Raw material for tablet production using 3D printer, tablet, and method for producing tablet

Abstract

To obtain a technology for producing tablets by means of a 3D printer.SOLUTION: A method includes: a first step (A) of forming a powder layer 103 containing a powder of a pharmaceutical agent, a powder of anhydrous dicalcium phosphate, and a powder of an organic binder; a second step (B), following the first step, of leveling the powder layer 103 with a roller 104; a third step (C), following the second step, of applying an aqueous solution 107 containing a surfactant to a specific region 105 of the powder layer 103; a fourth step (D) of repeating the first through third steps to form a laminate of multiple powder layers; and a step of drying the laminate to cure a portion 150 formed by the laminated specific regions, thereby producing a tablet.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a technology for producing tablets using a 3D printer. [Background technology]

[0002] A technology for manufacturing tablets using a 3D printer is known (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2023-78155 A Summary of the Invention [Problem to be solved by the invention]

[0004] When tablets are produced using a binder jetting (BJ) type 3D printer, there is a problem that the tablets end up with a diagonally deformed shape (see, for example, Figure 3(B)). In this respect, the technology for producing tablets using a 3D printer has had problems with practicality. In this context, the present invention aims to provide a technology for producing tablets using a 3D printer. [Means for solving the problem]

[0005] The present invention relates to a raw material powder for producing tablets using a 3D printer, which contains anhydrous calcium hydrogen phosphate powder and an organic binder powder and is used as an excipient that hardens in an aqueous solution to which a surfactant has been added.

[0006] The present invention relates to a tablet having a multilayer structure in which multiple layers each containing a drug, anhydrous calcium hydrogen phosphate, and an organic binder are laminated together. The present invention relates to a tablet composed of a laminate including a first layer containing a first drug, anhydrous calcium hydrogen phosphate, and an organic binder, and a second layer containing a second drug different from the first drug, anhydrous calcium hydrogen phosphate, and an organic binder.

[0007] The present invention provides a method for producing tablets, which includes a first step of forming a powder layer containing a drug powder, anhydrous calcium hydrogen phosphate powder, and an organic binder powder; a second step of flattening the powder layer after the first step by moving a member that has been brought into contact with the surface of the powder layer parallel to the powder layer; and a third step of applying an aqueous solution to which a surfactant has been added to a specific region of the powder layer after the second step. By repeating steps one to three, a laminate of multiple powder layers is formed, and by drying the laminate, the portion composed of the laminate in the specific region is hardened to produce a tablet. [Effects of the Invention]

[0008] According to the present invention, a technology for manufacturing tablets using a 3D printer is provided. [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 is a conceptual diagram showing the tablet production process using the present invention. [Figure 2] 1 is a conceptual diagram of a 3D printer embodying the invention. [Figure 3] 1A is a photograph of a tablet according to an embodiment, and FIGS. 1B and 1C are photographs of tablets according to a comparative example. [Figure 4] FIG. 1 is a conceptual diagram illustrating the phenomenon in which a tablet becomes obliquely deformed. [Figure 5] FIG. 1 is a conceptual diagram showing the cross-sectional structure of a tablet according to an embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0010] 1. First embodiment (overview) In this embodiment, tablets are manufactured using a binder jetting (BJ) type 3D printer. Figure 1 is a conceptual diagram showing the tablet manufacturing process using the present invention.

[0011] FIG. 1 shows a first step (FIG. 1(A)) of forming a powder layer 103 by scattering raw material powder 102, which is a mixture of a drug powder, anhydrous calcium hydrogen phosphate powder, and an organic binder powder, onto a surface to be formed; a second step (FIG. 1(B)) of flattening the powder layer 103 after the first step by moving a roller 104, which is a member in contact with the surface of the powder layer 103, parallel to the powder layer 103; a third step (FIG. 1(C)) of applying an aqueous solution 107 containing a surfactant to a specific region 105 of the powder layer 103 after the second step; a fourth step (FIG. 1(D)) of repeating steps 1 to 3 to form a laminate of multiple powder layers; and a step of drying the laminate to harden a portion (region) 150 composed of the laminate in the specific region.

[0012] The process of Fig. 1 will be described in detail below. First, raw material powder 102 is scattered on the surface of a modeling stage 101 having a flat surface to be formed, to produce a first unit powder layer 103 (Fig. 1(A)). In this example, the amount of raw material powder 101 to be scattered is adjusted so that the thickness dimension after recoating processing by roller 104 in Fig. 1(B) is 100 µm. At the stage in Fig. 1(A) (the state before recoating), the unit powder layer 103 is not uniform in thickness and density.

[0013] The raw material powder 101 is a mixture of an excipient powder of anhydrous dibasic calcium phosphate (CaHPO4), a drug powder, and a binder (organic binder) powder. The blending ratio of each component in the raw material powder 101 is 70 to 90% by weight of anhydrous dibasic calcium phosphate powder, 5 to 20% by weight of drug powder, and 5 to 15% by weight of binder (organic binder) powder.

[0014] The drug is the active ingredient of the final tablet product. The drug is not limited to pharmaceuticals, but may also be a quasi-drug, a nutritional supplement (a supplement ingredient), a food ingredient, or the like. A mixture of multiple drugs may also be used. Examples of binders (organic binders) that can be used include polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), corn starch, polyethylene glycol (PEG), polyvinyl acetate, polyvinyl butyral, polyacrylic acid, sodium polyacrylate, a copolymer of sodium polyacrylate and maleic acid, a copolymer of polyvinylpyrrolidone and vinyl acetate, cellulose derivatives (methylcellulose, ethylcellulose, ethylhydroxymethylcellulose, carboxymethylcellulose (CMC), sodium carboxymethylcellulose, hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), etc.), gum arabic, black locust gum, gelatin, starch, sucrose, dextrose, fructose, lactose, wheat flour, alginic acid, sodium alginate, citric acid, succinic acid, and other finely ground products.

[0015] After the raw material powder 101 is spread and the unit powder layer 103 is formed, a recoating process is performed in which the unit powder layer 103 is pressed and flattened using a roller 104 (FIG. 1(B)). In this process, the roller 104 is pressed against the surface of the unit powder layer 103 while moving in a specific direction parallel to the surface. The roller 104 has an elongated cylindrical shape, and in the above process, it moves while rotating in contact with the upper surface (exposed surface) of the unit powder layer 103. This allows the raw material powder to be spread evenly on the modeling stage 101, and the thickness is adjusted to a predetermined value (100 μm in this example). Note that in this recoating process, unnecessary raw material powder is pushed out in the Y-axis direction by the roller 104 and removed from the modeling stage 101.

[0016] If a unit powder layer has already been formed on the base, a new unit powder layer is formed on the upper surface (exposed surface) of this unit powder layer on the base as the formation surface, and the above-mentioned recoating process using roller 104 is performed on this unit powder layer.

[0017] In this example, the conditions of the recoating step of Fig. 1(B) are adjusted so that the thickness of the unit powder layer 103 becomes 100 µm. The thickness of the unit powder layer obtained in the step of Fig. 1(B) is selected from the range of 50 µm to 200 µm.

[0018] After the step in Figure 1(B), a hardening agent is selectively sprayed onto specific portions (areas) 105 of the unit powder layer 103 that will become tablets (Figure 1(C)). The hardening agent is a hardening liquid that hardens the raw material powder that makes up the unit powder layer, and in this case, an aqueous solution of water with a surfactant added is used.

[0019] FIG. 1(C) shows a state in which a curing agent 107 is sprayed (sprayed) from a nozzle 106 onto a specific portion 105. Examples of surfactants that can be used include Tween 80 (Polysorbate 80 (polyoxyethylene sorbitan oleate)), sodium lauryl sulfate, polyoxyethylene (160) polyoxypropylene (30) glycol, sorbitan fatty acid esters (Span series), glycerin monostearate, lauromacrogol, polyoxyl 40 stearate, and benzalkonium chloride. The surfactant content in the liquid component is preferably 0.01 to 10 parts by weight, more preferably 0.025 to 5 parts by weight, and particularly preferably 0.05 to 2.5 parts by weight. If the content is too low, tablet hardness tends to decrease, while if it is too high, the deposited layers tend to become misaligned during recoating.

[0020] The nozzle 106 is the printer head of a binder jetting (BJ) 3D printer, and in this case, it sprays the hardener toward the powder layer. The nozzle 106 corresponds to the part that ejects ink in a normal printer (a printing device that uses ink). The nozzle 106 is adjustable in distance from the surface to which the hardener is supplied, and can be moved vertically and horizontally on the surface (within the X-Y plane).

[0021] The nozzle 106 is moved above the specific region 105 and the hardener is then jetted downward, thereby jetting the hardener onto the specific region 105. The range over which the hardener is jetted is adjusted to fit the range of the specific region.

[0022] 1(C) shows four specific regions 105 where tablets are formed. In reality, a plurality of specific regions 105 are formed in a matrix. The specific regions 105 may have a shape as viewed from above, such as a circle, an oval, a square, a rectangle, a square or a rectangle with rounded corners, etc.

[0023] After the step of Fig. 1(C), the second unit powder layer is formed on the surface (exposed surface) of the unit powder layer 103 formed on the top layer at this point. The steps for forming the second unit powder layer are the same as those for the first unit powder layer. That is, the steps include forming the unit powder layer by scattering raw material powder (Fig. 1(A)), recoating the unit powder layer (Fig. 1(B)), and spraying a hardener onto localized portions of the unit powder layer that have been recoated (Fig. 1(C)).

[0024] In the same manner, the third, fourth, fifth, etc. unit powder layers are formed in sequence. That is, the steps of Figures 1(A) to 1(C) are repeated to stack a plurality of unit powder layers. Figure 1(D) shows the state where two unit powder layers 103a and 103b are stacked.

[0025] Here, in each stacked unit powder layer, the nozzle 106 is set to inject the curing agent (nozzle position) in the step of Fig. 1(C) so that the specific region that will become the tablet is aligned. Fig. 1(D) shows a stacked state in which the specific region 105a of the unit powder layer 103a and the specific region 105b of the unit powder layer 103b are aligned. A stack is formed by stacking a large number of unit powder layers.

[0026] This laminate has a plurality of partial laminates (portions indicated by reference numeral 150) into which the hardening agent for each unit powder layer has been sprayed. These partial laminates are portions into which the hardening agent has been selectively (locally) introduced, and harden in the subsequent drying process to form tablets.

[0027] Fig. 1(D) shows four partial laminates 150 onto which a curing agent has been sprayed. Fig. 1(D) shows partial laminate 150 composed of two laminate layers 105a and 105b, but in reality, the portion of 150 is formed as a laminate composed of several tens of unit powder layers. This partial laminate will eventually become a tablet.

[0028] The number of unit powder layers to be stacked is predetermined based on the required tablet thickness. When this predetermined number of layers is reached, the steps of Figures 1(A) to 1(C) are completed. The thickness of the stack of unit powder layers is, for example, about 2 mm to 5 mm. This value will be the thickness of the final tablet.

[0029] After obtaining a laminate in which several tens of unit powder layers are stacked, a drying process is carried out. The drying process is carried out, for example, for 3 to 6 hours in an atmosphere of 35 to 50°C. By carrying out the drying process, the moisture contained in the portion 105 (the portion indicated by the symbol 150) of each unit powder layer that will become a tablet evaporates, and that portion becomes hardened.

[0030] Next, the laminate with the unit powder layers stacked on top of each other is removed from the surface of the modeling stage 101. At this stage, the portions of the laminate other than the plurality of portions 150 that will become tablets have not hardened, and although they are layered, they remain as raw powder (powder). Therefore, when the laminate is peeled off from the modeling stage 101, the portions other than the portion marked with reference numeral 150 break down into powder, and when the resultant is filtered through a sieve, the laminate of the portion marked with reference numeral 150 is obtained as a solid (solid) tablet.

[0031] The process shown in FIG. 1 includes a first step (FIG. 1(A)) of forming a powder layer 103 containing a drug powder, anhydrous calcium hydrogen phosphate powder, and an organic binder powder; a second step (FIG. 1(B)) of flattening the powder layer 103 with a roller 104 after the first step; a third step (FIG. 1(C)) of applying an aqueous solution 107 containing a surfactant to a specific region 105 of the powder layer 103 after the second step; a fourth step (FIG. 1(D)) of repeating steps 1 to 3 to form a laminate of multiple powder layers; and a step of drying the laminate to harden a portion 150 composed of the laminate of the specific region, thereby manufacturing a tablet.

[0032] (Binder Jetting 3D Printer) Below, we will explain a binder jetting (BJ) 3D printer that creates tablets using the process shown in Figure 1. Figure 2 is a conceptual diagram of a binder jetting 3D printer 110 (hereinafter referred to as 3D printer 110). The 3D printer 110 is equipped with the modeling stage 101 shown in Figure 1. Tablets are created using powder as a raw material on the upper surface of the modeling stage 101. The modeling stage 101 can be moved up and down (movement in the positive and negative directions of the Z axis in Figure 2) by a linear drive mechanism 113 using a motor or the like as a drive source.

[0033] A raw material powder supply unit 111, and a hardener supply unit including a nozzle 106 and a roller 104 are arranged above the modeling stage 101. The raw material powder supply unit 111, the nozzle 106, and the roller 104 can be electrically moved together in the positive and negative directions of the Y axis in Fig. 2. Furthermore, the raw material powder supply unit 111, the nozzle 106, and the roller 104 can be individually adjusted in their vertical positions (positions in the Z axis direction).

[0034] The raw material powder supply unit 111 supplies raw material powder to the upper surface of the modeling stage 101 through a slit extending in the X-axis direction in Fig. 2. By supplying raw material powder from the raw material powder supply unit 111 onto the modeling stage 101 while moving the raw material powder supply unit 111 in the positive or negative direction of the Y-axis, a unit powder layer is formed on the modeling stage 101, or an additional unit powder layer is formed on the upper surface of a unit powder layer already formed on the modeling stage 101. The amount of raw material powder supplied from the raw material powder supply unit 111 is adjustable.

[0035] Nozzle 106, which is the hardener supply unit, can be electrically moved in both the positive and negative directions of the X axis along rails 112 extending in the X axis direction. Nozzle 106 sprays (supplies) the liquid hardener onto a pinpointed, limited area (for example, a circular area with a diameter of 1 mm). Here, water with a surfactant added (aqueous solution containing a surfactant) is used as the hardener.

[0036] The rail 112 can move in the positive and negative directions of the Y axis, and by moving the rail 112 in the positive and negative directions of the Y axis and by moving the nozzle 106 in the positive and negative directions of the X axis, the nozzle 106 can be moved within the XY plane. Using this mechanism, the hardener is injected with pinpoint precision into a predetermined location in the unit powder layer while moving the nozzle 106 within the XY plane.

[0037] The roller 104 is rotatable and electrically movable in the positive and negative directions of the Y-axis. By moving the roller 104 horizontally in the positive or negative direction of the Y-axis while in contact with the top surface of the unit powder layer, the recoating process for the unit powder layer shown in FIG. 1(B) is performed.

[0038] (Example) Tablets were produced using the apparatus shown in Figure 2 and the process shown in Figure 1. The tablets were cylindrical in shape.

[0039] (Raw material powder) The raw powder used was a mixture of 10% by weight of acetaminophen powder as a drug, 80% by weight of anhydrous calcium hydrogen phosphate powder as an excipient, and 10% by weight of finely ground polyvinyl alcohol (powder) as a binder (organic binder). Each powder had a particle size of 20 μm to 60 μm. Table 1 shows an example of the specifications and reference values ​​for the anhydrous calcium hydrogen phosphate powder used. Sample 1 was used in this example.

[0040] [Table 1]

[0041] [Table 2]

[0042] (3D printer settings) The thickness of each layer (thickness of the unit powder layer) was 100 μm, and a 0.5 W / V% aqueous solution of Tween 80 was used as the hardener. The print pattern of the tablets was a 5 × 5 print model.

[0043] (1) Example 1 Size: diameter 8.13mm x height (thickness) 3.734mm Weight: 150mg Shape: Cylindrical

[0044] (2) Example 2 Size: Diameter 14.73mm x Height (thickness) 3.734mm Weight: 500mg Shape: Cylindrical

[0045] (3) Example 3 Size: Diameter 20.84mm x Height (thickness) 3.734mm Weight: 1000mg Shape: Cylindrical

[0046] (evaluation) Table 3 below shows the mechanical properties of Example 2. From Table 3, it can be seen that the set dimensions and weights were obtained with good reproducibility.

[0047] [Table 3]

[0048] Figure 3(A) is a photograph, substituted for a drawing, of tablets of Examples 1 to 3. Figure 3(B) is a photograph, substituted for a drawing, of tablets of a comparative example. Figure 3(A) shows, from left to right, Examples 1, 2, and 3. Figure 3(B) shows tablets corresponding to Examples 1 to 3 from left to right, in which lactose powder was used as an excipient. The only difference between the examples and the comparative example is the type of excipient; the other conditions are the same.

[0049] As shown in Figure 3(A), the tablets obtained in the examples have a clean cylindrical shape. In contrast, the tablets of the comparative examples shown in Figure 3(B) are deformed obliquely in the thickness direction. That is, the laminate is formed with each layer (each unit powder layer) slightly shifting horizontally. This tendency is particularly evident in tablets with large diameters.

[0050] In addition, when the image of the embodiment of the present invention shown in Figure 3 (A) is enlarged, it can be confirmed that the obtained tablet has a multilayer structure stacked in the thickness direction. That is, when the side surface of the tablet obtained using the present invention is closely observed, it can be confirmed that it has a multilayer structure like a geological layer. Furthermore, it can be observed that the side surface of the tablet has an appearance in which fine irregularities are formed in the thickness direction due to the multilayer structure.

[0051] (Moldability) The factors that result in the good compactibility shown in Figure 3(A) are explained below. First, the poor compactibility shown in Figure 3(B) is considered. The deformation of the tablet shown in Figure 3(B) is thought to be related to the process shown in Figure 1(B).

[0052] Figure 3(C) shows how the lower layer shifts to the right as the layers are stacked. This direction of layer shift coincides with the direction of movement of roller 104 (the recoating direction) in the process shown in Figure 1(B). The dashed line in Figure 3(C) represents the shape of the tablet when it is manufactured according to the design data.

[0053] Figure 4 is a conceptual diagram showing how layers shift. After the formation and recoating of the first layer, a partial injection of hardener (binder jetting (BJ)) is performed, followed by the formation of the second layer, and then recoating of the second layer. During this recoating of the second layer, the binder-jetted portion of the first layer (corresponding to the portion indicated by reference numeral 105 in Figure 1) is subjected to a force via the second layer in the direction of recoating (the direction of movement of roller 104).

[0054] In this case, when lactose is used as an excipient, the part of the first layer where the hardener is introduced moves slightly in the direction of recoating due to the above force. This is an observed fact. This movement is thought to occur because the part in question is softened (partially dissolved) by the hardener (aqueous solution of water and surfactant) and becomes viscous. Therefore, the part of the first layer where the hardener is introduced is pulled (or pushed) by the second layer due to the above force.

[0055] Then, when the third layer is recoated, the portion where the hardener from the second layer has been introduced moves in the same way, and as if pulled by the movement of that portion of the second layer, the portion where the hardener from the first layer has been introduced also moves in the same direction (the direction of recoating). From the fourth layer onwards, the above mechanism also causes the portion where the hardener from the lower layer has been introduced to move in the direction of recoating. Here, the lower the layer, the greater the amount of movement because the movement during recoating is accumulated. As a result, as shown in Figure 4, each layer shifts in the direction of recoating as it goes downwards.

[0056] When anhydrous calcium hydrogen phosphate powder is used as an excipient, the powder is inorganic and insoluble in water, so the area where the hardener is introduced (the area where the binder jetting is performed) does not become viscous, and this area does not move during recoating of each layer. This allows for the production of cylindrical tablets as shown in Figure 3(A). In other words, cylindrical tablets as shown by the dashed line in Figure 3(C) can be obtained.

[0057] (superiority) This provides a technology for manufacturing pharmaceutical tablets using a 3D printer. Tablets can be manufactured using a 3D printer in the shape of the design data without any deformation. By using this invention, it becomes easy to adjust the shape and size of the tablet to suit the condition, physical condition, physique, age, etc. of the person taking the tablet.

[0058] 2. Second embodiment A second embodiment based on the first embodiment will be described below. In this embodiment, a first unit powder layer containing a drug and a second unit powder layer not containing a drug are used, and the drug content in the tablet is adjusted by adjusting the integrated thickness of the first unit powder layer and the integrated thickness of the second unit powder layer.

[0059] Fig. 5 is a cross-sectional view of a tablet of this embodiment. Fig. 5 shows a tablet 510. The tablet 510 has a structure in which first unit powder layers 511 and second unit powder layers 512 are alternately stacked. The thickness of each unit powder layer is, for example, 100 µm, and the number of layers is determined by the thickness of the tablet 150.

[0060] Here, unit powder layer 511 is composed of a mixture of drug powder, excipient powder, and organic binder powder. Unit powder layer 512 does not contain drug powder and is composed of excipient powder and organic binder powder. To obtain tablet 510, two types of raw material powders are prepared. The method of forming each powder layer, the method of introducing the curing agent, and the details of the materials used are the same as those in the first embodiment.

[0061] For example, unit powder layer 511 is formed using raw material powders consisting of 80% by weight of excipient powder, 10% by weight of drug powder, and 10% by weight of binder powder, while unit powder layer 512 is formed using raw material powders consisting of 90% by weight of excipient powder and 10% by weight of binder powder.

[0062] (Modification 1 of the second embodiment) Tablet 510 is a tablet in which the number of first unit powder layers and the number of second unit powder layers are the same (50%:50%). If the ratio of the number of first unit powder layers to the number of second unit powder layers is 25%:75%, the amount of drug in a tablet of the same size can be half that of tablet 510. In this case, a multilayer structure is formed by stacking the first powder layer-second powder layer-second powder layer-second powder layer as a unit.

[0063] (Modification 2 of the second embodiment) If the ratio of the number of first unit powder layers to the number of second unit powder layers is 75%:25%, the amount of drug contained in a tablet of the same size can be 1.5 times that of tablet 510. According to this embodiment, the amount of drug contained can be adjusted without changing the size of the tablet. In this case, a multilayer structure is formed by stacking the first powder layer-second powder layer-first powder layer-first powder layer as a unit.

[0064] 3. Third embodiment A third embodiment based on the second embodiment will be described below. In this embodiment, the thicknesses of the first and second unit powder layers are made different from each other, and the amount of drug contained in the tablet is adjusted by adjusting the thickness dimension. In this case, the amount of drug contained in the tablet is adjusted by adjusting the integrated thickness of the first unit powder layer and the integrated thickness of the second unit powder layer in the laminate that constitutes the tablet.

[0065] According to this embodiment, it is possible to produce tablets with an adjusted amount of drug. Conventionally, the amount of drug was adjusted to suit the user by changing the size and number of auxiliary agents. This method does not allow for fine adjustment. According to this embodiment, the amount of drug can be finely adjusted by adjusting the combination of multiple layers.

[0066] 4. Fourth Embodiment 5, a first unit powder layer contains a first drug, and a second unit powder layer contains a second drug different from the first drug. By adjusting the total number (or integrated thickness) of the first and second unit powder layers in a single tablet, the amounts of the first and second drugs contained in the tablet can be adjusted.

[0067] For example, in the past, when a painkiller tablet was prescribed, a gastrointestinal drug tablet was also prescribed at the same time to reduce the burden on the stomach and intestines. According to this embodiment, by employing a first unit powder layer containing a painkiller component and a second unit powder layer containing a gastrointestinal drug component, a tablet containing both drug components can be obtained.

[0068] Although the case where two types of drugs are used has been described here, it is also possible to use three or more types of drugs. When three or more types of drugs are used, the first drug is contained in the first unit powder layer, the second drug is contained in the second unit powder layer, and the third drug is contained in the third unit powder layer, and a tablet is made by combining these three types of unit powder layers.

[0069] In this embodiment, it is possible to combine the following modes: adjusting the thickness of each unit powder layer, using a unit powder layer that does not contain a drug, and containing multiple drugs in one unit powder layer.

[0070] This embodiment is a tablet having a structure in which multiple powder layers are laminated, and the laminate includes a first type of powder layer and a second type of powder layer, the first powder layer containing a first type of drug, and the second powder layer containing a second type of drug. According to this embodiment, by adjusting the number and thickness of each powder layer, it is possible to produce a tablet with an adjustable content of multiple drugs.

[0071] The form shown here is also applicable to cases where an excipient other than anhydrous calcium hydrogen phosphate is used.

[0072] (others) Recoating is the process of spreading the powder evenly, removing excess powder, and making the powder layer flat and to a specific thickness. Figure 1 shows a method of recoating using a roller. Another recoating method is to move a blade or brush in contact with the upper layer of the powder layer in the direction of the Y axis in Figure 1.

[0073] (Another invention disclosed in this specification No. 1) As shown in Figure 4, when lactose powder is used as the excipient, repeated recoating of each layer of the stacked unit powder layers results in greater positional deviation in the lower layers. Therefore, the recoating direction is not set to a fixed direction, but is set to a different direction (e.g., opposite directions) for each unit powder layer. This prevents the movement of the hardening agent-infused portion from accumulating in a specific direction, even if it moves due to recoating.

[0074] An example of a method for changing the recoating direction is to rotate the modeling stage 101. This embodiment can be implemented in a pattern in which the recoating direction is changed for each unit powder layer, or in a form in which the recoating direction is changed when multiple unit powder layers are stacked (for example, when two layers are stacked or when four layers are stacked). The details of the process for forming the unit powder layers and the powders used are the same as those described in the specification.

[0075] The embodiment described here includes a first step of forming a powder layer containing a drug powder, an excipient powder, and an organic binder powder; a second step of flattening the powder layer by moving a member in contact with the surface of the powder layer parallel to the powder layer after the first step; and a third step of applying an aqueous solution containing a surfactant to a specific region of the powder layer after the second step. By repeating steps one through three, a laminate of multiple powder layers is formed. In multiple of the second steps, the member is moved in different directions for the multiple powder layers, and the laminate is dried to harden the portion composed of the laminate in the specific region, thereby producing a tablet. This technique can also be used when an excipient other than lactose is used.

[0076] (Another invention disclosed in this specification, No. 2) As shown in Figure 4, when lactose powder is used as the excipient, repeated recoating of each layer of the stacked unit powder layers causes the misalignment of the portion where the hardening agent is introduced to become greater in the lower layers. Therefore, the introduction position (spray position) of the hardening agent is adjusted in each layer to accommodate this misalignment.

[0077] For example, in FIG. 4, the injection position of the hardener in the second layer (second injection position) is slightly shifted relative to the injection position of the hardener in the first layer (first injection position). The amount and direction of this shift correspond to the amount and direction of shift of the hardener introduction portion of the first layer in the recoating of the second layer. That is, in the case of FIG. 4, the area where binder jetting is performed is gradually shifted to the right as one moves toward the upper layer. This is achieved by fine-tuning the position of the nozzle 106. This method alleviates the problem of misalignment of the hardener introduction portion between the lower and upper layers due to recoating.

[0078] Details other than those relating to the adjustment of the injection position of the curing agent are the same as those in the first embodiment. This technique can also be used when an excipient other than lactose is used.

[0079] The embodiment described here comprises a first step of forming a powder layer containing a drug powder, an excipient powder, and an organic binder powder; a second step of flattening the powder layer after the first step by moving a member that has been in contact with the surface of the powder layer parallel to the powder layer; and a third step of applying an aqueous solution to which a surfactant has been added to a specific region of the powder layer after the second step. By repeating steps one through three, a plurality of stacks of the powder layers are formed, and in the third step, the aqueous solution is applied to different powder layers at positions shifted in the direction of movement, and the stack is dried to harden the portion composed of the stack in the specific region, thereby producing a tablet. This can be understood as a tablet manufacturing method.

Claims

1. A raw material powder for producing tablets using a 3D printer, anhydrous calcium hydrogen phosphate powder; Organic binder powder and Including, A raw material for manufacturing tablets using a 3D printer, used as an excipient that hardens when dissolved in an aqueous solution containing a surfactant.

2. A tablet having a multilayer structure in which multiple layers containing a drug, anhydrous calcium hydrogen phosphate, and an organic binder are stacked.

3. a first layer comprising a first agent, anhydrous calcium hydrogen phosphate, and an organic binder; a second layer comprising a second agent different from the first agent, anhydrous calcium hydrogen phosphate, and an organic binder; A tablet comprising a laminate comprising:

4. a first step of forming a powder layer including a drug powder, anhydrous calcium hydrogen phosphate powder, and an organic binder powder; a second step of flattening the powder bed by moving a member in contact with the surface of the powder bed parallel to the powder bed after the first step; a third step of applying an aqueous solution containing a surfactant to a specific region of the powder layer after the second step; and The first step to the third step are repeated to form a stack of a plurality of powder layers, A method for manufacturing tablets in which the laminate is dried to harden the portion formed by the laminate in the specific region, thereby manufacturing a tablet.

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