Tableting method

Abstract

To provide a technique capable of reducing an occurrence of cracking or chipping in tablets coated with an ink containing a medicinal ingredient.SOLUTION: A tablet (1) comprises a base (2) and a printed portion (3). The base (2) includes a first surface (21) facing one side in the thickness direction. A method for producing the tablet 1 with the printed portion (3) formed on the base (2), includes a step of applying ink containing a medicinal ingredient to an inner area (210) that is 1 mm or more spaced inward from a peripheral edge part (21E) of the first surface (21) of the base (2).SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The subject matter disclosed herein relates to a method for making tablets. [Background technology]

[0002] Conventionally, when manufacturing tablets as medicines, the medicinal ingredients (active ingredients) are mixed with excipients and then molded by a tablet press. However, in the above method, when the amount of medicinal ingredients is small, unevenness is likely to occur in the mixing process. In addition, the above method does not make it easy to produce a wide variety of products in small quantities.

[0003] In view of this, it has been proposed to impart a trace amount of a medicinal ingredient to a tablet by applying ink containing the medicinal ingredient to the tablet. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2020 / 218310 Summary of the Invention [Problem to be solved by the invention]

[0005] However, when ink is applied to a tablet, the tablet may swell and deform due to the penetration of the ink. For example, if a protrusion is formed on the tablet due to swelling and deformation, the tablet may crack or chip due to rubbing or collision of the protrusion.

[0006] An object of the present invention is to provide a technology capable of reducing the occurrence of cracks, chips, etc. in tablets coated with ink containing an active ingredient. [Means for solving the problem]

[0007] In order to solve the above problem, a first aspect is a method for manufacturing a tablet, comprising a step of applying an ink containing the medicinal ingredient to an area of ​​a base at least 1 mm inward from the peripheral edge by an inkjet method. Effect of the Invention

[0008] According to the first embodiment of the tablet manufacturing method, it is possible to reduce the occurrence of cracks, chips, etc. in tablets coated with ink containing an active ingredient. [Brief description of the drawings]

[0009] [Figure 1] FIG. 2 is a top view showing a tablet according to an embodiment. [Diagram 2] FIG. 2 is a side view of the tablet shown in FIG. 1. [Diagram 3] FIG. 13 is a diagram showing how a printed portion is formed on a base material. [Figure 4] FIG. 2 is a diagram showing a tablet according to a comparative example. [Diagram 5] FIG. 2 is a diagram showing a tablet manufacturing apparatus for manufacturing the tablet shown in FIG. 1. [Figure 6] FIG. 1 shows a graph of friability of tablets made with MF-10% (low viscosity) ink. [Figure 7] FIG. 1 shows a graph of friability of tablets made with MF-10% (high viscosity) ink. [Figure 8] FIG. 13 shows a graph of friability for MF-5% ink. [Figure 9] FIG. 13 shows a graph of abrasion for MF-0% ink. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Hereinafter, an embodiment of the present invention will be described with reference to the accompanying drawings. Note that the components described in the embodiment are merely examples, and are not intended to limit the scope of the present invention. In the drawings, the dimensions and numbers of each part may be exaggerated or simplified as necessary for ease of understanding.

[0011] <1. Embodiment> Fig. 1 is a top view showing a tablet 1 according to an embodiment, and Fig. 2 is a side view of the tablet 1 shown in Fig. 1.

[0012] As shown in FIGS. 1 and 2, a tablet 1 has a base 2 and a printed portion 3.

[0013] The base 2 is a granular edible body. The base 2 is a tablet such as an uncoated tablet (plain tablet), a sugar-coated tablet, or a film-coated tablet (FC tablet). The base 2 contains an excipient mainly composed of starch, lactose, or crystalline cellulose. The base 2 may contain a disintegrant or a lubricant.

[0014] The outer surface of the base 2 includes a first surface 21 and a second surface 22. The first surface 21 is a surface facing one side in the thickness direction of the base 2. The second surface 22 is a surface facing the other side in the thickness direction of the base 2. The first surface 21 and the second surface 22 face each other in the thickness direction. The "thickness direction" refers to a direction parallel to the vertical direction in a state in which the base 2 is stably placed on a horizontal plane (a plane perpendicular to the vertical direction in which gravity acts). The first surface 21 and the second surface 22 have surface expansion in two directions perpendicular to the thickness direction.

[0015] The outer surface of the base 2 further includes a third surface 23. The third surface 23 is located between the first surface 21 and the second surface 22 in the thickness direction. One end of the third surface 23 in the thickness direction is continuous with the peripheral portion 21E of the first surface 21, and the other end of the third surface 23 in the thickness direction is continuous with the peripheral portion 22E of the second surface 22.

[0016] The base 2 is a flat tablet having a disk shape. Specifically, the first surface 21 and the second surface 22 are flat surfaces and have a circular shape parallel to the direction perpendicular to the thickness direction. The third surface 23 is cylindrical parallel to the thickness direction. In addition, the boundary portion (peripheral portion 21E) between the first surface 21 and the third surface 23 may be rounded. Similarly, the boundary portion (peripheral portion 22E) between the second surface 22 and the third surface 23 may also be rounded.

[0017] The first surface 21 and the second surface 22 may have an elliptical shape, a polygonal shape, or a polygonal shape with some or all of the corners rounded. The third surface 23 may have an elliptical cylinder shape, a polygonal cylinder shape, or a polygonal cylinder with some or all of the corners rounded. The shape and size of the second surface 22 are the same as those of the first surface 21, but may be different from those of the first surface 21. The first surface 21 and the second surface 22 may be convex curved surfaces. The first surface 21 and the second surface 22 may have irregularities.

[0018] The printed portion 3 is a portion that contains medicinal ingredients (active ingredients) that exhibit the desired physiological activity. The printed portion 3 is formed on the base 2 by applying ink containing the medicinal ingredients to the base 2 by an inkjet method. The shape of the printed portion 3 may be a circle that corresponds to the peripheral portion 21E in a plan view, or may be changed as desired. The peripheral portion of the printed portion 3 (the end portion in the direction perpendicular to the thickness direction) is positioned away from the peripheral portion 21E and inward.

[0019] FIG. 3 is a diagram showing a state in which a printed portion 3 is formed on a base 2. The printed portion 3 is formed by applying ink to a region 1 mm or more inward from the peripheral portion of the base 2 (the end portion in the direction perpendicular to the thickness direction) in a plan view of the base 2 seen from one side in the thickness direction. In the case of the base 2 of this embodiment, the peripheral portion of the base 2 coincides with the peripheral portion 21E of the first surface 21. For this reason, as shown in FIG. 3, the printed portion 3 is formed by applying ink (ink droplets 9) to an inner region 210 in the base 2 that is a distance d (d is 1 mm or more) inward from the peripheral portion 21E of the first surface 21. Then, a non-applied portion where ink is not applied is formed around the printed portion 3 (annular region 1 mm or more from the peripheral portion 21E on the first surface 21).

[0020] When forming the printed portion 3, it is desirable to apply ink without gaps by so-called solid application to the inner region 210 of the first surface 21. By applying ink without gaps, it is possible to increase the amount of ink adhered compared to when the ink is applied with gaps.

[0021] The base 2 may be a placebo tablet that does not contain the medicinal ingredient contained in the ink. In this case, the tablet 1 containing a small amount of the medicinal ingredient can be produced by applying the ink. However, the base 2 may contain the medicinal ingredient. If the base 2 contains the medicinal ingredient, the medicinal ingredient contained in the tablet 1 can be easily added in a small amount by applying the ink, or another medicinal ingredient not contained in the tablet 1 can be added.

[0022] FIG. 4 is a diagram showing a tablet 1a according to a comparative example. In the comparative example shown in FIG. 4, ink is applied to the peripheral portion 21E of the first surface 21 of the base 2 or the vicinity thereof (less than 1 mm) (upper part of FIG. 4). In this case, the peripheral portion 21E swells due to the absorption of ink, and a convex portion 211 protruding laterally is easily formed (lower part of FIG. 4). When such a convex portion 211 is formed, cracks and chips are likely to occur, and the content of the medicinal ingredient may decrease. In contrast, as shown in FIG. 3, the formation of the convex portion 211 can be reduced by applying ink 1 mm or more inward from the peripheral portion 21E of the first surface 21. Therefore, the occurrence of cracks and chips can be reduced, and the reduction in the content of the medicinal ingredient can be reduced.

[0023] Fig. 5 is a diagram showing a tablet manufacturing apparatus 100 for manufacturing the tablet 1 shown in Fig. 1. The tablet manufacturing apparatus 100 is an apparatus that conveys a plurality of bases 2 and applies ink containing a medicinal ingredient to the surface of the bases 2. In the following explanation, the direction in which the bases 2 (or tablets 1) are conveyed in the tablet manufacturing apparatus 100 is simply referred to as the "conveyance direction". Moreover, the direction perpendicular to the conveyance direction is referred to as the "width direction".

[0024] As shown in FIG. 5, the tablet manufacturing apparatus 100 includes a carry-in mechanism 110, a conveying mechanism 120, an inkjet head 130, a drying section 140, a component inspection section 150, a carry-out mechanism 160, and a control section 170.

[0025] The carry-in mechanism 110 carries the plurality of bases 2 fed into the tablet manufacturing apparatus 100 to the conveying mechanism 120. The carry-in mechanism 110 has an alignment mechanism (not shown) and a carry-in drum 111. The alignment mechanism includes, for example, a vibration feeder, a rotary feeder, and a chute. The plurality of bases 2 are aligned in a plurality of rows (for example, three rows) by the alignment mechanism and supplied to the outer circumferential surface of the carry-in drum 111. The carry-in drum 111 rotates while adsorbing and holding the aligned bases 2 in a state in which they are separated one by one on the outer circumferential surface. As a result, the plurality of bases 2 are arranged at a predetermined interval in the conveying direction. In addition, the plurality of bases 2 held by the carry-in drum 111 are conveyed along an arc-shaped conveying path by the rotation of the carry-in drum 111 and delivered to the conveying mechanism 120.

[0026] The conveying mechanism 120 holds a plurality of bases 2 and conveys the plurality of bases 2 along a circular conveying path. The conveying mechanism 120 has a pair of pulleys 121, a conveying belt 122 stretched around the pair of pulleys 121, a conveying motor 123, and a suction mechanism 124. One of the pair of pulleys 121 is rotated by power obtained from the conveying motor 123. As a result, the conveying belt 122 rotates in the direction of the arrow in FIG. 5. The other of the pair of pulleys 121 is rotated following the rotation of the conveying belt 122.

[0027] A plurality of suction holes are provided on the holding surface, which is the outer peripheral surface of the conveyor belt 122. The plurality of suction holes are arranged at equal intervals in both the conveying direction and the width direction. The suction mechanism 124 sucks out gas from the space inside the conveyor belt 122. When the suction mechanism 124 is operated, the space inside the conveyor belt 122 becomes negative pressure lower than atmospheric pressure. The plurality of tablets 1 are sucked and held by the suction holes due to the negative pressure.

[0028] The inkjet head 130 applies ink containing a medicinal ingredient by an inkjet method to the surface of the base 2 being transported by the transport belt 122. The inkjet head 130 is located above the transport belt 122. A plurality of bases 2 are transported horizontally by the transport belt 122 below the inkjet head 130. The inkjet head 130 extends in the width direction. The inkjet head 130 has a large number of nozzles. The inkjet head 130 ejects ink droplets (ink drops) from the nozzles onto the surface of the base 2. As a result, the ink droplets are applied to the surface of the base 2. A piezo method or a thermal method may be adopted as the method for ejecting ink droplets from the inkjet head 130.

[0029] The drying section 140 dries the ink adhering to the surface of the tablet 1. The drying section 140 is located downstream of the conveying path and away from the inkjet head 130. The drying section 140 extends in the width direction. The drying section 140 is, for example, a hot air supply mechanism that blows heated gas (hot air) toward the tablet 1. Some of the ink adhering to the base 2 penetrates into the inside of the tablet 1, and some is dried by the hot air and fixed to the surface of the base 2. As a result, the printed portion 3 shown in FIG. 1 is formed on the surface of the base 2.

[0030] The component inspection section 150 detects the amount of the medicinal component applied to the base 2 being transported by the transport mechanism 120. The component inspection section 150 detects the amount of the medicinal component using, for example, near-infrared spectroscopy or Raman spectroscopy.

[0031] In detail, the component inspection unit 150 has a light source (such as a laser) that emits light to be irradiated onto the tablet 1, a spectroscope that separates the light reflected by the tablet 1, and a detector (such as a CCD detector) that detects the light separated by the spectroscope.

[0032] When using near-infrared spectroscopy, the component inspection unit 150 irradiates the tablet 1 with irradiation light in the near-infrared region (800 to 2500 nm) and detects the light reflected by the tablet 1. Then, the component inspection unit 150 performs quantitative analysis of the medicinal components based on the change in absorbance calculated from the detected light. When using Raman spectroscopy, the component inspection unit 150 irradiates the tablet 1 with monochromatic light (light consisting of only a single frequency) and measures the wavelength or scattering intensity of the light reflected by the tablet 1 (Raman scattered light), thereby performing quantitative analysis of the medicinal components.

[0033] In the tablet manufacturing apparatus 100, the inkjet head 130 applies ink to an inner region 210 that is 1 mm or more inward from the peripheral edge of the base 2, with respect to the base 2 being transported by the transport mechanism 120. Specifically, the inkjet head 130 ejects ink onto the inner region 210 that is 1 mm or more inward from the peripheral edge 21E of the first surface 21 of the base 2 (see FIG. 3).

[0034] The discharge mechanism 160 discharges the base 2 (i.e., the tablet 1) on which the printed portion 3 is formed from the conveying mechanism 120 to the outside of the tablet manufacturing apparatus 100. The discharge mechanism 160 has a discharge chute 161, a blowing mechanism 162, and a discharge conveyor (not shown). The discharge chute 161 is located downstream of the drying section 140 on the conveying path.

[0035] The discharge chute 161 faces the conveyor belt 122. When the tablet 1 adsorbed to the suction hole reaches the position of the discharge chute 161, the suction of the base 2 (tablet 1) is released by the blow mechanism 162. This causes the tablet 1 to fall from the conveyor belt 122 through the discharge chute 161 onto the upper surface of the discharge conveyor. The fallen tablet 1 is then discharged to the outside of the tablet manufacturing apparatus 100 by the discharge conveyor.

[0036] The control unit 170 is composed of a processor such as a CPU and a storage unit such as a semiconductor memory. The storage unit stores a program. The processor executes the program to control the operations of the loading mechanism 110, the conveying mechanism 120, the inkjet head 130, the drying unit 140, the component inspection unit 150, and the conveying mechanism 160. As a result, the conveying process and the printing process of the multiple bases 2 are performed in the tablet manufacturing apparatus 100.

[0037] In order to apply ink to the inner region 210 of the first surface 21 of the base 2, in the tablet manufacturing apparatus 100, the position of the base 2 is specified in advance before the ink is applied by the inkjet head 130. The position of the base 2 is specified, for example, from an image captured by a camera arranged upstream of the inkjet head 130, or is optically specified using a laser or the like. This position is specified, for example, by the control unit 170. The control unit 170 uses the specified position of the base 2 to determine the position at which the ink should be applied. Then, the control unit 170 causes the inkjet head 130 to apply ink to the determined position.

[0038] <Experimental Example> Next, the results of the tablet friability test will be described. Table 1 shows the composition of the base used in the test. In the following description, concentration (%) means mass % unless otherwise specified.

[0039] [Table 1]

[0040] As shown in Table 1, Ceolus (registered trademark) PH-102, which is crystalline cellulose, was used as an excipient, Primojel (registered trademark), which is sodium starch glycolate, was used as a disintegrant, and PRUV (registered trademark), which is sodium stearyl fumarate, was used as a lubricant.

[0041] <Friability test> A friability test was conducted on tablets having the composition shown in Table 1. Table 2 shows the results of the friability test. In this friability test, a base formed at a tableting pressure of 3 kN was used. The base was a flat tablet weighing 200 mg and having a diameter of 8 mm. In addition, 15 μl (microliters) of Liquid D shown in Table 3 was dropped as a pseudo ink. Liquid D mainly contains water as a solvent. In addition, the friability was measured according to the Tablet Friability Test Method (G6-5-181) specified in the 18th Revised Japanese Pharmacopoeia.

[0042] [Table 2]

[0043] [Table 3]

[0044] As shown in Table 2, the degree of wear when using Solution D was 0.6%, which was less than 1%. This result suggests that the composition shown in Table 1 is useful.

[0045] <Relationship between application method and degree of wear> Table 4 shows the results of friability tests using tablets with different ink application methods. In this friability test, a base having the composition shown in Table 1 (flat tablets with a tableting pressure of 3 kN, a weight of 200 mg, and a diameter of 8 mm) was prepared, and the base was coated with ink, and then the ink was allowed to dry naturally to obtain tablets. Thirty-three tablets were used in each test. In addition, the number of rotations of the drum was set to 250 rotations as harsh conditions, instead of the usual 100 rotations specified in the tablet friability test method.

[0046] The ink application methods used were "full surface application" and "inner surface application." In the full surface application, ink was applied to the entire first surface 21 of each base by an inkjet method (see FIG. 4). In the inner surface application, ink was applied to an inner region (a region with a diameter of 6 mm) 1 mm inward from the peripheral edge 21E on the first surface 21 of each base by an inkjet method (see FIG. 3).

[0047] In addition, in this friability test, four types of ink with different compositions were used, as shown in Table 5. The MF-10% (low viscosity) ink and the MF-10% (high viscosity) ink in Table 4 have the same concentration (10%) of the medicinal ingredient metformin hydrochloride, but different viscosities, as shown in Table 5. The MF-0% ink is an ink that does not contain metformin hydrochloride.

[0048] [Table 4]

[0049] [Table 5]

[0050] Figures 6 to 9 are graphs showing the measurement results of the abrasion degree shown in Table 4. Note that Figure 6 shows a graph of the abrasion degree for MF-10% (low viscosity) ink, and Figure 7 shows a graph of the abrasion degree for MF-10% (high viscosity) ink. Figure 8 shows a graph of the abrasion degree for MF-5% ink, and Figure 9 shows a graph of the abrasion degree for MF-0% ink. In Figures 6 to 9, the horizontal axis shows the amount of ink applied, and the vertical axis shows the abrasion degree.

[0051] As shown in Figures 6 to 9, in the case of inside coating, the friability could be kept lower than in the case of full coating for all inks. In particular, the increase rate of friability (ratio (slope) of the increase in the amount of friability to the increase in the amount of ink applied) was significantly smaller in the case of inside coating than in the case of full coating. These results suggest that by using inside coating, the occurrence of cracking and chipping of tablets can be significantly reduced even if the amount of ink applied is increased.

[0052] <2. Modification> Although the embodiment has been described above, the present invention is not limited to the above, and various modifications are possible.

[0053] For example, the tablet manufacturing apparatus 100 may be configured to apply ink containing a medicinal ingredient not only to the first surface 21 of the base 2 but also to the second surface 22. In this case, the conveying mechanism 120 may be provided with a mechanism for reversing the surface.

[0054] The tablet manufacturing apparatus 100 may be configured to apply ink containing a medicinal ingredient also to the third surface 23 of the base 2. In this case, an inkjet head that ejects ink toward the third surface 23 of the tablet 1 being transported by the transport mechanism 120 may be provided.

[0055] Although the present invention has been described in detail, the above description is merely illustrative in all respects, and the present invention is not limited thereto. It is understood that countless variations not illustrated can be envisioned without departing from the scope of the present invention. The configurations described in the above embodiments and variations can be appropriately combined or omitted as long as they are not mutually contradictory. [Explanation of symbols]

[0056] 1 tablet 2 Base 21E Periphery 3 Printed part

Claims

[Claim 1] A method for producing a tablet, comprising the steps of: applying an ink containing the medicinal ingredient to an area of ​​the base at a distance of 1 mm or more inward from the periphery by an inkjet method; A method for producing a tablet, comprising:

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