DE102023200219A1 - Process for the additive manufacturing of a medical and/or pharmaceutical product and corresponding product - Google Patents

Abstract

A method for the additive manufacturing of a medical and/or pharmaceutical product and a correspondingly manufactured medical and/or pharmaceutical product are described. At least one powder (P2) which has at least one pharmaceutical active ingredient is provided. One or more product layers (B1, B2, B3) of the product to be manufactured are produced, wherein to produce a product layer (B3) at least one powder portion (A3) of the at least one powder (P2) is applied by electrostatically charging the powder portion (A3), an application unit (7) is electrostatically charged at least in some areas, and the electrostatically charged powder portion (A3) is picked up by means of the application unit (7) which is electrostatically charged at least in some areas and transferred to an application surface (F). The applied powder portion (A3) is solidified.

Description

The invention relates to a method and device for the additive manufacturing of a medical and/or pharmaceutical product. The invention also relates to a medical product and a pharmaceutical product.

A pharmaceutical product or a pharmaceutical agent or medicinal product is a substance or preparation that is used to cure or alleviate illnesses or to ensure that an illness or symptoms do not occur in the first place. A pharmaceutical product can be, for example, a tablet, a dragee or a suppository. A medical product or medical device is a product with a medical purpose that is intended for use in humans and has a primarily physical effect. Examples of medical devices are prostheses, implants, stents and/or medical tools. Medical and/or pharmaceutical products, particularly medicinal products, are regularly manufactured using mass production processes. However, it has proven advantageous to adapt pharmaceutical and/or medical products to individual patients, for example by adapting an active ingredient composition to the patient's clinical picture and other patient characteristics, particularly height, weight, age and/or intolerances. There are already approaches to additively manufacture medical and/or pharmaceutical products, for example using the powder bed process or by printing hardenable pastes.

It is an object of the present invention to improve a method for the additive manufacturing of medical and/or pharmaceutical products, in particular to provide a method that enables a particularly flexible and individualized as well as economical production of these products.

This object is achieved by a method with the steps specified in claim 1. At least one powder that has at least one pharmaceutical active ingredient is provided. At least one product layer of a product to be manufactured is produced, wherein at least one powder portion of the at least one powder is applied to produce a product layer. To apply a powder portion, the powder portion is electrostatically charged, an application unit is electrostatically charged at least in some areas, in particular selectively, and the electrostatically charged powder portion is picked up by means of the application unit that is electrostatically charged at least in some areas and transferred to an application surface. The applied powder portion is solidified. Preferably, several product layers are produced.

According to the invention, it was recognized that electrophotographic powder application is particularly suitable for the additive manufacturing of medical and/or pharmaceutical products. Electrophotographic powder application allows targeted application of the at least one powder with the at least one pharmaceutical active ingredient. This allows the at least one pharmaceutical active ingredient to be applied specifically to the corresponding location on the pharmaceutical and/or medical product. The pharmaceutical and/or medical product can be easily and flexibly adapted to the respective application, in particular to the needs of a particular patient. A particular advantage of electrophotographic powder application is that only the amount of powder required for the manufacture of the pharmaceutical and/or medical product is applied. Powder consumption is thus minimized. This is particularly advantageous for expensive powders, especially for expensive pharmaceutical active ingredients. The amount and arrangement of the at least one pharmaceutical active ingredient can be specifically and precisely adjusted. Additive manufacturing has proven to be particularly suitable for medical products in the form of prostheses and/or implants, which can be specifically adapted to the patient's body structure.

Here and in the following, a medical and/or pharmaceutical product is also referred to as a product for the sake of simplicity. Pharmaceutical active ingredients are also referred to as active ingredients for the sake of simplicity.

The method according to the invention is particularly suitable for the parallel production of several medical and/or pharmaceutical products. For example, several pharmaceuticals, in particular several tablets, can be produced in parallel. In particular, different medical and/or pharmaceutical products can be produced in different areas of the application area by applying the respective powder proportions to these areas of the application area. The parallel production of several medical and/or pharmaceutical products, for example several tablets, from the same powders has proven to be particularly suitable. The powder application for the different products can take place simultaneously. Particularly preferred is the parallel production of similar products, for example a plurality of similar tablets.

The at least one powder can in particular be a pharmaceutical active ingredient that is present in powder form and can be processed. The at least one powder can also be a powder mixture, for example a mixture containing at least one active ingredient powder and another powder, in particular a ceramic powder, a metal powder and/or a polymer powder, preferably a mixture containing at least one active ingredient powder and a polymer powder. An active ingredient powder can consist of pure powdered active ingredient. The use of a combination of at least one pharmaceutical active ingredient and a carrier polymer has proven to be particularly suitable. Regardless of the type of active ingredient, good processability of the at least one powder can thus be ensured, in particular during electrophotographic powder application and/or subsequent solidification. Biocompatible polymers have proven to be particularly suitable carrier polymers. Powders made of surgical stainless steel and/or titanium have proven to be particularly suitable for medical products, in particular prostheses.

Biocompatible and/or pharmaceutical polymers have proven to be particularly suitable polymers, for example cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), methylcellulose (MC), ethylcellulose (EC), hydroxyethylcellulose (HEC), hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP), shellac, sodium carboxmethylcellulose (SCMC), zein and/or Eudragit, in particular Eudragit L-100-55. These polymers can be used in particular as carrier polymers for pharmaceutical active ingredients. Eudragit L-100-55 has proven to be particularly suitable for electrophotographic powder application.

Polymer powders and/or ceramic powders can be directly electrostatically charged. Dielectric components can be added to metallic powders to create an electrostatic charge.

For example, metallic powders can have a coating made of a dielectric material. The at least one powder can have further components, for example binders and/or additives. Suitable additives are in particular flow aids and/or charge control substances. Charge control substances can support charging of the powder, in particular triboelectric charging of the powder.

The process is particularly suitable for multi-material processing. By providing different powders, the process can be used to combine different materials and/or active ingredients into one product. The result is a one-piece product that has different materials and/or different active ingredients and/or different active ingredient concentrations in certain areas. Subsequent joining of prefabricated product components made of different materials and/or active ingredients is not necessary. For example, a combination of different commercially available materials, in particular commercially available polymer materials, is possible. Materials and/or active ingredients with very different properties can be combined particularly advantageously, in particular with very different mechanical and/or thermal properties, for example with very different melting temperatures. This makes it possible to manufacture products with properties that can be specifically adjusted, in particular locally adjusted. In particular, an adjustable, in particular delayed, release of active ingredients can be achieved. Different active ingredients can be released at different times and/or with different release rates.

The electrostatic charging of the powder components can be carried out by means of the triboelectric effect and/or gas discharge. The charging based on the principle of gas discharge can be carried out in particular with a corona wire and/or a scorotron. A scorotron, also called a corona grid, has proven to be particularly suitable because it enables control of the electric acceleration field for the ions generated by gas discharge. This enables a more precise setting of the desired surface potential of the powder layer to be charged. To generate different polarities, a powder charging unit can have a reversible voltage source. Using the reversible voltage source, a corona wire and/or a scorotron in particular can be charged with electrical voltage of different polarity.

The application unit can be electrostatically charged at least in certain areas, in particular selectively. This enables selective powder application. Electrophotographic methods have proven to be particularly suitable for electrostatic charging in certain areas, in particular selectively. For example, the application unit has a photoconductive layer, in particular a layer of arsenic(III) selenide (As ₂ Se ₃ ). A photoconductive layer is dielectric, but becomes conductive in the exposed area when exposed to suitable radiation. This is referred to as the photoelectric effect. The photoconductive layer of the application unit is also referred to below as the photoconductor layer. The photoconductive layer can be charged by gas discharge, in the The photoconductive layers can be electrostatically charged, particularly with the help of a corona wire and/or a scorotron. By specifically exposing individual areas of the electrostatically charged photoconductive layer, the exposed areas can be selectively discharged. The exposure is carried out using a light-emitting diode, for example. For a photoconductive layer made of arsenic(III) selenide, exposure with a wavelength of around 613 nm has proven to be particularly suitable.

In order to absorb the electrostatically charged powder portion, the powder particles of the powder portion are electrostatically attracted by the application unit, which is electrostatically charged at least in some areas. Depending on the relative polarity of the charge of the application unit and the powder portion, the powder particles adhere to electrostatically charged areas or to selectively discharged areas of the application unit, in particular a photoconductive layer of the application unit. The electrostatic charging of the powder portion and the absorption of the electrostatically charged powder portion by means of the application unit is also referred to as a development step.

To support the absorption of the electrostatically charged powder portion, the application unit preferably has a conductive base body. The base body can be made of aluminum, for example. The conductive base body of the application unit can be subjected to a receiving voltage that promotes the attraction and adhesion of the powder portion. The receiving voltage has a polarity that is opposite to the charge of the powder portion. The application unit preferably has a reversible application unit voltage source. By means of the reversible application unit voltage source, the application unit, in particular its base body, can be subjected to a receiving voltage with a polarity that is opposite to the respective charge of the powder portion. The size and polarity of the receiving voltage can be specifically adapted to the powder portion to be absorbed, in particular to a mass of the powder particles and/or their electrostatic charge.

The powder portion picked up by the application unit is transferred to an application surface. Transferring to the application surface includes in particular transferring the application unit with the adhering powder portion into a construction space and depositing the powder portion on the application surface. Transferring the powder portion, in particular depositing the powder portion, onto the application surface is also referred to as a printing step. The application surface is the surface onto which the powder portion is to be applied to produce the respective product layer. For the first product layer, this can in particular be a construction platform of the construction space and/or a substrate on which the product is to be produced. It is also possible for a product base body, for example a prosthesis base body, to be provided on which the further product layers are manufactured. The application surface can also be a surface of a provided product base body. For further product layers, the application surface is formed by the previously produced product layer.

For transfer into the construction space, the application unit can be displaced, in particular translationally displaced. Preferably, the application unit can be displaced in at least two translational degrees of freedom, in particular in the direction of a surface normal of the application surface and in a direction perpendicular to this. This enables simple and precise displacement of the application unit with the powder portion adhering to it into the construction space and simple and precise delivery relative to the application surface. The positioning of the application unit in the direction of the surface normal of the application surface can be carried out in particular depending on a product height already produced. Preferably, a distance of the application unit to the application surface is adjustable independently of product layers already produced. For displacement, the application unit can be arranged on a positioning system, for example. A linear axis and a precision lifting table, for example, have proven suitable for the translational movement and delivery relative to the construction space or to the application surface.

Preferably, the adhesion of the powder portion to the application unit is supported, particularly during transfer into the construction space, by a holding voltage applied to the application unit, particularly its base body. The holding voltage can in particular correspond to the receiving voltage. The holding voltage can be generated, for example, using the application unit voltage source.

Preferably, the application unit, in particular its base body, can be subjected to a deposition voltage. The deposition voltage particularly preferably has the same polarity as the electrostatic charge of the powder portion to be transferred. The deposition voltage supports the deposition of the powder portion onto the application surface. The deposition voltage can be generated, for example, by means of the application unit voltage source. To deposit the powder portion, the application unit voltage source can advantageously be reversed in order to switch from a holding voltage to the deposition voltage.

The powder portion transferred to the application surface is solidified to produce the respective product layer. For example, the applied powder portion can be thermally solidified. For this purpose, the powder portion or a component of the powder portion, for example a carrier polymer and/or a binder, can be melted. Thermal solidification is particularly suitable for processing polymer powders. The construction space can be heated for melting, in particular by means of heating rays and/or lasers. Melting of the powder component or at least one component thereof can also be carried out selectively, for example by electron beam melting and/or selective laser sintering. Solidification can also be carried out using alternative methods, for example by means of binder jetting. This enables solidification without melting the powder, which is particularly advantageous for high-melting powders, for example metallic and/or ceramic powders.

By producing the at least one product layer, in particular the multiple product layers, layer by layer, the product as a whole can be completed. However, after the product layers have been produced layer by layer, further manufacturing steps, in particular post-processing steps, can also be provided. For example, by producing the product layers layer by layer, a green part can be produced, from which the product is completed using suitable post-processing steps. In particular, if applied powder components are not solidified or not completely solidified, the product layers can be further solidified in a post-processing step after the product layers have been produced layer by layer to complete the product. For example, a previously produced green part can be debindered and/or sintered.

After a portion of the powder has been applied, any electrostatic charges that may still be present on the application unit, particularly its photoconductive layer, are eliminated. To do this, the photoconductive layer of the application unit can be fully exposed.

According to a preferred aspect of the method, at least two powders are provided and used to produce the at least one product layer. The preparation and processing of at least two powders enables a particularly flexible combination of different materials and/or active ingredients. When producing the product layers, powder fractions from different powders can be used to combine different materials, in particular different pharmaceutical active ingredients, in the product. For example, different product layers can be made from powder fractions of different materials. It is also possible to combine different materials in one product layer. For example, several powder fractions of different powders can be applied sequentially to produce a product layer.

Other powders provided can contain a pharmaceutical active ingredient, in particular another pharmaceutical active ingredient. It is also possible for other powders to contain no pharmaceutical active ingredient, for example to produce a coating or encapsulation of an active ingredient and/or a product base body. For example, a product base body, in particular a prosthesis base body, can be produced without a pharmaceutical active ingredient. One or more pharmaceutically active areas can be produced on a surface of the product base body from a powder with at least one pharmaceutical active ingredient.

The at least two powders are used in particular for the production of different product areas. Different materials and/or pharmaceutical active ingredients and/or active ingredient concentrations can be applied in a targeted manner in different product areas. It is also possible to apply the at least two powders in a common product area. For example, this can be used to create mixing areas in which different powders, in particular different carrier polymers and/or pharmaceutical active ingredients, are combined. This makes it possible in particular to integrate new active ingredient combinations into the medical and/or pharmaceutical product.

Here and in the following, a product area is understood to be a sub-area of the pharmaceutical and/or medical product to be manufactured. A product area can be, for example, a product base body, an area applied to a surface of a product base body, an area with a specific active ingredient and/or active ingredient concentration. Different product areas can be manufactured with different powders, for example. A product area containing at least one active ingredient is also referred to as an active ingredient area or, in particular in the case of medical products, as a pharmaceutically active product area. A product area can also be a transition area between two other product areas.

According to a preferred aspect of the method, the at least two powders comprise different pharmaceutical active ingredients and/or different active ingredient concentrations. This enables a particularly flexible combination of different active ingredients and/or active ingredient combinations. For example, different product areas with different active ingredients can lead to a more targeted release of active ingredients. In particular, it is possible to apply different active ingredients at different times, with different release rates and/or to different parts of the patient's body. In particular, it is possible to provide different product areas, in particular different pharmaceutically active product areas, with different active ingredients and/or different active ingredient concentrations on a medical product, for example on a prosthesis and/or an implant. In this way, the active ingredients required in each case can be applied specifically to the appropriate location, for example to promote the growth of a certain part of an implant and/or a prosthesis onto human tissue and to prevent it from growing elsewhere. In particular when manufacturing a pharmaceutical product, the use of different active ingredients and/or active ingredient combinations has the advantage that different active ingredients can be released at different times and/or with different release rates.

According to a preferred aspect of the method, powder fractions of the at least two powders are applied to the application surface to produce a product layer. The different powder fractions can be applied to the same surface area of the application surface or to different surface areas of the application surface. Different surface areas can be disjoint or overlap. This enables a combination of different powders, in particular different active ingredients and/or active ingredient concentrations, in individual product layers. Different powders can be combined particularly flexibly. This increases the design freedom and flexibility in the manufacture of the product. In particular, it is not necessary to manufacture entire product layers from just one material, in particular with just one active ingredient, an active ingredient combination and/or an active ingredient concentration. Different materials and/or active ingredients can be arranged and/or combined in a targeted manner in certain product areas. For example, an active ingredient area can be coated to enable the release of the active ingredient to be as delayed as possible.

According to a preferred aspect of the method, a transition area with a graduated transition between the different powders is produced between product areas that are made from different powders. In particular, a proportion of the respective powder can gradually increase or decrease. For example, a transition area between two product areas that are made from a first powder or a second powder can have a gradual increase in the proportion of the second powder from the product area of the first powder to the product area of the second powder with a simultaneous corresponding decrease in the proportion of the first powder. This enables a targeted transition between different active ingredients and/or active ingredient concentrations. The transition area allows particularly flexible and specifically adjustable active ingredient combinations, in particular with regard to their sequential delivery to the patient. The size of the transition area can be flexibly selected.

The graduated transition can be created, for example, by applying product layers consecutively. For example, the powder composition used to produce successive product layers can be individually adapted from product layer to product layer.

Electrophotographic powder application advantageously enables the production of graduated transitions within a product layer. For this purpose, for example, different powders, the proportion of which is to be gradually adjusted, can be electrostatically charged to different degrees. Additionally or alternatively, areas with different levels of electrostatic charge can be created on the application unit, for example by discharging the application unit to different degrees in certain areas. This allows the adhesion of the respective powders to be controlled in a targeted manner, for example to apply different amounts of powder to individual areas of the application surface.

According to a preferred aspect of the method, the at least one powder comprises a carrier polymer and the at least one active ingredient. The use of a carrier polymer has proven to be particularly suitable. In particular, the method is not limited to active ingredients that can be electrostatically charged and/or solidified, in particular melted. The use of the carrier polymer extends the applicability of the method to all common pharmaceutical active ingredients.

Particularly preferably, the at least one pharmaceutical active ingredient in the at least one powder has a proportion of 1 wt.% to 50 wt.%. The percentage weight of the active ingredient can be, for example, about 1 wt.%, 5 wt.%, 10 wt.%, 15 wt.%, 20 wt.%, 25 wt.%, 30 wt.%, 35 wt.%, 40 wt.%, 45 wt.% or 50% by weight. The active ingredient concentration can be flexibly adapted to the respective application.

According to a preferred aspect of the method, a product base body is provided on which the at least one product layer is produced, preferably several product layers are produced. This makes it possible to provide, in particular to manufacture, a product base body, for example an implant and/or prosthesis base body, independently of the application of the at least one powder with the at least one pharmaceutical active ingredient.

For example, product base bodies can be made of materials that cannot be processed in parallel with the at least one pharmaceutical active ingredient, for example because they are processed at very high temperatures. The product base body can preferably be made of ceramic and/or metal, in particular titanium. The provision, in particular manufacture, of the product base body does not affect the processability of the at least one powder with the at least one pharmaceutical active ingredient.

Preferably, different product layers, in particular with different pharmaceutical active ingredients and/or active ingredient concentrations, can be manufactured on different surface areas of the product base body provided. This makes it possible to apply pharmaceutically active areas in the product, in particular in a medical product, in a targeted manner.

According to a preferred aspect of the method, the product base body is additively manufactured from at least one powder, in particular using electrophotographic powder application. The at least one powder used to produce the product base body is in particular different from the at least one powder used to produce the product layers with at least one pharmaceutical active ingredient. For example, the powder used to produce the product base body can be a ceramic powder and/or a metal powder, in particular a titanium powder. The additive manufacturing of the product base body also allows the base body to be adapted in a particularly targeted manner to the respective application, in particular to the respective patient. Product base bodies and further product layers can be manufactured in sequential manufacturing processes. This makes it possible to combine materials that make simultaneous processing difficult, or in particular impossible, due to very different properties, in particular thermal properties.

The product base body is preferably manufactured by means of electrophotographic powder application and/or selective laser sintering. The product base body is particularly preferably manufactured by means of the method described above, wherein the at least one powder does not have to contain a pharmaceutical active ingredient. In particular, one or more of the advantageous aspects of the method can be used to manufacture the product base body. The product base body can be manufactured, for example, using the device described in more detail below. Following the manufacture of the product base body, one or more further layers of at least one powder can be applied, in particular using the same method and/or in the same manufacturing device. For this purpose, for example, a temperature of the construction space and/or an energy input of radiation used to solidify the applied powder parts, in particular laser radiation, can be changed, in particular reduced.

According to a preferred aspect of the method, the applied powder components are selectively melted, in particular by means of selective laser melting. The selective melting of the applied powder components enables particularly precise additive manufacturing of the medical and/or pharmaceutical product. The applied powder components are reliably connected to one another. This enables the simple manufacture of three-dimensional medical and/or pharmaceutical products.

According to a preferred aspect of the method, different powder components with different polarity to be applied to produce the at least one product layer, in particular to produce several product layers, are electrostatically charged. It has been recognized that by charging different powder components with different polarity, charge accumulation in the product layers produced is reduced. This improves the powder application of further powder components. Advantageously, electrostatic repulsion between different powder components and between the powder particles is reduced. The number of product layers that can be produced on top of one another is not limited by a successively increasing charge accumulation. In particular, the powder application is supported by the electrostatic attraction of powder components charged with different polarity. Further powder components can also be applied with greater precision and higher packing density. This allows the density and porosity of the manufactured product to be specifically adjusted. The overall design freedom when manufacturing the product is increased. The product can be manufactured with a high density and low porosity. This makes it possible to achieve products with improved mechanical properties.

Preferably, the powder components used to create different product layers are electrostatically charged with different polarities. This leads to an additional force of attraction between the powder components and product layers applied one after the other. The product layers created are additionally stabilized.

It is particularly preferred to electrostatically charge the powder components to be applied to produce successive product layers with alternating polarity. The alternating electrostatic charging of the powder components of successive product layers leads to a particularly advantageous application behavior. The mutual electrostatic attraction of the layers promotes powder application. The product layers produced are particularly stable. Charge accumulations are effectively avoided.

It is also possible to produce several product layers before the polarity of the powder components to be applied is changed. It has been found that an accumulation of charge in the product can also be compensated by increasing the deposition voltage. Increasing the deposition voltage is particularly possible until the dielectric strength of the product layers already produced and of a medium, in particular air, in the gap between the top product layer (application surface) and the application unit is reached. For an example air gap with a gap size of 1 mm, the maximum voltage difference is approximately ±3000 V.

If several product layers are produced with powders of the same polarity, the amount of the surface potential of the application surface increases. The inventors have recognized that good deposition results can be achieved with an unchanged polarity of the powder portion to be applied up to a limit surface potential of the application surface. If the amount of the surface potential of the application surface exceeds the limit surface potential, the polarity of the next powder portion to be applied can be changed. A suitable limit surface potential is, for example, around 1000 V. This means that the number of product layers that are successively applied with the same polarity can be increased, for example to 2 to 5 product layers.

Preferably, a surface potential of the application surface is measured in order to determine the polarity of the next powder portion to be applied. The measurement can be used to reliably determine the polarity of the next powder portion to be applied. For example, the next powder portion can be charged with a different polarity. It is also possible to compare an amount of the measured surface potential with a limit surface potential. If the limit surface potential is exceeded, the polarity of the powder portions to be applied can change. It is also possible to change the polarity of the powder portion to be applied if there is a risk of the limit surface potential being exceeded otherwise.

According to a preferred aspect of the method, the electrostatically charged powder component is picked up and/or transferred using the application unit without contact. The contactless application process reliably prevents contamination and/or damage to the application unit, in particular its photoconductor layer. In particular, the risk of powder components melted in the construction space adhering to the application unit is reduced. The contactless transfer, in particular the contactless deposit, of the powder component on the application surface is promoted by the reduced charge accumulation according to the invention. This applies in particular when charging the powder components to be applied to produce successive product layers with alternating polarity, since their attraction supports the transfer to the application surface.

According to a preferred aspect of the method, the powder portion is tempered at the application unit. Tempering, in particular preheating, the powder portion enables the temperature of the powder portion to be adjusted to the temperature in the construction space. Thermal shocks are avoided. This reduces adverse effects, such as thermal stresses in the product to be manufactured. In particular, when processing polymer powders, premature partial crystallization of the powder within the finished product and the resulting product distortion, known as curling, are avoided.

The tempering, in particular preheating, of the powder portion at the application unit can be carried out in particular by means of a tempering unit of the application unit. The tempering unit of the application unit enables the powder to be preheated during transfer into the construction space independently of other components of the production device. Suitable tempering units can be used for for example, have fluid channels for a heat transfer fluid, in particular a heat transfer oil. The fluid channels are formed, for example, in a base body of the application unit and preferably run in a meandering manner. The fluid channels are particularly preferably arranged in such a way that they enable uniform heating of the application unit, in particular a photoconductive layer of the application unit. The temperature control unit preferably has a temperature control device for heating the heat transfer fluid to a desired temperature and/or a pump for pumping the heat transfer fluid in the fluid channels. Additionally or alternatively, the temperature control unit can have heating wires and/or Peltier elements.

The tempering, in particular preheating, of the powder portion to be applied at the application unit also has the advantage that cooling of the top product layer in the build space is reduced, or in particular avoided. In addition, effects that can arise during powder application due to brief shading by heating devices in the build space, for example infrared radiators, are reduced.

The tempering, in particular preheating, of the powder portion to be applied on the application unit also has the advantage that only the powder portion to be applied is tempered. In comparison to doctor blade or roller-based coating systems, there is no need for lengthy heating up of the system, which can sometimes take several hours. In particular, there is no need to heat up all of the powder provided, for example in a powder bed. This increases the efficiency of the process. The effects of tempering, in particular heating up, on the at least one pharmaceutical active ingredient are reduced, in particular avoided.

The tempering of the powder portion on the application surface, in particular by means of a tempering unit of the application unit, can advantageously also be used for active cooling of the powder portion. This allows the heating of the powder portion, in particular heat transfer to a powder in the powder reservoir and/or in an application unit, to be minimized. The at least one pharmaceutical active ingredient is exposed to as little heat as possible. Negative effects of the heating on the at least one pharmaceutical active ingredient, in particular degradation of the same, are particularly reliably avoided.

If the powder portion is preheated by means of tempering, a heating temperature to which the application unit is heated to preheat the powder portion can preferably be selected depending on the amount and material composition of the powder to be applied. In particular for powders containing (carrier) polymers, for example semi-crystalline polymers, a heating temperature that is 1 °C to 5 °C above a temperature T to which the powder portion is to be preheated has proven to be practical. The powder portion can be further heated in the build space, for example by means of heat radiation and/or lasers.

• TS - ΔT < T < TS, wobei TS eine Schmelztemperatur, insbesondere die Onset-Schmelztemperatur, des Pulveranteils ist und ΔT 30 °C, insbesondere 15 °C, insbesondere 10 °C, insbesondere 5 °C, beträgt. Der Pulveranteil wird an der Auftragseinheit auf eine Temperatur knapp unterhalb der Schmelztemperatur TS aufgeheizt. Als Schmelztemperatur TS des Pulveranteils wird hier und im Folgenden die niedrigste Temperatur verstanden, bei der zumindest ein Bestandteil des Pulveranteils, beispielsweise ein Trägerpolymer, zu schmelzen beginnt. Durch das Vorheizen unterhalb der Schmelztemperatur ist gewährleistet, dass der Pulveranteil und dessen Bestandteile nicht an der Auftragseinheit aufschmelzen. Eine Verschmutzung und/oder Beschädigung der Auftragseinheiten durch Schmelzrückstände ist vermieden. Das Vorheizen auf knapp unterhalb der Schmelztemperatur ermöglicht zudem eine weitgehende Anpassung der Pulvertemperatur an die im Bauraum herrschenden Temperaturen. Nachteilige thermische Effekte sind zuverlässig vermieden.

For example, the powder portion of the application unit is preheated to a temperature T for which:

• TS - ΔT < T < TS, where TS is a melting temperature, in particular the onset melting temperature, of the powder portion and ΔT is 30 °C, in particular 15 °C, in particular 10 °C, in particular 5 °C. The powder portion is heated at the application unit to a temperature just below the melting temperature TS. The melting temperature TS of the powder portion is understood here and below to be the lowest temperature at which at least one component of the powder portion, for example a carrier polymer, begins to melt. Preheating below the melting temperature ensures that the powder portion and its components do not melt at the application unit. Contamination and/or damage to the application units due to melt residues is avoided. Preheating to just below the melting temperature also enables the powder temperature to be largely adapted to the temperatures prevailing in the construction space. Adverse thermal effects are reliably avoided.

The melting temperature TS can in particular be an onset melting temperature of the powder portion. This reliably prevents the powder portion from melting at the application unit. The onset melting temperature is the temperature at which the powder material begins to melt when it is heated. The onset melting temperature can in particular be determined using differential scanning calorimetry (DSC for short).

• TR - δT < T, wobei TR eine Rekristallisationstemperatur, insbesondere die Onset-Rekristallisationstemperatur, des Pulveranteils ist und δT 20 °C, insbesondere 15 °C, insbesondere 10 °C, insbesondere 5 °C, insbesondere 0 °C, beträgt. Dies hat insbesondere für (teil-)kristalline Pulvermaterialien, insbesondere teilkristalline (Träger-)Polymere, den Vorteil, dass eine Rekristallisation des Pulveranteils und damit ein Verzug des Baumaterials während des Auftragsprozesses vermieden sind. Bevorzugt erfolgt das Vorheizen auf eine Temperatur T oberhalb der der Rekristallisationstemperatur TR, insbesondere der Onset-Rekristallisationstemperatur (δT = 0 °C). Es hat sich jedoch gezeigt, dass auch ein Vorheizen auf Temperaturen T geringfügig unterhalb der Rekristallisationstemperatur, insbesondere der Onset-Rekristallisationstemperatur (δT > 0 °C), eine Rekristallisation ausreichend zuverlässig verhindern.

Preferably, the powder portion at the application unit is preheated to a temperature T for which:

• TR - δT < T, where TR is a recrystallization temperature, in particular the onset recrystallization temperature, of the powder portion and δT is 20 °C, in particular 15 °C, in particular 10 °C, in particular 5 °C, in particular 0 °C. This has the advantage, particularly for (partially) crystalline powder materials, in particular partially crystalline (carrier) polymers, that recrystallization of the powder portion and thus distortion of the building material are avoided during the application process. Preheating is preferably carried out to a temperature T above the recrystallization temperature TR, in particular the onset recrystallization temperature (δT = 0 °C). However, it has been shown that preheating to temperatures T slightly below the recrystallization temperature, in particular the onset recrystallization temperature (δT > 0 °C), can also prevent recrystallization sufficiently reliably.

The recrystallization temperature TR is preferably the onset recrystallization temperature. This ensures that recrystallization of the powder material is particularly reliably avoided. The onset recrystallization temperature is the temperature at which recrystallization of the powder material and/or a melted component thereof, for example a carrier polymer, begins when the powder material cools. The onset recrystallization temperature can be determined in particular by means of differential scanning calorimetry (DSC for short).

Preferably, the powder portion at the application unit is preheated to a temperature T for which the following applies: TR - δT < T < TS, where δT is 20 °C, in particular 15 °C, in particular 10 °C, in particular 5 °C, preferably 0 °C. The temperature range between the recrystallization temperature TR, in particular the onset recrystallization temperature, and the melting temperature TS, in particular the onset melting temperature, is also referred to as the quasi-isothermal process window. This temperature range has proven to be particularly advantageous for the processing of (partially) crystalline materials, in particular partially crystalline polymers. Negative effects of recrystallization, for example product distortion, and melting of the powder portion at the application unit are reliably avoided.

The quasi-isothermal process window is highly dependent on the material. In addition, the quasi-isothermal process window can show deviations due to different additives, for example with flow aids and/or optical scattering particles, and/or starting materials. This can, for example, lead to manufacturer-dependent deviations in the quasi-isothermal process window. The quasi-isothermal process window can preferably be determined in advance by a calibration measurement, in particular by means of differential scanning calorimetry (DSC for short). The powders can be preheated to a temperature T within the specific process window at the application unit, at least if the powders are applied without a heat-sensitive pharmaceutical active ingredient. For the above-mentioned exemplary biocompatible and/or pharmaceutical polymers, a particularly suitable process window is between about 120 °C and about 160 °C.

Preferably, the application surface, in particular an entire construction space, is preheated to a temperature T2 for which the following applies: TR < T2, in particular TR < T2 < TS. Preferably, the construction space is kept at a temperature T2 during the application of all powder components that lies within the quasi-isothermal process window. The temperature T2 preferably corresponds essentially to the temperature T to which the powder component is preheated on the application unit. A temperature shock during the powder application is avoided. In particular, a cooling process of the product to be manufactured can be controlled in a targeted manner. Preferably, cooling below the recrystallization temperature TR, in particular below the onset recrystallization temperature, only takes place after all product layers have been applied. This avoids premature recrystallization. The cooling process can be controlled. Particularly advantageously, this makes it possible to specifically influence the crystallization of the construction material and thus the crystallinity, in particular the size of resulting crystals (so-called spherulites) of the product to be manufactured. This allows a particularly precise and targeted influence on the mechanical properties of the product to be manufactured.

Preferably, the application unit is mechanically excited, in particular set in vibration, to transfer the powder portion to the application surface. The mechanical excitation enables a particularly effective and targeted transfer of the powder portion to the application surface. The mechanical excitation overcomes the mass inertia of the powder particles adhering to the application unit. The mechanical excitation increases the distances between individual powder particles, which reduces both the interparticle attraction forces due to the van der Waals interactions and the electrostatic attraction forces. The mechanical excitation can be carried out by strongly accelerating the application unit, in particular by means of the positioning system. Mechanical excitation using an actuator, in particular a piezo actuator, has proven to be particularly suitable. With the help of a piezo actuator, particularly efficient excitation patterns, in particular vibrations, can be generated. For example, the piezo actuator can be subjected to a periodic voltage to generate a vibration. Suitable examples are Sine, square and/or triangular voltages and combinations thereof. The excitation frequency can be between 100 Hz and 20 kHz, for example. Excitation frequencies in the frequency ranges 100 Hz to 500 Hz, 1 kHz to 2 kHz and/or 10 kHz to 18 kHz are particularly suitable. The peak-to-peak voltage of the excitation can be between 300 and 500 volts, for example. Excitation using a pulse sequence consisting of a strong pre-pulse and irregular follow-up pulses with a smaller amplitude has proven to be particularly advantageous. The pre-pulse can have a peak-to-peak voltage of around 1,000 volts, for example. For mechanical excitation, in particular for vibration excitation, several corresponding pulse sequences consisting of a strong pre-pulse and weaker follow-up pulses can be used.

Periodic excitation patterns, in particular sinusoidal excitation patterns, with an excitation frequency in the range of one of the natural frequencies of the application unit have proven to be particularly suitable. The excitation frequency preferably corresponds essentially to one of the natural frequencies of the application unit. This allows particularly large accelerations of the application unit to be achieved, which facilitates overcoming the Van der Waals forces.

Preferably, the excitation is carried out in such a way that the application unit is accelerated essentially in the deposition direction. The acceleration in the deposition direction supports the deposition of the powder particles. In contrast, an acceleration perpendicular to the deposition direction can lead to a lateral offset of individual powder particles (so-called false prints). Strong excitation amplitudes, in particular periodic excitations with a natural frequency of the application unit, can lead to strong accelerations in the deposition direction and/or perpendicular to it. This can increase the powder transfer while simultaneously increasing the misprint rate.

The mechanical excitation, in particular a periodic excitation with one of the natural frequencies of the application unit, is particularly preferably combined with an electrical transfer field, in particular with a deposition voltage. It has been shown that the combination of mechanical excitation and electrical transfer field particularly promotes powder deposition. In addition, the electrical transfer field reduces the misprint rate. The combination of mechanical excitation and electrical transfer field ensures powder deposition with high coverage of the deposition area and at the same time a low misprint rate. For example, mechanical excitation and switching on of the electrical transfer field occur essentially at the same time.

According to a preferred aspect of the method, an electrical transfer field is generated between the application unit and a transfer structure to transfer the powder portion to the application surface. The electrical transfer field ensures a particularly targeted and positionally accurate transfer, in particular deposition, of the powder portion on the application surface. The electrical transfer field is preferably generated between a conductive base body of the application unit and a grounded transfer structure. For this purpose, the application unit, in particular its base body, can be subjected to a deposition voltage.

The transfer structure is preferably grounded. The transfer structure can be arranged in the direction of a surface normal of the application surface between the application surface and the application unit. The transfer structure can preferably be displaceable in the direction of the surface normal of the application surface in order to precisely adjust the electric transfer field independently of the height of the product layers already produced.

The transfer structure preferably has a transfer frame made of conductive material. The transfer frame can be formed, for example, from conductors arranged in a frame shape, in particular copper rods. The transfer frame preferably has a larger extension in the direction perpendicular to the surface normal of the application surface than the application unit. The application frame preferably has an extension in a plane perpendicular to the surface normal of the application surface that exceeds the extension of the application unit, for example by 1 mm. In the direction perpendicular to the surface normal of the application surface, the transfer frame is preferably arranged circumferentially around the application unit. The transfer frames do not hinder the transfer of the powder portion. Lateral deflection of the powder during deposition is minimized.

According to a preferred aspect of the method, the application unit is mechanically excited after the electrical transfer field has been completely built up. The mechanical excitation only takes place when the electrical transfer field has been completely built up. Preferably, the mechanical excitation takes place immediately after the transfer field has been completely built up. In particular, the voltage supply, in particular the high voltage supply, for the electrical transfer field is activated first. After the electrical transfer field has been completely built up, the mechanical excitation, in particular at least one piezo actuator, is activated. This ensures particularly precise powder deposition in the deposition direction. For example, common high-voltage supplies can build up suitable deposition voltages (for example between ± 500 V and ± 3000 V) within about 0.1 s to about 30 s. The mechanical excitation should then only take place after the time required to build up the transfer field has elapsed.

Preferably, the at least one powder can be triboelectrically charged. Triboelectric powder charging is particularly advantageous for powders that are difficult to flow. In addition, triboelectric powder charging allows simple and targeted adjustment of the layer thickness of the powder components to be applied.

As the inventors have discovered, a particular advantage of triboelectric charging is the homogeneous, in particular complete, charging of the powder particles due to charge separation. Unlike gas discharge, by means of which only very thin powder layers can be charged, triboelectric charging can charge larger powder layers. This can increase the layer thickness of the powder portion picked up by the application unit. This enables product layers with a greater layer thickness to be deposited and thus faster production. For example, triboelectric charging can be used to produce layer thicknesses of the powder portion to be applied that correspond to between about 1 and about 5 average particle diameters of the powder particles of the powder portion. Depending on the particle diameter, layer thicknesses between about 60 µm and about 300 µm can be produced, for example. Gas discharge allows layer thicknesses of about 1 to about 2 average particle diameters, for example between about 60 µm and about 120 µm.

For example, the powder portion picked up by the application unit has a layer thickness perpendicular to the application unit that is greater than twice the average particle diameter of the powder particles of the powder portion. This enables fast and efficient production. The layer thickness is preferably between 2 and 5 average particle diameters. The powder portion can be charged in particular triboelectrically. Particularly preferably, triboelectrically chargeable powders with different polarities are provided in order to be able to apply and produce product layers with a high layer thickness and different polarities. It is also possible to choose different layer thicknesses for different product layers, in particular different powder portions to be applied. For example, a smaller layer thickness can be selected in areas with fine product structures to be produced than in other areas.

If at least two different powders are provided, they can be triboelectrically charged, in particular with different polarities. The use of such powders makes it easy to charge the powder components with different polarities using the triboelectric effect. For example, a powder charging unit used to charge the powders can have a magnetic brush system. This allows the respective powders to be electrostatically charged with different polarities. Various of the powders provided can be used to apply powder components charged with different polarities. The at least two powders can, for example, have different charge control substances which lead to different polarities in the electrostatic charging when the powder properties are otherwise the same. In this way, charging with different polarities and otherwise unchanged powder properties is possible.

Particularly suitable powders for triboelectric charging and their production are described below. The production of the powders and the corresponding powder formulation are an independent aspect of the invention, which is in particular independent of the charging of different powder components with different polarities. The powder formulation comprises polymer particles and charge control substances. Suitable charge control substances are in particular functionalized silica particles. In particular, the polymer particles are coated with the charge control substances, in particular the functionalized silica particles. The powder formulation preferably consists of polymer particles coated with functionalized silica particles.

To produce a preferred powder formulation, polymer particles are coated with silica particles, in particular dry-coated. Any mixer suitable for dry coating can be used for this purpose, for example shaker mixers, in particular 3D shaker mixers, horizontal and/or vertical mixers, in particular with different agitator geometries, drum mixers, cube mixers and/or cylinder mixers. This ensures a high degree of flexibility in the production of the powder formulation. In addition, mixing aids, for example in spherical form, can be used. The mixing aids can consist of glass and/or zirconium oxide, in particular glass beads. Suitable glass beads can have a medium Diameter of 1.5 mm and an average weight of 180 g. Mixing aids promote deagglomeration of the silica particles and can be easily separated by sieving after the mixing process.

The polymer particles can consist of any polymer. The powder formulation can in particular comprise commercially available powders coated with the functionalized silica particles. The powder formulation and its production are advantageously suitable for functionalizing any polymer powder for triboelectric charging in additive manufacturing, in particular for biocompatible and/or pharmaceutical polymers. The polymer powders can in particular also consist of mixtures, blends and/or composites of such polymers.

The polymer particles preferably have a particle size distribution in the range of 1 µm to 200 µm.

The functionalized silica particles preferably have an average particle size of between 10 nm and 60 nm. The functionalized silica particles serve as a charge control agent. They act as electron acceptors or electron donors and, as part of the powder formulation, ensure a targeted shift in the charge spectrum. Another advantage is that the functionalized silica particles act as flow aids, which improves the material supply for powder application.

Functionalized silica particles in the form of hexamethyldisilazane (HMDS), polydimethylsiloxane (PDMS) or a mixture thereof are particularly suitable for producing a powder formulation for triboelectric charging with negative polarity. Functionalized silica particles in the form of PDMS, nitrogen compounds -NR ₂ and -NR ₃ and/or mixtures thereof have proven particularly suitable for producing a powder formulation for triboelectric charging with positive polarity. Suitable functionalized silica particles are commercially available, for example under the trade name "HDK" from Wacker Chemie AG. HDK H05TX, for example, can be used for negative charging. HDK H05TA, for example, can be used for positive charging.

The proportion of charge control substances, in particular functionalized silica particles, in the powder formulation is in particular in the range between 0.05 wt.% and 1 wt.% based on the mass of the polymer. Such a proportion of charge control substances results in a particularly suitable shift in the charge spectrum.

The functionalization of the polymer powders described above is particularly suitable for biocompatible and/or pharmaceutical polymers, in particular for the exemplary biocompatible and/or pharmaceutical polymers mentioned above.

A device particularly suitable for carrying out the method is described below. The device has at least one powder reservoir for storing at least one powder, at least one powder charging unit for electrostatically charging powder components of the at least one powder and at least one application unit that can be electrostatically charged at least in some areas for receiving and transferring electrostatically charged powder components to an application surface.

The at least one powder charging unit is preferably designed to electrostatically charge different powder components of the at least one powder to produce one or more product layers with different polarity. The device enables an improved additive manufacturing process, in particular with the aid of electrophotographic powder application. Disadvantageous charge accumulations in the product to be manufactured are avoided. The device has in particular the features and advantages described in relation to the manufacturing process.

The functionality of the at least one powder charging unit is based in particular on the physical effect of the gas discharge. The at least one powder charging unit has, for example, a corona wire or a scorotron. The at least one powder charging unit can have a reversible voltage source to generate different polarities.

Alternatively or additionally, the at least one powder charging unit can use the triboelectric effect. For example, the at least one powder charging unit can comprise a magnetic brush system.

The device preferably has a control unit which is designed to control the device for carrying out the manufacturing method described above. In particular, the control unit is designed to control the device for additive manufacturing of the product in such a way that one or more product layers of the product to be manufactured are produced, wherein at least one powder portion of the at least one powder is applied to produce a product layer. wherein the powder portion is electrostatically charged by means of the at least one powder charging unit, the at least one application unit is electrostatically charged at least in some areas, and the electrostatically charged powder portion is picked up by means of the at least one application unit that is electrostatically charged at least in some areas and transferred to the application surface, wherein different powder portions with different polarity to be applied to produce the product layers are electrostatically charged. The control unit allows the manufacturing process to be carried out fully automatically using the device. The control unit can also be designed to carry out the advantageous method steps described above.

According to a preferred aspect of the device, the at least one application unit has a tempering unit for tempering powder components on the application unit. For example, by preheating, disadvantageous thermal effects, in particular thermal stresses in the products to be produced, are reduced, in particular avoided. In addition, heat-sensitive powders can be cooled on the application unit.

For example, the tempering unit has fluid channels for a heat transfer fluid, which are formed in a base body of the application unit. The fluid channels run in particular in a meandering manner in the base body. The fluid channels are particularly preferably arranged in such a way that uniform tempering of powder components over an entire surface of the application unit, in particular an entire photoconductive layer of the application unit, is ensured.

The temperature control unit preferably has a temperature control device for controlling the temperature of the heat transfer fluid and/or a pump for pumping the heat transfer fluid. The use of fluid channels for a heat transfer fluid has the advantage that it is possible to preheat the powder and, if necessary, also to cool the application unit and/or the powder to protect against the temperature prevailing in the construction space. Thermal damage to the application unit, in particular to its photoconductive layer, is avoided.

Alternatively or additionally, the temperature control unit can also have heating wires and/or one or more Peltier elements.

The application unit preferably has a conductive base body that is connected to a reversible application unit voltage source. The conductive base body of the application unit can be subjected to a pick-up voltage, holding voltage and/or deposit voltage that is adapted to the polarity of the electrostatic charge of the powder component by means of the reversible application unit voltage source. This supports the pick-up and transfer of the powder component by means of the application unit.

The application unit preferably has an actuator for generating a mechanical excitation, in particular a vibration excitation, of the application unit. The mechanical excitation supports the accurate and precise transfer of the powder components to the application surface. Undesirable adhesion of the powder components to the application unit is avoided. The actuator is preferably designed as a piezo actuator. With the help of a piezo actuator, particularly suitable excitation patterns, in particular vibration excitations, can be generated easily and specifically. The mechanical excitation can be flexibly adapted to the powder component to be transferred, in particular to the mass of the powder particles and/or their electrostatic charge.

The device preferably has a transfer structure for generating an electrical transfer field between the application unit and the transfer structure. The electrical transfer field supports the transfer, in particular the deposition, of the powder portion on the application surface. This ensures in particular that the powder portion is deposited in a precise position. The electrical transfer field is formed in particular between a conductive base body of the application unit and the transfer structure. For this purpose, the base body of the application unit can be subjected to a deposition voltage. The transfer structure is preferably grounded. The transfer structure in particular has a transfer frame. The transfer structure in particular has the features and advantages described in relation to the method.

It is a further object of the invention to improve a pharmaceutical.

This object is achieved by a pharmaceutical with the features specified in claim 15. The pharmaceutical is produced using the method described above. The pharmaceutical has the advantages described in relation to the method, in particular flexible and economical production. In particular, pharmaceutical active ingredients and/or combinations of active ingredients adapted to the respective application, in particular the respective patient, can be contained in the pharmaceutical. This preferably enables a targeted, timed release of one or more active ingredients, in particular a delayed release of the active ingredient. The pharmaceutical product may in particular be a tablet, a dragee and/or a suppository.

According to a preferred aspect of the pharmaceutical, it has product areas, in particular active ingredient areas, with different active ingredients and/or active ingredient concentrations. The different product areas can be created simply by using different powders during electrophotographic powder application. The combination of the pharmaceutical active ingredients and/or active ingredient combinations can be flexibly adjusted. For example, different product areas can have different active ingredients in order to enable the respective active ingredients to be released at different times. It is also possible to combine different active ingredients in individual product areas, for example by applying different powders to these product areas. For example, a new active ingredient combination can be created by combining different carrier polymers and/or pharmaceutical active ingredients. This makes it possible to create targeted active ingredient combinations for the respective application.

According to a preferred aspect of the pharmaceutical, one of the product areas is embedded in another product area, in particular completely encapsulated therein. For example, an active ingredient can be completely encapsulated in the other product area. The embedded, in particular encapsulated, active ingredient is only released after the surrounding area has dissolved. This allows a targeted delay in the release of the active ingredient to be set simply and efficiently, for example through the material and/or the thickness of the encapsulation.

According to a preferred aspect of the pharmaceutical, a transition area with a graduated transition between the different active ingredients and/or active ingredient concentrations is formed between different product areas. This can bring about a gradual change in the medication, in particular a targeted change in the release of the active ingredient. The transition area, in particular a gradual transition of the respective active ingredient proportions and/or active ingredient concentrations, can be adjusted in a targeted and precise manner using additive manufacturing.

It is a further object of the invention to improve a medical device.

This object is achieved by a medical device with the features specified in claim 19. The medical device is manufactured using the method described above. The medical device has the advantages achievable by the method, in particular an individually adaptable design and/or flexible material and/or active ingredient combination.

The medical device can in particular be a prosthesis and/or an implant.

According to a preferred aspect of the medical device, it has a product base body, on the surface of which at least one product area containing a pharmaceutical active ingredient has been additively manufactured. The product area containing a pharmaceutical active ingredient is also referred to as an active ingredient area or pharmaceutically active product area. The base body can be made in particular from metal, in particular from titanium and/or ceramic. The base body can, for example, represent the basic shape of an implant and/or a prosthesis. The base body itself can be manufactured additively, in particular by means of electrophotographic powder application. However, the base body can also be manufactured using other methods, in particular non-additively. The additive manufacturing of the product area containing a pharmaceutical active ingredient allows active ingredients to be applied in a targeted manner. In particular, different areas with different active ingredients and/or active ingredient concentrations can be manufactured.

According to a preferred aspect of the medical device, it has different product areas additively manufactured on the base body, which contain different pharmaceutical active ingredients and/or active ingredient concentrations. The medical device, in particular the prosthesis and/or the implant, is optimally adapted to the respective application. The different areas can each be manufactured additively, in particular by means of photographic powder deposition.

Between different product areas of the medical device, in particular between different active ingredient areas and/or between an active ingredient area and a product base body, a transition area can be formed in which the respective materials, active ingredients and/or active ingredient concentrations gradually merge into one another.

• 1 eine schematische Darstellung einer Vorrichtung zur additiven Fertigung eines medizinischen und/oder pharmazeutischen Produkts,
• 2 eine schematische Darstellung einer Auftragseinheit der Vorrichtung gemäß 1,
• 3 ein schematischer Verfahrensablauf für die additive Fertigung eines medizinischen und/oder pharmazeutischen Produkts, insbesondere unter Verwendung der Vorrichtung gemäß 1,
• 4 eine schematische Darstellung einer Aufladestation der Vorrichtung gemäß 1 bei der elektrostatischen Aufladung der Auftragseinheit,
• 5 eine schematische Darstellung einer Belichtungsstation der Vorrichtung gemäß 1 bei der selektiven Belichtung der Auftragseinheit,
• 6 eine schematische Darstellung einer Entwicklungsstation der Vorrichtung gemäß 1 bei der Aufladung eines Pulveranteils eines Pulvers für den elektrofotografischen Auftragsprozess,
• 7 die Entwicklungsstation gemäß 6 bei Aufnahme des elektrostatisch aufgeladenen Pulveranteils durch die Auftragseinheit,
• 8 eine schematische Darstellung einer Druckstation der Vorrichtung gemäß 1 bei der Übertragung eines Pulveranteils zur Erzeugung einer ersten Produkt-Schicht des zu fertigenden medizinischen und/oder pharmazeutischen Produkts,
• 9 die Druckstation gemäß 8 nach der Ablage eines weiteren Pulveranteils zur Erzeugung einer weiteren Produkt-Schicht des zu fertigenden medizinischen und/oder pharmazeutischen Produkts,
• 10 die Druckstation gemäß 8 nach der Ablage eines weiteren Pulveranteils eines unterschiedlichen Pulvers zur Fertigung einer weiteren Produkt-Schicht des zu fertigenden medizinischen und/oder pharmazeutischen Produkts,
• 11 eine schematische Darstellung eines weiteren Ausführungsbeispiels einer Entwicklungsstation für eine Vorrichtung zur additiven Fertigung eines medizinischen und/oder pharmazeutischen Produkts,
• 12 eine schematische Darstellung eines Ausführungsbeispiels eines additiv gefertigten Medizinprodukts und
• 13 eine schematische Darstellung eines Ausführungsbeispiels eines additiv gefertigten Pharmazeutikums.

Further advantages and details of the invention are explained in more detail below with reference to the drawings. In these:

• 1 a schematic representation of a device for the additive manufacturing of a medical and/or pharmaceutical product,
• 2 a schematic representation of an application unit of the device according to 1 ,
• 3 a schematic process flow for the additive manufacturing of a medical and/or pharmaceutical product, in particular using the device according to 1 ,
• 4 a schematic representation of a charging station of the device according to 1 in the electrostatic charging of the application unit,
• 5 a schematic representation of an exposure station of the device according to 1 in the selective exposure of the application unit,
• 6 a schematic representation of a development station of the device according to 1 when charging a powder portion of a powder for the electrophotographic application process,
• 7 the development station according to 6 when the electrostatically charged powder portion is absorbed by the application unit,
• 8th a schematic representation of a printing station of the device according to 1 in the transfer of a powder portion to produce a first product layer of the medical and/or pharmaceutical product to be manufactured,
• 9 the printing station according to 8th after depositing another portion of powder to produce another product layer of the medical and/or pharmaceutical product to be manufactured,
• 10 the printing station according to 8th after depositing another powder portion of a different powder to produce another product layer of the medical and/or pharmaceutical product to be manufactured,
• 11 a schematic representation of a further embodiment of a development station for a device for the additive manufacturing of a medical and/or pharmaceutical product,
• 12 a schematic representation of an embodiment of an additively manufactured medical device and
• 13 a schematic representation of an embodiment of an additively manufactured pharmaceutical.

Based on 1 to 10 A first embodiment of a device 1 for the additive manufacturing of a medical and/or pharmaceutical product and of an additive manufacturing method 2 therefor are described below.

1 shows a schematic representation of the device 1, which is set up for additive manufacturing by means of electrophotographic powder application. The device 1 has a charging station 3, an exposure station 4, a development station 5 and a printing station 6. An application unit 7 of the device 1 can be moved between the stations of the device 1. The charging station 3 is used to electrostatically charge the application unit 7. At the exposure station 4, the application unit 7 is selectively exposed and thus selectively discharged. The exposure station 4 is also used to erase remaining electrostatic charges on the application unit 7 after a portion of the powder has been transferred to the printing station 6. At the development station 5, a portion of the powder is electrostatically charged and picked up by the application unit 7. The picked up portion of the powder is transported to the printing station 6 by the application unit 7 and deposited there on an application surface. The printing station 6 forms a construction space for the product to be manufactured layer by layer.

The powder portion is picked up by the application unit 7 in the development station 5 and deposited in the printing station 6 without contact.

The device 1 is suitable for multi-material processing. Using the device 1, different materials can be combined to form a medical and/or pharmaceutical product. The materials intended for manufacturing the product are provided in the form of powders. For this purpose, the device 1 has various powder reservoirs. The 1 The embodiment shown has two powder reservoirs R1, R2 for two different powders P1, P2. In the embodiment shown, the powders P1, P2 each have at least one pharmaceutical active ingredient. The powders P1, P2 can themselves consist of powdered pharmaceutical active ingredients. Powders made from a carrier polymer and the pharmaceutical active ingredient are particularly suitable. The pharmaceutical active ingredient can in particular have a proportion of between 1% by weight and 50% by weight in the powder P1, P2. The two powders P1, P2 preferably have different carrier polymers and/or different pharmaceutical active ingredients and/or active ingredient concentrations. The powders P1, P2 can also be mixtures of a pharmaceutical active ingredient powder and a polymer, metal and/or ceramic powder. It is also possible for one of the powders P1, P2 to have no pharmaceutical active ingredient. Polymer and ceramic powders can be directly electrostatically charged for the electrophotographic application process. For example, metal powders are provided with a dielectric coating to make them electrostatically chargeable.

The device 1 has a positioning system 8 for moving the application unit 7. The positioning system 8 enables the application unit 7 to be moved between the stations of the device 1. The movement takes place translationally in the x direction. The positioning system 8 also enables the application unit 7 to be moved in the vertical direction (z direction). This allows the distance between the application unit 7 and the powder portion to be picked up at the development station 5 and an application surface at the printing station 6 to be precisely adjusted. The travel speed in the x direction can be between 0.2 m/s and 1.0 m/s, for example. The travel speed in the z direction is between about 10 mm/s and about 20 mm/s, for example.

At the printing station 6, the transferred powder components are solidified, in particular by melting the carrier polymer. High temperatures therefore regularly prevail at the printing station 6. The application unit 7 is connected to the positioning system 8 via a support arm 9. The support arm 9 ensures that the positioning system 8 is sufficiently spaced from the construction space and the temperatures prevailing therein. The support arm 9 can, for example, have a length of around 50 cm. For further thermal shielding of the positioning system 8, a thermal separating device 10 is also arranged between the application unit 7 and the positioning system 8. The thermal separating device 10 is, for example, a roller cover made of aluminized Kevlar. The thermal separating device 10 has, for example, a thickness of 0.8 mm and a width of 90 mm.

The positioning system 8 has a linear axis for displacement in the x-direction and a precision lifting table for displacement in the z-direction. Alternatively, other positioning systems are also possible, for example spindle-, belt- and/or chain-driven positioning systems.

The device 1 has a control unit 11. The control unit 11 controls the device 1 to carry out additive manufacturing. For example, design data, in particular CAD data, for the product to be manufactured are stored on the control unit 11. The control unit 11 controls the device 1 to carry out layer-by-layer manufacturing of the product in accordance with the design data.

In 2 the application unit 7 is shown schematically. The application unit 7 has a base body 12. The base body 12 is designed as an aluminum plate. The base body 12 is square in the plane formed by the x-direction and the y-direction. It has an exemplary side length of 100 mm. In the z-direction, the base body 12 has a height of, for example, 5 mm.

A photoconductor layer 13 is applied to the surface of the base body 12, which serves to absorb the powder portion. The photoconductor layer 13 is made of arsenic(III) selenide (As ₂ Se ₃ ). It has an exemplary layer thickness of between 80 µm and 120 µm. The photoconductor layer 13 is dielectric, but when excited with light it becomes locally conductive in the exposed area due to the photoelectric effect.

The base body 12 is connected to an application unit voltage source 14. Using the application unit voltage source 14, the base body 12 of the application unit 7 can be subjected to a high voltage. The voltage is applied in the form of a pick-up, holding and/or deposit voltage, as will be described below. The voltage supply can be reversed using the switches S 14a and S 14b. The switches S 14a, S 14b can be controlled by the control unit 11.

The application unit 7 has a tempering unit 15. The tempering unit 15 is used to preheat the powder portion adhering to the application unit 7 before it is deposited in the printing station 6. By preheating the powder portion, the temperature of the powder is adjusted to the temperatures prevailing in the construction space of the printing station 6. This reduces thermal stresses in the product to be produced. The disadvantageous effect of curling is avoided, particularly when carrier polymers are used. The tempering unit 15 heats the powder portion to a temperature just below its melting temperature. This prevents components of the powder portion from melting on the application unit 7 and sticking to it. Contamination and damage to the application unit due to melted powder components is avoided. It is also possible to actively cool the powder using the tempering unit 15. This is particularly advantageous for heat-sensitive powders, especially heat-sensitive pharmaceutical active ingredients.

The temperature control unit 15 has fluid channels 16 through which a heat transfer fluid in the form of a heat transfer oil is pumped. The fluid channels 16 run in a meandering manner in the base body 12 and cover the entire surface of the base body 12 evenly in the xy plane. The fluid channels 16 can have a diameter of 4.2 mm, for example. The heat transfer oil is brought to the desired temperature by means of a temperature control device 18 and pumped around in the fluid channels 16 by means of a pump 19. In 2 A fluid circuit of the heat transfer oil with the fluid channel 16, the temperature control device 18 and the pump 19 is indicated by arrows.

The application unit 7 is brought to a desired temperature by the heat transfer fluid pumped through the fluid channels 16. This preheats or cools the powder portion to be transferred by the application unit 7. In addition, the temperature control unit prevents the application unit 7 from heating up too much in the construction space. Damage to the photoconductor layer 13 due to the temperatures prevailing in the construction space is avoided.

In other embodiments not shown, the temperature control unit has at least one Peltier element and/or heating wires.

The application unit 7 has an actuator 17 in the form of a piezo actuator. The actuator 17 is used to mechanically excite the application unit 7. The mechanical excitation simplifies the deposition of the powder portion in the printing station 6. The mechanical excitation increases the distances between individual powder particles, which reduces both the interparticle attractive forces as a result of the van der Waals interaction and the electrostatic attractive forces. The mechanical excitation can be carried out in particular by applying a sinusoidal, rectangular and/or triangular voltage or combinations thereof to the piezo actuator 17. The peak-to-peak voltage is, for example, between 300 volts and 500 volts. The excitation frequency is, for example, in the frequency ranges 100 Hz to 500 Hz, 1 kHz to 2 kHz and/or 10 kHz to 18 kHz. Excitation with pulse sequences consisting of a strong pre-pulse and several irregular follow-up pulses of smaller amplitude has proven to be particularly suitable. The peak-to-peak voltage of the pre-pulse can be around 1,000 volts, for example.

In other embodiments not shown, the actuator 17 is not arranged directly on the application unit 7, but in the area of the support arm 9. In yet other embodiments, mechanical excitation can also be achieved by strong acceleration using the positioning system 8.

The further design of the device 1 and its stations 3 to 6 are explained in more detail below in the description of the manufacturing process 2. In 3 a schematic process flow of the manufacturing process 2 is shown. The manufacturing process 2 is carried out in particular with the device 1.

In a provision step 20, the powders required to manufacture the product, in this case the powders P1, P2, are provided. In the provision step 20, design data for the product to be manufactured can also be provided, for example by transferring them to the control unit 11.

The provision step 20 is followed by the layer-by-layer production of the product by creating several product layers. To create a product layer, at least one powder portion of the powders P1, P2 is applied and solidified. The creation of the product layers is controlled by the control unit 11 and includes the steps described below.

In an application unit charging step 21, the photoconductor layer 13 of the application unit 7 is electrostatically charged. The charging of the photoconductor layer 13 of the application unit 7 takes place in the charging station 3, as shown in 4 is shown by way of example. The charging station 3 comprises a charging voltage source 22, via which a corona wire 23 can be supplied with high voltage. The polarity of the voltage applied to the corona wire 23 can be set via the switches S22a, S22b, which can be controlled via the control unit 11. To charge the entire photoconductor layer 13, the corona wire 23 can be adjusted along the y-direction. To manufacture the first product layer, the corona wire 23 is connected to the positive pole of the charging voltage source 22. The photoconductor layer 13 is thereby positively charged, for example to a potential of 600 volts.

In other embodiments not shown, charging units that work differently, in particular charging units based on the principle of gas discharge, can be used instead of the corona wire 23. In an advantageous embodiment, a scorotron is used to charge the photoconductor layer 13.

The application unit charging step 21 is followed by an exposure step 24. The exposure step 24 is carried out using the exposure station 4, as shown in 5 is shown schematically. The exposure station 4 has an exposure device 25 for selectively exposing the photoconductor layer 13. To generate the radiation 27 required for this, the exposure device has a light-emitting diode 26. With the aid of the illumination device 25, the radiation 27 is selectively irradiated onto the areas of the photoconductor layer 13 to be exposed. The areas of the photoconductor layer 13 irradiated with the radiation 27 become temporarily conductive, so that the electrostatic charge generated in the application unit charging step 21 flows away locally. The selective irradiation causes the Photoconductor layer 13 of the application unit 7 is selectively discharged. When using a photoconductor layer 13 made of arsenic(III) selenide, the use of radiation 27 with a wavelength of 613 nm has proven to be particularly suitable. The exposure time is preferably adapted to the level of the powder charge. Example exposure times are between 10 ms and 300 ms. The selective irradiation and discharge of the photoconductor layer 13 defines those areas to which powder components adhere in a later development step and are transferred into the construction space of the printing station 6. The selective exposure thus defines a contour of the product in the product layer to be produced.

A development step 28 is carried out at the development station 5. The development step 28 is divided into a powder charging step 29 and a powder receiving step 30, which are described below with respect to the 6 or 7 be explained in more detail.

The development station 5 has a grounded base surface 31. A powder portion A1 of the powder P1 is applied from the powder reservoir R1 to the base surface 31 in the form of a layer of powder particles. A powder portion A1 is electrostatically charged using a powder charging device 32. The powder charging device 32 has a voltage source 33 that is connected to a corona wire 34. The corona wire 34 can be charged with a high voltage using the voltage source 33. The polarity of the voltage applied to the corona wire 34 can be changed using the switches S33a, S33b. To electrostatically charge the powder portion A1, the corona wire 34 is guided in the y-direction over the powder layer applied to the base layer 31. The corona wire 34 can also be positioned in the z-direction to ensure optimal adaptation to the powder P1 used, in particular the size of the powder particles. Depending on the switch position of the switches S33a, S33b, the corona wire 34 and thus the powder portion A1 are charged with different polarity. 6 In the powder charging step 29 shown for producing the first product layer, the powder is charged with a positive voltage, for example. The powder is charged to a potential between 400 volts and 1,000 volts, for example.

The powder charging step 29 can take place in parallel to the application unit charging step 21 and/or the exposure step 24.

Instead of the corona wire 34, other charging units, in particular charging units based on gas discharge, can also be used in other embodiments. Instead of the corona wire 34, a scorotron can be used in particular, which enables a more precise setting of the desired surface potential.

In the powder pick-up step 30, the powder portion A1 is picked up by the application unit 7. For this purpose, the application unit 7 is moved to the development station 5. For the sake of better clarity, 7 the powder charging device 32 of the development station 5 is not shown. The application unit 7 is also fed in the z-direction to pick up the powder portion A1. The feed is carried out in such a way that a distance d remains between the photoconductor layer 13 of the application unit 7 and the surface of the charged powder portion A1. The powder portion A1 is picked up without contact. The distance d is selected depending on the mass of the powder particles and their electrostatic charge. The distance d can be between 1 mm and 8 mm, for example.

To absorb the powder portion A1, the base body 12 of the application unit 7 is subjected to a receiving voltage by means of the application unit voltage source 14. The receiving voltage has a polarity opposite to the charge of the powder portion A1 and thus supports the electrostatic attraction of the powder particles. In the present case, the photoconductor layer 13 is positively charged in the non-exposed areas. The powder portion A1 is also positively charged. The non-exposed areas of the photoconductor layer 13 locally reduce the attraction on the powder particles generated by the receiving voltage. The receiving voltage, electrostatic charge of the photoconductor layer 13 and electrostatic charge of the powder portion A1 are coordinated in such a way that only powder particles of the powder portion A1 are attracted to and adhere to previously exposed and thus discharged areas of the photoconductor layer 13. Depending on the polarity, a suitable input voltage can be, for example, between -100 V and -300 V or between 100 V and 300 V.

A recording of the powder portion, in which powder particles adhere to previously exposed and discharged areas of the photoconductor layer 13, is referred to as white writing or in English “Discharged Area Development”. Alternatively, it is also possible to charge the photoconductor layer 13 and the powder portion A1 with opposite polarity. The charged areas of the photoconductor layer 13 that were not discharged by exposure then have an attractive effect on the powder particles charged with opposite polarity. If necessary, the powder particles only adhere to the non-exposed areas. Such a procedure is called This is also known as “Charged Area Development”.

After the powder portion A1 has been absorbed in the previously exposed areas of the photoconductor layer 13, a transfer step 35 is carried out to transfer the powder from the development station 5 to the printing station 6.

In the transfer step 3 5, the powder portion is transported to the printing station 6 with the aid of the application unit 7 by moving the application unit 7 into the printing station 6. During the transfer from the development station 5 to the printing station 6, the base body 12 of the application unit 7 is subjected to a holding voltage corresponding to the receiving voltage. The powder portion A1 adhering to the application unit 7 is preheated with the aid of the tempering unit 15. The preheating takes place to a temperature T which is just below the melting temperature TS of the powder portion, preferably to a temperature within the quasi-isothermal process window. This adapts the temperature of the powder portion A1 to be transferred to the temperature prevailing at the printing station 6.

A printing step 36 takes place at the printing station 6. In the printing step 36, the powder portion A1 is transferred to an application surface F by means of the application unit 7. For this purpose, the powder portion A1 is deposited on the application surface F. The printing station 6 and the printing step 36 are described below with reference to 8th explained in more detail.

The printing station 6 forms a construction space 37 with a construction platform 38. During the production of the first product layer, the surface of the construction platform 38 facing the application unit 7 forms the application surface F. A surface normal N of the application surface F is oriented parallel to the z-direction.

The construction space 37 can be filled with air or contain a protective gas. Suitable protective gases are, for example, nitrogen and/or a noble gas, in particular argon.

The printing station 6 has a transfer structure 39. The transfer structure 39 has a transfer frame made of four copper rods 40 arranged in a frame shape. The copper rods 40 are cylindrical and each have a diameter of 0.8 mm, for example. The copper rods 40 are welded together at their ends and thus form a square transfer frame. The transfer frame has a side length that exceeds the side length of the application unit 7, in particular its base body 12. In the x-y plane, the transfer structure 39 is therefore arranged circumferentially around the application unit 7. The copper rods 40 and thus the transfer structure 39 are grounded.

The transfer structure 39 can be displaced in the direction of the surface normal N of the application surface F. The transfer structure 39 can thus be displaced in the z-direction.

The application unit 7 is positioned above the application surface F and fed in the z-direction. This sets a distance D between the powder particles adhering to the photoconductor layer 13 and the application surface F. The distance D can be selected to be suitable for the contactless deposition of the powder particles of the powder portion A1, in particular taking into account the charge of the powder particles and their mass. An example distance D is between 1 mm and 8 mm.

The transfer structure 39 is arranged with the copper rods 40 in the direction of the surface normal N, i.e. in the z-direction, between the application surface F and the application unit 7. The transfer structure 39 is positioned in the z-direction such that a distance between the copper rods 40 and the application surface F essentially corresponds to the particle diameter of the powder particles of the powder portion A1.

To deposit the powder portion A1, the voltage applied to the base body 12 of the application unit 7 is reversed. The base body 12 is therefore subjected to a deposition voltage corresponding to the polarity of the charge of the powder portion A1. An electric field E, also referred to as a transfer field, forms between the voltage-charged base body 12 and the grounded transfer structure 39. The application unit 7 is mechanically excited with the aid of the actuator 17 in order to overcome interparticle attractive forces between the powder particles and the photoconductor layer 13. The powder particles of the powder portion A1 detach from the photoconductor layer 13 and are deposited along the transfer field E on the application surface F.

The powder portion A1 thus applied to the application surface F is solidified. The polymer powders used in the embodiment shown are melted for this purpose by heating the construction space 37 to a temperature above the melting temperature TS of the powder P1. The printing station 6 has a heating device 41 for heating the construction space 37. The heating device 41 preferably has lasers, in particular CO ₂ lasers and/or thulium lasers, for selectively melting the applied powder portions. In particular, the heating device has radiant heaters for preheating zen of the powder and lasers for selectively melting the powder. This is particularly advantageous for processing different powders with very different melting temperatures. In the case of high-melting powders, lasers can also be present for preheating and melting the powder. When processing a low-melting powder and a high-melting powder, the radiant heater can be used to preheat the low-melting powder, a first laser can be used to preheat the high-melting powder and a second laser can be used to homogeneously melt the respective powders.

Ceramic and/or metallic powders have significantly higher melting temperatures than polymultipowders. Correspondingly higher temperatures are required for thermal solidification. Solidification of metallic and/or ceramic powders is therefore preferably also carried out by selective energy input, for example by selective laser beam sintering and/or electron beam melting. In this case, the metallic and/or ceramic powders can be preheated. Since high temperatures, for example up to 600 °C, are regularly required for this, there is a risk of damage to the photoconductor layer. Metallic and/or ceramic powders are therefore often applied at room temperature. Solidification then takes place, for example, by irradiating a correspondingly higher energy input for selective melting. Higher laser intensities and/or other wavelengths can be advantageous for this. Metallic and/or ceramic structures can preferably be manufactured in an upstream manufacturing process, in particular additively manufactured. The temperatures or energies required to process these materials then have no negative influence on pharmaceutical active ingredients that are processed in a further production step. For example, a prefabricated product base body made of metal, in particular titanium, and/or ceramic can be provided in the provision step 20 with at least one powder that has at least one pharmaceutical active ingredient. The application area F is then formed by the surface of the product base body, on which pharmaceutically active areas can be created in a targeted manner using the above method. The product base body is preferably manufactured using the device 1.

Solidification of the applied powder components can alternatively or additionally be achieved by non-thermal methods, for example by binder jetting. In particular, when solidifying by binder jetting, a green part of the product to be manufactured is additively manufactured, which is debindered in a subsequent step and sintered to form the finished product.

After application of the powder portion A1, an erasure step 42 is carried out. In the erasure step 42, remaining charges of the photoconductor layer 13 of the application unit 7 are erased by exposing the entire surface to the radiation 27. The erasure step 42 is carried out using the exposure station 3. For example, exposure times of around 100 ms can be used to erase the charges.

The applied powder portion A1 forms a first product layer B 1. To apply further product layers, the above steps are repeated as shown in 3 is indicated by the repetition loop 43. In the production method 2, the powder components used to produce successive product layers are electrostatically charged with different polarities. For this purpose, the voltage source 33 of the powder charging unit 32 is reversed using the switches S33a, S33b to charge the powder components for different product layers. Accordingly, the take-up voltage, holding voltage and depositing voltage are applied to the base body 12 of the application unit 7 with the correspondingly adjusted polarity. For this purpose, the voltage application to the base body 12 is controlled accordingly using the switches S14a, S14b of the application unit voltage source 14 during the production of successive product layers. When the powder components are applied, the photoconductor layer 13 of the application unit 7 is charged with the same polarity in each case. The alternately charged powder components are then picked up and held by means of black and white writing alternately in the area of charged or discharged areas of the photoconductor layer 13. This procedure has the advantage that common photoconductor layers, each of which can only be charged with one polarity, can be used to apply powder components with different polarities.

The alternating charging of the powder components to create successive product layers prevents a disadvantageous accumulation of charge in the product to be manufactured. Electrostatic repulsion of the powder particles is reduced. Rather, the charging of the powder components with alternating polarity causes the powder components of successive product layers to electrostatically attract each other. This increases the stability of the product layers during production. In addition, the packing density of the powder particles is increased during production. The manufactured product has an increased density and improved mechanical properties.

In 9 The production of a further product layer B2 by applying a powder portion A2 is shown as an example. 9 concerns the printing step in the printing station 6. The previously applied and solidified product layer B 1 forms the application area F for the powder portion A2. The powder portion A2 is in 9 already deposited on the application surface F. The powder portion A2 is charged with a polarity opposite to that of the powder portion A1. Accordingly, the application unit voltage source 14 for generating the deposition voltage is reversed compared to the previous printing step. To generate the deposition voltage, the base body 12 of the application unit 7 is subjected to a voltage of negative polarity. Accordingly, the electric transfer field E has an opposite direction.

Due to the ability to move the application unit 7 in the z-direction, a desired distance D between powder components adhering to the application unit 7 and the application surface F can be maintained regardless of the height of the product layers already produced. Likewise, the ability to move the transfer structure 39 in the z-direction enables the position of the transfer device 39 to be adjusted to the height of the product layers already produced. By appropriately positioning the transfer structure 39 relative to the application unit 7, the strength of the transfer field E can be adjusted regardless of the product height already produced.

In 10 The creation of a further product layer B3 is shown as an example. 10 shows the printing station 6 after the deposit of a powder portion A3 on the already produced product layers B1, B2. The surface of the last produced product layer B2 forms the application area F for the application of the powder portion A3. The powder portion A3 consists of the powder P2. The product layer B3 is therefore made of a different material than the already produced product layers B 1, B2. While the corresponding powder portions A1, A2 were applied over the entire surface to produce the product layers B 1, B2, the powder application of the powder portion A3 takes place selectively.

In further process steps, a further powder portion can be applied to areas of the product layer B3 in which the powder portion A3 is not applied. In this way, different powder portions and thus different materials can be combined within a product layer. Different powder portions that are used to produce the same product layer are preferably charged with the same polarity.

In the embodiment shown, all powder components of a product layer are each charged with the same polarity. The powder components of different product layers are charged with alternating polarity. A powder component of a further product layer to be applied is charged with a polarity that is opposite to the polarity of the respective application area, i.e. the polarity of the previously applied product layer. This results in a particularly advantageous electrostatic attraction between successive product layers. In addition, charge accumulation in the product to be produced is reliably avoided.

In 11 Another embodiment of a development station 105, a device for additive manufacturing, is shown. Components that are related to the 1 to 10 shown embodiment have already been described, bear the same reference numerals and are not explained again in detail.

The development station 105 has a powder charging unit 132 for triboelectrically charging the powder components. The powder charging unit 132 is designed as a magnetic brush system. The powder component to be electrostatically charged is guided between the rollers 132a, 132b of the powder charging unit 132 and is thereby triboelectrically charged. The charged powder is applied to the grounded base plate 31 in the form of a powder layer. To charge different powder components with different polarities, the two different powders P1, P2 are used, which are each charged with different polarities when triboelectrically charged. To produce successive product layers, the powders P1, P2 are therefore used alternately so that the respective powder components are charged with different polarities. By means of the triboelectric charging of the powders P1, P2, powder fractions can be applied with a layer thickness of more than twice the average particle diameter of the respective powders P1, P2. For example, layer thicknesses of between about 1 and about 5 average particle diameters can be applied.

The powders P1, P2 are, for example, powder formulations with polymer particles that are coated with suitable charge control substances, in particular with functionalized silica particles. The powders P1, P2 have, for example, a base powder in the form of a commercially available polymer powder. For triboelectric charging with different polarities, the base powders are each coated with other charge control substances, in particular other functionalized silica particles. For triboelectric charging with different polarities, the base powders are each coated with other charge control substances, in particular other functionalized silica particles. For triboelectric charging with negative polarity, the base powder is coated with a mixture of hexamethyldisilazane (HMDS) and polydimethylsiloxane (PDMS). For triboelectric charging with positive polarity, the base powder is coated with a mixture of polydimethylsiloxane (PDMS) and nitrogen compounds - NR ₂ and - NR _3. The proportion of functionalized silica particles is between 0.05% and 1% by weight based on the mass of the polymer. The functionalized polymer powders serve, for example, as carrier polymers for one or more pharmaceutical active ingredients.

In 12 shows a schematic of an embodiment of an additively manufactured medical product 101 in the form of a prosthesis. The medical product 101 has a product base body 102 made of components 103, 104. The product base body 102 is additively manufactured from a metallic material, for example titanium. The prosthesis 101 has active ingredient regions 105 to 108 at positions that are relevant from a medical point of view. The active ingredient regions 105 to 108 were additively manufactured from at least one powder containing pharmaceutical active ingredient on the surface of the product base body 102 using the method described above. The additive manufacturing of the product base body 102 and the active ingredient regions 105 to 108 can take place separately, in particular sequentially, in order to prevent the pharmaceutical active ingredients contained in the active ingredient regions 105 to 108 from being exposed to the temperatures required for processing the product base body material.

In the embodiment shown, different hatching shows that the active ingredient regions 105 to 108 are made of different powders. In particular, the respective powders can have different carrier polymers and/or different pharmaceutical active ingredients and/or active ingredient concentrations.

A transition region 109 is formed between the active ingredient regions 105, 107 and the components 103, 104, in which a graduated transition between the respective materials takes place. To produce the transition region 109, powder portions of the powder for the product base body 102 and the powder for the active ingredient regions 105, 107 are applied and solidified to corresponding surface areas of the application surface for producing respective product layers in the same product layer.

The active ingredient areas 106, 108 are additively applied to the surface of the previously manufactured product base body 102. The pharmaceutical active ingredients contained in the active ingredient areas 106, 108 are not exposed to the temperatures required for processing the metallic and/or ceramic material of the product base body 102. This increases the flexibility in selecting suitable carrier polymers and/or pharmaceutical active ingredients. A sharp transition in the form of an interface 110 is formed between the pharmaceutically active areas 106, 108 and the base body component 104.

In 13 an embodiment of an additively manufactured pharmaceutical 201 in the form of a tablet is shown schematically.

The pharmaceutical 201 has two active ingredient areas 202, 203, which are made from different powders. A third active ingredient area 204 and a fourth active ingredient area 205 are also embedded in the active ingredient areas 202, 203, which in turn can be made from different powders. The embedded active ingredient areas 204, 205 are completely encapsulated in the active ingredient areas 202, 203. In particular, different active ingredient powders and/or different mixtures of pharmaceutical active ingredients with carrier polymers can be used to produce the active ingredient areas 202 to 205. For example, the respective powders have different carrier polymers, different pharmaceutical active ingredients and/or different active ingredient concentrations. The different active ingredient areas 202 to 205 therefore enable the release of different active ingredients, in particular at different release rates and/or at different release times. In particular, the embedded active ingredient regions 204, 205 enable a greatly delayed release of the active ingredient contained therein.

A transition region 206 is formed between the active ingredient region 202 and the active ingredient region 204 embedded therein. Transition regions 207, 208 are also formed between the active ingredient regions 202, 205 and 203. In the transition regions 206, 207, 208 there is a graded transition between the respective different pharmaceutical active ingredients and/or active ingredient concentrations. A separation zone 209 with a sharp transition between the active ingredient regions 202 and 203 is formed between the active ingredient regions 202 and 203.

Claims (21)

Method for the additive manufacturing of a medical and/or pharmaceutical product, comprising the steps of - providing at least one powder (P1, P2) which has at least one pharmaceutical active ingredient, and - producing at least one product layer (B1, B2, B3) of the product to be manufactured, wherein to produce a product layer (B1, B2, B3) at least one powder portion (A1, A2, A3) of the at least one powder (P1, P2) is applied and solidified, wherein to apply the at least one powder portion (A1, A2, A3) -- the powder portion (A1, A2, A3) is electrostatically charged, -- an application unit (7) is electrostatically charged at least in some areas, and -- the electrostatically charged powder portion (A1, A2, A3) is picked up by means of the application unit (7) which is electrostatically charged at least in some areas and transferred to an application surface (F). Procedure according to Claim 1 , characterized in that at least two powders (P1, P2) are provided and used to produce the at least one product layer (B1, B2, B3). Procedure according to Claim 2 , characterized in that the at least two powders (P1, P2) have different pharmaceutical active ingredients and/or different active ingredient concentrations. Method according to one of the Claims 2 or 3 , characterized in that to produce a product layer (B1, B2, B3) powder portions (A1, A2, A3) of the at least two powders (P1, P2) are applied to the application surface (F), in particular in different surface areas of the application surface (F). Procedure according to one of the Claims 2 until 4 , characterized in that between product areas (102, 105, 106, 107, 108; 202, 203, 204, 205) which are manufactured from different powders (P1, P2), a transition area (109; 206, 207, 208) with a graded transition between the respective powders (P1, P2) is manufactured. Method according to one of the preceding claims, characterized in that the at least one powder (P1, P2) comprises a carrier polymer and the at least one pharmaceutical active ingredient, wherein the at least one pharmaceutical active ingredient in particular has a proportion of between 1% by weight and 50% by weight in the powder (P1, P2). Method according to one of the preceding claims, characterized in that a product base body (104), in particular a metallic or ceramic one, is provided on which the at least one product layer is produced. Procedure according to Claim 7 , characterized in that the product base body (104) is additively manufactured from at least one powder, in particular by means of electrophotographic powder application. Method according to one of the preceding claims, characterized in that the applied powder components (A1, A2, A3) are selectively melted, in particular by means of selective laser melting. Method according to one of the preceding claims, characterized in that different powder portions (A1, A2, A3) to be applied to produce the at least one product layer (B 1, B2, B3) are electrostatically charged with different polarities, wherein in particular the powder portions (A1, A2, A3) to be applied to produce successive product layers (B 1, B2, B3) are electrostatically charged with alternating polarities. Method according to one of the preceding claims, characterized in that the picking up and/or transferring of the electrostatically charged powder portion (A1, A2, A3) by means of the application unit (7) takes place without contact. Method according to one of the preceding claims, characterized in that the powder portion (A1, A2, A3) is tempered at the application unit (7), in particular by means of a tempering unit (15) of the application unit (7). Method according to one of the preceding claims, characterized in that an electric transfer field (E) is generated between the application unit (7) and a transfer structure (39) for transferring the powder portion (A1, A2, A3) to the application surface (F). Procedure according to Claim 13 , characterized in that the application unit (7) is mechanically excited after the electric transfer field (E) has been completely built up. A pharmaceutical prepared by a process according to any one of the preceding claims. Pharmaceutical according to Claim 15 , characterized by several product areas (202, 203, 204, 205) with different pharmaceutical active ingredients and/or active ingredient concentrations. Pharmaceutical according to Claim 16 , characterized in that one of the product areas (204, 205) in another product area rich (202, 203), in particular completely encapsulated. Pharmaceutical according to one of the Claims 16 or 17 , characterized in that between different product areas (202, 203, 204, 205) a transition area (206, 207, 208) with a graded transition between the different pharmaceutical active ingredients and/or active ingredient concentrations is formed. Medical device manufactured by a process according to one of the Claims 1 until 14 . Medical device according to Claim 19 , characterized by a product base body (104), in particular made of metal or ceramic, on the surface of which at least one product region (105, 106, 107, 108) containing a pharmaceutical active ingredient has been additively manufactured. Medical device according to Claim 20 , characterized by a plurality of product areas (105, 106, 107, 108) additively manufactured on the product base body (104), which in particular have different pharmaceutical active ingredients and/or active ingredient concentrations.

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