SYSTEMS AND METHODS FOR ADDITIVE MANUFACTURING USING Omnidirectional MAGNETIC MOTION DEVICES

Abstract

A processing system and method for manufacturing articles using an omnidirectional magnetic motion system (20) having a transport surface and a manufacturing module having a forming surface that is omni-directionally transportable over the transport surface under control of a motion controller. An article forming system provides processing unit operations for forming articles on a forming surface when a manufacturing module moves asynchronously between a plurality of processing positions on a transport surface, and features a deposition apparatus (40) for placing the structural material on the forming surface and one or more processing apparatuses (50, 60) for forming the structural material into an article.

Description

Technical Field

[0001] The present invention relates to the use of an omnidirectional magnetic motion device for forming articles, such as dosage forms, using additive manufacturing techniques. Background Art

[0002] Industrial manufacturing of pharmaceutical dosage forms is well known in the art and has been practiced for over 100 years. The current state of the art in unit operation manufacturing of oral solid dosage pharmaceuticals is to combine a series of independent activities that can be performed in batch mode or continuously in series, using a variety of different processing unit operations, including powder distribution, powder mixing, powder grinding, wet or dry granulation, compression or encapsulation, coating and dosage form packaging. Processing unit operations are performed on large equipment that operates independently and are usually carried out in large physical spaces that are close to or far away from each other, and utilize linear and / or circuitous, intermittent or continuous processing. The traditional alignment or relationship between such operations results in the need to build separate equipment, rooms, and in some cases, entire facilities to produce new or common pharmaceutical dosage forms.

[0003] Magnetic motion devices are well known in the prior art. For example, U.S. Patent No. 9,202,719 discloses the basic structure and operation mode of an omnidirectional magnetic motion device, which is also called a planar motor, and its entire content is incorporated herein by reference. The omnidirectional magnetic motion device or system is capable of achieving asynchronous and / or random motion, positioning and orientation of one or more shuttles by a guide system along the planar transport surface of the stator and on it. WO 2018 / 176137 A1, the entire disclosure of which is incorporated herein by reference, discloses a magnetic motion device with many different designs of shuttles and stators, and teaches how to fix the stator with a guide rail in the transport area between the stator of the magnetic motion device and the statorless transport system (e.g., a conveyor belt, a robot fixture, etc.), so that the shuttle first floats from the stator into the guide rail, then slides on the guide rail (e.g., on rollers), and when the shuttle leaves the magnetic action area of ​​the stator, it moves forward through the statorless transport system. Summary of the invention

[0004] The present invention provides a processing system and method for forming an article or for processing materials or components of an article, including but not limited to additive manufacturing (including three-dimensional printing or "3DP"), including one or more processing unit operations, an omnidirectional magnetic motion device including a stator that generates a magnetic field, and one or more manufacturing modules, the omnidirectional magnetic motion device having a planar transport surface, the one or more manufacturing modules are combined with one or more magnetic field-actuated shuttles, which move with six degrees of freedom on the planar transport surface by magnetic suspension, including movement in the horizontal directions of the x and y axes and the vertical direction of the z axis. A motion controller including one or more processors and one or more sensors controls the omnidirectional movement of the one or more shuttles on the planar transport surface. A controller system provides a method for monitoring and controlling material processing, including the quality of processing, the quality and characteristics of the build material input, and the quality and characteristics of the articles produced by the unit operations and processing system.

[0005] Manipulate one or more substrates carried by a manufacturing module and moved by one or more shuttles so that the one or more substrates can be asynchronously and / or selectively moved, positioned and oriented between one or more processing unit operations, and one or more articles are formed or processed on the substrates. Combining one or more (and typically multiple) processing unit operations with an omnidirectional magnetic motion system can provide a means for optimizing size, production speed and flexibility to manufacture individual articles, such as, for non-limiting example, pharmaceutical dosage forms, at rates and capacities equal to or greater than those achieved with conventional processing unit operations.

[0006] In various embodiments, the processing unit operating system is designed and constructed to enable and optimize the flexibility of the number and type of processing unit operations and operating equipment using the omnidirectional magnetic motion system at a given time. For example, the processing system can provide and combine multiple structural materials at one time using a material deposition module. The module is used to deposit the same or equivalent structural materials, or different structural materials, which can be in different physical states, such as solid particles, semi-solid solutions or suspensions, liquids, or any combination thereof.

[0007] Similarly, the apparatus can be designed and constructed to employ a variety of liquid dispensing and / or printing techniques for article formation, such as, for example, piezoelectric inkjet printing, material jetting, fused deposition, extrusion, and hot melt extrusion.

[0008] Similarly, the device can be designed and constructed to employ a variety of process analysis technologies used in instantaneous, continuous or intermittent monitoring and control, including closed-loop feedback control of process and output quality and consistency, for example, near infrared (NIR) and short wave infrared (SWIR) spectrometers, 2D and 3D cameras that can incorporate artificial intelligence (AI) and machine learning capabilities.

[0009] The modular design can quickly and instantly change the utilization, function and maintenance of the processing unit operation without or taking less time to disassemble and reassemble the apparatus and assemblies usually associated with the traditional single, serial and parallel processing technology product manufacturing assemblies. In addition, the modular design of the processing system of the present invention can be used for development, simulation, testing, experimentation and similar activities on a smaller and more efficient production scale, which allows the qualification of the processing on the apparatus or apparatus module, which can be exactly the same as the modular apparatus adopted in the pilot or commercial scale manufacturing. Modularity allows the processing and operating conditions of the apparatus or apparatus module to be thoroughly and systematically tested and developed before the same apparatus or apparatus module is installed in the pilot or manufacturing facility of GMP certification. Modularity also allows the apparatus or apparatus module to be taken out from the pilot or manufacturing facility that meets the GMP standard and put into the processing facility for dynamic simulation processing on a small scale to help troubleshoot the processing adjustment and processing abnormality, and return the same apparatus or apparatus module to the pilot or manufacturing facility.

[0010] The various non-limiting sub-processing systems can include systems for processing gaseous, solid or liquid materials and compositions by one or more of: conveying, mixing, blending, dispensing, printing, flattening, irradiating, heating, boiling, cooling, freezing, evaporating, pressurizing, evacuating, covering with gas, sealing (one element to another element), dehumidifying, exhausting or purging gases or vapors, and other processing unit operations for forming an article on or in a substrate.

[0011] In various embodiments, one or more processing unit operations include a deposition system for structural materials and a phase change system for forming structural materials into articles. One or more processing unit operations can include three-dimensional printing (3DP) or other additive manufacturing processing operations. Articles can be any solid, semi-solid, semi-liquid or liquid products, and can include pharmaceutical forms, drugs or pharmaceutical dosage forms, and household, industrial or commercial products.

[0012] Non-limiting examples of substrates upon or in which articles can be formed can include trays, containers, sheets, mold parts, and packaging materials, more particularly blister cards.

[0013] The present invention provides a processing system for manufacturing products, comprising: i) an omnidirectional magnetic motion device, which includes a transport surface; ii) one or more manufacturing modules, which include a) at least one shuttle and b) at least one substrate, which includes one or more forming surfaces; iii) a product forming system, including: a) at least one deposition device, which is used to place a structural material on at least one of the one or more forming surfaces when the shuttle is located at a deposition position on the transport surface; and b) at least one processing device, which is used to perform a processing unit operation on the structural material when the shuttle is placed at a processing position on the transport surface; and iv) a motion controller, which is used to control the omnidirectional and asynchronous transportation of one or more manufacturing modules on the transport surface between at least the deposition position and at least one processing position to form products.

[0014] The present invention also provides one or more additional processes or procedures for efficiently and effectively forming the products of the present invention. In some embodiments, the processing system includes an inspection system located above one or more inspection stations, and one or more inspection systems include one or more sensors or detectors, each of which can be based on AI and / or machine learning. The method of forming a product can include online instant analysis and evaluation of the physical and / or chemical properties of the product (e.g., tablet form) and the intermediate form, and confirming the acceptability of the fully or partially formed product or product, or determining the necessity of reprocessing of the steps or unit operation processing of the fully or partially formed product to produce an acceptable complete product or product. In some embodiments, the inspection method and system can detect the physical properties of the product, for example, the physical properties of the product (e.g., tablet) or its intermediate form, or can detect processing conditions and parameters, for example, detecting liquid deposition position, specific compound content or uniformity, monolayer or total dosage space volume, residual solvent / moisture content, and broken or damaged dosage forms. Non-limiting examples of the processing performed on the product or its intermediate form can include pressing, compacting, etching, engraving, labeling, coloring, and visual printing. After inspection and evaluation of the inspection results, the manufacturing module with the substrate and processed article (as an example of asymmetric processing) can be directed back to one of the unit operation stations for further processing based on the inspection results.

[0015] Once the unit operation processing is fully completed, the manufacturing module with substrates and products can be moved under the control of both the processing unit operation controller and the motion controller to exit the unit operation processing system and move out of the magnetic motion device for additional processing, inspection, packaging, handling and distribution.

[0016] The omnidirectional magnetic motion system provides a trackless conveying system that allows flexible integration of a series of processing unit operations performed by equipment and devices. The omnidirectional magnetic motion device includes a plurality of sheet segments of a certain area, which are generally square in size and arranged side by side with one or more adjacent sheet segments. The various layouts and patterns of the sheet segments of the magnetic motion device provide flexible and instantaneous changes in the processing unit operation that cannot be achieved by a linear track or conveying system. In some embodiments, the transport surface of the magnetic motion device or system is an extended open area, for example, a square or rectangular, circular or elliptical, and the movement of the shuttle is controlled to limit or prevent the shuttle from moving to a designated area above the actuating coil. In other embodiments, the sheet segments can be arranged in various patterns to provide islands or peninsulas of non-sheet areas within or inside the periphery of the sheet pattern, thereby prohibiting the movement of the shuttle. For example, the sheet pattern can include a main elongated area and a plurality of sheet segments extending laterally from the main elongated area.

[0017] The motion controller of the omnidirectional magnetic motion system includes one or more processors and one or more sensors for detecting the real-time position of one or more shuttles, each shuttle having a unique identification address, and moving the one or more shuttles on a planar transport surface according to instructions provided by a process controller to form products on substrates associated with the one or more shuttles.

[0018] Combining a dosage forming processing unit operation of a structural material dispensing system and a phase change system with an omnidirectional magnetic motion system can provide a means for optimizing size, production speed and flexibility to manufacture individual products, such as pharmaceutical dosage forms, at rates and capacities equal to or greater than conventional processing unit operations.

[0019] The processing system, under the control of the motion controller of the omnidirectional magnetic motion system and the processing unit operation controller, intelligently and efficiently moves the forming substrate and its structural materials and / or intermediate products to achieve asymmetric processing of the products by moving the shuttles carrying the substrates to precise and sometimes asynchronous locations, positions and orientations, and within the precise and sometimes asynchronous times required for processing. The processing system and its controller operate multiple independent manufacturing modules through the processing unit operation system while maintaining the continuous and / or efficient utilization of each individual processing unit operation. As needed, the processing system and its controller are capable of reworking certain products on certain manufacturing modules while programming processing procedures for other manufacturing modules.

[0020] The association of the manufacturing modules with the control system, and the association of each individual substrate (e.g., blister card) and / or forming surface (e.g., depression) with its respective shuttle, allows the system sensors and controller to historically and accurately track and record the movement of the manufacturing modules and their respective shuttles, substrates and forming surfaces on the transport surface to the processing locations of the apparatus, and the processing unit operations performed thereon. The movement of the shuttles and their respective forming modules is controlled to independently move between the unit operation locations on the transport surface based on the calculated available space around other manufacturing modules moving on the transport surface, the travel speed, one or more planned unit operation durations, and other factors to determine and execute an optimal path through the transport surface to each processing station through the motion controller while avoiding collisions with other shuttles and manufacturing modules and maximizing the article manufacturing throughput of the processing system.

[0021] The present invention also provides a production system comprising one or more (usually multiple) production modules that utilize an omnidirectional magnetic motion system. A non-limiting example of a production module is a substrate forming system for forming a substrate from a stock material and placing or positioning the formed substrate on a carrier. Another non-limiting example of a production module is a packaging module for applying one or more packaging elements to a substrate loaded with an article and / or placing the substrate loaded with an article into an outer packaging material. Another non-limiting example of a production module is a separate processing system that performs one or more processing unit operations in conjunction with a product forming processing system, a non-limiting example of which is a system and method for printing or placing an identification mark on a substrate or a forming surface of a substrate.

[0022] The present invention also provides a containment system and related equipment, including a containment shell to provide a containment area above the transport surface of the stator. The containment shell has one or more transport openings in the side wall of the containment shell to provide an inlet and / or outlet for the manufacturing module to enter and exit the containment area, and one or more sealable openings through the top plate or side wall of the containment shell to provide a passage for the unit operation processing equipment to access the production system and the manufacturing module in the containment area. The containment shell can also have one or more airflow openings to allow ambient air or conditioned gas or air from outside the containment shell (hereinafter referred to as "external air") to enter and pass through the containment area (referred to as "process air" inside the containment shell). One or more airflow openings are placed at different positions along the containment shell to control the position and amount of external air sucked into the containment shell, and where and how the process air passes through the containment area. An air handling and filtering system including an air handling and filtering device (hereinafter referred to as "air handling device") sucks external air into the containment area and passes the process air through the containment area. The process air can contain airborne, entrained and suspended particles, dust and droplets. The air handling device is configured and operated to maintain a negative air pressure within the containment housing, which ensures that any air exchange is from outside the containment housing to inside the containment housing, and from inside the containment housing through the air handling device.

[0023] In various embodiments, the containment housing is designed and constructed to have sufficient vertical height to allow the manufacturing module to move above the transport surface and below the processing unit operation equipment that penetrates the ceiling and / or side walls of the containment housing. In some embodiments, the air flow rate within the containment area is controlled in the containment housing, especially the horizontal air flow rate, to provide effective entrainment and collection of droplets, particles and mixtures thereof without affecting the processing unit operations or the products formed on the substrate forming the module. In some embodiments, the ratio of the vertical height (or average vertical height) of the containment housing to the area of ​​the containment housing is generally at least 0.1 cm / m 2 , up to 100 cm / m 2 , and the ratio of the vertical height (or average vertical height) to the width (shorter lateral dimension) of the containment shell is at least 0.5 cm / m and at most 20 cm / m.

[0024] <1a> A non-limiting embodiment of the present invention provides a processing system for manufacturing articles, comprising: i) an omnidirectional magnetic motion device, which includes a transport surface and a stator disposed on the underside of the transport surface, the stator including a plurality of actuating coils that apply a primary magnetic field through the transport surface in response to a controlled current through an actuating circuit; ii) one or more manufacturing modules, which include a) at least one shuttle, the shuttle including a planar body and one or more magnetic components, the magnetic components responding to the primary magnetic field applied by the plurality of actuating coils to omnidirectionally levitate and transport the at least one shuttle on and above the transport surface, and b) at least one A substrate including one or more forming surfaces; iii) a motion controller for sending a controlled current through one or more of a plurality of actuation coils to control the levitation and transportation of one or more manufacturing modules; and iv) an article forming system comprising: a) a deposition device for placing a structural material on at least one of the one or more forming surfaces when the manufacturing module is in a deposition position on the transport surface; and b) a phase change device for forming at least a portion of the deposited structural material into an article within at least one of the one or more forming surfaces when the manufacturing module is in a phase change position on the transport surface. In some embodiments, the motion controller is configured to include one or more steps of asynchronously transporting the one or more manufacturing modules between at least a deposition position and a phase change position to form an article.

[0025] <1b> A non-limiting embodiment of the present invention provides a processing system for manufacturing an article, comprising: i) an omnidirectional magnetic motion device, which includes a transport surface and a stator disposed on the underside of the transport surface; ii) one or more manufacturing modules, which include a) at least one shuttle and b) at least one substrate, the substrate including one or more forming surfaces; iii) an article forming system, including: a) at least one deposition device for placing a structural material on at least one of the one or more forming surfaces when the shuttle is disposed at a deposition position on the transport surface; and b) at least one processing device for performing a processing unit operation on the structural material when the shuttle is disposed at a processing position on the transport surface; and iv) a motion controller for controlling the asynchronous transportation of the one or more manufacturing modules between at least a deposition position and at least one processing position on the transport surface to form an article. The stator includes a plurality of actuating coils, which apply a primary magnetic field through the transport surface in response to a controlled circuit current through the actuating circuit. The shuttle includes a planar body and one or more magnetic components, which respond to the primary magnetic field applied by the plurality of actuating coils to omnidirectionally levitate and transport at least one shuttle on and above the transport surface.

[0026] <1c> A non-limiting embodiment of the present invention provides a processing system comprising: i) an omnidirectional magnetic motion device comprising a transport surface; ii) one or more manufacturing modules comprising a) at least one shuttle comprising a planar body and one or more magnetic components that interact with the magnetic motion device to omnidirectionally levitate and transport the at least one shuttle on and above the transport surface, and b) at least one substrate comprising one or more forming surfaces; iii) a product forming system comprising: a) a deposition device for placing a structural material on at least one of the one or more forming surfaces when the shuttle is located at a deposition position on the transport surface; and b) a phase change device for forming at least a portion of the deposited structural material into a product within at least one of the one or more forming surfaces when the shuttle is located at a phase change position on the transport surface; and iv) a control system for controlling the deposition device and phase change device of the product forming system, and the movement of the one or more manufacturing modules on the transport surface of the omnidirectional magnetic motion device, wherein the motion controller is configured to include one or more steps of asynchronously transporting the one or more manufacturing modules at least between the deposition position and the phase change position to form the product.

[0027] <1d> In some embodiments, the present invention provides a processing system for manufacturing an article, including operating through one or more processing units. The AM system includes: i) a horizontal planar transport surface having a periphery extending in a first direction and a lateral second direction, and having an upper transport side and a lower side; ii) a stator, which is arranged on the lower side of the transport surface, including a primary actuation circuit having a plurality of primary pairs and a primary actuation coil, the primary actuation coil responding to a controlled current through the actuation circuit, applying a primary magnetic field through the transport surface and to the upper transport side; iii) one or more manufacturing modules, including a) at least one shuttle, which includes a planar body and one or more magnetic components, which interact with the plurality of actuation coils to enable the at least one shuttle to omnidirectionally levitate and transport on and above the transport surface, and b) at least one substrate, which includes one or more forming surfaces; iv) a motion controller for sending a controlled current through one or more of the plurality of actuation coils , to control the suspension and transportation of the one or more manufacturing modules, the transportation of the shuttle includes: a) movement of the shuttle in a first direction, a second direction or a combination thereof between two or more positions on the transport surface, b) rotation of the shuttle around at least one orthogonal axis of the shuttle, and c) a combination thereof; v) a product forming system, including: a) a deposition device for placing a structural material on at least one of the one or more forming surfaces when the shuttle is located at a deposition position of the transport surface; and b) a phase change device for forming at least a portion of the deposited structural material into a product in at least one of the one or more forming surfaces when the shuttle is located at a phase change position on the transport surface; wherein the motion controller is configured to include one or more steps of asynchronously transporting the one or more manufacturing modules between at least the deposition position and the phase change position to form the product.

[0028] <1e> An embodiment of the present invention provides a process system for manufacturing an article, comprising: i) an omnidirectional magnetic motion device, which includes a transport surface and a stator arranged on the lower side of the transport surface, the stator including a plurality of actuating coils that apply a primary magnetic field through the transport surface in response to a controlled current through an actuating circuit; ii) one or more manufacturing modules, which include a) at least one shuttle, the shuttle including a planar body and one or more magnetic components, the magnetic components responding to the primary magnetic field applied by the plurality of actuating coils to omnidirectionally levitate and transport the at least one shuttle on and above the transport surface, and b) at least one substrate, the substrate including one or more forming surfaces; iii) a motion controller for sending a controlled current through one or more of a plurality of actuation coils to control the suspension and transport of one or more manufacturing modules; and iv) an article forming system comprising: a) a deposition device for placing a structural material on at least one of the one or more forming surfaces when the manufacturing module is located at a deposition position on the transport surface; and b) a phase change device for forming at least a portion of the deposited structural material into an article within at least one of the one or more forming surfaces when the manufacturing module is located at a phase change position on the transport surface, wherein the motion controller is configured to include one or more steps of asynchronously transporting the one or more manufacturing modules between at least the deposition position and the phase change position to form the article.

[0029] <1> Embodiments of the present invention can include any of features <1a> to <1e>.

[0030] <2> In features <1a> to <2> In any of the embodiments, the motion controller is configured to include one or more steps of asynchronously transporting one or more manufacturing modules between at least a deposition location and a phase change location to form an intermediate article or a finished product.

[0031] <3> In features <1a> to <3> In any of the embodiments, the transport surface comprises a non-conductive continuously formed sheet, wherein the sheet can be made of a material selected from the group consisting of polymer, glass, titanium and stainless steel.

[0032] <4> In features <1a> to <3> In any of the embodiments, the transport surface is a rectangular area including a central area and a peripheral area, and optionally, the transport surface is a rectangular area including a central area and a peripheral area, and the surface temperature of the area can be controlled by circulating an appropriate heat transfer medium in the internal area of ​​the stator to control and maintain the temperature of the transport surface, and the width dimension of the peripheral area is at least the width of the manufacturing module, and the width dimension of the central area is at least the width of the manufacturing module.

[0033] In features <1a> to <4> In any of the embodiments, the stator includes a plurality of second pairs of second actuation circuits and second actuation coils, which apply a second magnetic field to the upper transport side through the transport surface in response to a controlled current passing through the actuation circuit, and the force of the second magnetic field is greater than the force of the first magnetic field.

[0034] <5> In features <1a> to <5> In any of the embodiments, one or more of the manufacturing modules further comprises a carrier for securing the substrate to the at least one shuttle.

[0035] <6> In features <1a> to <5> In any of the embodiments, one or more forming surfaces include one or more recesses.

[0036] In features <1a> to <6> In any of the embodiments, the step of transporting the shuttle also includes pivoting the shuttle about a horizontal axis passing through the shuttle, a vertical axis passing through the shuttle, or a combination of the horizontal axis and the vertical axis, sufficient to change the distribution of the structural material deposited on one or more forming surfaces, and preferably includes flattening the deposited structural material to a uniform thickness by controlling at least one or more factors of the pivot angle, acceleration and frequency.

[0037] In features <1a> to <6> In any of the embodiments, the movement of each of the plurality of manufacturing modules between a deposition position and a phase change position is independent and selective to provide the ability to asynchronously form a dosage form on at least one substrate of two different manufacturing modules.

[0038] In features <1a> to <6> In any of the embodiments, a deposition apparatus places structure material on one or more forming surfaces based on at least one of volume and mass.

[0039] <7> In features <1a> to <6> In any of the embodiments, one or more manufacturing modules include a plurality of manufacturing modules, and each of the plurality of manufacturing modules is independently and selectively moved back and forth between a deposition position and each of the phase change positions to provide the ability to asynchronously form products on at least one substrate of two different manufacturing modules.

[0040] <8> In features <1a> to <7> In any of the embodiments, the processing system or sub-processing system further includes a tool for flattening the deposited structural material to a uniform thickness.

[0041] <9> In features <1a> to <8> In any of the embodiments, the processing system or sub-processing system further comprises one or more additional processing equipment selected from drying equipment, structural material leveling equipment, surface finishing equipment, substrate loading equipment, substrate unloading equipment and combinations thereof.

[0042] <10> In features <1a> to <9> In any of the embodiments, the processing system or sub-process further comprises a surface finishing device for performing surface finishing on the upper surface of at least one of the structural material or the solid dosage form deposited in the surface when the shuttle is located at the surface finishing position on the transport surface.

[0043] <11> In features <1a> to <10> In any of the embodiments, the process system or sub-process further includes a deposition sensing device for detecting uniformity of distribution of deposited structural material on one or more forming surfaces.

[0044] <12> In features <1a> to <11> In any of the embodiments, the structural material can include an ingestible powder material; the structural material or the ingestible powder material can include an active agent, a non-limiting example of which is an API, a biological material, or a drug. The article can be a solid dosage form, and the phase change device includes a tool for dispersing a binding liquid that forms an ingestible powder material into the binding powder material, the binding powder material including an interconnected matrix of the ingestible powder material. The building powder material can include a particulate binder. The binding liquid can contain an active agent, a non-limiting example of which is an API or a drug. The binding liquid can include a soluble binding material. The interconnected matrix of the building powder material can be porous and, in some embodiments, rapidly orodispersive. The structural material can include at least one heat-meltable powder material, and the phase change device can include a tool for at least partially melting the heat-meltable material.

[0045] In features <1a> to <11> In any one of the embodiments, the processing system and the sub-processing system can also include equipment, devices or subsystems for storing, transmitting and / or depositing auxiliary active agents on structural materials or phase change structural materials. The non-limiting example of an active agent is an API or a medicine, and / or a material with a specific function, which is designed to impart a target site or a release rate of a bioactive agent. The auxiliary active agent can optionally be a solid, a particulate material or a liquid material, and can be a particle or liquid form, and one or more optional solvents, free-flowing aids, diluents and carrier materials.

[0046] The present invention also provides a method of using an omnidirectional magnetic motion system, which uses a guidance system to transport one or more shuttles on a stator. The omnidirectional magnetic motion system provides synchronous and / or asynchronous motion of one or more shuttles to transport and optimize the position orientation of one or more shuttles to transport substrates to unit operation processing equipment and transport substrates between operation processing equipment. In the example of asynchronous processing, corresponding processing unit operations are performed on the substrates in series, parallel and / or simultaneously to optimize processing efficiency and processing utilization.

[0047] The method and system for omnidirectionally and asynchronously moving substrates to and between processing devices, through the operation of one or more processing units, can simultaneously and selectively process one or more products in a small space and in a shorter time compared to conventional processing systems for the same products.

[0048] <13> Embodiments of the present invention provide a method of using a planar motor system for transporting one or more manufacturing modules through multiple processing unit operations used in the additive manufacturing of dosage forms, wherein the transportation is controlled (directly, or via machine learning, artificial intelligence or other position scheduling methods) to achieve asynchronous, synchronous and random positioning and orientation, thereby achieving asynchronous and synchronous utilization of the processing unit operations in the formation of the dosage form.

[0049] <14> In Features <13> In an embodiment of the present invention, the plurality of processing unit operations include dispensing a mass quantity of structural material onto one or more forming surfaces of a manufacturing module and phase changing the mass quantity of structural material disposed on the one or more forming surfaces of the manufacturing module into a solid dosage form.

[0050] <15> In Features <13> or <14> In any embodiment of the present invention, the plurality of processing unit operations further comprises one or more processing unit operations selected from the group consisting of mixing two or more different structural materials, flattening the upper surface of a quantity of structural material, finishing the outer surface of a solid dosage form, inspecting one or more physical properties of a material, and cleaning contaminated equipment or apparatus used in the method.

[0051] <16> In Features <13> to <15> In any of the embodiments, the structural material is an ingestible powder material, and the phase change includes printing a liquid material including a solvent or other volatile compound onto the ingestible powder material layer, and optionally drying excess solvent or other volatile compound in the wet powder layer.

[0052] <17> In Features <13> to <16> In any of the embodiments, the multiple processing unit operations include dispensing a certain amount of ingestible powder onto one or more forming surfaces of a manufacturing module, leveling the upper surface of the certain amount of ingestible powder set on one or more forming surfaces of the manufacturing module to form a powder layer, printing a liquid material including a solvent or other volatile compound onto the upper surface of the certain amount of set powder to form a wet powder layer on one or more forming surfaces of the manufacturing module, and optionally drying excess solvent or other volatile compound of the wet powder layer.

[0053] <18> In Features <13> to <17> In any of the embodiments of the present invention, the method further comprises a processing unit operation of printing a liquid material comprising a solvent onto a surface of the one or more forming surfaces of the substrate prior to dispensing the ingestible powder.

[0054] <19> In Features <13> to <18> In any of the embodiments, additive manufacturing of the dosage form is selected from the group consisting of binder jetting, material jetting, stereolithography, fused deposition, laser sintering, and extrusion.

[0055] <20> In Features <13> to <19> In any of the embodiments, cleaning of the equipment or instrument includes placing the cleaning substrate sufficiently close to a particular processing unit operation and spatially manipulating at least one of the cleaning substrate and the contaminated equipment or instrument to clean one or more surfaces in the contaminated equipment or instrument. BRIEF DESCRIPTION OF THE DRAWINGS

[0056] Figure 1 A processing system having an omnidirectional magnetic motion device, a containment system, and a plurality of processing unit operating systems for forming articles on a transport module is shown.

[0057] Figure 2 A containment housing having an access port for positioning a processing device on a transport surface is shown.

[0058] Figure 3 A plan view of the transport surface of an omnidirectional magnetic motion device is shown, showing the various sheet segments and unit operation processing stations between which a set of transport modules can be moved and positioned.

[0059] Figure 4 A bottom perspective view of a manufacturing module including a shuttle, a carrier, and a substrate is shown.

[0060] Figure 5 Shows Figure 4 A top side perspective view of a manufacturing module and a mask that can be positioned on a substrate.

[0061] Figure 6 Shows Figure 4 An exploded view of the components of the manufacturing module.

[0062] Fig. 7A and 7B An air manipulation and filtration device providing air manipulation and separation of airborne particles and droplets is shown.

[0063] Fig. 8A A top perspective view of a powder dosing device for dispensing powder material to various forming surfaces of a substrate is shown.

[0064] FIG. 8B shows Fig. 8AExploded view of the components of a powder dosing device.

[0065] Fig. 9A A partial cross-sectional view of the powder leveling device is shown in a raised position.

[0066] Fig. 9B Shows Fig. 9A Powder levelling device in lowered position.

[0067] Fig.10 A bottom perspective view of a liquid printing device is shown.

[0068] Fig.11A A bottom perspective view of a surface finishing apparatus for finishing a top surface of an article formed on a substrate is shown.

[0069] Fig. 11B Shows Fig.11A A top perspective view of a surface finishing apparatus.

[0070] Fig. 12A and FIG. 12 shows an imaging apparatus for scanning the surface profile of a substrate and a structured material deposited within a recess of the substrate.

[0071] Fig.13 Shown is a top front perspective view of a print nozzle cleaning device for use with a shuttle.

[0072] Fig.14 Shows Fig.13 A top and rear perspective view of a print nozzle cleaning device.

[0073] Fig.15 Shows Fig.14 Exploded view of the components of the print nozzle cleaning device.

[0074] Fig.16A A top front perspective view of a finishing surface cleaning apparatus for use with a shuttle is shown.

[0075] Fig. 16B Shows Fig.16A Bottom front perspective view of a finishing surface cleaning device.

[0076] Fig. 16C Shows Fig.16A Exploded view of the components of a finishing surface cleaning device.

[0077] Fig.17A A perspective view of a mask lifting apparatus for lifting and removing masks from a fabrication module is shown.

[0078] Fig. 17B Shows Fig.17AA perspective view of a manufacturing module in which a mask is lifted in an articulated manner by a mask lifting device.

[0079] Fig.18 A plan view of a processing system is shown, the processing system comprising a transport surface, a containment system, and a plurality of processing unit handling systems located within the containment system and above the transport surface for forming tablets.

[0080] Fig.19A A top perspective cutaway view of a generally recessed depression in a blister card is shown, the blister card being passed through the laser stripe plane to generate a first laser stripe image along a contoured surface of the blister card.

[0081] Fig.19B Shown according to Fig.19A Side cross-sectional view of the corrected height profile of the blister card profile surface determined from the laser stripe image generated in .

[0082] Fig. 20A Shows Fig.19A The top side three-dimensional cross-sectional view of the blister card is shown in FIG. 1 , and the laser bar plane passes through the second portion of the blister card to generate a second laser bar image along the contour surface of the blister card.

[0083] Fig. 20B Shown according to Fig. 20A Side cross-sectional view of the corrected height profile of the blister card profile surface determined from the laser stripe image generated in .

[0084] Fig.21A Shows Fig.19A A top side perspective cross-sectional view of a partially filled depression in a blister card of FIG. 1 , the blister card passing through a laser stripe plane to generate a laser stripe image along a contoured surface of the blister card.

[0085] Fig. 21B Shown according to Fig.21A Side cross-sectional view of the corrected height profile of the blister card profile surface with partially filled depressions determined from the laser stripe image generated in FIG.

[0086] Fig.22A Shows Fig. 20A A top side perspective cross-sectional view of a blister card, wherein a laser stripe plane passes through a second portion of the blister card having a partially filled recess to generate a laser stripe image along a contoured surface having the partially filled recess.

[0087] Fig. 22B Shown according to Fig.22A Side cross-sectional view of the corrected height profile of the contour surface of the partially filled recess of the blister card determined in the generated laser stripe image. DETAILED DESCRIPTION

[0088] definition:

[0089] "Active agent" can include, but is not limited to, one or more drugs, active pharmaceutical agents (API), nutrients, pharmaceutically acceptable agents, bioactive agents, therapeutic agents, diagnostic agents, and preservatives or disinfectants. Active agents can be compounds or compositions that provide biological activity in mammals or non-mammalian species; for example, producing pharmacological activity or other direct effects in the diagnosis, cure, relief, treatment, or prevention of a disease, or affecting the structure and function of a mammal or non-mammalian species. Diagnostic compositions can include imaging agents and / or radiolabeled compounds. Active agents can be small molecule therapeutics, peptides, and / or proteins.

[0090] As used herein, an "article" is an object or composition of matter. Non-limiting examples of an object are a tablet or an implant. Non-limiting examples of a composition of matter are a liquid, semi-solid or solid substance.

[0091] As used herein, "structural material" refers to a material (solid, semi-solid, liquid or liquefied gas) that becomes part or portion of an article or composition of matter, or an intermediate thereof, or a portion thereof.

[0092] As used herein, a "processing unit operation" includes, but is not limited to, operations involving the supply, delivery and distribution of structural materials or intermediate products for an article, or operations involving the handling of materials or compositions involved in the processing of an article or intermediate product, or operations involving physical changes or chemical transformations of compounds, compositions or materials (including structural materials), and can include the unit operations further described herein.

[0093] <Omnidirectional magnetic motion device>

[0094] Reference Figure 1 The omnidirectional magnetic motion device 20 has a horizontal and planar (xy coordinate) transport surface 16, along and above which one or more transport units (referred to herein as shuttles) including permanent magnets (or electromagnets) are capable of being transported in the xy direction in the horizontal plane to a specified xy position with a specified xy orientation. A drive coil called a stator positioned below the transport surface is controlled by a control unit to generate a variable and adjustable magnetic field across the transport surface so that one or more shuttles are suspended and move in a desired horizontal direction on the transport surface. Details of the design and construction of the omnidirectional magnetic motion device and system are described in International Patent Publications WO 2018 / 176137, WO 2020 / 073118, WO2020 / 243814, and WO 2021 / 119819, the entire contents of which are incorporated herein by reference.

[0095] Alternatively, the stator can be composed of permanent magnets, and the shuttle can be equipped to generate a controlled magnetic field for levitating motion on the stator. However, in conjunction with the present disclosure, the stator will be referred to as an assembly of fixed and controllable electromagnets, and the transport unit shall be referred to as a shuttle consisting of permanent magnets (or electromagnets) movable on the stator, regardless of the operating mode.

[0096] Figures 1 to 3 A processing facility 10 is shown, which includes an omnidirectional magnetic motion device 20 (hereinafter also referred to as a processing motion device 20) that is integrated with one or more (usually multiple) processing units. The processing facility 10 includes: a processing platform 12 that includes or accommodates the omnidirectional magnetic motion device 20, a functional processing part and electronic and electrical connections for operating the processing facility including the processing motion device. The processing facility 10 also includes a platform surface 13 covering the processing platform 12. A portion of the platform surface 13 includes a transport plane 16, and the omnidirectional magnetic motion device 20 is provided below the transport plane 16.

[0097] The processing motion device 20 includes a magnetic motion stator 21, which includes a plurality of magnetic motion sub-units or sheet segments 22, each sheet segment consisting of a stator or a stator integral group sealed in a shell. The sheet segments 22 are connected edge to edge and integrated to form a sheet segment matrix, each sheet segment is a square of about 9 inches (22 cm) square, or a square of about 1 foot (30 cm) square. The integrated sheet segments 22 can be oriented in a variety of forms. In the illustrated embodiment, the integrated sheet segments are arranged to be two (2) sheet segments wide by twelve (12) sheet segments long. The platform surface 13 is placed above the top surface of the shell of the integrated sheet segments 22, and the portion of the platform surface 13 directly above the integrated sheet segments provides a transport surface 16. The platform surface 13, and in particular the portion thereof above the integrated sheet segments, is a thin non-magnetic sheet, for example, a non-magnetic stainless steel plate. Figure 1 In the illustrated embodiment, the platform surface 13 has a rectangular area that is 4 feet wide and 13 feet long.

[0098] The transport surface 16 can have one or more processing stations, where unit operation processing equipment can be positioned above the processing stations, and one or more inspection stations, where inspection equipment can be positioned above the inspection stations. As described herein, the shuttle can move to a processing station and be positioned and oriented below the processing equipment, or can move to an inspection station and be positioned and oriented below the inspection equipment.

[0099] <Shuttle>

[0100] A plurality of driven magnets (permanent magnets or electromagnets) are arranged in a plane on the planar body of the shuttle and are covered or encased by stainless steel, durable plastic or similar continuous material. The magnetic fields of the onboard drive magnets interact with the generated controlled magnetic field of the stator to exert a driving force on the shuttle in the desired and indicated direction, moving the shuttle along the transport surface and moving the shuttle itself over the transport surface. The shuttle is capable of moving in three positional rotations (pitch, roll and yaw) and through three orthogonal directions of motion (including the horizontal x and y directions, and the vertical z direction) on the transport surface.

[0101] Thus, the multiple drive coils of the stator and the multiple driven magnets of the shuttle are arranged to enable the shuttle to move in all six degrees of motion, thereby providing the simplest to very complex movements of the shuttle with high precision.

[0102] The omnidirectional magnetic motion system can also include one or more sensors for transmitting the position of the shuttle. In some embodiments, using the real-time position of the shuttle, the motion controller can activate one or more stator drive circuits to drive the actuation coil assembly to interact with one or more magnets of the shuttle to move the shuttle on the transport surface.

[0103] Each shuttle of the omnidirectional magnetic motion system is provided with a unique shuttle identification code. The shuttle (magnetic mover) also includes at least one shuttle identification device, and the stator includes at least one stator identification device and one or more sensors, the stator identification device can operably interact with the at least one shuttle identification device to associate the unique shuttle identification code with a specific shuttle, and the sensor is used to sense the position of the specific shuttle. The control system can continuously track the position of the stator and the magnetic field generated in the stator to transport, stator and orient the shuttle as indicated and required.

[0104] The present invention provides a processing system and method using an omnidirectional magnetic (processing) motion device as a means for transporting substrates in a production process that operates by employing one or more, preferably multiple, processing units. Figures 4 to 6 A manufacturing module 70 is shown in combination with a shuttle for placing and moving the manufacturing module on the transport surface 16 of the omnidirectional magnetic motion device 20. The 24 sheet segments 22 (segments A1-A12 and B1-B12) are shown integrated into a single stator 21 that is located below the platform surface 13 and forms a single transport surface 16 portion of the platform surface 13.

[0105] The shuttle car typically has a square plan shape (but can also be made into other shapes), has a peripheral edge, and has a cover of a strong and durable plastic. Alternatively, the shuttle car can have a continuous, seamless stainless steel shell. The characteristics of the shuttle car allow a carrier to be attached to its upper surface or around its periphery, thereby allowing the shuttle car to transport the carrier and any material or object placed on the carrier.

[0106] In various embodiments, the system can include subsystems and processes executed to transfer a shuttle to a processing motion device and associate the shuttle having a unique identification address with the processing motion device.

[0107] <Transportation Module and Manufacturing Module>

[0108] The transport module is a magnetic motion device that includes at least one shuttle and (in various embodiments) a carrier. The carrier is a structural device whose lower portion is configured to be attached to the surface of the shuttle in a predetermined orientation and whose upper portion supports or is attached to the substrate. Typically, the carrier is fastened or fixed to the shuttle. Although the transport module can have a single shuttle, two or more shuttles can be combined into a single transport module. The structural device of the carrier can be any suitable structural material, for example, plastic, ceramic, metal or a composite thereof. The carrier docks the substrate with at least one shuttle.

[0109] As described herein, a manufacturing module is a transport module having a substrate attached or fixed to a carrier. The substrate can be any device or material on which the component materials of the article are placed or deposited, for example, solid, solid particles, semi-solid or liquid, or materials for ingredients, components or reactants of article processing or unit operations. Figure 4-6 An example of a manufacturing module 70 is shown.

[0110] The movement and positioning of the manufacturing module by the processing motion device is very important for the operation of the processing unit operation equipment associated with or interacting with the manufacturing module. For example, after the manufacturing module has been moved to the structural material dispensing equipment and is properly positioned and oriented, the motion controller can send instructions to the processing unit operation controller to notify or confirm that the specific manufacturing module has been properly positioned and oriented, and the processing unit operation controller can continue the processing unit operation and control of the processing operation equipment or device. In some processing unit operations, the processing unit operation continues when the manufacturing module is stationary in position and orientation, while in other processing unit operations, the processing unit operation continues when the manufacturing module moves. In some embodiments, the manufacturing module moves with the movement of the shuttle in any one or a combination of the six degrees of freedom of movement; for example, in the horizontal (x, y) direction; in the vertical (z) direction, through the rotational movement of the vertical axis normal to the planar body of the shuttle, or a combination thereof. In some embodiments, the shuttle can swing one or both of the horizontal axes through the planar body of the shuttle to achieve the same frequency of the swinging movement of the shuttle and the vibration of the manufacturing module fixed thereon.

[0111] The process motion controller tracks the movement and position of the manufacturing modules through one or more unit operations and should be able to fully control the article manufacturing process to produce single or more articles for a single, specific customer or patient on a personalized basis.

[0112] <Substrate>

[0113] The substrate is a device or forming material on which the component materials of the article, or the reactants of the processing unit operation used to make the article, are placed or deposited. Non-limiting examples of component materials are solid, solid particulate, semi-solid, liquid or liquefied gas components of the article manufactured at the processing facility 10.

[0114] The substrate can be formed in an integrated substrate forming system and processing, or more generally, in a processing system that is separated from and away from the processing and forming intermediates of the article or article. The formed substrate is then transferred to an omnidirectional magnetic motion system and / or a containment system for additional processing. The substrate forming system can include a substrate forming device that forms a substrate from a stock material (e.g., a thermoplastic film), a stock film supply device for supplying the stock material to the substrate forming device, and a loading system for positioning and placing the formed substrate on a carrier of a transport module. The substrate can be formed on demand when needed, or can be pre-formed in advance and stacked or grouped for use. In the embodiments below, the processing system can include a substrate temporary storage area, and includes a device for using a combination of a vertical lifting arm and a destacking mechanism to retrieve a stacked substrate (to separate a single top substrate from a stack of substrates) to place an unstacked substrate on a transport module (more specifically, on a carrier of a transport module).

[0115] In some embodiments, the substrate can be a flat surface, and one or more articles can be formed on the upper flat surface. In other embodiments, the substrate can be a container for one or more materials. In some embodiments, the container can be a molded form having one or more depressions, wherein the article is made by a processing unit operation, and the article is then released or ejected from one or more depressions. In some embodiments, one or more depressions of the molded form have the shape of a tablet or other dosage form, non-limiting examples being cylindrical or oblong.

[0116] In one particular embodiment, and in various embodiments of a process for forming an article on a substrate using processing facility 12, the substrate is a blister card having one or more (typically a plurality) depressions arranged in an array, which provides both a molded form for processing of the article and its packaging.

[0117] Blister cards can have any available area shape or size, and the number of blister depressions as desired or required. In various embodiments, the length and width of a blister card with a single forming surface formed as a depression can be at least 1 cm to several centimeters. Blister cards usually have several, even dozens or more forming surfaces formed as depressions, and can be about 5 cm to 20 cm in both length and width. The stock roll of blister cards that are usually divided into a plurality of individual blister cards can have hundreds or thousands or more forming surfaces formed as depressions. In a non-limiting example, the width of the blister card is about 10-15 cm, the length is about 16-20 cm, and there are 2-40 forming surfaces formed as depressions. In one embodiment, the blister card is about 20 cm long and about 13 cm wide, with 24 (6 x 4 layout) pre-formed depressions. In another embodiment, the blister card is about 13 cm long and about 10 cm wide, with 12 (6 x 2 layout) pre-formed depressions. Figure 6 An example of a blister card 80 is shown.

[0118] Non-limiting examples of substrates can include blister trays and 3D printing support structures having a planar structure and a connecting member that is detachably connected to a 3D printing tablet, as described in U.S. Patent Application Publication 2021 / 0205228, the entire contents of which are incorporated herein by reference.

[0119] In some embodiments, the substrate forming system and process include a marking system for marking (e.g., by printing) a unique identification code on the substrate (including on the forming surface of the substrate), such as a batch number, a digital address code, a 2D barcode, a DataMatrix, or a QR ("Quick Response") code. The marking can be a visible marking using suitable visible or invisible inks, or an invisible marking that is invisible to the naked eye. In various embodiments, the marking is formed on one or more surfaces of the substrate (e.g., the top and bottom surfaces of a blister card), or on each forming surface (e.g., the top surface of the recessed base, and / or the bottom surface or underside of the recessed base of each blister card). The marking can be detected and read by a scanner or imaging system, and the unique identification code is transmitted and input into a controller of a process control system. The process control system associates the unique identification code of the physical substrate with the unique shuttle identification code of a specific shuttle transporting the manufacturing module carrying the physical substrate thereon. When the manufacturing model carrying the substrate is moved to the unit operation processing station under the control of the motion controller, the processing unit operation controller associates the unique identification code of the substrate with the unit operation process and creates a record of the execution and completion of the unit operation process using the same unique identification code of the substrate. This control and recording process can be repeated at each unit operation processing station and inspection station used in product manufacturing.

[0120] In some embodiments, the substrate forming system and process can also include a substrate motion system, which consists of an omnidirectional magnetic motion system dedicated to the substrate forming system. The substrate forming system is positioned above the transport surface of the substrate motion device, and the substrate forming system includes a substrate forming device, a stock film supply device and a loading system. The transport module (a shuttle with its carrier) can be positioned adjacent to the loading system for positioning and placing the formed substrate on the carrier to provide a manufacturing module. A marking system can also be included to mark the substrate formed as described above. A scanning system can also be included to detect the identification code of the corresponding marked substrate and the transport module carrier. Then, the manufacturing module can move to the exit along the transport surface of the substrate motion device under the control of the motion controller. In various embodiments, the substrate motion device can be integrated with the processing motion device to achieve seamless movement between the transport module and the manufacturing module.

[0121] <Substrate Mask>

[0122] A mask having one or more openings can be placed on the upper surface of the substrate, with the one or more openings aligned with one or more forming surfaces of the substrate. In one embodiment, the mask is a sheet having a peripheral shape and size that overlaps or aligns with the periphery of the blister card substrate, and the mask sheet has a plurality of openings aligned with the corresponding openings of the recess of the blister card. In some embodiments, the mask sheet can have one or more openings of any regular, irregular or geometric shape, including, by non-limiting example, circular, oval and elliptical, as desired or required, which may be required to achieve the functional performance or design aesthetics of the article. Conventional blister cards typically have circular recesses and openings, so a typical mask will have a plurality of circular openings aligned with the circular openings of the recess.

[0123] In some embodiments, typically along the edge of the substrate (blister card), the mask can remove one or more portions of the sheet to form an opening or window that is aligned with the unique identification code printed on the substrate. This exposes the unique identification code of the substrate for scanning and / or imaging to identify and align the specifically identified substrate to the processing system and motion control system for subsequent movement, tracking and positioning of the blister card during unit operation processing.

[0124] In various embodiments, the mask includes means for releasably attaching to an upper surface or portion of the carrier to inhibit or prevent movement or separation between the blister card and the carrier and to cover the upper plane of the blister card film in a continuous area surrounding one or more recesses and to block and prevent deposition of structural material and phase change liquid onto the upper plane of the film which is subsequently contacted and sealed with the sealing film. Figure 6 An example of a mask 90 is shown.

[0125] Figure 4-6The manufacturing module shown includes a transport module consisting of a shuttle 75, a carrier 72, and a base plate 80, the shuttle being able to move on a transport surface by means of a stator. The carrier 72 has a base 73 having a planar cavity in which the shuttle 75 fits precisely. The base 73 is oriented to the shuttle 75 by a pair of fixings, shown as threaded screws 76 that pass through positioning holes 77 in the adjacent side walls of the base 73 and strike the sides of the shuttle 75. Four support columns 173 extend vertically from the four corners of the base 73. The carrier 72 also has an upper portion, called a nest 74, having four support holders 174, which consist of a short hollow cylinder into which the upper ends of the four support columns 173 extend, forming a semi-rigid structure of the carrier, wherein a spring 175 is provided between each support column 173 and the support holder 174. One or more springs 175 are selected to provide flexibility, and some of the springs will "spring-deform" as the nest 74 passes under the device in the load-bearing area. One function of the one or more springs is to suspend the nest 74 above the support posts 173 so that the top ends of the support posts 173 maintain clearance with the support retainers 174 and do not contact and become jammed in the support retainers 174 of the nest 74.

[0126] The nest 74 has a plurality of openings 78 formed through its upper surface to align with and accommodate all the recesses of the blister card. The base plate 80 is a double tray blister card having first and second six-recess blister cards 82a and 82b in a blister frame 81. The blister frame 81 has a universal fixing pin at each corner of the blister frame 81, which is aligned with a corresponding universal fixing slot 182 in the upper surface of the nest 74 in any direction of the blister frame. The nest 74 and the blister frame 81 also have a tool for positioning the blister frame 81 on the nest 74 in only one direction. The blister frame includes a pair of closely spaced orientation pins 186 on opposite longitudinal (or transverse) ends, and a pair of widely spaced orientation pins 187 on one longitudinal (or lateral) end. The closely spaced orientation pins 186 of the blister frame 81 align and fit only into the closely spaced orientation slots 183 of the nest 74 , and the widely spaced orientation pins 187 of the blister frame 82 align and fit only into the widely spaced orientation slots 184 in the nest 74 .

[0127] The mask 90 is placed on the blister frame 81 to protect the unformed film portion (the film portion surrounding the recess) of the blister card 82 from contact and contamination by the structural material and the processing material. Excessive spraying of printing liquid outside the recess and on the unformed film portion can interfere with the proper fixation of the sealing film on the formed dosage form of the blister card. Figure 5 and Figure 6As shown, the mask 90 has a planar frame 91 having a plurality of circular openings 92 that correspond and align with the openings in the plurality of recesses 84 of the blister cards 82a, 82b when oriented with the nest 74. The mask includes a pair of lift pins 94 extending from opposite sides of the frame 91 at the front end of the mask, and hinge members, shown as hinge pins 99 extending from opposite sides of the frame 91 at the rear end of the mask to engage with a pair of hinge members on opposite sides of the frame 91 at the rear end of the nest 74, shown as a pair of clamps 99 having slots for respectively receiving the pair of hinge pins 99 to form a pair of hinges, which allows the front end of the mask 90 to pivot upward and away from the nest 74.

[0128] The nest 74 also has a front edge with a recess 188 having an undercut pattern at the front end of the blister card 80 so that a user's finger or other tool can be placed in alignment with the recess to lift the front end of the blister card 80 when removing the blister card 80 from the nest 74. Similar recesses 88 are formed in the side edges of the nest 74 with an undercut pattern at the side edges of the blister card 80 so that a user's finger or other tool can be placed in alignment with the recess to lift the front end of the blister card 80 when removing the blister card 80 from the nest 74.

[0129] <Module Movement>

[0130] Each independent transport or manufacturing module can move independently of the other transport or manufacturing modules and can move in a different direction and mode than the other transport or manufacturing modules. The transport or manufacturing modules can move on the transport surface at a speed of up to 2 m / sec, typically between 0.1 and 0.75 m / sec, and can accelerate up to 5 m / sec 2 .

[0131] The movement of the shuttle can be configured to operate under the control of a motion controller, with the substrate fixed to the carrier and the carrier fixed to the shuttle. Once the substrate is separated from the carrier, the shuttle can be automatically moved to a temporary storage area away from the dosage form forming system under the control of the motion controller.

[0132] The shuttle is typically magnetically suspended above the transport surface at a height of up to about 4 mm, more typically about 3.5 mm, and can be controlled at a height of about 0.1-3.5 mm. More specifically, the planar bottom surface of the shuttle is above and parallel to the planar transport surface. After the manufacturing module is positioned and oriented at the processing station, the vertical lift shuttle is capable of lifting the substrate attached to the carrier transported by the shuttle to a non-contact position in contact with or closer to the unit operation equipment or device to improve processing accuracy and efficiency and reduce the loss of powder or droplet materials into the air space of the containment area.

[0133] Each shuttle can include multiple motion signaling devices that communicate with one or more static detectors within the stator to convey the position and orientation of the shuttle at any moment, as well as the motion of the shuttle on the transport surface. The accuracy resolution is typically about 0.2 mm or less, including about 0.02 or less, for example, about 5 microns, and the refresh interval (or delay) is less than 100 msec.

[0134] Each independent fabrication module is independently movable and positionable to a processing station or inspection station of the processing platform 12 to respectively position and / or orient the substrate and its one or more formation surfaces beneath or relative to the processing equipment or inspection equipment, respectively.

[0135] <Containment System>

[0136] The handling system can include a containment system. The containment system provides a containment area that includes and is typically composed of a volume space between an upper surface of the stator transport surface and a containment shell. The containment shell includes one or more transport openings and one or more sealable openings.

[0137] The transport opening can include an opening or port through the side wall of the containment shell, which extends from the transport surface to the side wall to provide an inlet and / or outlet for the manufacturing module to enter and exit the containment area. The lateral and height dimensions of the transport opening are sufficient to meet the needs, and are generally sized to allow one or more shuttles (including corresponding substrates and products formed thereon) to pass through the transport opening at the same time. The transport opening can also be used to provide an airflow inlet to allow airflow to enter the containment area from the outside. When air leaves the manufacturing module, the air flows into and passes through the manufacturing module to enhance the removal of loose particles. In some embodiments, a seal can be temporarily placed and sealed on the transport end opening and can be hinged or removable.

[0138] The sealable opening can include an opening or port through a top panel or side wall of the containment housing, which is usually in a sealed state during the operation of the processing system or sub-processing system. The unit operation processing equipment is positioned in one of the sealable openings of the containment housing for processing unit operations in the containment area. Usually the sealable openings have similar or uniform sizes. The unit operation processing equipment usually has a processing portion extending vertically to the containment area and an external portion extending outside the containment housing, which can be accessed or controlled from outside the containment housing. The processing portion extending in the containment area can be an element for dispensing compounds or processing materials, for example, a powder metering port or a liquid nozzle, a texturing element for tamping or manipulating structural materials or phase change materials, and a tool for contacting with structural materials or substrates to manipulate or move structural materials and / or phase change or processing materials, for example, a probe element. If necessary, each unit operation processing equipment can be equipped with a sealing adapter plate, which has an internal sealing portion that can be sealably attached to the processing equipment, and an external sealing portion that can be sealably positioned in the sealable opening, for example, with conventional or quick-disconnect fasteners.

[0139] The containment housing can also have one or more airflow openings to allow air (e.g., conditioned air or ambient air) to pass through the containment housing from the outside and into the containment area, optionally including a seal for sealing the air opening when necessary. The airflow openings can be placed at various locations along the containment housing to better control the amount and location of air drawn into the containment housing.

[0140] The containment system also includes air handling and filtration devices, such as high-efficiency particulate air (HEPA) filtration devices, which are used to provide air treatment and separation of airborne particles and droplets. Fig. 7A and 7BAn example of a commercially available HEPA filter device 18 is shown in FIG. One of the sealable openings 34 can be configured for mounting a HEPA filter, which includes a support 140 for mounting to a ceiling panel 33 of a containment housing, an air inlet 141 disposed within the containment housing, a particle separation device (e.g., a filter and / or cyclone separator), and an exhaust port. The HEPA filter device 18 is configured to draw an external air flow, typically a predetermined and / or continuous external air flow, into the containment area and into and through the particle collection device to ensure that the structure or treatment materials, including drugs or active particles and droplets, do not leave the containment area and escape into the external environment. Air within the containment area, which can contain airborne particles and / or droplets, is drawn into the air inlet 141 by the air blower of the HEPA filter device, filtered to separate and isolate the particles and / or droplets, and discharged into the atmosphere as filtered air. External air is drawn into the containment housing through the transport opening 36 and flows along or through the containment housing through areas of the processing unit operations and equipment (eg, powder material deposition equipment and / or phase change equipment).

[0141] In various embodiments, the design of the containment system, including the containment housing and the HEPA filtration system, is configured to always maintain a negative pressure within the containment housing relative to the environment outside the containment housing. This ensures that any exchange of air will be from the outside of the containment housing to the inside, and any air flowing from the inside of the containment housing to the outside will pass through the HEPA filtration device.

[0142] An example of a container system 90 is as follows Figure 2 As shown. The containment shell 30 includes a plurality of fixed panels, typically transparent panels, and an optional support frame. The plurality of panels include one or more upper roof panels 33 and a plurality of side wall panels, typically a series of side wall panels, including a first side wall panel 31 and a second side wall panel 32 providing a peripheral boundary on opposite sides of the containment shell 30. A transport opening 36 in the peripheral boundary is provided at the forward end of the containment shell 30. The transport opening 36 extends from the transport surface 16 to the roof panel 33 and is defined by an opposing panel 35. As described herein, the transport opening 36 provides an inlet and an outlet for the manufacturing module to enter and exit the containment area, and provides an inlet for airflow.

[0143] The top panel 33 and the side wall panels 31, 32, 35 are generally transparent or translucent, preferably transparent, so that the movement of the manufacturing modules between processing stations can be observed from outside the containment system, and the panels can be formed of sheets of transparent polymer material, such as polycarbonate ( ),acrylic acid( ), tempered glass, sapphire or polyvinyl chloride (PVC) of sufficient thickness to provide stability and support. The frame of the top panel and side wall panels can be made of conventional frame structures and conventional frame materials, non-limiting examples of which include aluminum or thermoplastic materials. In some embodiments, the frame provides rigidity and support for the top panel and side wall panels. In various embodiments, the equipment support for supporting the processing unit operating equipment above the transport surface 16 and above the containment shell 30 can include a lateral equipment support 15 that spans the width of the containment shell and is elevated with a support bracket 14.

[0144] In various embodiments, the containment housing is configured to minimize the number of devices within its gas space and to reduce exposure of device components within its gas space. Minimizing exposure of device components within its gas space also helps reduce gas flow velocity by reducing obstacles that the gas flow must bypass (which may cause the gas flow to increase in velocity as it bypasses the obstacles).

[0145] In various embodiments, the containment housing design provides a containment area of ​​sufficiently small volume to perform some or all of the processing unit operations on the structural material and / or phase change material deposited on or within the substrate.

[0146] In various embodiments, the vertical height of the containment housing is reduced to a height sufficient to move the substrate and its deposition surface over the transport surface and under the components of the device performing a series of processing unit operations. The processing unit operation equipment communicates with the manufacturing module through the top panel and / or side wall panel of the containment housing to transfer or deposit structural materials and / or perform phase change operations. For example, each of the powder deposition equipment and the adhesive liquid dispenser can deposit corresponding amounts of powder and adhesive liquid through a discharge nozzle, a print head, or a port extending through the top panel and / or side wall panel of the contaminated housing.

[0147] In various embodiments, only the portions or components of the unit operation equipment necessary to perform the processing unit operations extend vertically through the upper (ceiling) panel of the containment housing and into the interior thereof, thereby minimizing or limiting contact of airborne particulate matter with the remainder of the unit operation equipment or components. For example, a powder deposition device that deposits a structural material (e.g., a bondable powder material) onto an upper deposition surface of a substrate, such as a powder deposition device that deposits into a recess of a blister card, is configured to extend only the outlet or deposition port at the lower end of the device through the ceiling of the containment housing and into the volume thereof. By minimizing the vertical height of the containment housing, and therefore its volume, less air mass or volume is required to efficiently and effectively collect and extract airborne particles and droplets within the containment area.

[0148] The containment housing openings and the positioning of the processing unit operation equipment within the containment housing are designed, positioned and oriented to avoid excessive containment gas flow velocities, especially horizontal gas flow velocities, which would affect the effectiveness of the equipment in performing unit operations when forming articles on substrates.

[0149] In some embodiments, the lateral airflow velocity within the containment housing can be as high as 10 m / sec. The minimum airflow velocity into the air inlet opening is controlled to at least 0.5 m / sec to ensure that particulate matter cannot migrate through the opening or escape from the containment area. In various embodiments, the design of the containment system and the positioning of the processing unit operation equipment in the air space directly surrounding and adjacent to the unit operation processing, particularly powder deposition equipment and adhesive liquid printing systems, provide an average airflow through the containment system of less than 5 m / sec, more typically less than 2 m / sec.

[0150] For example, when a specific structural material is deposited onto a substrate, air can flow horizontally between a deposition device (e.g., a powder deposition device) and a substrate on which the structural material (e.g., a fixed amount of powder) is deposited, or when a structural material is phase-changed by a phase-change device (e.g., depositing a binding liquid onto a fixed amount of powder disposed on a substrate), air can flow horizontally between a liquid dispensing nozzle and a powder material disposed on a substrate. Excessive airflow directed through a containment system and between a unit processing device and a substrate can affect the precision and accuracy of powder placement on a substrate and / or liquid placement on a powder and / or substrate.

[0151] In particular, positional accuracy errors in dispensing liquid at the print nozzle are affected by the linear velocity at which the transport module carries the substrate (and the article being formed thereon) beneath the stationary print nozzle. Typically, a linear gas flow velocity of 1.0 meter per second (m / s) or less, preferably 0.6 m / s or less, is used to minimize errors in droplet position and phase change quality. Accuracy of droplet placement can also be improved by reducing the gap distance between the nozzle plate and the substrate, and / or increasing the droplet velocity to minimize the droplet flight time. The gap distance between the print nozzle plate and the substrate (e.g., a blister card or a protective mask covering a blister card as described herein) is less than 1 cm, more commonly about 8 mm or less, or 6 mm or less, such as about 5-8 mm, and can be incrementally controlled and / or infinitely controlled by a motion controller.

[0152] In some embodiments, in order to prevent or limit interference of airflow with the deposition of powder material on the substrate and the printing of binding liquid on the powder material layer, a barrier such as one or more baffles, internal walls or air curtains can be installed around the printing nozzle or device and / or the powder deposition device to reduce or prevent airflow and air vortices on the substrate surface and between the substrate surface and the processing equipment.

[0153] In various embodiments, the ratio of the vertical height (or average vertical height) of the containment housing to the area of ​​the containment region (generally, defined by the peripheral sidewalls of the containment housing) is 0.1-100 cm height per square meter (cm / m 2 ), more usually 0.5-20 cm / m 2 , even more commonly 5.0-10.0 cm / m 2 In one non-limiting example, the containment enclosure covers 20 square feet (approximately 1.8 m 2 ) area, and the containment housing has an internal height of approximately 12.5 cm, thereby providing approximately 7 cm / m 2 ratio.

[0154] In other embodiments, the ratio of the vertical height (or average vertical height) to the width (shorter transverse dimension) of the containment area is 0.5-20 cm / m, more typically 2-10 cm / m, even more typically 4-8 cm / m. The containment housing height from the transport surface of the stator to the top plate is preferably less than 50 cm, more preferably less than 15 cm.

[0155] In the volume space of the containment shell is a manufacturing module, which is suspended above the transport surface of the stator and "floats" in the gas space within the containment shell. Typically, when moving and operating in the containment shell, the height of the carrier and substrate is lower than the height of the space in which the containment system operates. In a common arrangement, the bottom of the shuttle car of the manufacturing module is about 1-5 mm, for example, about 1.5-3.5 mm, above the transport surface of the stator. The thickness of the shuttle car is usually 1-2 cm. The carrier fixed to the shuttle car and transported by the shuttle car can have a vertical height of at least 1 cm, preferably at least 5 cm, up to about 20 cm, preferably about 10 cm from the top surface of the shuttle car. In some cases, the carrier can have a larger vertical height, and when running in the containment shell, the carrier provides enough head space. In order to optimize the amount of airflow required for airborne particle control, the vertical height of the containment shell can be minimized, and its height is usually about 20-30 cm, preferably about 15 cm or less, for example, about 10 cm or less.

[0156] <Processing Unit Operation>

[0157] The present invention also provides one or more processing unit operations that can be interactively executed with an omnidirectional magnetic motion system, the omnidirectional magnetic motion system comprising an omnidirectional magnetic motion device, a shuttle, a carrier associated with the shuttle, and a substrate. One or more processing unit operations can be coordinated multiple unit operations.

[0158] Each processing unit operation is positioned near, and typically directly above, a corresponding unit operation station, which consists of an area of ​​a processing motion device designated for positioning and orienting a manufacturing module for performing unit operation processing on a specified one or more forming surfaces of a substrate. Under the control of a motion controller, each manufacturing module can be precisely positioned and oriented so that each manufacturing surface of the manufacturing module is positioned below the processing device to initiate a predetermined processing operation. In some embodiments, a predetermined processing operation can be performed while the manufacturing module and one or more forming surfaces thereon are fixed and stationary in a position on the processing motion device; for example, a stationary position and / or orientation for stationary processing when suspended above a transport surface. Alternatively, the same fixed and stationary manufacturing module can be lowered onto a physical platform surface (non-suspended) while performing a processing operation. In another embodiment, while performing a processing operation, the manufacturing module can be moved horizontally along the upper surface of the transport surface within the unit operation station under the control of a motion controller while performing a predetermined processing operation; for example, a changing position and / or orientation for dynamic processing when suspended above a transport surface.

[0159] For example, at a powder dosing (unit operation) station, a suspended manufacturing module and one or more of its forming surfaces (e.g., a blister card and its recesses) can be positioned and oriented (in the x, y plane) with the recesses being directly below and coaxial with the discharge port of the powder dosing device, and the blister card surface being spaced a minimum vertical gap distance below the discharge port of the powder doser, which distance is in the range of up to 10 mm, such as about 6 mm. With the manufacturing module fixed and suspended in place, the powder doser can deposit a dose of powder material downward from each discharge port and deposit it into the corresponding recess of the blister card substrate. The minimum vertical gap minimizes the vertical fall distance of the powder dose, thereby reducing the risk of dust cloud formation and powder splashing outside one or more recesses. Fig. 8A Examples of powder dosing devices are shown in and 8B.

[0160] In another example, at a powder leveling (unit operation) station, a manufacturing module, one or more of its forming surfaces and a dose of powder structure material (e.g., a blister card containing a dose pile of powder material and its depressions) can be positioned and oriented below a powder leveling device (in an x, y plane). With the manufacturing module fixed and grounded on a transport surface (non-suspended), one or more vibrating probes of a vibrating leveling device are lowered until the distal end contacts the upper surface of the manufacturing module and / or a substrate (e.g., a blister film web between adjacent depressions), and energy waves (e.g., sound waves) of a predetermined frequency and amplitude are axially transmitted from the distal end of the probe to and into the substrate, which causes the dose pile of powder material to disperse and diffuse within the cavity of the depression to reduce the unevenness of the surface of the powder material and form a powder layer with a flatter surface.

[0161] In another example, at a liquid printing (unit operation) station, a suspension manufacturing module, one or more forming surfaces thereof, and structural materials therein (e.g., a blister card containing a layer of powder material and its depressions) can be first positioned and oriented (in an x, y plane) such that the forming surface is disposed outside a target line of one or more rows of printing nozzles. Each printing nozzle selectively and independently ejects printing liquid within a unit target area below it at a predetermined volume rate. The suspension manufacturing module then passes under the printing nozzle and enters and passes through the target line of one or more rows of printing nozzles, while each printing nozzle independently dispenses a curtain of printing liquid onto the layer of powder material in a predetermined printing pattern, but not onto the substrate area outside the powder layer, under the control of a process controller.

[0162] Without being in any particular order or priority, the processing units can include: conveying and associating a shuttle to an omnidirectional magnetic motion device; conveying, associating and orienting a carrier to the shuttle; forming a substrate from a stock material, including forming a forming surface on which a structure material can be deposited, such as wells, cavities, penetrations, protrusions or other geometric modifications; conveying, associating and orienting the substrate to the carrier; conveying and dispensing a structure material to the substrate, which structure material can include a powder or granular material and a liquid material; leveling a powder or granular structure material on the substrate; conveying and dispensing a process material to the substrate to deposit the structure material; phase change or treatment; sterilizing or disinfecting substrates or their stock materials, structural materials, treatment or phase change fluids, and their products and intermediates using electromagnetic spectrum emissions or chemical reactants; surface modification of articles formed from structural materials or their intermediates, for example, to remove excess solidified material, including through subtractive manufacturing methods; electromagnetic (EM) radiation; thermal phase change; evaporation and drying; sterilization; product and process inspection and quality control; product marking and identification; unloading of completed products from substrates; and post-formation processing and packaging of substrates containing products to form complete master packaging units.

[0163] The omnidirectional motion system described herein for moving multiple manufacturing modules between two or more typically more processing unit operation stations allows asymmetric processing of intermediate and finished products to provide capabilities or advantages that are not or cannot be achieved using conventional processing systems. In one example, the asynchronous movement of multiple manufacturing modules allows each manufacturing module to stay at a specific unit operation station for the time required to perform the unit operation process without interfering with the movement of other manufacturing modules to other unit operation stations.

[0164] In another example, the position, orientation, and movement of each manufacturing module can be independently adjusted, so that the unit operation processing of a particular manufacturing module can be independently adjusted independently of other manufacturing modules. In a non-limiting example, by changing the orientation of the manufacturing module, liquid is dispersed onto subsequent powder layers at a different angle (e.g., 90 degrees or lateral) than it was applied to the previous powder layer, thereby adjusting the substrate pass under the liquid spray unit operation at each successive pass to wet the powder material layer deposited in one or more recesses of the substrate, which is not common or achievable in traditional conveyor systems.

[0165] In another example, the inspection system can include one or more inspection devices to detect defects or errors in intermediate or finished products in a particular manufacturing module or at a particular manufacturing location, or even to detect defects or errors at a particular manufacturing location on a particular manufacturing module, and can instruct the particular manufacturing module to be returned to the unit operation station for additional processing to prioritize the correction of the defect or error, or even temporarily interrupt the planning of the unit operation process at other manufacturing modules. This is particularly important in the following situations: a series of manufacturing modules are processed as a specific, unique batch, and the required additional processing would require inserting the specific manufacturing module into the queue sequence of the conveyor system, ahead of the unit operation process of other manufacturing modules, and then removing the same manufacturing module from the conveyor system after the unit operation to return it to the same batch of modules.

[0166] <Structural Materials>

[0167] Structural materials can include any liquid, liquefied gas, semi-solid or solid material that can be formed, transformed, reacted, mixed or incorporated into an article. Structural materials can be compositions, including one of two or more components of an article. Structural materials can also be (solid, semi-solid or liquid) intermediates or unfinished articles (e.g., tablet bodies), which are preformed and additionally processed in a processing system to form finished products or products. Solid structural materials can be powders comprising one or more granular compounds or compositions. Non-limiting examples of powders can be amorphous or crystalline fine particles, particles, powders, aggregates, coated (shell and core) particles and blocks.

[0168] Liquid structural materials can be free-flowing liquids or viscous or gel-like materials, including materials containing solid particles or particle suspensions or dispersions. Non-limiting examples of liquid structural materials include aqueous and non-aqueous liquids, organic and inorganic liquids, creams, emulsions, pastes, gels, and monomeric compounds.

[0169] The structural material can be one or more structural materials, can be a single compound or composition, or two or more different and independent compounds or compositions, as well as a mixture of two or more compounds and / or compositions.

[0170] In some embodiments, the material or the component of the material (e.g., one or more component compounds in the composition) can be a structural material, and can also be an element or component of a phase change system. In a non-limiting example, the binding liquid of the base powder can include a binding material and a solvent (a non-limiting example is water or alcohol, such as ethanol or isopropanol, etc.), wherein the binding material and a portion of the water or other solvent can become the component compounds of the formed binding powder dosage form, and also be a component of the phase change system of the base powder, which is formed by the wet binding of the binding material and the base powder to form the binding powder matrix of the dosage form.

[0171] In various embodiments, the structural material can include an active agent in powder or granular form or in liquid form, as well as, by way of non-limiting example, an API.

[0172] The structural material or its component or the component of the processing material can be the functional component of the formed product. The non-limiting example of the functional component, for example, in tablets or medicines, can include fillers, diluents, bonding agents, suspending agents, viscosity agents, polymer materials including release positioning polymers or release modification polymers, coatings, flavoring agents, disintegrants, sweeteners, preservatives, coloring agents, lubricants and sliding agents. The non-limiting examples of the compounds or components of these ingredients can include inorganic salts, acidic compounds, organic compounds such as sugars and sugar alcohols, modified starches and starches, cellulose ethers and esters, microcrystalline cellulose, carboxymethyl cellulose, crosslinked sodium carboxymethyl cellulose, glycols such as polyvinyl alcohol and propylene glycol, polyvidone, mineral hydrocarbons and fatty chemicals such as fatty alcohols, mineral stearic acid, glycerol and lipids.

[0173] In various embodiments, the structural material or its constituent elements can be transformed into a different form by mechanical processing (by way of non-limiting example, by compression, comminution, or by dissolution or suspension in a second liquid material), and / or the structural material can be transformed into a different physical state or phase (e.g., by heating or cooling the material to cause evaporation, or by sublimation, solidification, freezing, melting, spray drying, spray condensation, or condensation), and / or into a different chemical structure, for example, by chemical reaction with another compound, or by irradiation, curing, or polymerization. One or more of the processing unit operations requires the use of the processing equipment to be integrated into a processing system, which includes an omnidirectional magnetic motion system and controller, a containment system, and a processing unit operation controller.

[0174] In some embodiments, the powder material comprises a thermoforming powder that softens and / or melts when exposed to heat and high temperatures, and solidifies the build material when cooled. Non-limiting examples of thermoformable powder materials and methods, apparatuses, and systems for preparing dosage forms are described in U.S. Pat. Nos. 2009 / 0060983 (Bunick et al.), 6258381 (Luber et al.), 8313768 (Kriksunov et al.), 9511028 (Chen et al.), 10493026 (Koll et al.), and WO2018 / 096363 (UCL Business PLC), the entire contents of which are incorporated herein by reference. A thermoforming powder material comprising a thermoforming compound or material can be deposited in a depression and flattened into a single layer having a uniform thickness. Typically, the flattening step comprises moving the powder material deposited in the depression to form a layer of powder material having a flat or uniform upper surface. The height variation of the upper surface is less than 20% of the diameter of the depression, more preferably less than 10% or 5%, and even more preferably less than 2%. After the powder material layer is formed, the powder material layer is exposed to a phase change system to form a solidified porous or non-porous solid article, such as a dosage form. The phase change system can include thermal heating by conduction, convection, or radiation, using an electromagnetic (EM) spectroscopy system as described below. The thermoforming material in the powder material softens and partially melts to bond with other powder material particles. After cooling, the bonded thermoforming material solidifies and binds the powder material particles together to form a bonded powder material.

[0175] In other embodiments, the thermoformed powder can be deposited, flattened, and thermoformed two or more times as described above to form a multilayer article within the recess. Each layer in the thermoformed powder can have the same composition and ingredients, optionally including active materials, or have different compositions, optionally including active materials.

[0176] <Allocation of structural materials>

[0177] In various embodiments, the structural material is supplied and stored to the processing system, in particular the omnidirectional magnetic motion system and / or the containment system, by conventional means, including pumps, conveyors, tanks and boxes, according to its form (e.g., liquid or solid). Depending on the chemical type of the structural material and its state, the structural material can be dispensed or deposited onto the substrate of the manufacturing module in a well-known manner.

[0178] For distributing or depositing structural materials, or for distributing or depositing the usual type of materials for phase change systems. Powder structural materials can be stored in a tank or other container in a block, and can be delivered to a processing system by air delivery or gravity supply through fixed or flexible pipes, conduits or hoses. Equipment for distributing or depositing powder and other powdery materials can include iris valves, rotary valves, butterfly valves, auger conveyors, screw conveyors, belt conveyors, tubular drag conveyors (e.g., U.S. Patent Application Publication No. 2022-0184891 of Hewlett-Packard Development Company, the entire contents of which are incorporated herein by reference) and powder dosing devices. In various embodiments, the equipment for supplying and distributing powder materials can include modular containers for powder materials, including instantaneous and continuous mixing systems for feedback control, so that the supply of powder materials to processing equipment can be quickly and easily changed.

[0179] Structural materials in liquid form as described above can be stored in bulk in tanks or other containers and can be delivered to a processing system by gravity feed, pumps, hydraulic and pneumatic pressure, and through fixed or flexible pipes, tubes or hoses.

[0180] In various embodiments, the structure material dispensing module can include a probe for continuous and / or intermittent sampling of the structure material to measure, record and report the composition uniformity of the structure material. The control system can include a process incorporating intelligent data processing algorithms, including the use of artificial intelligence (AI) where appropriate, to analyze and evaluate whether the phase change dispensing process is in control and implement corrective actions or other controls.

[0181] <Powder doser>

[0182] In some embodiments, the structural material dispensing device is a powder doser for delivering a predetermined mass or volume or "dose" of a flowable powder material to one or more deposition sites of a substrate. The substrate can be a blister card, and the one or more deposition sites can be one or more depressions formed in the blister card. The powder doser delivers a predetermined mass (or volume) of flowable powder material to one or more or all of the depressions in the blister card. In various embodiments, the predetermined mass of the powder material deposited in any one depression can be about 1 mg or less, or at least about 1 mg, preferably about 15 mg to about 375 mg, and at most about 5 gm. Non-limiting examples of dosators are described in PCT Publications WO 2020 / 081561 and WO2021 / 21189, the entire contents of which are incorporated herein by reference.

[0183] In various embodiments, the doser deposits or is configured to deposit a consistent volume of powdered material.Consistently depositing a uniform volume of powdered material preferably provides the powdered material at a consistent bulk density to achieve uniform, repeatable mass dosage.

[0184] In various embodiments, multiple doses of powder material are simultaneously and independently deposited into a corresponding plurality of deposition surfaces, particularly a plurality of recesses. Ideally, the corresponding volume amounts of powder material deposited in all of the plurality of recesses will be the same, or at least have a statistically narrow variance; for example, a variance of about 3% or less, including a variance of about 2% or less, or a variance of 1% or less. Assuming that the mass density of the powder filling each recess is constant and the same, the mass dose of powder deposited into each recess will be the same, or within a statistically narrow variance.

[0185] In various embodiments, the doser system can include an integrated near infrared (NIR) spectroscopy sensor. NIR spectroscopy uses the transmission and absorption of light to measure various constituents in a sample material, such as moisture, starch, protein, fat, and oil. NIR can be used to detect these specific elements, understand the concentration of the elements, and / or detect changes in the overall composition. Since near infrared penetrates the bulk material more deeply than mid-infrared, it can provide better and more reliable measurements on the production line. In one embodiment, the NIR sensor can emit electromagnetic wavelengths in the range of 780-2500 nanometers, but is not limited thereto. The NIR irradiates the surface of the powder material passing through the channel in the doser assembly.

[0186] NIR sensors can be used, but are not limited to, to detect and monitor the uniformity of one or more compounds, including one or more active drugs and pharmaceutical ingredients, mixed with other excipient powders into a batch, to detect changes in the amount of the compound in the powder material, and correspondingly to detect changes in the volume of the compound dosed onto a substrate surface or depression. Detection and monitoring allow the processing system to be programmed to terminate or modify the process if the concentration of a compound (e.g., one or more active drugs and pharmaceutical ingredients) is detected to be too high or too low and outside a target acceptable range.

[0187] In other embodiments, the doser deposits, or is configured to deposit, a constant or statistically narrowly varying mass of powder material. Various methods can be used to control the mass of the powder material. In various embodiments, a weighing scale (load cell) can be disposed below a bulk powder hopper or an intermediate bulk powder feeder to measure or monitor the weight of the powder dispensed onto the substrate. In some embodiments, a weighing scale can be disposed within a carrier or below the substrate to detect the absolute or differential mass of powder material added to a specific forming surface (depression) or the entire substrate (blister card). In some embodiments, a controlled weighing scale is prepared to ensure consistent quality of powder material for deposition into a specific depression.

[0188] In various embodiments, the doser device provides a component assembly that delivers a predetermined dose of powder material onto (or into) one or more or all deposition surfaces of a substrate. When multiple doser devices are operated in parallel, each independent doser device can be assembled with components that deliver a different predetermined dose of powder material onto (or in) one or more or all deposition surfaces of a substrate, and the combination of these one or more doser devices provides greater and nearly unlimited control over the amount of powder material dosed onto (or in) one or more or all deposition surfaces of a substrate.

[0189] The lower surface of the doser deposition portion is positioned to provide a gap of no more than 1 cm, preferably no more than 6 mm, more preferably no more than 3 mm above the substrate.

[0190] Typically, the bulk density of the powder is usually 0.2 to 1.5 gm / cm 3 , more typically 0.4 to 1.0 gm / cm 3 , which can be determined by well-known methods.

[0191] Typically the supply box depositing the powder can include tools to assist or maintain the powder flow and maintain a consistent powder density from the supply box through the discharge port. A non-limiting example of such a tool is a volumetric feeder, such as a metering screw feeder. Another non-limiting example is a vibrating device, which should be isolated from the supply box. In addition, a powder agitator and / or spreader can be utilized, including rollers, blades, or other types of material spreading and mixing devices.

[0192] In various embodiments, when used at a mass level of about 0.05 to 5%, a powder flow aid can be used to improve the handling properties of the powder material. Examples of powder flow aids include fumed silica, stearates, tricalcium phosphate, calcium silicate, aluminum oxide, magnesium oxide, and zinc oxide. For example, fumed silica is provided by Degussa AG under the trademark AEROSILR).

[0193] Fig. 8A 8B shows a non-limiting example of a volumetric powder dosing device or powder doser 40, which is configured to deposit an equal amount of powder material into each of the depressions of a blister disk with minimal deviation. The build powder material from a supply container (not shown) is fed into a metering screw feeder 41 to connect to a corresponding connection port 42b of a feed base 42a. The feed base 42a is fixed to a frame 43 having a cylindrical cavity. A circular distribution plate 44 is rotatably positioned in the cylindrical cavity and has a plurality of openings extending to its periphery to distribute powder to the dose filling cavity below. A material plate 45a having a plurality of conical material ports 45b is positioned directly below the distribution plate 44 for accommodating a certain volume of material. The number of conical material ports 45b is selected and configured in an array to align with the manufacturing surface of the substrate, for example, the depression of a blister card. An electric drive 46 rotates the distribution plate in the cavity of the frame. Mounted below the frame 43 is an upper dose filling frame 47a and a lower dose discharge frame 49a. The upper dose filling frame 47a has three dose filling plates 47b arranged side by side, each of which has a row of precisely machined and formed dose filling cavities 47c. The upper dose filling frame 47a is driven by a driver 48a between a filling position and a dispensing position, in which the dose filling cavities 47c are aligned with the material ports 45b of the material plate 45a to fill the dose filling cavities 47c with powder.

[0194] The lower dose discharge frame 49a has three dose dispensing plates 49b arranged in parallel and aligned with the three dose filling plates 47b of the upper dose filling frame 47a. Each dose dispensing plate 49b has a row of dispensing ports 49c. The lower dose discharge frame 49a is driven by a driver 48b between a filling position and a dispensing position, in which the dose dispensing plates 49b block the bottom opening of the dose filling cavity 47c of the upper dose filling frame 47a, and in the dispensing position, the dispensing ports 49c are axially aligned with the dose filling cavity 47c to dispense powder from the dose filling cavity 47c into the recess of the blister card.

[0195] <Leveling>

[0196] Leveling is a processing unit operation that moves a large amount or a certain amount of structural material particles deposited on or in a substrate recess to a more flat powder layer, preferably to form a powder layer with a flat surface. In some embodiments, the powder layer provides a structural material layer with an upper plane. The leveled structural material layer is then subjected to a phase change process to form a solidified, single structural material layer.

[0197] In some embodiments, the structural material can be a powder, granular or pulverized material, with subsequent phase change processing forming a single coherent powder matrix having an upper planar surface.

[0198] In various embodiments, leveling can be achieved by using motion of the manufacturing module, which can be achieved by vibration or pitching of the shuttle around an axis passing through the shuttle, or by lateral acceleration of the shuttle on and along the transport surface. Under the control of the motion controller of the omnidirectional magnetic motion device, the motion stator can be actuated to cause the manufacturing module to oscillate and / or vibrate the shuttle at a certain frequency and amplitude through the magnetic force on the shuttle, so as to form the deposited powder into a powder layer having a substantially uniform thickness and a substantially uniform horizontal upper surface within the recess. In some embodiments, the cycle of oscillation or vibration can cause the body of the shuttle to rotate around a vertical axis passing through the shuttle, and / or to perform angular motion or pitch motion through a horizontal axis or line passing through the shuttle. The cycle time required to achieve powder dose leveling is less than 10 seconds; for example, typically less than 5 seconds, or 2 seconds or less, more typically 1 second or less.

[0199] In various embodiments, leveling of the powder dose on or in the substrate cavity can be accomplished at a separate processing station that includes a device for vibrating the substrate, such as a blister card having a plurality of depressions, to achieve leveling of the dose amount of loose powder dispensed therein. In some embodiments, the powder leveling device vibrates the blister card at a certain amplitude and frequency to convert a pile of powder dispensed into the blister card cavity into a powder layer having a horizontal or more horizontal upper surface, more preferably a flat surface. A non-limiting example of a vibrating leveling device uses a voice coil actuator to generate vibrations that are transmitted to the blister card to achieve movement of the powder material provided with the depressions.

[0200] Fig. 9A and 9B A vibration leveling device 52 is shown for leveling powder material on a substrate (e.g., a depression of a blister card) by transmitting vibrations to the blister card to effect movement of the powder material disposed in the depression. The vibration leveling device 52 includes a base 53 and an activator manifold 54 that supports a positioning voice coil actuator (VCA) 55. Each actuator 55 includes an elongated rigid probe 56 that extends axially below the actuator and reciprocates axially when actuated by the VCA. The rigid probe 56 has a top made of an elastic material that transmits vibrations of the probe 56 to the substrate. The base 53 is configured to be sealably attached to and conveniently removable from a top plate panel 33 of a containment housing. The vibration leveling device 52 includes a lifting mechanism 57 rigidly attached to the activator manifold 54 that vertically lowers and raises the activator manifold 54. In Fig. 9A In the raised position shown, the distal end of the probe 56 is raised into the collar 58 of the base 53, which protects the probe 56 and prevents the probe from extending into the containment area when installing and removing the vibration leveler 52 from the containment housing. Fig. 9B In the lowered position shown, the activator manifold 54 is lowered, causing the distal end of the probe 56 to be lowered to extend below the top plate 33 and into the load-bearing area. In the lowered position, the distal end of the probe is aligned with the manufacturing module 70 (in the lower portion) that has been positioned and oriented below the vibration leveler 52. Figure 4), more specifically, with a substrate 80 (one or more blister cards) or alternatively with a mask 90 placed on the substrate or with any other part of the nest that directly contacts the substrate. In various embodiments, two or more VCAs are positioned in the activator manifold 54 so that the distal ends of the probes 56 contact the upper surface of the substrate at symmetrical positions on the top surface of the substrate or mask. After the probes contact the substrate (or mask), the VCAs are activated to transmit vibrations into the bulk substrate. In some embodiments, the VCAs transmit vibrations at a frequency range of about 1-100 Hz and an amplitude of 1-10 volts, for example, 40 Hz with an amplitude of 1 volt. The vibration of the substrate, such as the vibration of the blister card or the mask contacting the upper surface of the substrate, vibrates the powder material within the recess into a powder layer with uniform thickness and a flat upper surface within the recess. This operation takes less than one second, typically 0.1 seconds or less.

[0201] In various embodiments, one or more springs are selected to provide a spring constant k that supports the weight of the nest 74, substrate 80 (e.g., blister card 82) and any structural materials (e.g., build powder and adhesive liquid), and mask 90, with a natural vibration frequency that matches or estimates the vibration frequency delivered by the VCA.

[0202] In various embodiments, then, the manufacturing module has been positioned at the leveling station, and the motion controller will cause the shuttle element of the manufacturing module to drop down and land on the processing surface 16, and remain on the processing surface 16 when the vibrating leveling device lowers the probe and during the leveling process. After the execution of the VCA and the leveling process are completed, the vibrating leveling device raises the probe and returns to the raised position, and the manufacturing module is raised from the processing surface 16 and moved out of the leveling station under the control of the motion controller.

[0203] In various embodiments, a leveling device can be used simultaneously with depositing a dose of powdered structural material.

[0204] Non-limiting examples of devices for leveling the volume of powdered material within a recess of a blister tray can be found in PCT publications WO 2020 / 081561 and WO 2021 / 211898, the entire contents of which are incorporated herein by reference.

[0205] <Liquid Dispenser>

[0206] Devices for dispensing or dispersing liquids (including aqueous and non-aqueous liquids, organic and inorganic liquids, solutions, suspensions, creams, emulsions, pastes, gels and monomeric compounds) can include pumps (including piston pumps, gear pumps, positive displacement pumps, peristaltic pumps and screw pumps), gravity feed dispensing valves, nozzles (including single fluid, two-fluid, ultrasonic atomizers and printing nozzles). The type of device for liquids can be selected according to the type, dosage and properties of the liquid (including temperature, density, viscosity, vapor pressure and surface tension). The device can deliver structured materials to a substrate to form a single product (e.g., a single dosage form) or to form multiple products sequentially or simultaneously.

[0207] The liquid structural material can be stored as a whole in a tank or other container and can be delivered to the processing system through a fixed or flexible pipe, conduit or hose by a pump or gravity feed. In some embodiments, the structural liquid or other processing liquid can be stored in a modular container. The modular container has an interior space for accommodating a certain volume of liquid, and includes a filling port for loading a certain volume of liquid into the interior space and a dispensing port for discharging the liquid from the interior space. The discharge port typically includes a quick connection feature, such as a bayonet connector and a sealing element, which cooperates with a corresponding receiving port of the liquid dispensing device, so that a used or empty liquid container can be quickly replaced, or replaced with a different liquid material.

[0208] The liquid can contain an active agent or compound. In some embodiments, the liquid is an aqueous liquid containing an API. In some embodiments, the active-containing liquid is dispensed onto a powder structural material during the phase change of the powder into a solid form. In some embodiments, the active-containing liquid is dispensed onto an intermediate or unfinished article (e.g., a sheet) that is further processed, for example, by drying off the volatile components of the liquid, leaving the API to form a finished article or product.

[0209] <Liquid spraying and printing>

[0210] Aqueous liquids and solvents can be dispersed in the form of multiple streams or droplets by a liquid printing device, which can be distributed to a substrate (usually through a nozzle) or applied to a mass or layer of a powder material. Non-limiting examples of nozzles that form liquid streams or droplets can include single-stream or dual-stream nozzles, ultrasonic atomizers, thermal inkjet nozzles, and piezoelectric inkjet nozzles. Large droplets can be distributed in milliliters and microliters through nozzles. The print head or print head nozzle can distribute droplet-sized liquids in the order of microliter, nanoliter, or picoliter droplets. Technicians can select a print head or print head nozzle based on the dosage of the liquid, processing parameters, and the characteristics of the liquid, wherein the processing parameters include process parameters of temperature and pressure, and the liquid characteristics include density, viscosity, vapor pressure, and surface tension.

[0211] Fig.10 A and 10B show examples of liquid printing devices. Liquid printing device 50 includes a printer housing 551, a pair of print nozzles 552 mounted on the bottom surface 556 of printer housing 551. Each printer nozzle 552 is composed of a series of elongated nozzle ports. The pair of printer nozzles 552 are parallel, axially staggered and laterally offset, wherein the last nozzle port at one end of one nozzle 552 overlaps axially with at least one nozzle interface in the other end of another nozzle 552. Printing device 50 also includes a support frame 553 and a lifting mechanism 555, which is used to vertically lift housing 551 between a lowered position and an elevated position, in which the bottom surface 556 and print nozzle 552 extend below the top panel 33 of the housing 30 and enter the loading area, and in the elevated position, the housing 551 and the bottom surface 556 are raised above the loading housing 30 to access and remove the printing housing 551 from the loading housing.

[0212] Other non-limiting examples of printheads or printhead nozzles are described in U.S. Patents 4,825,227, 4,875,619, 4,883,219, 4,937,598, 5,659,346, 5,757,391, 5,781,212, 9,217,700, 9,381,154, 1,056,2059, 1,0850,236, 1,0889,133, and 1,093,636 and U.S. Patent Application Publication 2012 / 0092416, the entire contents of which are incorporated herein by reference.

[0213] In some embodiments, a pattern of the dispensed liquid can be formed on a substrate or a block of powder material by dispensing liquid from selected jets of a fixed nozzle to emit one or more dispensed liquid curtains aligned in the plane of the print nozzle and advancing the substrate or block of powder material under one or more dispensed liquid curtains. The speed at which the substrate is advanced and the selection of jets for droplet emission are controlled to emit droplets only from jets directly above a lateral strip of the substrate or a block of powder material to be wetted. This process is well known in the art.

[0214] In some embodiments, the article can be a pharmaceutical dosage form, wherein the structural material comprises a powder material, and the phase change system can comprise a binding liquid printing system and a wet powder material drying system.

[0215] When printing liquid onto a deposition surface of a substrate or onto a layer of powder or other structural material, the resolution and accuracy of the printed liquid deposition can be improved by limiting the flight path of the liquid from the nozzle to the upper surface of the powder layer, the diameter or size of the droplet, and the velocity of the expressed droplet. Preferably, the substrate is controlled to a minimum gap of less than 2.5 cm (1 inch) or less, more generally less than 1 cm, below the printing nozzle.

[0216] Non-limiting examples of binding liquids that can be dispensed onto a layer of powder or other structural material are well known and described in PCT publications WO 2020 / 081561 (Aprecia Pharmaceuticals LLC) and WO 2021 / 211898 (Apreca Pharmaceutical LLC), the entire contents of which are incorporated herein by reference.

[0217] <Assisted active agent>

[0218] In any of the above embodiments, the system can also include an apparatus, device or subsystem for storing, delivering and / or depositing auxiliary active agents, such as API or drugs, on a structural material or a phase change structural material. The auxiliary active agent can be a granular material, other solid material, or a liquid material, or in liquid form with one or more solvents. In various embodiments, a certain mass or volume of auxiliary active agent can be deposited on a structural material (such as an ingestible powder material) or a phase change structural material. In U.S. Pat. No. 8,252,234 and U.S. Pat. No. 8,101,244 (both SmithKlineBeecham Corporation), an example of an apparatus, device or subsystem for storing, delivering and / or depositing auxiliary active agents, such as API or drugs on a structural material or a phase change structural material is described, and the entire contents of which are incorporated herein by reference.

[0219] <Surface modification>

[0220] In various embodiments, the processing unit operation can provide surface modification of the product or intermediate product. In various embodiments, the surface finishing device can include a surface finishing body having a bottom finishing surface. The finishing surface is configured to extend the bottom finishing surface onto the wet powder layer within the powder layer or the recess to change or modify the surface roughness of one of the powder layer or the wet powder layer. In some embodiments, the finishing surface provides a consistent profile and texture for the top surface of the intermediate product and / or the finished product. In some embodiments, the profile of the top surface can be rounded or slightly domed. The finishing surface can also provide a means for removing particles of powder material attached to the upper portion of the side wall of the recess. In some embodiments, the powder of the powder layer can be a dry, deposited or flat powder layer, while in other embodiments, the powder of the powder layer can be a wet or partially wet powder layer.

[0221] In some embodiments, the finishing surface contacts the powder layer at a portion higher than the finishing surface profile to reduce the protruding portion of the powder layer. The finishing surface is lowered in height until the forming surface of the finishing surface contacts the entire upper surface of the powder layer so that the powder layer is formed into an upper surface that matches the surface profile of the finishing surface. In various embodiments, the finishing surface is lowered outside the upper surface of the powder layer to compress or compact the powder material in the powder layer. In various embodiments, the material of the surface finishing body forming the finishing surface is a solid material made of metal or alloy, or a solid thermoplastic material. In a preferred embodiment, the material of the surface finishing body resists or prevents the adhesion of wet or dry particles of wet or dry powder materials. In various embodiments, the surface finishing body and the finishing surface can extend to the depth of the depression. Non-limiting examples of solid thermoplastic materials include, but are not limited to, polyethylene, particularly ultra-high molecular weight polyethylene (UHMWPE, or just UHMW), nylon, and polypropylene.

[0222] In various embodiments, the surface finishing body can also rotate around the axis of the surface finishing body and the finishing surface, and rotate or oscillate in an arc, or rotate at a certain rate to improve the smoothness of the powder layer surface. In some embodiments, the surface finishing body can rotate in one rotation direction or two rotation directions.

[0223] Fig.11A and 11B A surface finishing device 60 is shown which can be used to perform top surface finishing on an article formed on a substrate, and in particular, to finish a tablet formed within a recess 84 of a blister card 82 of a substrate 80. The surface finishing device 60 includes a base 61 and a pressing manifold 62, the pressing manifold including a plurality of presses having pressing rods 67 and pressing heads 68. The upper ends of the pressing rods 67 are vertically actuated by corresponding plurality of solenoids 65 located on the pressing manifold 62 on the top surface of the base 61. The pressing rods 67 extend through openings 66 on the underside of the manifold 62. The base is configured to be sealably attached to and easily detachable from the top panel 33 of the containment housing, and a plurality of pressing rods 67 and pressing heads 68 extend through openings 34d (see FIG. 1 ) in the top panel 33 of the containment housing 30. Figure 2 ). A lifting bracket 63 rigidly attached to the press manifold 62 can be moved vertically by a crane or hoist 64 to lift the press manifold 62, solenoids and press heads 68 upward and through the opening 34d in the top plate for removal, cleaning or maintenance. The plurality of press heads each have a head diameter and a lower surface for at least partially extending into the upper portion of the recess and contacting the structural material, powder layer or wetted powder layer. Fig.11AAs shown, the plurality of pressing heads 68 are arranged to provide a first set of six heads 68a aligned with corresponding six grooves of the first blister card 82a and a second set of six heads 68b aligned with corresponding six grooves of the second blister card 68b.

[0224] <Fuse Deposition Formation>

[0225] Fused Filament Fabrication (FFT) is a three-dimensional printing (3DP) process that uses a continuous filament of thermoplastic. The filament is fed from a large spool through a heated extrusion head, which deposits the molten thermoplastic onto a workpiece located on a table. When cooled, the thermoplastic hardens (phase changes) into the final shape. The extrusion head or the table, or both, moves under computer control to define the printed shape layer by layer. In some embodiments, the extrusion head moves in two lateral (x, y) dimensions, depositing a horizontal layer of thermoplastic at a time; the table or extrusion head is then moved vertically a short distance to start a new layer. The speed of the extrusion head can also be controlled to stop and start deposition and form a discontinuous plane without stringing or dripping between parts. A wide variety of materials can be formed into filaments and extruded, including thermoplastics such as polylactic acid (PLA), acrylonitrile butadiene styrene (ABS), polyethylene terephthalate glycol (PETG), polyethylene terephthalate (PET), high impact polystyrene (HIPS), thermoplastic polyurethane (TPU), and aliphatic polyamides (nylons).

[0226] The FFF device can be positioned above the transport surface of the omnidirectional magnetic motion device to extend the heated extrusion head. In some embodiments, the FFF device is configured to be able to be vertically (in + The heated extrusion head is raised and lowered in the x, y direction (in the x, y direction) while the substrate on which the molten thermoplastic material is deposited is moved in micro increments in the x, y horizontal plane under the control of the extrusion / printing operation (processing unit operation) controller and the motion controller. The article is made by extruding a first layer (or subsequent layers) of extruded thermoplastic plastic, then raising the heated extrusion heat by an incremental height, and then extruding the next layer of extruded thermoplastic plastic on top of the first layer (or previous layer). In some embodiments, the heated extrusion head is vertically stationary and moves in the x, y horizontal plane, while the substrate on which the molten thermoplastic material is deposited is able to move vertically (in + in the z direction).

[0227] In various embodiments, an article containing an active agent, such as a pharmaceutical dosage form or a medical device containing an active agent, can be manufactured in a processing system having a processing unit operation including fused filament deposition formation. One or more of the portions of the incremental volume of the extruded thermoplastic material contains an active agent compatible with the melting temperature at which the thermoplastic is melted and extruded from a heated extrusion head to form a pharmaceutical dosage form containing one or more, including two or more, active agents. Examples of dosage forms made using FFF processing and having an active agent are described in International Patent Publications WO 2016 / 038356 (University of Central Lancashire), WO 2018 / 206497 (Pharmaprint) and WO 2020 / 240028, WO 2020 / 244029, WO 2020 / 240030, WO 2021 / 115887 and WO 2021198308 (Dihesys Digital Health Systems GMBH), the entire contents of which are incorporated herein by reference. FFF printer apparatus useful for this method are described in US Pat. Nos. 6,070,107 and 1,0259,164, the entire disclosures of which are incorporated herein by reference.

[0228] In some embodiments, an intermediate or unfinished FFF formed article can be formed and a separate and predetermined mass or volume of an active-containing powder or active-containing liquid can be dispensed onto or into a cavity of the unfinished FFF formed article to provide a dose of the active substance to the resulting finished product.

[0229] <Electromagnetic Radiation>

[0230] Multiple bands of the electromagnetic spectrum can be used to perform a variety of processing unit operations, including X-ray, ultraviolet (UV), infrared (IR) and microwave wavelengths. Each of the wavelength spectrum can provide useful processing unit operation functions. These electromagnetic (EM) can be generated by a variety of devices. Microwaves are generated by electron tubes called magnetrons and can heat moisture in articles or intermediate forms for phase change and evaporation processes. Ultraviolet light (10 nm to 400 nm wavelength) is generated by lamps, light emitting diodes (LEDs) and lasers and is used for polymerization or curing of monomer resins for inks, coatings and adhesives, as well as disinfection and sterilization of surfaces and transparent liquids (water). Infrared light covers a wide wavelength range of about 0.78 to 1000 microns and is generated by lamps, light emitting diodes (LEDs) and lasers and can be used to heat compounds for evaporation and drying processes. In some embodiments, irradiation can be used to heat the temperature of energy absorbing compounds within the composition and increase its temperature to provide in-situ softening or melting of the compound, thereby serving as a binding material for the composition (e.g., a heat-formable powder composition). Examples of methods and systems can be found in U.S. Patents 9,511,028 (J&J), 11,229,577 (Merck Patent GmbH), U.S. Patent Application Publications US 2007 / 0238056 (DeGussa AG), US 2009 / 0060983 (J&J), US 2015 / 033291 (TNO), and US 2019 / 0374471 (UCL Business PLC), and International Patent Publications WO 2015 / 145353 (Orthopaedic Innovation Centre, Inc), WO 2017 / 190994 (Merck Patent GmbH), and WO 2018 / 096363 (UCL Business PLC), the disclosures of which are incorporated herein by reference in their entirety.

[0231] In some embodiments, tablets and other articles can be formed by spreading a powder material into one or a series of incremental layers, wherein the powder material includes a fusible material and an active ingredient, and spraying or printing a liquid containing an energy absorbing material onto the powder in a predetermined pattern (such as the pattern of a tablet). The fusible material is a material that melts and melts when heated and then solidifies when cooled, and can be a sugar alcohol, including one or a mixture of mannitol, polymers, polyvinyl pyrrolidone (PVP), etc. The energy absorbing material can be any material that absorbs infrared, near infrared, visible light, ultraviolet or microwave radiation and converts the radiation into heat, for example, water itself, carbon black, pigments, inorganic salts, etc. The irradiation heats the energy absorbing material, at least partially melting the fusible material to melt the powder layer. Once cooled, a complete bonded powder layer is formed. Alternatively, the molten material can be contained in the liquid printed onto the powder layer. Examples of such processes are described in U.S. Patent 11,229,577 and U.S. Patent Application Publications 2007 / 0238056, 2019 / 0374471, 2021 / 0196572, 2021 / 0205176, and 2021 / 0213678, the entire contents of which are incorporated herein by reference.

[0232] <Material Phase Change>

[0233] In various embodiments, the material can be transformed from one phase (liquid, solid or gas) to another phase by subjecting the structural material or intermediate product to a temperature change, for example, by heating or cooling the material, thereby causing evaporation, sublimation, solidification, freezing, melting or condensation. Cooling (energy removal) of a gaseous compound or composition can cause the compound or compounds in the composition to condense into a liquid form (e.g., steam or water vapor condenses into liquid water); or solidify (freeze) the compounds in a liquid compound or composition into a solid form (e.g., water turns into ice, or a molten thermoplastic polymer turns into a solid). Heating (energy input) of a liquid compound or composition can cause the compound or compounds in the composition to evaporate into a gaseous state (e.g., water or solvent evaporates into vapor); or melt the compounds in a solid compound or composition into a liquid form (e.g., ice turns into water, or solid thermoplastic polymer turns into molten liquid, or laser sintered metal particles turn into molten metal and then solidify back into solid metal); or sublimate water or moisture in the composition into vapor (e.g., freeze drying under sufficient vacuum conditions, or dry ice).

[0234] Energy removal or energy input can be affected by any one or more of conduction, convection or radiation.

[0235] In various embodiments, chemical reactions on structural materials or intermediate products can affect phase changes in materials. For example, monomeric and polymeric liquids, such as epoxies, silicones, and other adhesives, can be polymerized and cured using chemical reactants, such as pH changes, saponification, amination, or using irradiation with certain wavelengths of the electromagnetic spectrum, such as ultraviolet, infrared, and microwaves.

[0236] <Evaporation and drying>

[0237] The drying step of the wet powder layer can be performed after forming each wet layer, or after forming two or more layers, or after all wet layers, or after forming and surface finishing.

[0238] In some embodiments, the drying station can be built into the containment system, and the manufacturing module can be moved to the drying station within the containment system for processing. In other embodiments, the manufacturing module can be transferred out of the containment system, processed at a remote drying station, and returned as needed. A drying station built outside the containment system isolates the wet layer drying and solvent handling systems of the drying station from the containment system of the dosage form forming system.

[0239] The first aspect of the drying station is a device for moving a substrate that contains a wetted powder layer on one or more forming surfaces (e.g., within a recess). In various embodiments, the substrate is separated from the carrier and transferred to the drying station manually or mechanically. In some embodiments, the carrier with the attached substrate is removed from the shuttle manually or mechanically and transferred again manually or mechanically to the drying station. In other embodiments, the entire manufacturing module is transferred manually or mechanically to the drying station.

[0240] The drying station includes a device for evaporating water or other solvent of the printing liquid contained in excess in the wet powder material. The evaporation device can use one or more of infrared, microwave, ultrasonic energy, radiant heat and convection (hot air) heating to increase the vapor pressure of the solvent and evaporate the solvent, wherein the solvent can include water. In some embodiments, during the drying process, the surface temperature of the wet powder material can reach 90°C or higher.

[0241] The drying station also includes a solvent removal system for transporting the solvent vapor from the evaporation device to a solvent condensation and collection system. For printing liquids containing only water as a solvent or small amounts of organic solvents, the solvent vapor from the evaporation device can be exhausted to the atmosphere, for example, into a fume hood.

[0242] After the wetted powder material is dried, the dry powder layer contained on or within the substrate can be returned to the containment system for additional processing of the dosage form. In various embodiments, the substrate is reattached to a carrier and / or shuttle (the same carrier and / or shuttle from which the particular substrate was removed for drying) and transferred back to the transport surface and / or containment housing for additional processing.

[0243] <Sterilization and Disinfection>

[0244] The processing system can include systems and methods for sterilizing and / or disinfecting articles and objects within or introduced into a transport surface or a containment shell, including structural materials, processing materials, substrates, carriers, shuttles, transport modules, manufacturing modules, and inspection, processing, and sampling equipment. Depending on the type of contaminant, the article formed, and other processing performed within the processing system, the disinfection or sterilization can be electromagnetic spectrum emission or a compound or one or more compositions. Non-limiting examples of disinfection or sterilization can include ultraviolet light, such as Class C ultraviolet light, bleach, and peracids, etc.

[0245] <Product Inspection and Marking>

[0246] Embodiments of the processing methods or systems of the present invention can include process analytical technology (PAT), an overview and examples of which are provided in , the entire contents of which are incorporated herein by reference. The processing method or system can include one or more inspection devices, inspection systems and inspection processes for one or more processing unit operations and / or one or more intermediate or final products to improve the control of the processing system and the quality of the intermediate or final products. The inspection system can provide real-time monitoring of the process, equipment during operation, and intermediate and final products, and can include one or more cameras and other digital imaging devices, process parameter sensors, and intermediate and final product parameter sensors. The inspection system can provide real-time feedback of the real-time monitoring system to one or more processing unit operation controllers with and without processing control to improve the control and efficiency of the process and minimize or eliminate offline quality control inspections and facilities. In some embodiments, the inspection system can release one or more final products in real time. Non-limiting examples of inspection devices, inspection systems and inspection processes are described in U.S. Patents 8252234 and 8101244 (both SmithKlineBeecham Corporation), the entire contents of which are incorporated herein by reference.

[0247] In various embodiments, the processing system can include a visual sensor or camera to intermittently or continuously monitor the volume of structural material deposited on the substrate. By multiplying the determined or measured volume of structural material with the known or determined density of the structural material, the mass of structural material deposited into the cavity individually and in total can be determined.

[0248] In some embodiments, the processing system can employ a PAT system including a spectral sensor, a non-limiting example being a near infrared sensor, for intermittent or continuous monitoring of the uniformity of the material prior to depositing the material in one or more separate chambers to determine the accuracy and efficacy of a volume of structured material.

[0249] In some embodiments, the processing system can employ a PAT system including a sensor, a non-limiting example being a microwave resonant sensor, for intermittently or continuously monitoring the density of a material then deposited in one or more separate cavities to determine the mass of a volume of structural material.

[0250] In some embodiments, the processing system can employ a PAT system that includes spectral and visual sensors and cameras for intermittently or continuously monitoring the positioning of the structured material deposited and / or repositioned in one or more individual cavities to determine the accuracy of the dispensing device in dispensing a predetermined volume of the structured material. In some embodiments, the PAT system can be used to monitor, evaluate and control a leveling process as described herein that moves the powdered structured material deposited in a cavity or recess to form a layer of powdered material having a uniform or flat upper surface.

[0251] In one embodiment, a PAT system and / or apparatus can provide a method for detecting the outer surface of a particulate or viscous material or formation, particularly the outer upper surface, and determining its shape, texture, and size in three-dimensional coordinates (hereinafter referred to as "3D coordinates"). In addition, the system and / or apparatus can determine the 3D coordinates of the inner surface within a confined space (e.g., a cavity of a blister card depression) of a known or determined geometry of a substrate or other surface. Based on the 3D coordinates of the upper surface of the particulate or viscous material or the cavity surface of the substrate, the system can determine or calculate the actual volume of the particulate material or other type of material deposited in the cavity by determining the volume difference between the 3D coordinates of the upper surface of the material in the cavity before and after the deposition of the particulate material or other material, which may include liquids, suspensions, semi-solids, or the like.

[0252] In some embodiments, the particulate material is a powder material, and the process of forming the article is a binder jetting process, wherein a binding liquid is dispensed onto a layer of the powder material to form a wetted binding powder material, and then a dose or layer of the powder material is deposited on the upper surface of the wetted binding powder material. The PAT system detects the 3D coordinates of the upper surface of the wetted binding powder material in the cavity, and then detects the 3D coordinates of the upper surface of the powder material deposited on the wetted binding powder. The upper outer surface of the deposited powder material or the wetted binding powder material can be plane and flat, or it can be wavy, with curves and slopes on the upper surface. The volume difference can be determined based on the difference between the respective 3D coordinates of the upper surfaces of the deposited powder material and the wetted binding powder material. The volume of the powder material recently deposited in the cavity can be determined by the volume difference of the total amount of material in the cavity before and after deposition.

[0253] An example of a device for detecting the 3D coordinates of the upper surface of the powder material in the cavity space is a three-dimensional (3D) laser camera. Figure 1 , Fig. 12A and Fig. 12B An example of a 3D laser camera 95a is shown in FIG. The 3D laser camera 95a is mounted on an elevated frame 19 vertically above the containment housing 30 for imaging the containment area and manufacturing modules through the transparent ceiling panel 33. Examples of such 3D laser cameras are manufactured by Cognex Corporation, for example series.

[0254] 3D laser camera includes laser 295 ( Fig. 12A and 12B ), showing a tool for firing a laser plane onto a cavity contour surface or material within a cavity, as the case may be. The laser detector 296 of the 3D laser camera views the contour surface at a perspective angle to the laser plane and captures an image of where the laser plane strikes the contour surface, referred to as a laser bar. The captured image of the laser bar is then correlated to account for the perspective angle of the laser plane relative to a true vertical plane, and the viewing angle of the laser detector relative to the laser plane, thereby generating a corrected elevation profile of the laser bar along the contour surface.

[0255] When scanning an empty recess of a blister card, each corrected height profile generated provides a true reference profile of the empty recess surface taken along the laser plane, and the accumulated series of corrected height profiles provide 3D coordinates of the recess surface, including the bottom and side walls of the recess and the 3D coordinates of the top sheet of the blister card. Similarly, when the recess contains powder and / or wetted bonded powder material and passes under the 3D laser camera, each corrected height profile generated provides a true reference profile of the recess and the powder material surface taken along the laser plane, and the corresponding accumulated series of corrected height profiles provide 3D coordinates of the recess, the contour surface of the powder material in the recess, and the top sheet of the blister card.

[0256] The volume below or above the contour surface of the powder material can be determined by one of a variety of calculation methods. In a general method, the width spacing between each incremental laser bar is multiplied by the area below or above the incremental laser bar curve to obtain the incremental volume, and the sum of the incremental volumes provides the cumulative volume below or above the 3D contour surface of the powder material. By predetermining the total volume of material below the contour surface of the material in the cavity before depositing the powder material, the volume of the deposited powder material can be determined by the difference from the volume below the deposited powder material. Similarly, by predetermining the total volume of the space above the contour surface of the material in the cavity (until the recess opening) before depositing the powder material, the volume of the deposited powder material is determined by the difference from the spacing of the space above the deposited powder material in the cavity until the recess opening.

[0257] Once the volume of the deposited powder material is determined, the mass of the deposited powder material can be determined by multiplying the volume by the density of the powder material. The density of the powder material can be determined by one or more methods, including continuous measurement by microwave resonance or similar methods, such as described in U.S. Pat. No. 5,977,780, the entire contents of which are incorporated herein by reference, or predetermined density values ​​based on empirical data, which can be measured independently or simultaneously.

[0258] In one embodiment, the 3D coordinates of the profile surface of the material can be divided into a regular matrix of unit areas in two horizontal dimensions, and the height of each unit area can be defined by one, more or all height measurements detected within the unit area. The representation of the profile surface of the material as the average height of the horizontal plane is the average height of the total unit area detected on the profile surface of the material.

[0259] In one non-limiting example, the detection apparatus and method can be used during the article formation process to determine the volume of an incremental dose or layer of powder material deposited within one or more cavities of a blister card. Fig.19AAs shown, the usual recess 84 in the blister card 82 has slightly tapered sidewalls 86 and a flat bottom floor 87 to provide a circular cavity in the shape of a truncated cone. The dimensions of the blister cavity, including the reference depth hc of the base floor, the lower cavity radius rc of the floor 87, and the upper cavity radius Rc of the upper opening of the recess 84 in the sheet 85 of the blister card 82, can be determined by the above-described 3D scanning method. When the blister card passes through a fixed laser plane 96 emitted by the laser 295 of the 3D laser camera 95a, each blister card recess 84 is exposed to the laser plane 96, including the upper surface of the sheet 85 of the blister card 82, the sidewalls 86 and the floor 87, and the imaging assembly of the 3D laser camera (e.g., laser detector 296) consisting of the laser detector 296. Figure 1 An imaging camera 95 is shown capturing a sequence of multiple images of the laser stripe exposed on the blister card 82 and each recess 84 . Fig.19A A first laser stripe 97 is shown exposed along a first lateral portion of the blister recess, including a portion 97a along the bottom plate 87, a portion 97b along the inner wall, and a portion 97c along the sheet 85, Fig. 20A A second laser stripe 97' is shown exposed along a second lateral portion of the blister recess, including a portion 97'a along the bottom plate 87a, a portion 97'b along the inner side wall, and a portion 97c' of the sheet 85 along the recess 84. The PAT system then generates a corresponding sequence of corrected height profiles of the laser stripes along the contoured surface. The two corrected height profiles corresponding to the two captured images of the laser stripes 97 and 97' are Fig.19B The first corrected height profile 197 and Fig. 20B A second corrected height profile 197 ′ is shown.

[0260] The PAT system uses the sequence of corrected height profiles to generate 3D coordinates of the surface features and profiles of the cavity of the recess 84, from which the PAT system is able to calculate or determine the initial volume V0 of the empty recess 84, using the base plate 87 as a first reference distance, representing the base height h0, and using the upper surface of the sheet 85 of the blister card 82 as a second reference height, representing the upper height hmax.

[0261] After the powder material is deposited within the circular cavities of the depressions 84 and / or leveled, the partially filled depressions 84 are able to pass through the fixed laser plane 96 again, exposing the upper surface of the sheet 85, a portion of the sidewall 86, and the upper surface of the layer of powder material P disposed within the cavities of the depressions 84 to the laser plane 96. As the same blister card 82 and each partially filled depression 84 progressively pass beneath the laser plane 96, the imaging assembly of the 3D laser camera captures a new sequence of multiple images of the laser bar. Fig.21A A first laser stripe 98 is shown exposed along a first lateral portion of a partially filled blister recess, including a portion 98a along the bottom plate 87, a portion 98b along the inner wall, and a portion 98c along the sheet 85, Fig.22A A second laser stripe 98' is shown exposed along a second lateral portion of the partially filled blister recess, including a portion 98'a along the bottom plate 87a, a portion 98'b along the inner side wall, and a portion 98c' of the sheet 85 along the recess 84. The PAT system then generates a corresponding sequence of corrected height profiles of the laser stripes along the contoured surface of the partially filled recess. The two corrected height profiles corresponding to the two captured images of the laser stripes 98 and 98' are Fig. 21B The first corrected height profile 198 and Fig. 22B Corrected height profile 198' is shown.

[0262] The PAT system uses the sequence of corrected height profiles to generate 3D coordinates of the surface features and profiles of the partially filled recess 84, from which the PAT system is able to calculate or determine the initial volume V0 of the empty recess 84, using the base plate 87 as a first reference distance, representing the base height h0, and using the upper surface of the sheet 85 of the blister card 82 as a second reference height, representing the upper height hmax.

[0263] The PAT system uses the new sequence of corrected height profiles to generate 3D coordinates of the surface features and profile of the partially filled recess, including the exposed portion of the recess and the layer of powder material P disposed within the cavity of the recess 84. The PAT system determines, based on the average of the corrected height profiles of the upper surface of the layer of powder material P or a portion thereof, an average height of the contoured surface of the powder material (average upper surface height, hp), which can be described as a horizontal plane.

[0264] The volume of the powder material P can be calculated based on the volume of the truncated cone (V tc ) Equation calculation:

[0265] ,

[0266] Where: ∆h is the distance difference between the bottom horizontal plane and the top horizontal plane of the frustum, r is the radius of the bottom horizontal plane of the frustum, and R is the radius of the top horizontal plane of the frustum.

[0267] The empty recess of the commercial blister card has a recess bottom h0 and a recess wall top edge h r The height of the concave wall, the outer angle θ between the concave wall and the horizontal plane, the radius r0 of the concave bottom plate and the radius Rr of the top edge of the concave. The size and physical parameters of the concave of the blister can be measured using the current scanning system, or predetermined according to the manufacturing process of the blister card itself. Knowing the outer angle θ and either the radius Rr of the outer angle θ or the radius r0, or Both the radius r0 and Rr, the total depth of the detected empty recess can determine the empty volume from the recess floor to the top edge.

[0268] After depositing a first dose of powder material on the floor of the hollow recess, and optionally but preferably after leveling the powder material into a first incremental powder layer, the average height of the contour surface of the dose or incremental powder layer is detected as described above and designated as the average upper surface height hp of the powder. p1 It can also be estimated. Knowing the external angle θ and the radius r p1 or any one of the radii Rr, or if the radius r is known p1 and Rr, the detected average upper surface height of the first incremental powder layer can determine the volume of the first incremental powder. In one method, the average upper surface height of the first incremental powder layer is the bottom horizontal plane used to calculate the empty volume above the first incremental layer, and the volume of the first incremental powder layer is the difference from the empty volume of the recess. In another method, the average upper surface height of the first incremental powder layer is the top horizontal plane used to calculate the volume of the first incremental powder above the floor of the recess.

[0269] After printing the binder liquid on the first incremental powder layer, the average upper surface height of the first wetted powder layer can optionally be detected and determined.

[0270] After depositing a second dose of powder material on the first wet powder layer, and optionally but preferably after leveling the powder material into a second incremental powder layer, the average height of the profile surface of the second dose or incremental powder layer is detected as described above and designated as the average upper surface height hp of the second powder layer. The radius of the second powder layer r p2 It can also be estimated. Knowing the external angle θ and the radius r p2 or any one of the radii Rr, or the radius r p2 The detected average upper surface height of the second incremental powder layer and Rr enable the volume of the second incremental powder layer to be determined by any of the above methods. The procedure and determination of the volume of successive incremental powder layers are performed in the same manner.

[0271] Height measurements and other dimensions of detected blister depressions, such as the depression's upper edge radius, floor radius, and wall angles, can be automatically and instantly sent to a controller operating one or more software systems; for example, KAX Group software ProaXesS, which is used to calculate the average upper surface height of a powder layer using the generated 3D coordinates of the surface features, and the volume of incremental powder layers below or above the calculated average upper surface height.

[0272] In various embodiments, the controller uses the entire scanned surface of the deposited or leveled powder to determine the average upper surface height and volume of the powder layer. In some embodiments, the controller uses an area no less than 20%, more typically no less than 50%, and preferably no less than 75% of the scanned surface of the deposited or leveled powder. In some embodiments, the controller selects a single or two or more target areas that are no less than 20%, more typically no less than 50%, and preferably no less than 75% of the scanned surface of the deposited or leveled powder. In some embodiments, the selected area of ​​the scanned surface of the deposited or leveled powder used to calculate the average upper surface height is approximately 25 square millimeters (mm) selected from predetermined locations on the scanned surface of the deposited or leveled powder. 2 ) or larger. Depending on the total area (size) of the blister depression, the area of ​​the selected area can be from 25 mm 2 To about 100 mm 2 , the selected area accounts for not less than 20%, more usually not less than 50%, preferably not less than 75% of the deposited or leveled powder scanning surface.

[0273] <Material placement>

[0274] Embodiments of the process utilize one or more measurement devices, such as a short wave infrared camera, to monitor the quality and accuracy of printing fluid deposition.

[0275] The PAT system can include a subsystem for monitoring and evaluating the effectiveness of the liquid dispensing process. The subsystem can include a non-contact spectral imaging camera configured to use one or more bandpass filters in series or in parallel. In some embodiments, the device accurately detects and records the position data of a single dispensed or printed droplet and / or a deposition pattern formed by multiple droplets deposited on a substrate or structural material. The PAT system can then compare the position data with the print image and / or concentration specifications used by the processing system in real time to control the droplet dispensing rate and pattern, as well as the amount of one or more API compounds deposited in one or more separate cavities during product formation. The subsystem provides a device that continuously measures, records and reports the quality and consistency of the basic printing process throughout the process. The camera system can be combined with intelligent data processing algorithms, including artificial intelligence when appropriate, to evaluate and determine whether a product has passed the inspection or whether it needs to be reprocessed or isolated in the process.

[0276] In various embodiments, the above-mentioned device for continuously measuring, recording and reporting the quality and consistency of the basic printing process can be composed of an integrated short-wave infrared (SWIR) imaging sensor. The SWIR sensor can operate in the range of 550-2500 nanometers (nm) (but not limited to this), typically in the range of 1050-2500 nm, and more typically in the range of 1400-1650 nm, that is, the light wave region above the visible light and NIR range. The surface of the processed material can be illuminated with light in the SWIR range of known wavelength and intensity, which can be emitted from a separate SWIR light source or the SWIR sensor device itself. Depending on the composition of the material on or near the surface (SWIR wavelengths can penetrate the depth of many materials), some of the emitted SWIR light waves are absorbed by the compounds of the composition, and in combination with a bandpass filter, an image can be constructed based on the SWIR sound waves reflected by the target object and absorbed by the SWIR sensor. The image can be interpreted as identifying the location of the material or composition, as well as one or more components of the material. In one non-limiting example, during the process of dispensing an aqueous adhesive liquid as a plurality of droplets onto the surface of a powder material disposed within a blister cavity, a SWIR imaging sensor can monitor the effectiveness of the liquid dispensing process to dispense a known volume of adhesive liquid onto a predetermined target area. The control system can interpret the actual dispensing pattern and compare it to the predetermined target area and instruct the processing system to take subsequent actions.

[0277] In various embodiments, the SWIR imaging sensor can determine that a liquid dispensing process has failed to dispense a droplet of liquid from one of the dispensing nozzles (also referred to as an ejector), for example, due to a plugged ejector, which can result in an unprinted portion of the intended print pattern of liquid that the liquid dispensing system was programmed to employ, thereby leaving an unprinted area on the structure material. In a binder jetting process, a series of wetted bonding powder layers may inadvertently present overlapping lines of unwetted or weakly wetted powder. However, due to the error detected in the actual dispensing pattern, the processing system can be programmed to take one or more additional processing steps or reprocessing steps to avoid the dispensing error from having adverse effects in the processed article.

[0278] In one example, when a dispensing error is detected, the control system can generate new commands to print a correction pattern of liquid only in the unprinted areas using one or more properly functioning print nozzles, thereby dispensing liquid to the previously missing areas and correcting the print area to match the originally commanded print pattern.

[0279] In another example, the processing system can be programmed to instruct the conveyor system to pass the manufacturing module, substrate and structural material (powder material) thereon along a changed, laterally offset path under the printing nozzle array, and use a different printing nozzle group to print a predetermined target area on a subsequent powder material layer. During this process, if the jet is blocked and the binding liquid cannot be dispensed as instructed, the PAT system will identify a linear pattern of missing liquid in the wet powder surface, but when printing the next layer of powder material, it will take a changed laterally offset path and move the missing print area to a different position in the wet binding powder layer, which will cause the missing liquid lines of a series of gradually wetted binding powder layers to be laterally staggered.

[0280] In addition, once an unprinted structural material line is detected, the printing program can be commanded to dispense additional adhesive liquid from a nozzle or two nozzles adjacent to the faulty nozzle, placing the additional liquid near the unprinted powder material line, which can migrate laterally into the powder material and fill the powder material with enough liquid to fully bind the powder material together to avoid the adverse effects of the dispensing error. Alternatively, the processing system can command the liquid dispensing system to deposit a larger volume of liquid along the line or area with the missing liquid amount detected by the SWIR image sensor in a subsequent liquid printing pattern, thereby compensating for the missing adhesive liquid of the previous layer.

[0281] In another example, when a line of unprinted structural material is detected, the processing system can be programmed to command the conveyor system to pass the manufacturing module, substrate, and structural material (powder material) thereon under different rows of print nozzles in the print nozzle array to avoid passing areas of structural material under the clogged or blocked nozzle until the clogged nozzle can be cleaned, cleared, or replaced.

[0282] Alternatively, the system can be programmed to determine, based on the printed liquid pattern detected by the SWIR imaging camera, that a serious failure has occurred in the printing system and further processing should be stopped to repair or replace the print nozzle, restore proper operating conditions, or isolate the article in the build.

[0283] <Product Identification>

[0284] In various embodiments, a control or PAT process can include a product aesthetics assessment method that includes the step of acquiring a plurality of digital images of a processed product or one or more intermediate forms of a product. The diversity of images can be classified into one or more categories of product (or intermediate form) images, the image category selected from the group consisting of acceptable images and unacceptable images, the unacceptable images including at least one of rework images and quarantine images. Predefined and stored images of products (e.g., dosage forms) of acceptable quality are accumulated and assembled into acceptable image categories. Predefined and stored images of products (e.g., dosage forms) of unacceptable quality are accumulated and assembled into unacceptable image categories. Unacceptable images can be further divided into rework images and quarantine images based on whether the product in the image can be reworked to acceptable quality, or cannot be reworked and requires quarantine. The method also includes the step of using the plurality of acceptable images to create an algorithm that can distinguish real-time product images as acceptable images or unacceptable images. The step can also include the step of using a plurality of rework images to create an algorithm that can distinguish a live article image as a rework image or a non-rework image, or alternatively, distinguish a rework image or an isolated image. The process includes the step of acquiring a digital image of the article in real time, and the step of analyzing the live article image with one or more algorithms to distinguish the live article image as at least one of an acceptable image, an unacceptable image, a rework image, and an isolated image. The process includes the step of further processing the live article based on the analysis of the live article image, wherein if the live article image is determined to be an acceptable image, the live article proceeds to a subsequent processing step; if the live article image is determined to be a rework image, the live article proceeds to a rework processing step in which one or more previous processing steps performed on the article are repeated; and if the live article image is determined to be an isolated image, the article proceeds to an isolation processing step in which the live article is removed from the processing system and isolated. The article aesthetic evaluation method can be constructed from an image database that is continuously updated with additional article images produced by the processing system having an outer surface of acceptable quality and appearance, and over time, as the processing system produces articles, continuously reducing false negatives or false positives.

[0285] In various embodiments, a two-dimensional (2D) camera imaging system, such as a Cognex In-sight 9000 series camera, can be used to inspect the finished product after all processing is completed. In some embodiments, a 2D camera can image the surface of a structure material or a processed structure material (e.g., a wetted bonding powder layer) using the above-mentioned article aesthetic evaluation and determine the surface quality of the surface layer on the bonding powder matrix.

[0286] In various embodiments, the above-mentioned two-dimensional camera imaging system is installed and used to monitor, for example but not limited to, the top surface quality of the processed product. The control system can be programmed to take subsequent processing actions based on the evaluation results of the 2D camera imaging system. For example, if the 2D camera determines that the image of the top surface of the processed product is an unacceptable image and a rework image, the processing control system can command the processed product to be reprocessed (reprocessed) through the top surface smoothing / pressing unit operation, and then re-image the top surface of the reworked product to check and determine whether the unacceptable surface finish has been corrected. The processing control system can be configured to command the processed product to be reprocessed one or more times until a satisfactory result is achieved or it is isolated. Alternatively, if the 2D camera imaging determines that the image of the top surface of the processed product is an isolated image, the processing control system can command the product to be isolated. It can be determined that the processed product is over-reworked and / or isolated, and the processing system can stop additional processing operations until the inspection system operation is performed and corrective measures are taken.

[0287] <Unloading of completed products>

[0288] In various embodiments, after the article is formed on or in the substrate, the article is removed from the substrate for further processing, including packaging. Removal of the article from the substrate can be performed within the processing system, can also be performed on the transport surface of the magnetic motion device, and / or within the containment system.

[0289] In various embodiments, the substrate can provide a portion of the packaging for the article, in which case the article remains in the substrate and is further processed, including by further addition of structural materials and / or phase changes, which can include drying and / or packaging. For example, upon completion of the forming surface in or on the forming surface, the manufacturing module can be moved to an unloading station within the magnetic motion system. In some embodiments, the substrate having the formed article disposed within its forming surface, such as a blister tray loaded with a dosage form, is manually or mechanically removed from the transport module, more specifically, removed from the carrier of the transport module.

[0290] In a mechanical removal embodiment, the instrument separates and lifts the loaded substrate from the carrier and transports the separated loaded substrate to an area outside the processing system, more specifically, to a substrate or blister inspection device, and then to a substrate or blister sealing device for sealing the dosage form within the recess from the environment for storage and transportation.

[0291] In another embodiment, after forming the finished product on the substrate (e.g., forming a blister card with a dosage form in the recess), the manufacturing module is controlled to leave the loading area through a mask lifting device 190 located at the transport opening 36 of the loading housing. The mask lifting device 190 provides an antechamber in which the mask 90 of the manufacturing module can be lifted away from the substrate 80 and the nest 74 of the manufacturing module 70 and can be removed manually or mechanically. Fig.17A As shown, the mask lifting device 190 has a pair of side walls 191 forming an antechamber, and the pair of side walls 191 are spaced apart laterally to allow the manufacturing module to pass between the side walls with a close, non-contacting gap with the side walls 191. Each of the side walls 191 has a narrow groove 192 formed in the inner surface in a mirror-image pattern. Each manufacturing module 90 can have a pair of pins 94 ( Figure 6 ), the pins 94 extend laterally outward from the sides of the mask 90 and extend beyond the lateral sides of the nest 74. Each slot 192 has an entrance 193 at the leading edge of the side wall 193, and the height of the entrance 193 is aligned with the pins 94 of the mask 90. ​​When the manufacturing module 70 enters the vestibule, the pins 94 of the mask 90 enter and pass along the horizontal portion 195 of the slot 192, and are guided along the curve in the slot to a second inclined portion 196 that is approximately 45-75 degrees to the horizontal plane. When the pins 94 move upward along the inclined portion 196, the front end of the mask 90 is lifted and leaves the nest 74. Therefore, the mask is completely lifted away from the blister card in a hinged manner, thereby exposing the blister card (such as Fig. 17B ), for inspection, and manually or automatically removing the blister cards from the carrier and subsequent processing or handling. As described herein, the inspection of the blister cards (including the finished dosage forms) can also include inspecting the surface finish for defects or flaws. After removing one or more blister cards, the carrier can be manually or automatically reloaded with new blister cards, and the hinged mask element can be controllably lowered to a position covering the newly placed blister cards.

[0292] <Packaging and Sealing>

[0293] After the final dose is formed, the substrate with one or more complete dosage forms placed in the depressions of the blister card is moved to a blister card inspection device and then to a sealing and cutting device. The sealing and cutting of blister cards is well known in the art and can be configured within the containment system so that the sealed blister sheet is formed in the containment system, or transferred from the containment system, and sealed and cut in a packaging system outside the containment system.

[0294] <Restore Device>

[0295] The present invention also includes a recovery device that can clean or repair a deposition mechanism of a deposition device or a phase change mechanism of a phase change device when the deposition device or the phase change mechanism or the device is in place to restore its performance. In a non-limiting example, the print nozzle cleaning device includes a nozzle cleaning shuttle and a nozzle cleaning substrate fixed to the nozzle cleaning shuttle, the nozzle cleaning shuttle can pass under the print nozzle, and the nozzle cleaning substrate is configured to wipe and clean the print nozzle to restore its printing performance.

[0296] Figure 13-15 An embodiment of a print nozzle cleaning device 150 is shown. The device 150 includes a transport module consisting of a nozzle cleaning carrier 151 and a nozzle cleaning blade 155, and a shuttle 75 (as described elsewhere herein) that provides movement of the nozzle cleaning device 150 over the processing surface 16. The nozzle cleaning carrier 151 has a base 152 having a planar cavity in which the shuttle 75 is precisely mounted, and a frame 153 for securing one or more nozzle cleaning substrates 155. The base 152 is oriented to the shuttle 75 by one or more fixings (e.g., threaded screws 76) that pass through locating holes in the side walls of the base 152 and strike the sides of the shuttle 75. The frame 153 is composed of a container with an open top, and the container has a container volume 154, which is sufficient to receive and contain a certain volume of printing liquid that may remain in the printer housing 551 and the printer nozzle 552 when the liquid printing device 50 is repaired or replaced, or to receive a certain volume of printing liquid that may be dispensed from the printer nozzle 552 during the cleaning process. The frame 153 also includes a side wall 156 and a fixing plate 157 that are inclined upward and outward at a predetermined angle. The inclined side wall 156 has a plurality of threaded holes 159, which are aligned with a plurality of through holes 161 in the fixing plate 157 and are aligned with a plurality of through holes 160 on the nozzle cleaning blade 155. As shown in FIG. Fig.15 As shown, the nozzle cleaning blade 155 is secured to the inclined side wall 156 by passing a fixing screw 158 through a hole 161 in the fixing plate 157 and a hole 160 in the nozzle cleaning blade 155 , and threading the fixing screw 156 into a threaded hole 159 in the inclined side wall 156 .

[0297] In the illustrated embodiment, the nozzle cleaning blade 155 has an upper edge 165 along the length direction, and the upper edge is made of an elastomeric material, which can include natural or synthetic rubber or silicone, and generally has a low hardness, making the material flexible. The upper edge 165 engages with the nozzles of one or more print heads to wipe or scrape off any material that may accumulate on the nozzles and interfere with or hinder the distribution of droplets and / or streams. The design and construction of the frame 153 provides sufficient height for the upper edge 165 of the nozzle cleaning blade 155 so that when the print nozzle cleaning device 150 is magnetically suspended above the processing surface 16 by the processing motion device 20, the tip of the upper edge 165 is slightly deflected when engaging with the printer nozzle 552. When the print nozzle cleaning device 150 moves under the printer housing 551, the side wall opposite the inclined side wall 156 travels in a direction transverse to the length of the print nozzle 552, and the tip of the upper edge 165 rubs along the printer nozzle 552. To prevent the deflected tip of the upper edge 165 from throwing out any liquid or debris as the tip passes through and clears the last printer nozzle 552, the suspension height of the print nozzle cleaning device 150 can be slightly lowered when the blade disengages from the print nozzle to reduce contact and deflection of the tip of the upper edge 165 against the printer nozzle 552.

[0298] In another example, a surface finishing cleaning apparatus includes a shuttle and one or more press heads fixed to the surface finishing cleaning shuttle to clean the substrate, the apparatus being capable of removing a substrate from a surface finishing device (e.g., Fig.11A and 11B A surface finishing device 60 is shown passing underneath, wherein the surface cleaning substrate is configured to wipe and clean the finishing surface of the press head of the surface finishing device to remove any debris and restore the finished surface thereof.

[0299] Figures 16A to 16CAn embodiment of a surface cleaning apparatus 280 is shown. The surface cleaning apparatus 280 includes a transport module consisting of a nozzle cleaning carrier 281 and a cleaning substrate 285, and a shuttle 75 (as described elsewhere herein) that provides movement of the surface cleaning apparatus 280 over the treatment surface 16. The cleaning carrier 281 has a base 282 having a planar cavity in which the shuttle 75 is precisely mounted, and a frame 283 for securing one or more nozzle cleaning substrates 285. The base 282 is oriented to the shuttle 75 by one or more fixings (e.g., threaded screws 76) that pass through locating holes in the side walls of the base 282 and strike the sides of the shuttle 75. The frame 283 includes a pair of elongated rectangular recesses 289 and a support holder 288 consisting of a short hollow cylinder, the elongated rectangular recesses 289 being shaped to receive the cleaning substrates 285. Four support posts 284 extend vertically from the four corners of the base 282 into the support holders 288 of the frame 283, providing the frame 283 with sufficient height so that one or more cleaning substrates 285 engage with the bottom surface of the pressing head 68 of the surface finishing device 60. Each support post 284 has a spring 288 between it and the support holder 288 to provide flexibility and some "springiness" when the cleaning substrate 285 passes under the surface finishing device 60 or other equipment in the loading area. The frame 283 is fixed to the support posts 284 of the base 282 with fasteners (e.g., threaded screws).

[0300] In the illustrated embodiment, a pair of cleaning substrates 285 include an elongated rectangular body that fits into a recess 289 and blades 287 that taper along the length toward the edge. The cleaning substrates are made of an elastic elastomeric material that can include natural or synthetic rubber or silicone, and generally have a low hardness, making the material flexible. The upper edge of one or more blades 287 engages the bottom surface of the pressing head 68 of the surface finishing device 60 to wipe or scrape off any structural or processing material or other debris that may accumulate on the bottom surface of the pressing head 68, which may interfere with the smoothing or other finishing of the powder layer surface.

[0301] Example:

[0302] Provides a Figure 1 A processing system for manufacturing solid dosage forms as shown in and described herein. The system includes a processing motion device having an omnidirectional magnetic motion device, the processing motion device having a stator formed of twenty-four (24) sheet segments, each sheet segment is approximately 1 square foot square, which are arranged to be 2 sheet widths by 12 sheet lengths, and a thin stainless steel plate placed on the processing motion device stator, which has a rectangular area of ​​4 feet wide and 13 feet long. The containment area is formed by a containment shell, which has a stator formed by A transparent top plate and transparent side walls made of (polycarbonate) are placed on a stainless steel plate and are horizontally centered above the stator. The width of the containment housing is 3 feet, the length is approximately 10 feet, the height is approximately 5 inches, and there is an air inlet at the front end. The HEPA filter device, shown as element 18, is positioned and sealed on the upper surface of the top plate panel 33, and the air inlet of the HEPA filter device 18 extends through the opening 34c in the top plate panel 33 ( Figure 2 ). The HEPA filter device is positioned and supported above the top plate on an equipment support 15c raised by a pair of support brackets 14c.

[0303] Multiple manufacturing modules are movable under the control of an omnidirectional magnetic motion system to a processing unit operation station located at or above the transport surface enclosed by the containment housing. Examples of manufacturing modules are Figure 4-6 shown and described herein.

[0304] <Example 1>

[0305] As Figure 1 shown, the processing facility 10 provides a processing unit operation station and a processing system that includes a pair of powder dosers 40a, 40b, a pair of liquid printing devices 50, and a pair of surface finishing devices 60. As Figure 3 shown, the first powder dosing station is located above the stator segment B1, and the second powder dosing station is located above the stator segment A1. The first and second powder devices 40a, 40b are located and sealed in the upper surface of the top plate panel 33, and their powder discharges extend through the opening 34b in the top plate for discharging powder into the blister card recess.

[0306] <PAT Station>

[0307] The first liquid printing device 50a of the first printing station is located above the stator segment A3, and the second liquid printing device 50b of the second printing station is located above the stator segment A7. The first and second liquid printing devices 50a, 50b are located and removably sealed in the upper surface of the top plate panel 33, and their printing nozzles extend through the opening 34a in the top plate.

[0308] The first surface finishing device 60a at the first finishing station is located above the stator segments A5 - A6, and the second surface finishing device 60b at the second finishing station is located above the stator segment B7. The first and second surface finishing devices 60a, 60b are positioned and removably sealed in the upper surface of the top plate panel 33, and their finishing surfaces extend through the opening 34d in the top plate.

[0309] The first imaging device 95a at the inspection station is positioned above the stator sheet segment B4. The imaging device 95a is located above the containment housing 30 and is used to image the blister card and the structural material through the transparent top panel 33. The imaging device 95a is a Cognex 3D camera that is capable of detecting the position of the peripheral surface of the powder material within the recess of the blister card to estimate the volume of powder contained within the recess.

[0310] A second imaging device 95b is located at a second inspection station above the stator sheet segment B4. The imaging device 95b is located above the containment housing 30 and is used to image the blister card and the build powder and adhesive liquid through the transparent top panel 33. The imaging device 95b is a SWIR camera that detects the position and concentration of the adhesive liquid applied to the build powder layer in the depression of the blister card to identify the pattern and concentration of the adhesive liquid, as well as the specifications of the water and / or one or more solvents contained therein. The process controller system receives the images captured by the imaging device 95b and is able to perform real-time analysis of the accuracy of the printing operation.

[0311] A third imaging device 95c is located at a third inspection station above stator sheet segment A8. Imaging device 95c is located near the second liquid printing station at stator sheet segment A7 and is used to image the blister card and the build powder and adhesive liquid through the transparent top plate panel 33. Imaging device 95c is a SWIR camera that detects the location and concentration of the secondary or finishing adhesive liquid on the topmost layer of powder applied in the depression of the blister card to identify the pattern and concentration of the adhesive liquid, and in particular the specifications of the water and / or one or more solvents contained therein. The process controller system receives the images captured by imaging device 95b and can perform real-time analysis of the accuracy of the printing operation.

[0312] The fourth imaging device 95d is located at the fourth inspection station above the stator sheet segment B10. The imaging device 95d is located at the entrance outside the loading area and is used to detect and inspect the manufacturing module when it moves in and out of the loading housing 30. The imaging device 95d is a 2D imaging device or camera that can be used to image the identification marks on the manufacturing module and the substrate (blister card) to monitor, identify, monitor and control the movement and unit operations performed on the substrate in the loading area. The 2D imaging device 95d also captures images of empty substrates (blister cards) entering the loading area and processed substrates with finished dosage forms leaving the loading area, and can transmit the images to the control system, where the finished dosage is analyzed in real time to ensure the accuracy of the printing operation.

[0313] <Blister Card and Manufacturing Module>

[0314] In the remote forming station or facility, the substrate film blank is thermoformed into a substrate having first and second six-depression blister cards within a blister frame. The blister forming step also includes printing a unique identification code, such as a batch number or a QR code, on the top and bottom surfaces of the blister sheet and the bottom surface (underside) of each depression bottom. The unique 2D barcode (such as Figure 6 189 in the hinged mask 90 and is input into the data storage of the processing unit operation controller before the manufacturing module enters the loading area.

[0315] The processing system includes a processor for controlling the processing of six manufacturing modules at a time, each module according to a build program, the manufacturing modules moving asynchronously among several different processing unit operations until each build program is completed. The processing system is capable of using a single manufacturing module, or up to 10, up to 15, or up to 30 manufacturing modules simultaneously. Each of the six newly formed and identified substrates is placed on a corresponding nest of a carrier, which is fixed to a uniquely identifiable shuttle car to form six manufacturing modules. The operator places the first manufacturing module 70a (see Figure 3 ) is placed on a loading area located on the transport surface, which is located above one of the sheet segments of the omnidirectional magnetic motion device outside the containment shell (for example, B7), and the unique identification barcode of the first substrate (blister card) is scanned into the processing unit operation controller using a 2D camera 95d at the fourth inspection station. The motion controller of the omnidirectional magnetic motion device detects that the shuttle car of the first manufacturing module is located in the loading area, and confirms to the processing unit operation controller that the uniquely identifiable shuttle car is correctly located in the loading area, which associates the unique identification code of the first substrate with the uniquely identifiable shuttle car. The processing unit operation controller notifies the operator that the first manufacturing module has been correctly identified, and notifies the operator that the first manufacturing module can be moved into the containment system under the control of the motion controller.

[0316] <Asynchronous motion and unit operation processing>

[0317] The motion controller moves the manufacturing module (shuttle with fixed carrier and substrate) through the air inlet into the containment housing at one or more sheet segments A8-B8. Under the control of the processing unit operation controller and the motion controller, the first manufacturing module first moves to the 3D imaging device 95a to detect, evaluate and determine the volume within each empty blister recess.

[0318] The first manufacturing module then moves to the first liquid printing station at stator laminar segment A3. The first manufacturing module is properly positioned and oriented in the initial alignment position by the motion controller, which initiates controlled linear motion along the longitudinal axis toward stator laminar segment A4 at a programmable (in some embodiments, constant) linear speed so that the plurality of depressions 83 of the substrate pass directly under the jet nozzles of the first liquid printing device 50. The controlled motion of the shuttle of the manufacturing module includes incremental and / or continuous linear motion in the horizontal plane, including rotation of the manufacturing module about the vertical axis to manipulate the manufacturing module from one processing unit operation to the next processing unit operation, while simultaneously and independently manipulating the other five manufacturing modules (70b-70f, 70b-70f) through various processing unit operations, from one station to another, and through the same transport surface and load space. Figure 3 ), without contact or collision with other manufacturing modules, nor causing undue delays or "traffic jams". Under the control of the processing unit operation controller and according to the dosage printing program, a printing liquid of an appropriate pattern is deposited as a preliminary bonding liquid layer on the inner bottom surface of each recess of the blister substrate.

[0319] Then, the first manufacturing module moves to the first powder dosing station located above the stator lamellar segment B1 and is correctly positioned and oriented in the initial alignment position by the motion controller. Under the control of the processing unit operation controller, according to the dose printing program, the doser 40 dispenses a predetermined volume of powder material, such as Fig. 8A and 8B, and deposited into each depression of the blister substrate, on top of the preliminary bonding liquid layer, as a first powder deposition.

[0320] After depositing a certain volume of powder material, the first manufacturing module 70a then moves to the vibrating leveling device 55 at an adjacent position at the sheet segment A2. As described herein, the vibrating leveling device 55 has a voice coil actuator (VCA) vertically disposed above the transport surface 16. When the first manufacturing module is positioned below the voice coil actuator, the probe 56 extending vertically from the voice coil actuator extends downward and contacts the mask 90 of the carrier 72 (see Figure 4 ), and transmits vibrations at a frequency of about 40 Hz and an amplitude of 1 volt to the nest 74, directly to the mask 90, and through the mask 90 to the blister card 82 disposed thereunder. The vibrations of the blister card 82 form the first powder deposited in the recess into a powder layer having a uniform thickness and a uniform horizontal upper surface within the recess. Alternatively, the manufacturing module and its blister card can vibrate during the powder deposition process of the first powder dosing station, using the vibration force employed in the dosing device 40 to allow the powder material to flow freely into and through the dosing device to deliver a dose of powder material having a horizontal surface within the recess.

[0321] Alternatively, or in addition to the leveling provided in the vibratory leveling device 52 of the leveling station, the motion controller of the omnidirectional magnetic motion device can actuate the motion stator to vibrate the first manufacturing module (for example, at a frequency of about 40 Hz and an amplitude of about 1 volt) through the magnetic force on the shuttle, each vibration cycle consisting of a small angle rotation (pitch) through the longitudinal axis of the shuttle, which can cause the carrier and the substrate to vibrate until a substantially uniform first powder layer deposited into the cavity is formed within the recess of the blister card.

[0322] Then, under the control of the processing unit operation controller and the motion controller, the first manufacturing module moves back to the 3D imaging device 95a to detect, evaluate and determine the remaining volume within each empty blister recess above the first leveled uniform powder material layer.

[0323] Then, under the control of both the processing unit operation controller and the motion controller, the first manufacturing module moves to the first liquid printing station positioned above the stator sheet segment A3 and is correctly positioned and oriented in the initial alignment position by the motion controller. Then, the motion controller initiates a controlled linear motion along the longitudinal axis toward the stator sheet segment A4 at a constant linear speed (preferably 0.25 meters per second (m / s) or less), so that the plurality of recesses of the substrate containing the first uniform powder layer pass directly under the jet nozzle of the first liquid printing device. Under the control of the processing unit operation controller, according to the dosage printing program, the appropriate pattern and amount of printing liquid are deposited on the first uniform powder layer, thereby wetting the powder layer and forming a first wetted powder layer in each recess of the blister substrate.

[0324] The first manufacturing module is moved to the first inspection station located above the stator sheet segment B4, and the SWIR imaging device 95b takes one or more images of the upper surface of the manufacturing module to detect and evaluate the volume and distribution of the wetted powder material layer within the blister recess, and detect the position or accuracy of the printing droplets deposited on the first layer of powder when forming the wetted powder layer.

[0325] The first manufacturing module then moves back to the 3D imaging device 95a under the control of both the processing unit operation controller and the motion controller to detect, evaluate and determine the remaining volume within each empty blister recess above the first wetted powder material layer.

[0326] Then, the first manufacturing module (under the control of both the processing unit operation controller and the motion controller) moves back to the first powder dosing station (or the second powder dosing station, if another manufacturing module is already located at the first powder dosing station position, then moves back to the second powder dosing station) located above the stator sheet segment A1, and repeats the deposition of a second predetermined volume of powder material on top of the first wet powder layer in each recess as a second powder deposition, and the second powder deposition is flattened into a second uniform powder layer, which is performed after the first powder deposition is completed. Then, the first manufacturing module moves back to the 3D imaging device 95a to detect, evaluate and determine the remaining volume within each empty blister recess above the second flattened uniform powder material layer.

[0327] The first manufacturing module then moves to the first liquid printing station (or, if another manufacturing module is already located in the first liquid printing station, to the second liquid printing station located above the stator lamellar segment A7, although this is rare because the processing through the first liquid printing station proceeds quickly). The first manufacturing module moves along the longitudinal axis at a constant line speed (preferably 0.25 m / s or less) so that the plurality of recesses of the substrate containing the second uniform powder layer pass directly under the jet nozzle of the first liquid printing device, and deposits the appropriate pattern and amount of printing liquid for the second building layer on the second uniform powder layer according to the dose printing program, thereby wetting the layer and forming a second wetted powder layer in each recess of the blister substrate.

[0328] The first build module is again moved to the inspection station and the SWIR imaging device 95b captures one or more images of the upper surface of the build module to detect and evaluate the position or accuracy of the print droplets deposited on the second layer of powder when forming the wet powder layer.

[0329] The first manufacturing module repeats the cycle of moving on the transport surface and through the processing equipment to build and evaluate four additional wet powder layers through the first powder dosing station (or the second powder dosing station), leveling, detecting and determining the remaining volume within each empty blister recess above the leveled powder material layer at the 3D imaging device, printing liquid onto the second uniform powder layer, and checking the position and accuracy of the wet powder layer.

[0330] After the final powder material layer is deposited, leveled, and inspected by a 3D imaging device to determine the remaining volume within each empty blister recess above the final leveled powder material layer, the first manufacturing module, under the control of both the processing unit operation controller and the motion controller, moves to a first surface finishing station, which is located above one or more stator sheet segments A5-A6 and is correctly positioned and oriented at an initial alignment position by the motion controller. For example, Fig.11A and 11BThe press head of the surface finishing apparatus shown and described herein is lowered onto the dry, flat and uppermost powder layer to smooth the upper surface and shape it into a slightly domed circular profile.

[0331] The first manufacturing module is then moved to the finishing print station at the stator sheet segment A7 and is properly positioned and oriented by the motion controller in the initial alignment position. The motion controller is then moved in a controlled linear motion along the longitudinal axis toward the stator sheet segment A8 at a constant linear speed (preferably 0.25 meters per second (m / s) or less) so that the plurality of depressions of the substrate containing the fully formed wet dosage form pass directly under the jet nozzle of the second liquid printing device. Under the control of the processing unit operation controller, a first portion of a certain amount and pattern of finishing liquid is deposited on the top surface of the fully formed dosage form according to the dose printing program to form a first layer of finishing coating (whose composition is different or the same as the binder liquid applied by the first liquid printing device). The first manufacturing module is moved to the third inspection station, and the SWIR imaging device 95b takes one or more images of the upper surface of the manufacturing module to detect and evaluate the position or accuracy of the printed droplets of the finishing coating deposited on the final powder material layer.

[0332] Then, under the control of the process unit operation controller, the first manufacturing module is returned to the same finishing printing station three more times and three additional portions of the finishing liquid are deposited in amounts and patterns onto the top surface of the fully formed dosage form according to the dose printing program to form the remaining finishing coating layer (whose composition is different or the same as the binder liquid applied by the first liquid printing device). The first manufacturing module is then moved again to the third inspection station and SWIR imaging device 95c to detect and evaluate the position or accuracy of the printed droplets of the deposited final finishing coating.

[0333] The first manufacturing module with the final printed and completed dosage form placed in the recess then moves to the second surface finishing station at the stator laminar segment B7 (with Fig.11A and 11B The device shown is similar to the device shown in the figure) and is correctly positioned and oriented by the motion controller in the initial alignment position. Under the control of the processing unit operation controller, according to the dose printing program, the two sets of surface finishing bodies (UHMWPE) of the surface finishing device are lowered while slowly rotating, contacting the upper surface of the uppermost wet powder layer in the depression to reduce the surface roughness of the upper finishing surface of the dosage form. After completion, the rotating finishing body is slowly raised from the finishing surface.

[0334] Under the control of both the processing unit operation controller and the motion controller, the first manufacturing module with the blister substrate and twelve finished, fully formed wet powder dosage forms is moved out through the transport opening 36 in the containment shell 30 and moved to the fourth inspection station at the sheet segment B10 outside the containment area, where the fourth 2D imaging device 95d acquires one or more images of the upper finished surface of the constructed dosage form to detect and evaluate the appearance and texture of the upper surface of the constructed dosage form. The bar code of the blister card is also scanned into the processing unit operation controller by the 2D imaging device 95d. The motion controller of the omnidirectional magnetic motion device also detects the same uniquely identifiable shuttle, and the processing unit operation controller confirms that the shuttle is still associated with the same unique identification code of the first substrate. The processing unit operation controller then notifies the operator that the dosage form build of the first manufacturing module has been correctly identified and that the first manufacturing module is ready to be manually moved to the dosage form drying system to evaporate excess water and solvent within the wet dosage form.

[0335] The other five manufacturing modules (each having its own unique printed identification mark on the substrate and associated with its own uniquely identifiable shuttle) are run through the same processing unit operation as the first manufacturing module, with each manufacturing module being processed asynchronously through the same processing unit operation station as the other manufacturing modules in the six-module batch.

[0336] After all six manufacturing modules in the batch have been processed out of the containment housing at the unloading station, the drying operation is started. Optionally, when the manufacturing modules have been processed out of the containment housing, the drying operation can affect each loading substrate of the manufacturing modules independently. The corresponding substrate (blister tray) filled with the moistening dosage form is removed (lifted) from the carrier and passed through the drying system. After drying, the loaded blister tray is separated from the nest of the carrier and subjected to additional processing, including film sealing and packaging of the blister tray.

[0337] The modular design of the processing system of this example can be used for small-scale development, simulation, testing, experimentation and similar activities, and the dose forming instruments or instrument modules used can be adopted in pilot and commercial scale manufacturing. This modularity allows the process and operating conditions of these instruments and instrument modules to be thoroughly and systematically tested and developed before the same instruments or instrument modules are installed in GMP certified pilot or manufacturing facilities. The modularity of instruments and instrument modules can also be removed from pilot or manufacturing facilities that meet GMP standards and placed in processing facilities before returning the same instruments and instrument modules to pilot or manufacturing facilities to dynamically simulate processing on a smaller scale to help troubleshoot processing adjustments and processing anomalies.

[0338] Example 2: Masking to remove the antechamber

[0339] In a second example, the system and operations of Example 1 were used to form a first manufacturing module having a blister substrate with twelve finished, fully formed, wetted powder dosage forms. Figure 1 and Fig.17A and Fig. 17B As shown, the mask lifting device 190 is positioned at the transport opening 36 of the containment housing. The mask lifting device 190 provides an antechamber in which the mask 90 of the manufacturing module can be lifted away from the base plate 80 and the nest 74 of the manufacturing module 70 and removed manually or mechanically. When the front end of the mask 90 enters the antechamber opening between a pair of side walls 191, a pair of pins 94 of the mask 90 enter at the height of the narrow slot 192 on the inner surface of the antechamber, and as the manufacturing module passes forward through the antechamber, the pins 94 of the mask 90 pass upward along the curve in the slot to pivot the mask 90 upward away from the blister card. When the pins 94a move upward along the horizontal portion 195, the front end of the mask 90 is lifted and away from the nest 74, and the blister card is exposed to the 2D imaging device 95d to read its bar code and inspect and evaluate the appearance and texture of the upper surface of the constructed dosage form.

[0340] Example 3: Active Loaded Tablet System

[0341] An active loading tableting system is constructed using an omnidirectional magnetic motion device for moving a transport module to and between a set of processing unit operation stations to form tablets with active agent doses.

[0342] Fig.18 The plan layout diagram in FIG. 2 shows an active loading tablet system 210, including a stator transport surface, a containment system, and a set of processing unit operation stations, the set of processing unit operation stations including a base tablet supply system 240, an active agent distribution system 250, a drying system 260, and an optional coating system 270, each of which is located above a portion of the stator transport surface 16 of the omnidirectional magnetic motion device and / or within the containment housing 30. The base tablets used in the active loading tablet system 210 can be preformed by other manufacturing methods, for example, a compression tablet manufacturing system, and supplied to the base tablet loading system 240 of the active loading tablet system 210.

[0343] In this example, the base tablet is a preformed compressed tablet. The tablet includes a first side and an opposite second side and a peripheral edge. At least one of the sides (although in this example two of the sides) has a concave depression in the side extending inwardly from a slightly inner portion of the peripheral edge toward the center plane of the tablet. The active agent is in the form of a liquid active agent, which consists of a liquid composition comprising the active agent and one or more solvents or diluents.

[0344] The basic tablet placement and distribution system 240 is located above the tablet placement station at the stator lamellar segment B1. The basic tablet placement and distribution system 240 includes a loading container or hopper that contains basic tablets that are connected by gravity feeding into a loading slot that transfers the basic tablets into a storage system. The basic tablet distribution system has an upper inlet port disposed outside (and above) the containment housing 30, and a tablet distribution port that extends through a sealable port (not shown) in a top panel of the containment system. The basic tablet distribution system includes a placement device for positioning a predetermined number of basic tablets in a horizontal plane and arranging them into a predetermined arrangement or array, such as a 3 x 4 or 4 x 6 array, in which small portions (such as halves or quarters) or all of the tablets are equally spaced in a rectangular pattern. In this example, the array includes two groups of six basic tablets, which are arranged and sized as shown in FIG. Figure 6 The basic tablet dispensing system further comprises a tablet placement tool for vertically lowering and placing the arranged basic tablets on the upper surface of the substrate, which preferably has an array of concave depressions of the same size and arrangement as the placement device, so as to place each basic tablet in the placement device into a corresponding (array position) depression of the substrate. In this example, as described herein, the substrate is a blister substrate, which is arranged and oriented by the carrier element of the transport module, such as Figure 4 and Figure 6 As shown, a manufacturing module is provided, which uses a shuttle to controllably move the transport module on the stator of the omnidirectional magnetic motion device. Under the control of both the processing unit operation controller and the motion controller, the manufacturing module first moves to a tablet placement station below the dispensing device of the basic tablet placement and dispensing system 240, where one of a predetermined number of basic tablets is deposited into each corresponding recess of the blister substrate.

[0345] The active agent dispensing system 250 provides for adding a liquid dose of active agent to each deposited base tablet on the blister substrate, and includes real-time monitoring, feedback and adjustment of the distribution of the liquid active agent on each base tablet. The active agent dispensing system has an upper end disposed outside the containment system, one or more supply units for receiving the liquid active agent, and a liquid dispensing end extending through a sealable port (not shown) in the top panel of the containment housing 30.

[0346] The liquid dispensing end includes one or more dispensing modules for dispensing a predetermined or required mass or volume of active agent to at least the first side of the basic tablet. Each dispensing module can be connected to a corresponding active agent supply unit installed at the upper end of the dispensing system 250. The supply unit can be a replaceable cartridge, container or tank that can be easily inserted into or connected to the upper end of the dispensing system. Using more than one dispensing module can improve the speed and efficiency of active agent liquid dose distribution, and / or add different active agents to the basic tablet without cleaning or replacing the module, for example, by reprocessing the carrier tablet back to the active agent dispensing system and layering on the relative outer surface. Each dispensing module includes a pump having an inlet in communication with the supply unit liquid and an outlet in communication with one or more dispensing nozzles liquid. In this embodiment, the pump outlet is in communication with a plurality of dispensing nozzles liquid, and the dispensing nozzle is arranged identically with the array of the predetermined array as the substrate. The pump is preferably a metered positive displacement pump, for example, a peristaltic pump, a rotary gear pump or other pump types that can provide the same accuracy and speed, which can variably dispense a predetermined mass or volume of liquid active agent, including at least a single droplet, through a dispensing nozzle under the control of a control system. One example of an active agent dispensing system 250 is described in U.S. Patent 8,252,234, which is incorporated herein by reference in its entirety.

[0347] Under the control of both the processing unit operation controller and the motion controller, a manufacturing module having a base tablet deposited in each recess of the blister substrate is moved to a dispensing station below the active agent dispensing system and positioned and oriented relative to one or more dispensing nozzles. An example of a manufacturing module is Figure 4-6 Shown and described herein. When a single dispensing nozzle is used, the manufacturing module is controlled to position the depression and the base tablet contained therein directly below the single dispensing nozzle by moving the module under the control of the motion controller. The pump is then activated to dispense a predetermined amount of liquid active agent to the first side of the positioned base tablet. The manufacturing module is then similarly moved under control to position the next depression for dispensing the liquid active agent, and the pump is again activated to dispense a predetermined amount of liquid active agent to the first side of the positioned base tablet. Positioning of the manufacturing module and dispensing of the liquid active agent continue until the liquid active agent is applied to each base tablet, thereby forming an active-loaded tablet.

[0348] When using a dispensing nozzle array, the manufacturing module is positioned to align the plurality of depressions with the dispensing nozzle array to dispense the liquid active agent through the dispensing nozzles onto the corresponding array of base tablets.

[0349] In some embodiments of the base tablet, the loaded liquid active agent can partially or completely soak or migrate into the solid matrix of the base tablet, while in other embodiments, the liquid active agent can form a liquid pool within the concave first side of the loaded tablet.

[0350] When the liquid active agent is a liquid composition with one or more solvents, a drying system 260 is used to evaporate excess solvent from the loaded tablets. The drying system 260 is located above the drying station at the stator sheet segment A4. The drying system has a drying device or a drying monitor. The drying device provides heat and an optional air flow to the active loaded tablets to evaporate excess solvent and leave a solidified or fixed active agent film and / or an active agent film partially migrated into the tablet on the first side of the loaded tablet. The drying system 260 is integrated into the containment shell and can be optionally arranged outside the containment shell 30, but can be transferred from the containment area to the remote drying system by the manufacturing module with the loaded tablets under the control of both the processing unit operation controller and the motion controller, so that the omnidirectional magnetic motion device can be used to access. The drying device can have any one or combination of infrared (IR), convection, conduction and / or microwave heating. The drying system 260 can include a sensor for detecting conditions, for example, detecting the surface temperature of the tablets, the moisture content of the tablet surface.

[0351] After the loaded tablets are dried, additional amounts of the same or different liquid active agents can be applied to the same tablets. The manufacturing module with the dried tablets can be moved back to the active agent dispensing station 250 under the control of the processing unit operation controller and the motion controller to apply another amount of liquid active agent as needed and move to the drying system 260 to evaporate the solvent as needed.

[0352] After a certain amount of liquid active agent is loaded onto the tablet and optionally dried, the coating system 270 is placed above the coating station located at the stator sheet segment A6. The coating system 270 applies a coating over the loaded amount of active agent in the tablet to prevent abrasion and loss of any active agent during normal handling of the tablet. The coating can be a sealant and can provide a uniform appearance to the drug product by hiding or disguising the applied liquid dose. The coating system 270 preferably has a pad printing device located within the coating source and the coating dryer. The pad printing device transfers the coating to the upper surface of the loaded tablet, and this is advantageous because it effectively transfers the coating to the loaded tablet without waste, for example, without overspraying. By extending the pad printing device through a sealable port on the upper surface of the holding system, the coating system can be incorporated into the holding system to provide a coating station in which a manufacturing module having a base loaded tablet in each recess of the blister substrate is moved to the coating station below the coating system and positioned and oriented relative to the pad printing device under the control of the processing unit operation controller and the motion controller. The manufacturing module is controlled to sequentially position each recess and the loaded tablet contained therein directly below and aligned with the pad printing device so as to apply the coating material to the first side of the loaded tablet and then reposition to the next recess until the coating material is applied to each loaded tablet to form a coated tablet.

Claims

1. A processing system for manufacturing an article, comprising: i) an omnidirectional magnetic motion device comprising a transport surface and a stator, the stator being disposed on the underside of the transport surface and comprising a plurality of actuation coils, the plurality of actuation coils applying a primary magnetic field through the transport surface in response to a controlled current through an actuation circuit; ii) one or more manufacturing modules, including a) at least one shuttle vehicle including a planar body and one or more magnetic assemblies responsive to said primary magnetic field applied by said plurality of actuation coils to omnidirectionally levitate and transport said at least one shuttle vehicle above and above said transport surface, and b) at least one substrate including one or more forming surfaces; iii) a motion controller for sending a controlled current through one or more of the plurality of actuation coils to control levitation and transportation of the one or more manufacturing modules; as well as iv) Product forming system, including: a) a deposition device for placing a structural material on at least one of the one or more forming surfaces when the manufacturing module is positioned in a deposition position on the transport surface; as well as b) a phase change device for forming at least a portion of the deposited structural material into an intermediate or finished product on or in at least one forming surface when the manufacturing module is positioned at a phase change position on the transport surface.

2. The processing system according to claim 1, wherein: The motion controller is configured to include one or more steps of asynchronously transporting the one or more manufacturing modules between at least the deposition location and the phase change location to form an intermediate article or a finished product.

3. The processing system according to claim 1 or 2, wherein: The transport surface comprises a non-conductive continuously formed sheet, wherein the sheet can be made of a material selected from the group consisting of polymer, glass, titanium and stainless steel, and is preferably a stainless steel sheet.

4. The processing system according to any one of claims 1 to 3, wherein: The transport surface is a rectangular area including a central area and a peripheral area, and optionally, the transport surface includes the central area and the peripheral area, and the surface temperatures of the central area and the peripheral area can be controlled by circulating an appropriate heat transfer medium in the internal area of ​​the stator to control and maintain the temperature of the transport surface, and the width dimension of the peripheral area is at least the width of the manufacturing module, and the width dimension of the central area is at least the width of the manufacturing module.

5. The processing system according to any one of claims 1 to 4, wherein: The one or more manufacturing modules also include a carrier for securing the substrate to the at least one shuttle.

6. The processing system according to any one of claims 1 to 5, wherein: The one or more forming surfaces include one or more recesses.

7. The processing system according to any one of claims 1 to 6, wherein: The one or more manufacturing modules are multiple manufacturing modules, and the back and forth movement of each of the multiple manufacturing modules between the deposition position and each of the phase change positions is independent and selective to provide the ability to asynchronously form products on at least one substrate of two different manufacturing modules.

8. The processing system according to any one of claims 1 to 7, wherein: The system also includes means for leveling the deposited structural material to a uniform thickness.

9. The processing system according to any one of claims 1 to 8, wherein: The processing system or sub-processing system further comprises one or more additional processing equipment selected from the group consisting of drying equipment, structural material leveling equipment, surface finishing equipment, substrate loading equipment, substrate unloading equipment and combinations thereof.

10. The processing system according to any one of claims 1 to 9, wherein: The processing system or subprocess also includes a surface finishing device for surface finishing the upper surface of at least one of the structural material or the solid dosage form forming the surface in-deposition when the shuttle is positioned at the surface finishing position on the transport surface.

11. The processing system according to any one of claims 1 to 10, wherein: The processing system or sub-process also includes a deposition sensing device for detecting the uniformity of distribution of the deposited structural material on one or more forming surfaces.

12. The processing system according to any one of claims 1 to 11, wherein: At least: the structural material may include an ingestible powder material; the structural material or the ingestible powder material may include an active agent, a non-limiting example of which is an API, a bioactive material or a drug; the article may be a solid dosage form, and the phase change device may include a tool for dispersing a binding liquid forming the ingestible powder material into the binding powder material, the binding powder material including an interconnected matrix of the ingestible powder material; the building powder material may include a particulate adhesive; the binding liquid may include an active agent, a non-limiting example of which is an active pharmaceutical agent API or an active drug; the binding liquid may include a soluble adhesive material; the interconnected matrix of the building powder material may be porous and / or rapidly orally dispersible; and / or the structural material may include at least one heat-meltable powder material, and the phase change device may include a tool for at least partially melting the heat-meltable material.

13. A method of using a planar motor system for transporting one or more manufacturing modules through multiple processing unit operations used in the additive manufacturing of a dosage form, wherein the transportation is controlled (directly or via machine learning, artificial intelligence or other position scheduling methods) to achieve asynchronous, synchronous and random positioning and orientation, thereby achieving asynchronous and synchronous utilization of the processing unit operations in the formation of the dosage form.

14. The method according to claim 13, wherein: The plurality of processing unit operations include dispensing a quantity of a structural material onto one or more forming surfaces of a manufacturing module, and phase changing a quantity of a structural material disposed on the one or more forming surfaces of a manufacturing module into a solid dosage form.

15. The method according to claim 13 or 14, wherein: The plurality of processing unit operations also includes one or more processing unit operations selected from the group consisting of mixing two or more different structural materials, flattening the upper surface of a volume of structural material, finishing the outer surface of a solid dosage form, inspecting one or more physical properties of a material, and cleaning contaminated equipment or apparatus used in the method.

16. The method according to any one of claims 13 to 15, wherein: The structural material is an ingestible powder material, and the phase change includes printing a liquid material including a solvent onto the ingestible powder material layer, and optionally drying excess solvent of the wetted powder layer.

17. The method according to any one of claims 13 to 16, wherein: The multiple processing unit operations include dispensing a certain amount of ingestible powder onto one or more forming surfaces of a manufacturing module, flattening the upper surface of a certain amount of ingestible powder set on one or more forming surfaces of the manufacturing module to form a powder layer, printing a liquid material including a solvent onto the upper surface of a certain amount of set powder to form a wetted powder layer on one or more forming surfaces of the manufacturing module, and optionally drying excess solvent of the wetted powder layer.

18. The method of any one of claims 13 to 17, further comprising a processing unit operation of printing a liquid material comprising a solvent onto a surface of the one or more forming surfaces of the substrate prior to dispensing the ingestible powder.

19. The method according to any one of claims 13 to 18, wherein: The additive manufacturing of the dosage form is selected from the group consisting of binder jetting, material jetting, stereolithography, fused deposition, laser sintering and extrusion.

20. The method according to any one of claims 13 to 19, wherein: Cleaning of the equipment or instrument includes placing the cleaning substrate sufficiently close to a particular processing unit operation and spatially manipulating at least one of the cleaning substrate and the contaminated equipment or instrument to clean one or more surfaces in the contaminated equipment or instrument.

21. A processing system for manufacturing an article, comprising: i) an omnidirectional magnetic motion device including a transport surface; ii) one or more manufacturing modules, including a) at least one shuttle, and b) at least one substrate including one or more formation surfaces; iii) Product forming system, including: a) at least one deposition device for placing a structural material on at least one of the one or more forming surfaces when the shuttle is positioned at a deposition position on the transport surface; and b) at least one processing device for performing a processing unit operation on said structural material when said shuttle is positioned at at least one processing location on said transport surface; and iv) a motion controller for controlling asynchronous transport of one or more manufacturing modules between at least a deposition location and at least one processing location on the transport surface to form an article.

22. A processing system for forming an article or for processing a material or component of an article, comprising: a) one or more processing unit operations, b) an omnidirectional magnetic motion device comprising a stator generating a magnetic field, having a planar transport surface, and c) one or more manufacturing modules in combination with one or more magnetic field actuated shuttles that move with six degrees of freedom in motion, including in the horizontal directions of x and y axes and in the vertical direction of z axis, by magnetic suspension over the planar transport surface; and d) a motion controller, comprising one or more processors, for controlling omnidirectional motion of one or more shuttles on the planar transport surface.

23. The processing system of claim 22, further comprising one or more sensors that monitor and control the processing of materials, including the quality of the processing, the quality and characteristics of the build material input, and the quality and characteristics of the products produced by the unit operations and the processing system.

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