Abstract:
The invention relates to a device and a method for determining the weight of product ( 2 ), in particular a pharmaceutical product, which is located in a container ( 3 ). The device comprises at least one x-ray source ( 28 ), which produces a radiation path ( 18 ), for passing radiation through the container ( 3 ), and a sensor ( 14 ), which detects the radiation of the container ( 3 ) through which radiation is passed in the form of an image ( 12 ), wherein an evaluating apparatus ( 14 ), is provided, which divides the image ( 12 ) of the container ( 3 ) through which radiation is passed into at least one evaluation region ( 21 ) in which there is no product ( 2 ).

Description:
BACKGROUND OF THE INVENTION 
       [0001]    The invention proceeds from a device and a method for determining the weight of pharmaceutical products by means of an x-ray source. A generic device and method are already known from WO 2012/013368 A1. An x-ray source produces a radiation cone which irradiates at least one pharmaceutical product. A sensor element detects the radiation of the irradiated pharmaceutical product and feeds it to an evaluation device. A reference object is arranged in the radiation path of the radiation cone, the radiation of the x-rayed reference object being detected by means of sensor elements and fed to the evaluation unit, the pharmaceutical product and the reference object being positioned with reference to the radiation cone in a non-congruent arrangement with one another in the radiation cone. 
       SUMMARY OF THE INVENTION 
       [0002]    It is an object of the present invention further to improve the accuracy of the determination of weight. 
         [0003]    The device according to the invention and the method according to the invention have, by contrast, the advantage that the measuring accuracy can be markedly increased with reference to the net weight. It is therefore possible to have a 100% inline net weight determination during normal operation with high accuracy without the use of a gravimetric load cell. This is because the device according to the invention and the method according to the invention make use of specific information from, in particular, digital images of the containers filled with pharmaceutical products in order to determine the net weight with a higher accuracy than would be possible with a conventional gross weight determination. This is possible, in particular, because the weight of an empty container is determined on the basis of the part of a container which can be freely x-rayed, in particular the part thereof in which no product is located. This determined tare weight value is subsequently subtracted from the gross weight. The result is the net weight of the product located in the container. The evaluation can take place with the aid of only a single x-ray image. The net weight of the product, which is of greatest interest, is hence determined in targeted fashion, and no longer only the gross weight of container and product, as in the prior art. This is particularly advantageous especially in the case of small filling quantities, since in said instances the weight of the container greatly influences the accuracy of the determination of weight. Thus, given small filling quantities, manufacturing fluctuations in the tare weight of empty containers can be greater than maximum permissible fluctuations in filling quantities. This can result in containers with the correct filling quantity of the product being rejected as incorrectly filled, because the tare weight of the container has exhausted the weight tolerance. Conversely, this can also have the effect that a container filled with too much or too little filled product is wrongly recognized as being in order, because the tolerated container weight fluctuation has the opposite effect and compensates the erroneous dosing. The net weight determination described counteracts said unacceptable cases particularly advantageously. 
         [0004]    In an expedient development, it is provided that the evaluation device determines the tare weight of the container in that the evaluation device forms the ratio between a measure of an area of the evaluation region and a measure of an area of a contour of the entire irradiated container. It is particularly preferred to make use as measure of an area of the evaluation region and/or of the contour of such pixels of the sensor that lie within the evaluation region and/or within the contour. It is particularly easy to use the information of the flat sensor to extrapolate the tare weight to the entire container without the need for additional sensors or measurements. The structure of the device is thereby simplified. 
         [0005]    In an expedient development, it is provided that the evaluation device evaluates gray scale values and/or pixels of the sensor lying within the evaluation region and/or the contour in order to determine the weight. The accuracy of the determination of weight can be further increased by a targeted evaluation of the regions of interest. It is easy for variables corrupting the net weight determination to be removed by calculation. 
         [0006]    In an expedient development, it is provided that the device is trained to the containers being used, in particular empty containers. For this purpose, it is preferred to construct a reference line of the container material, in which case the reference to the gravimetric weight could be done with the aid of very accurate scales (tare adjustment). 
         [0007]    In an expedient development, it is provided that the device is trained to containers with filled product. In this case, the reference line of a container with product is constructed, it being possible for the reference to the gravimetric weight to be made with the aid of very accurate scales (gross adjustment). 
         [0008]    In an expedient development, it is provided that the device comprises means for imaging the container to be tested. A specific evaluation region is prescribed in targeted fashion. Said region is preferably in such a container area as is not filled with a product. Subsequently, said region of the part of the container which can be freely x-rayed is evaluated. This is done by using said part of the container which can be freely x-rayed, and by using the determined reference line in the course of the tare adjustment and extrapolation to the empty weight of a container (tare weight). 
         [0009]    In an expedient development, it is provided that the entire container, including the product, can now be evaluated with recourse to the already determined image. The gross weight is determined on the basis of this information and the reference line as determined in the course of the gross adjustment. 
         [0010]    In an expedient development, it is provided that the net weight of the container to be tested is determined by forming the difference between the gross weight and the tare weight, as determined in the prior method steps. 
         [0011]    In an expedient development, it is provided that at least one reference object is provided which is arranged in the radiation path of the x-ray source and which has different thicknesses, in which case, in order to determine the net weight, the evaluation unit respectively assigns the gray scale values of the differential image a thickness of the reference object which corresponds to the gray scale value of the reference object. It is precisely owing to the use of a reference object having different thicknesses which is likewise irradiated together with the container during operation that it is possible to convert the gray scale values reliably into a net weight. This can be performed in a particularly simple and accurate way with the aid of the corresponding thicknesses, conversion into a volume and assignment to a net weight by means of the reference line. 
         [0012]    In an expedient development, it is provided that at least a second reference object is provided which is arranged in the radiation path of the x-ray source and has different thicknesses. It would be possible in this case for one of the reference objects to be adapted to the material of an empty container, and for the other to be adapted to the container filling. The more that the empty container and product differ from one another with reference to their absorption properties, the greater the increases in accuracy that can be attained thereby. During the tare adjustment, the reference object tuned to the empty container would be used to construct the reference line. During the gross adjustment, the further reference object tuned to the container filling would be used to construct the reference line. During the subsequent actual measurement, the empty container extrapolation is carried out again with the aid of the reference object tuned to the empty container, and the gross measurement is carried out with the aid of the further reference object tuned to the container filling. Consequently, conversion into virtual volume and thus into the weight is carried out in a differentiated manner, depending on the material being considered, and leads to a once more improved accuracy. 
         [0013]    In an expedient development, an accommodating means, in particular a capsule holder, is provided for accommodating at least one container, the container being fed via a conveying means to a processing station and/or the x-ray source in order to produce the image. Said arrangement is suitable, in particular, for containers which are fed to different workstations at high speed. It is possible thereby to achieve high throughput rates. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0014]    An exemplary embodiment of the device according to the invention and of the method according to the invention are illustrated in the drawing and described in more detail below. 
           [0015]    In the drawing: 
           [0016]      FIG. 1  shows the fundamental principle of imaging, which is based on x-radiation, 
           [0017]      FIG. 2  shows a partially filled container, 
           [0018]      FIG. 3  shows an image of a filled container with established evaluation regions, 
           [0019]      FIG. 4  shows a device according to the invention, 
           [0020]      FIG. 5  shows a flowchart of the method according to the invention, 
           [0021]      FIG. 6  shows another filled container, 
           [0022]      FIG. 7  shows a once again modified device for determining weight, 
           [0023]      FIG. 8  shows an image of a plurality of irradiated containers and of the reference object for an arrangement according to  FIG. 7 . 
       
    
    
     DETAILED DESCRIPTION 
       [0024]    A plurality of containers  3  are located in a radiation path  36  of an x-ray source  28  which irradiates the containers  3 . Located downstream is a sensor  30  with a sensor surface  32  which faces the x-ray source  28 . The sensor  30  serves to produce an x-ray image or image  12  of the irradiated container. The sensor surface  32  preferably comprises a multiplicity of radiation-sensitive sensor elements such as, for example, CCD sensors or CMOS sensors which, depending on the incident radiation, respectively emit an output signal which is referred to below as gray scale value. By way of example, to this end a scintillation layer which converts the x-ray energy into visible light is applied over the pixels of the CMOS sensor. As a function of the light quantity, the pixel of the sensor generates a charge (analog) which is preferably converted into a digital signal (“gray scale value”) which is used for determining weight. The image  12  is produced via the output signals of the sensor elements arranged in two dimensions. It is also possible in principle to use other radiation detecting means as sensors. 
         [0025]    In the right-hand exemplary embodiment of  FIG. 1 , there is also located a reference element  35  in the radiation path  36  of the x-ray source  28 . The reference element  35  is arranged non-congruently next to the containers  3  and is likewise irradiated. The image  12  thereby produced is likewise recorded by the sensor  30 . 
         [0026]    The container  3  in accordance with  FIG. 2  is, for example, a capsule in which there is partially located a product  2  such as, for example, a pharmaceutical product. The container  3  thus has a region  20  which can be freely x-rayed and in which no product  2  is located, and a region  22  which cannot be freely x-rayed and in which the product  2  is located. 
         [0027]    In  FIG. 3 , the container  3 , in turn, has a region  22  which cannot be freely x-rayed, and a region  20  which can be freely x-rayed. An evaluation region  21  is now established for the region  20  which can be freely x-rayed, this being done in such a way that there is certainly no product  2  located within the evaluation region  21 . Moreover, a contour  24  of the container  3  which corresponds to the outer contour is established via a threshold value evaluation of the gray tones. 
         [0028]      FIG. 4  shows the device  10  which is suitable for carrying out the method described. This is described in an exemplary manner using the concrete example of a capsule filling machine for which the invention is particularly suited, but is not restricted thereto. 
         [0029]    A machine for filling and closing the container  3  consisting of a capsule base and a plug-on cap has a twelve-part conveyor wheel  40  which is turned in stepwise fashion about a vertical axis and at whose stations  1  to  12  the individual handling devices are arranged on the revolving section. Other divisions of the conveyor wheel  40  would also be conceivable, for example into 15 parts. In the case of stations  1  and  2 , the empty containers  3  to be filled are placed in unordered fashion, and are oriented. The containers  3  are subsequently fed in ordered fashion to a capsule holder  42  of a conveyor wheel  40 . The containers  3 , closed till now, are opened in station  3 . The container  3  is filled with the product  2  in station  5 . The filled container  3  is closed in station  7 . The containers  3  are weighed in station  8  by a weighing device  44 . The weighing device  44  can undertake different measurements. Firstly, the weighing device  44  can undertake to weigh the empty or filled container  3  for initialization. The weighing device  44  could also be used for comparative weighing while production is proceeding in order to check the measurement system described, which is based on x-radiation. The closing pressure for the closed container  3  is monitored in station  9 . Depending on the test in station  9 , defective containers  3  in station  10  are ejected for the first time in ordered fashion in station  11 . In station  11 , the containers  3  pass upward from the capsule holder  42  into the radiation path  36  of an x-ray source  28 . Depending on the weight of the product  2  as determined in step  103 , defective containers  3  can still be discarded with the aid of a switch  46 . 
         [0030]    In the exemplary embodiment in accordance with  FIG. 6 , an ampoule which is filled with a liquid product  2  is provided as container  3 . For this product, as well, it is possible to define a region  22  which cannot be freely x-rayed, and a region  20  which can be freely x-rayed. 
         [0031]      FIG. 7  illustrates a once again modified device  10  for determining weight. The device  10  has a conveyor wheel  51  which is turned in stepwise fashion in a vertically arranged axis of rotation  52 . Accommodating means  54  for the exchangeable fastening of format parts  55  are formed on an annular, vertically oriented outer wall  53  of the conveyor wheel  51  at regular angular spacings. Respectively formed in the format parts  55  are a plurality of accommodating bores  56  which, in particular, are likewise vertically oriented, act as accommodating means for the containers  3  and each have a height and/or length which enables a plurality of containers  3  to be respectively accommodated one above another in a row in the accommodating bores  56 . Moreover, the format parts  55  respectively have at least one reference object  35  which is arranged next to the accommodating bores  56  likewise in the radiation path  36  of the x-ray source  28 . The format parts  55  consist of a material, in particular of plastic, which is transparent to the x-radiation. The accommodating bores  56  of the format parts  55  are filled with the containers  3  by means of shaft-like feeding channels  57  from a bulk store (not shown), blocking devices respectively being arranged in the region of the feeding channels  57  corresponding to the device  10 . In the illustrated exemplary embodiment, a plurality of x-ray sources  28  are arranged on the conveyor path of the conveyor wheel  51  outside the outer circumference thereof. In this case, the number of the x-ray sources  28  preferably corresponds to the number of the feeding channels  57  so that, for example when three feeding channels  57  are present, the conveyor wheel  51  is respectively rotated further in stepwise fashion through a range of angular rotation which corresponds to the division of three feeding channels  57 . In order that individual containers  3  which have been recognized as “bad” can be discarded from the conveyor wheel  51  and/or the accommodating bores  56  of the format parts  55 , there are provided on the further conveyor path of the conveyor wheel  51  downstream of the x-ray sources  28  discarding rams  65  which can be moved up and down in accordance with the double arrow  61  and can enter the accommodating bores  56 , designed as stepped bores, of the format parts  55  in order thereby to discard the containers  3  located in the region of the accommodating bore  56 . The device  10  also comprises a weighing device  44  for training purposes, as described below. 
         [0032]    The image  12  in accordance with  FIG. 8 , which is produced in the arrangement according to  FIG. 7 , firstly shows the x-ray image of a plurality of containers  3  arranged next to and above one another. Visible on the right-hand side is the image of the irradiated reference object  35  which has different gray tones  38 . The reference object  35  is constructed in the form of scale steps with different thicknesses. In the case of the respective different thicknesses, different gray tones  38  are produced, as is stated in more detail below. For example, the evaluation region  21  and the contour  24  of the container  3  are already established and/or determined. 
         [0033]    In an alternative embodiment, at least a second reference object  35 ′ is provided which is arranged in the radiation path  36  of the x-ray source  28  and has different thicknesses. In this case, one of the reference objects  35 ′,  35 ″ could be adapted to the material of an empty container  3 , and the other could be adapted to the container filling  2 . The more that the empty container  3  and product  2  differ from one another with reference to their absorption properties, the greater the increases in accuracy which can be attained thereby. In the tare adjustment, the reference object  35 ′ tuned to the empty container  3  would be used to construct the reference line. In the gross adjustment, the further reference object  35 ″ tuned to the container filling would be used to construct the reference line. In the subsequent actual measurement, the empty container extrapolation is carried out again with the aid of the reference object  35 ′ tuned to the empty container, while the gross measurement is carried out with the aid of the further reference object  35 ″ tuned to the container filling. The conversion into virtual volume and thus into the weight is thus carried out in a differentiated manner, depending on the material being considered, and leads to a once more improved accuracy. 
         [0034]    The image  12  is evaluated firstly with regard to the contour  24  of the container  3 . To this end, the gray scale values assigned to the respective pixels are evaluated. Said gray scale values are compared with such gray scale values as are produced upon irradiation of the known reference object  35 . 
         [0035]    In principle, weight is determined in accordance with the arrangement shown in  FIG. 1 , as described in general below. The reference object  35  advantageously consists of a material which has atomic properties similar to the pharmaceutical product  2  to be irradiated, that is to say, in particular, has the same attenuation properties for the x-radiation. The reference object  35  has different thicknesses considered over the cross section. The reference object  35  can be of wedge-shaped design. Alternatively, the reference object  35  has a row of steps which effect a discrete change in the thickness of the reference object  35 . It is preferred to provide that the attenuation (gray scale value) of the reference object  35  is greater at one site and less at another site than the attenuation owing to the pharmaceutical product  2 . Owing to the geometrical form of the reference object  35  that has been mentioned, these have different thicknesses which produce different gray tones  38  at the sensor element  30  upon irradiation by means of the x-ray source  28 . Individual steps of the reference object  35  have different gray scale values  38 . 
         [0036]    The weight of the product  2  located in a container  3  is determined as follows, in principle: in an adjusting process (not shown) that takes place in advance, an image of the reference object  35  is recorded, and its gray scale values  38  detected by the sensor device  30  are assigned to the thicknesses of the reference object  35  on the basis of the known geometrical design of the reference object  35 . In other words, what this means is that a specific thickness of the reference object  35  at a specific site is inferred on the basis of a specific gray scale value  38  of the reference object  35 . Furthermore, a specific thickness can therefore be assigned to a specific gray scale value  38  of the reference object  35  on the basis of the known geometry of the reference object  35 . Said gray scale values  38  determined in advance in the calibration process, and their geometric assignment to the reference object  35 , are stored in the evaluation device  14 . If the aim is now, for example, to detect and/or check the weight, the image  12 , acquired by the sensor element  30 , of the container  3  is split into individual pixels. Said pixel displays a specific area, for example a square with an edge length of 100 □m. The detected gray scale value of the pixel is then assigned to an (identical) gray scale value  38  on the reference object  35  for each pixel of the container  3 . A specific thickness can be assigned to said gray scale value (on the basis of the assignment of the thicknesses to the gray scale values  38  on the reference object  35 ). Once this has been done pixel by pixel, a mean thickness is determined from individual thicknesses. Said mean thickness is now multiplied by the total number of the pixels and their known area so that a virtual volume of the product  2  can be determined. Finally, the weight of the product  2  located in the container  3  can be determined from the virtual volume. 
         [0037]    An image of the relevant reference object  35  is also concomitantly recorded simultaneously during the x-ray of the products  2 , in particular pharmaceutical ones. Changes in the gray tones on the reference object  35  can thereby be determined on temporally consecutive images which can occur owing to interference of the system or external interference. By way of example, should it be established that the gray scale value  38  of the reference object  35  changes at a specific step, the evaluation device  14  can verify said detected current gray scale value with a correction factor or offset, the result being that the current gray scale value is adapted to the original gray scale value, and the interference is thereby equalized. On the basis of said general procedure, the net weight is determined in accordance with the invention as described below by means of empty container extrapolation. 
         [0038]    The device  10  according to the invention operates as follows. In a first step  101 , the system is trained to the empty containers  3  being used. To this end, it is at least one empty container  3  and the reference element  35  arranged next to it that are irradiated. The sensor  30  situated downstream acquires the radiation falling onto the sensor surface  32  in the form of an image  12  with different gray scale values. Said image  12  is firstly evaluated to detect the contour, for example in that the contour  24  of the container  3  is inferred pixel by pixel in the case of a specific transition of gray scale values and/or threshold value. 
         [0039]    Subsequently, only such pixels as lie within the determined contour  24  of the container  3  are evaluated. The gray scale value of the respective pixel which lies within the contour is used to construct a reference line. The respective gray scale value is compared with that gray scale value  38  of the reference object  35  whose related thickness is known. A thickness is thus assigned to the respective pixel. This is performed for all pixels lying within the contour  24 , the result being a mean thickness for the known area of the contour  24 . A weight can be assigned to said volume. To this end, a weighing device  44  acquires the weight of the empty container  3 . This is called tare adjustment. The attenuation curve makes the connection between the respective gray scale values of the image  12  and/or pixel and the related empty weight of the container  3 . 
         [0040]    In a second step  102 , the system is trained to the containers  3  trained in the first step  101 , but now filled with product  2 . Once again, a reference line of the container  3  with product  2  is constructed as already done above (described for an empty container  3 ), the relation to the gravimetric weight being produced using the weighing device  44  which determines the weight of a container  3  filled with product  2 . The so-called gross adjustment is performed in this way. Once again, the respective gray scale values are assigned via the determined reference line to the corresponding weight of a filled container  3 . Said training steps  101  and  102  are executed before the start of the production phase of a new charge which differs from the preceding one both in the type of container  3  and/or of the filled product  2 . Said steps  101  and  102  can be carried out with a plurality of different containers  3 , and the results can be suitably averaged and/or interpolated. 
         [0041]    Alternatively, it could be provided that the operating parameters of a device  10  (as described above, for example) which is set uniquely for specific charge parameters can be stored and reloaded later for a similar charge. The adjustment steps  101  and  102  described could then be superfluous. 
         [0042]    In a third step  103 , the sensor  30  produces an image  12  of the container  3  which is located in the radiation path  36 , is to be checked and is filled with product  2 . The weight of the product  2  is to be determined by means of empty container extrapolation. 
         [0043]    In a fourth step  104 , at least one evaluation region  21  is established in the image  12  acquired in step  103 . To this end, the contour  24  of the irradiated container  3  can firstly be determined via appropriate image recognition. With the aid of the determined gray tones, the position or the geometry of the container  3  and/or with knowledge of the filled product  2 , the evaluation region  21  is then selected so that there is certainly no product  2  located in said evaluation region  21 . By way of example, at least the evaluation region  21  could be established manually in the course of the training phase by the operating staff via appropriate inputs. Alternatively, said establishing process could also be performed automatically on the basis of gray scale value, contour  24  of the container  3  or information relating to the volume to be expected of the filled product  2 . The selected evaluation region  21  is established once and retained for the subsequent steps for detecting weight. The subsequent steps  105  to  107  are then carried out as the production operation proceeds. 
         [0044]    In a fifth step  105 , the evaluation region  21  established in step  104 , specifically the part of the container  3  which can be freely x-rayed, is evaluated. The pixels lying in the evaluation region  21  are evaluated as described above with reference to their gray scale values. On the basis of said information and the reference line for an empty container  3  determined in the first step  101 , the empty weight of the container  3  x-rayed in the third step  103  is now extrapolated. The tare weight of the container  3  is thus determined. By way of example, in this case the ratio is formed between the area of the evaluation region  21  and the total area of the container  3 , in order thus to infer the total weight of the empty container  3 . The total area of the container  3  can be determined via the detected contour  24 . The number of the pixels lying within the contour  24 , whose magnitude is known, is a measure of the total area. However, other options would also be conceivable for the determination. By means of the weight of the portion of the area of the evaluation region  21  with reference to the total area of the container  3 , extrapolation to the weight of the complete empty container  3 , the tare weight which is available at the end of step  105 , is performed. 
         [0045]    In a sixth step  106 , the whole container  3  including product  2  is evaluated on the basis of the image  12  acquired in the third step  103 . For this purpose, all pixels lying within the contour of the entire container  3  are evaluated together with their gray scale values. The gross weight of the container  3  irradiated in the third step  103  is now determined from said information and the reference line for a filled container  3  determined in the second step  102 . A procedure for the corresponding determination of gross weight is as described above in general. The gray scale values of container  3  and product  2  overlap one another. Consequently, the determination of weight based on the gray scale values comprises both the weight of the empty container  3  and the weight of the product  2 . 
         [0046]    In a seventh step  107 , the net weight of the product  2  is determined in accordance with the relationship: net weight=gross weight (as determined in the sixth step  106 )−tare weight (as determined in the fifth step  105 ). The result is thus the pure net weight of the container filling, that is to say the weight of the product  2 . 
         [0047]    Owing to the procedure described, the net weight of the product  2  is determined in targeted fashion, and no longer only the gross weight of container  3  and product  2 , as in the prior art. This is particularly important especially in the case of small filling quantities, since in said instances the weight of the container  3  greatly influences the accuracy of the determination of weight. Thus, given small filling quantities, manufacturing fluctuations in the tare weight of empty containers  3  can be greater than maximum permissible fluctuations in filling quantities. This can result in containers  3  with the correct filling quantity of the product  2  being rejected as incorrectly filled, because the tare weight of the container  3  has exhausted the weight tolerance. Conversely, this can also have the effect that a container  3  filled with too much or too little filled product  2  is wrongly recognized as being in order, because the tolerated container weight fluctuation has the opposite effect and compensates the erroneous dosing. The net weight determination described counteracts said unacceptable cases by means of empty container extrapolation. 
         [0048]    The procedure described is suitable, in particular, for pharmaceutical hard gelatin capsules, but also for tablets, glass containers such as vials, ampoules or the like, but is not restricted thereto.