be blown into the target container by way of a specific number of cycles, on account of which a high reliability in terms of the process is provided.
In order to be able to vary the number of the pellets to be exhausted, an embodiment of the singularization device in which a plurality of first pressure differential ducts via the first duct mouths assigned thereto open into the metering duct can also be expedient. Depending on requirements, in this instance a duct mouth that is positioned so as to be more or less higher can be activated by way of negative pressure and serve as a block, wherein in this instance, depending on the chosen position in terms of height, a more or less large number of pellets are collected therebelow and ejected into the target container.
In all cases, the separation of a specific number of pellets is based on the fact that that negative pressure is built up in the first upper pressure differential duct, as a consequence of which a pellet is suctioned and retained at the assigned first duct mouth, wherein this suctioned and retained pellet acts as a block for the pellets that are located thereabove. It is achieved on account thereof that the one or the plurality of pellets that are collected therebelow can be exhausted in the envisaged number without further pellets prematurely moving on from above and falsifying the previously separated quantity.
Various types of handling can be considered for the pellets that are collected below the blocking pellet. For example, it can be sufficient for the lowermost pellet to simply stand on the base of the transversely running outlet duct and to herein lie in the effective range of the second pressure differential duct as soon. As a pulse of compressed air is exhausted by way of this second pressure differential duct, the pellet and optionally also the following pellets are conjointly carried to the target container by the compressed air or the compressed gas. However, in an advantageous embodiment the lowermost pellet is not simply left to stand on the base. Rather, the lowermost pellet prior to the pneumatic ejection is suctioned onto the second duct mouth in that the second pressure differential duct is temporarily impinged with negative pressure. On account thereof, above all while considering the effective minor weights, reliable replenishing of the pellets from top to bottom is facilitated. Moreover, the lowermost pellet is reliably fixed by way of a suction force to the duct mouth of the lower pressure differential duct, the lowermost pellet on account thereof being positioned in a locationally accurate manner. This facilitates an accurate counting process as well as a later exhausting procedure that is reproducible.
Various temporal profiles can be considered for suctioning the pellets onto the two duct mouths. However, the suctioning of the pellet that acts as the block onto the first duct mouth, and the suctioning of the lowermost pellet onto the second duct mouth is preferably performed in a temporally alternating manner. Temporal overlaps are indeed permitted herein. However, it any case, it should be ensured that there are time frames in which only one of the two pressure differential ducts is impinged with negative pressure. It is ensured on account thereof that the suctioning onto one of the two duct mouths is not influenced in a disadvantageous manner by suctioning onto the respective other duct mouth.
As soon as the desired number of pellets has been exhausted, a corresponding number of pellets has to move on from above. To this end, the holding negative pressure in the first pressure differential duct is switched off. It can be sufficient for the ambient pressure or a slight but no longer holding negative pressure to remain in this instance. In an advantageous embodiment, the first pressure differential duct is impinged in the sense of a gas pulse with positive pressure at least briefly. A downward movement of the pellet that is initially held on the first duct mouth is supported or facilitated, respectively, even in the case of a very slight positive pressure.
It can be sufficient for the entire process management to be carried out with air as a pressure and negative medium. A protective gas is expediently used for sensitive pellets such as cryo-pellets, wherein such a protective gas is advantageously introduced into the metering duct or into the outlet duct, respectively in the case of an impingement of the first and/or of the second pressure differential duct by positive pressure. It is considered on account thereof that cryo-pellets are typically extremely hygroscopic. Moreover, the protective gas can serve for rendering the pellets inert.
Pressure monitoring and/or flow-rate monitoring of the first and/or of the second pressure differential duct is preferably performed in an advantageous embodiment. Disturbances in the process can be identified, and counter measures can be initiated, by identifying irregularities in the profile of the pressure or the flowrate, respectively.
Overall, the method that is conceived so as to be simple, in a corresponding manner also requires a singularization device that is also conceived so as to be simple, wherein the substantial elements in the form of ducts and the like can be readily incorporated into a main body. This permits a plurality of singularization devices to be interconnected in the manner of modules and therefore to be able to be constructed in a flexible manner in the desired number and configuration. It can be expedient for the required ducts and the like to be configured as bores in such a main body. However, in one preferred variant, the storage space, the metering duct, the outlet duct, the first pressure differential duct, and/or the second pressure differential duct are/is incorporated into the surface of such a main body, and are/is closed by the main body of the neighboring singularization device. The production effort is minimized on account thereof, on the one hand. On the other hand, ready accessibility to all ducts can be achieved by way of disassembly, such that disturbances of any type can be readily remedied.
Depending on requirements, it can be expedient for cuboid-shaped main bodies to be interconnected in a linear sequence. Alternatively, it can be expedient for main bodies that in the footprint are shaped as circular segments to be interconnected in the shape of a circle or in the shape of circular segments, such that overall compact systems of a plurality of singularization devices are constructed, and wherein such individual main bodies can be replaced, removed, or added in a modular manner.
The invention will now be described with reference to the drawings wherein:
The singularization device 3 moreover includes at least one, presently exactly one, first pressure differential duct 8, and a second pressure differential duct 10. The first pressure differential duct 8 via a first duct mouth 9 above the connection point 7 opens into the metering duct 5. The second pressure differential duct 10 by way of a second duct mouth 11 above the first duct mouth 9 opens into the connection point 7. The first pressure differential duct 8 has a first duct axis 12, while the second pressure differential duct 10 has a second duct axis 13. The first duct axis 12 in the region of the associated duct mouth 9 lies transversely to the first longitudinal axis 28 of the metering duct 5, while the second duct axis 13 of the second pressure differential duct 10 in the region of the associated duct mouth 11 runs substantially parallel, presently even so as to be coaxial, with the second longitudinal axis 29 of the outlet duct 6. The two pressure differential ducts 8, 10 at the assigned duct mouths 9, 11 thereof are provided in each case with one retention means 18, 19 that prevents any ingress of foreign particles and in particular of the pellets 1, 1′, 1″ into the respective pressure differential ducts 8, 10. However, at the same time, the retention means 18, 19 are gas-permeable. Filter materials with fine pores, such as sintered filters, membrane filters, or the like are suitable therefor.
In order for the method to be carried out, it is necessary for the first, upper pressure differential duct 8 to be able to be impinged with negative pressure when required, while the second, lower pressure differential duct 10 is to be able to be impinged with positive pressure when required. However, in the embodiment shown, both pressure differential ducts 8, 10 are impingable in an alternating manner with negative pressure or else with positive pressure. To this end, in each case one negative pressure source 14 as well as in each case also one positive pressure source 15 are provided for both pressure differential ducts 8, 10, wherein the first pressure differential duct 8, or the second pressure differential duct 10, respectively, via a respective assigned switching valve 16 can be selectively connected to the associated negative pressure source 14 or to the associated positive pressure source 15. Of course, a position of the respective switching valve 16 in which the ambient pressure is set in the respective pressure differential duct 8, 10 is also possible. The operation of the singularization device 3 shown can be performed at atmospheric conditions, wherein compressed air via the negative pressure source 14 is fed into the system by way of the respective pressure differential duct 8, 10. Protective gas containers 17 in which protective gas is kept available under positive pressure are provided as positive pressure sources 15 in the embodiment shown. In the context of individual method steps that are described further below, the pressurized protective gas via the first pressure differential duct 8 and/or of the second pressure differential duct 10 is directed from the respective protective gas container 17 through the respectively assigned duct mouth 9, 11 into the metering duct 5 or into the outlet duct 6, respectively. In the interests of simplicity two protective gas containers 17 are drawn in according to
According to ab advantageous embodiment of the method, according to
In the initial position mentioned according to
In the combined view of
Once the one or the plurality of lower pellets 1′ have been exhausted according to
Air or compressed air, respectively, can be used as the process and positive pressure medium. To the extent that a protective gas container 17 is provided as a positive pressure source 15 according to the embodiment as per
The impingement of the two pressure differential ducts 8, 10 with negative pressure can be mutually overlapping to a certain extent. However, suctioning of the pellet 1″ that acts as a block onto the first duct mouth 9, and suctioning of the lowermost pellet 1′ onto the second duct mouth 11, is advantageously performed in a temporally alternating manner such that the holding negative pressure on the upper duct mouth 9 is at least temporarily switched off when the transfer and the moving-on of the lowermost pellet 1′ are performed via negative pressure at the lower, second duct mouth 11. In any case, the temporary negative pressure in the lower, second pressure differential duct 10 also supports the moving-on of the pellets 1 from the target container 2 into the metering duct 5. This can also be utilized for the initial filling of the metering duct 5 with pellets 1, 1′, 1″ for achieving the initial position as per
Subsequently to the method step according to
It can also be derived from the illustration as per
Deviating therefrom,
It can also be derived from the perspective illustration as per
In as far as not explicitly described or illustrated in the drawings so as to deviate therefrom, the embodiments as per
It is understood that the foregoing description is that of the preferred embodiments of the invention and that various changes and modifications may be made thereto without departing from the spirit and scope of the invention as defined in the appended claims.
This application is a continuation application of international patent application PCT/EP2015/001484, filed Jul. 18, 2015, designating the United States and the entire content of which is incorporated herein by reference.
Number | Date | Country | |
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Parent | PCT/EP2015/001484 | Jul 2015 | US |
Child | 15874732 | US |