ADDITIVE METHOD FOR THE THREE-DIMENSIONAL PRINTING OF OBJECTS CONTAINING ACTIVE INGREDIENTS
Patent Information
- Application Number
- AT2020728083T
- Authority / Receiving Office
- AT · AT
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2019-05-31
- Filing Date
- 2020-05-29
- Publication Date
- 2026-04-15
- Estimated Expiration
- 2040-05-29
Abstract
Description
[0001] Additive manufacturing process for the three-dimensional printing of objects containing active ingredients
[0002] The present invention relates to an additive manufacturing process for producing solid or semi-solid three-dimensional objects containing one or more pharmaceutical active ingredients, as well as the objects produced by the process, such as semi-solid or solid dosage forms or medical devices. The process is an additive, preferably three-dimensional, printing process in which individual, defined volume increments are printed, which are differentiated with respect to the active ingredients contained, the carrier materials used, the shape, size, color, active ingredient concentrations, and arrangement in the produced object.
[0003] They are essentially freely selectable.
[0004] From WO 2016 / 038356 A1, an additive 3D printing process for manufacturing is described.
[0005] pharmaceutical dosage forms are known to be produced using filament fusion fabrication (FFF).
[0006] The object of the present invention is to provide a method for the manufacture of drug-containing objects such as pharmaceutical dosage forms or drug-containing medical devices, which allows for increased flexibility in the choice of different base materials, active ingredients and their distribution in the drug-containing object.
[0007] The above problem is solved by the embodiments of the present invention as disclosed in the claims, the present description and the accompanying figures.
[0008] In particular, the present invention provides a method for producing a
[0009] three-dimensional object containing at least one pharmaceutical active ingredient, comprising the following steps:
[0010] (i) Creating a two- or three-dimensional representation of the object to be produced by predefined volume increments;
[0011] (ii) Printing a predefined volume increment onto a build-up device or onto an object arranged on the build-up device;
[0012] (iii) Printing a further volume increment such that the volume increments at least partially touch or overlap; and
[0013] (iv) Repeating steps (ii) and (iii) until the object is created; wherein at least one of the volume increments contains at least one pharmaceutical active ingredient and the volume increments are made from a base composition that is flowable at a pressure temperature compatible with the at least one active ingredient or
[0014] The base substance comprises a material that solidifies after printing the respective volume increment and / or the volume increments are superficially bonded together.
[0015] The term "three-dimensional object" is to be understood according to the invention as meaning that in the real world, every object produced by two- or three-dimensional printing processes, especially pharmaceutical dosage forms and medical devices, extends in three spatial directions. Insofar as the method according to the invention is based on the
[0016] If a build-up device or an object already present on the build-up device is used to print only a layer of at least partially contacting volume increments, the method according to the invention can also be described as a 2D printing method. If the volume increments are applied, for example, as droplets which
[0017] for example by subsequent moisture removal, e.g. by drying,
[0018] While macroscopically they represent two-dimensionally extended units, microscopically they are three-dimensional structures, so that in such embodiments of the invention the object also has a three-dimensional form.
[0019] exhibits expansion.
[0020] According to a preferred embodiment of the method according to the invention, the object is built up layer by layer, i.e., in steps (ii) and (iii) the
[0021] Volume increments are printed layer by layer. Preferably, the
[0022] Volume increments printed row by row or column by column.
[0023] The present invention is characterized in particular by the high flexibility of the
[0024] The composition and the multitude of possible structures for the produced semi-solid or solid object are key advantages. In preferred embodiments of the process, different volume increments can contain different active ingredients and / or different amounts of active ingredients and / or different base compositions or base substances. Furthermore, the shape and / or volume of the volume increments (hereinafter also referred to as "voxels") can be the same or different.
[0025] However, according to the invention, it is also provided that the object is made entirely of
[0026] volume increments are built up, all of which contain a single, identical active ingredient, and according to the invention it is also provided that each volume increment can contain the same amount of the active ingredient or the same concentration of the active ingredient.
[0027] The volume increments are essentially freely definable and can, for example, assume droplets, spheres, dots, cylinders, cubes, cuboids, or other shapes. According to the invention, the aforementioned geometric shapes (spheres, cylinders, cubes, cuboids) are to be understood as meaning that the voxels essentially assume this shape, preferably when solidified after printing. Therefore, other preferred voxel shapes according to the invention include, more generally, pellets, which preferably approximate a spherical or cylindrical shape, and granules. Preferred voxel shapes are thus, in particular, droplet-, pellet-, cylinder-, and granulate-shaped voxels. As already explained above, the shape (e.g., the examples mentioned above) and the volume size of the volume increments can be freely combined essentially independently of one another.
[0028] Certain preferred embodiments of the method according to the invention make use of the principle of free selection of the volumes of the printed volume increments:
[0029] In principle, the volume of a pharmaceutical dosage form shrinks from the outside inwards as it degrades towards the release site. This causes the amount of active ingredient released per unit of time to decrease. To ensure the most uniform possible release of the active ingredient throughout the degradation process,
[0030] To achieve the dosage form, the invention provides that
[0031] to print volume increments in such a way that the volume of the printed
[0032] Volume increments increase from the outside to the inside. According to the invention, this is achieved by printing corresponding layers of volume increments, wherein the volume of the volume increments increases from layer to layer or from group of layers of the same volume to further layers of the same volume from the outside to the inside.
[0033] As already explained, different pharmaceutical active ingredients (so-called APIs, active pharmaceutical ingredients) can be contained in the object using the method according to the invention. Furthermore, several (i.e., two or more) active ingredients can be contained in the volume increments. Of course, it is also possible to use other ingredients.
[0034] Volume increments are printed such that each volume increment contains one API, but different APIs (two or more) are present in separate volume increments. Volume increments containing different concentrations (i.e., amount of active ingredient per volume increment) of a pharmaceutical active ingredient can also be printed. In one embodiment of the process, the method can be designed such that the volume increments containing the active ingredient are structured and printed in such a way that at least one first group of touching or overlapping volume increments containing the same amount of active ingredient contains the same amount, and at least one second group of touching volume increments contains an amount of active ingredient that differs from the amount of active ingredient in the first group. In this way, concentration gradients can be created in an object produced by the process.This embodiment of the invention is also used in preferred variants of the invention.
[0035] Providing a consistent drug release is used, as above for the
[0036] The increase in volume of the volume increments in the dosage form is described from the outside inwards. This is done to ensure the most uniform distribution possible.
[0037] The release of the active ingredient(s) is preferably achieved by printing the volume increments in such a way that the concentration of the active ingredient preferably increases from the outside to the inside in the volume increments.
[0038] In the production of objects according to the inventive method, groups of volume increments with different pharmaceutical active ingredients can be formed. At least one first group of active ingredient-containing
[0039] Volume increments must be present, containing a first pharmaceutical active ingredient, and at least one second group of active ingredient-containing volume increments must be present, containing a second pharmaceutical active ingredient different from the first. The different groups of volume increments can be printed in such a way that they are grouped together within the object. That is to say, the
[0040] Volume increments of the first and / or second group (and, if applicable, each additional group if more than two active ingredients are to be present in the object to be printed) are printed in such a way that the volume increments of the respective group touch each other.
[0041] In further embodiments of the invention, it is also provided that active ingredient-containing volume increments are printed in such a way that they form one or more groups within the object, which are at least partially, and in other embodiments also completely, surrounded by non-active ingredient-containing volume increments that separate or shield the active ingredient-containing volume increments from the external environment, so that, for example, an object with an active ingredient-containing core or at least an inner group of interconnected active ingredient-containing volume increments (or several inner groups of adjacent volume increments with the same or
[0042] a core area (with different active ingredients or the same or different amounts of active ingredients) is created, around which non-active-ingredient volume increments are arranged. The "outer environment" can be the milieu surrounding the object. In this context, "outer environment" around a core area or an inner group of directly connected volume increments also includes other areas within the printed object; that is, non-active-ingredient volume increments can be located within it.
[0043] According to the invention, the object contains groups of volume increments containing active ingredients, at least partially, and optionally completely, separated from other individual or groups of increments.
[0044] Volume increments containing, for example, another (or several other) active ingredient(s) are surrounded to create separating layers or separation zones between the
[0045] to form differently equipped volume increments.
[0046] In preferred embodiments, such arrangements can be used for spatial
[0047] Isolation of the individual drug-containing volume increments can be used, for example, to...
[0048] to avoid chemical instabilities of the individual active ingredients and / or to separate different active ingredients that are chemically incompatible with each other (because they react with each other or otherwise impair their structure and / or effectiveness).
[0049] In other embodiments of the aforementioned type, for example, drug abuse deterrent tablets or capsules can also be provided that prevent, for example, an active ingredient (e.g., opioids or drugs with addictive potential) from being extracted from a dosage form, for example, by comminution or in some other way, and from being subjected to misuse. Thus, in preferred embodiments of the invention, groups or layers of volume increments containing the active ingredient(s) (e.g., the aforementioned potentially misusable substances) are printed, which are surrounded by groups or layers of volume increments containing a substance that neutralizes the effect of the active ingredient(s), degrades the active ingredient(s), or otherwise at least limits, and particularly preferably prevents, the potentially misused use of the active ingredient(s). Intermediate layers can be created between the groups (or layers) of active ingredient(s) and
[0050] The anti-abuse substance(s) may also include one or more groups or one or more layers of volume increments which do not contain an active ingredient or an anti-abuse substance (in preferred formulations).
[0051] In various embodiments, these volume increments are simply the ones used.
[0052] (containing the basic building block substance) and separate the active ingredient volume increments from the volume increments containing the abuse prevention substance(s).
[0053] Furthermore, such embodiments with active ingredient-containing volume increments, which are at least partially surrounded by non-active ingredient-containing volume increments, can be used according to the invention, for example, for the production of the slowly releasing active ingredient(s) embodiments such as sustained-release tablets or capsules or gastro-resistant tablets or capsules.
[0054] The method of the present invention can thus be used to produce objects, in particular pharmaceutical dosage forms, which deliver the API(s) to a selected location or area of the desired
[0055] Application release (so-called "drug targeting"), i.e., preferably used to control the release of the drug(s) from the printed dosage form. Such
[0056] These embodiments thus serve to deliver the drug(s) to the optimal site of action or target location, for example (and preferably) after oral administration. In certain embodiments of the invention, the volume increments are printed such that a core area of volume increments of a pharmaceutical dosage form according to the invention contains one or more desired active ingredient(s), and one or more layers of volume increments are arranged around this core area (or core volume). These layers are, for example, degraded or dissolved in the intestine in a pH-dependent manner, so that the core area is only exposed to the surrounding environment in the preselected region of the intestine through the pH-dependent degradation of the outer layer(s), thereby releasing the active ingredient(s).This is usually achieved through polymers present in the building material that are well known in the field (such as shellac, copolymers of methacrylic acid and...).
[0057] Methacryl methacrylate, modified celluloses, etc.) whose pH-dependent degradation or pH-dependent solubility is very finely controllable, so that pH-dependent release of the active ingredient-containing core region of the dosage form can be provided for each section of the intestine, in particular the small intestine (duodenum, jejunum, and ileum) according to the invention. The provision of targeted release at a specific site of action or target location, such as the intestine or a selected intestinal segment, is not limited to pH-dependently degradable or pH-dependently soluble layers of volume increments with corresponding pH-dependently degradable or pH-dependently soluble polymers contained in such building blocks. Alternative or additional mechanisms can also be implemented. For example, according to the invention, the
[0058] Volume increments are printed in such a way that one or more layers of volume increments are formed, for example, directly on a core area containing the active ingredient or on one or more intermediate layers that may be present, the composition of which contains or consists of a bacteriologically degradable component. Bacteriologically degradable polymers known to experts, such as starches, are suitable for this purpose.
[0059] Celluloses. Such layers preferably serve to release active ingredients in the colon. In preferred embodiments, the aforementioned layers, e.g., pH-dependent degraded layers (one or more) and bacteriodegradable layers, can be combined. For example, dosage forms for pharmaceutical drug combinations can be printed in this way, in which volume increments containing a first active ingredient are arranged in a core region, surrounded by one or more layers of volume increments containing bacteriodegradable substances.
[0060] The core component contains (or consists of) a base material. This is followed by one or more layers with volume increments containing a second active ingredient, followed by one or more layers containing (or consisting of) one or more pH-dependent degradable polymer(s) in the base material. Alternatively, in such an embodiment with multiple drug-targeting layers, only the core component can contain one or more active ingredients.
[0061] Since the process can also be carried out under sterile conditions, the
[0062] The printing methods according to the invention can also be used to provide implants and / or drug-releasing injections or drug depots.
[0063] Furthermore, according to the invention, the increased flexibility of the process is also enhanced by the fact that very different materials (active ingredients and base compositions or substances) can be used for the volume increments to be printed.
[0064] The bonding between the individual applied volume increments can be achieved in various ways. In one embodiment, for example, when using a fusible material, the bonding between such voxels can occur through solidification after application to the support structure. This solidification can be carried out by various mechanisms, such as simple cooling and / or chemically using known substances. In another embodiment, a suitable binder can be added to the voxel material, e.g., a dispersion or a solution, which causes the voxel to harden after application. This hardening by the binder can be achieved, for example, through heat supplied by a suitable heat source in the printing device, such as a light source, preferably a laser device.The curing by the binder can also be achieved chemically using appropriate starter molecules and / or light of a suitable wavelength, the latter preferably being emitted with the aid of a laser device. In a further embodiment, the fluid of the volume increment can contain one or more
[0065] Starting compounds, typically monomers, of one or more polymers are contained, and after the voxel is applied, a polymerization is initiated by suitable means such as light, heat or other polymerization initiators, which hardens the applied voxel and connects or bonds it to neighboring voxels.
[0066] Suitable carrier materials that are flowable at the printing temperature and in which the pharmaceutical active ingredient(s) is / are present are, for example, generally suitable for a
[0067] Hot melt extrusion (HME) uses carriers such as low-melting waxes and polymers. The HME mixture, or more generally the
[0068] The volume increment mixture can contain, in addition to the low-melting support, other components.
[0069] Processing agents and excipients such as binders, plasticizers, antioxidants, fragrances, sweeteners, or similar substances are included. Suitable HME carriers and plasticizers are disclosed, for example, in Crowley et al. (2007) Drug Development and Industrial Pharmacy, 33, 909-926 (carriers: pages 917 to 919, in particular Table 1; plasticizers: pages 917 and 920, in particular Table 2), and the present description expressly refers to these passages.
[0070] The method according to the invention is not limited to the complete de-a / ovo assembly of dosage forms or medical devices. The method can also be applied to objects already present on the assembly apparatus. This includes, for example, previously conventionally or otherwise manufactured components.
[0071] Dosage forms that are to be modified, for example, by the present procedure, or drug-free objects (also called placebo carriers) onto which drug-containing
[0072] Volume increments can be printed according to the invention. For example, drug-free films or other flat materials such as edible paper can be used to provide, for example, drug-containing ODF ("orally degradable film" or "orally dissolvable film") products. In other embodiments, pre-printed patch materials can, for example, be printed with volume increments according to the invention, which, for example,
[0073] They contain wound-healing active ingredients. In further embodiments, placebo carriers, which were produced, for example, by a fused layer modeling process, can be printed using the inventive method with API-containing volume increments and subsequent printing with solvent-containing liquids, whereby the printed layers can alternate.
[0074] The present additive 3D printing process is preferably carried out using computer-aided design. Typically, in step (i), a calculated three-dimensional image of the object to be printed is created, for example, using a common CAD program.
[0075] Computer-generated reproduction of the object to be printed can also be achieved by scanning an existing dosage form. In the present method, the computer-generated model image is then divided into the desired, essentially freely selectable volume increments (voxels), with the resolution of the real object increasing as the volume increments decrease. Each individual volume increment can be assigned, for example, an active ingredient, carrier or base substance, or a carrier or
[0076] Base compositions and / or other auxiliary substances such as colorants and other materials that may be required, as well as their quantity (concentration in the volume increment), are assigned and then printed. Suitable printing devices for the present process are described, for example, in US 2017 / 03,68755 A1 and US 6,070,107.
[0077] In a particularly preferred embodiment, the invention comprises
[0078] The method also includes applying at least one colored substance by means of 2D and / or 3D printing, preferably also by printing corresponding, preferably small-volume voxels according to the present method, and / or by another method, such as two-dimensional printing as in inkjet printing, to the object or to at least one section of the object, such that the applied substance forms at least one information structure visible on the object. The colored substance(s) can be applied separately from the volume increment(s) containing the active ingredient. It is preferred to apply the colored substance(s) together with volume increments containing pharmaceutical active ingredients. In one embodiment, each substance can thus be applied to the area(s) or...
[0079] Sections are marked to which the respective active ingredient has been applied. This embodiment can therefore convey information about the active ingredients contained in the object and their distribution throughout the entire object by means of color coding. In a further embodiment of this invention, different quantities or concentrations of the respective active ingredient can be stored in the active ingredient-containing sections, which in turn are reflected by the concentration of the corresponding colorant. Of course, different colorants can also be mixed, e.g., in a voxel according to the invention (e.g., embodiment), so that by appropriately selecting the mixture(s), the entire visible spectrum can generally be used.
[0080] According to the invention, the term "coloring substance" also includes substances that luminesce, in particular fluoresce.
[0081] The information structure created by the color substance(s) can be diverse
[0082] Information is represented, whereby several different information structures can be used through different color substances, which are essentially freely selectable and combinable. In particular, it is provided according to the invention that the at least one information structure contains information about the type of active ingredient(s) printed in the object and / or about the amount(s) of active ingredient present in the object and / or about the time or period of administration intended for a dosage form and / or about the dosage form intended for
[0083] Date of administration and / or patient-related data (such as name, age,
[0084] gender, medication and illness(es) of the patient) and / or about the health insurance provider and / or about the treating physician and / or about the dosage form
[0085] Providing pharmaceutical companies and / or the medical facility issuing the object, e.g. a dosage form or a medical device, are coded.
[0086] The information structure can be selected from a wide range of application possibilities. The substance(s) can be printed in the form of QR codes, letters, and / or numbers. Various patterns, such as lines, grids, dots, and solids, can also be printed, with voxel printing being the preferred method and offering the greatest versatility. The printed code can thus contain the active ingredient and simultaneously encode the desired data, as described above, regarding the patient, physician, pharmacist, and / or medical or pharmaceutical personnel.
[0087] It is evident to a person skilled in the art that, depending on the specific additive manufacturing process chosen, the color substance(s) present may be combined with the pharmaceutical active ingredient(s) in the respective printed
[0088] The base composition may be present. In the present process, it is preferred that the colorant (or several thereof) is preferably present together with the active ingredient(s) in the build-up substance provided for a given volume increment.
[0089] As already explained above, the dosage form can be of various types.
[0090] Information structures are included, preferably those mentioned in the procedure described above.
[0091] The printable objects containing active ingredients are, in particular, semi-solid or solid pharmaceutical dosage forms, such as tablets, capsules, implants, patches, suppositories, or thin films. These objects can be produced using the method according to the invention.
[0092] Tablets are diverse and include oblong tablets, lozenges, implant tablets, multiple-application tablets, dispersible tablets, sustained-release tablets, vaginal tablets and suppositories, ocular tablets, coated tablets, matrix tablets, chewable tablets, film-coated tablets, modified-release tablets, lacquered tablets, margarine-resistant tablets, and drug abuse deterrent tablets.
[0093] Other particularly suitable objects are medical devices such as topical drug formulations containing active ingredients, contact lenses, and plasters, which preferably release the active ingredient(s) for local application.
[0094] The present invention also relates to the two- or three-dimensional objects produced by the method (preferably those mentioned above), wherein these contain at least one pharmaceutical active ingredient.
[0095] The present invention is explained in more detail by the accompanying figures.
[0096] Fig. 1 shows a schematic representation of a cross-section of a three-dimensional object that is divided into individual volume increments (square in cross-section) (hereinafter also referred to as "voxelized").
[0097] Fig. 2 shows schematic representations of a three-dimensional object subdivided into cube-shaped volume increments (i.e., voxelized), where in Fig. 2A the resolution of the object is smaller due to larger voxels (i.e., coarser resolution) and in Fig. 2B the resolution is larger due to subdivision into smaller volume increments (i.e., finer resolution).
[0098] Resolution).
[0099] Fig. 3 shows a schematic representation of a cross-section of a three-dimensional object in which volume increments (shown as squares in the cross-section) without active ingredient or containing an active ingredient voxel (shown in light colors) and volume increments with active ingredient (shown in dark colors) are present, resulting in a concentration of voxels with active ingredient of, for example, 50%.
[0100] Fig. 4 shows a schematic representation of a cross-section of a three-dimensional object in which individual voxels contain active ingredient (shown in dark), such that 25% of the voxels contain the active ingredient. According to the invention, the ratio of voxels containing the active ingredient to voxels without the active ingredient, or the volume fraction of the voxels containing the different active ingredients, can be varied arbitrarily between 0.1% and 99.9%.
[0101] Fig. 5 shows a schematic representation of a cross-section of a three-dimensional object in which drug-containing voxels (dark) are grouped together in the interior and surrounded by non-drug-containing voxels (light), so that these can protect the drug-containing voxels from the environment, such as body fluids. Such a structure allows the release of the drug to be controlled. In other
[0102] In embodiments, the release control, as disclosed above, can be achieved using pH-dependent soluble or biodegradable polymers. The various concentrations and materials can yield very high-resolution dosage forms using the method disclosed and described herein. For example, in Fig. 5, the dark voxels can correspond to Fig. 3 and the light voxels to Fig. 4. In this way, tablets with abuse deterrent properties, as already explained above, can also be produced.
[0103] Fig. 6 shows a schematic representation of an object producible according to the invention, which further develops the embodiment described in Fig. 5: Voxels with a first active ingredient (blue) are surrounded by voxels with a second active ingredient (red), which in turn are surrounded by voxels without active ingredient. This embodiment can, for example, also be designed such that different active ingredients are used instead of different active ingredient concentrations.
[0104] Fig. 7 shows a schematic representation of a cross-section of a three-dimensional object, in which a concentration gradient of the active ingredient is built up in the object by decreasing density of the active ingredient-containing voxels (dark) from left to right.
[0105] Fig. 8 shows a schematic representation of an object that can be produced according to the invention, in which voxels containing three different active ingredients or concentrations of active ingredients (blue, red, green) are distributed in the object and surrounded by voxels containing no active ingredients.
[0106] In exemplary embodiments, the method according to the invention can, for example, adapt the drug release to the physiological needs of patients with heart disease or hypertension. For instance, a cholesterol-lowering drug (e.g., a statin) and two antihypertensive substances (e.g., a sartan and a beta-blocker) can be compressed into a single dosage form in such a way that the drug release over 24 hours optimally corresponds to the patient's physiological conditions. If the patient takes the dosage form in the morning, the antihypertensive substances can be released quickly, while the cholesterol-lowering drug is released only after a 12-16 hour delay in order to reduce nocturnal cholesterol synthesis.
[0107] In further examples of the method according to the invention, an up-titration of newly diagnosed patients with diseases such as Parkinson's, multiple sclerosis, heart attack, strokes or transplant patients and applications in geriatrics or
[0108] These medications are available for pediatric use. In all these cases, patient-specific dosing or release of active ingredients can optimize efficacy and reduce side effects.
[0109] The present invention relates in particular to the following aspects and preferred
[0110] Types of embodiment:
[0111] 1. Method for manufacturing an object containing at least one pharmaceutical active ingredient, comprising the steps:
[0112] (i) Creating a two- or three-dimensional representation of the object to be produced by predefined volume increments;
[0113] (ii) Printing a predefined volume increment onto a build-up device or onto an object arranged on the build-up device;
[0114] (iii) Printing a further volume increment such that the
[0115] Volume increments at least partially touch or overlap; and
[0116] (iv) Repeat steps (ii) and (iii) until the object is created;
[0117] wherein at least one of the volume increments is at least one
[0118] contains a pharmaceutical active ingredient and comprises volume increments consisting of a base composition or base substance that is flowable at a printing temperature compatible with at least one active ingredient and that solidifies and / or bonds together after printing the respective volume increment.
[0119] 2. Method according to point 1, wherein steps (ii) and (iii) are carried out such that the volume increments are printed layer by layer.
[0120] 3. Method according to point 1 or 2, wherein each volume increment contains an active ingredient.
[0121] 4. Method according to point 1 or 2 above, wherein different volume increments have different active ingredients and / or different amounts of active ingredients and / or different base compositions or base substances.
[0122] 5. Procedure according to one of the preceding points, wherein the form of the
[0123] Whether volume increments are the same or different.
[0124] 6. A method according to any of the preceding points, wherein the volume of the volume increments is the same or different. A method according to point 6, wherein the volume of the volume increments is different such that the volume of the volume increments in the printed object increases from the outside to the inside. A method according to any of the preceding points, wherein the shape of the
[0125] Volume increments are selected from the group consisting of drops, spheres, points, cylinders, cubes, and cuboids. A procedure according to one of the preceding steps, wherein the active ingredient is used.
[0126] Volume increments are constructed and printed such that at least one first group of touching or overlapping drug-containing volume increments contains the same amount of drug, and at least one second group of touching volume increments contains an amount of drug that differs from the amount of drug in the first group. A method according to any of the preceding points, wherein at least one first group of drug-containing volume increments is present, containing a first pharmaceutical active ingredient, and at least one second group
[0127] Active ingredient-containing volume increments are present, which contain a second pharmaceutical active ingredient different from the first active ingredient. Method according to point 10, wherein the volume increments of the first and / or the second group are printed such that the volume increments of the respective group touch each other. Method according to one of the preceding points, wherein the volume increments are printed such that active ingredient-containing volume increments form one or more groups within the object, which are separated from non-active ingredient-containing
[0128] Volume increments are surrounded, which shield the drug-containing volume increments from the environment. Method according to point 12, wherein the drug-containing volume increments in the object form a drug-containing core around which non-drug-containing volume increments are arranged. 14. Method according to point 12, wherein the volume increments are printed such that drug-containing volume increments form several groups, each of which is surrounded by non-drug-containing volume increments.
[0129] 15. Procedure according to point 13 or 14, wherein the non-active ingredient
[0130] Volume increments contain a substance that at least limits the effect of the active ingredient(s) in the active ingredient-containing volume increments when the printed object is shredded.
[0131] 16. Procedure according to one of points 13 to 15, wherein the / the
[0132] The active ingredient(s) is / are one or more substances with addictive potential.
[0133] 17. Procedure according to point 13, wherein the non-active-ingredient volume increments
[0134] printed in such a way that they form one or more pH-dependent degradable layers around an active ingredient-containing core in the intestine of a patient.
[0135] 18. Procedure according to one of points 14 to 17, wherein non-active ingredient
[0136] Volume increments caused a delayed release of the active ingredient(s).
[0137] 19. Procedure according to one of points 13 to 18, wherein non-active ingredient
[0138] Volume increments provide gastric juice resistance to the printed object.
[0139] 20. Method according to any of the preceding points, wherein the active substance-containing object is a semi-solid or solid pharmaceutical dosage form.
[0140] 21. Method according to claim 20, wherein the dosage form is selected from the group consisting of tablets, capsules, suppositories, patches or thin films.
[0141] 22. Procedure according to point 21, wherein the tablets are from the group consisting of
[0142] Oblong tablets, lozenges, implant tablets, multiple-application tablets, dispersible tablets, sustained-release tablets, lacquered tablets and gastro-resistant tablets, vaginal tablets and suppositories, eye tablets, coated tablets, matrix tablets, chewable tablets, film-coated tablets, modified-release tablets are selected.
[0143] 23. A method according to any of points 1 to 16, wherein the object is a medical device. A three-dimensional object containing at least one pharmaceutical active ingredient, manufactured by the method according to any of the preceding points.
Claims
Claims 1. Method for manufacturing an object containing at least one pharmaceutical active ingredient, comprising the steps of: (i) Creating a two- or three-dimensional representation of the object to be produced by predefined volume increments; (ii) Printing a predefined volume increment onto a build-up device or onto an object arranged on the build-up device; (iii) Printing a further volume increment such that the Volume increments at least partially touch or overlap; and (iv) Repeat steps (ii) and (iii) until the object is created; wherein at least one of the volume increments is at least one contains a pharmaceutical active ingredient and comprises volume increments consisting of a base composition or base substance that is flowable at a printing temperature compatible with at least one active ingredient and that solidifies and / or bonds together after printing the respective volume increment.
2. The method of claim 1, wherein steps (ii) and (iii) are performed such that the volume increments are printed layer by layer.
3. A method according to claim 1 or 2, wherein each volume increment contains an active ingredient.
4. Method according to claim 1 or 2, wherein different volume increments have different active ingredients and / or different amounts of active ingredients and / or different base compositions or base substances.
5. Method according to any one of the preceding claims, wherein the form of the Whether volume increments are the same or different.
6. A method according to any of the preceding claims, wherein the volume of the volume increments is the same or different.
7. The method of claim 6, wherein the volume of the volume increments The difference is such that the volume of the volume increments in the printed object increases from the outside in.
8. Method according to any one of the preceding claims, wherein the form of the Volume increments are selected from the group consisting of drops, spheres, points, cylinders, cubes and cuboids.
9. Method according to any of the preceding claims, wherein active ingredient-containing Volume increments are constructed and printed in such a way that at least one first group of touching or overlapping volume increments containing the same amount of active ingredient contains the same amount of active ingredient, and at least one second group of touching volume increments contains an amount of active ingredient that differs from the amount of active ingredient in the first group.
10. A method according to any of the preceding claims, wherein at least a first group of active ingredient-containing volume increments is present, comprising a first pharmaceutical active ingredient and at least a second group volume increments containing active ingredient are present, which contain a second pharmaceutical active ingredient different from the first active ingredient.
11. Method according to claim 10, wherein the volume increments of the first and / or the second group are printed such that the volume increments of the respective group touch each other.
12. Method according to any one of the preceding claims, wherein the Volume increments are printed in such a way that active ingredient-containing Volume increments within the object form one or more groups that are surrounded by non-active-ingredient volume increments, which shield the active-ingredient volume increments from the environment.
13. The method of claim 12, wherein the active ingredient volume increments in the object form an active ingredient core around which non-active ingredient volume increments are arranged.
14. Method according to claim 12, wherein the volume increments are printed such that active ingredient-containing volume increments form several groups, each of which is surrounded by non-active ingredient-containing volume increments.
15. Method according to claim 13 or 14, wherein the non-active ingredient Volume increments contain a substance that at least limits the effect of the active ingredient(s) in the active ingredient-containing volume increments when the printed object is shredded.
16. Method according to any one of claims 13 to 15, wherein the / the The active ingredient(s) is / are one or more substances with addictive potential.
17. The method of claim 13, wherein the non-active-ingredient volume increments are printed such that they form one or more pH-dependent degradable layers in the intestine of a patient around an active-ingredient core.
18. Method according to any one of claims 14 to 17, wherein non-active ingredient-containing Volume increments caused a delayed release of the active ingredient(s).
19. Method according to any one of claims 13 to 18, wherein non-active ingredient-containing Volume increments provide gastric juice resistance to the printed object.
20. Method according to any of the preceding claims, wherein the active substance-containing object is a semi-solid or solid pharmaceutical dosage form.
21. The method of claim 20, wherein the dosage form is selected from the group, consisting of tablets, capsules, suppositories, patches or thin films.
22. Method according to claim 21, wherein the tablets are selected from the group consisting of oblong tablets, lozenges, implant tablets, multiple-application tablets, dispersible tablets, sustained-release tablets, lacquer tablets and gastro-resistant tablets, vaginal tablets and suppositories, ocular tablets, coated tablets, matrix tablets, chewable tablets, film-coated tablets, modified-release tablets.
23. Method according to any one of claims 1 to 16, wherein the object is a medical device.
24. Three-dimensional object containing at least one pharmaceutical active ingredient, produced by the method according to any of the preceding claims.