Polyglycerol fatty acid ester-containing composition

Abstract

The present invention relates to a polyglycerol fatty acid ester-containing composition having three components: first, a polyglycerol fatty acid ester obtainable by esterifying a polyglycerol having 2-10 glycerol units with a fatty acid having 12-22 carbon atoms, second, a free polyglycerol having 2-10 glycerol units, and third, a polyglycerol fatty acid monoester having 2-10 glycerol units and a fatty acid group having 12-22 carbon atoms. The composition is particularly suitable for use in starting materials for 3D printing processes and can be easily combined with cosmetic and / or pharmaceutical active ingredients or other substances. The present invention also relates to a method for producing the corresponding starting material for the 3D printing process described above, and to the shaped bodies that can be produced using it.

Description

[Background technology]

[0001] Many polyglycerol fatty acid esters have good properties to act as pharmaceutical or cosmetic bases, or even in application areas such as the food industry, or generally in all areas where storage stability is required. In particular, in contrast to many other lipid-based materials such as triacylglycerols, some polyglycerol fatty acid esters do not show any useful polymorphism and therefore do not undergo volume changes, especially the volume increase known as "blooming", on long-term storage.

[0002] WO 2020 / 083411 already discloses polyglycerol fatty acid esters or blends thereof suitable for hot melt coating processes. Hot melt coating has the advantage over other coating or covering processes, since the coating material can be used without solvent, and thus no undesirable, possibly toxic, solvent residues have to be removed from the product using complex drying steps. The use of polyglycerol fatty acid esters for the preparation of products to be introduced into the human or animal body also has the advantage that the esterification of polyglycerol with at least an even number of fatty acids produces polyglycerol fatty acid esters that can be as free of toxic degradation products as possible in vitro and in vivo.

[0003] In addition to the use of substrates such as the above-mentioned polyglycerol fatty acid esters in the hot melt coating process, there is also a need to use materials with comparable properties in the field of 3D printing. In this regard, it is not successful to simply directly use the materials used for hot melt coating, since the 3D printing process requires starting materials that must be sufficiently softened or fluidized by heating so that they can be forced through the print head nozzle so that, after building up the given molded article, they can be properly hardened to form a body with a stable shape. In particular, although polyglycerol fatty acid esters such as those described in WO 2020 / 008411 can indeed be passed through a 3D printing nozzle, the stability of the shape of the molded article produced thereby by 3D printing is not sufficient to ensure stability during the industrial packaging process and also during handling of the product. Furthermore, at least when very bulky medicamentally or cosmetically active substances are mixed with the respective substrate, the problem arises that the physical properties of the starting materials for 3D printing can be altered in such a way that the product is not shape-stable, is not stable in storage, or cannot be printed into a product of uniform quality due to increased brittleness.

[0004] EP 3482774 discloses a system that self-emulsifies in vivo in contact with a physiological hydrophilic phase and can be produced by 3D printing with a lipophilic phase, a surfactant with an HLB value above 8, and an optional co-surfactant, the surfactant consisting of PEG esters, poloxamers, ethoxylated oils, ethoxylated vitamin E, and / or sugar residues generated from fatty acids. The disadvantage of that composition is that it is not possible to reliably eliminate toxic degradation products and to sufficiently improve the shape and stability during storage. In addition, according to the cited example, the mixture of pharmacoactive substances amounts to only less than 7% by weight of the starting material for 3D printing, which results in the problem that new investigations must be carried out for all kinds of mixtures regarding the processability of the starting mixtures containing the mixtures, due to the unfavorable tendency of the individual pharmacoactive substances for demixing and phase separation, even when the starting materials are not mixed. Compositions such as 50%-95% (by weight), preferably 85% glycerol monostearate with 5%-50%, preferably 15% (by weight) polyethylene glycol 300-6000, preferably PEG 1500, are in fact not completely stable on storage, although they can still be processed in 3D printing processes, despite their adhesive properties. Fresh PEG may contain ethylene oxide and dioxane. Formaldehyde may be formed as it ages. Moreover, they are potential allergens. Summary of the Invention

[0005] The object of the invention described below is to provide a composition that utilizes the advantages of polyglycerol fatty acid esters as already known for hot melt coating processes, in particular the absence of polymorphism, as well as the ability to process this composition by 3D printing, which can also be carried out independently of the amount of additional pharmaceutical and cosmetic active substances or other additives used, in particular in the proportions of mixtures or fillers usually used in practice, providing a form-stable and storage-stable product.

[0006] This object is achieved by a composition according to claim 1, a method for its production according to claim 10, a 3D printing process according to claim 24, a method according to claim 11 for the preparation of a starting material for a 3D printing process as well as a molded part produced by 3D printing according to claim 18, advantageous embodiments of which are defined in the respective dependent claims.

[0007] In order for the polyglycerol fatty acid ester-containing composition to be usable in a 3D printing process, the polyglycerol fatty acid ester-containing composition must produce both a starting material and a final product that is neither too soft nor too brittle. In the case of compositions containing polyglycerol fatty acid esters, this is not self-evident. When using polyglycerol fatty acid esters, the elasticity of the starting material formed into a filament for a 3D printing process, as is actually the norm, depends on the number of free hydroxyl groups in the composition. Up to a certain point, the number of free hydroxyl groups can be influenced by the degree of esterification of the polyglycerol fatty acid partial ester used, but surprisingly, a mixture of polyglycerol fatty acid monoester and free polyglycerol is more targeted and effective. Stronger bonds, such as ionic or covalent bonds, result in a harder and more brittle composition, but an increase in the proportion of hydrogen bonds through free hydroxyl groups reduces the bond strength and therefore increases the elasticity, since the reorientation of the individual molecules is facilitated by a greater degree of freedom. Furthermore, as the number of glyceryl units in the polyglycerol fatty acid monoester and free polyglycerol increases, it is not as easy to break the bonds between the smaller molecules due to steric effects and a more flexible reorientation due to internal shear of the composition, but the elasticity of the composition increases due to the longer chains of the molecules. Surprisingly, good properties in terms of the shape and storage stability of the printed product in the absence of processability and volume changes associated with polymorphism in the 3D printing process are obtained in a type of composition containing at least three components, namely, firstly, both polyglycerol fatty acid esters that can be obtained by esterification of polyglycerol containing 2 to 10 glyceryl units with fatty acids containing 12 to 22 carbon atoms, as well as, secondly, free polyglycerol containing 2 to 10 glyceryl units, and, thirdly, further polyglycerol fatty acid monoesters containing 2 to 10 glyceryl units and containing fatty acid residues containing 12 to 22 carbon atoms.

[0008] The advantageous properties of the proposed composition with regard to processability can be further improved in that, in addition to the above-mentioned third component, only polyglycerol fatty acid esters obtainable from the esterification of polyglycerol containing 2 to 6 glyceryl units are used as component 1, and polyglycerol containing only 3 to 6 glyceryl units is used as component 2. It has also been shown to be advantageous for component 1 to be present not as a complete ester, but as a partial ester with a hydroxyl value of 50 mg KOH / g to 350 mg KOH / g. Preferably, the saponification value of the first component is between 100 mg KOH / g and 250 mg KOH / g. The melting point of component 1, above 35°C and up to 80°C, has also been shown to be advantageous, which means that the low melting point allows lower processing temperatures and, in the case of thermolabile active substances with which the proposed composition is processed, harmless low temperatures can be used for the process.

[0009] As can be concluded from the above discussion, the hydroxyl value of the second component of the composition is also related to the elasticity of the entire composition, preferably between 800 mg KOH / g and 1400 mg KOH / g, while the third component, i.e., the polyglycerol fatty acid monoester, should preferably have a hydroxyl value between 400 mg KOH / g and 650 mg KOH / g.

[0010] The mixing ratio of the three components relative to each other also affects the properties of the composition. Good results are obtained when the weight percentage of the first component is at least 50%, the weight percentage of the second component is at least 5%, and the weight percentage of the third component is at least 10%, and the sum of the weight percentages of the three components is preferably at least 98%.

[0011] The balanced composition, which also has sufficient consistency to provide the starting material with desirable properties in the 3D printing process, contains palmitic acid as component 1 and a polyglycerol fatty acid ester obtainable from the partial esterification of hexaglycerol with component 3 containing fatty acid residues containing 16 carbon atoms, together with other solids as additives.

[0012] The proposed composition can be produced in a simple manner by melting and mixing components 1, 2 and 3, for example at 80° C., advantageously not exceeding or only slightly exceeding the melting temperatures of the individual components. The mixture is then solidified at a temperature between 15° C. and 25° C., i.e. at about room temperature, and at a pressure between 750 hPa and 1250 hPa. Usually, the mixture can be left to solidify by itself. The homogeneity of the mixture can sometimes be further assisted by moderate stirring of the melt.

[0013] It has been shown to be advantageous if the composition is to be used in a 3D printing process to first grind the solidified mixture and then sieve it through a sieve with a pore size of 800 μm or less, and to remove the sieved material. The sieved material can be fed to the 3D printing head nozzle using a suitable system with a melting chamber and a pump for highly viscous fluids and then used in the 3D printing process. Before being used in the 3D printing process, the starting material should be tested for its breaking strength. For this purpose, a portion of the starting material, while still capable of flowing during production, is cast into a plate 155 mm long, 45 mm wide and 15 mm thick, which, after hardening, is placed individually on two metal cubes, each with 30 mm sides separated from each other by 60 mm, whose sides are parallel and bridge the metal cubes in the longitudinal direction. For the measurements, a punch tool, also made of metal, 69 mm long and with a round punch edge oriented at right angles to the space between the metal cubes, is used to increase the force acting on the centre of the plate between the metal cubes until the plate breaks. To break this type of plate under the conditions described, no more than 90 N must be applied.

[0014] When processing by 3D printing, the filament is easier to use as starting material, since it only needs to be threaded through the print head nozzle using an electric motor. It is shown here to be advantageous to supply the filament wound on a spool by a double worm gear unit. In order to transform the sieved material, which is already suitable as starting material for the 3D printing process, into a filament that is easier to process, it is preferably extruded through the extruder nozzle head at a temperature at least 1 ° C lower than the melting temperature of the first component of the polyglycerol fatty acid ester-containing composition. In principle, the thickness of the filament is determined by the shape of the print head nozzle. The diameter of the print head nozzle can be selected depending on the specifications of the shape of the molded part to be printed. A larger nozzle has the advantage that it allows a higher throughput of the material and therefore faster production. The more delicate the molded part to be printed, the smaller the cross section selected should be in order to provide a print with sufficient precision. Filaments with a consistently uniform cross-sectional diameter of 1.52 mm to 1.96 mm have been shown to be advantageous in processing, and inconsistencies in the cross section of the filament up to an ellipticity of 0.06 can be tolerated. The ellipticity (O) of the cross section of each filament under consideration is here defined as its maximum diameter (D max ) and its minimum diameter (D min ) divided by their sum, i.e., O=2×(D max -D min ) / (D max +D min ) is defined as the minimum outer diameter of the filament. Preferably, the prepared filament is wound onto a spool with a minimum outer diameter of 0.23 mm, but may be higher. Winding onto a small diameter spool without breakage can be considered to indicate sufficient elasticity for processing in a 3D printing process. For polyglycerol fatty acid ester-containing compositions, the production of filaments may be carried out with a throughput of extrusion material at the extruder nozzle head of up to 7 kg / h, as long as the sieved powder is transformed into a soft mass due to the temperature used.

[0015] In principle, there are two possibilities for incorporating active or other substances into the product of the 3D printing process. Either the substance is already incorporated into the starting material for 3D printing and then printed by the 3D printing process to form a given molded part, or the starting material remains free of active or other substances and is then introduced into the cavity or chamber of the at least partially prepared molded article. The incorporation of the finely divided solid into the polyglycerol fatty acid ester-containing composition to form the starting material for the 3D printing process is preferably carried out by mixing one or more finely divided solids into the molten components of the polyglycerol fatty acid ester-containing composition, the weight percentage of which in the overall mixture should not exceed 10% so that the processability of the starting material thus obtained is maintained. In this regard, the type of substance mixed as the finely divided solid is of no practical importance. Preferably, the finely divided solid is from the group of pharmaceutical active substances or cosmetic active substances.

[0016] In the case of the second possibility for incorporating active substances or other substances into the product of the 3D printing process, the polyglycerol fatty acid ester-containing composition, preferably as a filament, can be printed itself to form a molded article with one or more cavities and / or chambers. A simple way to achieve this is to 3D print a molded article, for example in the form of a cup, into whose cavity the active substance or other substance, which may be solid, semi-solid or liquid, can be introduced as a filling material. The opening of the molded article can then be closed by a second molded part, for example in the form of a lid, suitable to fit into it in an interlocking and / or friction-fitting manner, preferably printed from the same starting material. A more elegant solution here is to incorporate the filling material into the molded article, where the printing of the molded article is first carried out to the point where sufficient cavities have been formed for filling, then the filling material can be introduced and then the 3D printing can be completed, preferably closing the filled cavities to form chambers provided with the filling material. All the advantages of the 3D printing process can be utilized in this way. Thus, it is possible to incorporate different substances, such as two or more different pharma- ceutical actives, into separate chambers of the same shaped article. The release of the actives can be controlled by the different wall thicknesses.

[0017] Thus, the polyglycerol fatty acid ester-containing compositions proposed herein allow a 3D printing process, allowing the incorporation of active substances or other substances into the starting material for the 3D printing process, and also the incorporation of solid, semi-solid or liquid filler materials into appropriately shaped molded articles. Moreover, both variants can be combined together, so that solids mixed with the starting material can be released directly from the material of the printed molded article, and filler materials located in chambers or cavities can only escape from the cavities or chambers after the collapse of the walls that bound them, or through channels of preferably narrow shape.

[0018] The printing procedure is preferably initiated by passing the polyglycerol fatty acid ester-containing composition, in the form of a powder or as a filament, in the applied 3D printing process, with or without the mixture, through a print head nozzle having an inlet and an outlet. The additive manufacturing of the article of a given three-dimensional shape is then carried out by a corresponding given movement of the outlet from the print head nozzle in various planes. Preferably, in this regard, a temperature-controllable print head nozzle is used, the temperature of which during the printing procedure is 1°C to 4.9°C higher than the melting temperature of the starting material.

[0019] The filling material can be introduced in various ways. It has already been mentioned above that the opening of the cavity filled with the second molded part is closed or that the filling material is introduced into a suitable cavity already formed in a part of the molded article before finishing the molded article as a whole, and then printed into the chamber or more developed cavity during finishing of the molded article. A third possibility is to fill the cavity or chamber of the already-made molded article with the filling material by means of a cannula, preferably before it is fully cured. Obviously, the above mentioned filling possibilities can be combined in any way.

[0020] If the filling material contains one or more medicamentously active substances, these are preferably glucocorticoids, mineralocorticoids, androgens, estrogens, gestagens, azole antifungals, ACE inhibitors or AT1 antagonists. This group of medicamentously active substances is also suitable as a mixture for the polyglycerol fatty acid ester-containing composition.

[0021] The invention will now be explained in more detail, without limitation, with the aid of a drawing and two examples. [Brief description of the drawings]

[0022] [Figure 1] Cup-shaped molded part (Figure 1a, Figure 1b, dimensions (mm)). [Diagram 2] Lid-shaped molded part (Figure 2a, Figure 2b, dimensions (mm)). EXAMPLES

[0023] Example 1 80.5% by weight of hexaglyceryl palmitate partial ester with an average hydroxyl number of 160 was used as component 1. 8.0% by weight of hexaglycerol was used as component 2 and 11.5% by weight of hexaglyceryl monopalmitate was used as component 3. The components were mixed together and melted. The melt was homogenized by stirring and left to solidify at room temperature of 20° C. and at a pressure of 1005 hPa. Portions of the melt were placed in five identical molds and thus formed into plates of 155 mm×45 mm×15 mm, which, after hardening, were subjected to bending fatigue tests as described above. The average force required to break the plates was 83 N. The solidified mass was crushed and passed through a sieve with a pore size of 800 μm. The sieved material was extruded at a temperature of 49° C. to form filament strands with a uniform continuous cross section of 1.75 mm and a maximum ellipticity of 0.02. The filament was wound onto a spool with a minimum diameter of 23 mm. The spool of filament was inserted into the 3D printer and 3D printing was started with a print nozzle temperature of 50.5 °C. The printed molded part was in the form of a handless cup (Figure 1a, Figure 1b, dimensions (mm)). A filler material consisting of 10 mg of micronized prednisolone was introduced into the cup-shaped molded part. At the same time that the cup-shaped molded part was formed (Figure 1a, Figure 1b, dimensions (mm)), a lid-shaped molded part (Figure 2a, Figure 2b, dimensions (mm)) that fits into the opening of the cup-shaped molded part (Figure 1a, Figure 1b, dimensions (mm)) was printed from the same starting material. The opening of the cup-shaped molded part (Figure 1a, Figure 1b, dimensions (mm)) was closed by the lid-shaped molded part (Figure 2a, Figure 2b, dimensions (mm)) to form the finished prednisolone-containing product.

[0024] Example 2 67.7% by weight of hexaglyceryl palmitate partial ester with an average hydroxyl value of 160 was used as component 1. 13.6% by weight of hexaglycerol was used as component 2 and 9.6% by weight of hexaglyceryl monopalmitate was used as component 3. 9.1% by weight of micronized dexamethasone was added. The components were mixed together and melted. The melt was homogenized by stirring and left to solidify at room temperature of 20°C and a pressure of 1005 hPa. The solidified mass was crushed and passed through a sieve with a pore size of 800 μm. The sieved material was extruded at a temperature of 49°C to form a filament strand with a uniform continuous cross section of 1.75 mm and a maximum ellipticity of 0.02. The filament was wound onto a spool with a minimum diameter of 23 mm. The spool of filament was inserted into a 3D printer and 3D printing was started with a print nozzle temperature of 50.5°C. The printed molded part was in the form of a flattened cylinder, providing the finished dexamethasone-containing product in the form of a tablet. The present invention includes the following preferred embodiments. (1) Ingredients include: Component 1, i.e. polyglycerol fatty acid esters obtainable from the esterification of polyglycerols containing from 2 to 10 glyceryl units with fatty acids containing from 12 to 22 carbon atoms; Component 2, i.e., a free polyglycerol containing 2 to 10 glyceryl units, and A polyglycerol fatty acid ester-containing composition, characterized by component 3, i.e., a polyglycerol fatty acid monoester containing 2 to 10 glyceryl units and containing a fatty acid residue containing 12 to 22 carbon atoms. (2) Component 1 can be obtained from the esterification of polyglycerol containing 2 to 6 glyceryl units, and component 2 consists of free polyglycerol containing only 3 to 6 glyceryl units. Characterized in that A composition containing a polyglycerol fatty acid ester according to (1). (3) Component 1 has a hydroxyl value of 50 mg KOH / g to 350 mg KOH / g. Characterized in that A polyglycerol fatty acid ester-containing composition according to (1) or (2). (4) Component 1 has a melting point in the temperature range of 35°C to 80°C. Characterized in that A polyglycerol fatty acid ester-containing composition according to any one of (1) to (3). (5) Component 1 has a saponification value within the range of 100 mg KOH / g to 250 mg KOH / g. Characterized in that A polyglycerol fatty acid ester-containing composition according to any one of (1) to (4). (6) Component 2 has a hydroxyl value of 800 mg KOH / g to 1400 mg KOH / g. Characterized in that A polyglycerol fatty acid ester-containing composition according to any one of (1) to (5). (7) Component 3 has a hydroxyl value of 400 mg KOH / g to 650 mg KOH / g. Characterized in that A polyglycerol fatty acid ester-containing composition according to any one of (1) to (6). (8) The weight percentage of component 1 is at least 50%, the weight percentage of component 2 is at least 5%, the weight percentage of component 3 is at least 10%, and the sum of the weight percentages of components 1 to 3 is at least 98%. Characterized in that A polyglycerol fatty acid ester-containing composition according to any one of (1) to (7). (9) Component 1 can be obtained by partial esterification of hexaglycerol with palmitic acid, and in component 3, the fatty acid residue contains 16 carbon atoms. Characterized in that A polyglycerol fatty acid ester-containing composition according to any one of (1) to (8). (10) The process is as follows: i) melting and mixing components 1, 2 and 3 together; ii) solidifying the mixture at a temperature between 15°C and 25°C and a pressure between 750hPa and 1250hPa Characterized by: A method for producing a polyglycerol fatty acid ester-containing composition according to any one of (1) to (9). (11) The process is as follows: i) (step i according to 10), ii) (step ii according to 10), iii) grinding the solidified mixture; iv) sieving the ground mixture through a sieve having a pore size of 800 μm or less and recovering the sieved powder. Characterized by: How to make starting materials for the 3D printing process. (12) Further steps of: v) extruding the starting material prepared as described in (11) through an extruder nozzle head to form filaments at a temperature at least 1° C. lower than the melting temperature of component 1 of the starting polyglycerol fatty acid ester-containing composition described in (11). Characterized by: The method according to (11). (13) Further steps of: vi) selecting filaments having a continuous uniform cross-sectional diameter in the range of 1.52 mm to 1.96 mm, with a non-uniformity in the cross-section of each filament, taking into account an ellipticity of up to 0.06; Characterized by: The method according to (12). (14) Further steps of: vii) A process for winding the filament emerging from the extruder nozzle head onto a spool having a minimum outer diameter of 23 mm or more. Characterized by: The method according to (12) or (13). (15) In step v), the sieved powder, which has been transformed into a soft mass due to the temperature conditions, is fed to the extruder nozzle head with a throughput of up to 7 kg / h. Characterized in that The method according to any one of (12) to (14). (16) In step ii) one or more finely divided solids, which together do not exceed 10% by weight of the total mixture, are mixed with the molten components. Characterized in that The method according to any one of (11) to (15). (17) The solid is associated with a group formed by a pharmaceutical or cosmetic active substance Characterized in that The method according to (16). (18) The polyglycerol fatty acid ester-containing composition according to any one of (1) to (10) above, A molded part produced by 3D printing, comprising one or more chambers and / or one or more cavities. (19) At least one chamber or cavity contains a filler material; Characterized in that (18) A molded part according to (18). (20) The fill material is or comprises a pharma- ceutical active substance; Characterized in that A molded part according to (18) or (19). (21) The filling material is in solid, semi-solid or liquid form. Characterized in that The molded part according to any one of (18) to (20). (22) At least two different filler materials Characterized by: The molded part according to any one of (18) to (21). (23) The different fill materials are or contain different pharma- ceutical active substances. Characterized in that (22) A molded part according to (22). (24) The process is as follows: i) passing a starting material produced according to any one of (11) to (17) through a print head nozzle having an inlet and an outlet; ii) building up an article of predetermined three-dimensional shape layer by layer by corresponding predetermined movements of the print head nozzle outlets in various planes. 3D printing process. (25) The print head nozzle is heated to 1°C to 4.9°C above the melting temperature of the starting material; Characterized in that (24) 3D printing process. (26) The process is as follows: i) step i) according to (24) or (25), ii) step ii) according to (24) or (25), which is divided into the following substeps: ii-a) building up portions of the molded part step by step until all of the chambers or cavities provided for filling are produced as partial or complete cavities that can be filled; ii-b) filling the cavities provided for filling, partially or completely, with the respective filling material; ii-c) The process of completing the molded part Characterized by: 3D printing process according to (24) or (25). (27) Further steps of: iii) Closing the opening of the cavity by placing a second molded part manufactured by the 3D printing process according to any one of (24) to (26). Characterized by: The 3D printing process according to any one of (24) to (26). (28) The finished molded part has at least one chamber into which the fill material is introduced by a cannula. Characterized in that The 3D printing process according to any one of (24) to (27). (29) The one or more filler materials contain at least one pharma- ceutical active substance from the group formed by glucocorticoids, mineralocorticoids, androgens, estrogens, gestagens, azole antifungals, ACE inhibitors or AT1 antagonists. Characterized in that A 3D printing process according to any one of (24) to (28).

Claims

1. The following steps: i) component 1, i.e., polyglycerol fatty acid esters which are esters of polyglycerol containing from 2 to 10 glyceryl units with fatty acids containing from 12 to 22 carbon atoms; Component 2, i.e., free polyglycerol containing 2 to 10 glyceryl units, and Component 3, i.e., polyglycerol fatty acid monoesters containing 2 to 10 glyceryl units and containing fatty acid residues containing 12 to 22 carbon atoms. melting and mixing together; ii) solidifying the mixture at a temperature between 15°C and 25°C and a pressure between 750hPa and 1250hPa; iii) grinding the solidified mixture; and iv) sieving the ground mixture through a sieve having a pore size of 800 μm or less and recovering the sieved powder. Characterized by: A method for producing starting materials for the 3D printing process.

2. The weight percentage of component 1 is at least 50%, the weight percentage of component 2 is at least 5%, the weight percentage of component 3 is at least 10%, and the sum of the weight percentages of components 1-3 is at least 98%. Characterized in that The method of claim 1 .

3. Further steps of: v) extruding the starting material produced as claimed in claim 1 or 2 through an extruder nozzle head to form filaments at a temperature at least 1°C below the melting temperature of component 1. Characterized by: The method according to claim 1 or 2.

4. Further steps of: vi) selecting filaments having a continuous uniform cross-sectional diameter in the range of 1.52 mm to 1.96 mm, with inconsistencies in the cross-section of each filament, taking into account an ellipticity of up to 0.06; Characterized by: The method according to claim 3.

5. Further steps of: vii) winding the filament exiting the extruder nozzle head onto a spool having a minimum outer diameter of 23 mm or more; Characterized by: The method according to claim 3 or 4.

6. In step v), the sieved powder, which has been transformed into a soft mass due to the temperature conditions, is fed to the extruder nozzle head with a throughput of up to 7 kg / h. Characterized in that The method according to any one of claims 3 to 5.

7. In step ii), one or more finely divided solids, which together do not exceed 10% by weight of the total mixture, are mixed with the molten components. Characterized in that The method according to any one of claims 1 to 6.

8. The solid is associated with a pharmaceutical or cosmetic active substance Characterized in that The method of claim 7.

9. The composition comprises a polyglycerol fatty acid ester-containing composition comprising components 1, 2 and 3 according to claim 1 or 2. A molded part produced by 3D printing, comprising one or more chambers and / or one or more cavities.

10. At least one chamber or at least one cavity comprises a filler material; Characterized in that 10. The molded part of claim 9.

11. The fill material is or comprises a pharma- ceutical active substance; Characterized in that 11. The molded part of claim 10.

12. The filling material is in solid, semi-solid or liquid form. Characterized in that 12. Moulded part according to claim 10 or 11.

13. At least two different filler materials Characterized by: Moulded part according to any one of claims 10 to 12.

14. The different fill materials are or contain different pharma- ceutical active substances. Characterized in that 14. The molded part of claim 13.

15. The following steps: i) passing a starting material produced according to any one of claims 1 to 8 through a print head nozzle having an inlet and an outlet; ii) building up an article of predetermined three-dimensional shape layer by layer by corresponding predetermined movements of the print head nozzle outlets in various planes; 3D printing process.

16. The print head nozzle is heated to 1°C to 4.9°C above the melting temperature of the starting material; Characterized in that 16. The 3D printing process of claim 15.

17. The 3D printing process according to claim 15 or claim 16, characterized by a modified step ii) defined in the following substeps, in which step ii-b1) is added: ii-a1) building up a portion of the molded part in stages until all of the chambers or cavities provided for filling are produced as partial or complete cavities that can be filled; ii-b1) filling the partial or complete cavities provided for filling with the respective filling material; and ii-c1) Completing the molded part.

18. The 3D printing process according to claim 15 or claim 16, characterized by a modified step ii) defined in the following substeps, in which step ii-b2) is added: ii-a2) building up the moulded part step by step until all of the cavities provided for filling are produced as complete cavities which can be filled; ii-b2) filling the complete cavities provided for filling with the respective filling material; and ii-c2) Closing the opening of the complete cavity by placing a second molded part produced by the 3D printing process according to claim 15 or 16.

19. The finished molded part has at least one chamber into which the fill material is introduced by a cannula. Characterized in that 3D printing process according to any one of claims 15 to 18.

20. The filling material comprises at least one pharma- ceutical active agent selected from the group consisting of glucocorticoids, mineralocorticoids, androgens, estrogens, gestagens, azole antifungals, ACE inhibitors, or AT1 antagonists. Characterized in that 20. The 3D printing process according to any one of claims 17 to 19.

Images