JP2024026817A - Manufacturing method of powder-encapsulated container - Google Patents

Abstract

To provide a method for manufacturing a powder-encapsulated container, which can accurately determine the presence of foreign matter in powder in a transparent container and has a low defective product rate.SOLUTION: A manufacturing method of powder-encapsulated container includes: an encapsulation step of encapsulating powder 21 in a vial 20; an inspection step to inspect foreign matter in the powder 21; and a defective product sorting step in which the vial 20 determined to contain foreign matter is regarded as a defective product. In the inspection step, while the vial 20 is vibrated via a clamp 12 that supports the vial 20, the clamp 12 is reciprocally vibrated in a vertical direction 5 and a horizontal direction 7 to allow the powder 21 in the vial 20 to flow and the flowing powder 21 is optically photographed through the vial 20, and it is determined whether or not foreign matter is present in the powder 21 based on the photographed image.SELECTED DRAWING: Figure 2

Description

TECHNICAL FIELD The present invention relates to a foreign matter inspection method for inspecting whether there is a foreign matter in powder in a transparent container, and a method for manufacturing a powder enclosure container.

Conventionally, transparent containers such as vials have been used to package powder medicines such as injections, powders, fine granules, and granules. Visual inspection and inspection by analyzing optically obtained image data are known as methods for inspecting whether foreign matter is present in the powder in the transparent container (Patent Document 1). The foreign object detection method described in Patent Document 1 applies combined vibration in the vertical and horizontal directions to a transparent container filled with powder, and optically detects foreign objects in the powder.

Patent No. 5307459

However, powder with poor fluidity does not flow while being scattered by synthetic vibrations, but instead flows as a lump, so foreign particles contained in the flowing powder do not appear on the surface of the powder lump, and foreign particles There is a problem that the detection rate is not good. As a result, even though foreign matter is present in the powder, it may be determined that the powder is a good product with no foreign matter present.

The present invention has been made in view of the above circumstances, and its purpose is to provide a method for manufacturing a powder-enclosed container that can accurately determine the presence of foreign matter in powder in a transparent container and has a low defect rate. The goal is to provide the following.

(1) The method for manufacturing a powder enclosure according to the present invention includes an enclosing step of enclosing powder in a transparent container, an inspection step of inspecting the powder for foreign matter, and the transparent container in which it is determined that the foreign matter is present. and a defective product sorting process in which the products are determined to be defective products. The inspection step includes applying vibration to the transparent container via a support section that supports the transparent container, and applying reciprocating vibration to the support section in a first direction and a reciprocating vibration in a second direction intersecting the first direction. and causing the powder in the transparent container to flow, and optically photographing the flowing powder through the transparent container, and based on the photographed image, it is determined that foreign matter is present in the powder. Determine whether

In the inspection process, vibrations applied via the support part cause the powder lumps in the transparent container to collapse, making it easier for the powder to scatter. The reciprocating vibration in the first direction and the reciprocating vibration in the second direction cause the powder to circulate in the transparent container. As a result, the powder flows while being scattered in the transparent container, so that foreign matter in the powder is likely to be exposed during the inspection process, and the foreign matter is likely to appear in the photographed image. In the defective product selection step, transparent containers determined to have foreign matter present are determined to be defective, so that the foreign matter contamination rate of the manufactured powder-filled containers is low.

(2) Preferably, the transparent container includes a container body having a mouth, a side wall continuous with the mouth, and a bottom continuous with the side wall, and a lid that is plugged into the mouth. In the enclosing step, the lid is plugged onto the container body that stores the powder.

Powder sealed in a transparent container is accurately inspected for foreign matter contamination, and a powder enclosing container with a low foreign matter contamination rate is manufactured.

(3) Preferably, in the inspection step, the first direction and the second direction are perpendicular to each other, and the support part is configured to move a third direction in which the mouth part and the bottom part face each other to the first direction. The powder is supported perpendicularly to the direction and the second direction, and the flowing powder is photographed through the side wall.

Since the powder accumulated on the bottom side of the transparent container flows along the side wall, foreign matter in the powder is likely to be exposed, and the foreign matter is likely to appear in the photographed image.

(4) Preferably, the third direction is inclined with respect to the horizontal direction, with the mouth section being above the bottom section.

Since the powder flowing along the side wall of the transparent container is located on the bottom side, it is easy to limit the range in which images are taken.

(5) Preferably, in the inspection step, the flowing powder is photographed from below the transparent container.

Since a photograph is taken of the collision between the powder that falls due to gravity while flowing in the transparent container and the transparent container that vibrates back and forth, foreign matter is likely to appear in the photographed image.

(6) Preferably, the angle of repose of the powder is within the range of 30 degrees to 60 degrees.

According to the present invention, since it is possible to accurately determine the presence of foreign matter in the powder in the transparent container, it is possible to obtain a powder enclosure with a low foreign matter contamination rate.

FIG. 1 is a perspective view of a vial 20. FIG. FIG. 2 is a schematic diagram of the foreign matter inspection device 10. FIG. 3 is a diagram showing the inclination of the vial 20 held by the clamp 12. FIG. 4 is a diagram showing the powder 21 moving elliptically within the vial 20.

Embodiments of the present invention will be described below with reference to the drawings as appropriate. Note that the embodiments described below are merely examples of the present invention, and it goes without saying that the embodiments of the present invention can be modified as appropriate without changing the gist of the present invention. In the following description, a vertical direction 5 is defined with the top and bottom as a reference, and a front-back direction 6 (a direction perpendicular to the paper surface of FIG. 2) is defined in a direction perpendicular to the top-bottom direction 5. A left-right direction 7 is defined in a direction perpendicular to each other.

[Vial 20 and powder 21]
As shown in FIG. 1, the object to be inspected by the foreign matter inspection apparatus 10, which will be described later, is a vial 20 (an example of a transparent container and a powder enclosure container) containing powder 21. Although not shown, the vial 20 is sealed by a known method, for example, by wrapping the lid 22 and the container body 23 with an aluminum cap. The powder 21 is a drug such as an injection, a powder, a fine granule, or a granule. Drugs are not particularly limited, but include, for example, cell wall synthesis inhibitory antibiotics, cell membrane inhibitory antibiotics, nucleic acid synthesis inhibitory antibiotics, protein synthesis inhibitory antibiotics, folic acid metabolic pathway inhibitory antibiotics, and β-lactamases. Inhibitors, sulfa drugs, anti-infectives are preferred. In addition, the drugs include ampicillin, bacampicillin, amoxicillin, pivmecillinam, amoxicillin, sultamicillin, piperacillin, aspoxilin, benzylpenicillin, cloxacillin, oxacillin, carbenicillin, cephaloclu, cefuroxazine, cefadroxil, cefixime, cefteram pivoxil, cefuroxime axetil, cefpo Doximeproxetil, cefothiamhexetil, cefdinir, ceftibuten, cefditoren pivoxil, cefcapene pivoxil, cefazolin, cefozopran, cefmetazole, cefothiam, cefsulodine, cefoperazone, cefotaxime, cefmenoxime, ceftriaxone, ceftazime, cefodisime, cefpirome, cefepime , faropenem, imipenem, panipenem, meropenem, biapenem, doripenem, aztreonam, vancomycin, teicoplanin, fosmicin, polymyxin B sulfate, colistin sulfate, gramicidin S, amphotericin B, levofloxacin, ofloxacin, norfloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin , sparfloxacin, gatifloxacin, prulifloxacin, moxifloxacin, pazufloxan, rifampicin, dibekacin, tobramycin, amikacin, isepamycin, micronomycin, streptomycin, kanamycin, gentamicin, erythromycin, rokitamycin, josamycin, loxuro Mycin, clarithromycin, azithromycin, telithromycin, doxycycline, minocycline, chloramphenicol, lincomycin, clindamycin, trimethoprim, clavulanic acid, sulbactam, tazobactam, sulfamethoxazole, salazopyrin, isoniazid, rifampicin, pyrazinamide , ethambutol, griseofulvin, amphotericin B, 5-fluorocytosine, fluconazole, miconazole, itraconazole, acyclovir, ganciclovir, foscavir, idoxuridine, amantadine, interferon gamma, ribapirin, ramipudine, metronidazole, tinidazole, fluconazole, mebendazole, pyrantel pamoate, Diethylcarbamazine, praziquantel, albendazole, ivermectin, quinupristin, dalfopristin, linezolid, spectinomycin, netilmycin, sisomycin, lincosamine, ramoplanin, telithromycin, nystatin, Examples include fusidic acid, chlorhexidine, and polyhexanid.

The characteristics of the powder 21 include, for example, the angle of repose, particle size, filling amount, and bulk density. Specifically, the angle of repose of the powder 21 is in the range of 30 degrees to 60 degrees, preferably in the range of 33 degrees to 60 degrees. Specifically, the particle size of the powder 21 is such that the average particle diameter (median diameter: d50) is in the range of 20 μm to 70 μm, preferably in the range of 21.1 μm to 55.7 μm. The amount of powder 21 contained in the vial 20 is at least 0.25 g, and even if the amount is large, it can be inspected by the foreign substance inspection device 10. The bulk density of the powder 21 is specifically in the range of 0.300 g/mL to 0.700 g/mL, preferably in the range of 0.340 g/mL to 0.670 g/mL.

As shown in FIG. 1, the vial 20 (an example of a transparent container) has a lid 22 and a container body 23. The lid 22 is molded from resin such as rubber or elastomer. The container body 23 is made of transparent glass, for example. The container body 23 only needs to have enough light transmission to allow the photographing device 15 (see FIG. 2) to optically photograph the powder 21 in the internal space.

The container body 23 has a mouth 24 forming an opening communicating with the interior space, a side wall 25, and a bottom 26. The container body 23 has a generally cylindrical shape as a whole, and is a so-called narrow-mouthed container in which the outer diameter of the mouth portion 24 is smaller than the outer diameter of the side wall 25 . The mouth portion 24 and the bottom portion 26 are opposed to each other. The bottom portion 26 is disk-shaped, and the container body 23 stands up with the bottom portion 26 placed on a desk or the like with the opening of the mouth portion 24 facing upward. The side wall 25 has a cylindrical shape. The mouth portion 24 is continuous with the side wall 25. The mouth portion 24 has a shape whose outer diameter gradually increases toward the side wall 25 . The side wall 25 and the bottom 26 are continuous. The outer diameter of the side wall 25 and the outer diameter of the bottom portion 26 are equal.

The lid 22 has a shape in which a convex portion that enters and fits into the opening formed by the mouth portion 24 projects from a disc that is in close contact with the mouth portion 24 . For example, the container body 23 is filled with powder 21 using a filling machine, the lid 22 is plugged into the mouth 24, and the aluminum cap is rolled up to seal the container body 23.

[Foreign object inspection device 10]
The foreign matter inspection device 10 is for inspecting whether foreign matter is mixed into the powder 21 sealed in the vial 20. As shown in FIG. 2, the foreign object inspection device 10 includes a frame 11, a clamp 12 (an example of a support part), a vibration generator 13, a composite vibration generator 14, an imaging device 15, and an analysis device 16. , and a lighting device 17. The support portion 12 , the vibration generator 13 , the composite vibration generator 14 , and the photographing device 15 are supported by the frame 11 . The frame 11 can change its posture so that the front-rear direction 6 is inclined from the horizontal direction while supporting the support portion 12, the vibration generator 13, the composite vibration generator 14, and the photographing device 15. The analysis device 16 is connected to the imaging device 15 for data communication.

The clamps 12 are divided into a pair in the left-right direction 7, and by moving in the left-right direction 7, the clamps 12 change between a state in which the vial 20 is clamped and a state in which the vial 20 is not clamped. The clamp 12 clamps the side wall 25 of the vial 20 from the left and right directions 7. When the clamp 12 holds the vial 20, the direction in which the mouth portion 24 and the bottom portion 26 face each other (an example of the third direction), that is, the axial direction of the container body 23 is parallel to the front-rear direction 6.
Further, in a state where the clamp 12 holds the vial 20, a part of the side wall 25 of the vial 20 is exposed in the vertical direction 5.

The vibration generator 13 is fixed in each of the pair of clamps 12 at a position where it does not come into contact with the vial 20. The vibration generator 14 generates vibrations by, for example, rotation of an eccentric motor. The vibrations generated by the vibration generator 13 are transmitted to the vial 20 via the clamp 12.

The composite vibration generator 14 provides the clamp 12 with reciprocating vibration in the vertical direction 5 (an example of the first direction) and reciprocating vibration in the horizontal direction 7 (an example of the second direction). The synthetic vibration generator 14 includes a motor 40, a vertical vibration generating mechanism 41, and a horizontal vibration generating mechanism 42. The motor 40 generates a driving force that is transmitted to the vertical vibration generating mechanism 41 and the horizontal vibration generating mechanism 42.

The vertical vibration generating mechanism 41 includes an eccentric disk cam 43, a cam shaft 44, a link arm 45, and a slider 46. The eccentric disk cam 43 is rotatably supported by a cam shaft 44 that is supported by the frame 11 and extends along the front-rear direction 6. The camshaft 44 is provided with an eccentric disc cam 43. The eccentric disk cam 43 projects from the camshaft 44 in the radial direction. The length of the eccentric disk cam 43 protruding from the camshaft 44 changes continuously in the circumferential direction of the camshaft 44.

The link arm 45 is slidably fitted to the eccentric disc cam 43. As the rotation of the eccentric disc cam 43 is transmitted to the link arm 45, the link arm 45 rotates while being displaced in the vertical direction 5. The link arm 45 is connected to the slider 46 via a shaft 47. The slider 46 is movable in the up-down direction 5 by fitting into a slide rail 54 provided on the slider 51 of the left-right vibration generating mechanism 42 . Therefore, the slider 46 reciprocates in the vertical direction 5 according to the movement width in the vertical direction 5 during the rotation of the link arm 45 .

The link arm 45 has a support arm 55 extending along the left-right direction 7. The support arm 55 supports the clamp 12 and the vibration generator 14.

The left-right vibration generating mechanism 42 includes an eccentric disk cam 48, a cam shaft 49, a link arm 50, and a slider 51. The eccentric disk cam 48 is rotatably supported by a cam shaft 49 that is supported by the frame 11 and extends along the front-rear direction 6. The camshaft 49 is provided with an eccentric disc cam 48 . The eccentric disc cam 48 projects from the cam shaft 49 in the radial direction. The length of the eccentric disc cam 48 protruding from the camshaft 49 continuously changes in the circumferential direction of the camshaft 49.

The link arm 50 is slidably fitted to the eccentric disk cam 48. As the rotation of the eccentric disc cam 48 is transmitted to the link arm 50, the link arm 50 rotates while being displaced in the left-right direction 7. The link arm 50 is connected to a slider 51 via a shaft 52. The slider 51 is movable in the left-right direction 7 by fitting into a slide rail 53 provided on the frame 11 . Therefore, the slider 51 reciprocates in the left-right direction 7 according to the movement width in the left-right direction 7 during the rotation of the link arm 50 .

A slide rail 54 extending in the vertical direction 5 is formed at the left end of the slider 51. The slide rail 54 is fitted with the slider 46 of the vertical vibration generating mechanism 41. The reciprocating movement of the slider 51 in the left-right direction 7 is transmitted to the slider 46 via the slide rail 54 . Thereby, the slider 46 reciprocates in the left-right direction 7 and also reciprocates in the up-down direction 5. That is, the combined vibration of the reciprocating movement in the left-right direction 7 and the reciprocating movement in the up-down direction 5 is transmitted to the support arm 55.

Assuming that the amplitude of the reciprocating movement in the vertical direction 5 by the vertical vibration generating mechanism 41 and the amplitude of the reciprocating movement in the horizontal direction 7 by the horizontal vibration generating mechanism 42 are the same, the phase difference between the eccentric disc cams 43 and 48 is adjusted. By doing so, the resultant vibration becomes either circular motion, linear motion, or elliptical motion. For example, the phase difference between the eccentric disc cams 43 and 48 is set so that the resultant vibration becomes an elliptical motion.

The photographing device 15 is installed below the clamp 12. The photographing device 15 is a camera that optically photographs the powder 21 inside the vial 20 through a part of the side wall 25 exposed in the vertical direction 5 in the vial 20 held between the clamps 12 . The photographing device 15 photographs a plurality of images of the vibrating vial 20 at a frame rate of, for example, 30 or 60 images per second in a predetermined period of time.

The analysis device 16 is a computer installed with determination software that analyzes the image taken by the photographing device 15 and determines whether foreign matter is mixed in the powder 21. The analysis device 16 is connected to the photographing device 15 so as to be able to transmit and receive data. The analysis device 16 includes, for example, an input device such as a keyboard and a mouse, and a display device such as a display. The image received from the imaging device 15 may be displayed on the display of the analysis device 16.

The determination software determines whether foreign matter is mixed in the powder 21 of the vial 20 based on the image of the vial 20 taken by the imaging device 15, that is, the image data. Specifically, one piece of image data obtained is divided into a predetermined number of vertically and horizontally subdivided areas, and the color density of each area is identified into multiple levels. If the powder 21 is white, the foreign matter will be recognized as black. Then, it is determined whether a foreign object is present based on the peak value (color density of the foreign object) and intensity area value (length x width of the foreign object) in the image data. For example, the determination software determines that if both the peak value and the intensity area value are within predetermined conditions, for example, if each value is greater than or equal to the threshold and there is a continuous predetermined range, then the inside of the powder 21 in the vial 20 It is determined that there is a foreign object in the Note that the detectable foreign matter is not particularly limited, and may be any foreign matter that can be seen in the image with a brightness different from that of the powder 21.

The lighting devices 17 are installed above and below the clamp 12, respectively. The two illumination devices 17 irradiate the vial 20, which is held between the clamps 12 and vibrates, with light from the upper and lower directions 5, respectively. The illumination device 17 located below the clamp 12 does not overlap the region where the photographing device 15 and the clamp 12 face each other, and is located at a position offset in the front-rear direction 6 with respect to the region.

[Method for manufacturing vial 20 filled with powder 21]
Hereinafter, a method for manufacturing the vial 20 containing the powder 21 will be explained. The method for manufacturing vial 20 includes the following steps.
(1) Enclosing step of enclosing the powder 21 into the vial 20.
(2) Inspection process of inspecting foreign matter in the powder 21 (an example of an inspection method).
(3) A defective product selection step in which vials 20 determined to have foreign matter present in the powder 21 are determined to be defective products.

In the enclosing step, the powder 21 is filled into the container body 23 using an auger-type filling machine. Then, the lid 22 is plugged onto the container body 23 that stores the powder 21, and the aluminum cap is tightened to seal the boundary between the lid 22 and the container body 23. As a result, a vial 20 whose internal space is sealed with powder 21 is obtained.

The inspection process is performed using the foreign matter inspection device 10. The vial 20 whose internal space is sealed with powder 21 is held between the clamps 12 of the foreign object inspection device 10. The axial direction C (see FIG. 3) of the vial 20 held between the clamps 12 is parallel to the front-back direction 6.

When the foreign object inspection device 10 is activated, the frame 11 is tilted. As shown in FIG. 3, by tilting the frame 11, the axial direction C of the vial 20 is tilted with respect to the front-rear direction 6 (horizontal direction) with the opening 24 of the container body 23 being above the bottom 26. do. The angle of inclination is within the range of 0 degrees to 15 degrees, preferably within the range of 1 degree to 10 degrees. When the foreign object inspection device 10 is activated, the lighting device 17 is turned on.

After the frame 11 is tilted, the vibration generator 13 is activated and the motor 40 is activated. When the vibration generator 13 is activated, vibrations are applied to the vial 20 held between the clamps 12. By applying vibration to the vial 20, even if the powder 21 is attached to the side wall 25 in the vial 20, the powder 21 is separated from the side wall 25 due to the vibration. Moreover, the lump of powder 21 is broken down. This makes it easier for foreign substances mixed in the powder 21 to appear on the inner surface of the side wall 25 of the vial 20.

When the motor 40 operates, the synthetic vibration generator 14 applies a synthetic vibration to the vial 20 that causes an elliptical motion when viewed from the front-rear direction 6 . Due to this combined vibration, the powder 21 flows in the internal space of the vial 20 while circulating in an ellipse as shown in FIG. In this flow of the powder 21, foreign matter having a size and weight different from each particle of the powder 21 causes a flow different from that of the powder 21. For example, foreign matter that is heavier than each particle of the powder 21 tends to move outside the circulation of the flowing powder 21 and is therefore more likely to appear on the inner surface of the side wall 25 of the vial 20.

Further, since the axial direction C of the vial 20 is inclined with respect to the front-rear direction 6 with the opening 24 of the container body 23 being above the bottom 26, the powder 21 tends to accumulate toward the bottom 26. Further, foreign substances heavier than each particle of the powder 21 tend to move toward the bottom 26 than the powder 21, so they tend to appear on the inner surface of the side wall 25 near the bottom 26 of the vial 20.

The analysis device 16 determines whether or not there is a foreign object in the powder 21 inside the vial 20 based on an image of the vial 20 taken by the imaging device 15 when vibration and combined vibration are applied to the vial 20. do.

In the defective product selection process, vials 20 that are determined to have foreign matter in the powder 21 are excluded from shipment as defective products.

[Operations and effects of embodiment]
According to the embodiment described above, in the inspection process, the vibration applied via the clamp 12 causes the lumps of the powder 21 in the vial 20 to collapse, or the powder 21 to separate from the side wall 25, causing the powder to deteriorate. Body 21 becomes easier to scatter. Further, due to the combined vibrations in the vertical direction 5 and the horizontal direction 7, the powder 21 is circulated in the vial 20. As a result, the powder 21 flows while being scattered in the vial 20, so that foreign matter in the powder 21 is likely to be exposed during the inspection process, and the foreign matter is likely to appear in the photographed image. In the defective product selection step, the vial 20 determined to have foreign matter present is determined to be a defective product, so that the rate of foreign matter contamination in the manufactured vial 20 is low.

Further, in the inspection process, since the vial 20 is supported with the axial direction C parallel to the front-rear direction 6, the flowing powder 21 is photographed through the side wall 25 of the vial 20.

Further, in the inspection process, since the axial direction C of the vial 20 is inclined from the front-rear direction 6, the powder 21 accumulated on the bottom 26 side of the vial 20 flows along the side wall 25. Thereby, the foreign matter in the powder 21 is easily exposed, and the foreign matter is likely to appear in the photographed image. Further, since foreign matter tends to appear near the bottom 26 of the side wall 25 of the vial 20, the range in which images are taken for foreign matter determination is limited.

Further, in the inspection process, since the flowing powder 21 is photographed from below the vial 20, the powder 21 falling due to gravity while flowing inside the vial 20 collides with the side wall 25 of the vibrating container body 23. The condition is photographed. As a result, foreign objects are likely to appear in the captured image.

10... Foreign object inspection device 11... Frame 12... Clamp (support part)
13... Vibration generator 14... Composite vibration generator 15... Imaging device 16... Analysis device 20... Vial 21... Powder 22... Lid 23... Container body 24 ... Mouth 25 ... Side wall 26 ... Bottom

Claims (6)

an encapsulation process of encapsulating the powder in a transparent container;
an inspection step of inspecting foreign matter in the powder;
A method for manufacturing a powder-filled container, comprising: a defective product sorting step in which the transparent container determined to contain foreign matter is considered to be a defective product,
The above inspection process is
While applying vibration to the transparent container via a support part that supports the transparent container, reciprocating vibration in a first direction and reciprocating vibration in a second direction intersecting the first direction are applied to the support part. , causing the powder in the transparent container to flow,
Optically photographing the flowing powder through the transparent container,
A method for manufacturing a powder enclosure, in which it is determined whether foreign matter is present in the powder based on a photographed image. The transparent container has a container body having a mouth, a side wall continuous with the mouth, and a bottom continuous with the side wall, and a lid that is plugged into the mouth,
2. The method for manufacturing a powder enclosure container according to claim 1, wherein in the enclosure step, the lid is plugged onto the container body that stores the powder. In the above inspection process,
the first direction and the second direction are orthogonal to each other,
The support part supports a third direction in which the mouth part and the bottom part face each other orthogonally to the first direction and the second direction,
The method for manufacturing a powder enclosure according to claim 2, wherein the flowing powder is photographed through the side wall. 4. The method for manufacturing a powder enclosure container according to claim 3, wherein the third direction is inclined with respect to the horizontal direction with the mouth section being above the bottom section. 5. The method for manufacturing a powder-filled container according to claim 1, wherein in the inspection step, the flowing powder is photographed from below the transparent container. 6. The method for manufacturing a powder enclosure container according to claim 1, wherein the angle of repose of the powder is within a range of 30 degrees to 60 degrees.

Images