WO2014202343A1

WO2014202343A1 - Apparatus and method for determining the weight of a pharmaceutical product, in particular

Info

Publication number: WO2014202343A1
Application number: PCT/EP2014/060882
Authority: WO
Inventors: Iulian Maga; Martin Vogt; Jens Schlipf
Original assignee: Robert Bosch Gmbh
Priority date: 2013-06-19
Filing date: 2014-05-27
Publication date: 2014-12-24
Also published as: DE102013211512A1

Abstract

An apparatus and a method for determining the weight of a pharmaceutical product (2), in particular, which is in a container (3) are proposed. The apparatus comprises at least one sensor (14) which records the radiation of the irradiated container (3) in the form of an image (12, 3). An evaluation device (14) is provided, which evaluation device evaluates a first image (12) of an irradiated empty container (3) and a second image (13) of a container (3) filled with a product (2) by virtue of the evaluation device (14) generating a difference image (15) by subtracting the second image (13) from the first image (12) and then determining a net weight of the product (2) in the container (3) on the basis of the difference image (15).

Description

description

title

Device and method for determining the weight of a particular pharmaceutical product

The invention relates to a device and a method for

Weight determination, in particular of pharmaceutical products according to the preamble of the independent claims. A generic device and method are already known from WO 2012/013368 AI. A

X-ray source produces a cone of radiation that transmits at least one pharmaceutical product. A sensor element detects the radiation of the irradiated pharmaceutical product and leads it one

Evaluation device to. In the beam path of the radiation cone is a

Reference object arranged, with the radiation of the transilluminated

Reference object detected by the sensor element and the evaluation unit is supplied, wherein the pharmaceutical product and the reference object are positioned with respect to the radiation cone in non-overlapping arrangement to each other in the radiation cone.

It is an object of the present invention, the accuracy of a

Weight determination continues to improve. This object is solved by the features of the independent claims.

Advantages of the invention

The device according to the invention and the method according to the invention with the features of the independent claims have the advantage that the accuracy of weight determination is further increased. For this purpose, the invention provides that an evaluation device a first image of an irradiated empty container and a second image of a with a Evaluated product filled container by the evaluation device generates a difference image by subtracting the second image of the first image and then determined based on the difference image, a net weight of the product in the container. In this procedure, the first image ("tare" in which the empty container is visible) becomes the second image

Subtracts ("gross", in which the container filled with product is visible) .There is then only information for the difference image, what was filled between the two shots in the container

Information is directly proportional to the net weight of the filling. This determines the net weight of the product, which is of primary interest, and not just the gross weight of the container and product as in the prior art. This is especially true for small quantities of

particular advantage, since in these cases, the weight of the container has a great influence on the accuracy of weight determination. For example, manufacturing variations of the tare weight can become emptier for small quantities

Containers should be larger than the maximum permissible capacity fluctuations. This may result in containers with correct product fill being rejected as incorrectly filled because the tare weight of the container has exhausted the weight tolerance. Conversely, this can also lead to a container filled with too much or too little filled product being wrongly recognized as being in order, because the container is tolerated

Behältnisgewichtsschwankung behaves inversely and compensates for the incorrect dosage. These unacceptable cases have the effect described

Net weight determination particularly advantageous contrary.

In an expedient development it is provided that the

Evaluation device determines the association between difference image and net weight of the product in the container using a reference line. This is done particularly expediently by assigning to the difference image or a volume derived from the difference image a weight of the container and / or of the product determined with a weighing device. As part of the learning process, a very accurate reference can be made to the actual net weight even in the most diverse

Products and containers. This type of learning is a high

Accuracy of the net weight determination sure. For the subsequent Normal operation is no longer required weighing device. It can also be in a simple manner a fast, within the usual

Ensure production process based weight determination with high accuracy.

In an expedient development it is provided that a receiving means, in particular a capsule holder, is provided for receiving at least one container, wherein the container is moved via a conveyor to a filling station, which fills the container with a product, wherein the container of the X-ray source is supplied for generating the second image. This arrangement is particularly suitable for containers with high

Speed can be supplied to different workstations. As a result, high application rates can be achieved.

In an expedient development it is provided that at least one reference object is provided, which in the radiation passage of

X-ray source is arranged, and having different thicknesses, wherein the net weight determination, the evaluation unit the gray values of the difference image each one the gray value of the reference object

corresponding thickness of the reference object assigns. Straight through the

Using a reference object with different thicknesses, which is also irradiated during operation with the container, the gray values can be reliably converted into a net weight. This can be done with the help of appropriate thicknesses, transfer into a volume and

Assignment to a net weight by means of the reference line in a particularly simple and accurate manner.

Further expedient developments emerge from further dependent claims and from the description.

drawing

An embodiment of the device according to the invention and the

inventive method are illustrated in the drawings and will be described in more detail below. Show it:

Fig. 1 shows the basic principle of image formation, which on

X-ray based,

2 shows images of an empty and a filled container and the resulting difference image,

3 is a flow chart of the method according to the invention,

4 shows a device according to the invention,

5 another filled container,

Fig. 6 is an image of several irradiated containers and the

Reference object.

Several containers 3 are located in a steel passage 36 of a

X-ray source 28, which irradiates the containers 3. Behind it is a sensor 30 with a sensor surface 32, the

X-ray source 28 faces. The sensor 30 is used to create an X-ray image or an image 12, 13 of the irradiated container 3. The sensor surface 32 preferably comprises a plurality of

radiation-sensitive sensor elements such as CCD or CMOS sensors, depending on the incident radiation each one

Output signal, which is referred to below as the gray value. For this purpose, for example, over the pixels of the CMOS sensor is a

Scintillation layer applied, which converts the X-ray energy into visible light. The pixel of the sensor generates a charge (analog) depending on the amount of light, which is preferably converted into a digital signal C.Greyvalue "), which is used for weight determination

Output signals of the areally arranged sensor elements, the image 12 is generated. In principle, other radiation detection means can be used as sensors.

In the right embodiment of Figure 1 is also a

Reference element 35 in the beam path of the X-ray source 28. The reference element 35 is in non-overlapping arrangement next to the Containers 3 and is also irradiated. The resulting image, the sensor 30 also takes and is shown by way of example in Figure 6.

In FIG. 2, a first image 12 is shown, in which the sensor 30 receives from an empty container 3 which is irradiated through. This first image 12 is recorded in a first step 101. After the container 3 has been filled with a product 2, a second image 13 is taken. A slightly darker area there is the filled product 2 assigned. By subtracting second image 13 and first image 12, a difference image 15 is created. As a result, the gray values of the contours of the container 3, which is present in both images 12, 13, are extinguished. Only the product 2 remains in the difference image 15.

FIG. 4 shows the device 10 which is suitable for carrying out the described method. This is described by way of example on the concrete example of a capsule filling machine, for which the invention is particularly suitable, but not limited thereto.

A machine for filling and closing of a capsule lower part and an attached cap container 3 has a twelve-part, gradually rotated about a vertical axis feed wheel 40, at its stations 1 to 12 on the circulation path, the individual

Treatment facilities are arranged. Other divisions of the feed wheel 40 such as a 15-piece would be conceivable. At stations 1 and 2 to be filled, empty containers 3 are abandoned disorderly and aligned by the radiation path 36 of the X-ray source 28 out. The first image 12 is recorded here. The containers 3 are then ordered into a capsule holder 42 of a feed wheel 20. In station 3, the still closed containers 3 are opened. In station 5, the filling of the container 3 takes place with the product 2, which corresponds to step 102. At station 7, the filled container 3 is closed. At station 8, the containers 3 are weighed by a weighing device 44. The weighing device 44 can make different measurements. Firstly, the weighing device 44 for initialization according to the first step 101 and second step 102, a weighing of the empty or filled container 3 make. The weighing device 44 could also be used for comparison weighing during ongoing production for checking the described X-ray based measuring system. In station 9, a closing pressure check of the sealed container 3 takes place. Depending on the test in station 9, faulty

Containers 3 in station 10, properly ejected only in station 11. In station 11, the containers 3 pass from the capsule holder 42 upwards again into the radiation passage 36 of a further X-ray source 28. Depending on the weight of the product 3 determined in step 103, faulty containers 3 can still be discarded with the aid of a switch.

In the embodiment according to FIG. 5, an ampoule is provided as a container 3, which is filled with a liquid product 2. For this container 3, the described net weight determination of the product 2 can preferably be carried out.

FIG. 6 shows by way of example the second image 13 of several adjacent and

On the right side, the image of the irradiated reference object 35 is visible, which has different levels of gray 38. The reference object 35 is constructed in a staircase shape with different thicknesses. At the respective different thicknesses arise

different gray levels 38 as explained in more detail below.

In principle, a weight determination is carried out according to the arrangement shown in Figure 1 as generally described below. Advantageously, the reference object 35 is made of a material having similar atomic properties as the pharmaceutical product 2 to be irradiated, i.

especially for the X-ray radiation has the same damping properties. The reference object 35 has different thicknesses when viewed over the cross section. The reference object 35 may be wedge-shaped. Alternatively, the reference object 35 has a series of steps that cause a discrete change in the thickness of the reference object 35. Preferably, it is provided that the attenuation (gray value) of the reference object 35 is greater at one point and smaller at another point than the attenuation by the pharmaceutical product 2. Due to the mentioned geometric design of the reference object 35, these have different thicknesses which, when irradiated by means of the x-ray radiation source 28, produce different gray levels 38 on the sensor element 30. Individual stages of the reference object 35 have different gray values 38.

The weight determination of the product 2 located in a container 3 takes place in principle as follows: In an advance process, which is not shown in advance, an image of the reference object 35 is taken and its gray values 38 detected by the sensor device 30 become due to the known geometric configuration of the reference object 35 Thicknesses of the reference object 35 assigned. In other words, this means that due to a certain gray value 38 of the reference object 35 to a certain thickness of the reference object 35 at a certain point

is closed. Furthermore, due to the known geometry of the

Reference object 35 so that a certain gray value 38 of the reference object 35 are assigned a certain thickness. These gray values 38 determined in advance in the adjustment process and their geometric assignment to the

Reference object 35 are stored in the evaluation device 14. If, for example, the weight is to be detected or checked, then the image 12 of the container 3 captured by the sensor element 30 is divided into individual pixels. This pixel represents a certain area, for example a square with an edge length of ΙΟΟμηη. Then, for each pixel of the container 3, the detected gray value of the pixel is assigned to an (identical) gray value 38 on the reference object 35. This gray value can

(Due to the assignment of the thicknesses to the gray values 38 on the reference object 35) a certain thickness can be assigned. After this is done pixel by pixel, an average thickness is determined from individual thicknesses. This average thickness is then multiplied by the total number of pixels and their known area, so that a virtual volume of the product 2 can be determined. From the virtual volume, the weight of the product 2 located in the container 3 can be determined last.

During the transillumination of the particular pharmaceutical products 2, an image of the relevant reference object 35 is also included at the same time. This allows changes to the grayscale on Detect reference object 35 on temporally successive images, which may occur due to disturbances of the system or due to external disturbances. If, for example, it should be established that the gray value 38 of the reference object 35 changes at a certain level, then the evaluation device 14 may include this detected gray-scale value

Correction factor or offset occupy what the current gray value is

original gray value and thus equalizes the interference.

Based on this general approach is done below

described inventive net weight determination means

Empty container subtraction on the basis of the flow chart according to FIG. 3.

The first image 12 shown in FIG. 2 becomes the first step 101

added. After the container 3 has been filled with the product 2 in the second step 102, a second image 13 is recorded in the third step 103. The slightly darker area there is the filled product 2 assigned.

From subtraction of second image 13 and first image 12, a difference image 15 is created in a fourth step 104 from the relationship:

Difference image 15 = second image 13 - first image 12.

As a result, the contours of the container 3, which are present in both images 12, 13, extinguish. Only the product 2 remains imaged in the difference image 15. For this purpose, the gray values of the pixels of the first image 12 are subtracted from the corresponding gray values of the pixels of the second image 13. For this purpose, a positionally correct assignment of the pixels of the first

Image 12 to those of the second image 13. This could possibly be done via a contour recognition of the containers, in which case the pixels based on the matching contours each for

Difference formation are used. Alternatively, subtracting equally sized regions may be sufficient, the area of the first image 12 must be the

Surface of the second image 13 correspond. If the containers 3 are different from each other, there are shadowy so-called ghost contours, which, however, have no overall influence on the measuring accuracy, because they are one and the same container 3. In sum, the difference image 15 alone includes the damping of the container filling and thus their net weight. In a fifth step 105, a first coarse assignment of the product 2 recognizable on the differential image 15 takes place

Gray value information of the difference image 15 associated with the net weight. For this purpose, the evaluation unit 14 creates a reference line. The attenuation curve ultimately establishes the relationship between the information detected by the sensor 30, such as the respective gray values of the difference image 15 or the pixels and the associated net weight of the product 2. The gray values are preferably compared with the known reference object 35 for weight determination. Due to the difference formation only those pixels are evaluated, which capture the image of the irradiated product 2. The respective gray value of these pixels is compared with the gray value 38 of the

Reference object 35 compared, the associated thickness is known. This assigns a thickness to the respective pixel. This is done for all pixels whose gray values exceed a certain threshold, which indicates the presence of the product 2. About the known area of the

Evaluation used pixels results in an average volume.

This virtual volume can be assigned a weight.

If the net weight is to be determined gravimetrically, there are at least two possibilities. The first would be both the tara and the

Gross balance installed in the normal process sequence. Alternatively, one and the same gross balance may be used in the normal process flow to determine both the tare and the gross weight of a container 3.

By way of the relationship between the detected virtual volume of the surface and the weight determined by the weighing device 44, the evaluation unit 14 assigns, for example via a linear curve, the virtual volume of the irradiated product 2 and the net weight of the product 2 Evaluation unit 14 back to this reference line.

In a sixth step 106, the first four steps 101 - 104 are repeated with a second container 2. Once again, with the second filled container 3, the gross detection of the net weight of the product 2 takes place. based on the difference image 15 from the difference between the second image 13 and the first image 12 as already described.

The steps 101 to 104 can be repeated with further containers 3. This results in a more accurate reference line, which is a specific

Gray value information assigns the corresponding net weight of the product 2.

Thus, if the system has been taught with sufficient accuracy, the weight associated with the difference image 15 is determined in a seventh step 107. This is done by evaluating the gray value information with the aid of the conversion curve determined in the fifth step 105. From the sixth step 106, the weight detection of the product 2 is now carried out during operation. For this purpose, steps 101 to 104 and 107 are performed, but not step 105.

In step 107, the evaluation unit 14 determines the net weight of the product 2. Again, the gray values are compared with the known reference object 35 for weight determination. Due to the difference formation only those pixels are evaluated, which capture the image of the irradiated product 2. The respective gray value of these pixels is compared with the gray value 38 of the reference object 35, whose associated thickness is known. This assigns a thickness to the respective pixel. This is done for all pixels whose gray values exceed a certain threshold, which indicates the presence of the product 2. Over the known area of the pixels used for the evaluation results in an average thickness.

For example, the number of lying within the evaluation region 11 pixels whose size is known, is a measure of this area. This virtual volume of the area on which the product 2 is located is assigned the net weight of the product 2 via the reference line determined in step 105. As already mentioned, the evaluation does not necessarily have to relate only to the region of the first image 12, but rather the entire area of the difference image 15 can be evaluated and the weight derived directly. In continuous operation, steps 106 and 107 are continuously repeated (step 108).

The two images 12, 13 can be either by a single

X-ray source 28 are generated, or there will be two

X-ray sources 28 are used, one for tara imaging (first image 12) and one for gross imaging (image 13). In the first case, the container 3 must pass the same X-ray source 28 twice, once before the filling of the container 3 and once after the filling. Thus, a 100% inline net weight determination with high accuracy is possible.

The procedure described specifically determines the net weight of the product 2 and no longer merely the gross weight of container 3 and product 2 as in the prior art. This is particularly important for small quantities of particular importance, since in these cases, the weight of the container 3 has a great influence on the accuracy of weight determination. Thus, in the case of small filling quantities, production fluctuations of the tare weight of empty containers 3 may be greater than the maximum permissible

Capacity fluctuations. This can lead to containers 3 with correct filling quantity of the product 2 being sorted out as incorrectly filled because the tare weight of the container 3 has exhausted the weight tolerance. Conversely, this can also result in a container 3 filled with too much or too little product 2 being erroneously recognized as being in order, because the tolerated container weight fluctuation behaves in the opposite direction and compensates for the incorrect dosage. These unacceptable cases counteract the described net weight determination by means of differential imaging.

The procedure described is particularly suitable for hard gelatin capsules, but also for glass containers such as vials, ampoules, or the like, but is not limited thereto.

Claims

claims

Device for weight determination of a particular pharmaceutical product (2), which is located in a container (3), comprising at least one X-ray source (28) which generates a beam path (18) for

Radiation of at least one container (3), comprising at least one sensor (14), which detects the radiation of the irradiated container (3) in the form of an image (12, 13), characterized in that an evaluation device

(14) is provided, which is a first image (12) of an irradiated empty

Container (3) and a second image (13) of a filled with a product (2) container (3) evaluates by the evaluation device (14) a difference image

(15) generates by subtracting the second image (13) from the first image (12) and then, based on the difference image (15), a net weight of the product (2) located in the container (3).

2. Apparatus according to claim 1, characterized in that the

Evaluation device (14) determines the association between the difference image (15) and the net weight of the product (2) located in the container (3) with the aid of a reference line.

Device according to one of the preceding claims, characterized

characterized in that the evaluation device (14) for determining the

Net weight a reference line created by the difference image (15) or a derived from the difference image (15) volume with a

Weighing device (44) assigns determined weight of the container (3) and / or the product (2).

Device according to one of the preceding claims, characterized

characterized in that a receiving means, in particular a capsule holder (42), is provided for receiving at least one container (3) that the container (3) via a conveying means (40) to a filling station (43) is moved, the container (3 ) with a product (2) that the container (3) of the X-ray source (28) is supplied to generate the second image (13).

Device according to one of the preceding claims, characterized

in that at least one reference object (35) is provided, which is arranged in the radiation path (18) of the X-radiation source (28) and which has different thicknesses, wherein for determining the net weight

Evaluation unit (14) the gray values of the difference image (15) each one of the gray value (38) of the reference object (35) corresponding thickness of

Assigns reference object (35).

Method for determining the weight of a particular pharmaceutical product (2), which is located in a container (3), wherein a

X-ray source (28) at least one container (3), wherein at least one sensor (14) detects the irradiated container (3) in the form of an image (12, 13), characterized in that a first image (12) of an irradiated empty container (3) and a second image (13) of a container (3) filled with a product (2) is created such that a difference image (15) is produced by subtracting the second image (13) from the first image (12) then, based on the difference image (15), a net weight of the product (2) in the container (3) is determined.

Method according to the preceding method claim, characterized

in that the association between the difference image and the net weight of the product (2) in the container (3) is determined by means of a reference line.

Method according to one of the preceding method claims, characterized in that to determine the net weight, the reference line is determined by assigning the difference image (15) and one with the aid of a

Weighing device (44) determined weight. Method according to one of the preceding method claims, characterized in that a plurality of difference images (15) for different

Containers (3) are created and from a damping curve is determined.

10. Method according to one of the preceding method claims, that after the container (3) has been irradiated, a receiving means (42), preferably a capsule holder, receives the container (3), that the container (3) is moved to a filling station (43), that the container (3) is filled there with a product (2) and that the container (3) of the X-ray source (28) is supplied to produce the second image (13).

11. Method according to one of the preceding method claims, characterized in that at least one reference object (35) is irradiated and gray values (38) resulting therefrom are transmitted through corresponding thicknesses of the reference object

(35) are assigned, wherein the gray values of the

Difference image (15) of the respective gray value (38) of the reference object (35) corresponding thickness of the reference object (35) are assigned.