JP7691806B2 - Manufacturing method of powder-filled container - Google Patents

Description

The present invention relates to a foreign matter inspection method for inspecting powder in a transparent container for foreign matter and a method for manufacturing a powder-sealed container.

Conventionally, powdered pharmaceuticals such as injections, powders, fine granules, and granules are packaged in transparent containers such as vials. Known methods for inspecting whether foreign objects are present in the powder in these transparent containers include visual inspection and inspection by analyzing optically obtained image data (Patent Document 1). The foreign object detection method described in Patent Document 1 applies a composite 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, powders with poor fluidity do not disperse and flow due to the combined vibration, but rather flow in clumps, meaning that foreign matter contained in the flowing powder does not appear on the surface of the powder clumps, resulting in a problem of poor detection rate for foreign matter. As a result, there is a risk that a product that does not contain foreign matter may be determined to be non-defective even though foreign matter is actually present in the powder.

The present invention was made in consideration of the above circumstances, and its purpose is to provide a method for manufacturing a powder-filled container that can accurately determine the presence of foreign matter in the powder inside a transparent container and has a low reject rate.

(1) The method for manufacturing a powder-filled container according to the present invention includes a filling step for filling a transparent container with powder, an inspection step for inspecting the powder for foreign matter, and a defective product selection step for classifying the transparent container in which a foreign matter is determined to be present as a defective product. The inspection step includes applying vibrations to the transparent container via a support part that supports the transparent container, while applying reciprocating vibrations to the support part in a first direction and in a second direction intersecting the first direction to cause the powder in the transparent container to flow, optically photographing the flowing powder through the transparent container, and determining whether or not a foreign matter is present in the powder based on the photographed image.

In the inspection process, the vibration applied via the support part breaks up the powder clumps in the transparent container, making the powder more likely to scatter. The reciprocating vibration in the first direction and the reciprocating vibration in the second direction cause the powder to flow so as to circulate within the transparent container. As a result, the powder flows while scattering within the transparent container, so that foreign matter in the powder is more likely to be exposed during the inspection process and to appear in the captured image. Then, in the defective product selection process, transparent containers determined to contain foreign matter are deemed defective, so the rate of foreign matter contamination in the manufactured powder-filled containers is low.

(2) Preferably, 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 fitted to the mouth, and in the sealing process, the lid is fitted to the container body that stores the powder.

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

(3) Preferably, in the inspection process, the first direction and the second direction are perpendicular to each other, and the support portion supports the third direction in which the mouth portion and the bottom portion face each other perpendicular to the first direction and the second direction, and the flowing powder is photographed through the side wall.

Since the powder that has accumulated at the bottom of the transparent container flows along the side wall, foreign objects in the powder are easily exposed and tend to appear in the captured image.

(4) Preferably, the third direction is inclined with respect to the horizontal direction, with the mouth portion being higher than the bottom portion.

Since the powder flowing along the side wall of the transparent container is located at the bottom, it is easy to limit the area in which an image is captured.

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

The camera captures the collision between the powder, which flows through the transparent container and falls due to gravity, and the transparent container, which vibrates back and forth, so foreign objects are likely to appear in the captured image.

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

The present invention makes it possible to accurately determine the presence of foreign matter in the powder inside a transparent container, thereby making it possible to obtain a powder-sealed container with a low rate of foreign matter contamination.

FIG. 1 is a perspective view of a vial 20. FIG. 2 is a schematic diagram of the foreign matter inspection device 10. As shown in FIG. FIG. 3 is a diagram showing the inclination of the vial 20 held by the clamp 12. As shown in FIG. FIG. 4 is a diagram showing powder 21 undergoing elliptical motion within a vial 20. As shown in FIG.

Below, an embodiment of the present invention will be described with reference to the drawings as appropriate. Note that the embodiment described below is merely one example of the present invention, and it goes without saying that the embodiment of the present invention can be modified as appropriate without changing the gist of the present invention. Note that in the following description, the up-down direction 5 is defined based on the top and bottom, the front-to-back direction 6 (the direction perpendicular to the paper surface of FIG. 2) is defined as a direction perpendicular to the up-down direction 5, and the left-to-right direction 7 is defined as a direction perpendicular to the up-down direction 5 and the front-to-back direction 6.

[Vial 20 and Powder 21]
As shown in Fig. 1, the object to be inspected by the foreign matter inspection device 10 described later is a vial 20 (an example of a transparent container and a powder-sealed container) containing a powder 21. Although not shown, the vial 20 is sealed by a known method, for example, by rolling up a lid 22 and a 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. The drug is not particularly limited, but is preferably, for example, a cell wall synthesis inhibitory antibiotic, a cell membrane inhibitory antibiotic, a nucleic acid synthesis inhibitory antibiotic, a protein synthesis inhibitory antibiotic, a folate metabolic pathway inhibitory antibiotic, a β-lactamase inhibitor, a sulfa drug, or an anti-infective drug. In addition, the drugs include ampicillin, bacampicillin, amoxicillin, pivmecillinam, amoxicillin, sultamicillin, piperacillin, aspoxiline, benzylpenicillin, cloxacillin, oxacillin, carbenicillin, cephalosporin, cefroxadine, cefadroxil, cefixime, cefteram pivoxil, cefuroxime axetil, cefpodoxime proxetil, cefotiam hexetil, cefdinir, ceftibuten, cefditoren pivoxil, cefcapene pivoxil, cefazolin, cefozopran, cefmetazole, cefotiam, cefsulodin, cefoperazone, cefotaxime, cefmenoxy ceftazisim, cefodisim, 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, pazufloxacin, rifampicin, dibekacin, tobramycin, amikacin, isepamicin , micronomycin, streptomycin, kanamycin, gentamicin, erythromycin, rokitamycin, josamycin, roxromycin, 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, These include ganciclovir, foscavir, idoxuridine, amantadine, interferon gamma, ribapirin, lamipudine, metronidazole, tinidazole, fluconazole, mebendazole, pyrantel pamoate, diethylcarbamazine, praziquantel, albendazole, ivermectin, quinupristin, dalfopristin, linezolid, spectinomycin, netilmicin, sisomycin, lincosamin, ramoplanin, telithromycin, nystatin, 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. The angle of repose of the powder 21 is specifically in the range of 30 degrees to 60 degrees, and preferably in the range of 33 degrees to 60 degrees. The particle size of the powder 21 is specifically in the range of 20 μm to 70 μm in average particle size (median diameter: d50), and preferably in the range of 21.1 μm to 55.7 μm. The filling amount of the powder 21 contained in the vial 20 is at least 0.25 g or more, and even if the filling amount is large, it is possible to inspect it by the foreign matter 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, and 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 a resin such as rubber or elastomer. The container body 23 is made of transparent glass, for example. The container body 23 only needs to be translucent enough to allow the imaging device 15 (see FIG. 2) to optically image the powder 21 in the internal space.

The container body 23 has a mouth 24, a side wall 25, and a bottom 26 that form an opening leading to the internal space. The container body 23 is generally cylindrical overall, and is a so-called narrow-mouth container in which the outer diameter of the mouth 24 is smaller than the outer diameter of the side wall 25. The mouth 24 and the bottom 26 face each other. The bottom 26 is disc-shaped, and the container body 23 stands with the opening of the mouth 24 facing upward when the bottom 26 is placed on a desk or the like. The side wall 25 is cylindrical. The mouth 24 is continuous with the side wall 25. The mouth 24 has a shape in which the outer diameter gradually expands 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 26 are equal.

The lid 22 is shaped like a disk that is in close contact with the mouth 24, with a protruding convex portion that fits into the opening formed by the mouth 24. The container body 23 is filled with powder 21, for example, by a filling machine, the lid 22 is plugged into the mouth 24, and an aluminum cap is tightened to seal the container body 23.

[Foreign substance inspection device 10]
The foreign matter inspection device 10 inspects whether a foreign matter is mixed into the powder 21 sealed in the vial 20. As shown in FIG. 2, the foreign matter inspection device 10 includes a frame 11, a clamp 12 (an example of a support unit), a vibration generator 13, a composite vibration generator 14, a photographing device 15, an analyzing device 16, and a lighting device 17. The support unit 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 unit 12, the vibration generator 13, the composite vibration generator 14, and the photographing device 15. The analyzing device 16 is connected to the photographing device 15 so as to be able to communicate data with each other.

The clamps 12 form a pair separated in the left-right direction 7, and each of them moves in the left-right direction 7 to change between a state in which the vial 20 is clamped and a state in which the vial 20 is not clamped. The clamps 12 clamp the side wall 25 of the vial 20 from the left-right direction 7. When the clamps 12 clamp the vial 20, the direction in which the mouth 24 and the bottom 26 face each other (an example of a third direction), i.e., the axial direction of the container body 23, is parallel to the front-rear direction 6.
In addition, when the clamp 12 is holding the vial 20 , a portion of the side wall 25 of the vial 20 is exposed in the up-down direction 5 .

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

The composite vibration generating device 14 applies reciprocating vibration in the up-down direction 5 (an example of a first direction) and reciprocating vibration in the left-right direction 7 (an example of a second direction) to the clamp 12. The composite vibration generating device 14 has a motor 40, a up-down vibration generating mechanism 41, and a left-right vibration generating mechanism 42. The motor 40 generates a driving force that is transmitted to the up-down vibration generating mechanism 41 and the left-right vibration generating mechanism 42.

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

The link arm 45 is slidably fitted with the eccentric disk cam 43. When the rotation of the eccentric disk cam 43 is transmitted to the link arm 45, the link arm 45 rotates while displacing its position in the vertical direction 5. The link arm 45 is connected to the slider 46 via a shaft 47. The slider 46 is movable along the vertical direction 5 by fitting with a slide rail 54 provided on the slider 51 of the left-right vibration generating mechanism 42. Therefore, the slider 46 moves back and forth in the vertical direction 5 according to the movement width in the vertical direction 5 of the rotation of the link arm 45.

The link arm 45 has a support arm 55 that extends 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 has an eccentric disk cam 48, a camshaft 49, a link arm 50, and a slider 51. The eccentric disk cam 48 is rotatably supported on a camshaft 49 that is supported on the frame 11 and extends along the front-rear direction 6. The camshaft 49 is provided with an eccentric disk cam 48. The eccentric disk cam 48 protrudes radially from the camshaft 49. The length by which the eccentric disk cam 48 protrudes from the camshaft 49 changes continuously in the circumferential direction of the camshaft 49.

The link arm 50 is slidably fitted with the eccentric disk cam 48. When the rotation of the eccentric disk cam 48 is transmitted to the link arm 50, the link arm 50 rotates while displacing its position 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 along the left-right direction 7 by fitting into a slide rail 53 provided on the frame 11. Therefore, the slider 51 moves back and forth in the left-right direction 7 depending on the movement width in the left-right direction 7 of the rotation of the link arm 50.

A slide rail 54 extending in the vertical direction 5 is formed on the left end of the slider 51. The slide rail 54 is fitted to 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. As a result, the slider 46 reciprocates in the vertical direction 5 while also reciprocating in the left-right direction 7. In other words, the composite vibration of the reciprocating movement in the left-right direction 7 and the reciprocating movement in the vertical direction 5 is transmitted to the support arm 55.

If the amplitude of the reciprocating movement in the up-down direction 5 by the up-down vibration generating mechanism 41 is the same as the amplitude of the reciprocating movement in the left-right direction 7 by the left-right vibration generating mechanism 42, the composite vibration will be circular, linear, or elliptical motion by adjusting the phase difference between the eccentric disk cams 43 and 48. For example, the phase difference between the eccentric disk cams 43 and 48 is set so that the composite vibration is elliptical motion.

The image capturing device 15 is installed below the clamp 12. The image capturing device 15 is a camera that optically captures the powder 21 in the vial 20 through a portion of the side wall 25 exposed in the vertical direction 5 of the vial 20 held by the clamp 12. The image capturing device 15 captures multiple images of the vibrating vial 20 in a given period of time, for example, at a frame rate of 30 or 60 frames per second.

The analysis device 16 is a computer installed with judgment software that analyzes the images captured by the photographing device 15 and judges 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 send and receive data. The analysis device 16 has, for example, input devices such as a keyboard and a mouse, and a display device such as a display. The images received from the photographing device 15 may be displayed on the display of the analysis device 16.

The judgment software judges whether a foreign object is mixed in the powder 21 of the vial 20 based on the image of the vial 20 captured by the image capture device 15, i.e., image data. Specifically, the obtained single image data is divided into a predetermined number of vertical and horizontal sub-areas, and the color density of each sub-area is identified in multiple stages. If the powder 21 is white, the foreign object is recognized as black. Then, the judgment software judges whether a foreign object is present based on the peak value (color density of the foreign object) and the intensity area value (length x width of the foreign object) in the image data. For example, if both the peak value and the intensity area value are within a predetermined condition, for example, if each value is equal to or greater than a threshold value and there is a predetermined continuous range, the judgment software judges that a foreign object is present in the powder 21 of the vial 20. Note that there are no particular limitations on the detectable foreign object, and it is sufficient if it appears 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. The two lighting devices 17 irradiate light from the top and bottom directions 5 onto the vial 20 that is held in the clamp 12 and vibrating. The lighting device 17 located below the clamp 12 does not overlap with the area where the imaging device 15 and the clamp 12 face each other, and is offset from that area in the front-back direction 6.

[Method of manufacturing vial 20 containing powder 21]
A method for manufacturing the vial 20 containing the powder 21 will be described below. The method for manufacturing the vial 20 includes the following steps.
(1) A process of sealing powder 21 in a vial 20.
(2) An inspection step of inspecting the powder 21 for foreign matter (an example of an inspection method).
(3) A defective product selection process in which a vial 20 determined to contain a foreign substance in the powder 21 is deemed to be defective.

In the sealing process, the powder 21 is filled into the container body 23 by an auger-type filling machine. Then, the lid 22 is attached to the container body 23 storing the powder 21, and an aluminum cap is tightened to seal the boundary between the lid 22 and the container body 23. This results in a vial 20 with the powder 21 sealed in the internal space.

The inspection process is carried out using a foreign matter inspection device 10. A vial 20 with powder 21 sealed in the internal space is clamped and held by a clamp 12 of the foreign matter inspection device 10. The axial direction C (see FIG. 3) of the vial 20 held by the clamp 12 is parallel to the front-rear direction 6.

When the foreign body inspection device 10 is operated, the frame 11 tilts. As shown in FIG. 3, when the frame 11 tilts, the axial direction C of the vial 20 tilts with respect to the front-rear direction 6 (horizontal direction) with the mouth 24 of the container body 23 above the bottom 26. The tilt angle is within the range of 0 degrees to 15 degrees, and preferably within the range of 1 degree to 10 degrees. When the foreign body inspection device 10 is operated, the lighting device 17 is turned on.

After the frame 11 is tilted, the vibration generator 13 is operated and the motor 40 is also operated. By operating the vibration generator 13, vibration is applied to the vial 20 held by the clamp 12. By applying vibration to the vial 20, even if the powder 21 is attached to the side wall 25 inside the vial 20, the powder 21 will separate from the side wall 25 due to the vibration. In addition, clumps of the powder 21 will break up. As a result, foreign matter mixed in the powder 21 will be more likely to appear on the inner surface side of the side wall 25 of the vial 20.

When the motor 40 is operated, the composite vibration generator 14 applies a composite vibration to the vial 20 that forms an elliptical motion when viewed from the front-to-rear direction 6. This composite vibration causes the powder 21 to flow while circulating in an ellipse in the internal space of the vial 20, as shown in FIG. 4. In this flow of the powder 21, foreign matter that is different in size or weight from each particle of the powder 21 flows differently from the powder 21. For example, foreign matter that is heavier than each particle of the powder 21 tends to move to the outside of the circulation of the flowing powder 21, and is therefore more likely to appear on the inner surface side of the side wall 25 of the vial 20.

In addition, the axial direction C of the vial 20 is inclined with respect to the front-rear direction 6, with the mouth 24 of the container body 23 being higher than the bottom 26, so the powder 21 tends to accumulate toward the bottom 26. In addition, foreign matter that is heavier than each particle of the powder 21 tends to move toward the bottom 26 rather than the powder 21, and is therefore likely 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 the image of the vial 20 captured by the image capture device 15 when the vibration and the compound vibration are applied to the vial 20.

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

[Effects of the embodiment]
According to the embodiment described above, in the inspection process, the vibration applied via the clamp 12 causes clumps of the powder 21 in the vial 20 to crumble and the powder 21 to separate from the side wall 25, making the powder 21 more likely to scatter. In addition, the combined vibration in the up-down direction 5 and the left-right direction 7 causes the powder 21 to flow in a circulating manner in the vial 20. As a result, the powder 21 flows and scatters in the vial 20, so that foreign matter in the powder 21 is more likely to be exposed in the inspection process and the foreign matter is more likely to appear in the captured image. In the defective product selection process, the vials 20 determined to contain foreign matter are deemed defective, so the rate of foreign matter contamination in the manufactured vials 20 is low.

In addition, during the inspection process, the axial direction C of the vial 20 is supported parallel to the front-rear direction 6, so that the flowing powder 21 is photographed through the side wall 25 of the vial 20.

In addition, in the inspection process, since the axial direction C of the vial 20 is inclined from the front-rear direction 6, the powder 21 that has accumulated on the bottom 26 side of the vial 20 flows along the side wall 25. This makes it easy for foreign matter in the powder 21 to be exposed, and the foreign matter is likely to appear in the captured image. In addition, since foreign matter is likely to appear near the bottom 26 of the side wall 25 of the vial 20, the range in which an image is captured to determine whether or not the foreign matter is present is limited.

In addition, in the inspection process, the flowing powder 21 is photographed from below the vial 20, so the image shows the powder 21 flowing inside the vial 20 and falling due to gravity colliding with the side wall 25 of the vibrating container body 23. This makes it easy for foreign objects to appear in the photographed image.

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

Claims (1)

An encapsulation step of encapsulating powder in a transparent container;
an inspection step of inspecting the powder for foreign matter;
a defective product sorting step for classifying the transparent container determined to contain a foreign matter as a defective product,
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 fitted onto the mouth,
The angle of repose of the powder is within the range of 30 degrees to 60 degrees,
The average particle size of the powder is in the range of 20 μm to 70 μm,
In the sealing step, the lid is plugged onto the container body storing the powder,
The above inspection process is as follows:
a support part supporting the transparent container supports the transparent container in such a manner that a third direction in which the mouth part and the bottom part face each other is perpendicular to the first direction and a second direction perpendicular to the first direction , intersects with the vertical direction, and supports the transparent container with the mouth part tilted above the bottom part with respect to the horizontal direction; a composite vibration of a reciprocating vibration in the first direction and a reciprocating vibration in the second direction is applied to the support part to cause the powder in the transparent container to flow, while a vibration different from the composite vibration is applied to the transparent container via the support part;
The flowing powder is optically photographed from below the transparent container through a side wall of the transparent container while irradiating the transparent container with light from above and below;
A method for manufacturing a powder-containing container in which a photographed image is divided into a predetermined number of vertical and horizontal regions, the black and white intensity in each of the regions is identified into multiple levels of intensity, and whether or not a foreign object is present in the powder is determined based on whether or not there is a predetermined range in which each of the regions, in which the identified black and white intensity is equal to or above a threshold value for recognition as black, is continuous vertically or horizontally.

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