Additive manufacturing system for continuously producing drug product and method

Abstract

Disclosed are an additive manufacturing system for producing a drug product and a method for operating the system. In some embodiments, the system allows for additive manufacturing for a drug product in a mode of continuous feeding and production, and also ensures precise allocation of the amount of a printed material to guarantee the accuracy, quality, and consistency of the drug product.

Description

Additive manufacturing system and method for continuous production of pharmaceutical products

[0001] Cross-references to related applications

[0002] This application claims priority to PCT / CN2024 / 138554, filed on December 11, 2024, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] This disclosure generally relates to additive manufacturing technology, and more specifically, to 3D printing technology for the continuous and efficient use of high-viscosity pharmaceutical printing materials to manufacture high-precision, high-quality, and highly consistent pharmaceutical products. Background Technology

[0004] Additive manufacturing, also known as 3D printing, is a rapid prototyping technology that involves joining or curing materials to create three-dimensional objects. Specifically, based on a digital model, materials are typically added together layer by layer. A computer system operates the additive manufacturing system and controls the flow of material and the movement of the printing nozzles until the desired shape is formed. Commonly used 3D printing technologies include material extrusion, binder jetting, powder bed fusion, and photopolymerization.

[0005] In recent years, researchers have attempted to apply additive manufacturing technology to the production of high-quality, high-precision, and highly consistent pharmaceutical products using high-viscosity pharmaceutical printing materials. These products include drug dosage units (e.g., tablets, capsules, small tablets), medical devices, and implantable stents, with the aim of achieving industrial-scale production. However, due to the higher quality, higher precision, and higher consistency requirements of pharmaceutical products compared to general pharmaceutical products (such as plastics, food, rubber, and resins), and the unique requirement for pharmaceutical products to undergo more stringent certifications (such as FDA certification) before being marketed, the applicant and inventors have encountered some new challenges during their research and development efforts to achieve industrial-scale mass production of pharmaceutical products using additive manufacturing technology.

[0006] Specifically, the printing materials required in the production environment often have high viscosity. To obtain high-precision, high-quality, and highly consistent pharmaceutical products, it is necessary to ensure an ideal printing environment and strictly control the printing process. This includes maintaining constant desired temperature, pressure, flow rate, and flow volume in the printing environment, and strictly controlling parameters such as heating and holding time, temperature, pressure, and the amount of printing material distributed in the printing process. In traditional 3D printing systems, after the material is heated and melted into a molten mass, it needs to be heated and held under pressure in a barrel for a period of time (e.g., 15 to 30 minutes) before being extruded from the nozzle of the print head to form a pharmaceutical product. Therefore, after the material in one barrel is used up, printing needs to be paused to prepare the new material supplied to the barrel, as mentioned above, after heating and holding under pressure for a period of time (e.g., the ideal heating and holding time for a certain material is 30 minutes) before printing can resume. This cycle repeats, requiring a pause and idle time between printing of the material in one barrel, which is inefficient and significantly affects the production capacity. Therefore, traditional 3D printing systems cannot continuously supply printing materials to the print head, making continuous production impossible to meet the high capacity and high throughput requirements of industrial-scale pharmaceutical manufacturing.

[0007] Furthermore, leakage of the printing material (melt) during the drug product manufacturing process using conventional 3D printing technology remains a long-standing and unresolved technical challenge. Material leakage leads to an inability to precisely control the amount of printing material dispensed, affecting the accuracy, quality, and consistency of the subsequent drug product. Specifically, when using solid raw materials to melt and print a one-piece structure for a drug product, the solid raw material must first be filled into the system's filling cavity through an open filling channel, and then the filling channel must be closed. After closing the filling channel, it is necessary to ensure that the system's filling cavity and other cavities form a sealed, interconnected cavity to prevent leakage of the molten printing material (melt) during the drug product manufacturing process (e.g., in melt extrusion drug product manufacturing, if the aforementioned cavity is connected to the outside (e.g., with gaps), and the high-viscosity melt cannot flow independently and requires a certain amount of extrusion pressure to move, if the cavity is not highly sealed to the outside, the melt may leak to the outside through gaps when being transported under extrusion pressure). In this case, a large volume of air will also leak out. The air entering the aforementioned sealed and connected cavity during the filling process cannot be expelled. More specifically, the air will temporarily remain between the newly filled solid raw material and the previously filled molten melt. When the newly filled solid raw material melts into a melt and is compressed, the aforementioned retained air will become compressed air between the previously filled molten melt and the new melt formed by the newly filled solid raw material. This compressed air is different from the small amount of air mixed, stirred, or extruded during the material mixing, stirring, or melt extrusion process in the prior art (this small amount of air can generally be automatically expelled from the set exhaust port). The original volume of the compressed air is relatively large, which will further lead to the inability to accurately control the amount of the subsequently printed drug product, and cannot meet the requirements of high quality, high precision, and high consistency of the printed drug product.

[0008] Furthermore, conventional 3D printing technology also attempts to increase productivity and throughput by operating multiple printing units simultaneously. However, its parallel printing systems also have drawbacks, such as inconsistencies and low precision introduced between multiple printing units in terms of printing form (e.g., volume, shape, weight, and / or composition). Such systems are also costly to manufacture and maintain, inefficient, and complex to operate. Moreover, due to their inability to achieve continuous production, the increased productivity and throughput achieved by using multiple printing units are limited.

[0009] Furthermore, configuring multiple 3D printers to work together to produce a batch of pharmaceutical products when using conventional 3D printing technology does not yield satisfactory results. Specifically, inconsistencies between multiple 3D printers (e.g., inconsistencies in hardware and software configurations) can lead to inconsistent final pharmaceutical products that fail to meet quality standards. In addition, systems involving coordination between multiple 3D printers are generally inefficient to operate and costly to maintain; and the increased production capacity achieved by using multiple printers is limited due to their inability to support continuous production.

[0010] Therefore, there is a need for systems and methods to 3D print pharmaceutical products (e.g., tablets, capsules, printed tablets) in an accurate, precise, and cost-effective manner, while ensuring high throughput and high production capacity. There is also a need for systems and methods capable of precisely controlling the amount of high-viscosity pharmaceutical printing material dispensed to prevent leakage and ensure high precision, high quality, and high consistency of pharmaceutical products. Summary of the Invention

[0011] An exemplary additive manufacturing system for producing pharmaceutical products includes: a supply unit, which includes a supply unit and a printing unit. The supply unit includes: a melt extrusion module for receiving printing material to generate the pharmaceutical product and forming the printing material into a melt; the melt extrusion module includes a first melt extrusion chamber and a second melt extrusion chamber. The printing unit includes a printing chamber for receiving the melt and a printing channel for distributing the melt to the printing channel to form the pharmaceutical product. The supply unit further includes: a release switch module configured to selectively connect the first melt extrusion chamber and the second melt extrusion chamber according to preset parameters, and to distribute the melt in the first melt extrusion chamber or the melt in the second melt extrusion chamber to the printing unit.

[0012] In some embodiments, the release switch module includes:

[0013] A valve and a release channel communicating with the printing chamber, the valve being configured to rotate and / or move via a first drive to selectively communicate one of the melt extrusion chambers with the release channel.

[0014] The first drive device is configured to rotate and / or move according to the preset parameters.

[0015] In some embodiments, the preset parameters include one or more of the following parameters: time length, melt pressure value in the first melt extrusion chamber, melt pressure value in the second melt extrusion chamber, weight value in the first melt extrusion chamber, weight value in the second melt extrusion chamber, temperature value in the first melt extrusion chamber, temperature value in the second melt extrusion chamber, melt volume value in the first melt extrusion chamber, and melt volume value in the second melt extrusion chamber.

[0016] In some embodiments, the first melt extrusion chamber includes a first extrusion channel, the second melt extrusion chamber includes a second extrusion channel, and the valve has a first state and a second state; in the first state, the release channel is connected to either the first extrusion channel or the second extrusion channel; in the second state, the release channel is disconnected from both the first extrusion channel and the second extrusion channel.

[0017] In some embodiments, the valve includes a valve body and a valve core, the valve body including a first valve body channel connected to the first extrusion channel, a second valve body channel connected to the second extrusion channel, and the release channel;

[0018] The valve core includes a communicating cavity, which includes a first port and a second port, the shape and size of which match.

[0019] In some embodiments, the first valve body channel includes a third port connected to the first extrusion channel and a fourth port connected to the communicating cavity, and the second valve body channel includes a fifth port connected to the second extrusion channel and a sixth port connected to the communicating cavity; the fourth port and the sixth port are both matched with the shape and size of the first and second ports.

[0020] In some embodiments, the projection angle formed by the central axis of the first port and the central axis of the second port is 120°.

[0021] In some embodiments, the projection angle formed by the central axis of the third port and the central axis of the fourth port is 120°.

[0022] In some embodiments, the projection angle formed by the central axis of the fifth port and the central axis of the sixth port is 120°.

[0023] In some embodiments, the communicating cavity includes a straight cavity segment connected to a first port, a straight cavity segment connected to a second port, and an arc-shaped cavity segment located in the middle of the straight cavity segment.

[0024] In some embodiments, the valve is configured to be in either a first state or a second state whenever it is driven by the first drive device.

[0025] In some embodiments, the valve further includes:

[0026] A rotating shaft, configured to rotate under the drive of the first driving device;

[0027] One end of the rotating shaft is connected to the output shaft of the first driving device, and the other end is connected to the valve core.

[0028] In some embodiments, the valve further includes a position compensation device configured to compensate for the gap between the valve core and the rotating shaft.

[0029] In some embodiments, the position compensation device includes a relative reference position positioning unit and an absolute position measuring unit, wherein the relative reference position positioning unit is configured to determine the position of the rotating shaft in a second state, and the absolute position measuring unit is configured to determine the position of the rotating shaft in a first state.

[0030] In some embodiments, the relative reference position positioning unit includes a light blocking plate disposed on the rotating shaft and a photoelectric sensor disposed on the valve, which is configured to cut off the optical path between the transmitting end and the receiving end of the photoelectric sensor when the valve rotates to the position corresponding to the photoelectric sensor.

[0031] In some embodiments, the shaft may rotate along a first direction and / or a second direction, wherein the first direction and the second direction are opposite.

[0032] In some embodiments, when the valve is in the first state, the valve is in the first state or the second state after the rotating shaft rotates once in the first direction or the second direction; and when the valve is in the second state, the valve is in the first state after the rotating shaft rotates once in the first direction or the second direction.

[0033] In some embodiments, the melt extrusion module is configured to alternately release the melt in the first melt extrusion chamber and the melt in the second melt extrusion chamber into the printing chamber, and / or

[0034] The melt extrusion module is configured such that the first melt extrusion chamber and the second melt extrusion chamber alternately receive the printing material.

[0035] In some embodiments,

[0036] The melt extrusion module is configured such that, when the melt in the first melt extrusion chamber is released into the printing chamber, the second melt extrusion chamber receives printing material and / or forms melt from the printing material and / or maintains the melt in a molten state.

[0037] The melt extrusion module is configured such that when the melt in the second melt extrusion chamber is released into the printing chamber, the first melt extrusion chamber receives printing material and / or forms a melt from the printing material and / or keeps the melt in a molten state.

[0038] In some embodiments, the release channel is provided with a pressure sensor configured to detect the melt pressure value within the release channel.

[0039] In some embodiments, the supply unit further includes a plunger corresponding to each of the melt extrusion cavities.

[0040] The plunger is configured to:

[0041] When receiving printing material, move the melt extrusion chamber toward the end furthest from the release switch module to increase the volume of the melt extrusion chamber; and

[0042] When the printing material is discharged, it moves toward the end of the melt extrusion chamber closer to the release switch module to reduce the volume of the melt extrusion chamber.

[0043] In some embodiments, the preset parameter is the stroke of the plunger. When the stroke of the plunger connected to the first melt extrusion chamber or the second melt extrusion chamber reaches the target value, the release switch unit selects to connect to the first melt extrusion chamber or the second melt extrusion chamber.

[0044] In some embodiments, the printing material is a preceding product unit, which includes a plurality of preceding products of the same weight and composition.

[0045] In some embodiments, the preceding product unit

[0046] Prepared by a preceding product forming module, the preceding product forming module comprising:

[0047] Feed inlet and screw extrusion unit

[0048] The screw extrusion device is used to mix at least two raw materials to form a preliminary melt and discharge the preliminary melt into a corresponding tube through an outlet.

[0049] In some embodiments, the tube includes a cylindrical cavity structure and bosses located at both ends of the cylindrical cavity structure.

[0050] In some embodiments, the preceding product forming module further includes a first air pressure control module;

[0051] The preceding product forming module has a preceding product melting cavity.

[0052] The first air pressure control module is connected to the preceding product melting chamber and is used to control the air pressure of the preceding product melting chamber to a first air pressure preset value.

[0053] In some embodiments, the preceding product molding module further includes a negative pressure control device configured to remove air from the preceding product melt molding cavity so that the air pressure in the preceding product melt molding cavity is reduced to a first preset air pressure value.

[0054] In some embodiments, the supply unit further includes a filler module for receiving printing material for generating the pharmaceutical product; the filler module further includes a filler cavity and a filler channel for receiving printing material for generating the pharmaceutical product.

[0055] In some embodiments, the filling cavity is configured such that the filling channel is open when receiving printing material, and the filling channel is closed after the filling cavity has finished receiving printing material.

[0056] In some embodiments, the packing cavity includes a first packing cavity and a second packing cavity, wherein the first packing cavity is connected to the first melt extrusion cavity and the second packing cavity is connected to the second melt extrusion cavity.

[0057] In some embodiments, the supply unit further includes a second air pressure control module;

[0058] The second air pressure control module is connected to the packing cavity and is used to control the air pressure of the packing cavity, the corresponding melt extrusion cavity and the printing cavity to the second air pressure preset value.

[0059] In some embodiments, the second air pressure control module includes an air pressure control device.

[0060] The air pressure control device includes:

[0061] Air pressure control channel;

[0062] An air pump is used to remove air from the packing cavity and the melt extrusion cavity through the air pressure control channel so that the air pressure in the packing cavity, the corresponding melt extrusion cavity and the printing cavity reaches the second preset air pressure value.

[0063] In some embodiments, the preset value of the second air pressure is -65 kPa to -100 kPa.

[0064] In some embodiments, the air pressure control channel has a third state and a fourth state;

[0065] In the third state, the air pressure control channel has its opening located inside the packing cavity, so that the air pressure control channel and the packing cavity are interconnected.

[0066] In the fourth state, the air pressure control channel has its outlet located outside the packing cavity, so that the air pressure control channel and the packing cavity are not connected.

[0067] In some embodiments,

[0068] The supply unit also includes a second drive device for driving the air pressure control channel to move back and forth between the third and fourth states.

[0069] In some embodiments, the supply unit further includes a material conveying module for conveying the printing material from the filler cavity to the corresponding melt extrusion cavity.

[0070] In some embodiments, the feeding module includes:

[0071] Material conveying chamber;

[0072] A plunger rod, configured to reciprocate axially within the feeding chamber, is used to push the printing material into the corresponding melt extrusion chamber.

[0073] In some embodiments, the air pressure control channel is connected to the interior of the packing cavity and / or the air pressure control channel is connected to the interior of the packing cavity or the material conveying cavity.

[0074] In some embodiments, the second air pressure control module further includes an air pressure detection device for detecting the air pressure value in the packing cavity or the conveying cavity.

[0075] In some embodiments, the air pressure detection device includes an air pressure sensor and an air pressure detection channel;

[0076] The air pressure detection channel is connected to the inside of the packing cavity or the inside of the conveying cavity.

[0077] In some embodiments, the air pressure detection channel has a fifth state and a sixth state;

[0078] In the fifth state, the air pressure detection channel has its channel opening located inside the packing cavity and / or the conveying cavity;

[0079] In the sixth state, the air pressure detection channel has its outlet located outside the packing cavity and / or the conveying cavity.

[0080] In some embodiments, the system further includes a third drive mechanism for driving the pressure detection channel to move back and forth between the fifth state and the sixth state.

[0081] In some embodiments, the pneumatic control channel includes multiple pneumatic control sub-channels, which are configured to operate in parallel, partially in parallel, or independently, so that the air pressure of the filling chamber, the corresponding melt extrusion chamber, and the printing chamber reaches a second preset air pressure value, or so that the air pressure of the filling chamber, the corresponding melt extrusion chamber, the feeding chamber, and the printing chamber reaches a second preset air pressure value.

[0082] In some embodiments, the system further includes a pressure control module for controlling the melt pressure of the supply unit and / or printing unit to a corresponding preset pressure value.

[0083] In some embodiments,

[0084] The system also includes a temperature control module, which is used to control the melt temperature of the supply unit and / or printing unit to the corresponding preset temperature value.

[0085] In some embodiments, the temperature control module includes one or more heaters and / or one or more coolers, and a temperature detection device;

[0086] The temperature detection device includes one or more temperature sensors;

[0087] The system is configured to adjust the temperature of each heater and / or each cooler in response to a temperature measurement sensed by the temperature sensor.

[0088] In some embodiments, the melt has a viscosity of about 100 Pa·s or higher.

[0089] In some embodiments, the melt has a viscosity of about 10,000 Pa·s or higher.

[0090] In some embodiments, the printing channel of the printing unit includes a nozzle assembly for printing the pharmaceutical product.

[0091] In some embodiments, the supply unit further includes a diversion module, the inlet of which is connected to a release switch module, and the outlet of which is connected to the nozzle assembly.

[0092] The flow distribution module is used to distribute the melt released by the release switch module to the nozzle group.

[0093] In some embodiments, the printing unit further includes a printing platform configured to receive the melt, wherein the printing platform is configured to move to form a batch of the pharmaceutical product.

[0094] In some embodiments, the printing unit further includes multiple printing platforms and multiple printing devices.

[0095] Each of the printing devices includes a printing channel comprising a nozzle assembly for printing the pharmaceutical product;

[0096] The system is configured to:

[0097] Each printing platform can be moved to a position below one of the nozzles in any of the nozzle groups of the printing device to receive the pharmaceutical product or a portion thereof printed by that nozzle.

[0098] In some embodiments, the pharmaceutical product includes a drug, which includes, but is not limited to, pharmaceutical products, medical devices, and dietary supplements.

[0099] In some embodiments, the printing material is a preceding product.

[0100] An exemplary method for manufacturing a pharmaceutical product using an additive manufacturing system for producing pharmaceutical products.

[0101] The system includes:

[0102] Supply unit, the supply unit comprising:

[0103] The melt extrusion module includes a first melt extrusion chamber and a second melt extrusion chamber.

[0104] And the release switch module;

[0105] The printing unit includes a printing cavity for receiving the molten material and a printing channel.

[0106] The method includes:

[0107] Printing material for manufacturing the pharmaceutical product is received via the first melt extrusion chamber and / or the second melt extrusion chamber;

[0108] The printing material in the first melt extrusion cavity is used to form a first melt and / or the printing material in the second melt extrusion cavity is used to form a second melt;

[0109] The release switch module selectively connects the first melt extrusion chamber and the second melt extrusion chamber according to preset parameters, and distributes the melt in the first melt extrusion chamber or the melt in the second melt extrusion chamber to the printing chamber;

[0110] The melt from the printing cavity is distributed to the printing channel to form a pharmaceutical product.

[0111] In some implementations, the release switch module includes:

[0112] The method further includes: a valve and a release channel communicating with the printing cavity.

[0113] The valve is rotated and / or moved by the first drive device to selectively connect one of the melt extrusion chambers to the release channel.

[0114] The first driving device rotates and / or moves according to the preset parameters.

[0115] In some implementation methods, the preset parameters include one or more of the following parameters: time length, melt pressure value in the first melt extrusion chamber, melt pressure value in the second melt extrusion chamber, weight value in the first melt extrusion chamber, weight value in the second melt extrusion chamber, temperature value in the first melt extrusion chamber, temperature value in the second melt extrusion chamber, melt volume value in the first melt extrusion chamber, and melt volume value in the second melt extrusion chamber.

[0116] In some implementations, the first melt extrusion chamber includes a first extrusion channel, the second melt extrusion chamber includes a second extrusion channel, and the valve has a first state and a second state; the method further includes:

[0117] The valve rotates and / or moves to a first state, connecting the release channel with the first extrusion channel or the second extrusion channel;

[0118] The valve rotates and / or moves to the second state, disconnecting the release channel from both the first extrusion channel and the second extrusion channel.

[0119] In some implementation methods, the method further includes:

[0120] The valve is driven by the first driving device, so that the valve is in either the first state or the second state.

[0121] In some implementations, the valve includes a valve body and a valve core, the valve body including a first valve body channel connected to the first extrusion channel, a second valve body channel connected to the second extrusion channel, and the release channel;

[0122] The valve core includes a communicating cavity, and the method further includes:

[0123] The melt in the first melt extrusion cavity or the melt in the second melt extrusion cavity is sequentially distributed to the printing cavity via the first valve body channel or the second valve body channel, the connecting cavity, and the release channel.

[0124] In some implementations, the communicating cavity includes a first port and a second port, the shape and size of which match the shape and size of the first port and the second port; the first valve body channel includes a third port connected to the first extrusion channel and a fourth port connected to the communicating cavity; the second valve body channel includes a fifth port connected to the second extrusion channel and a sixth port connected to the communicating cavity; the fourth port and the sixth port both match the shape and size of the first port and the second port.

[0125] In some implementations, the valve further includes a rotating shaft, one end of which is connected to the output shaft of the first drive device, and the other end of which is connected to the valve core. The method further includes:

[0126] The first driving device drives the rotating shaft to rotate, and the rotating shaft rotates in turn, causing the valve core to rotate, such that:

[0127] The communicating cavity of the valve core is connected to either the first valve body channel or the second valve body channel, or

[0128] The communicating cavity of the valve core is disconnected from both the first valve body channel and the second valve body channel.

[0129] In some implementations, the rotation of the shaft and the resulting rotation of the valve core includes: compensating for the gap between the valve core and the shaft.

[0130] In some implementations, compensating for the gap between the valve core and the rotating shaft includes:

[0131] The position of the rotating shaft in the second state is determined by a relative reference position positioning unit, and the position of the rotating shaft in the first state is determined by an absolute position measurement unit.

[0132] The position of the rotating shaft in the first state includes a first sub-position and a second sub-position. In the first sub-position, the connecting cavity is connected to the first valve body channel; in the second sub-position, the connecting cavity is connected to the second valve body channel. The method further includes:

[0133] When the rotating shaft switches between the first sub-position and the second sub-position

[0134] The rotating shaft drives the valve core to rotate to the position of the rotating shaft in the second state. Then, the rotating shaft drives the valve core to rotate from the position of the rotating shaft in the second state to the first sub-position or the second sub-position. The absolute value of the angle between the first sub-position and the position of the rotating shaft in the second state is then rotated to the first sub-position or the second sub-position.

[0135] In some implementations, the absolute value of the angle between the first sub-position or the second sub-position and the position of the rotating shaft in the second state is 60°.

[0136] In some implementations, the position of the rotating shaft in the second state is at the midpoint between the first sub-position and the second sub-position.

[0137] In some implementations, the relative reference position positioning unit includes a light-blocking plate disposed on the rotating shaft and a photoelectric sensor disposed on the valve; the method further includes:

[0138] When the valve rotates to the position corresponding to the photoelectric sensor, the light blocking plate cuts off the optical path between the transmitting end and the receiving end of the photoelectric sensor.

[0139] In some implementations, the method further includes: determining the position of the rotating shaft in a second state based on the light-blocking plate cutting off the optical path between the photoelectric sensor transmitter and receiver.

[0140] In some implementation methods, the method further includes:

[0141] The shaft rotates along a first direction and / or a second direction, wherein the first direction and the second direction are opposite.

[0142] In some implementations, the method further includes: when the valve is in the first state, the valve is in the first state or the second state after the rotating shaft rotates once along the first direction or the second direction; and when the valve is in the second state, the valve is in the first state after the rotating shaft rotates once along the first direction or the second direction.

[0143] In some implementations, the method further includes: alternately releasing the melt from the first melt extrusion chamber and the melt from the second melt extrusion chamber into the printing chamber, and / or

[0144] The printing material is received alternately via the first melt extrusion chamber and the second melt extrusion chamber.

[0145] In some implementation methods, the method further includes:

[0146] When the melt in the first melt extrusion chamber is released into the printing chamber, the printing material is received via the second melt extrusion chamber and / or a melt is formed from the printing material and / or the melt is kept in a molten state.

[0147] When the melt in the second melt extrusion chamber is released into the printing chamber, the printing material is received via the first melt extrusion chamber and / or a melt is formed from the printing material and / or the melt is kept in a molten state.

[0148] In some implementations, the passageway is equipped with a pressure sensor, and the method further includes:

[0149] The pressure value of the melt in the release channel is detected by the pressure sensor.

[0150] In some implementation methods, the method further includes:

[0151] Based on the detected melt pressure value, the melt pressure value is adjusted to a desired constant pressure value.

[0152] In some implementations, the supply unit further includes a plunger corresponding to each of the melt extrusion cavities, and the method further includes:

[0153] Upon receiving printing material, the plunger moves toward the end of the melt extrusion chamber furthest from the release switch module to increase the volume of the melt extrusion chamber; and

[0154] When the printing material is discharged, the end of the melt extrusion chamber that is closer to the release switch module moves to reduce the volume of the melt extrusion chamber.

[0155] In some implementation methods, the preset parameter is the stroke of the plunger, and the method further includes:

[0156] When the plunger stroke connected to the first melt extrusion chamber or the second melt extrusion chamber reaches the target value, the release switch module selects to connect to the first melt extrusion chamber or the second melt extrusion chamber.

[0157] In some implementations, the printing material is a preceding product unit, which includes multiple preceding products of the same weight and composition.

[0158] In some implementations, the system further includes a preceding product forming module, which includes a feed inlet and a screw extrusion device; the method further includes:

[0159] At least two raw materials are mixed via the screw extrusion device to form a preliminary melt, and the preliminary melt is discharged through an outlet into a corresponding tube to form the preliminary product.

[0160] In some implementations, the preceding product forming module further includes a first air pressure control module; the preceding product forming module has a preceding product melting chamber, and the first air pressure control module is connected to the preceding product melting chamber; the method further includes:

[0161] The pressure of the preceding product melting chamber is controlled to a first preset pressure value via the first pressure control module.

[0162] In some implementations, the preceding product forming module further includes a negative pressure control device, and the method further includes:

[0163] The negative pressure control device removes air from the melting and molding cavity of the preceding product, bringing the air pressure in the melting and molding cavity of the preceding product to a first preset air pressure value.

[0164] In some implementations, the supply unit further includes a packing module; the packing module further includes a packing cavity and a packing channel, and the method further includes:

[0165] The printing material for generating the pharmaceutical product is received via the filling cavity.

[0166] In some implementation methods, the method further includes:

[0167] The filling channel is opened to receive printing material through the filling cavity, and the filling channel is closed after the filling cavity has finished receiving the printing material.

[0168] In some implementations, the packing cavity includes a first packing cavity and a second packing cavity, wherein the first packing cavity is connected to the first melt extrusion cavity, and the second packing cavity is connected to the second melt extrusion cavity.

[0169] In some implementations, the supply unit further includes a second air pressure control module, which is connected to the packing cavity.

[0170] The method further includes:

[0171] The second air pressure control module controls the air pressure of the filler cavity, the corresponding melt extrusion cavity, and the printing cavity to the second air pressure preset value.

[0172] In some implementations, the second air pressure control module includes an air pressure control device, which includes an air pressure control channel and an air pressure pump; the method further includes:

[0173] Through the air pressure control channel, the air in the packing cavity and the melt extrusion cavity is purged by the air pressure pump so that the air pressure in the packing cavity, the corresponding melt extrusion cavity and the printing cavity reaches the second preset air pressure value.

[0174] In some implementations, the second air pressure is preset to -65 kPa to -100 kPa.

[0175] In some implementations, the air pressure control channel has a third state and a fourth state;

[0176] The method further includes:

[0177] Before the air pressure control begins, the air pressure control channel is switched from the fourth state to the third state, so that the air pressure control channel is connected to the packing cavity.

[0178] The air pump is activated to control the air pressure in the packing chamber, the corresponding melt extrusion chamber, and the printing chamber to the second preset air pressure value; and

[0179] When the air pressure control ends or when the air pressure control is completed, the air pressure control channel is switched from the third state to the fourth state so that the air pressure control channel is not connected to the packing cavity.

[0180] In some implementations, the supply unit further includes a second drive device, and the method further includes:

[0181] The pneumatic control channel is moved by the second driving device, causing the pneumatic control channel to switch between the third state and the fourth state.

[0182] In some implementations, the supply unit further includes a material conveying module, and the method further includes:

[0183] The printing material is transported from the filler cavity to the corresponding melt extrusion cavity via the feeding module.

[0184] In some implementations, the material conveying module includes a material conveying cavity and a plunger rod, and the method further includes:

[0185] The printing material is pushed to the corresponding melt extrusion chamber by the plunger rod moving back and forth in the axial direction within the feeding chamber.

[0186] In some implementations, the air pressure control channel is connected to the interior of the packing cavity and / or the air pressure control channel is connected to the interior of the packing cavity or the material conveying cavity.

[0187] In some implementations, the second air pressure control module further includes an air pressure detection device, and the method further includes:

[0188] The air pressure value in the packing cavity or conveying cavity is detected by the air pressure detection device.

[0189] In some implementations, the air pressure detection device includes an air pressure sensor and an air pressure detection channel; the air pressure detection channel is connected to the inside of the packing cavity or the conveying cavity, and the method further includes:

[0190] The pressure sensor detects the pressure value inside the packing cavity or the conveying cavity via the pressure detection channel.

[0191] In some implementations, the air pressure detection channel has a fifth state and a sixth state;

[0192] The method further includes:

[0193] Before the air pressure test begins, switch the air pressure test channel from state six to state five to make the air pressure test channel interconnected with the packing cavity and / or the conveying cavity.

[0194] The air pump is started to detect the air pressure value in the packing cavity and / or the conveying cavity; and

[0195] When the air pressure detection ends or after the air pressure detection is completed, switch the air pressure detection channel from the fifth state to the sixth state so that the air pressure detection channel is not connected to the packing cavity and / or the conveying cavity.

[0196] In some implementations, the supply unit further includes a third drive device, and the method further includes:

[0197] The air pressure detection channel is moved by the third driving device, causing the air pressure detection channel to switch between the fifth state and the sixth state.

[0198] In some implementation methods, the air pressure control channel includes multiple air pressure control sub-channels, and the method further includes: operating all of the multiple air pressure control sub-channels in parallel, partially in parallel, or independently, so that the air pressure of the filling cavity, the corresponding melt extrusion cavity, and the printing cavity reaches a second preset air pressure value, or so that the air pressure of the filling cavity, the corresponding melt extrusion cavity, the feeding cavity, and the printing cavity reaches a second preset air pressure value.

[0199] In some implementations, the system further includes a pressure control module, and the method further includes:

[0200] The melt pressure of the supply unit and / or printing unit is controlled to the corresponding preset pressure value via the pressure control module.

[0201] In some implementations, the system further includes a temperature control module;

[0202] The temperature control module includes one or more heaters and / or one or more coolers.

[0203] In some implementations, the one or more heaters and / or one or more coolers are respectively located at different positions in the melt extrusion module and the printing unit.

[0204] In some implementations, the temperature control module further includes a temperature detection device;

[0205] The temperature detection device includes one or more temperature sensors;

[0206] The method further includes:

[0207] In response to the temperature measurement value sensed by the temperature sensor, the temperature of each module of the system is controlled and adjusted to the desired temperature via one or more heaters and / or one or more coolers.

[0208] In some implementations, the printing channel of the printing unit includes a nozzle assembly;

[0209] The system also includes a traffic splitting module;

[0210] The method further includes:

[0211] The first melt and / or the second melt released by the release switch module are distributed to the nozzle group via the flow distribution module.

[0212] In some implementations, the printing material is a preceding product.

[0213] An exemplary non-transitory computer-readable storage medium stores one or more programs, the one or more programs including instructions that, when executed by an additive manufacturing system having one or more processors and memory, cause the system to perform a method comprising the steps described above. Attached Figure Description

[0214] To better understand the various embodiments described, reference should be made to the specific implementation in conjunction with the following figures, wherein the same reference numerals refer to corresponding parts throughout the figures.

[0215] Figure 1 shows a plan view of an additive manufacturing system for producing pharmaceutical products according to one embodiment of this application.

[0216] Figure 2A shows a perspective structural schematic diagram of an exemplary supply unit (second air pressure control module) according to some embodiments of this application.

[0217] Figure 2B shows a perspective structural schematic diagram of an exemplary supply unit (second air pressure control module) according to some embodiments of this application.

[0218] Figure 3A shows a schematic diagram of the structure of an exemplary supply unit (the printing material is a solid printing material) according to some embodiments of this application.

[0219] Figure 3B shows a schematic diagram of the structure of an exemplary supply unit (the printing material is a solid printing material) according to some embodiments of this application.

[0220] Figure 3C shows a schematic diagram of the structure of an exemplary supply unit (the printing material is a solid printing material) according to some embodiments of this application.

[0221] Figure 4A shows a schematic diagram of the structure of an exemplary supply unit (printing material is the printing material of a preceding product) according to some embodiments of this application.

[0222] Figure 4B shows a schematic diagram of the structure of an exemplary supply unit (printing material is the printing material of a preceding product) according to some embodiments of this application.

[0223] Figure 4C shows a schematic diagram of the structure of an exemplary supply unit (printing material is the printing material of a preceding product) according to some embodiments of this application.

[0224] Figure 4D shows a schematic diagram of the structure of an exemplary supply unit (printing material is the printing material of a preceding product) according to some embodiments of this application.

[0225] Figure 5 shows a schematic diagram of the structure of an exemplary supply unit (splitter module) according to some embodiments of this application.

[0226] Figure 6 is a flowchart of a method for controlling air pressure through an exemplary supply unit according to one embodiment of this application.

[0227] Figure 7 illustrates a flowchart of a method for manufacturing a pharmaceutical product using an exemplary supply unit (pressure detection device) according to different embodiments of this application.

[0228] Figure 8 shows a flowchart of a method for manufacturing a pharmaceutical product using an exemplary supply unit (pressure detection device and pressure control device) according to different embodiments of this application.

[0229] Figure 9 depicts an exemplary apparatus for controlling a system and method according to some embodiments.

[0230] Figure 10A depicts a front view schematic diagram of a pneumatic control device (third state) according to some embodiments.

[0231] Figure 10B depicts a structural schematic diagram of the top portion of a pneumatic control device according to some embodiments.

[0232] Figure 11A depicts a schematic layout of the printing unit and the splitter module according to some embodiments.

[0233] Figure 11B depicts a schematic layout of the printing unit and the splitter module according to some embodiments.

[0234] Figure 11C depicts a schematic layout of the printing unit and the splitter module according to some embodiments.

[0235] Figure 12 depicts an exemplary additive manufacturing system for producing pharmaceutical products according to some embodiments.

[0236] Figure 13 depicts an exemplary method of operating a melt extrusion module according to some embodiments.

[0237] Figures 14A-14J depict exemplary printing station and melt extrusion module assemblies according to some embodiments.

[0238] Figure 15 shows a schematic diagram of the structure of an exemplary supply unit (release switch module) according to some embodiments of this application.

[0239] Figures 16A-16E show schematic diagrams of the structure of exemplary release switch modules (multi-way valves) according to some embodiments of this application.

[0240] Figures 17A-17E show schematic diagrams of switching of exemplary release switch modules (multi-way valves) according to some embodiments of this application.

[0241] Figure 18 shows a schematic diagram of the structure of an exemplary supply unit (continuous feeding of preceding products) according to some embodiments of this application.

[0242] Figure 19 shows a schematic diagram of the structure of an exemplary supply unit (preceding product forming module) according to some embodiments of this application.

[0243] Figure 20 shows a schematic diagram of the structure of an exemplary air pressure control module according to some embodiments of this application.

[0244] Figures 21A-21C illustrate flowcharts of a method for manufacturing pharmaceutical products using a printing apparatus of an exemplary additive manufacturing system for producing pharmaceutical products according to some embodiments of this application.

[0245] Figure 22A shows a schematic diagram of the flow channel cross-section of a supply unit according to some embodiments of the prior art (the cross-section 43 at the junction of the two channels 41, 42 is misaligned).

[0246] Figure 22B shows a schematic diagram of the flow channel cross-section of an exemplary supply unit according to some embodiments of this application (the cross-section 53 at the junction of the two channels 51, 52 is completely overlapping).

[0247] Figures 23A-23B show schematic diagrams of the structure of an exemplary release switch module (multi-way valve) according to other embodiments of this application.

[0248] Figures 24A-24B show schematic diagrams of the structure of exemplary release switch modules (mechanical limiters) according to other embodiments of this application.

[0249] Figures 25A-25D show schematic diagrams of the structure of exemplary release switch modules (on / off valves) according to other embodiments of this application.

[0250] Figures 26A-26D illustrate structural schematic diagrams of exemplary tubes, preceding products, and preceding product units according to other embodiments of this application. Detailed Implementation

[0251] This document describes systems, methods, and non-transitory storage media for additive manufacturing (e.g., 3D printing, 4D printing, 5D printing) of pharmaceutical products (further including pharmaceuticals, medical devices, dietary supplements, etc.) in a continuous feeding and production manner, while ensuring precise distribution of the amount of printing material to guarantee the accuracy, quality, and consistency requirements of the pharmaceutical products, and maintaining high throughput over time. Embodiments of this disclosure can be configured in different ways to meet the diverse manufacturing needs of different pharmaceutical products (with different structures / parts, such as shells, one or more cores, one or more caps), and thus can meet different manufacturing needs in a more efficient and precise manner. According to some embodiments, the printing system employs a release switch module that can selectively connect to one of multiple melt extrusion chambers. This allows the melt in one of the multiple melt extrusion chambers to be released into the printing chamber. While the melt is being released from that chamber, the other melt extrusion chambers continue to receive printing material and generate melt or maintain molten and / or pressurized melt to complete melt preparation. This saves a significant amount of preparation waiting time, ensures a continuous supply of melt to support high-throughput printing, and prevents the printing material (e.g., the active pharmaceutical ingredient (API) of a pharmaceutical product) from aging or changing its properties during the printing process. This enables efficient and continuous production of pharmaceutical products and increases the capacity of industrial-scale pharmaceutical production. According to some embodiments, the release switch module utilizes a valve device for positioning relative to a reference position. This compensates for installation gaps and positioning errors of the valve device, allowing the release channel to selectively align perfectly with a specific extrusion channel of multiple melt extrusion cavities. This ensures unobstructed flow and guarantees that the melt is released from the same or different melt extrusion cavities to the printing cavity at a constant melt pressure. Furthermore, this enables continuous feeding and production of additive manufacturing of pharmaceutical products while ensuring precise allocation of printing material to guarantee the accuracy, quality, and consistency of the pharmaceutical products. According to some embodiments, a pre-formed product molding module is used to pre-prepare the pharmaceutical product raw materials into an integrally formed solid printing material, pre-removing any small amount of air trapped in the raw materials to ensure the accuracy, quality, and consistency of the subsequently printed pharmaceutical products. Furthermore, by utilizing a second air pressure control module, a large amount of air entering the sealed cavity of the system during the filling process can be removed from the supply unit, further ensuring precise allocation of printing material to guarantee the accuracy, quality, and consistency of the pharmaceutical products. According to some embodiments, a flow distribution module is used to precisely control multiple nozzles to distribute multiple streams for 3D printing a batch of pharmaceutical products (e.g., pharmaceutical dosage forms), thus achieving consistency between pharmaceutical products / forms / units within a single batch and across multiple batches, while maintaining high throughput. According to some embodiments, the printing system is configured with varying numbers of melt extrusion cavities to continuously supply printing melt to the flow distribution module and multiple printing channels (e.g., nozzles).In high-throughput printing setups where multiple printing channels (such as nozzles) print simultaneously, the melt extrusion module can be configured in this way to create a flexible system for additive manufacturing (e.g., 3D printing) of pharmaceutical products by using different modules (e.g., splitting modules, preceding product forming modules, air pressure control modules, printing units) to meet different needs.

[0252] Furthermore, the printing system includes an environment (e.g., a closed environment such as a temperature-controlled oven, an open environment such as a printing platform) for additive manufacturing (e.g., 3D printing) of the pharmaceutical product. According to some embodiments, multiple closed-loop control systems are used to control temperature, pressure, flow rate, weight, volume, and other relevant parameters in the environment at multiple stages of the manufacturing process. Specifically, control systems and methods are implemented to precisely adjust the nozzle opening, particularly the opening of the needle valve mechanism at the nozzle, to ensure consistent nozzle output. In some embodiments, the pharmaceutical product is small in size and weight, such as 100 mg, 200 mg, 300 mg, etc., and the inconsistency in pharmaceutical product / form / unit weight (i.e., inconsistency between pharmaceutical products / forms / unit weights within the same batch) is typically less than 10% (e.g., 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 9.5%, 10%). In some embodiments, batch weight inconsistency (i.e., inconsistency between batch weights) is less than 10% (e.g., 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 9.5%, 10%). Based on the different formulations, materials, and compositions of different pharmaceutical products / units, the control system can adjust parameters accordingly to ensure high-quality, high-precision, and high-throughput additive manufacturing (e.g., 3D printing) and allow the system to manufacture a variety of high-quality pharmaceutical products.

[0253] In some embodiments, the printing material is non-filamentous (e.g., powder, granules, or liquid). In some embodiments, the viscosity of the printing material is 0.01-10000 Pa·s when dispensed from the system. For example, the viscosity of the printing material is approximately 100 Pa·s or higher when dispensed from the printing cavity. As another example, the viscosity of the printing material is approximately 800 Pa·s or higher when dispensed from the printing channel (e.g., nozzle). As another example, the viscosity of the material is approximately 400 Pa·s or higher when dispensed from the printing channel (e.g., nozzle). As another example, the viscosity of the printing material is approximately 1000 Pa·s or higher when dispensed from the printing channel (e.g., nozzle). In some embodiments, the material is a melt (e.g., semi-solid / molten form) when dispensed from the printing channel (e.g., nozzle) and can be dispensed and deposited using melt extrusion deposition (MED) technology. In some embodiments, the viscosity of the material is approximately 0.01 Pa·s. When dispensing material from the printing channel (e.g., nozzle), the material can be liquid and can be dispensed by spraying using inkjet printing technology. In some embodiments, the printing material is melted at a temperature of about 50°C to about 400°C (e.g., 80°C). In some embodiments, the printing material is dispensed from the printing channel at a temperature of about 50°C to about 400°C (e.g., 140°C). In some embodiments, the material is dispensed from the printing channel at a temperature of about 90°C to about 300°C.

[0254] In some embodiments, each supply unit includes a plurality of melt extrusion modules. Each melt extrusion module is used to supply melt to one or more printing cavities of one or more printing units, wherein the materials of the melts are the same, partially the same, or different. In some embodiments, each melt extrusion module includes the same or different numbers of melt extrusion cavities.

[0255] In some embodiments, the system includes multiple printing units. Each printing unit can be used to print one or more portions of a batch of pharmaceutical product (e.g., the shell, core, lower half, and upper half of the pharmaceutical product). A portion of the pharmaceutical product may include one or more layers of a first printing material (e.g., a first melt). For example, the printing unit may include two or more printing units, each capable of printing a portion of a batch of pharmaceutical product. In some embodiments, the amount (e.g., weight, volume) of the corresponding printing material required for different portions of the pharmaceutical product may vary. For example, the first printing material required to print the shell of the pharmaceutical product may be more than two or three times the second printing material required to print the core of the pharmaceutical product. In some embodiments, different numbers of printing units may be assigned to print different portions of the pharmaceutical product. For example, one printing unit may be assigned to print the core portion, while four printing units may be assigned to print the shell portion. In some embodiments, the printing units used to print different portions of the pharmaceutical product may operate at different printing speeds. In some embodiments, the printing units used to print different portions of the pharmaceutical product may be equipped with different numbers of melt extrusion modules. For example, a first printing unit for printing the outer shell layer may be equipped with multiple melt extrusion modules, while a second printing unit for printing the inner core may be equipped with a single melt extrusion module. Furthermore, multiple printing units can operate in parallel, allowing for the simultaneous printing of multiple batches of pharmaceutical products. In some embodiments, a single multi-station system can manufacture 3,000-5,000 pharmaceutical products (e.g., drug tablets) per day. In some embodiments, the system reduces inconsistencies between pharmaceutical products (e.g., drug dosage units) in the same patch and in different patches to ±2.0% (e.g., weight, volume). In some embodiments, the multi-station system is easy to clean and maintain, thus meeting the requirements for standardized pharmaceutical production, particularly for pharmaceutical manufacturing (e.g., GMP).

[0256] The following description is presented to enable those skilled in the art to make and use various embodiments. The description of specific apparatuses, techniques, and applications is provided by way of example only. Various modifications to the embodiments described herein will be readily apparent to those skilled in the art, and the general principles defined herein can be applied to other embodiments and applications without departing from the spirit and scope of the various embodiments. Therefore, the various embodiments are not intended to be limited to the embodiments described and shown herein, but are to be accorded the scope consistent with the claims.

[0257] Although the following description uses the terms "first," "second," etc., to describe various elements, these elements should not be limited by these terms. These terms are used only to distinguish one element from another. For example, a first melt extrusion chamber may be referred to as a second melt extrusion chamber, and similarly, a second melt extrusion chamber may be referred to as a first melt extrusion chamber, without departing from the scope of the various embodiments described. Both the first melt extrusion chamber and the second melt extrusion chamber are melt extrusion chambers, but they are not the same melt extrusion chamber.

[0258] The terminology used in the description of the various embodiments described herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used in the description of the various embodiments described and the appended claims, unless the context clearly indicates otherwise, the singular forms “a” and “the” are also intended to include the plural forms. It should also be understood that the term “and / or” as used herein refers to and includes any and all possible combinations of one or more of the associated listed items. It will be further understood that when the terms “includes” and / or “comprises” are used in this specification, the presence of the stated features, integers, steps, operations, elements, and / or components is specified, but the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof is not excluded.

[0259] Depending on the context, the term "if" may optionally be interpreted as meaning "when," "after," "in response to determining," or "in response to detecting." Similarly, depending on the context, the phrase "if determined" or "if [the condition or event] is detected" may optionally be interpreted as "after determining," "in response to determining," "after detecting," or "in response to detecting."

[0260] Embodiments of this disclosure include an exemplary continuous feeding and additive manufacturing system for producing high-precision, high-quality, and highly consistent pharmaceutical products. The system includes a supply unit and a printing unit. In some embodiments, the supply unit provides a melt for generating the pharmaceutical product, which is then delivered to the printing unit via a release switch module. Specifically, the supply unit includes a melt extrusion module for receiving printing material for generating the pharmaceutical product and forming a melt from the printing material, and a release switch module. The melt extrusion module includes at least two melt extrusion chambers, such as three, four, or six melt extrusion chambers. The release switch module is configured to selectively communicate with one of the plurality of melt extrusion chambers and also with the printing chamber, for selectively releasing the melt from one of the melt extrusion chambers to the printing unit, i.e., providing the melt from the selected melt extrusion chamber to the printing unit. In some embodiments, each of the aforementioned melt extrusion chambers includes an extrusion channel through which the melt from the selected melt extrusion chamber is discharged. In some embodiments, the printing unit is used to dispense the melt into the printing channel to form a pharmaceutical product, specifically including an inlet and a printing cavity for receiving the melt from the melt extrusion module, and further including a printing channel, for example, a group of nozzles (one or more nozzles) for printing pharmaceutical products (e.g., pharmaceutical formulations, tablets, capsules, printed tablets). The additive manufacturing system can use one or more 3D technologies, such as MED technology, inkjet technology, selective laser sintering (SLS) technology, PB technology, FDM technology, Arburg Plastic Freeforming (APF) technology, Mirco droplet jetting technology, etc.

[0261] In some embodiments, a nozzle group may include 1, 2, 4, 8, 16, 32, or more nozzles. In some embodiments, a nozzle group may include 1, 3, 9, 18, 21, or more nozzles. In some embodiments, a nozzle group may include 1, 6, 12, 24, 48, or more nozzles. The number of nozzles may be determined based on the manufacturing technology involved, target quality, target output, etc. Nozzles within the same nozzle group may be controlled together or independently. For example, a nozzle group may include 32 nozzles. These 32 nozzles may be controlled together. Alternatively, each subgroup having 4 or 8 nozzles may be controlled together, but different subgroups may be controlled independently. Alternatively, each nozzle within a nozzle group may be controlled independently.

[0262] Figure 12 depicts a schematic diagram of an exemplary additive manufacturing system 20 (e.g., a 3D printing system) according to some embodiments of the present invention. Figure 15 depicts a schematic diagram of an additive manufacturing apparatus 70 of the exemplary additive manufacturing system 20 according to some embodiments of the present invention. As shown in Figures 15 to 20, the apparatus 70 includes a supply unit 710 and a printing unit 720, as described below. In some embodiments, the supply unit 710 is used to provide a melt for generating a pharmaceutical product 900, the melt being released to the printing unit 720 via a release switch module 717 of the supply unit 710. Specifically, the printing unit 720 includes a melt extrusion module 711 for receiving printing material for generating the pharmaceutical product 900 and melting the printing material (e.g., solid printing material 731A, preceding product printing material 731B) into a melt, and a release switch module 717, wherein the melt extrusion module 711 includes a first melt extrusion chamber 713A and a first melt extrusion chamber 713B. In some embodiments, the melt extrusion module 711 can be expanded to include multiple melt extrusion chambers, such as three, four, or six melt extrusion chambers. The release switch module 717 is configured to selectively connect the first melt extrusion chamber 713A and the second melt extrusion chamber 713B according to preset parameters, and to release the melt in the first melt extrusion chamber 713A or the melt in the second melt extrusion chamber 713B to the printing unit 720, that is, to provide the melt in the selected melt extrusion chamber to the printing chamber 721 of the printing unit 720. In some embodiments, as shown in FIG17A, the first melt extrusion chamber 713A includes a first extrusion channel 713C, and the second melt extrusion chamber 713A includes a second extrusion channel 713D. The melt in the selected melt extrusion chamber is discharged to the selected melt extrusion chamber through the corresponding extrusion channel. In some embodiments, the printing unit 720 is used to dispense the melt to the printing channel (e.g., a nozzle), the melt is discharged from the printing channel and deposited on the printing platform 722 to form a pharmaceutical product 900, specifically including an inlet for receiving the melt from the melt extrusion module 711 and a printing cavity 721, and further including a printing channel (e.g., a group of nozzles (one or more nozzles) for printing the pharmaceutical product 900 (e.g., a pharmaceutical formulation, tablet, capsule, printed tablet).

[0263] In some embodiments, the preset parameters include one or more of the following parameters: time length, melt pressure value in the first melt extrusion chamber 713A, melt pressure value in the second melt extrusion chamber 713B, weight value of the first melt extrusion chamber 713A, weight value of the second melt extrusion chamber 713B, temperature value of the first melt extrusion chamber 713A, temperature value of the second melt extrusion chamber 713B, melt volume value in the first melt extrusion chamber 713A, and melt volume value in the second melt extrusion chamber 713B.

[0264] In some embodiments, for example, when the time it takes for the melt to be discharged from the first melt extrusion chamber 713A to the printing chamber 721 reaches the release time threshold, the release switch module 717 disconnects from the first melt extrusion chamber 713A, selects to connect to the second melt extrusion chamber 713B, and supplies material to the printing chamber 721 through the second melt extrusion chamber 713B; when the time it takes for the melt to be discharged from the second melt extrusion chamber 713B to the printing chamber 721 reaches the release time threshold, the release switch module 717 disconnects from the second melt extrusion chamber 713B, selects to connect to the first melt extrusion chamber 713A, and supplies material to the printing chamber 721 through the first melt extrusion chamber 713A. In some embodiments, for example, when the melt in the first melt extrusion chamber 713A heats and / or holds pressure to the time threshold of heating and / or holding pressure, the release switch module 717 selects to connect with the first melt extrusion chamber 713A and supplies material to the printing chamber 721 through the first melt extrusion chamber 713A; when the melt in the second melt extrusion chamber 713B heats and / or holds pressure to the time threshold of heating and / or holding pressure, the release switch module 717 selects to connect with the second melt extrusion chamber 713B and supplies material to the printing chamber 721 through the second melt extrusion chamber 713B. In other embodiments, for example, when the melt pressure value in the first melt extrusion chamber 713A reaches the desired melt supply pressure value, the release switch module 717 selects to connect with the first melt extrusion chamber 713A and supplies material to the printing chamber 721 through the first melt extrusion chamber 713A; when the melt pressure value in the second melt extrusion chamber 713B reaches the desired melt supply pressure value, the release switch module 717 selects to connect with the second melt extrusion chamber 713B and supplies material to the printing chamber 721 through the second melt extrusion chamber 713B. In some embodiments, for example, when the temperature of the first melt extrusion chamber 713A reaches the desired melt supply temperature value, the release switch module 717 selects to connect with the first melt extrusion chamber 713A and supplies material to the printing chamber 721 through the first melt extrusion chamber 713A; when the temperature of the second melt extrusion chamber 713B reaches the desired melt supply temperature value, the release switch module 717 selects to connect with the second melt extrusion chamber 713B and supplies material to the printing chamber 721 through the second melt extrusion chamber 713B. In some embodiments, for example, when the weight of the first melt extrusion chamber 713A reaches the desired melt supply weight value, the release switch module 717 selects to connect with the first melt extrusion chamber 713A and supplies material to the printing chamber 721 through the first melt extrusion chamber 713A; when the weight of the second melt extrusion chamber 713B reaches the desired melt supply weight value, the release switch module 717 selects to connect with the second melt extrusion chamber 713B and supplies material to the printing chamber 721 through the second melt extrusion chamber 713B.In other embodiments, for example, when the melt volume in the first melt extrusion chamber 713A reaches the desired melt supply volume, the release switch module 717 selects to connect with the first melt extrusion chamber 713A and supplies material to the printing chamber 721 through the first melt extrusion chamber 713A; when the melt volume in the second melt extrusion chamber 713B reaches the desired melt supply volume, the release switch module 717 selects to connect with the second melt extrusion chamber 713B and supplies material to the printing chamber 721 through the second melt extrusion chamber 713B. In some of the foregoing embodiments, before the release switch module 717 selects to connect with the first melt extrusion cavity 713A, it first disconnects from the second melt extrusion cavity 713B; before the release switch module 717 selects to connect with the second melt extrusion cavity 713B, it first disconnects from the first melt extrusion cavity 713A. That is, the first melt extrusion cavity 713A and the second melt extrusion cavity 713B are connected to the release switch module 717 in turn, and provide melt for the printing cavity 721.

[0265] In some embodiments, the release switch module 717 includes a valve and a release channel 723 communicating with the printing cavity 721. The valve is configured to rotate and / or move via a first drive device 7173 (e.g., a motor, actuator, etc.) to selectively connect one of the melt extrusion cavities to the release channel 723. The first drive device 7173 is configured to rotate and / or move according to preset parameters.

[0266] In some embodiments, as shown in FIG23A and FIG23B, the valve can be a switching valve, which can switch between two melt extrusion cavities 771A and 771B, so that one of the melt extrusion cavities 771A and 771B is connected to the printing cavity 721, or disconnects the connection between the melt extrusion cavities 771A and 771B and the printing cavity 721 while maintaining the high sealing requirements of the aforementioned melt extrusion cavities 771A and 771B. The switching valve includes a release channel, which includes an inlet channel 71741 and an outlet channel 71742 that are interconnected. That is, the inlet channel 71741 and the outlet channel 71742 constitute a connecting cavity 71714. The inlet channel 71741 can be selectively connected to one of the melt extrusion cavities 771A and 771B, and the outlet channel 71742 is connected to the printing cavity 721. In this way, the melt from the melt extrusion cavities 771A and 771B is released to the inlet channel 71741 and transported to the printing cavity 721 via the outlet channel 71742. In some embodiments, as shown in FIG23A and FIG23B, the valve body is cylindrical in shape, and an inlet channel 71741 is provided on the outer circumferential sidewall of the body. The first end of the body is provided with an outlet channel 71742 communicating with the printing cavity 721. The inlet channel 71741 and the outlet channel 71742 are interconnected and are roughly L-shaped. The channels are connected by an arc transition (not shown in the figure) to reduce the pressure loss of the melt flow. The valve body 7174 is fixedly connected to the second end of the driving device 71743 (such as plug-in, snap-fit, bolt connection, key connection, etc.). The valve body 7174 is driven to rotate around the axis of the body 7174 by the driving device 71743 (such as rotary cylinder, motor, actuator, etc.) so that the inlet channel 71741 on the sidewall of the valve body 7174 is selectively aligned and connected with one of the extrusion channels of the melt extrusion cavities 771A and 771B.

[0267] In some embodiments, as shown in Figures 23A and 23B in conjunction with Figures 24A and 24B, the rotational position of the valve body 7174 can be positioned by mechanical limiting. The valve also includes a valve seat 7175, which is provided with a valve seat inlet 71751 that is fully aligned and connected to the extrusion channels of all melt extrusion chambers 771A and 771B (Figure 23B only shows one inlet as an example). The valve seat inlet 71751 is provided in a one-to-one correspondence with the extrusion channels of the melt extrusion chambers 771A and 771B, and the mating point between the valve seat inlet 71751 and the extrusion channel can maintain good sealing. The inlet channel 71741 of the valve body 7174 can be selectively aligned and connected with the valve seat inlet 71751 to achieve selective communication between the inlet channel 71741 of the valve body 7174 and the extrusion channels of the melt extrusion chambers 771A and 771B. In some embodiments, referring to FIG24A (the figure is only schematic to illustrate the mechanical limiting structure), a rotating protrusion 71753 is provided on the outer circumferential side wall of the valve body 7174. Correspondingly, the valve seat 7175 is provided with a through hole to accommodate the valve body. The inner wall of the through hole is also provided with a plurality of rotating grooves 71752. The rotating protrusion 71753 can rotate back and forth in the rotating grooves 71752 to achieve mechanical limiting. Typically, the number of grooves 71752 is one greater than or equal to the number of the second state. For example, in an embodiment with two melt extrusion chambers 771A and 771B, three rotating grooves 71752 are provided. When the protrusion 71743 rotates clockwise (or counterclockwise) in the first rotating groove until it can no longer rotate, the valve body inlet channel 71741 is not connected to any of the extrusion channels. When the protrusion 71743 rotates clockwise (or counterclockwise) in the second rotating groove until it can no longer rotate, the valve body inlet channel 71741 is completely aligned and connected to the first extrusion channel 713C. When the protrusion 71743 rotates clockwise (or counterclockwise) in the third rotating groove until it can no longer rotate, the valve body inlet channel 71741 is completely aligned and connected to the second extrusion channel 713D. In other embodiments, referring to Figure 24A (the figure is only schematic to illustrate the mechanical limiting structure), a buckle 71744 is provided on the outer circumferential side wall of the valve body 7174. Correspondingly, the valve seat 7175 is designed with a through hole inside to accommodate the valve body 7174. The inner wall of the through hole is also provided with multiple slots 71754. When the valve body is inserted into the through hole of the valve seat 7175 for installation, the buckle 71744 aligns with the slot 71754 and snaps into the slot 71754 to achieve mechanical positioning.Typically, the number of slots 71754 is one greater than or equal to the number in the second state. In some preferred embodiments, the latches 71744 have a certain degree of flexibility and are made of materials with high fatigue strength, such as composite materials made of PA6, PA66, etc., combined with glass fiber, or metal materials such as high-strength steel, titanium alloy, and nickel-based alloy, allowing the latches 71744 to be repeatedly disassembled and engaged. The connection between the latch and the valve seat body can also be enhanced with rounded corners (not shown in the figure) and reinforcing ribs to increase fatigue strength.

[0268] In some embodiments, as shown in FIG25A, the release switch module 717 includes multiple on / off valves 71761 and 71762 and a release channel 71763. The on / off valves 71761 and 71762 are configured one-to-one with the melt extrusion cavities 771A and 771B, i.e., each melt extrusion cavity 771A and 771B is equipped with one on / off valve. Each on / off valve 71761 and 71762 is used to control the connection and disconnection between its corresponding melt extrusion cavity 771A and 771B and the printing cavity 721. In some embodiments, as shown in FIG25B, the on / off valves 71761 and 71762 are gate valves. The gate lever controls the gate plate to move back and forth or rise and fall in the direction of the arrow in the figure to control the flow of the melt, i.e., the movement of the gate plate controls the release or closure of the melt extrusion cavities 771A and 771B. In some embodiments, as shown in FIG25C, the on / off valves 71761 and 71762 employ plunger-type valve needles. The flow of the melt is controlled by the reciprocating movement of the plunger-type valve needles in the direction of the arrows shown in the figure. That is, the release or closure of the melt extrusion chambers 771A and 771B is controlled by the movement or lifting of the plunger-type valve needles. In some embodiments, as shown in FIG25D, the on / off valves 71761 and 71762 employ ball valves. The ball valves have a through hole in the center. The flow of the melt is controlled by the rotation of the ball valves (e.g., driven by a rotary cylinder). When the ball valves rotate so that the through hole is completely aligned and connected with the extrusion channels of the melt extrusion chambers 771A and 771B, the melt in the melt extrusion chambers 771A and 771B is released to the printing chamber 721. When the ball valves rotate so that the through hole is completely disconnected from the extrusion channels of the melt extrusion chambers 771A and 771B, the extrusion channels of the melt extrusion chambers 771A and 771B are closed. It should be understood that the present invention does not limit the specific on / off mode of the on / off valves 71761 and 71762, and those skilled in the art can also select on / off valves 71761 and 71762 with other structures according to actual needs.

[0269] In some embodiments, as shown in Figures 17A-17E, the first melt extrusion chamber 713A includes a first extrusion channel 713C, and the second melt extrusion chamber 713B includes a second extrusion channel 713D. The valve has a first state and a second state. As shown in Figures 17A and 17C, in the first state, the release channel is connected to either the first extrusion channel 713C or the second extrusion channel 713D. As shown in Figure 17B, in the second state, the release channel is disconnected from both the first extrusion channel 713C and the second extrusion channel 713D. In some embodiments, as shown in Figures 17A to 17C, the valve is configured such that any actuation by the first drive device 7173 (such as a motor or actuator) results in either the first state or the second state.

[0270] In some embodiments, as shown in Figures 17A-17E, the release switch module 717 includes a valve. In some embodiments, the valve includes a valve body and a valve core 7171. The valve body includes a first valve body channel 725 connected to a first extrusion channel 713C, a second valve body channel 726 connected to a second extrusion channel 713D, and the release channel. In some embodiments, the valve core 7171 includes a communicating cavity 71714, the communicating cavity 71714 including a first port 71714A and a second port 71714B, the first port 71714A and the second port 71714B having matching shapes and dimensions. In some embodiments, the first valve body channel 725 includes a third port 725A connected to the first extrusion channel 713C and a fourth port 725B connected to the communicating cavity 71714; the second valve body channel 726 includes a fifth port 726A connected to the second extrusion channel 713D and a sixth port 726B connected to the communicating cavity 71714; the fourth port 725B and the sixth port 726B are both matched in shape and size to the first port 71714A and the second port 71714B. In some embodiments, the projection angle formed by the central axis of the first port 71714A and the central axis of the second port 71714B is 120°. In some embodiments, the projection angle formed by the central axis of the third port 725A and the central axis of the fourth port 725B is 120°. In some embodiments, the projection angle formed by the central axis of the fifth port 726A and the central axis of the sixth port 726B is 120°. In some embodiments, the connecting cavity 71714 includes straight cavity segments 71714C and 71714D connected to the first port 71714A, a straight cavity segment 71714C connected to the second port 71714B, and an arc-shaped cavity segment 71714E located between the straight cavity segments 71714C and 71714D. The technical solutions in the foregoing embodiments, through matching the shapes and sizes of the various ports and / or setting the angles between the various ports and / or setting the cavity segments of the connecting cavity 71714, can minimize melt pressure loss when the melt sequentially passes through the first valve body channel 725 or the second valve body channel 726, the connecting cavity 71714, and the release channel 723 to the printing cavity 721, ensuring that the melt pressure remains at a constant desired pressure value. In some embodiments, the aforementioned constant desired pressure value is 3 MPa to 50 MPa.

[0271] In some embodiments, the cross-sectional shape and area of ​​the first extrusion channel 713C and the second extrusion channel 713D are the same as the cross-sectional shape and area of ​​the release channel. Thus, when the melt moves from the first extrusion channel 713C or the second extrusion channel 713D to the release channel of the release switch module 717, the melt pressure loss is minimized because the flow channel diameter remains unchanged, ensuring that the melt pressure remains at a constant desired pressure value. It should be understood that the aforementioned identical cross-sectional area is not limited to a specific cross-sectional shape; for example, the cross-sectional shape can be any shape such as circular, square, elliptical, triangular, or isosceles trapezoid. In some preferred embodiments, the aforementioned channel cross-sectional shape is hexagonal, which can reduce pressure loss and melt residence time distribution (RTD). In some embodiments, the aforementioned constant desired pressure value is 3 MPa to 40 MPa.

[0272] In some embodiments, as shown in Figures 16A-16D, the valve includes a valve core 7171 and a rotating shaft 7172. The valve core 7171 has a communicating cavity 71714; the rotating shaft 7172 is configured to be driven to rotate by a first driving device 7173; one end of the rotating shaft 7172 is connected to the output shaft of the first driving device 7173, and the other end is connected to the valve core 7171. In some embodiments, the valve core 7171 is generally cylindrical, and a first port 71714A of the communicating cavity 71714 is provided on the outer circumferential wall of one end of the valve core 7171. The melt is selectively extruded from one of the two melt extrusion cavities into the communicating cavity 71714 through the aforementioned first port 71714A, and then released to the printing cavity 721 through the outlet 71714B of the communicating cavity 71714. In some embodiments, when the rotating shaft 7172 and the valve core 7171 are installed together, as shown in Figures 16B and 16C, the rotating shaft 7172 is generally cylindrical, and its end (the part where it is mounted and connected to the valve core 7171) is provided with a U-shaped inner hole. The valve core 7171 is generally cylindrical, and one end 71713 of the valve core 7171 (the part where it is mounted and connected to the rotating shaft 7172) is correspondingly U-shaped, and the U-shaped end 71713 of the valve core 7171 is inserted into the U-shaped inner hole of the rotating shaft 7172.

[0273] In some embodiments of the present invention, as shown in FIG16A, the valve further includes a position compensation device configured to compensate for the gap between the valve core 7171 and the rotating shaft 7172.

[0274] In some embodiments, as shown in FIG16A, the position compensation device includes a relative reference position positioning unit and an absolute position measuring unit. The relative reference position positioning unit is configured to determine the position of the rotating shaft 7172 in a second state, and the absolute position measuring unit is configured to determine the position of the rotating shaft 7172 in a first state.

[0275] In some embodiments, as shown in FIG16A, the relative reference position positioning unit includes a light blocking plate disposed on the rotating shaft 7172 and a photoelectric sensor 718 disposed on the valve, which is configured to cut off the optical path between the transmitting end and the receiving end of the photoelectric sensor 718 when the valve rotates to the position corresponding to the photoelectric sensor 718.

[0276] In some embodiments, as shown in FIG16A in conjunction with FIG17A to 17E, the rotating shaft 7172 is rotatable along a first direction and / or a second direction, the first direction and the second direction being opposite. The first direction can be clockwise or counterclockwise. If the first direction is clockwise, the second direction is counterclockwise, and vice versa.

[0277] In some embodiments, when the valve is in the first state, the valve is in either the first or second state after the rotating shaft 7172 rotates once in either the first or second direction; and when the valve is in the second state, the valve is in the first state after the rotating shaft 7172 rotates once in either the first or second direction. As shown in Figures 17A to 17C, when the valve is in the first state, regardless of whether the rotating shaft 7172 rotates clockwise or counterclockwise, the valve is either in the first state or the second state. When the valve is in the second state, regardless of whether the rotating shaft 7172 rotates clockwise or counterclockwise, the valve can only be in the first state.

[0278] In some preferred embodiments, as shown in Figures 16A and 16D in conjunction with Figures 17A-17C, the valve has a first state (e.g., point A - the release channel is connected to the first extrusion channel 713C, point B - the release channel is connected to the second extrusion channel 713D) and a second state (e.g., point O - the release channel is connected to the first extrusion channel 713C and the second extrusion channel 713D is disconnected). In the first state, the first port 71714A of the valve core 7171 is aligned and connected to either the first extrusion channel 713C or the second extrusion channel 713D, allowing the melt in the connected melt extrusion chamber to be released to the printing chamber 721 through the second port 71714B. In the second state, the first port 71714A of the valve core 7171 is disconnected from both the first extrusion channel 713C and the second extrusion channel 713D. When the first port 71714A is disconnected from the first extrusion channel 713C or the second extrusion channel 713D, the melt from all melt extrusion cavities 713A and 713B is not supplied to the printing cavity 721 of the printing unit 720. The rotating shaft 7172 is configured to rotate, based on its position in the second state, the absolute value of the angle between its position in the first state and its position in the second state back to its position in the first state. In some embodiments, as shown in FIG16A and FIG16D, the position of the rotating shaft 7172 in the first state includes a first sub-position and a second sub-position. When the rotating shaft 7172 is in the first sub-position, the communicating cavity 71714 of the valve core 7171 is connected to the first valve body channel 725; when the rotating shaft 7172 is in the second sub-position, the communicating cavity 71714 of the valve core 7171 is connected to the second valve body channel 726. In some embodiments, the position of the rotating shaft 7172 in the second state is an angular position region located between adjacent first and second sub-positions. For example, as shown in FIG16D, the position of the rotating shaft 7172 in the first state has two sub-positions—first sub-position A and second sub-position B. First sub-position A and second sub-position B correspond to the first valve body channel 725 and the second valve body channel 726, respectively. The angular position region between points A and B is the position of the rotating shaft 7172 in the second state. Thus, compared to the prior art, the position of the rotating shaft 7172 in the second state is a relative reference position. In some embodiments, the angle range of the angular position region is less than or equal to 180°. In some embodiments, the release switch module 717 further includes a valve control device for controlling the rotation of the rotating shaft 7172, so that the first port 71714A of the valve core 7171 is fully aligned with and connected to the first valve body channel 725 or the second valve body channel 726. In some embodiments, the valve control device is electrically connected to the first drive device 7173 (e.g., a motor, actuator, rotary cylinder, etc.) and the position compensation device.In some embodiments, as shown in FIG16D, the relative reference position positioning unit of the position compensation device includes a photoelectric sensor 718 mounted on the valve base 724 and a light-blocking plate 719 mounted on the rotating shaft 7172. The relative reference position positioning unit is configured to determine the position (0 point) of the rotating shaft 7172 in its second state based on the fact that when the valve rotates so that the light-blocking plate 719 moves to the position corresponding to the photoelectric sensor 718, the light-blocking plate 719 cuts off the optical path between the transmitting end and the receiving end of the photoelectric sensor 718, and the optical path between the transmitting end and the receiving end of the photoelectric sensor 718 is cut off. The aforementioned rotation includes initial rotation and load rotation. During the initial rotation, as shown in FIG16B, 16C and 16D, the mating surfaces of the rotating shaft 7172 and the valve core 7171 are not completely mated, and the rotating shaft 7172 rotates clockwise by α degrees on its own. At this time, the rotating shaft 7172 abuts against the valve core 7171, and the gap compensation is completed. The aforementioned clockwise rotation is not limited in this embodiment, and clockwise or counterclockwise rotation is set according to the actual application scenario. When the load rotates, the rotating shaft 7172 abuts against the valve core 7171, and the rotating shaft 7172 rotates synchronously with the valve core 7171. That is, when the rotating shaft 7172 rotates by β degrees (β = m + n), the valve core 7171 also rotates synchronously by β degrees (β = m + n). In some embodiments, the rotating shaft 7172 has a first end and a second end. The first end has an inner cavity, and the second end is fixedly connected to the output end of the first driving device 7173. Thus, the first driving device 7173 drives the second end of the rotating shaft 7172 to rotate, and the first end of the rotating shaft 7172 rotates synchronously with the second end of the rotating shaft 7172. When it is necessary to align and connect the first port 71714A with the first extrusion channel 713C or the second extrusion channel 713D, the rotating shaft 7172 first rotates initially to compensate for the gap. Then, the rotating shaft 7172 drives the valve core 7171 to continue rotating synchronously. When the optical path between the transmitter and receiver of the photoelectric sensor 718 is cut off, it indicates that the rotating shaft 7172 and the valve core 7171 are synchronously in the second state (point 0). At this time, the first port 71714A is disconnected from both the first extrusion channel 713C and the second extrusion channel 713D. Then, the rotating shaft 7172 drives the valve core 7171 to continue rotating synchronously to the position of the rotating shaft 7172 in the first state (point A or point B), thereby achieving complete alignment between the first port 71714A and the first extrusion channel 713C or the second extrusion channel 713D.The aforementioned rotating shaft 7172 in the second state (point O) is the reference position of the valve. In other words, this reference position is a relative reference position that can be dynamically adjusted. It does not require high precision in installation. Compared with the fixed position of the prior art, it can effectively avoid installation errors and ensure that the first port 71714A is completely aligned with the first extrusion channel 713C or the second extrusion channel 713D. Furthermore, the rotating shaft 7172 performs an initial rotation to compensate for the installation gap between itself and the valve core 7171, and then drives the valve core 7171 to rotate synchronously to ensure that the first port 71714A is completely aligned and connected with the first extrusion channel 713C or the second extrusion channel 713D.

[0279] In some embodiments, the valve further includes a valve body, which includes a first valve body channel 725 connected to the first extrusion channel 713C, a second valve body channel 726 connected to the second extrusion channel 713D, and the release channel. The first valve body communication channel, the second valve body communication channel, and the release channel are all normally open. The third port 725A of the first valve body communication channel is connected to the first extrusion channel 713C, and the fifth port 726A of the second valve body communication channel is connected to the second extrusion channel 713D. The valve core 7171 is provided with the communication cavity 71714. The first port 71714A of the valve core 7171 is aligned and connected to the first extrusion channel 713C or the second extrusion channel 713D by aligning and connecting with the fourth port 725B of the first valve body communication channel or the sixth port 726B of the second valve body communication channel. The second port 71714B of the valve core 7171 is connected to the printing cavity 721 by connecting with the release channel. In some embodiments, the first drive device 7173 (e.g., a motor, actuator, rotary cylinder, etc.) in some embodiments includes an absolute position measuring unit comprising an angle measuring device (e.g., a motor encoder) for measuring the rotation angle of the valve, and can also be used to measure the angle value of the position of the shaft 7172 in the first state relative to the position of the shaft 7172 in the second state.

[0280] The following detailed explanation uses a three-way valve as an example: After the three-way valve is installed, 1) firstly, the photoelectric sensor 718 of the valve position compensation device is installed. Similarly, the light blocking plate 719 of the position compensation device is installed in the corresponding area on the rotating shaft 7172. When the rotating shaft 7172 rotates so that the light blocking plate 719 is at the position corresponding to the photoelectric sensor 718, the light path between the transmitting end and the receiving end of the photoelectric sensor 718 is cut off by the light blocking plate 719. The position (0 point) of the rotating shaft 7172 in its second state is determined by the cutting off of the light path between the transmitting end and the receiving end of the photoelectric sensor 718. 2) Obtain the absolute values ​​of the angle differences, m degrees and n degrees, between the first sub-position A (the position of the shaft 7172 in the first state) and the second sub-position B (the position of the shaft 7172 in the first state) and the relative reference position O (the position of the shaft 7172 in the second state) relative to the reference position O, respectively, by means of the rotation angle of the shaft 7172 (such as the motor encoder). The m degrees and n degrees obtained by the angle measuring device (such as the motor encoder) have high accuracy (the angle deviation of the motor encoder can usually reach less than 0.1 degrees). The workflow of the release switch module 717 in this embodiment is as follows: 1) The rotating shaft 7172 rotates from point A along the first direction, and then drives the valve core 7171 to rotate synchronously to the relative reference point O (judged by the photoelectric sensor 718). At this time, the valve core 7171 and the rotating shaft 7172 reach the relative reference point O synchronously. This process includes automatic compensation of the installation gap α degree, and the specific value of α degree does not need to be measured; 2) The rotating shaft 7172 continues to drive the valve core 7171 to rotate synchronously along the first direction by n degrees (e.g., the rotating shaft 7172 is rotated by n degrees by controlling the rotating shaft 7172 to rotate by n degrees through the motor encoder) to point B. At this time, the first port 71714A of the valve core 7171 is completely aligned and connected with the sixth port 726B of the second valve body communication channel. 3) The rotating shaft 7172 rotates from point B along the second direction, and then drives the valve core 7171 to rotate synchronously to the relative reference point O (judged by photoelectric sensor 718). At this time, the valve core 7171 and the rotating shaft 7172 reach the relative reference point O synchronously. This process includes automatic compensation of the installation gap α degree, and the specific value of α degree does not need to be measured; 4) The rotating shaft 7172 continues to drive the valve core 7171 to rotate synchronously along the second direction by m degrees (e.g., the rotating shaft 7172 is rotated by m degrees by motor coding) to point A. At this time, the first port 71714A of the valve core 7171 is completely aligned with the fourth port 725B of the first valve body connecting channel, ensuring that the two channels are connected smoothly.Thus, in this embodiment, by setting a relative reference position 0 (dynamically variable) and first rotating to the relative reference position 0 before rotating the absolute value of the relative angle, it is not required that the photoelectric sensor 718 be precisely installed at a desired fixed reference position. Furthermore, the gap α degree is automatically compensated during the rotation of the valve core 7171 to the relative reference position 0, and there is no need to precisely measure the specific angle of the gap. In addition, by using an angle measuring device to accurately measure the absolute value of the relative angle between points A and O, and between points B and O, the absolute value of the relative angle of the valve core 7171's rotation is accurate. This ensures that the first port 71714A of the valve core 7171 is completely aligned with the fourth port 725B of the first valve body connecting channel or the sixth port 726B of the second valve body connecting channel, allowing the cross-section 53 through which the melt flows (the cross-sections 51 and 52 of the two channels shown in Figure 22B are completely overlapping) to be equal to the desired maximum cross-section, ensuring smooth connection between the two channels. In some embodiments, the rotating shaft 7172 and the valve core 7171 are connected via a cross coupling. The cross coupling has a certain degree of flexibility, allowing the valve core 7171 to actively deform (oscillate) during rotation to resist friction with the valve body and prevent wear on the outer circumference of the valve core 7171. In some embodiments, the first sub-position A and the second sub-position B are symmetrically or asymmetrically arranged with respect to the second state O. In some embodiments, angles m and n are equal or unequal. In some preferred embodiments, the rotating shaft 7172 is positioned at the midpoint between the first sub-position A and the second sub-position B at the second state O. In some embodiments, both angles m and n are 60°.

[0281] In some embodiments, as shown in FIG12, the melt extrusion module includes a first melt extrusion chamber 2071A and a second melt extrusion chamber 2071B, a first melt extrusion chamber discharge control device 2075A, and a second melt extrusion chamber discharge control device 2075B. The melt extrusion module is configured to alternately release the melt in the first melt extrusion chamber and the melt in the second melt extrusion chamber to the printing chamber, and / or the melt extrusion module is configured to alternately receive the printing material in the first melt extrusion chamber and the second melt extrusion chamber. In some embodiments, the second melt extrusion chamber is configured to receive the printing material and / or form a melt from the printing material and / or maintain the melt in a molten state when the melt in the first melt extrusion chamber is released to the printing chamber, and the melt extrusion module is configured to receive the printing material and / or form a melt from the printing material and / or maintain the melt in a molten state when the melt in the second melt extrusion chamber is released to the printing chamber. Thus, the first or second melt extrusion chamber supplies melt to the printing unit 2003, while the second or first melt extrusion chamber, which is not currently being fed, simultaneously prepares for melt extrusion, enabling efficient continuous printing of pharmaceutical products. In some embodiments, by discharging melt via different melt extrusion chambers and allowing continuous melt supply for printing, the melt extrusion module 2007 advantageously maintains the desired properties of the printing material during the printing process (e.g., preventing the printing material from aging during printing and reducing residence time distribution (RTD)). By allowing continuous melt supply for printing, pharmaceutical products can be printed continuously (e.g., compared to a single melt extrusion chamber embodiment, where printing can only be paused while printing material is being received in the melt extrusion chamber, pending preparation such as melting and / or pressurizing the received material in the single melt extrusion chamber). Printing can only be restarted after the process is completed. Furthermore, when continuously producing large batches of pharmaceutical products, the volume of a single melt extrusion chamber is set much larger than that of multiple single melt extrusion chambers to meet the needs of large-scale production. The larger the melt volume, the longer the heating or holding time required. The risk of degradation and denaturation of the pharmaceutical printing material significantly increases as the melt remains in the single melt extrusion chamber for an extended period. Additionally, the melt at the end of the single melt extrusion chamber furthest from the printing module remains in the single melt extrusion chamber for even longer, further increasing the risk of degradation and denaturation of the pharmaceutical printing material.

[0282] In some embodiments, the release channel 2035 is provided with a pressure sensor 2076, which is used to detect the melt pressure value within the release channel 2035. In some embodiments, the expected value of the aforementioned pressure is 3 MPa to 50 MPa. In some embodiments, the expected value of the aforementioned pressure is 6 MPa. In some embodiments, the expected value of the aforementioned pressure is 12 MPa. In some embodiments, the expected value of the aforementioned pressure is 25 MPa. In some embodiments, the difference between the melt pressure and the expected pressure does not exceed 0.5 MPa. In some embodiments, the difference between the melt pressure and the expected pressure does not exceed 1 MPa. In some embodiments, the difference between the melt pressure and the expected pressure does not exceed 2 MPa. In some embodiments, the difference between the melt pressure and the expected pressure does not exceed 3 MPa. Different printing materials and different printing process parameters result in different expected pressure values ​​and different acceptable pressure deviation ranges. When the detected pressure value exceeds or falls below the expected pressure value by a certain deviation range (e.g., exceeding or falling below the expected pressure value by 3 MPa), the melt pressure is either too high or too low. This pressure instability can lead to an increase or decrease in the amount of melt subsequently distributed to the printing unit, or an intermittent melt flow, further affecting the accuracy of the final printed drug product and the consistency between multiple drug products. In some embodiments, when the detected melt pressure value in the release channel 2035 exceeds or falls below the expected pressure value, the melt pressure value in the release channel 2035 can be adjusted by regulating the melt pressure value in the first melt extrusion chamber and / or the pressure value in the second melt extrusion chamber. This can be achieved by increasing or decreasing parameters such as the holding pressure and holding time of the first and / or second melt extrusion chambers.

[0283] In some embodiments, the release times of the first melt extrusion chamber 2071A and the second melt extrusion chamber 2071B may be the same or different. For example, when the preset parameter is the length of time the printing material is processed in the first melt extrusion chamber 2071A and the second melt extrusion chamber 2071B, then the release times of the first melt extrusion chamber 2071A and the second melt extrusion chamber 2071B are the same. When the preset parameter is the melt pressure value in the first melt extrusion chamber 2071A and the second melt extrusion chamber 2071B, then the material is released after the melt pressure value in the corresponding melt extrusion chamber reaches the target pressure value, and the release times of the first melt extrusion chamber 2071A and the second melt extrusion chamber 2071B are different.

[0284] In some embodiments, as shown in FIG12, the melt extrusion module is configured to release the melt from the first melt extrusion chamber and the second melt extrusion chamber with the same or different extrusion parameters (such as extrusion rate, extrusion flow rate, volume, etc.). For example, when the first melt extrusion chamber and the second melt extrusion chamber alternately provide the same melt to the printing unit, they are usually released with the same extrusion parameters (such as extrusion rate, extrusion flow rate, volume, etc.). As another example, after the first melt extrusion chamber finishes printing (such as after printing the first part of the drug product), the second melt extrusion chamber changes the printing material (receives a different printing material) and provides a different melt to the printing unit to print the second part of the drug product. Usually, due to the difference in the melt, it is released with different extrusion parameters (such as extrusion rate, extrusion flow rate, volume, etc.) from the first melt extrusion chamber and the second melt extrusion chamber. In some embodiments, the first melt extrusion chamber discharge control device 2075A is configured to control the discharge speed of the melt in the first melt extrusion chamber 2071A, and the second melt extrusion chamber discharge control device 2075B is configured to control the discharge speed of the melt in the first melt extrusion chamber 2071B. The melt extrusion chamber discharge control devices 2075A and 2075B may be a single screw or plunger, or a combination of a single screw or plunger, located near the release switch module 2073, or a flow control valve located at the release switch module 2073, such as a pneumatic flow control valve, an electromagnetic flow control valve, or a hydraulic flow control valve.

[0285] In some embodiments, as shown in FIG12, the first melt extrusion chamber discharge control device 2075A and the first melt extrusion chamber discharge control device 2075B shown in FIG12 can employ a plunger structure. The supply unit further includes a filler module for receiving printing material used to generate the pharmaceutical product and a plunger corresponding to each of the melt extrusion chambers. The plunger is configured to: reduce the internal volume of the melt extrusion chamber to discharge printing material from the melt extrusion chamber into the printing chamber when the release switch module connects one of the melt extrusion chambers to the printing chamber; and increase the internal volume of the melt extrusion chamber to receive the printing material from the filler module into the melt extrusion chamber when the release switch module disconnects the melt extrusion chamber from the printing chamber. In some embodiments, the preset parameter is the stroke of the plunger; when the stroke of the plunger connected to the first melt extrusion chamber or the second melt extrusion chamber reaches a target value, the release switch unit selects to connect to the first melt extrusion chamber or the second melt extrusion chamber.

[0286] In some embodiments, the melt extrusion chamber screw control device is configured to maintain the desired properties of the printing material (e.g., through extrusion) to ensure the quality of the pharmaceutical ingredients. Additionally, in some embodiments, the melt extrusion chamber control device advantageously controls the flow of printing material (e.g., upon receipt and upon discharge) to ensure accurate, stable, and rapid delivery of the printing unit 720, thereby optimizing the precision and high throughput of the pharmaceutical product. Furthermore, the melt extrusion module 711 ensures that the printing material is in a first-in, first-out (FIFO) manner (e.g., earlier received printing material is released earlier in subsequent release steps), thereby optimizing the effectiveness of the printing material (e.g., the effectiveness of the pharmaceutical ingredients in the pharmaceutical product). Moreover, by allowing the printing material to be in a FIFO manner, aging and undesirable build-up within the melt extrusion chamber can be avoided (compared to FIFO devices).

[0287] In some embodiments, the supply unit further includes a plunger corresponding to each of the melt extrusion cavities, the plunger being configured to: retract from the end of the melt extrusion cavity near the release switch module when receiving printing material; and advance toward the end of the melt extrusion cavity near the release switch module when discharging the printing material.

[0288] In some embodiments, as shown in FIG. 12, the melt extrusion module 2007 further includes a temperature control device 2023 installed in each of the said melt extrusion chambers or these melt extrusion chambers. In some embodiments, the melt extrusion module 2007 includes a melt extrusion chamber that may require heating or insulation to ensure that the stored melt is always in a molten form (e.g., to ensure the quality of the pharmaceutical components of a pharmaceutical product). In some embodiments, the melt extrusion module 2007 includes a heating plate installed in the melt extrusion chamber for heating the melt or maintaining the melt at a certain temperature to keep the melt in a molten form.

[0289] In some embodiments, the printing material is a preceding product.

[0290] In some embodiments, as shown in Figures 26A and 26B, the printing material is a preceding product unit 735, which includes multiple preceding products 734 of identical weight and composition. In some embodiments, as shown in Figure 12 in conjunction with Figures 26A and 26C, the preceding product unit 735 is prepared by a preceding product forming module 712, which includes a feed inlet and a screw extrusion device. The screw extrusion device is used to mix at least two raw materials to form a preceding melt and discharge the preceding melt through an outlet into a corresponding tube 733. Specifically, as shown in Figure 19 in conjunction with Figure 12, the additive manufacturing system further includes a preceding product forming module 712. The preceding product forming module 712 includes a feeding module 7121, a preceding product melt forming device 7124, and an outlet 7123. The feeding module 7121 receives raw materials for the pharmaceutical product 900, the preceding product melt forming device 7124 forms a preceding product melt from the raw materials and discharges the preceding product melt, and the outlet 7123 dispenses the preceding product melt and forms an integrated solid printing material outlet 7123. In some embodiments, the feeding module 7121 is configured to supply the raw materials to the preceding product melt forming device 7124 in a preset ratio, such as when one of the raw materials is a pharmaceutical active ingredient, thus allowing control of the pharmaceutical active ingredient to the desired ratio from the source. In some embodiments, the preceding product melt forming device 7124 is a screw extruder. In some embodiments, the preceding product melt molding apparatus 7124 includes a twin-screw extruder 7122, which is used to mix at least two raw materials to form a preceding product melt and discharge the preceding product melt through the outlet 7123 into a corresponding pipe 733 to form an integrally molded solid printing material. Thus, the twin-screw extruder has the function of mixing two raw materials and generating a preceding product melt and completing extrusion molding. Compared with other molding devices (such as piston injection extruders), it saves a mixing process and reduces production time and cost; compared with single-screw extruders, it has better mixing effect and higher efficiency.

[0291] In some embodiments, as shown in FIG26A, the tube 733 includes a cylindrical cavity structure and bosses 7331 located at both ends of the cylindrical cavity structure. This facilitates clamping during subsequent transport of the tube 733 and demolding during the preparation of preceding products.

[0292] In other embodiments, as shown in Figures 26C and 26D, the tube 733 includes a cylindrical cavity structure and an arc-shaped recess 7332 located in the middle of the cylindrical cavity structure. In some embodiments, the number of arc-shaped recesses 7332 is multiple (e.g., 4, 6, 3, etc.), evenly distributed along the cylindrical cavity structure, which facilitates the clamping of the tube 733 from various directions during subsequent transport of the tube 733.

[0293] In some embodiments, as shown in FIG19, the preceding product forming module 712 further includes a first air pressure control module 7125; the preceding product melt forming apparatus 7124 has a preceding product melt forming cavity, and the first air pressure control module 7125 is connected to the preceding product melt forming cavity for controlling the air pressure of the preceding product melt forming cavity to a first air pressure preset value, which is between -60 kPa and -100 kPa. In some embodiments, the preceding product forming module 712 further includes a negative pressure control device, which is configured to remove air from the preceding product melt forming cavity so that the air pressure of the preceding product melt forming cavity reaches the first air pressure preset value. Of course, those skilled in the art can set different first air pressure preset values ​​according to raw materials with different performance parameters. Preparing the preceding product under negative pressure can eliminate gases generated during the mixing or melting of at least two raw materials, ensuring the quality of the final printed drug product from the source. In some embodiments, the first air pressure control module 7125 is provided with an exhaust port to achieve air pressure control by automatically venting gas from the twin-screw extruder 7122.

[0294] In some embodiments, as shown in FIG20, the supply unit 710 further includes an air pressure control submodule 716 disposed at different locations within the unit, for controlling the air pressure at different locations within the unit to corresponding preset air pressure values. In some embodiments, the preset air pressure value is between -65 kPa and -100 kPa.

[0295] As shown in Figure 12, in some embodiments, system 20 may further include a delivery module 2001, wherein the delivery module 2001 has a hopper 2011 configured to receive and deliver initial material, the hopper 2011 having an inlet 2012 and an outlet 2013. During the printing process of 3D printing system 20, delivery module 2001 receives initial material through inlet 2012 of hopper 2011 and discharges initial material outside of preceding product melting and forming apparatus 2002 through outlet 2013. The initial material used for 3D printing system 20 may be a powder or granular material. As shown in Figure 12, hopper 2011 is a funnel-shaped shell with a flared opening. In some embodiments, the initial material may alternatively be filamentous, blocky, or another shape; and correspondingly, the hopper may have a corresponding shape to accommodate the shape of the initial material. In addition, a hopper discharge control device 2014 is disposed in hopper 2011. The hopper discharge control device 2014 controls the discharge rate of the initial material at the discharge port 2013 of the hopper 2011. The hopper discharge control device 2014 shown in Figure 12 is positioned near the discharge port and connected to a motor and gear mechanism (not shown in Figure 12), which drive the hopper discharge control device 2014 to move. The rotational speed of the screw of the hopper discharge control device 2014 is adjusted by a drive mechanism to control the discharge rate of the initial material at the discharge port 2013. Additionally, the mixing and delivery method of the material can be controlled by the pitch and thread of the screw portion on which the screw is mounted. Although the hopper discharge control device 2014 shown in Figure 12 is a single screw, in some embodiments, the hopper discharge control device may alternatively be a twin screw 2027, or a combination of a twin screw and a single screw. In some embodiments, the hopper discharge control device 2014 may further include a common mechanism capable of controlling the discharge rate of the initial material at the discharge port 2013. In some embodiments, the hopper discharge control device further includes a baffle or barrier disposed at the discharge port 2013 for controlling whether material is discharged from the discharge port 2013. In some embodiments, the hopper discharge control device 2014 may alternatively be a flow control valve disposed at the discharge port 2013, such as a pneumatic flow control valve, an electromagnetic flow control valve, or a hydraulic flow control valve, for controlling the discharge rate of the initial material at the discharge port 2013 by means of the size of the flow control valve.

[0296] System 20 may further include a second delivery module 2081. As shown in the figure, the structure of the second delivery module 2081 is the same as or similar to that of the delivery module 2001. The second delivery module 2081 also includes a second hopper 2091 having an inlet 2092 and an outlet 2093, and also includes a hopper discharge control device 2094 disposed in the hopper 2091, wherein the hopper discharge control device 2094 is configured to control the discharge speed of the initial material at the outlet 2092. During a specific printing process of the apparatus, the second delivery module 2081 may receive a second initial material through the inlet 2092 of the hopper 2091, the second initial material being different from the initial material received by the delivery module 2001; and discharge the second initial material through the outlet 2093 to the preceding product melt-forming apparatus 2002. It is understood that the ratio of the initial material to the second initial material received by the preceding product melt-forming apparatus 2002 can be controlled by controlling the hopper discharge control device 2014 of the delivery module 2001 and the hopper discharge control device 2094 of the second delivery module 2081, so as to ultimately control the ratio of the initial material to the second initial material in the drug product to be printed, ensuring the accurate amount of printing material components delivered to the preceding product melt-forming apparatus 2002 for mixing and melting. In some embodiments, the hopper discharge control device 2014 and the hopper discharge control device 2094 are controlled based on the composition of the drug product components according to a program and / or preset parameters.

[0297] In some embodiments, referring to FIG12, the supply unit further includes a filler module 2072 configured to selectively receive integrally formed solid printing material prepared by a preceding product forming module. For example, as shown in FIG12, the filler module 2072 selectively provides preceding product printing material 2025 to a second melt extrusion chamber 2071B. For example, the preceding product printing material is filled into the filler module 2072 via a robotic arm, and then the filler module 2072 conveys the preceding product printing material 2025 to the second melt extrusion chamber 2071B. At a second time, the filler module 2072 provides preceding product printing material 2025 to a first melt extrusion chamber 2071A. For example, the preceding product printing material is filled into the filler module 2072 via a robotic arm, and then the filler module 2072 conveys the preceding product printing material 2025 to the first melt extrusion chamber 2071A. In some embodiments, the filler module 2072 has a filler cavity that can selectively supply preceding product printing material 2025 to one of at least two melt extrusion cavities. In other embodiments, the filler module 2072 has at least two filler cavities, the number of which is equal to the number of melt extrusion cavities, and the filler cavities are configured in a one-to-one correspondence with the melt extrusion cavities. For example, if the filler module 2072 selects to supply preceding product printing material 2025 to the first melt extrusion cavity 2071A, then the first filler cavity of the filler module 2072 receives and fills with the preceding product printing material 2025, and then the preceding product printing material 2025 moves from the first filler cavity to the first melt extrusion cavity 2071A.

[0298] In some embodiments, the supply unit further includes a filling module for receiving printing material used to generate the pharmaceutical product; the filling module further includes a filling cavity and a filling channel for receiving the printing material used to generate the pharmaceutical product. In some embodiments, the filling cavity is configured such that the filling channel is open when receiving printing material, and the filling channel is closed after the filling cavity has finished receiving printing material. In some embodiments, the filling cavity includes a first filling cavity and a second filling cavity, the first filling cavity communicating with a first melt extrusion cavity, and the second filling cavity communicating with a second melt extrusion cavity. When it is necessary to provide the preceding product printing material 2025 to the first melt extrusion chamber 2071A, the first filling chamber receives the preceding product printing material 2025 and fills it in, and then the preceding product printing material 2025 moves from the first filling chamber to the first melt extrusion chamber 2071A; when it is necessary to provide the preceding product printing material 2025 to the second melt extrusion chamber 2071B, the second filling chamber receives the preceding product printing material 2025 and fills it in, and then the preceding product printing material 2025 moves from the second filling chamber to the second melt extrusion chamber 2071B.

[0299] In some embodiments, the release switch module 2073 is configured to select a melt extrusion chamber from which melt is discharged. For example, as shown in FIG12, the release switch module 2073 selects a first melt extrusion chamber 2071A to discharge the melt in the first melt extrusion chamber 2071A (e.g., by connecting the extrusion channel of the first melt extrusion chamber 2071A to the release channel 2035). At a second time, the release switch module 2073 may select a second melt extrusion chamber 2071B to discharge the melt in the second melt extrusion chamber 2071B (e.g., by connecting the extrusion channel of the first melt extrusion chamber 2071B to the release channel 2035).

[0300] In some embodiments, the filler module 2072 allows the melt to be received by different melt extrusion cavities at different times, and the release switch module 2073 allows the melt to be discharged via different melt extrusion cavities at different times. This allows the melt extrusion module 2070 to maintain the desired properties of the printing material during the printing process (e.g., preventing the printing material from aging during printing) and ensures high quality of the pharmaceutical product. For example, at a first time, the filler module 2072 fills into the second melt extrusion cavity 2071B (and disconnects from the first melt extrusion cavity 2071A) to receive the printing material (integrated solid material, melt) in the second melt extrusion cavity 2071B. At a first time, the release switch module 2073 connects the extrusion channel of the first melt extrusion cavity 2071A to the release channel 2035 to discharge the melt from the first melt extrusion cavity 2071A to the release channel 2035 for printing. At the second time, the filler module 2072 fills the first melt extrusion chamber 2071A (and disconnects from the second melt extrusion chamber 2071B) to receive printing material (integrated solid material, melt) in the first melt extrusion chamber 2071A. At the second time, the release switch module 2073 connects the extrusion channel of the second melt extrusion chamber 2071B to the release channel 2035 to discharge the melt from the second melt extrusion chamber 2071B to the release channel 2035 for printing. The operations of the filler module 2072 and the release switch module 2073 at the first and second times can be repeated until the corresponding printing step is completed. In some embodiments, the filler module 2072 and the release switch module 2073 operate in conjunction with each other.

[0301] In some embodiments, the melt extrusion module 2007 is positioned horizontally or vertically as shown in FIG12.

[0302] It should be understood that, in some embodiments, as shown in FIG12, the additive manufacturing system further includes a preceding product forming module 2026, which includes a feeding module, a preceding product melt forming device, and an outlet. The feeding module is used to receive raw materials for the pharmaceutical product and to convey the raw materials to the preceding product melt forming device through its outlet 2024. The preceding product melt forming device is used to form a preceding product melt from the raw materials and to discharge the preceding product melt through the outlet.

[0303] Although the 3D printing system 20 describes two melt extrusion chambers, the 3D printing apparatus may include more than two melt extrusion chambers (each melt extrusion chamber may include one or more plungers or screws for controlling the corresponding material discharge from the melt extrusion chamber). For example, the 3D printing apparatus includes more than two melt extrusion chambers. At a first time, a first melt extrusion chamber can be selected for receiving the melt, and a second set of melt extrusion chambers, different from the first, can be selected for discharging the melt. At a second time, a second melt extrusion chamber can be selected for receiving the melt, and a first melt extrusion chamber can be selected for discharging the melt.

[0304] In some embodiments, the supply unit is configured to pre-treat the melt released through the release channel of the release switch module before it is conveyed to the diversion module. In some embodiments, pre-treatment includes mixing, heating, and / or pressurizing (e.g., heating to a target temperature range, pressurizing to a target pressure range) the printing material according to predetermined settings to convert the printing material into a melt (e.g., in a molten / semi-solid state). In some embodiments, the molten printing material (melt) may be stored in a melt extrusion module before being conveyed to the diversion module. The molten printing material (melt) may be conveyed to the diversion module via the release channel. In some embodiments, a continuous flow of molten printing material is supplied to the diversion module via the release channel. In some embodiments, the pressure of the molten printing material (melt) in the release channel is higher than that in the diversion module.

[0305] In some embodiments, the supply unit includes one or more heaters configured to heat and melt printing material. In some embodiments, the supply unit includes one or more temperature sensors configured to detect the temperature of the melted printing material within the supply unit. In some embodiments, the one or more temperature sensors are connected to a computer system that operates the one or more heaters in response to the temperature reported by the one or more temperature sensors.

[0306] In some embodiments, one or more pressure sensors are connected to a computer system that operates a supply unit to pressurize printing material to the desired pressure in response to pressure reported by the pressure sensors. In some embodiments, the printing pressure differs from the desired pressure by no more than about 0.05 MPa.

[0307] In some embodiments, the printing material (melt) is pressurized to a higher pressure in the supply unit (e.g., a melt extrusion module) before being delivered to the flow divider module. The printing material pressure gradually decreases from the release channel (through the flow divider module) to the printing channel of the printing unit. A first pressure of the printing material (melt) in the release channel is higher than a second pressure in the flow divider die. The second pressure is higher than a third pressure in the printing channel of the printing unit. In some embodiments, the supply unit includes a plunger mechanism, a screw mechanism (single screw, twin screw, 3 screw, 4 screw, 5 screw, 8 screw, micro screw), a screw pump mechanism, a gear mechanism, a plunger pump mechanism (e.g., a valveless metering pump mechanism), or any combination thereof. Additional details on several other features of the supply unit and printing system are provided in PCT / CN2018 / 071965 entitled "Precision Pharmaceutical 3D Printing Device", WO2018210183 entitled "3D Printing Device and Method", and PCT / CN2023 / 101745 entitled "Flexible, Extendable, and Modularized Pharmaceutical Additive Manufacturing System", the entire contents of which are incorporated herein by reference.

[0308] In some embodiments, referring to FIG12, the splitting module 2037 includes branch channels configured to split a single flow of printing material (e.g., melt supplied by a melt extrusion module) into multiple flows. In some embodiments, the splitting module is modular. In some embodiments, the splitting module 2037 includes one or more layers (e.g., 1, 2, 3, 4, 5, 10, 50, 100, etc.), each layer including one or more splitting plates for further distributing the received flow into a greater number of flows, as described below. In some embodiments, the splitting module 2037 can split a single flow into 2 flows, then into 4 flows, then into 8 flows, then into 16 flows, then into 32 flows. In some embodiments, the splitting module can directly split a single flow into 2 flows, 3 flows, 4 flows, 5 flows... or n flows. In some embodiments, the splitting module can split a single flow into 3 flows, then into 9 flows, then into 27 flows.

[0309] The printing unit includes multiple printing channels 2031 (e.g., nozzles). Multiple streams from the splitting module 2037 can be distributed by the system's printing channels 2031 (e.g., nozzles) to generate 3D-printed pharmaceutical products, such as tablets, capsules, or printed pills, through a printing platform. The number of printing channels (e.g., nozzles) is greater than or equal to the number of streams generated by the splitting module.

[0310] Figure 13 depicts an exemplary method 3 of operating a melt extrusion module according to some embodiments. In some embodiments, method 3 is performed using the disclosed 3D printing apparatus. It should be understood that the steps of method 3 utilize the features and advantages of the disclosed 3D printing apparatus. Although method 3 is shown as including the described steps, it should be understood that steps in a different order, additional steps (e.g., combinations with other methods or operations disclosed herein), or fewer steps may be included without departing from the scope of this disclosure.

[0311] In some embodiments, method 3 includes receiving printing material at a second melt extrusion chamber while printing material is being discharged from a first melt extrusion chamber (step 31). For example, at a first moment, a filler module fills the second melt extrusion chamber, thereby receiving printing material in the second melt extrusion chamber. At the same first moment, a release switch module connects the extrusion channel of the first melt extrusion chamber to a release channel, thereby discharging melt from the first melt extrusion chamber to the printing unit for printing.

[0312] In some embodiments, method 3 includes receiving printing material at the first melt extrusion chamber while the printing material is being discharged from the second melt extrusion chamber (step 32). For example, at a second time, a filler module fills the first melt extrusion chamber, thereby receiving the printing material in the first melt extrusion chamber. At the second time, a release switch module connects the extrusion channel of the second melt extrusion chamber to the release channel, thereby discharging the melt from the second melt extrusion chamber to the printing unit for printing.

[0313] In some embodiments, by discharging the melt via different melt extrusion cavities and allowing a continuous supply of melt for printing, method 3 advantageously allows the desired properties of the printing material to be maintained during the printing process (e.g., preventing the printing material from aging during printing, reducing residence time distribution (RTD)). By allowing a continuous supply of melt for printing, pharmaceutical products can be printed continuously (e.g., compared to a single melt extrusion cavity embodiment, where printing is paused while printing material is being received in the melt extrusion cavity).

[0314] Although method 3 describes two melt extrusion cavities, it should be understood that for more flexible systems, more than two melt extrusion cavities can be operated. For example, a 3D printing apparatus may include more than two melt extrusion cavities. At a first time, a first set of melt extrusion cavities (e.g., one of three, two of five) can be selected to receive printing material and generate melt, and a second set of melt extrusion cavities (e.g., the remaining two of three, the remaining three of five) different from the first set can be selected to discharge melt. At a second time, the second set of melt extrusion cavities can be selected to receive melt, and the first set of melt extrusion cavities can be selected to discharge melt.

[0315] In some embodiments, the melt extrusion module is mobile, enabling the corresponding 3D printing system to be reconfigurable and flexible. Traditional pharmaceutical manufacturing processes may require a large and inflexible physical structure to support the end-to-end process (ensuring a continuous flow of printing material (melt)). In some embodiments, the disclosed methods and systems allow pharmaceutical manufacturing (e.g., via thermoplastic extrusion) to be effectively continuous, autonomous, precise, and flexible—capable of this with conventional methods and systems—paving the way for smart pharmaceuticals and reducing the space requirements of traditional pharmaceutical processes. Scalability can be crucial for pharmaceutical manufacturing due to the varying requirements and needs of different drugs.

[0316] Figures 14A to 14J depict an exemplary melt extrusion module assembly 5000 and a printing station 5050 according to some embodiments. As shown, portions of the printing station 5050 are shown as transparent to reveal station details. In some embodiments, the melt extrusion module assembly 5000 includes a melt extrusion module 5007, which may be a single-screw, plunger, twin-screw, or any of the disclosed melt extrusion modules. The melt extrusion module 5007 may include a plunger configuration different from the configuration associated with the melt extrusion modules described in the figures (or the melt extrusion module may not include a plunger).

[0317] In some embodiments, the melt extrusion module assembly 5000 is configured to align with the VL plate 5052 (e.g., an alignment structure) of the printing station 5050 (e.g., a terminal station) for more precise alignment between the melt extrusion module assembly 5000 and the terminal. In some embodiments, the VL plate includes a concave V-shaped feature and an L-shaped surface. In some embodiments, the VL plate 5052 is located near the bottom of the supply unit or the bottom of the 3D printing station, and the position of the melt extrusion module assembly (e.g., the bottom of the melt extrusion module assembly on one side of the melt extrusion channel) is configured to align with the VL plate. For example, after the AGV reaches a position near the terminal, the AGV is configured to perform more precise movements to dock the melt extrusion module assembly relative to the VL plate. Advantageously, the VL plate enables alignment accuracy of ±5 mm and / or ±2° along the XY plane between the center and endpoint of the melt extrusion module assembly. This allows for more precise (e.g., more precise connection of the melt inlet to the supply unit and the extrusion channel to the 3D printing station) and efficient transfer of the melt between the melt extrusion module and the endpoint, ensuring consistent quality in high-volume pharmaceutical products. Additional alignment accuracy can be achieved using the printing station's guide structure and / or cantilever.

[0318] In some embodiments, for more precise alignment along the Z-direction (e.g., considering height differences in non-planar factory floors), the feed port and extrusion channel of the melt extrusion module 5007 are configured to move along the Z-direction. For example, the feed port and extrusion channel are configured to move ±2 mm along the Z-direction to accommodate height differences in the factory floor. In some embodiments, the printing station 5050 includes a cantilever for aligning the melt extrusion module along the Z-direction. In some embodiments, after the melt extrusion module is in place and aligned with the endpoint, printing material is discharged from the melt extrusion module to the printing station (or received from the melt extrusion module from a supply unit, if the endpoint is a supply unit), as described herein. Because pharmaceutical products are small in size compared to manufactured components, precise alignment between the melt extrusion module and the endpoint is critical to ensuring the quality of high-volume, highly complex pharmaceutical products (e.g., slight deviations can lead to a large number of finished products failing to meet stringent pharmaceutical safety requirements).

[0319] In some embodiments, the delivered printing material is stored in a feed storage assembly 5062 (e.g., one melt extrusion chamber, two melt extrusion chambers) of the printing station 5050 (for storage and subsequent printing). In some embodiments, the delivered printing material is passed to the printing unit of the printing station 5050 (for printing). In some embodiments, the printing station 5050 includes a first melt extrusion chamber and a second melt extrusion chamber. The first melt extrusion chamber receives printing material, while the second melt extrusion chamber provides melt for printing. When the melt in the second melt extrusion chamber is low, the first melt extrusion chamber can be used for printing while the second melt extrusion module assembly provides melt to refill the second chamber. The configuration of the first and second melt extrusion chambers allows for the continuous printing of portions of the pharmaceutical product.

[0320] In some embodiments, the printing station 5050 further includes a lower electrical cabinet 5054, a guide structure 5056, a bottom frame 5058, an XYZ assembly 5060, a feed storage assembly 5062, a second electrical cabinet 5064B (not shown in FIG. 14A, but near the opposite side of the printing station, is a first electrical cabinet 5064A), a second printing unit 5066B (not shown in FIG. 14A, but near the opposite side of the printing station is a first printing unit 5066A), a truss manipulator 5068, an upper electrical cabinet 5070, a door 5072, a lifting door 5074, and a first movable door 5076A.

[0321] In some embodiments, guide structure 5056 corresponds to guide structure 806. In some embodiments, one or more printing units 5066A and 5066B of printing station 5050 correspond to printing unit 2003. In some embodiments, a first printing unit of printing station is configured to manufacture a first portion of a pharmaceutical product (e.g., shell, core, lower half, upper half), and a second printing unit of printing station is configured to manufacture a second portion of a pharmaceutical product (e.g., a pharmaceutical ingredient; another of shell, core, lower half, upper half). In some embodiments, the first printing unit and / or the second printing unit may print layer by layer. The first portion of the pharmaceutical product includes one or more layers of a first printing material, and the second portion of the pharmaceutical product includes one or more layers of the first printing material or one or more layers of the second printing material. In some embodiments, the one or more printing units of printing station 5050 include a 1-to-32 splitter module. In some embodiments, one or more of the lower electrical cabinet 5054, the first electrical cabinet 5064A, the second electrical cabinet 5064B, and the upper electrical cabinet 5070 are configured to house electrical components for controlling printing station 5050. In some embodiments, door 5072 includes a display for configuring, controlling, and monitoring parameters of print station 5050 (e.g., modules, sensors, printing processes, etc.). The display is configured to present information related to print station 5050 and to receive input for controlling print station 5050. In some embodiments, first active door 5072A is configured to access print station 5050 (e.g., for maintenance, updating components of print station (e.g., manifolds), for repair, for sterilization).

[0322] In some embodiments, the XYZ assembly 5060 is configured to move more precisely (e.g., along the XYZ direction) to move the corresponding printing unit to the printing tray for conveying manufactured pharmaceutical components for subsequent processing. In some embodiments, the turntable 5080 is configured to convey pharmaceutical product components between one or more of two printing units and one or more measurement modules (e.g., two) of the printing station 5050. In some embodiments, the measurement modules are configured to determine whether a portion of the pharmaceutical product conveyed to the measurement module meets a quality threshold (e.g., weight, composition, dimensions are within acceptable tolerances). In some embodiments, the measurement module includes a line laser for inspecting the portion of pharmaceutical product conveyed to the measurement module (e.g., measuring the portion to determine whether it meets the quality threshold).

[0323] In some embodiments, the turntable 5080 includes a plurality of tables (e.g., four), and the tables are configured to rotate about a central axis of the turntable (e.g., the center of the printing station). In some embodiments, plates (e.g., glass plates, plastic plates) are loaded onto the tables (e.g., using a robotic arm and suction cups to pick up the plates and load them onto the tables) and secured (e.g., vacuum-secured to the tables, using protrusions on the tables for alignment). In some embodiments, the robotic arm includes one or more suction mechanisms, and the robot is configured to activate one or more suction mechanisms to pick up the plates from a descending position and deactivate one or more suction mechanisms to place the plates. In some embodiments, the plate is configured for handling the manufacturing portion of pharmaceutical products on a table. In some specific embodiments, the glass plate is advantageously flat (e.g., with a roughness within 0.1 mm), which can meet the precision requirements of pharmaceuticals. Furthermore, the glass plate may be easier to clean to meet Good Manufacturing Practice (GMP) requirements in pharmaceutical manufacturing.

[0324] For example, the first stage of the turntable may be in a first state for receiving a first portion of the pharmaceutical product (e.g., comprising one or more layers of a first printing material (first melt)) (after they have been printed by the first printing unit), and the first portion of the pharmaceutical product may be mounted on a plate. After the desired amount of the first portion has finished printing, the first stage (and the portion on the first stage) rotates to a second state for measurement or inspection by a measurement module. Acceptable portions of the pharmaceutical product (e.g., the first portion determined by the measurement module to exceed a quality threshold, or considered acceptable by the measurement module) may remain on the first stage (and unacceptable portions may be discarded; described in more detail herein). In some embodiments, the first stage rotates back to the first state (first printing unit) for further processing. In some embodiments, based on the determination that the first portion meets a quality threshold, the first stage rotates back to the first state (first printing unit) (e.g., for further printing of the first portion). In some embodiments, the first stage (and the acceptable portion thereon) rotates to a third state for further processing (e.g., rotating to a second printing unit to receive a second portion of the pharmaceutical product (e.g., comprising one or more layers of a second printing material (first melt), or one or more layers of a first printing material (second melt)) into the gantry manipulator 5068, the subsequent station). In some embodiments, after receiving the second portion of the pharmaceutical product, the first stage may rotate to a fourth state for measurement or inspection by a second measurement module. In some embodiments, while the first portion of the pharmaceutical product is conveyed through the first stage for different processing, the second stage of the turntable 5080 may convey and process other portions of the pharmaceutical product in parallel.

[0325] In some embodiments, a measuring module (e.g., located between two printing units 5066A and 5066B) is configured to determine and control the quality of a portion of a pharmaceutical product manufactured by one or more of the two printing units 5066A and 5066B. In some embodiments, based on the determination that the manufactured portion of the pharmaceutical product meets a quality threshold, the portion of the pharmaceutical product is conveyed to a gantry manipulator 5068 (for subsequent processing) or a second printing unit (for subsequent processing, as described above). In some embodiments, based on the determination that the manufactured portion of the pharmaceutical product does not meet a quality threshold, the portion of the pharmaceutical product is discarded (and not conveyed to the gantry manipulator 5068). In some embodiments, the pharmaceutical product is configured to convey (e.g., from the printing unit) the printed pharmaceutical product or a portion of the pharmaceutical product for subsequent processing. In some embodiments, the gantry manipulator 5068 is configured to have multiple degrees of freedom to more efficiently convey the pharmaceutical product or a portion of the pharmaceutical product for subsequent processing. Although examples of conveying pharmaceutical product portions have been described with respect to a turntable, it should be understood that these portions can be conveyed in different ways.

[0326] As shown in Figure 14B, in some embodiments, the printing station 5050 further includes a first electrical cabinet 5064A, a second movable door 5076B, and a storage rack 5078. In some embodiments, the storage rack 5078 is configured to store portions of the manufactured pharmaceutical products before they are conveyed to the gantry manipulator 5068.

[0327] In some embodiments, the interior of print station 5050 is sterilized. For example, print station 5050 is configured to prevent contaminants from entering its interior. As another example, print station 5050 is configured to sterilize its interior (in response to a sterilization command).

[0328] In some embodiments, the printing station 5050 further includes a structure (hidden outside the station) comprising an upper first frame (located on a first side of the station), a measurement module top frame, an upper second frame (located on a second side of the station), a first base plate (located on a first side of the station for supporting components on the first side), a turntable base, a second base plate (located on a second side of the station for supporting components on the second side), a lower first frame (located on a first side of the station), a lower second frame (located on a second side of the station), a docking guide plate mounting bracket, and a plurality of columns.

[0329] It should be understood that the features of the printing station described in Figures 14A and 14B are not intended to be limiting. The printing station may include additional components, fewer components, or different components. For example, the printing station may include one or more printing units, one or more gantry manipulators, one or more mass valve controls, and / or one or more storage racks. It should also be understood that the interaction between the melt extrusion module assembly and the printing station described in Figures 14A and 14B is not intended to be limiting. Some of the described features of the interaction may apply to the interaction between the melt extrusion module assembly and the supply unit. For example, the supply unit may include an alignment structure (e.g., a VL plate) for docking the melt extrusion module assembly to the supply unit.

[0330] Furthermore, the printing station can be configured to connect to more than one melt extrusion module assembly. For example, as shown in FIG14C, in some embodiments, printing station 5050 is configured to connect to two melt extrusion module assemblies 5000A and 5000B, each of which may include the disclosed melt extrusion module. A first melt extrusion module assembly 5000A may arrive at the printing station first. The first melt extrusion module assembly may deliver a first printing material (e.g., for printing a first component of a pharmaceutical product). As the first melt extrusion module assembly 5000A approaches the first VL plate 5052A of the printing station, the first melt extrusion module assembly 5000A may dock relative to the first VL plate 5052A at the printing station, and the first melt extrusion module assembly 5000A may be aligned with the first guide structure 5056A of the printing station, as described herein.

[0331] After the first melt extrusion module assembly 5000A is aligned and engaged with the printing station (as described herein), the first melt extrusion module assembly 5000A can deliver the first printing material to the first printing unit 5066A for printing. Alternatively, the first melt extrusion module assembly 5000A can deliver the first printing material to a feed storage assembly (e.g., feed storage assembly 5062 of FIG. 14A) for subsequent processing (e.g., printing at a later time, mixing with a second printing material to be delivered to the printing station). After a portion of the pharmaceutical product (e.g., comprising one or more layers of printing material (melt)) has been printed, the portion can be delivered to a measurement module for subsequent processing (e.g., measuring the structure of the pharmaceutical product portion using a line laser measuring instrument, delivering it to a gantry manipulator 5068 for subsequent delivery of the pharmaceutical product portion (e.g., for processing, for packaging), and to a second printing unit (e.g., for additional processing)). The pharmaceutical product portion formed from the first printing material can be processed together with a pharmaceutical product portion formed from the second printing material (e.g., from the second melt extrusion module assembly 5000B described below) (e.g., on a storage rack 5078).

[0332] The second melt extrusion module assembly 5000B may arrive at the printing station at a second time (e.g., a time different from the first time, or the same time as the first time). The second melt extrusion module assembly may deliver a second printing material (e.g., for printing a second portion of a pharmaceutical product (e.g., including one or more layers of the second printing material (melt)) and for delivering additional material to print a first portion of the pharmaceutical product). As the second melt extrusion module assembly 5000B approaches the second VL plate 5052B of the printing station, the second melt extrusion module assembly 5000B may dock relative to the second VL plate 5052B of the printing station, and the second melt extrusion module assembly 5000B may be aligned with the second guide structure 5056B of the printing station, as described herein.

[0333] After the second melt extrusion module assembly 5000B is aligned and engaged with the printing station (as described herein), it can deliver a second printing material to the second printing unit 5066B for printing. Alternatively, the second melt extrusion module assembly 5000A can deliver the second printing material to a feed storage assembly (e.g., feed storage assembly 5062 of FIG. 14A) for subsequent processing (e.g., printing at a later time, mixing with a third printing material to be delivered to the printing station). After a portion of the pharmaceutical product (e.g., comprising one or more layers of printing material (melt)) has been printed, the portion can be delivered to corresponding measurement modules 5082A and 5082B (e.g., each printing unit coupled to a corresponding measurement module) for inspection prior to subsequent processing (e.g., delivery to a gantry manipulator 5068 for subsequent delivery of the portion of the pharmaceutical product (e.g., for processing, for packaging, for transport to the next processor), to the second printing unit for additional processing). In some embodiments, measurement modules 5082A and 5082B include a line laser for measuring the portion of the pharmaceutical product. The portion of the pharmaceutical product formed from the second printing material can be processed together (e.g., on a storage rack 5078) with a portion of the pharmaceutical product formed from the first printing material (e.g., from the first melt extrusion module assembly 5000B described above). In some embodiments, the portions of the pharmaceutical product formed from the first and second printing materials are different portions that can be combined together in printing station 5050 to form a pharmaceutical product. In some embodiments, the portions of the pharmaceutical product formed from the first and second printing materials are identical portions, effectively doubling the throughput of printing station 5050.

[0334] Traditional pharmaceutical processes, even for the manufacture of a single drug product, may require a large and inflexible physical structure to support the end-to-end process (ensuring a continuous flow of the printed material (melt)). In some embodiments, the disclosed printing system's ability to use varying numbers of modules for different materials and processes allows for drug product manufacturing (e.g., via melt extrusion) that is effectively continuous, autonomous, precise, and flexible—something impossible with conventional methods and systems—reducing the space requirements of traditional pharmaceutical processes. The melt extrusion module assemblies and printing system further enable scalability and flexibility, which can be crucial for drug product manufacturing due to the different requirements and needs of various drugs.

[0335] It should be understood that printing materials can be stored in different ways during transport, instead of the melt extrusion module assemblies 5000A and 5000B. In some embodiments, the material delivered to the printing station is in a non-molten state (e.g., preceding product printing material supplied by a supply station, as described below), and the non-molten material can be stored in a preceding product cassette. The non-molten material can be supplied to the printing station, and the printing station melts the non-molten material before supplying it to the printing unit.

[0336] For example, Figures 14D-14J illustrate an exemplary printing station for receiving preceding product printing material (such as a monolithic solid material with tube 733) and an example for transporting the preceding product printing material. In some embodiments, as shown in Figure 14D, the preceding product printing material is stored in a preceding product cassette (e.g., preceding product cassettes 5084A-5084C). As shown, the preceding product cassette may include six tubes, and each tube stores preceding product printing material. Examples of how preceding product printing material is created will be described in more detail below. In some embodiments, the number of tubes in each preceding product cassette may be based on system timing. For example, in some embodiments, by including six tubes in each preceding product cassette, the system can optimally create, load, transport, and load preceding product printing material into the printing station while minimizing interruptions at each step (e.g., waiting for a step to complete before proceeding to the next step).

[0337] The preceding product box can be transported via the melt extrusion module assembly 5000C. In some embodiments, the melt extrusion module assembly 5000C includes an AGV 8002 and a ring guide 5085. In some specific embodiments, the preceding product box is placed and arranged on the ring guide 5085. Examples of how the preceding product box is placed and arranged will be described in more detail below. For the sake of brevity, some common components associated with the melt extrusion module assemblies 5000A and 5000B are not described here.

[0338] In some embodiments, the printing station 5050 includes a filling module 5086 for receiving a preceding product cartridge and a melt extrusion chamber (e.g., a first melt extrusion chamber 5089A and a second melt extrusion chamber 5089B) of the printing station 5050. In some embodiments, the melt extrusion chambers are configured to mix, melt, and / or pressurize the received preceding product printing material (e.g., via a plunger in a respective melt extrusion chamber) and supply the molten material to a printing unit for printing pharmaceuticals. In some embodiments, the filling module 5086 includes a mechanism 5088 (e.g., an XY-axis alignment mechanism, a cylinder) for aligning the filling module with the melt extrusion module assembly 5000C and receiving the preceding product cartridge from the melt extrusion module assembly 5000C.

[0339] As an example, after the melt extrusion module assembly 5000C is aligned with the printing station 5050, the filling module 5086 is aligned with the melt extrusion module assembly 5000C to receive the preceding product box 5084B and provide the preceding product box 5084C to the melt extrusion chambers 5089A and / or 5089B. After the preceding product box is provided to the filling module 5086, the ring guide 5085 can be rotated such that a second preceding product box is positioned to be received by the filling module 5086.

[0340] The tubes of the preceding product cartridge 5084C can be alternately coupled to melt extrusion chambers 5089A and 5089B to provide preceding product printing material. For example, a first tube can be used and coupled to a first melt extrusion chamber 5089A, and a plunger in the first melt extrusion chamber empties the preceding product printing material in the tube into the first melt extrusion chamber (e.g., by pushing it onto the tube). After the first tube is emptied, it can return to the preceding product printing material cartridge 5084C. The first melt extrusion chamber can provide the printing unit with processed (e.g., mixed, melted, and / or pressurized) preceding product printing material. A second melt extrusion chamber 5089B can be provided with a second tube, and a plunger in the second melt extrusion chamber empties the preceding product printing material in the tube into the second melt extrusion chamber. The second melt extrusion chamber can provide the printing unit with processed (e.g., mixed, melted, and / or pressurized) preceding product printing material. After the second tube is emptied, it can be returned to the preceding product printing material tank 5084C. Remaining preceding product printing material tubes can be supplied to the corresponding melt extrusion chambers in a similar manner.

[0341] When the melt content in the melt extrusion chamber is low, the second melt extrusion chamber can be used to supply processed preceding product printing material to the printing unit, while the first melt extrusion chamber receives more preceding product printing material (e.g., from a third tube). The configuration of the first and second melt extrusion chambers allows for continuous printing of pharmaceuticals.

[0342] After all tubes in the preceding product cartridge have been emptied, these tubes can be placed back onto the preceding product cartridge 5084C. Based on the determination that the preceding product cartridge barrel is empty, the ring guide 5085 can rotate so that the filling module 5086 can place the empty preceding product cartridge into a usable position on the ring guide 5085. After the empty preceding product cartridge is removed, the filling module can receive a preceding product cartridge containing preceding product printing material (e.g., via the ring guide, as described above). A second preceding product cartridge can be provided to the melt extrusion chamber in a similar manner to the first preceding product cartridge.

[0343] It should be understood that the preceding product printing material supplied to the printing station may differ from the methods described above. For example, the first tube and the second tube may be continuously coupled to the same melt extrusion chamber (e.g., the second tube of preceding product printing material is supplied to the first melt extrusion chamber after the first tube of preceding product printing material has been supplied to the first melt extrusion chamber). As another example, the preceding product printing material in both chambers may be supplied to the printing unit simultaneously. As yet another example, the preceding product printing material may be supplied after one or more tubes of preceding product printing material have been loaded into the respective melt extrusion chambers.

[0344] Although a portion of a printing station and an AGV are shown, it should be understood that the printing station can receive material from multiple AGVs via a preceding product box. For example, Figure 14E depicts an exemplary printing station 5050 configured to receive material from two AGVs via a preceding product box. As shown, in some embodiments, printing station 5050 includes filling modules 5086A and 5086B. In some embodiments, each filling module 5086A and 5086B includes filling module 5086 described relative to Figure 14D, and it should be understood that filling modules 5086A and 5086B include similar features and advantages.

[0345] For example, after the melt extrusion module assembly (not shown in Figure 14E) is aligned with the printing station 5050, the filling module 5086A is aligned with the melt extrusion module assembly to receive the preceding product cartridge 5084D and to supply the preceding product cartridge 5084D to the melt extrusion cavities 5089A and / or 5089B (shown in more detail in Figure 14F). Mechanism 5088A can align the preceding product cartridge 5084D to the melt extrusion cavity for receiving the tube from the preceding product cartridge. It should be understood that the filling module 5086B can perform similar operations as described.

[0346] Figure 14F depicts an exemplary print station 5050 configured to receive material from two AGVs via a preceding product cassette, with the filling module concealed for clarity. The tubes of the preceding product cassette 5084D (not shown) can be alternately coupled to melt extrusion chambers 5089A and 5089B to provide preceding product printing material. A mechanism 5088A (not shown) can position the preceding product cassette to allow a barrel to be coupled to the corresponding melt extrusion chamber. For example, a first barrel can be positioned and coupled to a first melt extrusion chamber 5089A, and a plunger 5090A of the first melt extrusion chamber 5089A empties the preceding product printing material from the tube into the first melt extrusion chamber. After the first tube is emptied, it can return to the preceding product cassette 5084D. The first melt extrusion chamber can supply the print unit with processed (e.g., mixed, melted, and / or pressurized) preceding product printing material. The second melt extrusion chamber 5089B may be provided with a second tube, and the plunger 5090B of the second melt extrusion chamber 5089B empties the preceding product printing material in the tube into the second melt extrusion chamber. The second melt extrusion chamber may supply the printing unit with processed (e.g., mixed, melted, and / or pressurized) preceding product printing material. After the second tube is emptied, the second tube may return to the preceding product cartridge 5084D. The remaining preceding product printing material tube may be supplied to the corresponding melt extrusion chamber in a similar manner. It should be understood that melt extrusion chambers 5089C and 5089D, respectively including plungers 5090C and 5090D, may perform similar operations as described.

[0347] When the melt content in the first melt extrusion chamber is low, the second melt extrusion chamber can be used to supply processed preceding product printing material to the printing unit, while the first melt extrusion chamber receives more preceding product printing material (e.g., from a third tube). The configuration of the first and second melt extrusion chambers allows for continuous printing of pharmaceuticals.

[0348] When the melt content in the first melt extrusion chamber is low, the second melt extrusion chamber can be used to supply processed preceding product printing material to the printing unit, while the first melt extrusion chamber receives more preceding product printing material (e.g., from a third preceding product cartridge). The configuration of the first and second melt extrusion chambers allows for continuous printing of pharmaceuticals.

[0349] Figures 14G-14H illustrate examples of coupling between a tube and a melt extrusion chamber. For example, Figures 14G-14H show the coupling of tube 5092 (preceding product box 5084D) and melt extrusion chamber 5089A. As described above, taking melt extrusion chamber 5089A as an example, after aligning the preceding product box 5084D (not shown) with melt extrusion chamber 5089A, tube 5092 can be placed in a slot corresponding to melt extrusion chamber 5089A. In some embodiments, tube 5092 can be picked up and placed in the corresponding slot. In some embodiments, tube 5092 can be placed into the slot by clamping device 5091A or clamping device 5091B.

[0350] In some embodiments, clamping devices 5091A (or 5091B) are in the open position before tube 5092 is placed into the corresponding slot (e.g., corresponding to storage chambers 5090A or 5090B), as shown in FIG14G. After tube 5092 is placed into the corresponding slot (e.g., corresponding to melt extrusion chambers 5089A or 5090B), clamping devices 5091A (or 5091B) are in the closed position, as shown in FIG14H, and the corresponding plunger empties the preceding product printing material from the tube, as described above. In some specific embodiments, a wedge structure is used to further secure the tube position. Although clamping devices 5091A and 5091B are shown in the open and closed positions, it should be understood that the clamping devices can be opened or closed independently of each other.

[0351] Figure 14I shows an example cross-sectional view of the print station assembly. As shown in Figure 14, Figure 14I shows a cross-section of the plunger 5090A of the melt extrusion chamber 5089A, the plunger 5090B of the melt extrusion chamber 5089B, and the tube 5092. The plunger can be pushed upwards to empty the preceding product printing material from the tube. As shown in Figure 14J, the preceding product printing material melt can be pushed into the flow channel 5093 of the diversion module, which is configured to allow the preceding product printing material melt to flow from the melt extrusion chamber 5089A or 5089B to the diversion module 5094 (e.g., the diversion module described herein) via a release switch module. In some embodiments, the melt from the melt extrusion chamber is selected by a valve device corresponding to the release switch module of each melt extrusion module. For example, if preceding product printing material from melt extrusion chamber 5089A is selected to flow to diversion module 5094, the valve device corresponding to melt extrusion chamber 5089A rotates to deliver melt through flow channel 5093 to diversion module 5094. In some embodiments, rotation of the valve device corresponding to melt extrusion chamber 5089B causes melt to stop flowing through flow channel 5093 to diversion module 5094. If preceding product printing material melt from melt extrusion chamber 5089B is selected to flow to diversion module 5094, the valve device corresponding to melt extrusion chamber 5089B rotates to deliver melt through flow channel 5093 to diversion module 5094. In some embodiments, rotation of the valve device corresponding to melt extrusion chamber 5089A causes melt to stop flowing through flow channel 5093 to diversion module 5094. In some embodiments, flow channel 5093 includes an upper plate and a lower plate.

[0352] In some embodiments, the pharmaceutical product includes a drug, which includes, but is not limited to, pharmaceutical products, medical devices, and dietary supplements.

[0353] In some embodiments, as shown in Figures 3A to 3C, the supply unit further includes a second air pressure control module 315. The second air pressure control module 315 is connected to the packing cavity 3122 and is used to control the air pressure of the packing cavity 3122, the corresponding melt extrusion cavity, and the printing cavity to a second air pressure preset value.

[0354] In some embodiments, the second air pressure control module 315 includes an air pressure control device, which includes an air pressure control channel 3151 and an air pressure pump. The air pressure pump is used to remove air from the packing cavity 3122 and the melt extrusion cavity through the air pressure control channel 3151 so that the air pressure in the packing cavity 3122, the corresponding melt extrusion cavity, and the printing cavity reaches the second preset air pressure value.

[0355] In some embodiments, the preset value of the second air pressure is -65 kPa to -100 kPa.

[0356] In some embodiments, the pressure control channel 3151 has a third state and a fourth state. In the third state, the opening of the pressure control channel 3151 is located inside the packing cavity 3122, so that the pressure control channel 3151 and the packing cavity 3122 are in communication. In the fourth state, the opening of the pressure control channel 3151 is located outside the packing cavity 3122, so that the pressure control channel 3151 and the packing cavity 3122 are not in communication.

[0357] In some embodiments, the supply unit further includes a second drive device for driving the pneumatic control channel 3151 to move back and forth between a third state and a fourth state.

[0358] In some embodiments, the supply unit further includes a material conveying module for conveying the printing material from the filler cavity 3122 to the corresponding melt extrusion cavity.

[0359] In some embodiments, the feeding module includes a feeding chamber 3112 and a plunger rod. The plunger rod is configured to reciprocate axially within the feeding chamber 3112 for pushing the printing material to a corresponding melt extrusion chamber.

[0360] In some embodiments, the air pressure control channel 3151 is connected to the interior of the packing cavity 3122 and / or the air pressure control channel 3151 is connected to the interior of the packing cavity 3122 or the interior of the conveying cavity 3112.

[0361] In some embodiments, the second air pressure control module 315 further includes an air pressure detection device for detecting the air pressure value in the packing cavity 3122 or the conveying cavity 3112.

[0362] In some embodiments, the air pressure detection device includes an air pressure sensor and an air pressure detection channel 3161. The air pressure detection channel 3161 communicates with the inside of the packing cavity 3122 or the inside of the conveying cavity 3112.

[0363] In some embodiments, the air pressure detection channel 3161 has a fifth state and a sixth state. In the fifth state, the air pressure detection channel 3161 has its channel opening located inside the packing cavity 3122 and / or the conveying cavity 3112; in the sixth state, the air pressure detection channel 3161 has its channel opening located outside the packing cavity 3122 and / or the conveying cavity 3112.

[0364] In some embodiments, the system further includes a third drive device for driving the pressure detection channel 3161 to move back and forth between the fifth state and the sixth state.

[0365] In some embodiments, the pneumatic control channel includes multiple pneumatic control sub-channels, which are configured to operate in parallel, partially in parallel, or independently, so that the air pressure of the filling chamber, the corresponding melt extrusion chamber, and the printing chamber reaches a second preset air pressure value, or so that the air pressure of the filling chamber, the corresponding melt extrusion chamber, the feeding chamber, and the printing chamber reaches a second preset air pressure value.

[0366] A more specific implementation of the second control module in the above embodiments will be further described below.

[0367] Second air pressure control module

[0368] Figure 1 illustrates, by way of example, a schematic diagram of an additive manufacturing system for producing pharmaceutical products according to an embodiment of the present invention. As shown in Figure 1, the additive manufacturing system is further defined as a 3D printing device having a pneumatic control module.

[0369] 3D printing equipment includes environments (e.g., enclosed environments such as incubators, open environments such as printing platforms) for additive manufacturing (e.g., 3D printing) of pharmaceutical products such as drug dosing units. Multiple closed-loop control systems are used to control temperature, pressure, flow rate, weight, volume, and other relevant parameters in the environment at multiple stages of the manufacturing process. In some embodiments, the inconsistency in unit weight (i.e., the inconsistency between unit weights within the same batch) is less than 10% (e.g., 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 9.5%, 10%). In some embodiments, the inconsistency in batch weight (i.e., the inconsistency between batch weights) is less than 10% (e.g., 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 9.5%, 10%).

[0370] Depending on the different types of printing materials and compositions required, the system can adjust the control parameters. This allows the printing system to be used to efficiently manufacture various high-quality, high-precision, and highly consistent drug dosing units.

[0371] In some embodiments, the 3D printing equipment 1000 shown in FIG1 includes a preliminary product forming module 0102, a printing unit 0103, a supply unit 0107, and a platform unit 0104. During the printing process, the preliminary product forming module heats the received initial drug printing material (such as granular or powdered material) to melt it into an initial melt and extrudes and cools the initial melt to form a preliminary product printing material (such as a cylindrical integrated preliminary product printing material or a shell (or tube) preliminary product printing material). The preliminary product printing material is automatically or manually filled into the supply unit. The supply unit melts the preliminary product printing material into a preliminary product melt and transfers it to the printing unit 0103. The printing unit 0103 extrudes the preliminary product melt to a designated position on the platform unit 0104 according to a pre-set data model or program. Through the layering and accumulation of the preliminary product melt on the platform unit 0104, the desired 3D drug product is finally formed. In other embodiments, the preceding product forming module heats the received initial drug printing material (such as granules or powder) to melt it into an initial melt. This initial melt is automatically or manually filled into the melt extrusion cavity of the supply unit. The melt is transferred from the selected melt extrusion cavity to the printing unit 0103. The printing unit 0103 extrudes the preceding product melt to a designated position on the platform unit 0104 according to a pre-set data model or program. Through the stacking and accumulation of the preceding product melt on the platform unit 0104, the desired 3D drug product is finally formed.

[0372] As shown in Figure 1, in some embodiments, the preceding product forming module 0102 may further include a feeding module 0101, which has a hopper 0111 for receiving and transferring the initial drug printing material. The hopper 0111 has an inlet 0112 and an outlet 0113. During the printing process of the 3D printing equipment 1000, the feeding module 0101 receives the initial drug printing material through the inlet 0112 of the hopper 0111 and discharges the initial drug printing material to the preceding product melting and forming device of the preceding product forming module 0102 through the outlet 0113. The initial drug printing material used in the 3D printing equipment 1000 can be a powder or granular material. Correspondingly, as shown in Figure 1, the hopper 0111 is a funnel-shaped shell with a flared opening. In some embodiments, the initial drug printing material can also be filamentous, blocky, or other shapes. Correspondingly, the hopper can also be configured with a shape adapted to the initial drug printing material. The hopper 0111 is also equipped with a hopper discharge control device 0114, which controls the discharge speed of the initial drug printing material at the discharge port 0113 of the hopper 0111. The hopper discharge control device 0114 shown in Figure 1 is a single-screw device, positioned near the discharge port and connected to a motor and transmission device (not shown in the figure) that drive its movement. By adjusting the rotational speed of the screw device 0114 through the drive mechanism, the discharge speed of the initial drug printing material at the discharge port 0113 can be controlled. Furthermore, by adjusting the pitch and thread of the screw portion of the screw device 0114 itself, the mixing and conveying method of the material can be controlled. Although the hopper discharge control device 0114 shown in the figure is a single-screw device, in some embodiments, the hopper discharge control device can also be a twin-screw device, or a combination of a twin-screw device and a single-screw device. In some embodiments, the hopper discharge control device 0114 may further include a commonly used mechanism for controlling the initial discharge speed of the pharmaceutical printing material at the discharge port 0113. In some embodiments, the hopper discharge control device further includes a baffle or baffle disposed at the discharge port 0113, which controls whether material is discharged from the discharge port 0113. In some embodiments, the hopper discharge control device 0114 may also include a flow control valve disposed at the discharge port 0113, such as a pneumatic flow control valve, an electromagnetic flow control valve, a hydraulic flow control valve, etc. The discharge speed of the initial pharmaceutical printing material at the discharge port 0113 is controlled by adjusting the size of the flow control valve.

[0373] The 3D printing equipment 1000 may also include a second feeding module 0201. As shown in the figure, the second feeding module 0201 has the same or similar structure as the first feeding module 0101, and also includes a hopper 0211 with an inlet 0212 and an outlet 0213, and also includes a hopper discharge control device 0214 disposed in the hopper 0211 for controlling the discharge speed of the initial drug printing material at the outlet 0212. During the actual printing process, the feeding module 0201 can receive a second initial drug printing material, which is different from the initial drug printing material received by the feeding module 0101, through the inlet 0212 of the hopper 0211, and discharge the second initial drug printing material to the preceding product through the outlet 0213. It is understandable that by controlling the hopper discharge control device 0114 of the feeding module 0101 and the hopper discharge control device 0214 of the second feeding module 0201, the ratio of the initial drug printing material and the second initial drug printing material received by the preceding product melting and forming device can be controlled, thereby ultimately controlling the ratio of the aforementioned initial drug printing material and the second initial drug printing material in the printed drug product.

[0374] As shown in Figure 1, the preceding product forming module 0102 is configured to perform initial pretreatment on the initial drug printing material before it is filled into the supply unit. In some embodiments, the pretreatment includes melting and pressurizing the printing material based on predetermined settings (e.g., to a target temperature range, to a target pressure range). In some embodiments, the preceding product forming module 0102 includes a processing chamber 0121, a preceding product melting and forming device 0122, and a processing chamber heating device 0123. The processing chamber 0121 is a hollow shell with an inlet 0124 and an outlet 0125, through which the initial drug printing material discharged from the outlet 0113 enters the processing chamber 0121 through the inlet 0124. The processing chamber heating device 0123 is disposed on the peripheral wall of the processing chamber 0121 for heating the material inside the processing chamber 0121. The preceding product melting and forming device 0122 mixes, extrudes, and / or shears the material in the processing chamber 0121. Under the combined action of the processing chamber heating device 0123 and the preceding product melting and forming device 0122, the initial drug printing material melts into an initial melt and is discharged through the discharge port 0125, forming the preceding product printing material. The processing chamber 0121 also has an exhaust port. A small amount of air mixed in during the mixing, extrusion, and / or shearing of the material in the processing chamber 0121 by the preceding product melting and forming device 0122 can be discharged through the aforementioned exhaust port, avoiding air inclusion in the subsequent preceding product printing material. Especially when the preceding product printing material is an integrally formed solid product, the small amount of air that may be mixed in the preceding product printing material can be removed in advance to ensure that the solid material does not contain air, which facilitates the control of the accuracy of the subsequently printed drug product. Furthermore, the integrated solid material, compared to granular solid raw materials, allows for pre-mixing or preparation, facilitating precise control over the amount subsequently added to the supply unit. This enables precise control over the quantity of printed drug products from the outset. Compared to molten raw materials, the integrated solid material is easier to transport and can shorten preparation time such as heating and / or pressure holding (unlike molten raw materials which require continuous heating to maintain a molten state during transport). This avoids prolonged exposure of raw materials to high-temperature environments, preventing degradation and denaturation.

[0375] As shown in Figure 1, the preceding product melt-forming device 0122 can be a twin-screw extruder housed within the processing chamber 0121. The twin-screw extruder is connected to a drive motor 0129 via a speed change device 0128. Driven by the drive motor 0129, the twin screws of the twin-screw extruder rotate and extrude the material within the processing chamber 0121, driving the material towards the discharge port 0125. Simultaneously, the internal heat generated by the twin screws' rotation and extrusion work heats the material within the processing chamber 0121. Although the preceding product melt-forming device 0122 shown is a twin-screw extruder, in some embodiments, the hopper discharge control device can also be a single-screw extruder. In some embodiments, the preceding product melt-forming device 0122 can also be a commonly used screwless extruder, such as a plunger extruder.

[0376] As shown in Figure 1, the heating device 0123 of the processing chamber can be configured to surround the outer wall of the processing chamber 0121 in segments for segmented heating, thereby achieving more precise heating temperature control. In some embodiments, the heating device 0123 of the processing chamber is a common electric heating device, such as a thermocouple wound around the outside of the processing chamber 0121. It is understood that although the heating device 0123 of the processing chamber is disposed on the outer wall of the processing chamber 0121 as shown in the figure, in some embodiments, the heating device 0123 of the processing chamber can also be disposed inside the processing chamber 0121, such as a heating rod disposed inside the processing chamber 0121. The processing chamber 0121 also includes a pressure control module (not shown in the figure). The pressure control module has a pressure sensor for testing the pressure value of the initial melt in the processing chamber 0121. The pressure control module adjusts the pressure of the initial melt in the processing chamber 0121 in real time according to the real-time monitored pressure value, so that the pressure of the initial melt is maintained at the desired preset pressure value and its pressure is kept constant. The pressure control module can be a screw extrusion mechanism, a piston extrusion mechanism, or other common pressure control modules. The pressure control module is driven by pneumatic or hydraulic, electric motor, or other common drive devices to control the pressure of the initial melt in the processing chamber 0121.

[0377] In some embodiments, the preceding product forming module 0102 further includes a melt extrusion discharge control device (not shown in the figure), which is configured to control the discharge speed of the melt at the discharge port 0125 of the processing chamber 0121. Similar to the structure of the hopper discharge control device 0114 described above, the melt extrusion discharge control device can be a flow control valve disposed at the discharge port 0125, such as a pneumatic flow control valve, a hydraulic flow control valve, an electromagnetic flow control valve, etc., which controls the discharge speed of the melt at the discharge port 0125. In some embodiments, the melt extrusion discharge control device may also have a baffle or baffle disposed at the discharge port 0125 to control whether the melt is discharged at the discharge port 0125. It should be noted that the preceding product melt forming device 0122 of the preceding product forming module 0102 can also control the discharge speed of the melt at the discharge port 0125 by controlling the extrusion power of the initial drug printing material and the melt within the extrusion processing chamber 0121. In some embodiments, the preceding product melt forming apparatus is a screw extrusion apparatus. Specifically, in the twin-screw apparatus shown in FIG12, the discharge speed of the melt at the discharge port 0125 can be controlled by controlling the rotational speed of the screw apparatus. In some embodiments, the discharge speed of the preceding product forming module 0102 at the discharge port 0125 can also be adjusted by controlling the feeding speed of its inlet 0124, for example, by increasing the feeding speed of its inlet 0124, thereby increasing the discharge speed of its discharge port 0125. The feeding speed of the preceding product forming module 0102 at the inlet 0124 can be achieved by adjusting the discharge speed of the feeding module 0101 at the discharge port 0113 as described above.

[0378] In some embodiments, the 3D printing equipment 1000 further includes a recirculation loop (not shown in the figure), one end of which is connected to the melt passage after the outlet 0125 of the processing chamber 0121, and the other end is connected to the processing chamber 0121, thereby allowing a portion of the melt to flow back into the processing chamber 0121. In some embodiments, the recirculation loop is further provided with a flow control valve, which is used to regulate the amount and speed of the melt flowing back into the processing chamber 0121 through the recirculation loop.

[0379] Referring again to Figure 1, the printing unit 0103 may include a barrel 0133 having an outlet and an inlet. The barrel 0133 is constructed of a hollow shell, with a printing channel at its lower part. In some embodiments, the printing channel is a printing channel (nozzle) 0131. In some embodiments, the diameter of the nozzle opening is between 0.1 mm and 1 mm. The inlet of the barrel 0133 of the printing unit 0103 is connected to the outlet 0125 of the processing chamber 0121. The initial drug printing material is heated and melted into an initial melt, which is then extruded to generate a preceding product printing material. This preceding product printing material is filled into a supply unit, melted into a preceding product melt by the supply unit, and supplied to the barrel 0133, ultimately being extruded through the printing channel (nozzle) 0131. Although the printing unit 0103 shown in the figure has only a single printing channel (nozzle) 0131, in some embodiments, the printing unit 0103 may include multiple nozzles, thereby enabling mass production and overcoming the limitation of currently used fused deposition modeling 3D printing equipment being unsuitable for mass production. The multiple nozzles can be arranged in an array or other regular arrangement suitable for mass production. The printing unit 0103 also includes a printing unit drive mechanism (not shown in the figure). This drive mechanism can be an actuator, hydraulic cylinder, stepper motor, or other commonly used drive mechanism. The printing unit 0103 is mounted on the drive mechanism, thereby driving the printing channel (nozzle) 0131 of the printing unit 0103 to move relative to the platform unit 0104. As shown in Figure 1, the barrel 0133 of the printing unit 0103 can also be provided with a temperature regulating device 0134, the structure and arrangement of which are the same as or similar to the heating device 0123 of the processing chamber described above. It can be an electric heating device arranged in segments around the barrel 0133. In some embodiments, the temperature regulating device 0134 can also be a heating rod disposed on the barrel 0133. It should be noted that the temperature regulating device can also have a cooling function, thereby reducing the temperature of the melt at the printing unit 0103 when the temperature is too high, such as a semiconductor heating and cooling chip, etc. The temperature regulating device 0134 is preferably located near the printing channel (nozzle) 0131, thereby enabling rapid and precise control of the temperature of the melt extruded from the printing channel (nozzle) 0131. The barrel 0133 also includes a pressure control module (not shown) for regulating the pressure of the melt at the printing unit 0103. In some embodiments, the pressure control module can be a screw extrusion device as described above, specifically a single-screw device, a twin-screw device, or a combination thereof. This screw extrusion device is located within the barrel 0133 and controls the extrusion power of the melt by controlling the screw's rotational speed, thereby controlling the pressure of the melt at the printing unit 0103, particularly at the printing channel (nozzle) 0131.In other embodiments, the pressure control module may also be a piston extrusion mechanism disposed inside the barrel 0133. The piston is driven to move by pneumatic or hydraulic means, thereby controlling the pressure of the melt at the printing unit 0103, especially at the printing channel (nozzle) 0131.

[0380] As shown in Figure 1, the platform unit 0104 includes a printing platform 0141 and a platform drive mechanism 0142 for driving the printing platform 0141. The printing platform 0141 can be a plate-like structure configured to receive melt extruded via the printing channel 0131 (nozzle) and stack it on the printing platform. Although only one printing platform 0141 is shown in the figure, in some embodiments, the platform unit 0104 may also include multiple printing platforms to suit mass production needs for simultaneous high-volume printing.

[0381] A printing platform 0141 is mounted on a printing platform drive mechanism 0142, which drives the printing platform 0141 to move relative to the printing channel (nozzle) 0131. In some embodiments, the platform drive mechanism 0142 may be a stepper motor based on a Cartesian coordinate system, enabling it to drive the printing platform 0141 to move along one or more of the X, Y, and Z axes. In other embodiments, the 3D printing apparatus 1000 further includes a printing unit drive mechanism for driving the printing channel (nozzle) 0131 of the printing unit 0103 to move relative to the platform unit 0104. In still other embodiments, the platform drive mechanism 0142 may be a conveyor belt. Accompanying the relative movement of the printing platform 0141 and the printing channel (nozzle) 0131, molten material is deposited on the printing platform 0141 to form the final pharmaceutical product with various complex structures and configurations desired.

[0382] Referring again to Figure 1, the 3D printing equipment 1000 further includes a supply unit 0107. The supply unit 0107 has a filling cavity for receiving preceding product printing material and a melt extrusion cavity for generating a melt from the preceding product printing material and extruding the melt via a release switch module to the printing unit. The filling cavity has a filling channel 0172 for receiving preceding product printing material from the outside, and the melt extrusion cavity has an outlet 0173. The filling channel 0172 receives solid material extruded or generated by the processing cavity 0121; the outlet 0173 is connected to the printing unit 0103 via a feeding channel 0135. The solid material extruded from the outlet of the processing cavity 0121 is filled into the filling cavity through the filling channel 0172, melts into a preceding product melt in the melt extrusion cavity, and is pressurized and extruded. The preceding product melt flows into the printing unit 0103 for printing through the outlet 0173 of the melt extrusion cavity. As shown in the figure, the supply unit 0107 also includes a heating device 0174 disposed in the melt extrusion chamber for heating the preceding product printing material in the melt extrusion chamber. The heating device 0174 is disposed on the outer wall of the melt extrusion chamber. In some embodiments, the heating device 0174 is a thermocouple surrounding the melt extrusion chamber. In some embodiments, the heating device 0174 may also be disposed inside the melt extrusion chamber, such as a heating rod disposed inside the melt extrusion chamber. In some embodiments, the outer wall of the filler chamber is also provided with a heat insulation sleeve for heat preservation of the remelted material in the melt extrusion chamber.

[0383] In some embodiments, the supply unit 0107 further includes a pressure control module 0171. The pressure control module 0171 has a pressure sensor for testing the pressure value of the preceding product melt within the supply unit 0107. The pressure control module adjusts the pressure of the preceding product melt in the supply unit 0107 in real time based on the pressure value monitored by the pressure sensor, so that the pressure of the preceding product melt is maintained at a desired preset pressure value and kept constant. The pressure control module can be a screw extrusion mechanism, a piston extrusion mechanism, or other common pressure control modules. The pressure control module is driven by pneumatic or hydraulic, electric motor, or other common drive devices to control the pressure of the melt within the supply unit 0107.

[0384] In some embodiments, the system further includes a pressure control module for controlling the melt pressure of the supply unit and / or printing unit to a corresponding preset pressure value.

[0385] In some embodiments, the supply unit 0107 further includes a discharge control device (not shown) for controlling the discharge rate of the molten material from the discharge port 0173 of the packing cavity. Similar to the hopper discharge control device 0114, the discharge control device can be a single-screw or twin-screw device, or a combination thereof, located near the discharge port 0173, or a flow control valve located at the discharge port 0173, such as a pneumatic flow control valve, an electromagnetic flow control valve, a hydraulic flow control valve, etc. In some embodiments, the discharge port 0173 of the packing cavity is also provided with a baffle or baffle plate to control whether material is discharged from the discharge port 0173.

[0386] The embodiments disclosed in this invention include an exemplary high-quality and high-precision additive manufacturing system for producing pharmaceutical products. The system includes a filler module, a melt extrusion module, a feeding module, a printing unit, and a platform module, wherein the filler module, melt extrusion module, and printing unit can be considered as a single integrated supply unit. The various modules of the additive manufacturing system disclosed in this invention can be arbitrarily added or removed, and designed to match the fine structure of the pharmaceutical product to be printed. For example, three filler modules can be set according to the different requirements of the raw materials and excipients of the pharmaceutical product. Multiple filler modules enter the preceding product melt forming device in the same or different proportions, forming a uniformly distributed melt through mixing and heating. Depending on the different printing processes of the pharmaceutical product, the melt or the solid material formed from the melt enters one or more feeding units. The supply unit can be arranged horizontally, vertically, or obliquely; this invention does not specifically limit its arrangement. The supply unit forms a melt from the printing material and provides the melt to the printing unit via a release switch module. The aforementioned printing material includes granular solid printing material, integrated solid printing material, and shelled solidified raw materials. The printing unit includes an inlet for receiving molten printing material (also called melt) from the supply unit, and further includes a printhead, such as a group of nozzles (one or more nozzles) for printing pharmaceutical dosage forms (e.g., tablets, capsules, printed pills); for example, a micro-screw printhead. Additive manufacturing systems for producing pharmaceutical products can use one or more 3D technologies, such as MED technology, inkjet technology, selective laser sintering (SLS) technology, PB technology, FDM technology, Arburg Plast ic Freeforming (APF) technology, micro-injection molding technology, etc.

[0387] Example 1 of the second air pressure control module

[0388] Figure 2A shows a perspective structural schematic of an additive manufacturing system 100 for producing pharmaceutical products according to one embodiment of this application. As shown in Figure 2A, the additive manufacturing system 100 for producing pharmaceutical products includes a filler module 112, a melt extrusion module 113, a printing unit 121, and a second air pressure control module 115. The filler module 112 includes an openable and closable filler channel 1121 and a filler cavity. In the open state, the filler channel 1121 is used to receive printing material 131. The melt extrusion module 113 includes a melt extrusion cavity (although only one melt extrusion cavity is shown in Figure 2A, it should be understood that the melt extrusion module 113 includes at least two melt extrusion cavities as shown in Figure 2A) for receiving the printing material 131 and forming a melt 132 from the printing material 131. The printing unit 121 includes a printing cavity and an openable and closable valve connected to the printing cavity. A printing channel is used to receive the melt 132 from the melt extrusion module 113 and distribute the melt 132 to the printing channel to form a drug product. The filling chamber, melt extrusion chamber, and printing chamber are connected to allow the printing material 131 to move from the filling chamber to the melt extrusion chamber and to allow the melt to be supplied from the melt extrusion chamber to the printing chamber via a release switch module. The second air pressure control module 115 is connected to the filling chamber and is used to control the air pressure of the filling chamber, melt extrusion chamber, and printing chamber to a preset value, such as -65 kPa or below. Further, when the system 100 is used for large-scale batch production of drug products, the end of the melt extrusion chamber near the printing chamber is usually loaded with the melt 132 (molten printing material) to be supplied to the printing chamber during the drug product preparation process. When the filling is completed and the filling channel 1121 is closed, the melt extrusion chamber and the filling chamber form a closed and connected cavity. The filling module 112, the melt extrusion module 113, and the second air pressure control module 115 constitute the supply unit 110. In this embodiment, the supply unit 110 is vertically arranged, with the filling module 112 located above the melt extrusion module 113. Therefore, after the printing material 131 is filled into the filling cavity, it will fall to the melt extrusion module 113 due to its own gravity. It should be understood that, depending on actual needs and application considerations, the supply unit 110 can also be horizontally or obliquely arranged; this invention does not impose specific limitations. Furthermore, the printing unit 121 also has a printing platform 122, which is used to receive the melt and generate the pharmaceutical product. In some embodiments, the printing material 131 applicable to the additive manufacturing system 100 for producing pharmaceutical products is further limited to solid materials, such as granular solid materials, bullet-shaped solid materials, cylindrical solid materials, integrated solid structural materials, and solid materials of the preceding product after removing the shell from the shelled printing material.In some embodiments, the filling channel 1121 is further disposed on the sidewall of the filling cavity to allow the printing material 131 to be filled into the filling cavity from the outside; the filling channel 1121 can be switched between an open state and a closed state; when in the open state, the printing material 131 is filled into the filling cavity from the filling channel 1121, and air also enters the filling cavity at this time; after the printing material 131 is filled, the filling channel 1121 is closed. When the filling channel 1121 is in the closed state, the filling cavity and the melt extrusion cavity with the melt 132 loaded at the end are interconnected and form a sealed cavity (the aforementioned sealed cavity is to ensure the effectiveness of subsequent air pressure control, prevent melt leakage during the manufacturing process of the drug product, and...). To ensure that the melt 132 within the aforementioned sealed cavity maintains a nearly constant temperature and pressure, precise control over the quantity of subsequently printed drug products and improved consistency among them are crucial. More specifically, if the cavity is not sealed and is open to the outside (e.g., with gaps), the second pressure control module 115 may fail to control the pressure to the desired preset value. Furthermore, as described in the background art, the melt may leak to the outside when transported under extrusion pressure. The inability to maintain constant temperature, pressure, and air pressure within the sealed cavity can lead to a reduction or excess in the quantity of printed drug products, and significant quantity deviations between printed drug products. The air that enters the sealed cavity during the filling process remains trapped within it. When newly added solid raw materials melt into a molten state and are compressed, the trapped air becomes compressed air between the previously added molten melt and the newly added solid raw materials forming a new molten state. On the one hand, if the air pressure in the cavity is not controlled to the desired preset value, the aforementioned compressed air will further lead to quality defects in the subsequently printed drug products, such as stringing, collapse, bubbles, sponginess, and voids. This will prevent the production of relatively small, delicate, complex drug products with high consistency requirements, such as drug dosing units (e.g., tablets, capsules, printlets), medical devices, and implantable stents. The technical solution proposed in this embodiment uses a second air pressure control module to control the air pressure in the aforementioned sealed cavity to the desired preset value, such as removing air from the aforementioned sealed cavity to control the air pressure at or below -65 kPa. In this way, maintaining a suitable and constant air pressure environment can avoid quality defects such as stringing, collapse, bubbles, sponginess, and voids in the subsequent drug products, thereby improving the quality of the drug products.On the other hand, if the chamber pressure is not controlled to the desired preset value, the aforementioned compressed air can cause a small amount of printing material to be distributed / leaked at the end of subsequent drug product printing (e.g., a leak of 15mg of melt). This melt leakage will reduce the amount of drug product printed in the next printing. For example, if the standard amount of drug product is 200mg, the amount of drug product in the next printing may be 185mg. In addition, in some continuous printing additive manufacturing systems, the melt leaked in the previous printing (e.g., a leak of 15mg of melt) will continue to be extruded into 15mg filaments at the filler channel (e.g., nozzle). The longer 15mg filaments will not be deposited in the ideal position during the second filament deposition, resulting in drug product stringing or long filament tails, and even affecting the overall shape of the drug product. It is impossible to accurately control the amount of printing material distributed each time to ensure the consistency between the same batch or different batches of drug products. Furthermore, melt leakage may also cause the printing channel (e.g., nozzle) to become blocked and prevent printing, affecting the orderly progress of production. The aforementioned compressed air can also cause the compressed air to explode during the subsequent drug product printing process, causing the melt to leak from the printing channel. The intermittent extrusion from the printing channel of the unit prevents the formation of continuously extending filaments. Consequently, the drug product cannot be formed, or the formed drug product is not of the desired shape or size, or even exhibits deformation, stringing, twisting, or long tails (extra structures). Alternatively, the compressed air may cause the extruded filaments to turn white or have uneven thickness, resulting in subsequent drug products that also turn white or have gaps, or even alter their properties. The technical solution proposed in this embodiment uses a second air pressure control module to control the air pressure in the aforementioned sealed cavity to the desired preset value, such as excluding air from the aforementioned sealed cavity to control the air pressure at or below -65 kPa. This also prevents the melt in the printing cavity from being undesirably discharged or leaked from the printing channel (such as the nozzle) along with the compressed air in the melt at the end of printing or during printing. Therefore, air pressure control plays a role in preventing undesirable material extrusion, avoiding a reduction or excess of printing material, and enabling precise control of the melt amount. At the same time, the good sealing performance of the cavity can maintain the melt in a suitable and constant temperature and air pressure environment, further ensuring the accuracy of the printed drug product and guaranteeing the consistency between single or multiple batches of drug products.Furthermore, through numerous experiments, the inventors of this invention discovered that the desired preset value of the second air pressure is related to the performance parameters of the printing material (such as glass transition temperature (TG), viscosity, etc.). Different preset values ​​of the second air pressure can be adjusted for printing materials with different performance parameters. For example, the inventors conducted numerous experiments with various printing materials and found that materials such as polyvinylpyrrolidone (VA64) and hydroxypropyl methylcellulose acetate succinate (HPMCAS) require higher preset values ​​of the second air pressure to achieve a better effect in preventing undesirable leakage of the printing material. Therefore, this preset value is usually obtained based on the size of the cavity, the performance of the material, the performance of the second air pressure control module (such as power), and experimental data.

[0389] In some embodiments, the additive manufacturing system can print 32 pharmaceutical products simultaneously, with each of the 32 filaments averaging 12.32 mg.

[0390] In some embodiments, the additive manufacturing system printed two batches of drug tablets. One batch consisted of 20 drug tablets, with an average weight of 204.32 mg; the other batch consisted of 15 drug tablets, with an average weight of 208.13 mg.

[0391] In some embodiments, when the weight of the drug tablet is less than 300 mg, the relative deviation of the weight is about ±10% or less, such as about ±9% or less, about ±8% or less, about ±7.5% or less, about ±7% or less, about ±6% or less, about ±5% or less, about ±4% or less, or about ±3% or less, or about ±2% or less, or about ±1% or less.

[0392] In some embodiments, when the weight of the drug tablet is equal to or greater than 300 mg, the relative deviation of the weight is about ±5% or less, for example, about ±4% or less, about ±3% or less, about ±2% or less, or about ±1% or less.

[0393] In some embodiments, the inconsistency in unit weight (i.e., the inconsistency between unit weights within the same batch) is less than 10% (e.g., 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 9.5%, 10%). In some embodiments, the inconsistency in batch weight (i.e., the inconsistency between batch weights) is less than 10% (e.g., 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 9.5%, 10%).

[0394] In the additive manufacturing system 100 for producing pharmaceutical products shown in Figure 2A, the second air pressure control module 115 includes an air pressure control channel 1151 communicating with the interior of the filling cavity and an air pressure pump 1152. In some embodiments, the filling channel is an openable and closable filling cap with a through hole through which the air pressure control channel 1151 communicates with the interior of the filling cavity. As mentioned above, in the pharmaceutical product preparation process, the filling cavity and the melt extrusion cavity, which is loaded with melt 132 at one end near the printing cavity, constitute a sealed and connected cavity. Therefore, the air pressure pump 1152 can expel air from the filling module 112 and the melt extrusion module 113 through the air pressure control channel 1151 so that the air pressure in the filling cavity, the melt extrusion cavity, and the printing cavity reaches the preset value. In some embodiments, the preset value of the second air pressure is -65 kPa to -100 kPa. Those skilled in the art can set different preset values ​​of the second air pressure according to different material properties (such as viscosity), the amount of drug product, etc. For example, the inventors found through multiple experiments that a certain printing material with a viscosity of 600 Pa·s can reach the preset value (-76 kPa) when the air pressure is controlled for 8 seconds, and there is no undesirable melt discharge during the printing process and at the end, and the printed multiple drug products (drugs) can meet the requirements of high precision, high quality, and high consistency of drug products (drugs); then the preset value can be set to -76 kPa, and the air pressure pump can work for 8 seconds or more (such as 10 seconds) to ensure that the air pressure of the filling cavity, the melt extrusion cavity, and the printing cavity reaches the preset value of -76 kPa. In some existing technical solutions, the air pressure control channel 1151 is located at the melt extrusion chamber, where the material is in a molten fluid state. Under the influence of the air pressure control pressure (negative pressure), the melt 132 is at risk of being drawn back and causing blockage of the air pressure control channel 1151. This not only leads to air pressure control failure but also damages the air pressure control channel and the air pressure pump, making cleaning and maintenance impossible. In this embodiment, during the drug product preparation process, the filling chamber receives the filled solid printing material (such as the printing material of the preceding product) or the shelled printing material; the end of the melt extrusion chamber near the filling chamber is empty or filled with solid printing material 131, while the end of the melt extrusion chamber near the printing chamber is filled with melt 132; therefore, the filling chamber and the melt extrusion chamber are two independent but interconnected chambers. The air pressure control channel 1151 is located at the filling chamber, typically 20-150 cm away from the melt extrusion chamber. The air pressure control channel 1151 is far from the melt extrusion chamber, so the melt is usually not drawn back into the filler chamber, nor will it block the air pressure control channel 1151. Even if some melt tends to be drawn back, the melt has already solidified during the drawing process, so it will not block the air pressure control channel 1151. In this way, it can effectively eliminate the molding defects of the subsequent drug products, improve the quality and performance of the drug products, and effectively prevent the backflow of molten material.

[0395] In some embodiments, the second air pressure control module 115 of system 100 also includes a control valve (not shown in the figures) connected to the air pressure pump 1152 and used to start and stop the air pressure pump 1152, such as a solenoid valve, a pneumatic valve, etc.

[0396] In some embodiments, system 100 further includes a pressure detection device 1153 for detecting the pressure value inside the packing cavity. The pressure detection device 1153 includes at least one pressure sensor. In this embodiment, the pressure sensor senses the pressure inside the packing cavity through a pressure control channel 1151 and feeds it back to the second pressure control module 115. In some embodiments, the pressure sensor is further defined as a pressure gauge capable of displaying real-time pressure measurements. It should be understood that in some embodiments, the pressure sensor may also sense the pressure inside the packing cavity and feed it back to the second pressure control module 115 through a pressure detection channel different from the pressure control channel 1151.

[0397] In some embodiments, the pneumatic pump 1152 is configured to stop pressure control when a first threshold pressure is determined based on measurements from the pressure detection device 1153. Specifically, when the pressure reading displayed on the pressure gauge reaches the first threshold pressure, the operating end (operator or robotic arm) stops the pneumatic pump 1152, or the system feeds back the pressure reading to a controller (not shown in Figure 2A) of the second pressure control module. The controller sends a stop pressure command to the control valve, which then controls the pneumatic pump 1152 to stop operating. In some embodiments, the pneumatic pump 1152 includes at least one of a rotary vane pump, a water circulation pump, and a diaphragm pump; those skilled in the art can also choose any disclosed or future disclosed pneumatic pump according to actual needs.

[0398] In some embodiments, the second air pressure control module 115 further includes a blockage alarm mechanism (not shown in Figure 2A) that generates an alarm signal when a second threshold air pressure is determined to be reached based on measurements from the air pressure detection device 1153. In some embodiments, the aforementioned second threshold air pressure is a preset alarm air pressure value (e.g., -50 kPa) for air pressure control channel blockage. When the measurement value from the air pressure detection device 1153 is determined to reach the second threshold air pressure, it indicates that the air pressure control channel is blocked, and the operating end (operator or robotic arm) clears the air pressure control channel. In other embodiments, the measurement value from the air pressure detection device 1153 is further limited to the absolute value of air pressure change within a preset time period monitored by the air pressure detection device 1153, such as the absolute value of air pressure change within 5 seconds. When the absolute value of air pressure change within 5 seconds from the air pressure detection device 1153 is determined to reach the second threshold air pressure (e.g., -50 kPa), it indicates that the air pressure control channel is blocked, and the operating end (operator or robotic arm) clears the air pressure control channel. In some embodiments, the clogging alarm mechanism includes a filter for filtering the printed melt 132. The filter is disposed within the pneumatic control channel to filter out residual material for easy subsequent cleaning. The filter includes a filter screen with multiple sieve holes. The shape and size of the sieve holes are set according to the material's performance parameters, etc. For example, in one embodiment, the sieve holes are circular with a diameter of 0.4 mm to 0.6 mm.

[0399] In other embodiments, system 100 further includes a material conveying module 111, which includes a material conveying chamber communicating with the filling chamber for conveying printing material 131 from the filling chamber to the melt extrusion chamber. The aforementioned material conveying chamber, filling chamber, melt extrusion chamber, and printing chamber are connected to allow printing material 131 to move from the filling chamber to the melt extrusion chamber and to allow melt to be supplied from the melt extrusion chamber to the printing chamber via a release switch module; and the material conveying chamber, filling chamber, and melt extrusion chamber, with melt 132 loaded at one end near the printing chamber, constitute a sealed, interconnected chamber. In some embodiments, the supply unit 110 of system 100 is horizontally positioned, and the printing material does not automatically move from the filling chamber to the melt extrusion chamber by its own gravity. The aforementioned material conveying module 111 can convey printing material 131 from the filling chamber to the melt extrusion chamber. The feeding module 111 includes a plunger housed within a feeding chamber, which can move back and forth within the feeding chamber. The plunger pushes printing material 131 from the filler chamber to the melt extrusion chamber. A pneumatic control channel 1151 communicates internally with the filler module 112 and / or the pneumatic control channel communicates internally with the feeding chamber. In this embodiment, during the drug product preparation process, the filling cavity receives the integrated solid printing material or the shell-type printing material; the end of the melt extrusion cavity near the filling cavity is empty or loaded with solid printing material 131, and the end of the melt extrusion cavity near the printing cavity is loaded with melt 132; the conveying cavity is located on the side of the filling cavity away from the melt extrusion cavity and is connected to the filling cavity (the conveying cavity can also be regarded as part of the filling cavity). The conveying cavity and the melt extrusion cavity are also two independent but connected cavities. Compared with a system without a conveying module, the distance between the conveying cavity and the melt extrusion cavity is farther than the distance between the filling cavity and the melt extrusion cavity. If the air pressure control channel 1151 is set at the position of the conveying cavity, it is usually 20-150 cm away from the melt extrusion cavity. The air pressure control channel 1151 is far from the melt extrusion chamber and there is a filling chamber in between. Therefore, the melt will not be drawn back into the feeding chamber, nor will it block the air pressure control channel 1151. This ensures that the molding defects of the subsequent drug products are effectively eliminated, the quality and performance of the drug products are improved, and the molten material can be effectively prevented from flowing back.

[0400] In some embodiments, as shown in Figures 3A-3B, an additive manufacturing system 300 for producing pharmaceutical products according to one embodiment of this application, considering the special characteristics of printing materials typically having high viscosity (e.g., 800 Pa·s and higher), includes a filler module for receiving printing material 331 for generating pharmaceutical products, a feed module for pushing the printing material 331, a melt extrusion module for receiving the printing material 331 pushed by the feed module and forming a melt 332 from the printing material 331, a printing unit 321 for receiving the melt 332 from the melt extrusion module and generating pharmaceutical products from the melt 332, and a second air pressure control module for controlling the internal air pressure of the filler module, the feed module, and the melt extrusion module. The filler module, the feed module, the melt extrusion module, and the second air pressure control module constitute a horizontally arranged supply unit. Even with the supply unit vertically positioned and the filler module located above the melt extrusion module, high-viscosity printing material (melt) cannot move from the filler module to the melt extrusion module at the ideal flow rate and pressure based on its own gravity. Therefore, the feed module is used to push the high-viscosity printing material from the filler module to the melt extrusion chamber. Furthermore, the printing unit 321 of system 300 also has a printing platform 322, which receives the melt and generates the drug product 900. System 300 has a structure basically the same as system 100; the structural construction of the remaining parts of system 300 is the same as that of system 100 and will not be repeated here unless the context clearly indicates otherwise. Figures 3A-3C show schematic diagrams of system 300 with the feed module in different positions. The filler module of system 300 also has a filler channel 3121, and its feed module further defines it as including a feed chamber 3112 and a plunger rod 3111. The plunger rod 3111 can reciprocate axially within the feeding chamber 3112, and is used to push the printing material 331 to the melt extrusion chamber 3131. It should be understood that when the printing material is a monolithic solid printing material, its volume is typically larger than that of granular or powdered raw materials. Compared to other forms of feeding mechanisms (such as screw extrusion mechanisms), the plunger-type feeding module facilitates the pushing of larger monolithic solid printing materials and also facilitates subsequent cleaning of the feeding chamber. In some embodiments, the feeding module can also be a feeding device with other structures and forms, such as a single-screw feeding mechanism or a twin-screw feeding mechanism; this patent does not limit this.Further elaboration: As is known to those skilled in the art, screw conveying mechanisms have multiple screw channels. When using screw conveying mechanisms to push hot-melt materials, they are often suitable for manufacturing pharmaceutical products with low cleanliness or purity requirements, such as plastics, resins, and rubber. When changing materials to prepare pharmaceutical products, these mechanisms only need to use new materials to fill the pharmaceutical product and then discard the transitional pharmaceutical product to meet the cleaning requirements. There is no need for disassembly or special consideration for cleaning. Therefore, the structure is often complex, and cleaning and disassembly are inconvenient, making it unsuitable for manufacturing pharmaceutical products with high cleanliness or purity. However, pharmaceutical dosage units (e.g., tablets, capsules, printlets) require the entire closed cavity to be completely cleaned. Therefore, frequent disassembly and cleaning of the sealed cavity are required to meet the cleanliness or purity requirements of the pharmaceutical product. Compared to the aforementioned screw conveying mechanisms, plunger-type conveying modules have a simpler structure and are easier to clean. Furthermore, the reason for using an integrated solid printing material filler in this embodiment is to consider the high quality, high precision, and high consistency requirements of pharmaceutical products. Using an integrated solid printing material filler allows for the removal of small amounts of air trapped during material mixing or stirring during solid printing material preparation, further ensuring the high-quality preparation of the final pharmaceutical product from the source. Additionally, compared to granular or powdered raw materials, using an integrated solid material filler also avoids the introduction of dust or other non-pharmaceutical substances into the filler cavity during the filling process, ensuring the cleanliness and purity of the printing material and improving the quality of the final pharmaceutical product. Moreover, compared to granular materials, there is no air trapped within the granular material during the filling process. The small amount of air trapped within granular materials is more difficult to expel than air within the cavity, as the granular materials may form tiny enclosed spaces from which air cannot escape. Furthermore, using an integrated solid printing material filler enables quantitative filling, allowing for precise control of the filler quantity without the need for additional quantitative steps.

[0401] In some embodiments, the printing material 331 of system 300 is a cylindrical solid printing material, such as a bullet-shaped solid printing material or a cylindrical pre-printed solid material after the shell of a shelled printing material has been removed. In some embodiments, the filling cavity 3122 has a cylindrical cavity structure. The outer diameter d2 of the printing material 331 is less than or equal to the outer diameter d4 of the plunger rod 3111, facilitating pushing. The plunger rod 3111 has a cylindrical structure, and its outer diameter d4 is less than the inner diameter d3 of the filling cavity. The melt extrusion module 113 includes a melt extrusion cavity with a cylindrical cavity structure. The inner diameter d1 of the melt extrusion cavity is equal to the outer diameter d4 of the plunger rod. In some embodiments, the plunger rod 3111 is also fitted with a sealing ring (not shown), which can further ensure good sealing between the plunger rod 3111 and the melt extrusion cavity 3131 to prevent melt leakage and prevent changes in gas pressure within the cavity. An arc-shaped transition surface 3123 exists between the melt extrusion chamber 3131 and the filler chamber 3122. In some embodiments, a radial gap exists between the outer wall of the printing material 331 and the inner wall of the filler chamber 3122, and a gap exists between the outer wall of the plunger rod and the inner wall of the filler chamber; there is no gap between the outer wall of the plunger rod and the inner wall of the melt extrusion chamber, and the area of ​​the plunger rod 3111 with the sealing ring is interference-fitted with the inner wall of the melt extrusion chamber 3131. This ensures good sealing between the plunger rod 3111 and the melt extrusion chamber 3131 to prevent melt 332 leakage and pressure changes within the chamber, while also preventing frequent friction between the plunger rod 3111 and the filler chamber 3122 to further avoid scratching the sealing ring on the outer wall of the plunger rod 3111, extending the service life of the sealing ring, avoiding frequent disassembly and replacement, ensuring sufficient sealing of the chamber, and ensuring effective pressure control over a long period. It should be noted that in other embodiments, the plunger rod, the filling cavity, the melt extrusion cavity, and the solid printing material have other shapes and structures, such as cuboids, polygons, elliptical cylinders, etc. As long as good sealing is ensured between the plunger rod 3111 and the melt extrusion cavity 3131 and no friction occurs between the plunger rod 3111 and the filling cavity 3122, the same technical effect as the cylindrical structure can be achieved.

[0402] In some embodiments, as shown in Figures 3A-3C, the second air pressure control module 315 of system 300 is similar to the second air pressure control module 115 of system 100, also including an air pressure control channel 3151 and an air pressure pump 3152 communicating with the inside of the packing cavity. Activating the air pressure pump 3152 can expel air from the packing cavity, melt extrusion cavity, and conveying cavity, causing the air pressure inside the cavity to reach the desired preset value. If a negative pressure is formed, its function is the same as that of the second air pressure control module 115 of system 100. In some embodiments, as shown in Figures 3A-3B, the second air pressure control module 315 also includes an air pressure detection device for detecting the air pressure value inside the packing cavity 3122 of the packing module. In some embodiments, as shown in 3A, the pressure detection device includes a pressure detection channel and a pressure sensor 3161. The pressure detection channel and the pressure control channel 3151 share a single channel, which communicates with the interior of the packing cavity 3122. In this embodiment, the pressure sensor 3161 is a pressure display capable of detecting and displaying real-time pressure. Of course, the second pressure control module 315 of system 300 can also be identical in structure and form to the second pressure control module 115 of system 100. For example, the pressure detection device could be a pressure gauge 3161 capable of displaying real-time pressure measurements, sensing the pressure inside the packing cavity through the pressure control channel 3151. Alternatively, the pressure gauge could sense the pressure inside the packing cavity through a pressure detection channel different from the pressure control channel 3151; this is not limited here.

[0403] In some embodiments, the plunger rod 3111 is configured to begin moving toward the melt extrusion module and push the printing material 331 into the melt extrusion cavity when the measurement value from the air pressure detection device determines that a first threshold air pressure has been reached. The aforementioned first threshold air pressure is a preset ideal air pressure value in the sealed cavity after effective air pressure control. When the measurement value from the air pressure detection device determines that the first threshold air pressure has been reached, it indicates that the air pressure control is successful and the air pressure control ends. At this time, the plunger rod 3111 starts the pushing operation.

[0404] In some embodiments, the second air pressure control module further includes a blockage alarm mechanism (not shown) that generates an alarm signal when a second threshold air pressure is reached based on measurements from an air pressure detection device. The aforementioned second threshold air pressure is a preset alarm air pressure value (e.g., -50 kPa) for air pressure control channel blockage. When the measurement value from the air pressure detection device determines that the second threshold air pressure has been reached, it indicates that the air pressure control channel is blocked, and the operating end (operator or robotic arm) clears the air pressure control channel. In other embodiments, the measurement value from the air pressure detection device 3153 is further limited to the absolute value of air pressure change within a preset time period monitored by the air pressure detection device, such as the absolute value of air pressure change within 5 seconds. When the absolute value of air pressure change within 5 seconds from the air pressure detection device 3153 is determined to have reached the second threshold air pressure, it indicates that the air pressure control channel is blocked, and the operating end (operator or robotic arm) clears the air pressure control channel. Of course, it could also be the air pressure change value within a preset time period such as 3 seconds, 6 seconds, or 7 seconds. In some embodiments, the blockage alarm mechanism includes a filter for filtering the printed melt 332. The filter is disposed within the pneumatic control channel 3151 to filter out residual material for easy subsequent cleaning. The filter includes a filter screen with multiple sieve holes. The shape and size of the sieve holes are set according to the material's performance parameters, etc. For example, in one embodiment, the sieve holes are circular with a diameter of 0.4 mm to 0.6 mm.

[0405] In some embodiments, the pneumatic control channel 3151 has a third state and a fourth state. In the third state, the channel opening of the pneumatic control channel 3151 is located inside the packing cavity and / or the conveying cavity. In the fourth state, the channel opening of the pneumatic control channel 3151 is located outside the packing cavity and / or the conveying cavity. In some embodiments, the system further includes a second drive device, such as a cylinder, hydraulic cylinder, actuator, lead screw module, motor, etc., for driving the pneumatic control channel 3151 to reciprocate between the third and fourth states.

[0406] In some embodiments, system 300 further includes a displacement detection module (not shown) for detecting the displacement of plunger rod 3111. In some embodiments, plunger rod 3111 is configured to pause movement toward the melt extrusion module when a first threshold displacement is determined to have been reached based on measurements from the displacement detection module. Plunger rod 3111 is configured to stop movement toward the melt extrusion module when a second threshold displacement is determined to have been reached based on measurements from the displacement detection module. The first threshold displacement is a preset first displacement value (as shown in Figure 3B) when the feeding end of the plunger rod 3111 enters the melt extrusion cavity 3131. When the measurement value of the displacement detection module determines that the first threshold displacement has been reached, it indicates that the printing material 331 has been pushed into the melt extrusion cavity 3131. Then, as the melt 332 of the melt extrusion cavity 3131 is gradually extruded out of the melt extrusion cavity, the plunger rod continues to push the printing material 331 at a suitable speed, displacement, or torque. The specific pushing parameters can be selectively set by those skilled in the art based on the performance of the printing material 331, the cavity structure and size of the melt extrusion cavity, the structure and size of the plunger rod, and other parameters. The second threshold displacement is a preset second displacement value for the feed end of the plunger rod entering the melt extrusion chamber (as shown in Figure 3C). When the measurement value of the displacement detection module determines that the second threshold displacement has been reached, it indicates that the printing material 331 has been completely transformed into melt 332 and pushed into the melt extrusion chamber 3131 near the end of the extrusion channel. At this time, the entire stroke of the plunger rod 3111 ends, and it will then return to the starting position in the feed chamber 3112. In some embodiments, the displacement detection module includes a displacement sensor. In other embodiments, the displacement detection module is replaced by a position detection module, which is used to detect the position of the plunger rod and includes a position sensor.

[0407] In some embodiments, as shown in Figures 3A-3B, the plunger rod 3111 of system 300 has a seventh state, an eighth state, and a ninth state. In the seventh state, the end of the plunger rod 3111 is located within the feed chamber 3112. In the eighth state, the end of the plunger rod 3111 is located within the melt extrusion chamber 3131, near the packing chamber 3122. In the ninth state, the end of the plunger rod 3111 is located within the melt extrusion chamber, away from the packing chamber. Thus, the entire stroke of the plunger rod 3111 is within the sealed cavity formed by the packing chamber 3122, the conveying chamber 3112, and the melt extrusion chamber 3131. This design is adopted because if the seventh state of the plunger rod 3111 is located outside the conveying chamber 3112, the seal on the outer circumference of the plunger rod needs to be tightly sealed to the inner wall of the sealed cavity to prevent leakage. Therefore, the requirements for the seal between the plunger rod 3111 and the end of the conveying chamber 3112 are high. During the frequent back-and-forth movement of the plunger during advancement and retraction, the plunger seal is subjected to high-frequency friction, which damages the plunger seal and affects its service life. This can further lead to seal failure, causing inconsistent air pressure in the sealed cavity and affecting the subsequent defects of the finished drug product. However, in the technical solution of this embodiment, the entire stroke of the plunger rod 3111 is within the sealed cavity, eliminating the need to consider the sealing problem between the plunger rod 3111 and the end of the conveying chamber 3112. This ensures effective control of air pressure and maintains constant air pressure and pressure in the sealed cavity, guaranteeing the manufacture of high-quality drug products and ensuring the consistency of the drug products.

[0408] In some embodiments, the feeding module is connected to the preceding product melt-forming device, and the outlet of the feeding module is directly or indirectly connected to the inlet of the preceding product melt-forming device. Different drugs or excipients enter the preceding product melt-forming device, are mixed and melted by a screw extruder, and excess air is expelled through an exhaust port to prevent air bubbles from remaining in the drug preceding product formed after melt extrusion. In this embodiment, the drug preceding product is a solid drug or excipient preceding product with almost uniform shape, size, and weight. Compared with molten drug or excipient preceding products, the inventors have found that uniform solid drug or excipient preceding products can increase the number of drug quality checkpoints, ensuring a high degree of consistency in the drugs produced by the additive manufacturing system. The solid preceding product enters the feeding unit, which includes a filling chamber and a melt extrusion chamber. The shape and size of the solid preceding product match the filling chamber and the melt extrusion chamber. The solid preceding product moves from the filling chamber to the melt extrusion chamber under negative pressure. The solid precursor product is molten at one end near the melt extrusion chamber and solid at the other end near the filler chamber. Therefore, the solid precursor product itself acts as a barrier to prevent backflow of the melt. The other end of the melt extrusion chamber is connected to at least one nozzle of the printing unit. After melting, the solid precursor product is distributed to the platform module through the nozzle. In this embodiment, a negative pressure environment is set in the feeding unit and the nozzles to ensure a consistent pressure environment among the multiple nozzles, allowing the melt to be evenly distributed from the nozzles.

[0409] Example 2 of the second air pressure control module

[0410] Figure 2B illustrates an additive manufacturing system 200 for producing pharmaceutical products according to one embodiment of this application. The system 200 is primarily adapted to a shell-mounted solid printing material, which includes a shell 233 and an integrated solid printing material 231. The shell accommodates the solid printing material 231 and allows the solid printing material 231 to detach from it under external force. In some embodiments, the preceding product is the shell-mounted solid printing material.

[0411] An additive manufacturing system 200 for producing pharmaceutical products includes a filler module, a feeding module 211, a melt extrusion module 213, a printing unit 221, and a second air pressure control module 215. The filler module has a filler channel for receiving printed material with a shell. The feeding module 211 includes a feeding chamber for pushing solid printed material 231 within the shell. The melt extrusion module 213 includes a melt extrusion chamber (although only one melt extrusion chamber is shown in Figure 2B, it should be understood that the melt extrusion module 113 includes at least two melt extrusion chambers as shown in Figure 2A) for receiving the solid printed material 231 pushed by the feeding module 211 and forming a melt 232 from the solid printed material 231. The printing unit 221 includes a printing chamber and a printing channel connected to the printing chamber for receiving the melt 232 from the melt extrusion module 213 and distributing the melt 232 to the printing channel to form a pharmaceutical product. In this embodiment, the filling channel is an open filling port. The housing 233 is filled into the filling module through the filling channel and fastened to the filling module. At this time, the housing 233 is connected to the filling cavity, the feeding cavity, and the printing cavity to allow the solid printing material 231 to move from the housing 233 to the melt extrusion cavity and to allow the melt to be supplied from the melt extrusion cavity to the printing cavity via the release switch module. Furthermore, the housing 233, the feeding cavity, and the melt extrusion cavity 213, which is loaded with melt 232 near the printing unit, constitute a closed and connected cavity. Therefore, in this embodiment, the housing 233 is equivalent to the filling cavity of the system 100. It is worth noting that in some embodiments, the filling module also has a filling cavity. After the solid, shelled printing material is filled into the filling cavity, the shell is fastened inside the filling cavity. There is a certain gap between the outer periphery of the shell and the outer periphery of the filling cavity. Therefore, the feeding cavity, the filling cavity, and the printing cavity constitute a closed and interconnected cavity, similar to the closed and interconnected cavity of system 100. Those skilled in the art can choose different system structures according to actual application needs and scenarios, which will not be elaborated here. The second air pressure control module 215 is connected to the filling cavity or the feeding cavity and is used to remove air from the shell 233, the feeding cavity, and the melt extrusion cavity so that the air pressure of the shell, the feeding cavity, the melt extrusion cavity, and the printing cavity is brought to the desired preset value, such as removing air from the aforementioned sealed cavity to control the air pressure at -65KPa and below. The shell 233, the feeding module 211, the melt extrusion module 213, and the second air pressure control module 215 constitute the supply unit 210. In some embodiments, the supply unit 210 of the system 200 is vertically arranged, and the melt extrusion chamber is located above the housing. As mentioned above, the solid printing material needs to be subjected to external force to detach from the housing. Therefore, by setting the aforementioned feeding module 211, the solid printing material 231 can be pushed from the housing to the melt extrusion chamber.Furthermore, the printing unit 221 of system 200 also has a printing platform 222, which is used to receive the melt and generate the drug product. The structure of system 200 is basically similar to that of system 100. The structural construction of the remaining parts of system 200 is the same as that of system 100 and will not be repeated here unless the context clearly indicates otherwise. It should be understood that the supply unit as a whole can also be arranged in any orientation, such as horizontally or obliquely, and the melt extrusion cavity can also be located below, obliquely below, or obliquely above the shell. In this way, the system 200 can maintain a suitable air pressure environment during the preparation of drug products, which can avoid quality defects such as collapse, bubbles, sponginess, and voids in the subsequent drug products and improve the quality of drug products. On the other hand, if the air in the aforementioned sealed cavity is removed and the air pressure is controlled at -65 kPa or below, it can also prevent the melt in the printing cavity from being undesirably discharged or leaked from the printing channel along with large bubbles in the melt at the end of printing. Therefore, air pressure control plays a role in preventing material leakage, enabling precise control of the amount of melt, ensuring the accuracy of printed drug products and guaranteeing the consistency between single or multiple batches of drug products.

[0412] In some embodiments, the preset value of the second air pressure is -65 kPa to -100 kPa. Those skilled in the art can set different preset values ​​of the second air pressure according to different material properties (such as viscosity), the amount of drug product, and other factors. For example, the inventors found through multiple experiments that a certain printing material with a viscosity of 1100 Pa·s can reach the preset value (-94 kPa) when the air pressure is controlled for 6 seconds, and there is no undesirable melt discharge during the printing process and at the end, and the printed multiple drug products can meet the requirements of high precision, high quality, and high consistency of drug products. Then the preset value can be set to -94 kPa, and the air pressure pump can work for 6 seconds or more (such as 8 seconds) to ensure that the air pressure of the filling cavity, the melt extrusion cavity, and the printing cavity reaches the preset value of -94 kPa.

[0413] In some embodiments, the additive manufacturing system can print 32 pharmaceutical products simultaneously, with each of the 32 filaments averaging 12.32 mg.

[0414] In some embodiments, the additive manufacturing system printed two batches of drug tablets. One batch consisted of 20 drug tablets, with an average weight of 204.32 mg; the other batch consisted of 15 drug tablets, with an average weight of 208.13 mg.

[0415] In some embodiments, when the weight of the drug tablet is less than 300 mg, the relative deviation of the weight is about ±10% or less, such as about ±9% or less, about ±8% or less, about ±7.5% or less, about ±7% or less, about ±6% or less, about ±5% or less, about ±4% or less, or about ±3% or less, or about ±2% or less, or about ±1% or less.

[0416] In some embodiments, when the weight of the drug tablet is equal to or greater than 300 mg, the relative deviation of the weight is about ±5% or less, for example, about ±4% or less, about ±3% or less, about ±2% or less, or about ±1% or less.

[0417] In some embodiments, the inconsistency in unit weight (i.e., the inconsistency between unit weights within the same batch) is less than 10% (e.g., 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 9.5%, 10%). In some embodiments, the inconsistency in batch weight (i.e., the inconsistency between batch weights) is less than 10% (e.g., 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 9.5%, 10%).

[0418] Furthermore, through numerous experiments, the inventors of this invention discovered that the desired preset value of the second air pressure is related to the performance parameters of the printing material (such as glass transition temperature (TG), viscosity, etc.). Different preset values ​​of the second air pressure can be adjusted for printing materials with different performance parameters. For example, the inventors conducted numerous experiments with various printing materials and found that materials such as polyvinylpyrrolidone (VA64) and hydroxypropyl methylcellulose acetate succinate (HPMCAS) require higher preset values ​​of the second air pressure to achieve a better effect in preventing undesirable leakage of the printing material. Therefore, this preset value is usually obtained based on the size of the cavity, the performance of the material, the performance of the second air pressure control module (such as power), and experimental data.

[0419] In other embodiments, shelled solid printing materials are used as fillers. Firstly, this ensures that the preceding product does not deform during transport and transfer. Compared to shellless integrated solid printing materials, especially those with lower viscosity, which are prone to deformation, damage, or even loss during transport and transfer, shelled solid materials protect the preceding product from deformation, damage, and maintain its integrity. Secondly, compared to granular materials, air is not trapped within the granular material during filling, and trapped air is more difficult to expel than air within the cavity. Thirdly, the shell allows for a wider range of printing materials with varying viscosities, such as some low-viscosity pharmaceutical printing materials (e.g., 800 Pa·s), as long as the material does not leak out of the shell. Shellless integrated solid printing materials, on the other hand, require complete solidity for transport, filling, and handling. Finally, since the preceding product is an integrated solid printing material, quantitative filling can be achieved without the need for additional quantitative steps to precisely control the amount of filler. Furthermore, in some fully automated, continuous production embodiments of pharmaceutical products, even without shelled solid printing materials, using shellless integrated solid printing materials directly requires shellless integrated solid printing materials of a specific desired size to achieve continuous production. For example, an integrated solid printing material with a diameter of 30mm is convenient for a certain feeding device of a 30mm diameter feeding module to push. In this case, obtaining a preceding product with a diameter of 30mm requires a tube 733 or tooling of the corresponding size to be formed, and an additional shell removal process is required after the forming is completed. Therefore, directly using shelled solid printing materials can reduce one shell removal process and has the aforementioned advantages, ensuring the high quality, high precision, and high consistency of the subsequently printed pharmaceutical products while achieving efficient continuous production.

[0420] In some embodiments, the second pneumatic control module 215 of system 200 includes a pneumatic control channel 2151 and a pneumatic pump. The pneumatic pump can be used to remove air from the housing 233, the conveying chamber, and the melt extrusion chamber through the pneumatic control channel 2151. The pneumatic control channel 2151 has a third state and a fourth state. The third state (the dashed line portion in Figure 2B) is the pneumatic control operating position. The fourth state is the initial position of the pneumatic control channel 2151. In the third state, the outlet of the pneumatic control channel 2151 is located inside the conveying chamber. In the fourth state, the outlet of the pneumatic control channel 2151 is located outside the conveying chamber. In existing technologies, the air pressure control channel opening of some technical solutions is directly set on the side wall of the melt extrusion cylinder. Not only may the melt be drawn back and block the air pressure control channel, but the feeding device of its feeding module will move towards the melt extrusion module when feeding material. When a second feeding is required, it will first return to its initial position before feeding material again. During the back-and-forth movement of the feeding device, a small amount of printing material may also be brought back and adhere to the air pressure control channel opening, blocking the air pressure control channel. This will cause the air pressure control to fail and will damage the air pressure control channel and air pressure pump, which cannot be cleaned or repaired. In this embodiment, the air pressure control channel 2151 can move back and forth between a third state and a fourth state. Thus, even if a small amount of printing material is brought back and adheres to the air pressure control channel opening during the previous retraction of the feeding module to its initial position, after the next filling, the air pressure control channel 2151 will move from its fourth state back to its third state, passing through the side wall of the feeding module 211 to reach the interior of the feeding module 211, pushing out the material adhering to the air pressure control channel opening and ensuring the air pressure control channel 2151 remains unobstructed. After the air pressure control ends, the air pressure control channel 2151 returns to its fourth state to ensure continued effective air pressure control after the next filling. Therefore, the air pressure control channel 2151 has two functions: providing an air pressure control channel for the air pump and automatically cleaning the air pressure control channel opening to ensure unobstructed air pressure. This ensures effective air pressure control and, through good cavity sealing, ensures constant air pressure and pressure within the sealed cavity, guaranteeing the manufacture of high-quality pharmaceutical products and ensuring the consistency of the pharmaceutical products.

[0421] In some embodiments, the second air pressure control module 215 of system 200 further includes an air pressure detection device 216 for detecting the air pressure value inside the conveying cavity 211. The air pressure detection device 216 includes an air pressure detection channel 2161 and an air pressure sensor. In this embodiment, the air pressure sensor senses the air pressure inside the packing cavity through the air pressure control channel 2161 and feeds it back to the second air pressure control module 215. In some embodiments, the air pressure sensor is further defined as a pressure gauge capable of displaying real-time air pressure measurements. In some embodiments, the air pressure detection channel 2161 has a fifth state and a sixth state. In the fifth state (the dashed line portion in Figure 2B), the outlet of the air pressure detection channel 2161 is located inside the conveying cavity. In the sixth state, the outlet of the air pressure detection channel 2161 is located outside the conveying cavity. Similarly, after the next filling, the air pressure detection channel 2161 will move from its sixth state to its third state, passing through the side wall of the conveying cavity to reach the inside of the conveying cavity, pushing out the material adhering to the air pressure detection channel opening into the conveying cavity, ensuring that the air pressure detection channel 2161 is unobstructed; after the air pressure control ends, the air pressure detection channel 2161 returns to the fourth state. In this way, it can be ensured that the detected air pressure value is the real air pressure value inside the closed cavity, rather than the false air pressure value inside the air pressure detection channel 2161 sealed after the air pressure detection channel opening is blocked by the printed melt 332, ensuring effective air pressure measurement; therefore, the air pressure detection channel 2161 has two functions, one is to detect air pressure, and the other is to ensure that the air pressure detection channel 2161 is unobstructed to ensure that the detected air pressure is effective. Furthermore, the air pressure detection channel 2161 and the air pressure control channel 2151 are two different channels. Even if the air pressure control channel 2151 is blocked, the air pressure sensor (such as a barometer) will still sense the actual air pressure value inside the sealed cavity through the air pressure detection channel 2161.

[0422] In some embodiments, the air pressure inspection channel and the air pressure control channel are located close to each other, and the same drive mechanism can be used to control the air pressure inspection channel and the air pressure control channel to open or close simultaneously.

[0423] In some embodiments, as shown in Figures 10A and 10B, the pneumatic control channel includes a pneumatic control cylinder 11 with one end connected to the first conveying chamber, an ejector 12 movably inserted into the pneumatic control cylinder 11, and a drive mechanism 13 for pushing the ejector 12 to move axially within the pneumatic control cylinder 11. The drive mechanism 13 is inserted into the other end of the pneumatic control cylinder 11, and the connection is sealed by sealing devices 14 and 15. A pneumatic adjustment port 24 connected to a pneumatic pump is provided on the side wall of the pneumatic control cylinder 11. The ejector 12 includes an ejector head 23 and an ejector body 22. A pneumatic control channel 21 arranged axially is provided on the side wall of the ejector body 22. The pneumatic control channel 21 is a through channel. The pneumatic adjustment port 24 is connected to the pneumatic control channel 21. When the ejector 12 of the pneumatic control channel moves axially toward the first conveying cavity along the pneumatic control cylinder until the ejector head 23 is inside the first conveying cavity, its pneumatic adjustment port 24 communicates with the first conveying cavity through the aforementioned pneumatic control channel 21. Gas A inside the first conveying cavity flows along the direction of the arrow through the pneumatic control channel 21 and the pneumatic adjustment port 24. When the ejector head 23 of the pneumatic control channel is outside the first conveying cavity, that is, when it retracts into the pneumatic control cylinder 11, its pneumatic adjustment port 24 is not connected to the first conveying cavity. At this time, the pneumatic control channel 21 and the pneumatic adjustment port 24 of the pneumatic control channel form a sealed cavity. In some embodiments, the pneumatic detection channel is set up almost the same as the pneumatic control channel, and also has a corresponding pneumatic detection cylinder, ejector, drive mechanism, etc., only the pneumatic pump is replaced by a pneumatic sensor; it will not be described in detail here.

[0424] In some embodiments, an additive manufacturing system 400 for producing pharmaceutical products according to one embodiment of the present application is shown in Figures 4A-4C, with Figures 4A-4C showing schematic diagrams of the system 400 with the material delivery module in different positions.

[0425] System 400 is primarily adapted to shelled solid printing materials, which include a shell 433 and an integrated solid printing material 431. The shell is used to contain the solid printing material 431 and allows the solid printing material 431 to detach from it under external force. The additive manufacturing system 400 for producing pharmaceutical products includes a filler module, a material conveying module 411, a melt extrusion module 413, a printing unit 421, and a second air pressure control module 415. The filling module has a filling channel for receiving printed material with a shell; the feeding module 411 includes a feeding cavity for pushing solid printed material 431 inside the shell; the melt extrusion module 413 includes a melt extrusion cavity 4131 for receiving the solid printed material 431 pushed by the feeding module 411 and forming melt 432 from the solid printed material 431; the printing unit 421 includes a printing cavity and a printing channel connected to the printing cavity for receiving melt 432 from the melt extrusion module 413 and distributing the melt 432 to the printing channel to form a pharmaceutical product. In this embodiment, the filling channel is an open filling port. The housing 433 is filled into the filling module through the filling channel and fastened to the filling module. At this time, the housing 433 is connected to the filling cavity, the feeding cavity, and the printing cavity to allow the solid printing material 431 to move from the housing 433 to the melt extrusion cavity 4131 and to allow the melt to be supplied from the melt extrusion cavity 4131 to the printing cavity. Furthermore, the housing 433, the feeding cavity, and the melt extrusion cavity 4131, which is loaded with melt 432 near the printing unit, constitute a closed and connected cavity. Therefore, in this embodiment, the housing 433 is equivalent to the filling cavity of the system 100. It is worth noting that in some embodiments, the filling module also has a filling cavity. After the solid, shelled printing material is filled into the filling cavity, its shell is fastened inside the filling cavity. There is a certain gap between the outer periphery of the shell and the outer periphery of the filling cavity. Due to the existence of this gap, the material conveying cavity is not divided into two independent and non-connected material conveying cavities, but remains a single material conveying cavity. Therefore, the material conveying cavity, the filling cavity, and the printing cavity constitute a closed and connected cavity, similar to the closed and connected cavity of system 100. Those skilled in the art can choose different system structures according to actual application needs and scenarios, which will not be elaborated here. The second air pressure control module 415 is connected to the feeding chamber and is used to remove air from the housing 233, the feeding chamber, and the melt extrusion chamber 4131 to bring the air pressure in the feeding chamber, the melt extrusion chamber 4131, and the printing chamber to a desired preset value, such as removing air from the housing 233, the feeding chamber, and the melt extrusion chamber 4131 to reduce the air pressure to a negative pressure of -65 kPa or below. The housing 433, the feeding module, the melt extrusion module, and the second air pressure control module constitute a supply unit.In some embodiments, the supply unit of the system 400 is vertically oriented, with the melt extrusion chamber 4131 located above the housing. As mentioned earlier, the solid printing material requires external force to detach from the housing 433. Therefore, by providing the aforementioned feeding module 411, the solid printing material 431 can be pushed from the housing 433 to the melt extrusion chamber 4131. Furthermore, the printing unit 421 also has a printing platform 422, which receives the melt and generates the drug product 900. The structure of system 400 is basically the same as that of system 200. The structural construction of the remaining parts of system 400 is the same as that of system 200 and will not be repeated here unless the context clearly indicates otherwise. It should be understood that the supply unit can also be arranged horizontally, obliquely, or in any other direction, and the melt extrusion chamber 4131 can also be located below, obliquely below, or obliquely above the housing.

[0426] In some embodiments, as shown in Figures 4A, 4B, and 4C, the feeding module 411 includes a first feeding cavity 4112 and a second feeding cavity 4113 divided by the shelled printing material. That is, when the shelled printing material (including integrated solid printing material) is filled into the filling module, the solid shelled printing material divides the feeding cavity into two independent feeding cavities that are not connected to each other. In this way, the shell 433 of the shelled printing material can directly replace the function of the filling cavity 3122 as shown in Figures 3A-3B, except that the feeding cavity is divided into two feeding cavities. It is worth noting that in some embodiments, the filling module also has a filling cavity. After the solid, shelled printing material is filled into the filling cavity, its shell is fastened inside the filling cavity. There is a certain gap between the outer periphery of the shell and the outer periphery of the filling cavity. Due to the existence of this gap, the material conveying cavity is not divided into two independent and non-communicating material conveying cavities, but remains a single material conveying cavity. Those skilled in the art can choose different system structures according to actual application needs and scenarios, which will not be elaborated here. The second air pressure control module includes an air pressure control device, which includes an air pressure control channel and an air pressure pump. The air pressure pump can be used to remove air from the shell 433, the material conveying cavity, and the melt extrusion cavity 4131 through the air pressure control channel 4151. Since the material conveying module of the system 400 in this embodiment has two material conveying cavities, the air pressure control channel includes a first air pressure control channel 4151 and a second air pressure control channel 4153. A first air pressure control channel 4151 is connected to a first conveying cavity 4112; a second air pressure control channel 4153 is connected to a second conveying cavity 4113. In some embodiments, as shown in Figures 4A to 4C, the first air pressure control channel 4151 has a third state and a fourth state. As shown in Figure 4A, in the third state, the opening of the first air pressure control channel 4151 is located inside the first conveying cavity 4112. As shown in Figure 4B, in the fourth state, the opening of the first air pressure control channel 4151 is located outside the first conveying cavity 4112. In this embodiment, the first air pressure control channel 4151 is disposed in the first feeding cavity 4112. The first air pressure control channel 4151 can move back and forth between the third state and the fourth state. Thus, even if the feeding device 4111 brings back a small amount of printing material 432 adhering to the opening of the first air pressure control channel during the previous retraction of its initial position, after the next filling, as shown in FIG4A, the first air pressure control channel 4151 will move from its fourth state to the third state, passing through the side wall of the first feeding cavity 4112 so that its air pressure channel opening reaches the first feeding cavity 4112, pushing the material adhering to the opening of the first air pressure control channel into the interior of the first feeding cavity 4112, ensuring that the air pressure control channel is unobstructed. After the air pressure control ends, the first air pressure control channel 4151 retracts to the fourth state to ensure that effective air pressure control continues after the next filling.In some embodiments, the second air pressure control channel opening can also be configured, like the first air pressure control channel 4151, to switch between inside and outside the second feeding cavity 4113. Alternatively, the second air pressure control channel opening 4153 can be directly located on the side wall of the second feeding cavity 4113. The specific configuration can be determined or adjusted by those skilled in the art based on actual needs, such as the properties of the printing material and the distance between the second feeding cavity and the melt extrusion cavity 4131. Furthermore, in some embodiments, the air pressure control channel 1151 of the second air pressure control module 115 of system 100, as shown in FIG2A, can also be configured, like the first air pressure control channel 4151 of system 400, to switch between inside and outside its filling module 112. Alternatively, as shown in FIG2A, the air pressure control channel opening 1151 can be directly located on the side wall of the filling module 112. As shown in Figure 4D, there is a certain gap 455 between the outer periphery of the shell (containing the integrated solid printing material) and the outer periphery of the filler cavity. Due to the existence of this gap, the feeding cavity is not divided into two independent and unconnected feeding cavities, but remains a single feeding cavity. After the first solid printing material is fed into the feeding cavity for melting, the second solid printing material is fed into the feeding cavity. Gas in the cavity is discharged through this gap, avoiding the generation of air bubbles inside the melt in the feeding cavity. This method replaces the pneumatic control module, eliminating the need for a pneumatic control module. In some embodiments, one end of the first solid printing material is arc-shaped. In some embodiments, one end of the second solid printing material is arc-shaped. The arc-shaped solid printing material is more conducive to the discharge of air in the feeding cavity through the gap 455. In some embodiments, as shown in Figure 4A, the system 400 also includes a second driving device for driving the pneumatic control channel to move back and forth between the third and fourth states. The type and structure of the drive device are not limited; it can be any one or more drive devices such as a lead screw module, hydraulic drive device, pneumatic drive device, or electric motor drive device.

[0427] In some embodiments, as shown in Figures 4A-4B, the system 400 further includes a pressure detection device for detecting the pressure value inside the first conveying cavity 4112. The pressure detection device includes a pressure sensor disposed within the first conveying cavity 4112 and a pressure detection channel 4161 communicating with the interior of the first conveying cavity 4112. In some embodiments, the pressure sensor is further defined as a pressure gauge 4162 capable of displaying real-time pressure measurements. In some embodiments, the pressure detection channel 4161 communicates with the interior of the conveying cavity. In some embodiments, the pressure detection channel 4161 has a fifth state and a sixth state. In the fifth state, the opening of the pressure detection channel 4161 is located inside the packing cavity or the conveying cavity; in some embodiments of the system where the packing module also has a packing cavity, as described above, the opening of the pressure detection channel can be selectively located inside the packing cavity or the conveying cavity. In the sixth state, the air pressure detection channel 4161 has its opening located inside the packing cavity or outside the conveying cavity. In some embodiments of the system described above, where the packing module also has a packing cavity, the air pressure detection channel opening can be selectively located inside the packing cavity or outside the conveying cavity. During material conveying, the conveying module moves towards the melt extrusion module. When secondary material conveying is required, it first returns to its initial position before proceeding with the next conveying. During this back-and-forth movement, the conveying module may also bring back a small amount of printing material 431 that adheres to the opening of the air pressure detection channel 4161. In this embodiment, the air pressure detection channel 4161 can move back and forth between the fifth and sixth states. Thus, even if the feeding module brings back a small amount of printed melt 432 adhering to the air pressure detection channel opening during its return to its initial position, after the next filling, the air pressure detection channel 4161 will move from its fourth state to its third state, passing through the side wall of the feeding module to reach the inside of the feeding module, pushing out the material adhering to the opening of the air pressure detection channel 4161 into the feeding module, ensuring that the air pressure detection channel 4161 is unobstructed. This ensures that the detected pressure is the actual air pressure value inside the closed cavity, rather than the false air pressure value inside the air pressure detection channel 4161 sealed after the air pressure detection channel opening is blocked by the printed melt 432, ensuring effective air pressure measurement. It is worth noting that the air pressure detection channel 4161 and the first air pressure control channel 4151 are two completely independent channels, as shown in Figure 4A. The air pressure detection channel 4161 and the first air pressure control channel 4151 of the system 400 are two parallel and completely independent channels. The air pressure detection channel 4161 is set up as a separate channel and is connected to the second conveying chamber 4112. Compared with the air pressure detection channel and air pressure control channel 1151 sharing a single channel in Figure 3A, even if the first air pressure control channel 4151 of the system 400 is blocked or malfunctions, it can ensure that the air pressure detection channel 4161 is not affected. The air pressure measurement value is still the air pressure value of the entire closed chamber, not the air pressure value in the blocked air pressure control channel.

[0428] In some embodiments, as shown in Figures 4A-4C, system 400 further includes a third drive device for driving the pneumatic detection channel 4161 to reciprocate between a fifth state and a sixth state. The type and structure of the drive device are not limited; it can be any one or more drive devices such as a lead screw module, a hydraulic drive device, a pneumatic drive device, or a motor drive device. In some embodiments, as shown in Figures 4A-4C in conjunction with Figure 2B, the second pneumatic control module includes: a pneumatic control channel having a third state and a fourth state; when the pneumatic control channel is in the third state, its channel opening is located inside the material conveying module; when the pneumatic control channel is in the fourth state, its channel opening is located outside the material conveying module. In some embodiments, system 400 further includes two drive devices that independently drive the pneumatic detection channel to reciprocate between the fifth and sixth states and the pneumatic control channel to reciprocate between the third and fourth states; thus, the movement of the pneumatic detection channel and the movement of the pneumatic control channel are independent of each other, providing greater flexibility in actual production. In some embodiments, as shown in FIG4A, the air pressure detection channel 4161 and the air pressure control channel 4151 are arranged side by side. The system 400 also includes a drive device 417 that synchronously drives the air pressure detection channel 4161 to move back and forth between the fifth and sixth states and the air pressure control channel 4151 to move back and forth between the third and fourth states. In this way, the air pressure detection channel 4161 and the air pressure control channel 4151 share a single drive device 417 for synchronous movement, which can ensure that the air pressure detection and air pressure control actions are consistent, while the structure is compact, saving installation space and reducing the cost of the drive device.

[0429] In some embodiments, the second air pressure control channel of the system 400 is also provided with a corresponding second air pressure detection device. The structure of the second air pressure detection device is the same as that of the air pressure detection device, and will not be described again here. Therefore, the second air pressure detection channel corresponding to the second air pressure detection device can also be set in the same way as the first air pressure detection channel 4161, switching between the inside of the second feeding cavity 4113 and the outside of the second feeding cavity 4113. Alternatively, the second air pressure detection channel can be directly set on the side wall of the second feeding cavity 4113. How to set it specifically can be determined or adjusted by those skilled in the art according to actual needs, such as according to the specific parameters such as the performance of the printing material and the structure of the feeding cavity. Furthermore, in some embodiments, the system 100 shown in FIG2A is also provided with a pressure detection module. The structure of the pressure detection module is the same as that of the pressure detection device, and will not be described again here. In this way, the corresponding pressure control channel can also be set to switch between inside and outside the packing module 112, just like the first pressure detection channel port of the system 400. Alternatively, the pressure detection channel port can be directly set on the side wall of the packing module 112.

[0430] In some embodiments, the filling module of the system 400 does not have filling channels; the filling module is simply a portion of space not occupied by any entity. The printing material is the preceding product printing material after the shell of the shelled printing material has been removed. The aforementioned shelled printing material includes an integrated solid printing material 431 and a shell 433. The shell 433 is used to contain the solid printing material 431 and allows the solid printing material 431 to detach from it under external force. In some embodiments, during filling, the shelled printing material is directly inserted into the space of the filling module and secured between the feeding chamber and the melt extrusion chamber 4131. At this time, the shell 433 is connected to the filling chamber, the feeding chamber, and the printing chamber to allow the solid printing material 431 to move from the shell 433 to the melt extrusion chamber 4131 and to allow the melt to be supplied from the melt extrusion chamber 4131 to the printing chamber. Furthermore, the shell 433, the feeding chamber, and the melt extrusion chamber 4131, which is loaded with melt 432 near the printing unit, constitute a closed and connected cavity. Therefore, in this embodiment, the shell 433 of the shelled printing material can also directly replace the function of the filling chamber 3122 as shown in Figures 3A-3B.

[0431] In some embodiments, the material delivery module of system 400 is further defined to include a plunger rod 4111. In some embodiments, the plunger rod 4111 is also configured to pass through housing 433 and push solid printing material 431 from housing 433 to melt extrusion chamber 4131.

[0432] In some embodiments, the plunger rod 4111 is configured to begin moving toward the melt extrusion module and push the solid printing material 431 into the melt extrusion cavity when the measurement value from the pressure detection device determines that a first threshold pressure has been reached. The aforementioned first threshold pressure is a preset ideal pressure value in the sealed cavity after effective pressure control. When the measurement value from the pressure detection device determines that the first threshold pressure has been reached, it indicates that the pressure control is successful and the pressure control ends. At this time, the plunger rod 4111 starts the pushing operation.

[0433] In some embodiments, the second air pressure control module further includes a blockage alarm mechanism (not shown) that generates an alarm signal when a second threshold air pressure is reached based on measurements from an air pressure detection device. The aforementioned second threshold air pressure is a preset alarm air pressure value (e.g., -50 kPa) for air pressure control channel blockage. When the measurement value from the air pressure detection device determines that the second threshold air pressure has been reached, it indicates that the air pressure control channel is blocked, and the operating end (operator or robotic arm) clears the air pressure control channel. In other embodiments, the measurement value from the air pressure detection device 4151 is further limited to the absolute value of air pressure change within a preset time period monitored by the air pressure detection device, such as the absolute value of air pressure change within 5 seconds. When the absolute value of air pressure change within 5 seconds from the air pressure detection device 4151 is determined to have reached the second threshold air pressure, it indicates that the air pressure control channel is blocked, and the operating end (operator or robotic arm) clears the air pressure control channel. Of course, it could also be the air pressure change value within a preset time period such as 3 seconds, 6 seconds, or 7 seconds. In some embodiments, the blockage alarm mechanism includes a filter for filtering the printed melt 432. The filter is disposed within the first air pressure control channel 4151 to filter out residual material for easy subsequent cleaning. The filter includes a filter screen with multiple sieve holes. The shape and size of the sieve holes are set according to the material's performance parameters, etc. For example, in one embodiment, the sieve holes are circular with a diameter of 0.4 mm to 0.6 mm.

[0434] In some embodiments, system 400 further includes a displacement detection module (not shown) for detecting the displacement of plunger rod 4111. In some embodiments, plunger rod 4111 is configured to pause movement toward the melt extrusion module when a first threshold displacement is determined to have been reached based on measurements from the displacement detection module. Plunger rod 4111 is configured to stop movement toward the melt extrusion module when a second threshold displacement is determined to have been reached based on measurements from the displacement detection module. The first threshold displacement is a preset first displacement value (as shown in Figure 4B) when the feeding end of the plunger rod 4111 enters the melt extrusion cavity 4131. When the measurement value of the displacement detection module determines that the first threshold displacement has been reached, it indicates that the solid printing material 431 has been pushed into the melt extrusion cavity 4131. Then, as the melt 432 of the melt extrusion cavity 4131 is gradually extruded out of the melt extrusion cavity, the plunger rod continues to push the solid printing material 431 at a suitable speed, displacement, or torque. The specific pushing parameters can be selectively set by those skilled in the art based on the performance of the solid printing material 431, the cavity structure and size of the melt extrusion cavity, the structure and size of the plunger rod, and other parameters. The second threshold displacement is a preset second displacement value of the feed end of the plunger rod entering the melt extrusion cavity (as shown in Figure 4C). When the measurement value of the displacement detection module determines that the second threshold displacement has been reached, it indicates that the solid printing material 431 has been completely turned into melt 432 and pushed into the melt extrusion cavity 4131 near the end of the extrusion channel. At this time, the entire stroke of the plunger rod 4111 ends, and then it will return to the starting position in the second feed cavity.

[0435] In some embodiments, as shown in Figures 4A-4B, the plunger rod 4111 of system 400 has a seventh state, an eighth state, and a ninth state. In the seventh state, the plunger rod 4111's end is located within the second feeding chamber. In the eighth state, the plunger rod 4111's end is located within the melt extrusion chamber 4131 near the packing module (housing 433). In the ninth state, the plunger rod 4111's end is located within the melt extrusion chamber away from the packing module (housing 433). Thus, the entire stroke of the plunger rod 4111 is within the sealed cavity formed by the housing 433, the feeding chamber, and the melt extrusion chamber 4131. This design is adopted because if the seventh state of the plunger rod 4111 is located outside the second feeding chamber, the seal on the outer circumference of the plunger rod needs to be tightly sealed to the inner wall of the sealed cavity to prevent leakage. Therefore, the requirements for the seal between the plunger rod 4111 and the end of the second feeding chamber are high. During the frequent back-and-forth movement of the plunger during advancement and retraction, the plunger seal is subjected to high-frequency friction, which damages the plunger seal and affects its service life. This can further lead to seal failure, causing the air pressure in the sealed cavity to be inconsistent, which affects the subsequent defects of the finished drug product. However, in the technical solution of this embodiment, the entire stroke of the plunger rod 4111 is within the sealed cavity, so there is no need to consider the sealing problem between the plunger rod 4111 and the end of the second feeding chamber. This can ensure that the air pressure in the sealed cavity is constant, ensuring the manufacture of high-quality drug products and ensuring the consistency of the drug products.

[0436] In this embodiment, after the shelled printing material is filled into the filler module, its shell 433 is automatically secured by the tooling. The plunger rod 4111 moves toward the melt extrusion cavity 4131, detaching the solid printing material 431 from the shell 433 and pushing it into the melt extrusion cavity 4131. In some embodiments, the cross-sectional shape and size of the solid printing material 431, the cross-sectional shape and size of the plunger rod 4111, and the inner cross-sectional shape and size of the melt extrusion cavity 4131 are the same. As shown in Figure 2B combined with Figure 4A, the cross-sections of the solid printing material 431, the plunger rod 4111, the melt extrusion cavity 4131, the first feeding cavity 4112, and the second feeding cavity 4113 are all circular, and the outer diameter d2 of the solid printing material 431, the outer diameter d4 of the plunger rod 4111, the inner diameter d3 of the first feeding cavity 4112 and the second feeding cavity 4113, and the outer diameter d1 of the melt extrusion cavity are equal. If the sealed cavity is vertically positioned, this design ensures that the solid printing material 431 can be easily and accurately ejected from the housing 433. Furthermore, it ensures that the solid printing material 431 is pushed more easily and accurately into the melt extrusion cavity 4131 by the plunger rod 4111, while also guaranteeing a tight seal between the plunger rod 4111 and the melt extrusion cavity 4131 to prevent melt 432 leakage. It should be noted that in other embodiments, the plunger rod, filling cavity, melt extrusion cavity, and solid printing material may have other shapes and structures, such as cuboids, polygons, or elliptical cylinders, as long as a good seal between the plunger rod 3111 and the melt extrusion cavity 3131 is maintained.

[0437] In some embodiments, as shown in Figures 2A to 5, the number of air pressure control channels in systems 100, 200, 300, and 400 is one or more. In some embodiments, as shown in Figures 4A to 4B, the number of air pressure pumps is one or more. In some embodiments, as shown in Figures 4A to 4B, the plurality of air pressure control channels 4151 and 4153 are controlled by one or more air pressure pumps 4152, 4154, and 4155. For example, if the structure of a sealed cav...

Claims

1. An additive manufacturing system for producing pharmaceutical products, characterized in that, include: Supply unit, the supply unit comprising: A melt extrusion module is used to receive printing material for generating the pharmaceutical product and form the printing material into a melt. The melt extrusion module includes a first melt extrusion chamber and a second melt extrusion chamber. A printing unit includes a printing cavity for receiving the melt and a printing channel for dispensing the melt into the printing channel to form a pharmaceutical product; The supply unit also includes: The release switch module is configured to selectively connect a first melt extrusion chamber and a second melt extrusion chamber according to preset parameters, and to distribute the melt in the first melt extrusion chamber or the melt in the second melt extrusion chamber to the printing unit.

2. The additive manufacturing system according to claim 1, characterized in that, The release switch module includes: A valve and a release channel communicating with the printing cavity, the valve being configured to rotate and / or move via a first drive device to selectively communicate one of the melt extrusion cavities with the release channel, the first drive device being configured to rotate and / or move according to the preset parameters.

3. The additive manufacturing system according to claim 1 or 2, characterized in that, The preset parameters include one or more of the following parameters: time length, melt pressure value in the first melt extrusion chamber, melt pressure value in the second melt extrusion chamber, weight value in the first melt extrusion chamber, weight value in the second melt extrusion chamber, temperature value in the first melt extrusion chamber, temperature value in the second melt extrusion chamber, melt volume value in the first melt extrusion chamber, and melt volume value in the second melt extrusion chamber.

4. The additive manufacturing system according to any one of claims 1 to 3, characterized in that, The first melt extrusion chamber includes a first extrusion channel, the second melt extrusion chamber includes a second extrusion channel, and the valve has a first state and a second state; when the valve is in the first state, the release channel is connected to either the first extrusion channel or the second extrusion channel; when the valve is in the second state, the release channel is disconnected from both the first extrusion channel and the second extrusion channel.

5. The additive manufacturing system according to claim 4, characterized in that, The valve includes a valve body and a valve core. The valve body includes a first valve body channel connected to the first extrusion channel, a second valve body channel connected to the second extrusion channel, and the release channel. The valve core includes a communicating cavity, which includes a first port and a second port, the shape and size of which match.

6. The additive manufacturing system according to claim 5, characterized in that, The first valve body channel includes a third port connected to the first extrusion channel and a fourth port connected to the communicating cavity; the second valve body channel includes a fifth port connected to the second extrusion channel and a sixth port connected to the communicating cavity; the fourth port and the sixth port are both matched with the shape and size of the first and second ports.

7. The additive manufacturing system according to claim 5, characterized in that, The projection angle formed by the central axis of the first port and the central axis of the second port is 120°.

8. The additive manufacturing system according to claim 6, characterized in that, The projection angle formed by the central axis of the third port and the central axis of the fourth port is 120°.

9. The additive manufacturing system according to claim 6, characterized in that, The projection angle formed by the central axis of the fifth port and the central axis of the sixth port is 120°.

10. The additive manufacturing system according to claim 5, characterized in that, The communicating cavity includes a straight cavity segment connected to the first port, a straight cavity segment connected to the second port, and an arc-shaped cavity segment located in the middle of the straight cavity segments.

11. The additive manufacturing system according to claim 4, characterized in that, The valve is configured to be in either the first state or the second state whenever it is driven by the first drive device.

12. The additive manufacturing system according to claim 5, characterized in that, The valve also includes: A rotating shaft, configured to rotate under the drive of the first driving device; One end of the rotating shaft is connected to the output shaft of the first driving device, and the other end is connected to the valve core.

13. The additive manufacturing system according to claim 12, characterized in that, The valve further includes a position compensation device configured to compensate for the gap between the valve core and the rotating shaft.

14. The additive manufacturing system according to claim 13, characterized in that, The position compensation device includes a relative reference position positioning unit and an absolute position measuring unit. The relative reference position positioning unit is configured to determine the position of the rotating shaft in a second state, and the absolute position measuring unit is configured to determine the position of the rotating shaft in a first state.

15. The additive manufacturing system according to claim 14, characterized in that, The relative reference position positioning unit includes a light blocking plate disposed on the rotating shaft and a photoelectric sensor disposed on the valve, which is configured to cut off the optical path between the transmitting end and the receiving end of the photoelectric sensor when the valve rotates to the position corresponding to the photoelectric sensor.

16. The additive manufacturing system of claim 12, characterized in that, The shaft can rotate in a first direction and / or a second direction, wherein the first direction and the second direction are opposite.

17. The additive manufacturing system of claim 16, characterized in that, When the valve is in the first state, the valve is in the first state or the second state after the rotating shaft rotates once in the first direction or the second direction; and when the valve is in the second state, the valve is in the first state after the rotating shaft rotates once in the first direction or the second direction.

18. The additive manufacturing system of claim 1, characterized in that, The melt extrusion module is configured to alternately release the melt in the first melt extrusion chamber and the melt in the second melt extrusion chamber into the printing chamber, and / or The melt extrusion module is configured such that the first melt extrusion chamber and the second melt extrusion chamber alternately receive the printing material.

19. The additive manufacturing system according to claim 18, characterized in that, The melt extrusion module is configured such that, when the melt in the first melt extrusion chamber is released into the printing chamber, the second melt extrusion chamber receives printing material and / or forms melt from the printing material and / or maintains the melt in a molten state. The melt extrusion module is configured such that when the melt in the second melt extrusion chamber is released into the printing chamber, the first melt extrusion chamber receives printing material and / or forms a melt from the printing material and / or keeps the melt in a molten state.

20. The additive manufacturing system according to claim 2, characterized in that, The release channel is equipped with a pressure sensor, which is configured to detect the melt pressure value within the release channel.

21. The additive manufacturing system according to claim 1, characterized in that, The supply unit also includes a plunger corresponding to each of the melt extrusion cavities. The plunger is configured to: When receiving printing material, move the melt extrusion chamber toward the end furthest from the release switch module to increase the volume of the melt extrusion chamber; and When the printing material is discharged, it moves toward the end of the melt extrusion chamber closer to the release switch module to reduce the volume of the melt extrusion chamber.

22. The additive manufacturing system according to claim 21, characterized in that, The preset parameter is the stroke of the plunger. When the stroke of the plunger connected to the first melt extrusion chamber or the second melt extrusion chamber reaches the target value, the release switch unit selects to connect to the first melt extrusion chamber or the second melt extrusion chamber.

23. The additive manufacturing system according to claim 1, characterized in that, The printing material is a preceding product unit, which includes multiple preceding products with the same weight and composition.

24. The additive manufacturing system according to claim 23, characterized in that, The preceding product unit is prepared by a preceding product forming module, which includes: Feed inlet and screw extrusion unit The screw extrusion device is used to mix at least two raw materials to form a preliminary melt and discharge the preliminary melt into a corresponding tube through an outlet.

25. The additive manufacturing system according to claim 24, characterized in that, The tube includes a cylindrical cavity structure and bosses located at both ends of the cylindrical cavity structure.

26. The additive manufacturing system according to claim 24, characterized in that, The preceding product forming module also includes a first air pressure control module; The preceding product forming module has a preceding product melting cavity. The first air pressure control module is connected to the preceding product melting chamber and is used to control the air pressure of the preceding product melting chamber to a first air pressure preset value.

27. The additive manufacturing system according to claim 26, characterized in that, The preceding product molding module also includes a negative pressure control device, which is configured to remove air from the preceding product melting molding cavity so that the air pressure in the preceding product melting molding cavity is reduced to a first preset air pressure value.

28. The additive manufacturing system according to claim 1, characterized in that, The supply unit further includes a filler module for receiving printing material for generating the drug product; the filler module further includes a filler cavity and a filler channel for receiving printing material for generating the drug product.

29. The additive manufacturing system according to claim 28, characterized in that, The filling chamber is configured such that the filling channel is open when receiving printing material, and the filling channel is closed after the filling chamber has finished receiving printing material.

30. The additive manufacturing system according to claim 28 or 29, characterized in that, The packing cavity includes a first packing cavity and a second packing cavity, wherein the first packing cavity is connected to the first melt extrusion cavity and the second packing cavity is connected to the second melt extrusion cavity.

31. The additive manufacturing system according to claim 30, characterized in that, The cross-sectional diameter of the first packing cavity is larger than the cross-sectional diameter of the preceding product.

32. The additive manufacturing system according to claim 30 or 31, characterized in that, The cross-sectional diameter of the second packing cavity is larger than the cross-sectional diameter of the preceding product.

33. The additive manufacturing system according to claim 28, characterized in that, The supply unit also includes a second air pressure control module; The second air pressure control module is connected to the packing cavity and is used to control the air pressure of the packing cavity, the corresponding melt extrusion cavity and the printing cavity to the second air pressure preset value.

34. The additive manufacturing system as described in claim 33, characterized in that, The second air pressure control module includes an air pressure control device. The air pressure control device includes: Air pressure control channel; An air pump is used to remove air from the packing cavity and the melt extrusion cavity through the air pressure control channel so that the air pressure in the packing cavity, the corresponding melt extrusion cavity and the printing cavity reaches the second preset air pressure value.

35. The additive manufacturing system as described in claim 34, characterized in that, The second air pressure preset value is -65KPa to -100KPa.

36. The additive manufacturing system as described in claim 34, characterized in that, The air pressure control channel has a third state and a fourth state; In the third state, the air pressure control channel has its opening located inside the packing cavity, so that the air pressure control channel and the packing cavity are interconnected. In the fourth state, the air pressure control channel has its outlet located outside the packing cavity, so that the air pressure control channel and the packing cavity are not connected.

37. The additive manufacturing system as described in claim 36, characterized in that, The supply unit also includes a second drive device for driving the air pressure control channel to move back and forth between the third and fourth states.

38. The additive manufacturing system as claimed in claim 24, characterized in that, The supply unit also includes a material conveying module for conveying the printing material from the filler cavity to the corresponding melt extrusion cavity.

39. The additive manufacturing system as described in claim 38, characterized in that, The material conveying module includes: Material conveying chamber; A plunger rod, configured to reciprocate axially within the feeding chamber, is used to push the printing material into the corresponding melt extrusion chamber.

40. The additive manufacturing system as claimed in claim 39, characterized in that, The air pressure control channel is connected to the inside of the packing cavity and / or the air pressure control channel is connected to the inside of the packing cavity or the conveying cavity.

41. The additive manufacturing system as claimed in claim 33, characterized in that, The second air pressure control module also includes an air pressure detection device for detecting the air pressure value in the packing cavity or the conveying cavity.

42. The additive manufacturing system as claimed in claim 41, characterized in that, The air pressure detection device includes an air pressure sensor and an air pressure detection channel; The air pressure detection channel is connected to the inside of the packing cavity or the inside of the conveying cavity.

43. The additive manufacturing system as described in claim 42, characterized in that, The air pressure detection channel has a fifth state and a sixth state; In the fifth state, the air pressure detection channel has its channel opening located inside the packing cavity and / or the conveying cavity; In the sixth state, the air pressure detection channel has its outlet located outside the packing cavity and / or the conveying cavity.

44. The additive manufacturing system as described in claim 43, characterized in that, The system also includes a third drive device for driving the air pressure detection channel to move back and forth between the fifth state and the sixth state.

45. The additive manufacturing system as described in claim 44, characterized in that, The air pressure control channel includes multiple air pressure control sub-channels, which are configured to operate in parallel, partially in parallel, or independently, so that the air pressure of the filling cavity, the corresponding melt extrusion cavity, and the printing cavity reaches the second air pressure preset value, or so that the air pressure of the filling cavity, the corresponding melt extrusion cavity, the feeding cavity, and the printing cavity reaches the second air pressure preset value.

46. ​​The additive manufacturing system according to any one of claims 1-45, characterized in that, The system also includes a pressure control module, which is used to control the melt pressure of the supply unit and / or printing unit to the corresponding preset pressure value.

47. The additive manufacturing system according to any one of claims 1-45, characterized in that, The system also includes a temperature control module, which is used to control the melt temperature of the supply unit and / or printing unit to the corresponding preset temperature value.

48. The additive manufacturing system as claimed in claim 47, characterized in that, The temperature control module includes one or more heaters and / or one or more coolers, as well as a temperature detection device; The temperature detection device includes one or more temperature sensors; The system is configured to adjust the temperature of each heater and / or each cooler in response to a temperature measurement sensed by the temperature sensor.

49. The additive manufacturing system according to any one of claims 1-45, characterized in that, The melt has a viscosity of about 100 Pa·s or higher.

50. The additive manufacturing system according to any one of claims 1-45, characterized in that, The melt has a viscosity of about 10,000 Pa·s or higher.

51. The additive manufacturing system according to any one of claims 1-45, characterized in that, The printing channel of the printing unit includes a nozzle assembly for printing the pharmaceutical product.

52. The additive manufacturing system as claimed in claim 51, characterized in that, The supply unit also includes a diversion module, the inlet of which is connected to the release switch module, and the outlet of which is connected to the nozzle assembly. The flow distribution module is used to distribute the melt released by the release switch module to the nozzle group.

53. The additive manufacturing system according to any one of claims 1-45, characterized in that, The printing unit further includes a printing platform configured to receive the melt, wherein the printing platform is configured to move to form a batch of the pharmaceutical product.

54. The additive manufacturing system according to any one of claims 1-45, characterized in that, The printing unit also includes multiple printing platforms and multiple printing devices. Each of the printing devices includes a printing channel comprising a nozzle assembly for printing the pharmaceutical product; The system is configured to: Each printing platform can be moved to a position below one of the nozzles in any of the nozzle groups of the printing device to receive the pharmaceutical product or a portion thereof printed by that nozzle.

55. The additive manufacturing system according to any one of claims 1-45, characterized in that, The pharmaceutical products include drugs, including but not limited to pharmaceuticals, medical devices, and dietary supplements.

56. The additive manufacturing system according to any one of claims 1-45, characterized in that, The printing material is a preceding product.

57. A method for manufacturing a pharmaceutical product using an additive manufacturing system for producing a pharmaceutical product, characterized in that, in: The system includes: Supply unit, the supply unit comprising: The melt extrusion module includes a first melt extrusion chamber and a second melt extrusion chamber. And the release switch module; The printing unit includes a printing cavity for receiving the molten material and a printing channel. The method includes: Printing material for manufacturing the pharmaceutical product is received via the first melt extrusion chamber and / or the second melt extrusion chamber; The printing material in the first melt extrusion cavity is used to form a first melt and / or the printing material in the second melt extrusion cavity is used to form a second melt; The release switch module selectively connects the first melt extrusion chamber and the second melt extrusion chamber according to preset parameters, and distributes the first melt in the first melt extrusion chamber or the second melt in the second melt extrusion chamber to the printing chamber; The melt from the printing cavity is distributed to the printing channel to form a pharmaceutical product.

58. The method for manufacturing a pharmaceutical product according to claim 57, characterized in that, The release switch module includes: a valve and a release channel communicating with the printing cavity, and the method further includes: The valve is rotated and / or moved by the first drive device to selectively connect one of the melt extrusion chambers to the release channel. The first driving device rotates and / or moves according to the preset parameters.

59. The method for manufacturing a pharmaceutical product according to claim 57 or 58, characterized in that, The preset parameters include one or more of the following parameters: time length, melt pressure value in the first melt extrusion chamber, melt pressure value in the second melt extrusion chamber, weight value in the first melt extrusion chamber, weight value in the second melt extrusion chamber, temperature value in the first melt extrusion chamber, temperature value in the second melt extrusion chamber, melt volume value in the first melt extrusion chamber, and melt volume value in the second melt extrusion chamber.

60. The method for manufacturing a pharmaceutical product according to any one of claims 57-59, characterized in that, The first melt extrusion chamber includes a first extrusion channel, the second melt extrusion chamber includes a second extrusion channel, and the valve has a first state and a second state; the method further includes: The valve rotates and / or moves to a first state, connecting the release channel with the first extrusion channel or the second extrusion channel; The valve rotates and / or moves to the second state, disconnecting the release channel from both the first extrusion channel and the second extrusion channel.

61. The method for manufacturing a pharmaceutical product according to claim 60, characterized in that, The method further includes: The valve is driven by the first driving device, so that the valve is in either the first state or the second state.

62. The method for manufacturing a pharmaceutical product according to claim 60, characterized in that, The valve includes a valve body and a valve core. The valve body includes a first valve body channel connected to the first extrusion channel, a second valve body channel connected to the second extrusion channel, and the release channel. The valve core includes a communicating cavity, and the method further includes: The melt in the first melt extrusion cavity or the melt in the second melt extrusion cavity is sequentially distributed to the printing cavity via the first valve body channel or the second valve body channel, the connecting cavity, and the release channel.

63. The method for manufacturing a pharmaceutical product according to claim 62, characterized in that, The communicating cavity includes a first port and a second port, the shape and size of which match the shape and size of the first port and the second port; the first valve body channel includes a third port connected to the first extrusion channel and a fourth port connected to the communicating cavity; the second valve body channel includes a fifth port connected to the second extrusion channel and a sixth port connected to the communicating cavity; the shape and size of the fourth port and the sixth port are both matched with those of the first port and the second port.

64. The method for manufacturing a pharmaceutical product according to claim 62, characterized in that, The valve further includes a rotating shaft, one end of which is connected to the output shaft of the first driving device, and the other end of which is connected to the valve core. The method further includes: The first driving device drives the rotating shaft to rotate, and the rotating shaft rotates, causing the valve core to rotate, such that: the communicating cavity of the valve core is connected to the first valve body channel or the second valve body channel, or The communicating cavity of the valve core is disconnected from both the first valve body channel and the second valve body channel.

65. The method for manufacturing a pharmaceutical product according to claim 64, characterized in that, The rotation of the rotating shaft and the resulting rotation of the valve core include: compensating for the gap between the valve core and the rotating shaft.

66. The method for manufacturing a pharmaceutical product according to claim 65, characterized in that, The compensation for the gap between the valve core and the rotating shaft includes: The position of the rotating shaft in the second state is determined by a relative reference position positioning unit, and the position of the rotating shaft in the first state is determined by an absolute position measurement unit. The position of the rotating shaft in the first state includes a first sub-position and a second sub-position. In the first sub-position, the connecting cavity is connected to the first valve body channel; in the second sub-position, the connecting cavity is connected to the second valve body channel. The method further includes: When the rotating shaft switches between the first sub-position and the second sub-position The rotating shaft drives the valve core to rotate to the position of the rotating shaft in the second state. Then, the rotating shaft drives the valve core to rotate from the position of the rotating shaft in the second state to the first sub-position or the second sub-position. The absolute value of the angle between the first sub-position and the position of the rotating shaft in the second state is then rotated to the first sub-position or the second sub-position.

67. The method for manufacturing a pharmaceutical product according to claim 66, characterized in that, The absolute value of the angle between the first sub-position or the second sub-position and the position of the rotating shaft in the second state is 60°.

68. The method for manufacturing a pharmaceutical product according to claim 66, characterized in that, The position of the rotating shaft in the second state is at the midpoint between the first sub-position and the second sub-position.

69. The method for manufacturing a pharmaceutical product according to claim 66, characterized in that, The relative reference position positioning unit includes a light blocking plate disposed on the rotating shaft and a photoelectric sensor disposed on the valve, and the method further includes: When the valve rotates to the position corresponding to the photoelectric sensor, the light blocking plate cuts off the optical path between the transmitting end and the receiving end of the photoelectric sensor.

70. The method for manufacturing a pharmaceutical product according to claim 69, characterized in that, The method further includes: determining the position of the rotating shaft in the second state based on the light path between the transmitter and receiver of the photoelectric sensor being cut off by the light blocking plate.

71. The method for manufacturing a pharmaceutical product according to claim 64, characterized in that, The method further includes: The shaft rotates along a first direction and / or a second direction, wherein the first direction and the second direction are opposite.

72. The method for manufacturing a pharmaceutical product according to claim 71, characterized in that, The method further includes: when the valve is in the first state, the valve is in the first state or the second state after the rotating shaft rotates once along the first direction or the second direction; and when the valve is in the second state, the valve is in the first state after the rotating shaft rotates once along the first direction or the second direction.

73. The method for manufacturing a pharmaceutical product according to claim 72, characterized in that, The method further includes: The melt from the first melt extrusion chamber and the melt from the second melt extrusion chamber are alternately released into the printing chamber, and / or The printing material is received alternately via the first melt extrusion chamber and the second melt extrusion chamber.

74. The method for manufacturing a pharmaceutical product according to claim 73, characterized in that, The method further includes: When the melt in the first melt extrusion chamber is released into the printing chamber, the printing material is received via the second melt extrusion chamber and / or a melt is formed from the printing material and / or the melt is kept in a molten state. When the melt in the second melt extrusion chamber is released into the printing chamber, the printing material is received via the first melt extrusion chamber and / or a melt is formed from the printing material and / or the melt is kept in a molten state.

75. The method for manufacturing a pharmaceutical product according to claim 58, characterized in that, The passageway is equipped with a pressure sensor, and the method further includes: The pressure value of the melt in the release channel is detected by the pressure sensor.

76. The method for manufacturing a pharmaceutical product according to claim 75, characterized in that, The method further includes: Based on the detected melt pressure value, the melt pressure value is adjusted to a desired constant pressure value.

77. The method for manufacturing a pharmaceutical product according to claim 57, characterized in that, The supply unit further includes a plunger corresponding to each of the melt extrusion cavities, and the method further includes: Upon receiving printing material, the plunger moves toward the end of the melt extrusion chamber furthest from the release switch module to increase the volume of the melt extrusion chamber; and When the printing material is discharged, the end of the melt extrusion chamber that is closer to the release switch module moves to reduce the volume of the melt extrusion chamber.

78. The method for manufacturing a pharmaceutical product according to claim 77, characterized in that, The preset parameter is the stroke of the plunger, and the method further includes: When the plunger stroke connected to the first melt extrusion chamber or the second melt extrusion chamber reaches the target value, the release switch module selects to connect to the first melt extrusion chamber or the second melt extrusion chamber.

79. The method for manufacturing a pharmaceutical product according to claim 57, characterized in that, The printing material is a preceding product unit, which includes multiple preceding products with the same weight and composition.

80. The method for manufacturing a pharmaceutical product according to claim 79, characterized in that, The system further includes a preceding product forming module, which includes a feed inlet and a screw extrusion device, and the method further includes: At least two raw materials are mixed via the screw extrusion device to form a preliminary melt, and the preliminary melt is discharged through an outlet into a corresponding tube to form the preliminary product.

81. The method for manufacturing a pharmaceutical product according to claim 81, characterized in that, The preceding product forming module further includes a first air pressure control module; the preceding product forming module has a preceding product melting chamber, and the first air pressure control module is connected to the preceding product melting chamber; the method further includes: The pressure of the preceding product melting chamber is controlled to a first preset pressure value via the first pressure control module.

82. The method for manufacturing a pharmaceutical product according to claim 81, characterized in that, The preceding product forming module further includes a negative pressure control device, and the method further includes: The negative pressure control device removes air from the melting and molding cavity of the preceding product, bringing the air pressure in the melting and molding cavity of the preceding product to a first preset air pressure value.

83. The method for manufacturing a pharmaceutical product according to claim 57, characterized in that, The supply unit further includes a packing module; the packing module further includes a packing cavity and a packing channel, and the method further includes: The printing material for generating the pharmaceutical product is received via the filling cavity.

84. The method for manufacturing a pharmaceutical product according to claim 83, characterized in that, The method further includes: The filling channel is opened to receive printing material through the filling cavity, and the filling channel is closed after the filling cavity has finished receiving the printing material.

85. The method for manufacturing a pharmaceutical product according to claim 83 or 84, characterized in that, The packing cavity includes a first packing cavity and a second packing cavity, wherein the first packing cavity is connected to the first melt extrusion cavity and the second packing cavity is connected to the second melt extrusion cavity.

86. The method for manufacturing a pharmaceutical product according to claim 83, characterized in that, The supply unit further includes a second air pressure control module, which is connected to the packing cavity. The method further includes: The second air pressure control module controls the air pressure of the filler cavity, the corresponding melt extrusion cavity, and the printing cavity to the second air pressure preset value.

87. The method for manufacturing a pharmaceutical product according to claim 86, characterized in that, The second air pressure control module includes an air pressure control device, which includes an air pressure control channel and an air pressure pump. The method further includes: Through the air pressure control channel, the air in the packing cavity and the melt extrusion cavity is purged by the air pressure pump so that the air pressure in the packing cavity, the corresponding melt extrusion cavity and the printing cavity reaches the second preset air pressure value.

88. The method for manufacturing a pharmaceutical product according to claim 87, characterized in that, The second air pressure preset value is -65KPa to -100KPa.

89. The method for manufacturing a pharmaceutical product according to claim 87, characterized in that, The air pressure control channel has a third state and a fourth state; The method further includes: Before the air pressure control begins, the air pressure control channel is switched from the fourth state to the third state, so that the air pressure control channel is connected to the packing cavity. The air pump is activated to control the air pressure in the packing chamber, the corresponding melt extrusion chamber, and the printing chamber to the second preset air pressure value; and When the air pressure control ends or when the air pressure control is completed, the air pressure control channel is switched from the third state to the fourth state so that the air pressure control channel is not connected to the packing cavity.

90. The method for manufacturing a pharmaceutical product according to claim 88, characterized in that, The supply unit further includes a second driving device, and the method further includes: The pneumatic control channel is moved by the second driving device, causing the pneumatic control channel to move back and forth between the third and fourth states.

91. The method for manufacturing a pharmaceutical product according to claim 80, characterized in that, The supply unit further includes a material conveying module, and the method further includes: The printing material is transported from the filler cavity to the corresponding melt extrusion cavity via the feeding module.

92. The method for manufacturing a pharmaceutical product according to claim 91, characterized in that, The material conveying module includes a material conveying cavity and a plunger rod, and the method further includes: The printing material is pushed to the corresponding melt extrusion chamber by the plunger rod moving back and forth in the axial direction within the feeding chamber.

93. The method for manufacturing a pharmaceutical product according to claim 92, characterized in that, The air pressure control channel is connected to the inside of the packing cavity and / or the air pressure control channel is connected to the inside of the packing cavity or the conveying cavity.

94. The method for manufacturing a pharmaceutical product according to claim 86, characterized in that, The second air pressure control module further includes an air pressure detection device, and the method further includes: The air pressure value in the packing cavity or conveying cavity is detected by the air pressure detection device.

95. The method for manufacturing a pharmaceutical product according to claim 94, characterized in that, The air pressure detection device includes an air pressure sensor and an air pressure detection channel; The air pressure detection channel is connected to the inside of the packing cavity or the conveying cavity, and the method further includes: The pressure sensor detects the pressure value inside the packing cavity or the conveying cavity via the pressure detection channel.

96. The method for manufacturing a pharmaceutical product according to claim 95, characterized in that, The air pressure detection channel has a fifth state and a sixth state; The method further includes: Before the air pressure test begins, switch the air pressure test channel from state six to state five to make the air pressure test channel interconnected with the packing cavity and / or the conveying cavity. The air pump is started to detect the air pressure value in the packing cavity and / or the conveying cavity; and When the air pressure detection ends or after the air pressure detection is completed, switch the air pressure detection channel from the fifth state to the sixth state so that the air pressure detection channel is not connected to the packing cavity and / or the conveying cavity.

97. The method for manufacturing a pharmaceutical product according to claim 96, characterized in that, The supply unit further includes a third driving device, and the method further includes: The air pressure detection channel is moved by the third driving device, causing the air pressure detection channel to switch between the fifth state and the sixth state.

98. The method for manufacturing a pharmaceutical product according to claim 97, characterized in that, The air pressure control channel includes multiple air pressure control sub-channels, and the method further includes: running all of the multiple air pressure control sub-channels in parallel, running some in parallel, or running all of them independently, so that the air pressure of the filling cavity, the corresponding melt extrusion cavity, and the printing cavity reaches the second air pressure preset value, or so that the air pressure of the filling cavity, the corresponding melt extrusion cavity, the feeding cavity, and the printing cavity reaches the second air pressure preset value.

99. The method for manufacturing a pharmaceutical product according to any one of claims 57-98, characterized in that, The system further includes a pressure control module, and the method further includes: The melt pressure of the supply unit and / or printing unit is controlled to the corresponding preset pressure value via the pressure control module.

100. The method for manufacturing a pharmaceutical product using an additive manufacturing system as described in any one of claims 57-98, characterized in that, The system also includes a temperature control module; The temperature control module includes one or more heaters and / or one or more coolers.

101. The method for manufacturing a pharmaceutical product using an additive manufacturing system as described in claim 100, characterized in that, The one or more heaters and / or one or more coolers are respectively located at different positions in the melt extrusion module and the printing unit.

102. The method for manufacturing a pharmaceutical product using an additive manufacturing system as described in claim 100, characterized in that, The temperature control module also includes a temperature detection device; The temperature detection device includes one or more temperature sensors; The method further includes: In response to the temperature measurement value sensed by the temperature sensor, the temperature of each module of the system is controlled and adjusted to the desired temperature via one or more heaters and / or one or more coolers.

103. The method for manufacturing a pharmaceutical product using an additive manufacturing system as described in any one of claims 57-98, characterized in that, The printing channel of the printing unit includes a nozzle assembly; The system also includes a traffic splitting module; The method further includes: The first melt and / or the second melt released by the release switch module are distributed to the nozzle group via the flow distribution module.

104. The method for manufacturing a pharmaceutical product according to any one of claims 57-98, characterized in that, The printing material is a preceding product.

105. A non-transitory computer-readable storage medium, characterized in that, The system stores one or more programs, which include instructions that, when executed by an additive manufacturing system having one or more processors and memory, cause the system to perform a method comprising any of the steps of claims 1-104.

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