RU2792691C2 - System and method for manufacturing pharmaceutical products by 3d printing - Google Patents

Abstract

FIELD: 3D printing of pharmaceutical products.

SUBSTANCE: a system for the manufacture of pharmaceutical products selected from tablets, granules or capsules by means of 3D printing, containing a machine (2) for 3D printing with a mechanical system (3) movable in one or more directions, at least one print head ( 5) with at least one nozzle (37) moved by means of a mechanical system (3) and a base system (4), on which a base (6) for printing is located, designed to receive the prepared mixture (27) applied by the print head (5), while the system contains at least one holder (35) for holding the cartridge (28), and the print head (5) is temperature-controlled, while the print head (5) contains a housing (42) with recesses, ribs or channels for direction of the thermoregulating agent, and the print head (5) contains a tool (47) for mixing, in particular a screw located in the housing (38, 42) of the print head, while the tool (47) for mixing i is at least partially compressible, in particular, the tool (47) for mixing contains a compressible head (48). A method for the manufacture of pharmaceutical products using the above system.

EFFECT: manufacture of pharmaceutical products, such as tablets, granules and capsules in the form of individual products.

28 cl, 41 dwg

Description

The present invention relates to a system and method for manufacturing pharmaceutical objects through 3D printing.

The present invention, in particular, relates to the technology of manufacturing 3D objects by applying, accumulating or creating layers to form products through 3D printing and, in particular, to a system that is specially modified for the manufacture of large quantities of tablets, granules, capsules, suppositories. , implants and other pharmaceutical products.

The system according to the present invention for the manufacture of tablets, granules and capsules by means of 3D printing has not been known in the art until now. Until now, 3D printing has not been widely used in the field of pharmaceuticals and the manufacture of pharmaceutical or non-pharmaceutical tablets, granules or capsules.

In the considered technical field, only international application WO2017034951 is known, which proposes a 3D printing device and a system for the manufacture of pharmaceutical tablets. According to this invention, the powder mixture is applied to a moving belt, creating the first layer of the tablet, before spraying the binder liquid, leveling the mixture and preparing it to receive the next layer. This procedure is repeated many times, resulting in a hard but particularly porous tablet that dissolves in the mouth with water.

The main disadvantage of the invention according to the mentioned international application is the method of manufacturing tablets, since it involves the continuous application of a mixture, part of which is not used for the manufacture of tablets, which leads to loss of raw materials. Moreover, it is a limiting factor that the proposed device can only produce porous tablets using a powder mixture, which prevents the production of other types of products, such as capsules or compact granules, and does not allow printing objects using liquid raw materials, and the printing process is carried out by continuous application of layers of substance in several repeated steps until the formation of a porous tablet is completed.

Most drugs are administered through the digestive tract for absorption in the intestines, or injected into the bloodstream through the oral mucosa or rectal mucosa. Ingestion of medications (swallowing) has many advantages as it is painless and relatively easy to do, with abundant secretion of digestive enzymes aiding drug dissolution, while pH changes along the digestive tract create a suitable environment for absorption of virtually all drugs. In addition, the considerable mobility, large surface area, and abundant blood supply to the mucosal lining of the gastrointestinal tract greatly facilitate absorption. The rate of absorption may vary depending on the composition of the tablet, for example, the ease of disintegration, the solubility of the shell and/or the size of the granules within the capsule. Finally, the relatively slow absorption by the digestive system creates the possibility of early intervention in case of any mistake.

Although the manufacture of drugs taken through the digestive tract shows a number of advantages, the manufacture of granules, tablets, capsules and related pharmaceutical or non-pharmaceutical substances has hitherto been a complex and rather costly process. The cost of research and development of new drugs, manufacturing units, specialized equipment and substances used in the manufacture of drugs, as well as increased costs for paying there, contribute to a significant increase in the price of drugs.

Another disadvantage is due to the high cost of maintaining the necessary stocks of medicines in case of emergencies. Especially in remote and inaccessible or hard-to-reach areas, the potential for emergency situations leads to the need to store certain stocks of medicines, which often remain unused until the expiration date.

Therefore, one of the objectives of the present invention is to effectively overcome the above-mentioned disadvantages and the disadvantages of the prior art by providing a system for the manufacture of pharmaceutical objects such as tablets, granules and capsules through 3D printing.

Another object of the present invention is to adapt the proposed system for the manufacture of pharmaceutical objects such as tablets, granules and capsules through 3D printing to produce individual "printed" products of the choice of the individual user.

The stated problem is solved by a system for manufacturing pharmaceutical objects such as tablets, granules and capsules by 3D printing, comprising a 3D printing machine with a mechanical system moving in one or more directions.

In the context of the present invention, pharmaceutical objects include pills, tablets, granules and capsules, suppositories and other pharmaceutical products administered or placed in the body of a mammal.

The printing system further comprises a print head with a nozzle moved by said mechanical system. The printing system preferably contains one print head.

The printing system further comprises a base system carrying a base for receiving the prepared mixture applied by the print head.

The print head performs the operation of printing products in this system by applying repeating layers of substance over the basis for printing in order to form an object of a given shape.

The print head contains at least one print nozzle. This nozzle is the part of the print head that allows material to flow onto the surface of the print base. The nozzle and head may or may not have a material flow control valve depending on the characteristics of the various fluids such as powders, granules, liquids, gels, creams, pastes, and the like.

The printing system further comprises at least one holder for fixing at least one cartridge, and this cartridge is filled with a substance for printing. The cartridge can be removed and/or replaced.

Each cartridge may contain one or more of a wide variety of active substances (APIs), including, but not limited to, substances from the following families: antibiotics, statins, stimulants, antiseptics, antipyretics, chemotherapeutics, anti-inflammatory drugs, antifungins, hormonal drugs, diuretics, contraceptives, psychotropic drugs (antidepressants, neuroleptics, etc.), etc.

Cartridges may contain one or more of a variety of (inert) excipients, including, but not limited to, binders, coatings, release agents, colorants, flavors, polymer resins, glidants, lubricants, sorbents, carriers, sweeteners, solvents, inert powders, biodegradable polymers, waxes, preservatives, leavening agents (disintegrants), etc.

The cartridges may contain one or more of a variety of substances used in oriental medicine, including but not limited to herbal pharmacological substances and the like.

The cartridges may contain one or more of a variety of substances used in homeopathy, including but not limited to tinctures and the like.

The cartridges may contain one or more of a variety of substances used in biotech medicine, including but not limited to stem cells and the like.

Cartridges may contain one or more of a variety of composite substances created by mixing analogues of the above families of substances.

Cartridges may contain one or more of a variety of substances that may be under development or research today and have not yet been discovered.

An advantage of the present invention is to provide a system for the manufacture of pharmaceutical objects such as tablets, capsules and granules by 3D printing, which can use cartridges having the appropriate active agent and the appropriate plastic or binder for use in the 3D printing process.

When the cartridge is empty or when another substance is needed, this cartridge can be removed from the holder and a new cartridge can be inserted in its place.

Another advantage of the present invention, in order to provide its usefulness, is to provide a system for the manufacture of pharmaceutical objects such as tablets, capsules and granules, of various sizes, so that this system can have, as an option, additional features to satisfy both simple and more complex 3D printing requirements.

In addition, the system may include multiple cartridge holders, each containing a different substance for sequential or simultaneous printing of more than one unit of drug at a time.

The holders can hold several cartridges with a specific set of printing substances for printing a certain class of pharmaceutical objects. When it is necessary to print a pharmaceutical object of a different class, it is possible to replace the entire group of several cartridges.

In a preferred embodiment, the printing system includes more than one print head.

The mechanical system may include a mechanical arm which terminates in a print head and which can be moved in one, two or three directions to accurately print the item of current need through the print head.

An example of such a mechanical arm is a robotic manipulator arm, usually programmable, with similar functions to a human arm; this arm may be a whole mechanism or may be part of a more complex robot. The links of such a manipulator are connected by hinges that allow rotational movement (as in a robot with articulated joints) or traditional (rectilinear) movement. We can assume that these links of the manipulator form a kinematic chain. The end of this kinematic chain of the manipulator is called the working body and is similar to the human hand.

In the proposed system, robotic arms-manipulators of the following types can be used:

- Cartesian robot (Cartesian robot) / Gantry robot: Used for handling operations (pick and place), sealant application, assembly operations, power tool handling and arc welding. This is a robot whose arm has three prismatic joints, the axes of which coincide with the axes of a rectangular (Cartesian) coordinate system.

- Cylindrical robot (cylindrical coordinate system robot): Used for assembly operations, power tool operation, spot welding, and injection molding machine operation. This is a robot whose axes form a cylindrical coordinate system.

- Spherical Robot (Spherical Coordinate Robot) / Polar Robot (Polar Coordinate Robot): Used for power tool operation, spot welding, injection molding, filling machine operation, gas welding and arc welding. This is a robot whose axes form a polar coordinate system.

- Robot type SCARA: Used for handling operations, sealant application, assembly operations and mechanical tool operation. This robot has two parallel rotational joints for in-plane compliance.

- Articulated robot: Used for assembly operations, injection molding, filling machine operation, gas welding, arc welding and spray painting (using a spray gun). This is a robot whose arm has at least three rotational joints.

- Robot with parallel programming code: One use case is a mobile platform for controlling flight simulators in the cockpit of an aircraft. This is a robot whose arms have parallel prismatic or rotational joints.

- Anthropomorphic Robot: This robot reproduces the shape of a human hand, for example with independent fingers.

The mechanical system may include a platform, also called a bridge, which is a mechanical structure commonly used in 3D printers. The platform is assembled from vertical and ground-parallel structures. This platform carries the print head and moves it up and down and/or in the x-axis and/or in the y-axis direction, or remains stationary and the print base makes all the necessary movements.

The system may include a supply tube to establish a fluid connection between the holder and the print head. The substance used for printing can flow through this supply tube from the cartridge installed in the holder to the print head. The feed tube may be flexible so that the holder may remain in a fixed position while the print head is moved by the mechanical system to the print position.

Alternatively, the holder and printhead may be placed close together to create a direct fluid connection between the holder-mounted cartridge and the printhead.

Preferably, the system comprises a magazine assembly having at least one holder, preferably multiple holders.

In particular, at least part of the magazine assembly is movable so that the holder can move.

For example, as a result of movement of the magazine assembly, a cartridge fixed in one of several holders can be moved to a delivery position where a fluid connection can be established between the cartridge and the print head. After another movement of the magazine assembly, another cartridge can be moved to the supply position so that several substances can be sequentially supplied to the print head.

The magazine assembly may comprise a drive, in particular: a servomotor, a pneumatic drive, a hydraulic drive, a chain drive or a magnetic drive, allowing movement of at least a part of the magazine assembly, in particular, so that one holder or a group of several holders can be moved.

Several holders can be placed on the magazine, so that all holders must be moved to move one cartridge. Alternatively, a plurality of holders may be placed in a row on a guide rail and may be moved to bring them into a feeding position.

Preferably, the system includes at least one movable push rod, preferably attached to a holder, to push the substance out of the cartridge. Therefore, the cartridges used for this system do not need special mechanical equipment to unload the printable substance from the cartridge. The movable pusher rod and the drive for moving this rod provide accurate and reproducible dosing of the amount of the substance measured in accordance with the selected recipe.

The system may further comprise an opening device, preferably connected to the holder, for opening the cartridge. For example, the holder may have a cartridge piercing needle, a cap removal mechanism, or a pin for opening the cartridge valve.

The system may further comprise a closure device, preferably connected to the holder, to at least partially close the cartridge when it is not needed for printing.

The system may include a reader, preferably connected to the holder, for identifying an identification mark made on the cartridge. Therefore, the system can recognize the type of substance in the cartridge, expiration date, target amount, or other data associated with the cartridge.

This reader allows for logistical support such as statistics or automated reordering. The advantage of such logistics is the possibility of reducing the volume and weight, as well as the required level of energy consumption.

Preferably, the system comprises a holder with a temperature control device. Such a holder may heat and/or cool the cartridges.

In a preferred embodiment, the system includes a print head with a thermal control device. Such a printhead may be heated and/or cooled.

In particular, the print head includes a housing with recesses, fins or channels for guiding a thermal control agent, such as a thermal control liquid or a thermal control gas, such as cooling air. Alternatively, the printhead may include a thermal conductor that can be electrically heated.

If high temperatures are required, the printhead can be covered with a heat shield.

In a preferred embodiment, the print head includes a housing that forms a volume for the printed matter. The body of the printhead may have an opening for receiving fluid from the cartridge, which, in particular, may be connected to the supply tube.

Preferably, the print head includes a tool for mixing and/or discharging the material, in particular an auger located in the housing of the print head.

This mixing and/or discharging tool may be movable, for example rotated within the print head housing.

The mixing tool mixes several substances coming from several cartridges into the print head.

The substance discharging tool may discharge a certain amount of substance through the print head during printing. This eject tool may be a push tool that can move within the print head housing. The printhead may contain a tool suitable for blending and ejection.

Preferably, the system comprises a drive for driving the agitating and/or pushing tool.

Alternatively, the print head may include a substance discharging tool to reduce the size of the print head body, such as a squeezing tool or a squeezing tool, such that the pressurized substance is squeezed out through the print head nozzle as the volume of the print head body is reduced.

Preferably, the system comprises a drive for driving the substance discharging tool.

The print head may comprise a double housing: a) an outer housing of a cylindrical or other shape, preferably made from a recyclable substance, and b) an inner reservoir made of an elastic/flexible/compressible substance. At the top of the head there may be a plug, and at the bottom there may be a cap connected to both bodies and equipped with a printing nozzle, which may be provided with a valve.

Another advantage of the present invention is to provide a system for the manufacture of pharmaceutical objects such as tablets, granules and capsules through 3D printing, which has an ejection tool containing a punch head to eject the correct amount of substance from the print head at a time in order to print a unit medicines.

In the preferred embodiment, the print head contains a tool that is suitable for mixing and ejection. For this purpose, the mixing tool may be at least partially compressible, in particular this mixing tool comprises a compressible head.

A squeezable head stirrer can be made from Kevlar, or carbon fibers, or epoxy.

This squeezable head can create a vacuum effect in the printhead nozzle to prevent dripping.

Preferably, the printhead comprises a nozzle with a valve, such as a check valve, reed valve, ball valve or needle valve.

The print head may include a spray nozzle and an inlet tube for supplying compressed air, water vapor, water, solvents, pharmaceutical colors, multi-colored food colors, and other similar substances.

Water vapor can bond with very dry materials, allowing very high production rates for objects and finished products with very high porosity. Water vapor may accelerate pharmacokinetics.

The same can be done using a combination of steam, adhesives, pharmaceutical binders/solvents and water.

Compressed air can help dry manufactured articles, or can be used in a similar manner as steam, but for pills (etc.) made from substances that heat and/or water can adversely affect.

Multi-colored dyes can be used to label different dosages.

In a preferred embodiment of the present invention, the system comprises a thermal head equipped with an auger to agitate the mixture prior to 3D printing.

Another advantage of the present invention is the use of a squeezable print head which, in addition to agitation, extracts air from the mixture, creating more compact tablets, granules or capsules when needed.

Preferably, the system includes an energy emitter associated with the print head. This energy emitter can be mounted on a mechanical system and can move with the print head, or this energy emitter can be directly connected to the print head. The energy emitter provides drying or fixation of a portion of the substance after it has left the nozzle of the print head.

In particular, the energy emitter may be a photopolymer lamp, an infrared source, a laser, a microwave source, a spray nozzle, a compressed air nozzle, or a steam nozzle.

The print head can contain multiple nozzles. Therefore, it is possible to print several pharmaceutical objects in parallel.

In one preferred embodiment of the present invention, the system includes a cleaning assembly for cleaning the printhead and/or cartridge. The cleaning unit may include a wash tub and/or a wash port. The flush port may be connected to a cleaning fluid reservoir and/or to a cleaning fluid filtration system.

After use, the print head, preferably together with the mixing and/or ejection tool, can be cleaned so that no contamination remains in this print head before using it next time with a different print recipe.

The cleaning node is a special place reserved in the system for 3D printing. The cleaning assembly may include an enclosed area with doors necessary to allow the printheads to be loaded inside.

These doors or openings are preferably equipped with all the necessary automation so that the states of the doors (open, closed, locked) can be controlled and monitored, as well as all other mechanisms within this area.

These doors or openings preferably have the necessary seals to make the enclosed area isolated from the rest of the system, so as not to adversely affect important system functions such as vacuum and climate control, if used, due to the evaporation of used or fluids stored in the system or as a result of the use of steam. The print head is moved to this area immediately after use by a mechanical system.

The cleaning assembly preferably comprises a source of heated air for drying the print head, nozzles for supplying steam, compressed air, water and/or solvent spray, vacuum suction to remove steam and excess liquids, brushes, needles for cleaning very narrow nozzles, valves , breathing valves, a bath containing solvents and/or water into which the printhead can be immersed for cleaning, an ultrasonic transducer, or a specialized laser cleaning transducer.

The bath may have a fluid circulation system which may include circulation pumps, filters such as activated carbon filters, microfilters and specialized pharmaceutical filters such as HEPA H13, and associated necessary tubing.

Preferably, the system comprises a thermal control system for controlling the temperature of the print base. The print base system may include ducts or channels for directing flows of a temperature control agent, such as a temperature control fluid or a temperature control gas, such as cooling air.

The temperature of the print base can be adjusted from -5 to 40°C. Preferably, the print base is heated to promote evaporation and help dry the "printed" objects.

Preferably, the system comprises a print base having formatted printable areas in order to obtain a pharmaceutical object of the desired shape, in particular raised depressions. The agent may be applied to a formatted print area that affects the shape of the pharmaceutical object. The underside of the object may, for example, be convex rather than flat.

Formatted printable areas allow a pharmaceutical object, such as a pill, to be created in the same shape as most such objects made by traditional methods. Such pills may have a symmetrical lenticular shape.

In addition, more complex shapes can be created to facilitate immediate visual recognition of manufactured objects, such as: heart shape, diamond shape, teddy bear shape for pediatric use.

The underside may also be shaped like a Gummy Bear, Santa Claus, Easter Bunny, or some other typical food product shape, so that the pharmaceutical object can be printed in the typical shape of such a food product.

The print base may have a recess for receiving a blister pack for pills. Typically, such a blister pack is made by vacuum forming sheets of a suitable plastic. Pharmaceutical objects can be printed inside the blister set in a predetermined position. This saves time and also avoids contact with anything other than the sterile environment of the 3D printer itself.

After printing is completed, the closing device may apply a sealing membrane or film to seal the blister.

The next operation may be to mark the sealed blisters with a marking device such as a laser connected to a mechanical system.

The system may have a base for printing, containing a thermal conductor, in particular, located on the side opposite the side having formatted areas for printing. Therefore, the print base can be heated directly, for example, to dry the printed matter.

The system may include a temperature sensor for monitoring the temperature of the print base. This temperature sensor may be a contact type sensor or a non-contact sensor such as an infrared or laser sensor.

The system may include a thermal control unit having a temperature sensor, a thermostat and/or a thermal switch.

The print base can be made from metal and/or metal alloys such as alclad, a corrosion resistant aluminum sheet made from high purity aluminum with surface layers metallurgically bonded to a high strength aluminum alloy core such as various grades of stainless steel, for example: 310-310S, a high alloy austenitic stainless steel used for high temperature applications. The high chromium and nickel content gives this steel excellent corrosion resistance as well as high strength at high temperatures. 316 steel is also suitable, excellent for use in the food industry and also for food contact and surgery, and the addition of molybdenum to the molten steel prevents some special forms of corrosion due to increased resistance to chloride corrosion, and other grades of steel.

The print base may be made of plastics and/or composite materials. This print base may be made of tempered glass such as borosilicate glass, 7740 glass. The print base may comprise ceramics such as glass ceramic. Glass-ceramic has the technological advantages of glass and at the same time has the special properties of ceramics. Glass ceramics can withstand brazing temperatures up to 700°C while maintaining properties such as zero porosity, high strength, hardness, low thermal expansion, high thermal stability, machinability, high chemical resistance, biocompatibility, insulating ability. From a technological point of view, glass-ceramic is valued for having the strength of ceramic combined with the ability to be hermetically sealed like glass.

Preferably, the print base has a coating, in particular a glazed ceramic coating. The printed pharmaceutical object can be separated from the print base and does not stick to the print base.

Many types of coatings can be used here, for example: ceramic glaze, impermeable layer or coating with a glassy substance that has been fused to the ceramic block by firing, silicon oxide nano-coating, silver nano-coating with antibacterial and antifungal properties, titanium dioxide (TiO ₂ ), nanoparticles , which are sterilizing and have anti-fouling properties.

The base system may also include a device for deleting an object.

The object removal device may be formed by a tilt mechanism that tilts the print base so that the printed pharmaceutical objects slide from the print base to a collector, such as a bin.

The object removal device may be formed by movable extraction pins or gas nozzles connected to formatted print areas on the print base. Each printed object can be ejected from the printable area by the pressure of the ejector pin popping out of the hole in the printable area, or by the pressure of the air jet coming out of the hole in the printable area.

In a preferred embodiment of the present invention, the base system includes a base holder for mounting a print base. This print base can be removed and/or replaced.

Print bases with different formatted print areas can be used in the same system. The print base carrying the printed object can be removed from the system and replaced with another print base.

In a further preferred embodiment, the 3D printing system comprises a mechanical base system capable of moving the print base in one or more directions.

The print base may, for example, be raised to the level for printing and may then be lowered after printing. The print base can also move in addition to the movement of the mechanical system for moving the print head in order to achieve full 3D printing also using only one or two dimensional print head movement.

The preferred system for 3D printing tablets, granules or capsules contains a temperature-controlled base with formatted printable areas, which has air ducts for precise control of the temperature and humidity of the printed products.

Preferably, the system comprises a chamber, in particular with a door, for establishing a controlled temperature. The system is equipped with individual units such as purge filters, ventilation ducts, air filters, activated carbon filter, air conditioning system, air dryer system, vacuum system with vacuum pump and head cleaning tank.

An advantage of the present invention lies in the ability of the proposed system to work alone or in combination with a computer to receive orders for 3D printing of granules, tablets and capsules.

The operation of the system is preferably controlled by a computer or a series of computers. This computer uses an operating system such as: Windows, Linux, IOs, etc. and is equipped with all the software needed to perform system tasks.

The computer preferably controls all operations and activities of the system. Each subsystem, device and mechanism can be controlled and function under the control of the controller. The controller is a comparison device that takes an input from a measured process variable, compares the value it receives with the value of a set setpoint, and determines the appropriate output value needed for the final control elements to take corrective action in the control loop, programmable logic controller (PLC) , erasable programmable read-only memory (EPROM), etc.

In many cases, the same cables that connect each device to the computer can also supply power to that device (for example, the USB bus). The computer may be equipped with all necessary subsystems for interfacing with the user of the system, such as a screen (touch screen, capacitive screen, liquid crystal display (LCD) or other screen), an input device (touch screen, keyboard, multi-function buttons or other elements), a sound system and / or visual alarms, on / off buttons and any other means of an interaction system.

The computer may be equipped with the necessary software to perform these functions.

The computer is preferably capable of self-diagnosing each subsystem of the mechanism and informing the user of the need for service or repair of any part of the system, or of impending failure. This approach reduces the cost of maintaining the system and increases its availability.

The computer preferably takes care of the calibration of the moving mechanisms as needed.

The computer preferably maintains a database for selecting any available mixture and any method suitable for making any product, as well as the form of each product (pills, granules, tablets, suppositories, etc.).

The computer preferably maintains a database of usage statistics and can inform the user that a cartridge containing a particular substance or mixture of substances is close to empty, or even directly order the required cartridge via the Internet (online), thereby optimizing logistics operations.

The databases necessary for the operation of the system may be stored in a computer storage device and/or on the Internet (Internet data storage, remote server, cloud, etc.). These databases can be updated as new products become available (as well as software updates) or can be restored using external storage in case of failures.

To achieve this goal, the computer may be equipped with a modem (modem, router, etc.) connected to the Internet using wired or wireless (radio) technology. Backup copies of computer programs, databases, etc. can be recorded on flash memory devices, external hard drives, network storages, etc.

The computer can communicate with other devices (external computers, computer accessories such as mice, keyboards, webcams, portable hard drives, microphones, printers, scanners and tablets with speakers, smartphones, screens, etc.) via cable (USB, DVI, HDMI, etc.) or wirelessly.

In the case of smaller systems (desktop or laptop), the computer may be external to the system (independent).

All electronic control subsystems - controllers, regulators and others, can communicate directly (via cable) or indirectly (using Bluetooth, WIFI, IR or other system) using an interface device (system to computer) containing the necessary drivers and programs (or applications) to be installed on your computer.

All subsystems of the system under consideration can be powered by a module containing an electrical input (cable(s) and/or wireless charger), a power converter such as 220/12V, a battery or rechargeable battery, an uninterruptible power supply (uninterruptible power supply, UPS, or A backup battery/flywheel is an electrical device that provides emergency power to a load in the event of an input power or mains failure), an auxiliary or emergency power system, or a standby generator, as well as power outlets (USB or otherwise).

The problem is also solved by the method of manufacturing pharmaceutical objects such as tablets, granules and capsules through 3D printing, in particular using the system described above.

The method contains the following steps.

At least one pharmaceutical substance is provided in at least one cartridge. The cartridge is installed in the holder. A fluid connection is established between the cartridge and the print head so that said pharmaceutical agent can exit the print head through the print head nozzle. This print head nozzle moves according to the 3D printing program, and the pharmaceutical substance comes out onto the printing base.

The cartridge can be moved to the print head and can move with the print head.

Preferably, a metered amount of at least one pharmaceutical substance is transferred from the cartridge to the print head and this substance is mixed in the print head, in particular several pharmaceutical substances are mixed.

The printing method can be used to apply a pharmaceutical liquid formulated and mixed according to a predetermined formulation.

A plurality of cartridges, each containing a different pharmaceutical agent, may be mounted in a magazine, which magazine may be moved relative to a printhead to a position where a selected cartridge can establish fluid communication with that printhead. A metered amount of an appropriate pharmaceutical substance can be transferred to the print head, so that a pharmaceutical mixture is prepared in accordance with a pharmaceutical prescription.

In a preferred embodiment, the system comprises a plurality of printheads which move independently and each of which releases a substance onto the print base. The first printhead may be filled with an agent to form a shell or coating, another printhead may be filled with the first active agent, and the next printhead may contain another active agent so that such pharmaceutical objects can be printed within the internal structure.

The method according to the present invention is advantageous in situations where it is necessary to routinely release individually designed pharmaceutical objects of similar composition, as is necessary, for example, in hospitals, nursing homes, cruise ships, ships or refugee camps.

It is easier to store matrix substances than to store raw materials for any and all implementations of certain pharmaceutical products.

This achieves a reduction in packaging volumes with a corresponding environmental benefit and cost savings.

A print base having formatted print areas can be set in the base system for printing before printing. The pharmaceutical substance can be dispensed onto these formatted printable areas.

After printing, the print head can be cleaned.

Preferably, the method comprises the step of providing at least one substance in at least one cartridge, which substance contains at least one of fat mass, starch, flour, gelatin, sweetener, natural flavor, artificial flavor and color.

These nutrients facilitate digestibility and provide palatability to printed objects.

The cartridge may also contain other nutritional substances that can be used as excipients, such as: emulsifiers, stabilizers, thickeners, binders, brighteners, sugar additives for coatings, antiblocking agents, acidifiers, acidity regulators, defoamers, blowing agents, antioxidants , fillers, food colors, color stabilizers, flavors, flavor enhancers, glazing agents, moisturizers, preservatives, etc.

These additional substances can be provided in separate cartridges so that a composite substance containing pharmaceutical substances in accordance with a given formulation can be obtained in the print head.

In a preferred embodiment of the proposed method, the pharmaceutical substance loaded into at least one cartridge contains at least one of an antipyretic agent, an analgesic agent, an antimalarial agent, an antibiotic, an antiseptic, psychiatric agents, a mood stabilizer, a hormone replacement therapy agent, an oral contraceptive, stimulant, tranquilizer and/or statin.

An antipyretic, such as acetaminophen, reduces fever and fever. An analgesic or pain reliever, such as acetaminophen, non-steroidal anti-inflammatory drugs, or opioids, reduces pain. Antimalarials such as chloroquine and hydroxychloroquine treat malaria. Antibiotics inhibit the growth of bacteria. Antiseptics prevent the growth of germs near burns, cuts, and wounds. Mood stabilizers are, for example, lithium and valpromide.

Hormone replacement therapy agents are, for example, estrogen or progesterone. Oral contraceptives are, for example, Enovid, "biphasic" pills and "triphasic" pills. Stimulants are, for example, methylphenidates and amphetamines. Chlorpromazine is an example of an antipsychotic agent. Chlordiazepoxide, diazepam, and alprazolam are examples of sedative and hypnotic drugs in the benzodiazepine class. Statins are, for example, lovastatin, pravastatin and simvastatin.

The system and method of the present invention can be applied to the formulation of paracetamol for pediatric use.

Children aged 6 to 8 years old should take 250 mg, children aged 8 to 10 years old - 375 mg each, children aged 10 to 12 years old - 500 mg each, children aged 12 to 15 years old - 750 mg each. mg every 4 to 6 hours.

In one example, for the manufacture of, for example, 250 mg tablets of paracetamol, cocoa butter, cocoa powder, sugar and milk or chocolate mass are suitable, which, together with the appropriate amount of paracetamol, are fed into the print head, mixed and ensure the coalescence of fine particles to enlarge them. The print head is heated to reach the temperature needed to melt the ingredients.

The main factor behind the lack of use of chocolate and other palatable substances to date has been the fact that they can be misidentified as treats, leading to intoxication due to overdose.

By fabricating such pharmaceutical objects with a 3D printer capable of precise dosing, this danger is virtually eliminated, also due to the fact that the shape of such tablets can be made to be easily distinguishable, as well as exceptionally small quantities can be produced.

On the other hand, substances like chocolate can make it easier to take medications for those who don't normally like them.

The manufacture of such a tablet will be used as an example of the performance of the functions of a 3D printing system.

In the first step, data is entered into the system specifying the desired product, for example a chocolate tablet containing 250 mg of paracetamol for pediatric use.

The system selects the cartridges containing the required ingredients (substances), and after sequentially removing their protective caps, fills the printhead located in the filling position. Thereafter, the nozzles of the cartridges are cleaned with a cleaning device and their caps are returned to their place.

The printhead is heated to between 30 and 35 degrees Celsius to help melt the excipients while the mixing mechanism starts to fuse the pharmaceutical agent and excipients.

The print head is placed over the print base and the printing procedure is started according to the command of the special software.

The printing base, in turn, cools the objects printed on it to help them solidify quickly at a temperature of 20 degrees Celsius. At the same time, the air flow in the system and the temperature control devices contribute to the cooling of the formed tablets.

The procedure concludes with the print base transferring the finished products to packaging, while the print head and base are thoroughly cleaned and sterilized in order to prepare for the next job of the system.

Other excipients can be used to obtain the desired taste and texture of tablets, for example: cocoa butter, cocoa powder, sugar, milk, white chocolate, caramel, strawberry flavor, dark chocolate and other flavors.

These and other objects, features and advantages of the present invention will become apparent from the following detailed description.

The present invention will become apparent to those skilled in the art with reference to the accompanying drawings, in which the invention is illustrated by way of example in a non-exhaustive manner.

In FIG. 1 is a schematic perspective view of an exemplary basic 3D printing system for making tablets, granules and capsules;

in fig. 2 is a schematic perspective view of an illustrative basic version of a system for making tablets, granules and capsules by 3D printing with an open door;

in fig. 3 is a schematic perspective view of an example of an embodiment of a manufacturing system connected to a computer, and also shows the two printheads in the system;

in fig. 4 is a schematic perspective view of another exemplary embodiment of a system for manufacturing tablets, granules and capsules by 3D printing;

in fig. 5 is a rear perspective view of a system for making tablets, granules and capsules through 3D printing, which also shows how the supply voltage is applied;

in fig. 6 is a sectional view of a variant of a 3D printed tablet, granule and capsule manufacturing system, showing the individual components of the system;

in fig. 7 is a perspective view of yet another embodiment of a system for making tablets, granules and capsules by 3D printing with an open door;

in fig. 8 is a sectional perspective view of the above exemplary system embodiment;

in fig. 9 is a front sectional view of the system, showing the individual components of this system;

in fig. 10 is a rear sectional view of the system shown in FIG. 7;

in fig. 11 is a rear sectional view of the above system from a different angle to make other details visible;

in fig. 12 is yet another example of a rear view of the system shown in FIG. 7;

in fig. 13 - an example of a variant of a 3D printing machine equipped with two print heads and a movable mechanical base;

in fig. 14 is an alternative 3D printing machine in the illustrated system capable of continuously supplying a mixture for printing;

in fig. 15 is another alternative 3D printing machine with an arm movable in one or more directions, with the print head and base movable in one or more directions;

in fig. 16 - an alternative version of the machine for 3D printing as part of the illustrated system;

in fig. 17 is a robotic arm that can be used for 3D printing of tablets, granules and capsules in the system according to the present invention;

in fig. 18 - an alternative stand that can be used in the proposed system as a machine for 3D printing;

in fig. 19 is a partial longitudinal section of the cartridge used by the present invention for 3D printing of granules, tablets and capsules;

in fig. 20 is a longitudinal section of a cartridge containing a mixture suitable for each case;

in fig. 21 - an alternative version of the cartridge with a different type of tip;

in fig. 22 - holder of an elongated cartridge, which can be used in the proposed system, together with a punch for ejecting the mixture;

in fig. 23 - a variant of the cartridge holder, which can be rotated;

in fig. 24 is a sectional view of an alternative 3D printed tablet, granule and capsule manufacturing system showing the arrangement of cartridges and printheads;

in fig. 25 - thermal head with support base and accessory holder;

in fig. 26 - the back surface of the thermal head with the corresponding cooling fan;

in fig. 27 - thermal head with a substance supply device and a photopolymerization light source on the head holder;

in fig. 28 (a) and (b) is a thermal print head and its corresponding section showing depressions contributing to heat loss;

in fig. 29 (a) and (b) - a temperature-controlled printing base having formatted areas for printing or a surface of a simple type for printing products;

in fig. 30 - view of the base in section with air ducts for air circulation;

in fig. 31 is a compressible screw that can be used in the production system according to the present invention;

in fig. 32 is a perspective view of a screw with active substance inlets and air outlets, respectively;

in fig. 33 is a sectional view of the base of the compressible screw shown in FIG. 32;

in fig. 34 - compressible screw at the moment of full compression;

in fig. 35 is a cross-sectional view of a multi-output printhead with a screw that can be used in a system for producing tablets, granules and capsules by 3D printing according to the present invention;

in fig. 36 - base for printing with formatted areas for printing;

in fig. 37 - an example of a basic system;

in fig. 38 is another example of a basic system;

in fig. 39 - base for printing with extracting pins (a) in the passive position and (b) in the extracting position;

in fig. 40 is a compressible cartridge option, in the first position (a), in the second position (b) and in the third position (c);

in fig. 41 - cartridge holders installed in the store unit.

In the following, with reference to the drawings, exemplary embodiments of the 3D printed tablet, granule, and capsule manufacturing system will be described in order to make its operation clear.

The basic structure of the system is shown in Fig. 1 and contains a display 1 with keys or touch buttons, through which the user can enter the necessary data and control the indication presented on the display during the operation of the system. The structure also comprises a 3D printing machine 2 having a mechanical system 3 comprising a mechanical arm movable in one or more directions, a base system 4 which may be fixed or may be movable in one or more directions, and a printhead 5 which releases mixture, depending on the commands coming from the software, for 3D printing of tablets, granules and capsules on a basis of 6 to be printed. The 3D printing machine 2 is located in a chamber 7 which is closed by a door 8 as shown in FIG. 2, to create a controlled environment during printing.

The system for making tablets, granules and capsules by 3D printing according to the present invention also includes a power cord 9 as shown in FIG. 3 and may be connected to computer 10. This connection may be wired or wireless. However, the system itself may also have a built-in computer unit on the base 11, so that in this case a connection to an external computer 10 is not required for the operation of the system.

In an alternative embodiment of the present invention, a system for making tablets, granules and capsules through 3D printing can be implemented in the system shown in FIG. 4 in a form similar to that containing the display 1, the power cord 9 shown in FIG. 5 and a printing chamber 7 in which the 3D printing machine 2 is located.

However, the system further comprises one or more ventilation ducts 12 involved in ensuring proper air circulation inside the printing chamber 7. The system is also equipped with an air filter 13 shown in FIG. 6, to clean the circulating air. The filter can be removable so that it can be washed or replaced when needed. The computer unit 14 and the power supply unit 15 for the whole system can make this system completely autonomous.

In yet another alternative embodiment of the present invention, the 3D printed tablet, granule, and capsule manufacturing system may include additional functionality to enable it to be used in more complex applications.

The system shown in Fig. 7 has a display 1 and a door 8, as well as a power supply 15 with a voltage stabilizer shown in FIG. 10 as well as the UPS 16 shown in FIG. 9, to ensure the smooth operation of the system.

An air conditioning and dehumidification system 17 is provided to control and maintain a suitable atmosphere in the printing chamber 7, as well as in the system as a whole, and ventilation ducts 12 allow ambient air to flow in when required. The air conditioning and drying system 17 is connected via one or more air supply and return ducts 18 to the printing chamber 7 and to the interior of the printing system as a whole, so that when this air conditioning system is turned on, it helps to create and maintain suitable conditions within the printing system.

The system also includes, shown in FIG. 8, an activated carbon filter 19 to absorb carbon dioxide and other harmful substances from the circulating air, while a vacuum pump 20 and a negative pressure tank 21 are involved in creating a vacuum or a suitable pressure, depending on the requirements.

The system may have a cleaning unit 67 comprising a wash bath 22, inside which the print head 5 is placed for washing and cleaning through the wash bath opening 23 shown in FIG. 12. In this case, the system includes a reservoir 24 of cleaning liquid for the print head 5 and a filter system 25 for this cleaning liquid for the head, ensuring that any contaminants from this liquid are removed after cleaning the print head 5.

The cleaning liquid may be selected from the following examples.

- Organic acids, surfactants, corrosion inhibitors that can be used on precious metals, stainless steel, non-ferrous metals, chromium-plated metals, glass, plastics, semi-precious stones, quartz, ceramics to remove lapping pastes, oxide films and tint colors such as hydroacetic acid.

- Acids, solubilizers, wetting agents for removing oxide films from non-ferrous metals without corroding metal surfaces and/or removing lime deposits, such as phosphoric acid.

- Alkalis, complexing agents, chelating agents, solubilizers, surfactants, surfactants for removing synthetic polymer resins, amorphous polymer resin mixtures, polishing and abrasive materials, e.g. bactericidal and antiviral activity.

- Neutral pH cleaners (pH 6-9) for cleaning aluminum and other soft metals, such as sterile or neutral detergents with NpH.

The cleaning fluid is preferably phosphate and chlorine free.

After 3D printing, the print head preferably passes through a stream of pre-filtered drying air that is heated shortly before entering the cleaning unit. This air can be filtered again with a suitable filter, for example in Europe it is required to filter with a HEPA H13 filter. The detergent can be used in combination with sonication, or solution spray technology, or as a foaming detergent.

The printing system will have a corresponding computer unit 14 shown in FIG. 11 to process and execute commands as previously reported.

Each system has, as noted above, a 3D printing machine 2 (as shown in Fig. 13) comprising a mechanical system 3 terminating in one or more printheads 5 for printing on a base system 4. The base system 4 can be fixed or movable in one or more directions depending on the axial degrees of freedom 26 . Similarly, in alternative embodiments of the present invention, the mechanical system may move in one direction, such as up and down, as shown in FIG. 15 in two directions, such as up-down and right-left, as shown in FIG. 16, or even have a different shape with more degrees of freedom, as shown in FIG. 17.

For example, the 3D printing machine 2 shown in FIG. 18 has a basic system 4 with a base 6 moving in two dimensions and a mechanical system 3 similarly moving in two dimensions. 3D printing of tablets, granules and capsules requires one or more mixtures of active substances and substances with plastic (binder) properties, depending on what final product is to be made.

The mixture 27 (FIG. 19), which may be solely the active substance without plastic or binder components or combinations thereof, may be in liquid form inside the cartridge 28, from where it enters the print head 5, or it may continuously enter the print head through the one shown in Fig. 14 tank 29 connected by a supply tube 30, for example, a dispensing tube, with a print head 5.

The number of reservoirs 29 connected to the print head 5 may be more than one. Additionally and alternatively, the cartridge 28 can be permanently connected to the head 5 and be replaced separately from other components and assemblies after it is empty. In another alternative, mixture 27 may be in the form of a strand.

Since the viscosity of the mixtures used varies depending on the product being manufactured, the cartridge 28 has a different cross-section at the outlet end. It may have a large cross-sectional area at the exit end 31, as shown in FIG. 20, or a small cross-sectional area as shown in FIG. 21. A cap 32 may be used to close the cartridge 28 from below, but the use of some suitable plug is also possible. At the top of the cartridge 28 there is a downwardly sliding cover which, under the pressure of the punch 34, as shown in FIG. 22 extrudes the mixture 27 into the print head 5. The cap 33 may be equipped with a suitable device, such as an RFID tag, so that the punch 34 can determine the exact position of the cap as well as read the relevant information about the cartridge 28.

Each cartridge may have a valve in its outlet nozzle to prevent loss of substance, drying out, etc. A valve is a device that regulates, directs or controls the flow of a fluid (gases, liquids, liquefied solids or suspensions) by opening, closing or partially obstructing various passageways. From a technical point of view, valves are fittings, but are usually discussed as a separate category. Through the open valve, fluid flows in a direction from higher pressure to lower pressure.

The simplest and most ancient valve is simply a free-hanging damper that falls to block the flow of a fluid (gas or liquid) in one direction, but is pushed to the open position by flow in the opposite direction. Such a valve is called a check valve because it prevents or "locks" flow in one direction. Modern check valves can control pressure or flow downstream of the valve and operate in complex automated systems. These valves may be spring-loaded, elastic - made of a silicone substance or other substance with similar elasticity characteristics, have a hole or notch (straight, curved, etc.) to allow the substance to exit the cartridge when the stem presses on the plug. In this case, the protective cap on the cartridge nozzle can be equipped with a small needle. Alternatively, in the case of cutouts on the valve, at least one blade matched to the shape of the cutout, such as a curved shape, may be used.

Valves can be of various types, for example: a device such as a dispenser to control the flow if the substance loaded inside the cartridge is dry (solid), such as powders, granules, conglomerates, etc., or an on/off valve (valve valves, ball valves , needle valves, etc.) for use with liquids. Valves can be pressed into cartridge nozzles or glued. In the case of solids, the valve mechanism may form the bottom of the cartridge itself.

Each system may be equipped with more than one cartridge 28 with the same or different mixtures 27 and with the same or different end configuration 31.

Cartridges 28 are mounted in holders 35 which may be oblong or even rotatable as shown in FIG. 23. Holders 35 are mechanically driven by a servomotor or other suitable device to bring the desired cartridge 28 into loading position so that punch 34 pushes the appropriate amount of mixture 27 into the print head to start the process. The holders 35 may be arranged in the 3D printing machine 2 as shown in FIG. 24 and pass over the base system 4 to start the process, or they can be fixed at the point where the arm 36 shown in FIG. 17 receives these cartridges 28 at the right time. The size of the holders 35 and the number of cartridges 28 that can be mounted on them are only limited by space in the system.

Cartridges may have different sizes or shapes depending on the manufacturing method. They can be larger for mass production, such as in factories, medium sized for pharmacies or hospitals, or smaller for desktop or mobile use.

Cartridges are preferably made using materials that do not interact with or contaminate in any way the substance loaded into such a cartridge (example: oxidation of metal in contact with aqueous or alcoholic solvents).

These materials include a wide range of metals such as stainless steel, aluminum alloys, and in any case, membrane-like coating technologies can be used to isolate the substance contained in the cartridge from any metal that could potentially damage this substance, so that in theory it is possible use any metal for the cartridge. Examples of such technologies include the following: electroplating, spray or dip painting, ceramic coating, or even internal extrusion of a suitable polymeric membrane.

These materials include a wide range of plastics, but in this case care should be taken to avoid contamination that may result from reaction (for example, alcohol solvent with some types of polyethylene-based plastics), or the emission of volatile gases, and / or oily substances, contained in the plastic itself (for example, in some materials based on polyethylene, polyurethane and polyester resins).

In any case, a wide variety of plastics can be selected for use, such as epoxy materials, some types of nylon, polyethylene-based materials, and an even greater variety of composite materials (for example, injection molded nylon with glass microspheres, or epoxy resin). combined with ceramic microspheres).

In the case of plastics, the technologies mentioned earlier can be used either to further enhance the protection of the substances in the cartridge, or to allow the use of unsuitable materials by forming an inner layer of a protective material specially selected for a particular job (for example, double extrusion of polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG) and acrylonitrile-butadiene-styrene copolymer (ABS. Such technologies are often used in the manufacture of plastic disposable bottles for plain and soda water). Harder or non-extrusionable plastics can be temporarily made electrically conductive and electroplated, or simply sprayed or dip-coated with a suitable agent.

In any case, glass and ceramics can be used.

Preferably, the cartridges use a variety of identification methods (RFID or other chips, bar code, or other methods) to communicate with a reader 66 (FIG. 41) located on the cartridge holder or reservoir. This information allows the system to recognize the ingredients in the cartridge so that you can choose the correct volume, or recognize the shelf life of each product, the remaining volume in each cartridge, frequency of use and other data. This information can be used as statistics to optimize production and, if required, to automate the supply chain by ordering substances in a timely manner to replace or refill cartridges.

The printhead 5 is a device designed to apply the required amount of mixture 27 to produce the appropriate granule, tablet or capsule. This printhead 5 has, as shown in FIG. 26, a nozzle 37 from which the mixture 27 exits, and a print head housing 38, for example in the form of a cylinder with a shell 39. The print head also has, as shown in FIG. 28(a) a support 40 by which it is held either in the head holder 41 shown in FIG. 24, or in hand 36.

The printhead may be thermal, as shown in FIG. 25 to improve temperature control of the mixture 27. To this end, the head has a heated body 42 with heat dissipation recesses 43 and may also be provided with a cooling fan 44 shown in FIG. 26 on the back of the head for further improved thermal management.

In yet another alternative, the printhead 5 may be equipped with an energy emitter 45, in this example shown in FIG. 27 light curing lamp mounted on arm 46 for use with blends 27 that require it.

In another alternative, the print head 5 may have a liquid nitrogen spray nozzle for direct cooling of the printed article.

In one alternative embodiment of the present invention, the print head 5 may be provided with an agitation and/or discharge tool 47, in this example the one shown in FIG. 22 an auger rotated continuously or intermittently by a servomotor and agitating the mixture inside the print head 5. With this approach, the mixture 27 will maintain the correct viscosity depending on the particular application for which it is being used.

In yet another alternative embodiment of the present invention, the screw 47 may have, as shown in FIG. 31 a compressible head 48 which, in addition to agitating the mixture 27, compresses it suitably by removing air. To do this, in the upper part shown in Fig. 32 of the head 48, there is an opening 51 through which the solvent, the active drug substance or the mixture as a whole is introduced, and an opening 50 from which air is expelled by compression. The holes can be closed by the ones shown in FIG. 33 plugs 52 when the use of these holes is not required. Compressible head 48 can be made from stainless steel, thermoplastic materials, and composite materials such as para-aramid synthetic fibers or shape memory metals, as shown in FIG. 34.

In a further alternative, print head 5 may have an auger 48 with or without a compressible head 48, it may or may not have a heated housing 42, and may have more than one nozzle 37 as shown in FIG. 35 so that 3D printing can take place at a higher speed.

Such 3D printing of tablets, granules and capsules is carried out, as noted above, in the FIG. 29(b) base 6 installed on base system 4.

The print base 6 may also be temperature controlled and may have formatted print areas 49 as seen in FIG. 29(a) and FIG. 36 to make a tablet, granule or capsule by applying mixture 27.

After the 3D printing is completed, the products are removed from the base 6 and the base is returned to the base system 4 for the subsequent process. The base 6 may have, as shown in FIG. 30 air ducts 50 allowing natural or forced air flow through the base 6 in order to reduce the evaporation of moisture from the manufactured products.

In FIG. 37 shows an example of a heated base system 4. The print base system 4 comprises a thermal control system 68 with air ducts 53 and channels 54 for directing the thermal control agent, as well as a fan 55.

The base 6 for printing is mounted on the holder 57, so that it can be put on and removed from this holder.

In FIG. 38 shows an additional example of a basic system 4 in which the fan 55 is located on the side of the print base 6.

In FIG. 39 shows a base system 4 including ejector pins 56. FIG. 39(a) the ejector pins 56 are in a passive position, covering holes 58 in the formatted print areas 49. The ejector pins 56 are located on a plate 59 that can move vertically. When the plate has moved up, the extraction pins 56 are in the extraction position as shown in FIG. 39(b). These ejection pins 56 extend upward from holes 58 and can eject printed products (not shown explicitly) from formatted print areas 49.

In FIG. 40 shows an embodiment of a squeezable cartridge 28 in a first position (a), a second position (b), and a third position (c).

The cartridge 28 may have a double housing: an outer rigid housing 60 of a cylindrical shape and an inner reservoir 61 made of a compressible material. There is a plug 62 at the top of the housing which can be pressed down to push printing matter (not shown explicitly) from the bottom end 31 of the cartridge 28.

The cartridge 28 can be used as a print head when the cartridge is mounted on a mechanical system and when there is a print nozzle (not shown) mounted on the lower end 31.

In FIG. 41 shows cartridge holders 35 mounted in magazine assembly 63. Each cartridge holder 35 can receive a cartridge 28. Magazine assembly 63 includes rotary drives 64 and a belt 65 for moving cartridges 28. Each holder 35 includes a reader 66 for reading cartridge 28 identification information.

When the cartridge 28 is needed to supply a material to a printhead (not shown), the top cap 69 is removed by the top cap removal mechanism 70. The holder 35 adjacent to this top cap removal mechanism 70 is shown without the cartridge for clarity. In addition, the bottom cap 71 is removed by the bottom cap removal mechanism 72 . The cartridge then moves to an unload position 73 where holder 35 tilts with cartridge 28. The cartridge is brought into contact with a push rod actuator 74 which forces a predetermined amount of material from cartridge 28 into the print head.

After discharging the material, the cartridge 28 can be cleaned in the wash bowl 75, which can be lifted by the wash bowl drive 76 for this purpose.

It should be noted that the description of the present invention has been made with reference to examples of embodiments of the invention, however, the invention is not exhausted by these examples. Any changes or modifications to the shape, dimensions, structure, materials and components used in the manufacture and assembly, unless they constitute a new creative stage and do not contribute to the technical development of the already known, are considered to fall within the scope and objectives of the present invention.

Aspects of the present invention

I. System for the manufacture of tablets, granules and capsules by 3D printing, containing a display (1), a base (11) with an integrated computer unit (14), a power cord (9) and a machine (2) for 3D printing in a chamber ( 7) with a door (8), with a mechanical arm system (3) movable in one or more directions, with a base system (4) movable in one or more directions and carrying a base (6), and with a printhead (5) on the system (3) of a mechanical arm, with a nozzle (37) and a cylinder (38) of a head with a shell (39), characterized in that the print head (5) supplies the prepared mixture (27) for 3D printing to the base (6) tablets, granules and capsules.

II. System for the manufacture of tablets, granules and capsules by 3D printing, according to aspect I, characterized in that it has ventilation ducts (12) and air filters (13) for circulating and cleaning the air inside the chamber (7).

III. System for the manufacture of tablets, granules and capsules by 3D printing, according to aspect I, characterized in that it has a power supply unit (15) with a voltage stabilizer and an uninterruptible power supply (16).

IV. The system for the manufacture of tablets, granules and capsules by 3D printing, according to aspect I, characterized in that through the air ducts (18) for supplying and returning air to the chamber (7) for printing, an air conditioning and drying system (17) is connected.

V. System for the manufacture of tablets, granules and capsules by 3D printing, according to aspect I, characterized in that it has an activated carbon filter (19) to absorb carbon dioxide.

VI. System for the manufacture of tablets, granules and capsules by 3D printing, according to aspect I, characterized in that it has a vacuum pump (20) and a reservoir (21) with negative pressure to create a vacuum.

VII. System for the manufacture of tablets, granules and capsules by 3D printing, according to aspect I, characterized in that it has a rinsing bath (22), a rinsing hole (23) connected to a reservoir (24) with a cleaning liquid and a filtration system (25) cleaning fluid to clean the print head (5).

VIII. System for the manufacture of tablets, granules and capsules by 3D printing, according to aspect I, characterized in that the mixture (27) enters the print head (5) through the cartridge (28).

IX. System for the manufacture of tablets, granules and capsules by 3D printing, according to aspect I, characterized in that the cartridges (28) are mounted on a holder (35).

X. System for the manufacture of tablets, granules and capsules by 3D printing, according to aspect I, characterized in that the mixture (27) enters the print head (5) through the supply tube (30) from the reservoir (29).

XI. System for the manufacture of tablets, granules and capsules by 3D printing, according to aspect I, characterized in that the mixture (27) is in the form of a thread.

XII. Cartridge for use in a 3D printed tablet, granule and capsule manufacturing system according to aspect I, characterized in that it contains a printable mixture (27) and has a capped end (31) and a removable cap (33 ) on the top side.

XIII. A printhead for use in a 3D printed tablet, granule and capsule manufacturing system according to aspect I, characterized in that it has a heated housing (42) with recesses (43) and a cooling fan (44) for controlling the temperature of the mixture (27 ).

XIV. A printhead for use in a 3D printed tablet, granule and capsule manufacturing system according to aspect I, characterized in that it has a photopolymer lamp (45) on the arm (46).

XV. A printhead for use in a 3D printed tablet, granule and capsule manufacturing system according to aspect I, characterized in that it has a nozzle for spraying liquid nitrogen.

XVI. A print head for use in a 3D printed tablet, granule and capsule production system according to aspect I, characterized in that it carries a screw (47) driven by a servomotor to stir the mixture (27).

XVII. A printhead for use in a 3D printed tablet, granule and capsule manufacturing system according to aspects I and XV, characterized in that the screw (47) has a compressible head (48) for compressing the mixture (27) with holes (49, 50 ) for solvent inlet and air outlet, respectively.

XVIII. A printhead for use in a 3D printed tablet, granule and capsule manufacturing system according to aspect I, characterized in that it has more than one nozzle (37).

XIX. A print base for use in the 3D printing system according to aspect I, characterized in that it has formatted areas (49) for printing in order to form tablets, granules and capsules.

XX. A printing base intended for use in the 3D printing system according to aspect I, characterized in that it has air ducts (50) to create a natural or forced air flow on the base (6).

Numerical designations

display 1

printing machine 2

mechanical system 3

base system 4

print head 5

print base 6

camera 7,

door 8,

power cord 9

computer 10

base 11

ventilation ducts 12

air filter 13

computer block 14

power supply 15

voltage stabilizer 15

uninterruptible power supply 16

air drying system 17

return ducts 18

carbon filter 19

vacuum pump 20

negative pressure tank 21

washing bath 22

rinsing bath opening 23

reservoir 24

filter system 25

axial degrees of freedom 26

mix 27

cartridge 28

tank 29

feeding tube 30

end 31

cap 32

cover 33

punch 34

holders 35

hand 36

nozzle 37

head cylinder 38

shell 39

support 40,

head holder 41

heated body 42

grooves 43

cooling fan 44

photopolymerization lamp 45

hand 46

mixing and/or unloading tool (47)

compression head 48,

formatted areas for printing 49

hole 49

hole 50

hole 51

plugs 52

air ducts 53

channels 54

fan 55

extraction pins 56

base holder 57

holes 58

plate 59

hard case 60

inner tank 61

plug 62

store knot 63

rotary drives 64

tape 65

reader 66

cleansing knot 67

thermal management system (68)

top cap 69

top cap removal mechanism 70

bottom cap 71

lower cap removal mechanism 72

unloading position 73

push rod drive 74

wash bowl 75

bowl drive 76

Claims (38)

1. System for the manufacture of pharmaceutical products selected from tablets, granules or capsules by 3D printing, containing a machine (2) for 3D printing with a mechanical system (3), movable in one or more directions, at least one print head (5) with at least one nozzle (37) moved by means of a mechanical system (3) and a base system (4) on which a printing base (6) is located, designed to receive the prepared mixture (27) applied by the print head (5), while the system contains at least one holder (35) for holding the cartridge (28), and the print head (5) is temperature-controlled, while the print head (5) contains a housing (42) with recesses, ribs or channels for directing the temperature control agent, wherein the print head (5) comprises a mixing tool (47), in particular a screw, located in the print head housing (38, 42), wherein the mixing tool (47) is i is at least partially compressible, in particular, the tool (47) for mixing contains a compressible head (48). 2. The system according to claim 1, which contains a supply tube (30) for establishing a fluid connection between the cartridge installed in the holder (35) and the print head (5). 3. The system according to claim 1 or 2, which contains a magazine assembly (63) with at least one holder (35), preferably with a plurality of holders (35), in particular, the magazine assembly (63) is movable, so that the holder ( 35) has the ability to move. 4. The system according to claim 3, in which the magazine unit (63) contains a drive (64), in particular a servomotor, a pneumatic drive, a hydraulic drive, a chain drive or a magnetic drive. 5. The system according to any one of paragraphs. 1-4, which contains at least one movable push rod, preferably attached to the holder (35), for emptying the cartridge (28). 6. The system according to any one of paragraphs. 1-5, which comprises an opening device, preferably connected to the holder (35), for opening the cartridge (28), in particular a needle or mechanism for removing the cap, and/or a closing device, preferably connected to the holder (35), for closing the cartridge (28). 7. The system according to any one of paragraphs. 1-6, which contains a reader (66), preferably connected to the holder (35), for identifying the identification mark located on the cartridge (28). 8. The system according to any one of paragraphs. 1-7, in which the printhead (5) includes a housing (38, 42) with an opening for receiving fluid from the cartridge. 9. The system according to any one of paragraphs. 1-8, which contains an energy emitter (45) connected to the print head (5), in particular a photopolymer lamp, or an infrared emitter, or a nozzle for spraying liquid nitrogen, or a nozzle for supplying compressed air, or a nozzle for supplying water vapor. 10. The system according to any one of paragraphs. 1-9, in which the print head (5) contains a plurality of nozzles (37). 11. The system according to any one of paragraphs. 1-10, which contains a cleaning unit (67) for cleaning the print head and/or cartridge, in particular, containing a flushing bath (22) and/or flushing hole (23) connected to a reservoir (24) for cleaning fluid and/or with filter system (25) for cleaning liquid. 12. The system according to any one of paragraphs. 1-11, which contains a thermal control system (68) for controlling the temperature of the substrate (6) for printing. 13. The system according to claim 12, in which the basic system (4) contains air ducts (53) and/or channels (54) for guiding the thermostatic agent. 14. The system according to any one of paragraphs. 1-13, which contains a base (6) for printing, containing formatted areas (49) for printing for molding pharmaceutical products, in particular convex recesses. 15. The system according to any one of paragraphs. 1-14, which contains a base (6) for printing containing a thermal conductor, and if the base (6) for printing contains formatted areas (49) for printing, then the specified conductor is located on the side opposite to the side where the formatted areas are located (49) for printing. 16. The system according to any one of paragraphs. 1-15, which contains a printing base (6) having a coating, in particular a glazed ceramic coating. 17. The system according to any one of paragraphs. 1-16, in which the base system contains a mechanism for removing products. 18. The system of claim. 15, in which the base system contains a mechanism for removing products containing movable ejection pins (56) or gas nozzles connected to formatted areas (49) for printing base (6) for printing. 19. The system according to any one of paragraphs. 1-18, in which the base system (4) includes a base holder (57) for receiving a base (6) for printing. 20. The system according to any one of paragraphs. 1-19, which contains a chamber (7), in particular with a door (8), for setting a controlled temperature, while the system is equipped with individual units, such as - vacuum system with vacuum pump (20), - air conditioning system, - air filter (13), - ventilation ducts (12), - system (17) for drying air and - filter (19) with activated carbon. 21. Method for the manufacture of pharmaceutical products selected from tablets, granules or capsules, by 3D printing using a system according to any one of paragraphs. 1-20, wherein the method includes: - providing at least one pharmaceutical substance in at least one cartridge, - installation of the cartridge in the holder, - establishing a fluid connection between the cartridge and the print head so that the pharmaceutical substance can leave the print head through the print head nozzle, - moving the print head in accordance with the 3D printing program and supplying the pharmaceutical substance to the print base. 22. The method of claim. 21, in which the cartridge is moved to the print head and move along with the print head. 23. The method of claim. 21, in which the amount of at least one pharmaceutical substance is dispensed from the cartridge into the print head, while the substance is mixed in the print head, in particular, several pharmaceutical substances are mixed. 24. The method according to claim 23, wherein a plurality of cartridges containing different pharmaceutical substances are installed in the magazine and the magazine is moved relative to the print head to a position in which the selected cartridge is fluidly connected to the print head, and a metered amount of the corresponding pharmaceutical substance is fed into the print head, thereby preparing the pharmaceutical mixture in accordance with the pharmaceutical formulation. 25. The method according to any one of paragraphs. 21 to 24, in which the print base (6) having formatted print areas is placed on the print base system (4). 26. The method according to any one of paragraphs. 21-25, in which the print head (5) is cleaned after printing. 27. The method according to any one of paragraphs. 21-26 which includes the step of providing at least one substance in at least one cartridge, wherein the substance contains at least one of fat mass, starch, flour, gelatin, sweetener, natural flavor, artificial flavor and color. 28. The method according to any one of paragraphs. 21-27, wherein the pharmaceutical agent comprises at least one of an antipyretic, an anesthetic, an antimalarial, an antibiotic, an antiseptic, a mood stabilizer, a hormone replacement agent, an oral contraceptive, a stimulant, an anxiolytic, and/or a statin.

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