Cartridge, system and method for the automated and customised production of medicines, supplements, cosmetics and / or functional foods

Abstract

The present invention relates to a cartridge, system and method for the automated and customised production of medicines, supplements, cosmetics and / or functional foods, wherein it includes a processing / formulating apparatus to operate the hoppers and refill the cartridges with specific quantities and in an ordered logical sequence according to pre-established parameters, an extruder apparatus to operate the cartridges loaded with the already formulated ink and extrude it precisely to obtain the final pharmaceutical form, a data processing unit: computer or computer system that controls the entire mixing, formulation and extrusion process, and a database: data storage that stores information on raw materials, formulations and method parameters.

Description

[0001] CARTRIDGE, SYSTEM AND METHOD FOR THE AUTOMATED AND CUSTOMIZED PRODUCTION OF MEDICINES, SUPPLEMENTS, COSMETICS AND / OR FUNCTIONAL FOODS

[0002] DESCRIPTION

[0003] OBJECT OF THE INVENTION

[0004] The present invention relates to a cartridge, system and method for the automated and personalized production of medicines, supplements, cosmetics and / or functional foods, applied in the field of health sciences, pharmaceutical technology, such as magistral preparations, hospital medicines or personalized medicine, and also intended for research and development (R&D) laboratories.

[0005] STATE OF THE ART

[0006] Traditional manufacturing of medicines and other related products such as supplements is based on the large-scale production of uniform batches of products, which ensures process efficiency and consistency in quality.

[0007] The process that is usually used is molding manufacturing, a confirmatory manufacturing process where the raw material is forced (by pressure, compression molding, or by melting, known as injection molding) to acquire the shape and dimensions of an external mold.

[0008] These techniques are primarily used to produce solid dosed forms such as tablets and capsules, suitable for large-scale production.

[0009] These manufacturing methods provide precise and uniform dosing in each unit produced, and the costs per unit decrease significantly with increasing production volume.

[0010] Once the molds are created, production can be very fast, with the resulting products having good chemical stability and a long shelf life.

[0011] However, these methods are difficult to adapt to produce small batches that meet specific or individual needs.

[0012] In general, these production methods are applied to standardized, high-turnover products. Additive manufacturing, or 3D printing, is a technology that involves creating solid, dosed shapes by adding material layer by layer.

[0013] This technology represents a versatile tool that has the potential to generate a paradigm shift in the way products are made in the production sector, as it allows: • Obtaining innovative geometries, difficult to achieve with traditional molding methods, such as hollow or porous structures.

[0014] • Create, with the same equipment and without changes in assemblies (molds, dies, punches), solid structures of different shapes and sizes without loss of precision.

[0015] • Combine materials with different physicochemical properties (hydrophobicity / hydrophilicity) and specific formulations with different loaded active ingredients. The different specific formulations can even be placed, without being mixed, in different layers or surfaces of the structure.

[0016] Specifically in pharmaceutical technology, various production methods have been explored: a) fused deposition model (FDM),

[0017] b) powder deposition method,

[0018] c) pressure-assisted microextrusion of semi-solids or microjehnga (PAM),

[0019] d) selective laser sintering (SLS) and

[0020] e) photopolymerization methods or stereolithography (SLA).

[0021] While the fundamentals of additive manufacturing are the same, the different methods use completely different materials, processes, and equipment, each exhibiting comparative advantages (in speed and precision) but above all different disadvantages that hinder their use in pharmaceutical systems, especially when applied to decentralized production, that is, at the point of care, which in English is conceptualized as Point-Of-Care Manufacturing.

[0022] From now on we will use the term “ink” to refer to the specific formulations that contain one or more active ingredients along with the excipients necessary for the technique to operate.

[0023] Point-of-care production is key to unlocking the potential of additive manufacturing for personalized treatments. Additive manufacturing is, by definition, an automated process where the quality of the resulting solid objects is determined by the production platform (hardware, ink, and digital file that directs the process), making it completely independent of the operator and the location of use.

[0024] By simply modifying the "ink" and / or the file (which contains the specifications for the equipment to operate), it is possible to create differentiated solid forms (FS), using exactly the same equipment.

[0025] In this way, if pharmacies have a robust system capable of adapting inks and / or files to the patient's needs, it would be possible to produce batches of products personalized for each patient using the same equipment. The application of this type of automated technology will reduce the manual handling currently performed by compounding pharmacies in small-scale preparations, thus improving the quality and safety of the products, regardless of where they are prepared, and potentially even speeding up the process.

[0026] It is worth noting that currently, there is no additive manufacturing equipment that allows for complete customization in pharmacies.

[0027] The equipment best suited to additive manufacturing in pharmacies are the extrusion-based printing systems from nozzles, where we find the FDM and syringe-assisted extrusion methods.

[0028] The FDM method is a technique that, during operation, requires no prior or subsequent steps, but it does rely on thermoplastic filaments that must be loaded with active ingredients (AIs). This process requires high temperatures (which can affect many AIs) and uses robust equipment adapted to industrial production. However, due to cross-contamination, it is not suitable for small-batch production.

[0029] This technique allows for the customization of solid shapes, but it is based on standardized inks and is restricted to non-thermolabile drugs.

[0030] In the case of syringe-assisted extrusion methods, they can be operated using any ink or formulation that meets the conditions of the method, that is, that has a viscosity of the mixture low enough to be extruded at low pressure and high enough to form a filament without collapsing on the printing platform.

[0031] This same technology can be used for automated molding, provided the print bed can be loaded with molds. Instead of depositing the material as a filament that forms the layer, it is extruded in a precise volume into a container. To achieve this, the material must be in a more fluid state. While this technique has the significant advantage of being able to work with custom inks that incorporate almost any AI, it does not operate through a direct and automated method. Instead, it requires preliminary procedures related to weighing, homogeneous mixing of the powders, melting / formulation, and loading the mixture into the syringes that will later be extruded. Furthermore, the files that control the operation of this equipment are unaware of the ink concentration and are limited to simply creating a geometric shape from which an approximate weight can be estimated.

[0032] Regarding these techniques, there are many devices capable of molding or 3D printing objects from a formulated syringe, with or without heat, and some have even been used for medications. However, there is no system that involves devices and equipment that allows, directly and with virtually no human intervention, the creation of inks and files to feed an extruder and ultimately mass-produce personalized medications in small batches (the amount needed for a single patient) without intermediate cleaning processes.

[0033] Related to the concept of direct printing, there is a printing method called direct powder extrusion (DPE), with small extruders attached to the melter, to which the powdered solid mixture can be added directly. See Figure 1 (Boniatti, J.; Januskaite, P.; Fonseca, LBd; Vigosa, AL; Amendoeira, FC; Tuleu, C.; Basit, AW; Goyanes, A.; Ré, M.-l. Direct Powder Extrusion 3D Printing of Praziquantel to Overcome Neglected Disease Formulation Challenges in Paediatric Populations. Pharmaceutics 2021, 13, 1114).

[0034]

[0035] ) and Figure 2 (A. Goyanes, N. Allahham, SJ Trenfield, S. Stoyanov, S. Gaisford, AW Basit. Direct powder extrusion 3D printing: Fabrication of drug products using a novel single-step process. International Journal of Pharmaceutics, 567 (2019), p. 118471 ).

[0036] This technology is designed as a modification of the fused deposition modeling (FDM) method, which is the most widely used method for 3D printing solid objects. Using the extruder connected to the melter makes it possible to use active ingredients that were previously incompatible with FDM, as well as increasing the final dosage of the printed material.

[0037] However, it still has the drawback that the high temperatures at which FDM is generally operated pose to the active ingredient.

[0038] On the other hand, these extruders have the disadvantage that they are not disposable, and must undergo cleaning processes before and / or after printing to avoid cross-contamination.

[0039] Another problem with the system described above is that the powders loaded into the feed hopper must receive pretreatment to ensure homogeneous mixing of the excipients (EX) and the active pharmaceutical ingredients (IA).

[0040] Generally, the formulation consists of pellets or granules. While this is feasible, mixing the materials with the active ingredients can, in some cases, cause stability problems for those active ingredients, especially when solvents other than water, or water itself, are incorporated.

[0041] As an alternative solution to this, the company "Triastek" patented a molten extrusion deposition (MED) method, a continuous and modular additive manufacturing process that directly converts raw materials into finished products.

[0042] Using a large-scale printer (see Figure 3), the powdered raw materials are mixed and fused directly into a mobile semi-solid, then extruded with high precision, printed layer by layer, and formed into drug tablets with a pre-designed three-dimensional structure. See PS:^

[0043]

[0044] As can be seen in Figure 3, the printer is designed for large-scale use, as it utilizes hoppers and up to five augers that must undergo washing processes before being used with a new active ingredient. In other words, all these techniques and methodologies are not applicable to a small-scale, decentralized drug production model, where pharmacies can have a system with equipment to produce customized products with active ingredients and variable dosages for their patients (P).

[0045] DESCRIPTION OF THE INVENTION

[0046] The present invention provides a cartridge, system, and method, including equipment, machines, and automatic devices, that allow the mixing of raw materials in different states (mostly powders but also liquids and semi-solids) in a cartridge or device, formulating them directly into a mobile semi-solid, extruding them with high precision (by additive manufacturing or injection molding) to form tablets, and that can be quickly used with another device loaded with other different raw materials.

[0047] Additionally, this type of automated technology allows not only the production of solid forms, but also customized semi-solid and liquid formulations, expanding its use for obtaining cosmetic products and functional foods.

[0048] The cartridge, system, and method of the invention allow for efficient, precise, and flexible tablet production, adapting to the needs of different formulations and improving the overall productivity of the manufacturing process, through the following components:

[0049] > 1. Devices

[0050] Cartridges: Specific devices for mixing and formulating raw materials (mostly powders) into a mobile semi-solid. The cartridge also allows for the extrusion of this formulation.

[0051] or Hoppers: Interchangeable containers that store raw materials and allow their precise dosing in the mixing process.

[0052] > 2. Automated Equipment:

[0053] o Formulating / manufacturing equipment: Equipment designed to operate the hoppers and fill the cartridges, with specific quantities and in a logical sequence ordered according to pre-established parameters.

[0054] o Extruder equipment: Equipment designed to operate the cartridges loaded with the already formulated ink and extrude it precisely to obtain the final pharmaceutical form.

[0055] > 3. Peripheral Operating Media: o Data Processing Unit: Computer or computer system that controls the entire mixing, formulation and extrusion process.

[0056] or Database: Data storage system that stores information about raw materials, formulations, and process parameters.

[0057] The operational linking of these components results in a method of producing pharmaceutical forms characterized by the following steps:

[0058] a) Personalization of patient treatment:

[0059] • Based on the patient's own information and that stored in the database, the steps to be followed by the equipment to obtain the personalized treatment for each patient are obtained.

[0060] b) Mixture of Powdered Raw Materials:

[0061] • Raw materials are stored in hoppers.

[0062] • The cartridge-hoppers are operationally linked to the formulating equipment.

[0063] • The automated system controls the dosage and mixing of raw materials according to the specific formulation stored in the database.

[0064] c) Mobile Semisolid Formulation:

[0065] • Once mixed, the raw materials, which are mostly or entirely powders, are transformed into a mobile semi-solid.

[0066] • This mobile semi-solid is prepared for the high-precision extrusion process. d) Extrusion and Tablet Formation:

[0067] • The mobile semi-solid is extruded with high precision to form the tablets.

[0068] • Extrusion is performed according to the specific parameters of each formulation.

[0069] e) Cartridge Exchange:

[0070] • The system allows for the quick exchange of cartridge-hoppers with different raw materials.

[0071] • This facilitates the production of different tablets without the need to stop the process for long periods.

[0072] The advantages of the present invention include:

[0073] • High Precision: Precise extrusion and formulation ensure tablet quality and consistency.

[0074] • Flexibility: The ability to quickly exchange cartridges allows for the manufacture of a wide variety of tablets.

[0075] • Automation: Reduces manual intervention, increasing efficiency and decreasing the risk of errors. • Quality Control: The use of an operationally linked database allows for strict control over raw materials and process parameters. The cartridge is associated with the corresponding automated equipment adapted to it, which allows for the controlled mixing, fusion / formulation, and extrusion of raw materials. The cartridge can then be removed (and even discarded) to be replaced with a new one.

[0076] This cartridge is loaded automatically from different hoppers containing the unmixed raw materials, which occurs in the same automated equipment, and alternatively this process can be carried out in a second complementary automated equipment.

[0077] Said at least one automated team is programmed to work exclusively with a DATA PROCESSING UNIT (computer or computer system that controls the entire mixing, formulation and extrusion process) that defines, from the patient information and the database, the qualitative-quantitative formula of the inks and the processes for their preparation in the cartridges, as well as the extrusion operation that allows achieving a print or a mold with a specific weight and / or a desired geometry (internal and external).

[0078] Additionally, this processing unit allows remotely blocking the use of equipment and devices when they do not meet security conditions, such as when they are used outside of designated areas.

[0079] The present invention provides a system composed of equipment and devices that, working in a linked manner, allow, by an established method, the automated and personalized production of medicines, supplements, cosmetics and / or functional foods.

[0080] The system and method of the invention respond to the need to obtain customized products whose production is not feasible through traditional manufacturing methods.

[0081] Conventional manufacturing of these types of products relies on large-scale production of homogeneous batches, ensuring process efficiency and consistent quality. Each product's qualitative and quantitative composition must be recorded, and the quality of each batch must be controlled using methods that are often destructive. Furthermore, while production is fast and efficient, it adheres to strict protocols between batches, such as rigorous cleaning procedures to prevent cross-contamination of active ingredients. Due to all these factors, manufacturing products tailored to the specific needs of a small group of patients or for individualized use is highly complex and costly, in terms of formulation changes, equipment / process modifications, and distribution.It is important to emphasize that when we talk about personalization of treatments, it does not only refer to the possibility of changing the dose of the active ingredient (often required by genetic variations or functional physiological changes such as kidney failure) or the excipient (for example, due to allergies), but in most cases what is needed is the combination of active ingredients.

[0082] There is a huge number of people who, for health reasons or out of necessity, must consume compressed steam inhalations daily, many of them simultaneously.

[0083] Scientific evidence has shown that when active ingredients are combined into a single tablet, patients adhere more to treatment compared to administering the same drugs separately, which impacts the effectiveness of treatments and consequently reduces the side effects of the disease and healthcare costs.

[0084] Despite this evidence, there is a low supply of industrially produced combination tablets, and those that are available are rarely chosen by prescribing professionals, who are restricted to selecting from industry-approved standardized combinations. If one were to analyze the number of active ingredients (AIs) among drugs, vitamins, trace elements, nutrients, proteins, enzymes, prebiotics, probiotics, etc., it would be easy to see that the number of possible combinations is infinite, and this number increases even further when dosage variations are taken into account.

[0085] The number of possible customized products is impossible to standardize and therefore unattainable under the current production logic.

[0086] Today, those offering personalized medications are compounding pharmacies. A compounded medication is an individualized preparation for a specific patient, according to the prescription of their healthcare professional, prepared, packaged, and labeled by a pharmacist in the pharmacy's laboratory and dispensed there.

[0087] Compounding is legally permitted and is particularly useful for dealing with what industry cannot deal with.

[0088] Despite its advantages, compounding presents certain challenges regarding the quality and safety of the medications produced. In particular, the processes used by compounding pharmacies are often manual and require a certain level of experience and specialized training.

[0089] Although there are standards and procedures that help ensure product quality, the truth is that these manual and heterogeneous processes can exhibit high interpersonal variability (depending on who is carrying out the process) and inter-institutional variability (between different pharmacies depending on the procedures they follow), variability that is ultimately reflected in the quality of the product obtained, with many of them not meeting the required specifications (see James KL, Barlow D., McArtney R., Hiom S., Roberts D., Whittlesea C. Incidence, type and causes of dispensing errors: A review of the literature. Int. J. Pharm. Pract. 2009;17:9-30) and still reaching the patient.

[0090] According to the above, a first object of the invention is a cartridge for mixing and extruding ingredients for the production of medicines, supplements, cosmetics and / or functional foods, according to claim 1.

[0091] By definition, a cartridge is an interchangeable device that operates only in coordination with certain machines, apparatus, and instruments. In this case, the cartridge has been designed to be: 1) Tamper-proof (it cannot be manipulated outside of the equipment and becomes unusable upon completion,

[0092] 2) Capable of transmitting heat homogeneously without burning the active ingredients, 3) Capable of being fed externally,

[0093] 4) Capable of mixing raw materials and fusing them into an extrudable semi-solid,

[0094] 5) Compatible with the use of different commercial needles or nozzles, including those used for FDM (fused deposition modeling) and

[0095] 6) Capable of precisely extruding the material to allow layer-by-layer deposition if required.

[0096] In particular, the mixing cartridge that is the subject of the invention comprises:

[0097] a body-shell with a proximal end (PE) and a distal end (D),

[0098] a plug-piston located inside the proximal end (PE),

[0099] an outlet nozzle with a connection at the distal end (D), and

[0100] a mixing paddle for mixing the ingredients housed inside said body-casing.

[0101] Additional features of the cartridge of the invention are set out in claims 2 to 10.

[0102] In one solution, the cartridge body comprises two parts with coupling means between them, a first part consisting of a proximal cylindrical body and a second part consisting of a conical distal body with an outlet nozzle or connection. Alternatively, the body comprises a single part, with the proximal cylindrical end and the conical distal end forming a single body, without the possibility of separation and without coupling means between them.

[0103] The mixing paddle is preferably located at the proximal end (PE) of the piston plug and has a coupling connection to an external rotation shaft, which, upon connection of the paddle to this shaft, will cause the paddle to rotate. In a preferred embodiment, between the mixing paddle and the piston plug, the cartridge has a shaft coupled to the piston plug and equipped with a coupling connection to the external rotation shaft, so that the mixing paddle rotates when said external rotation shaft rotates. Preferably, the coupling connection of the piston plug to the external rotation shaft comprises a central retainer.

[0104] In another preferred embodiment, the piston-plug has an external shape similar to that of the interior of the distal end of the housing, and further comprises at least one access port at its proximal end. Preferably, this access port has a separate sealing piece that airtightens the cartridge after the ingredients have been added. In another embodiment, instead of a separate sealing piece, the access port has an elastic membrane that airtightens the cartridge after the ingredients have been added.

[0105] Additionally, the cartridge may have at least one O-ring between the plug-piston and the body-housing.

[0106] This device or cartridge is specially designed as a central and differentiating element of a system for the automated and personalized production of medicines, supplements, cosmetics, and / or functional foods. The cartridge distinguishes the system from other equipment used for the same purpose that employs syringes or mechanical or pneumatic devices. While these latter devices allow for extrusion, they are not designed to be automatically loaded and formulate the inks precisely before extrusion and within the same device. This is crucial for ensuring both the stability of the formulation and its functional properties, which determine the final product.

[0107] A second object of the invention is a system for the automated and personalized production of medicines, supplements, cosmetics and / or functional foods according to claim 11. The cartridge, when used in the system, allows to be filled, by means of feed hoppers, with the exact quantities of ingredients, specifically, active ingredients (AI) and excipients (EX), and to carry out, by linking with a head or heads designed for that purpose, the formulation and extrusion operations without human intervention, which ensures that it is always produced in exactly the same way, increasing the quality of the products obtained.

[0108] This system features:

[0109] at least one data processing unit connected to a cloud of ingredient databases, specifically excipients (EX) and active ingredients (IA) and ink formulations based on said ingredients, configured to receive information related to a patient's treatment (P) and to create, based on the information received, preparation orders (OP) and / or extrusion / printing orders (OE / OI), at least one formulating-manufacturing unit, which manufactures the inks in at least one cartridge with the characteristics described above, from the preparation orders (OP) and with at least two hoppers, at least one hopper containing the active ingredients (IA) and / or at least one hopper containing the excipients (EX), at least one extruder unit with a formulating arm head and a printing arm head,that produces the final personalized product (PP) in an automated manner from the extrusion / printing order (OE / OI) and from at least one cartridge made with the ingredients, the contents of which are poured onto an extrusion bed to provide a finished product in a primary container, or disposable surface, intended for the patient (P),

[0110] presenting means of operational linking between both teams and at least the data processing unit through said database cloud.

[0111] Preferably, the formulating equipment has a shaft, complementary to the shaft of the cartridge paddle, to enable the rotation of the mixing paddle. In a preferred solution, at least one cartridge, which may be empty (without ingredients) or pre-filled with ingredients (either active ingredients, excipients, or both), and at least two hoppers include an NFC (Near Field Communication) code (or similar technology).

[0112] The formulating and extruding equipment may be separate, either in different locations or in the same location. Alternatively, the formulating and extruding equipment may form a single integrated automated unit, comprising a formulating component (equivalent to the formulating and extruding equipment) and an extruding component (equivalent to the extruding equipment).A third object of the invention is a method according to claim 16, which relates to a method employing the system described above for the automated and personalized production of medicinal products, supplements, cosmetics, and / or functional foods. The system is used with an empty cartridge that is filled with ingredients from hoppers, at least one containing excipients and at least one containing active ingredients. After mixing in the cartridge, an ink is created, and the cartridge becomes a cartridge containing the ink. This method comprises the following steps:

[0113] a) load the patient's personalized treatment (P) into said at least one data processing unit,

[0114] b) prepare the preparation orders (PO) and the extrusion / printing orders (EO / OI), based on the information on the treatment and the study of the ingredients stored in the database, c) load manually or automatically, at least one empty cartridge into said at least one formulating-processing unit or formulating-processing component of the integrated automated equipment,

[0115] d) manually or automatically load said at least two hoppers into said at least one formulating-processing unit or formulating-processing component of the integrated equipment,

[0116] d) execute the preparation orders (PO) which include preparing the inks in said at least one empty cartridge, based on the ingredients of said at least two hoppers, and execute the preparation orders, obtaining the cartridge prepared with ink,

[0117] e) manually or automatically load said at least one cartridge made with ink and primary packaging, or disposable surface, into the extruder equipment or extruder component of the integrated automated equipment, and

[0118] f) produce the personalized products (PP), based on at least one cartridge prepared and loaded with the ink(s) prepared in step d) and the work of the printheads of the extruder equipment, or extruder component of the integrated automated equipment, which follow the instructions contained in the extrusion / printing orders (OE / OI), depositing the inks in a controlled and orderly manner in the primary packaging, or disposable surface, until reaching the final product intended for the patient (P).

[0119] Another object of the invention is a method according to claim 17, employing a system with a cartridge pre-filled with an ingredient, either an excipient or an active ingredient, which is filled with the ingredient not contained in the cartridge from one of the hoppers, and which, after mixing both ingredients in the cartridge, creates an ink, the cartridge then becoming a cartridge made with ink. This method comprises the following steps:

[0120] a) load the patient's personalized treatment (P) into said at least one data processing unit,

[0121] b) prepare the preparation orders (PO) and the extrusion / printing orders (EO / OI), based on the information on the treatment and the study of the raw materials stored in the database,

[0122] c) manually or automatically load at least one pre-filled cartridge with ingredients into said at least one formulating unit or formulating component, d) manually or automatically load said at least one hopper into said at least one formulating unit or formulating component of the integrated automated equipment, d) execute the preparation orders (PO) that comprise preparing the inks in said at least one pre-filled cartridge, based on the ingredients in said at least one hopper, and execute the preparation orders, obtaining the cartridge prepared with ink,

[0123] e) manually or automatically load said at least one cartridge made with ink and primary packaging, or disposable surface, into the extruder equipment or extruder component of the integrated automated equipment, and

[0124] f) produce the personalized products (PP), based on at least one cartridge prepared and loaded with the ink(s) prepared in step d) and the work of the printheads of the extruder equipment, or extruder component of the integrated automated equipment, which follow the instructions contained in the extrusion / printing orders (OE / OI), depositing the inks in a controlled and orderly manner in the primary packaging, or disposable surface, until reaching the final product intended for the patient (P).

[0125] A final object of the invention is a third method according to claim 18, which employs the aforementioned system, using a cartridge pre-filled with both ingredients, the excipient and the active ingredient, such that after mixing both ingredients in the cartridge, an ink is created, the cartridge then becoming a cartridge made with ink. This method comprises the following steps:

[0126] a) load the patient's personalized treatment (P) into said at least one data processing unit,

[0127] b) prepare the preparation orders (PO) and extrusion / printing orders (OE / OI), based on the treatment information and the information stored in the database regarding pre-filled cartridges with ingredients,

[0128] c) manually or automatically load at least one pre-filled cartridge into at least one formulating unit or formulating component of the integrated automated equipment,

[0129] d) execute the preparation orders (PO) which include preparing the inks in said at least one cartridge pre-filled with ingredients, and execute the preparation orders, obtaining the cartridge prepared with ingredients that make up the ink,

[0130] e) manually or automatically load said at least one cartridge made with ink and the primary packaging, or disposable surface, into the extruder equipment or extruder component of the integrated automated equipment, and

[0131] f) produce the personalized products (PP), based on at least one cartridge prepared and loaded with the ink(s) prepared in step d) and the work of the printheads of the extruder equipment, or extruder component of the integrated automated equipment, which follow the instructions contained in the extrusion / printing orders (OE / OI), depositing the inks in a controlled and orderly manner on the primary packaging or disposable surface, until reaching the final product intended for the patient (P).

[0132] The preparation instructions based on the treatment information vary depending on whether the cartridge used in the procedure is empty, partially pre-filled, or fully pre-filled. In either case, it will be necessary to fill the empty cartridge or finish filling the pre-filled cartridge, then heat and agitate the cartridge contents before venting the air. If the cartridge is already pre-filled and no further filling is required, the preparation instructions are simply to heat and agitate the cartridge contents before venting the air.

[0133] BRIEF DESCRIPTION OF THE FIGURES

[0134] Figures are included to allow a better understanding of the form, structure, and operation of this present invention.

[0135] Figure 1 shows a schematic of a prior art solution.

[0136] Figure 2 shows a schematic of an alternative state-of-the-art solution.

[0137] Figure 3 shows a schematic of a large-scale printer according to a state-of-the-art solution.

[0138] Figure 4 illustrates a schematic view of all the components involved in the system of the present invention. The system in this case is operated by two pieces of equipment, which can operate in independent locations or establishments, one that manufactures the cartridge (8) and another that extrudes it.

[0139] Figure 5 illustrates a perspective view of the system components interacting functionally during the method of the present invention, with a unique equipment in which the processing part (analogous to the processing-formulating equipment) is connected to the extruding part (analogous to the extruding equipment) by means of an automatic arm or carriage.

[0140] Figure 6 illustrates in detail the empty cartridge (5) and its three main components: the body-housing (13), the mixing paddle (14) and the plug-piston (16).

[0141] Figure 7 illustrates alternative forms of the mixing paddle (14) which can take on different morphologies and be aligned by a shaft (15) of different lengths.

[0142] Figure 8 illustrates alternative forms of the plug-piston (16), which may have up to two access ports and be made of elastic materials or be formed from a rigid material complemented by at least one O-ring (21), a central retainer (22), and a closing piece (23) that rotates independently, allowing the closure of the access port(s) at the end of venting. Figure 9 illustrates an alternative of the housing (13) formed by two pieces that fit together. In this version, there is a proximal cylindrical body (24) and a conical distal body (25) that ends with the outlet nozzle (17) or a Luer or Luer Lock connection.

[0143] Figure 10 shows an alternative turbine-shaped mixing paddle (14) with its shaft (15).

[0144] Figure 11 shows in detail the empty cartridge (5) with a turbine-shaped mixing paddle (14), and its other two main components: the body-housing (13) and the plug-piston (16).

[0145] DETAILED DESCRIPTION OF THE INVENTION

[0146] The objective of the present invention is to allow any authorized pharmacy, or any place authorized to produce / deliver medicines, to manufacture personalized products (PP) with a homogeneous and high quality, equivalent to that achieved by the pharmaceutical industry, making it possible not only to personalize the dose required by the patient (P) but also its combinations and conjunction of preferences, always tending to minimize the number of daily tablets consumed by patients (Ps).

[0147] Within the framework of this invention, personalized products (PP), which may be pharmaceuticals, supplements, cosmetics, and / or functional foods, are obtained by a method that uses additive manufacturing or by molding formulations. These formulations, generically referred to as "ink," are extruded in a controlled and directed manner, layer by layer or onto a mold, at room temperature or higher, into the primary packaging intended for the patient (P).

[0148] This technology allows the creation of solid geometric structures differentiated in size and shape, with the possibility of combining materials of different natures.

[0149] By simply modifying the "ink" and / or the file (which contains the specifications for extrusion) it is possible to create solid shapes (FS), and if necessary semi-solid or liquid shapes, differentiated using exactly the same equipment.

[0150] Additive manufacturing, which includes 3D printing, is by definition an automated process where the quality of the objects obtained is determined by the production platform (equipment, ink and digital file that directs the process), being completely independent of the operator and the place of use.

[0151] The application of this technology allows for the production of high-quality products at a cost independent of the number of units produced and in a small workspace. In addition to this advantage, it enables the creation of systems unattainable with traditional compounding methods, such as modified or controlled-release formulations, gastroretentive systems, site-specific release systems (colon), nanosystem carriers, and formulations containing multiple active ingredients in a single matrix or in multilayers.

[0152] The components involved in the system of the invention are:

[0153] M: Doctor

[0154] AI: active ingredients

[0155] EX: excipients

[0156] OP: Preparation Order

[0157] OE: Extrusion order

[0158] OI: Print order

[0159] PP: Customized product.

[0160] 1. Data processing unit formulations

[0161] 2. Cloud / databases: patient information / EX / AI

[0162] 3. Development / formulation team

[0163] 4. Extruder equipment

[0164] 5. Empty or pre-filled cartridge (with excipients or even with the mixture of AI powders and excipients)

[0165] 6. Hopper active ingredient (AI) or pre-formulated (AI or mixture of AIs pre-treated with excipients, e.g., coated AI)

[0166] 7. Excipient hopper (EX)

[0167] 8. Cartridge loaded with formulation

[0168] 9. Formulated arm head of the extruder equipment (4).

[0169] 10. Print arm head of the extruder equipment (4).

[0170] 11. Extrusion bed with container

[0171] 12. Primary packaging (Blister pack - Tablet)

[0172] 13. Body-casing

[0173] 14. Mixing paddle

[0174] 15. Axis

[0175] 16. Plug-piston

[0176] 17. Outlet nozzle

[0177] 18. Central opening

[0178] 19. First access point

[0179] 20. Second access point.

[0180] 21 O-Ring or Tonca Gasket

[0181] 22 Central valve retainer 23 Closing piece

[0182] 24 Proximal cylindrical body of the two-piece housing

[0183] 25 Two-piece tapered distal body of the housing

[0184] For the method to work, the different components of the system must coexist. The hoppers will contain the raw materials or combinations thereof, which will then be dispensed into the cartridges to produce the inks, which are designed and developed based on the study of the materials.

[0185] Based on this information, formulations compatible with extrusion methods are developed, taking into account the nature of the excipients, their compatibility with the active ingredients, the compatibility of the active ingredients with each other, the physicochemical stability of the components throughout the process (e.g., thermal changes), the physicochemical stability over time, and the pharmaceutical-technical quality of the final form, which is generally an oral solid form, although it can also be a semi-solid or a liquid and be intended for another route of administration, such as ophthalmic.

[0186] Each ink is composed of at least one active ingredient (AI) (drug, vitamin, nutrient, trace element, prebiotic, probiotic, protein, enzyme, etc.) and an excipient (EX), which are mixed in the required proportions, according to the concentration to be achieved and the limitations of the method, in an ordered sequence, requiring processing (example: heating, stirring, kneading, resting, etc.) that results in the final formulation which is extruded to give the final shape in the primary container.

[0187] Given that patients (P) consume more than one active ingredient (AI), research and studies are focused on using this information to meet patients' needs with the fewest possible inks. In other words, whenever the compatibility of the active ingredients allows, the goal is to formulate a single ink.

[0188] When this cannot be achieved, for example, due to chemical incompatibility or because an active ingredient (AI) must be released in a different region of the intestinal tract to promote its action, the final form is made from more than one ink, which is mixed additively following precise instructions.

[0189] According to the system of the present invention, high-quality personalized medicines, supplements, and / or functional foods are obtained through methods or procedures based on an in-depth study and characterization of the excipients (EX) and active ingredients (IA) that give rise to a series of inks. The qualitative and quantitative composition, manufacturing procedure (which we will call the preparation order), and the manner in which they must be extruded (which we will call the extrusion order or printing order) are perfectly defined and stored in a database. The main difference between an extrusion order (EO) and a printing order (OI) is the way in which the pharmaceutical form is obtained. In the EO, the formulation is volumetrically extruded in the precise amount of material into a container, taking on the shape of the container.When the material is formed into a solid shape, this process is called OSAM, which stands for "one-shot additive manufacturing." OE (Extraction) can involve the deposition or extrusion of more than one material, one on top of the other. In RO (Operational Injection), the material is deposited onto a smooth bed, and the print head moves precisely along the X, Y, and Z axes until the digitally designed shape is formed.

[0190] This database is linked to the system by means of a processing unit (software) configured to receive information related to the patient's treatment or indication (P); create, based on the information received and the information stored in the database, the preparation and / or extrusion / printing orders and finally interpret these orders to indicate to the automated equipment, part of the system, the steps to follow to obtain the personalized product (PP).

[0191] The automated equipment, which is part of the described system, can be conceptually divided into two pieces of equipment: one for ink production and the other for extrusion. These can operate in the same facility or even be separated into two independent facilities: one for cartridge production and the other for the production of customized products. This equipment operates using:

[0192] 1) the information provided by the processing unit, the preparation and extrusion / printing orders, respectively, and

[0193] 2) the devices, cartridge and hoppers, specially designed to operate in the context of automated equipment that accurately reproduces the orders that give rise first to the ink(s) and then to the medicines and / or personalized preparations (PP).

[0194] Both the equipment and the devices are designed so that all stages of the process (weighing, mixing, heating, homogenization, extrusion, etc.) can be achieved with minimal or no human intervention, with the aim of eliminating human error and achieving quality assured by the process.

[0195] The equipment has a region that we will call the processing part, which can be an independent processing unit, which is equipped with hoppers loaded with the raw materials or combinations of them, which give rise to the inks.

[0196] There is not just one hopper, but as many as there are possible raw materials validated for the design of inks.

[0197] These hoppers may be pre-mounted on the equipment or loaded manually depending on the product being prepared. A hopper contains a single component, such as:

[0198] a) a pure active ingredient (AI) (drug, vitamin, probiotic, etc.)

[0199] b) an active ingredient (AI) pre-formulated with one or more excipients that fulfill a specific function such as improving its stability, its powder rheology or allowing site-specific release (coated drug)

[0200] b) an excipient (EX) (Polyethylene glycol 400, 4000, 6000, Gelucine 50 / 13, Propylene glycol, Gelatin, etc.) or

[0201] c) preformulated excipients (EX) (i.e., mixtures of excipients such as, for example, 90% PEG 4000, 8% Propylene Glycol, 2% Stearic Acid).

[0202] Each hopper is designed and configured to accurately dispense the component it is loaded with, with a minimal margin of error.

[0203] The material inside, on the other hand, must be processed (sieved, granulated, etc.) to meet this dosage.

[0204] The hoppers are designed to fit snugly with the cartridges, which are where the raw materials are deposited for mixing and formulating the ink. The cartridges can start the process empty or pre-filled with certain excipients or even mixtures of excipients and active ingredients. The pre-filled cartridge can be produced at a different facility than where the ink application will be carried out, using an empty cartridge and the mixing equipment, following the method guidelines, or another production process can be used. Having a pre-filled cartridge allows for faster production of certain inks or products with high demand. This pre-filled cartridge, containing high-turnover excipients and active ingredients, can be used as is or loaded into the mixing equipment to be filled with other compatible active ingredients for the formulation.

[0205] The mixing unit, or the mixing section of the single-unit equipment, uses the hoppers and at least one empty or pre-filled cartridge to follow the guidelines of the preparation order created in the data processing unit. It connects the cartridge to each of the corresponding hoppers according to the qualitative formula, depositing the precise amount of active ingredients (AIs) and excipients (EXs) based on the previously studied ink design, the prescribed dose, and the frequency of use. The complementary use of both devices aims to use the minimum number of cartridges per patient (P). Thus, if the patient (P) requires two active ingredients (AIs) simultaneously, and if they are compatible, they are mixed with one or more excipients (EXs) in the cartridge to produce an ink with a concentration determined by the patient's (P) needs and in a quantity sufficient to cover the treatment period prescribed by the physician.If there is a third active ingredient (AI) that is incompatible with the other two, it will be formulated in a second cartridge and incorporated in solid form additively, i.e., deposited on top of the layers created with the first ink.

[0206] Alternatively, the system can also produce a second package with this third active ingredient (AI) or another active ingredient (AI) that, for example, needs to be taken at a different time than the other active ingredients (AI).

[0207] The system always seeks to simplify patient (P) treatment as much as possible, but this does not imply that all AIs are always in a single solid form.

[0208] In order for the ink to be formulated and extruded / printed, in addition to the hopper-cartridge coupling, a specially designed printhead is needed to allow the heating, stirring and extrusion of the mixture contained in the cartridge.

[0209] The articulation of the cartridge with its printhead allows the processing (heating, agitation, mixing, resting, etc.) of the components that give rise to the ink to occur with two differentiating characteristics:

[0210] 1) This formulation occurs without human intervention, which ensures that it is always produced in exactly the same way and

[0211] 2) This formulation is produced just before extrusion / printing, a fact that is key to ensuring both the stability of the formulation and its Teological properties, which condition the result.

[0212] Finally, when the ink is already formulated, the equipment uses the loaded cartridge, the same specially designed printhead and the extrusion / printing order generated by the processing unit, to deposit the material into the primary container and thus create the personalized product (PP) adapted to the needs of the patient (P).

[0213] This last part of the method takes place in an extrusion region that has a bed specially designed to accommodate the blisters, capsules or product packaging, something that could be a separate piece of equipment that we will call the extruder equipment.

[0214] The system creates the customized products (PP) directly onto the blisters, or in primary packaging with two fundamental objectives:

[0215] 1) to be able to organize the patient's medication intake (P) when the pharmacology requires intake at different times and

[0216] 2) To prevent cross-contamination between patients (P) and patients (P). Finally, the pharmacist removes the primary packaging (or capsules) for subsequent quality control, if required, and reseals the package, a process that can also be automated.

[0217] In summary, the system for the automated and personalized production of medicines, supplements and / or functional foods of the present invention comprises: A) A processing unit connected to a cloud of databases of excipients (EX), active ingredients (IA) and studied formulations (inks).

[0218] It contains the specifications that allow the preparation (quantities, temperatures, times and speed of stirring, etc.) and extrusion (extrusion force, temperature, path, times, order of deposition, etc.) of the inks.

[0219] The unit uses information provided by medical prescriptions, other patient needs (e.g., vitamin requirements or special conditions such as celiac disease) and database information to calculate the necessary quantities of active ingredients (AIs) and excipients to prepare the designed ink(s).

[0220] The unit also takes into account the required dose, the compatibility of the prescribed active ingredients (AIs), the frequency of use and the duration of treatment, with the aim of minimizing the amount of inks, cartridges and target intakes of the patient.

[0221] The preparation and extrusion / printing orders are the inputs that allow for a quality assured by the process.

[0222] The system's equipment only functions to the extent that the data processing unit allows, being an element not only of quality control but also of safety.

[0223] B) Two devices necessary for its operation are:

[0224] i- Cartridges. A cartridge is by definition an interchangeable device that operates only in coordination with certain machines, apparatuses and instruments.

[0225] In this case, the cartridge has been designed to be:

[0226] 1) Inviolable (it cannot be manipulated outside the equipment and is rendered unusable upon completion,

[0227] 2) Capable of transmitting heat homogeneously without burning the active ingredients, 3) Capable of being fed externally,

[0228] 4) Capable of mixing raw materials and fusing them into an extrudable semi-solid,

[0229] 5) Compatible with the use of different commercial needles or nozzles, including those used for FDM (fused deposition modeling) and

[0230] 6) Capable of precisely extruding the material to allow layer-by-layer deposition if required.

[0231] This specially designed device is a central and differentiating element of the system compared to other equipment for the same purpose that use syringes or mechanical or pneumatic devices that, although they allow extrusion, are not prepared to be loaded automatically and formulate the inks at the exact moment prior to extrusion and within the same device, a fact that is key to ensuring both the stability of the formulation and its theoretical properties, which condition the result.

[0232] The cartridge allows to be filled, by means of feeding hoppers, with the exact quantities of active ingredients (AI) and excipients (EX), and to carry out, by linking with a head designed for that purpose, the formulation and extrusion operations without human intervention, which ensures that it is always produced in exactly the same way, increasing the quality of the products obtained.

[0233] As illustrated in Figure 6, the empty cartridge (5) comprises 3 main components: the body-housing (13), the mixing paddle (14) and the plug-piston (16).

[0234] The body-shell (13) allows the containment and precise distribution of the active ingredient (AI) and the excipient (EX), for proper mixing and subsequent extrusion.

[0235] This body has a central opening (18) with the full diameter at its proximal end and an outlet nozzle (17) or a Luer or Luer Lock connection at the distal end. The plug-piston (16) moves, with full internal adjustment, from the proximal end to the distal end.

[0236] It is manufactured from a material capable of withstanding high temperature ranges, and must exhibit high chemical resistance to both acidic and basic substances; the material can be translucent and opaque or caramel in color, which provides it with inactinic qualities, thus preventing the direct chemical action of electromagnetic radiation and UV rays in the mixture.

[0237] The mixing paddle (14) serves to homogenize the ingredients within the housing (13) at an optimal temperature. It is constructed of a material capable of withstanding thermal differences without bending, cracking, or breaking. Its morphology is defined by a shaft (15), to which mixing paddles (14) are connected and aligned with said shaft (15). As illustrated in Figure 7, the mixing paddle (14) can have different shapes and be aligned with a shaft (15) of varying lengths, as long as it continues to perform its functions.

[0238] Its outline coincides with the profile of the body-shell (13) of the empty cartridge (5) and ends at the distal end, having a margin against the wall of the same around its entire perimeter to allow the components (active ingredient (IA) and excipients (EX) to move inside a chamber of said body.

[0239] At its proximal end, it has a raised relief, concentric to the axis (15), which has a housing where a traceable code or other similar technology is located that allows its identification and traceability in the process, and where it is coupled to the head axis to execute its rotation.

[0240] Its color and shape may vary depending on the type of custom product (PP) to be mixed and extruded. The plug-piston (16) is the most complex component of the system and has multiple functions. Firstly, it serves as a plug and loading access point for supplies (lA-Excipients). Secondly, it houses the aligned mixing paddle (14) and allows its rotation while the head system rotates it according to the program required for proper mixing.

[0241] Furthermore, once the mixing program is completed, the plug-piston (16) serves to house the two push shafts arranged in the head that move the plug-piston (16) through the chamber from the proximal end to the distal end, passing through the mixing paddle (14), which at this point is blocked and disabled for possible rotation.

[0242] In this last phase, the plug-piston (16) moves the entire homogeneous mixture towards the distal end, while expelling the air stored in the chamber through its vent holes.

[0243] The plug-piston (16) is made of a friction-resistant elastomeric material and can move within the body-casing (13) without breaking or cracking; it must be resistant to thermal changes and different chemical compounds for medical or food-grade applications.

[0244] Initially located at the open end of the housing (13), the plug-piston (16) isolates the chamber, ensuring the integrity of the customized product (PP), and houses the mixing paddle (14) along its axis (15) of symmetry. This ensures its correct position, allowing for its rotation and subsequent compression of the mixture. After printing is complete, the mixing paddle (14) is positioned inside the housing.

[0245] The excipients (EX) and active ingredients (IA) enter the body-casing (13) through one or two channels located in the piston-plug, the first and second access ports (19, 20), which have elastic membranes that, once the loading perfusion is removed, seal the ports, preventing the expulsion of the medication during its extrusion from the proximal end. The membrane also allows the controlled release of air while the medication is being extruded.

[0246] As illustrated in Figure 8, the plug-piston (16) may not be made of an elastomeric material and may consist of a rigid material complemented by at least one O-ring (21) that prevents fluid leakage as the plunger moves, a central retainer (22) that surrounds the vane stem to prevent material loss, and a closing piece (23) that rotates independently, allowing the closure of the access port(s) (19, 20) after venting.

[0247] The cartridge can also incorporate alternative body-housing options (13). It can be a single piece or consist of two interlocking parts (Figure 9). In the latter case, there is a proximal cylindrical body (24) and a distal conical body (25) that terminates in the outlet nozzle (17) or a Luer or Luer Lock connection. This alternative is designed to use the cartridge (5) in an inverted position, with the excipients (EX) and active ingredients (IA) entering through the distal part of the device, without the conical body section. This alternative also modifies the piston plug (16) and the mixing paddle (14), which function as a complementary unit. In this case, the paddle shaft is significantly shorter than the original design and, at the start of the formulation process, is completely housed within the piston plug (16).This new plug has no access ports (19, 20) or vent holes. The plug can be made of an elastomeric material or a rigid material reinforced with at least one O-ring (21) and a central retainer (22). In this alternative version, the paddle remains housed and locked inside the plug-piston (16) until the cartridge (5) is inserted upside down into the formulating unit (3). At this point, the paddle is attached to a shaft of the formulating unit, which unlocks and pushes the paddle into the proximal cylindrical section (24) of the housing (13) outside the plug-piston (16), allowing it to agitate the deposited material. In this alternative version, the formulation process is completed by attaching the distal conical section (25) of the housing (13) and venting it through the outlet nozzle (17).Following this operation, the manufactured cartridge (8) can be operated identically to the original version. Using the two-part housing (13) mentioned above, there is a third alternative where the plug-piston (16) and the mixing paddle (14) operate independently. In this alternative, the plug-piston (16) has no access ports (19, 20) or vent holes, nor does it have a housing for the paddle. This plug can be made of an elastomeric material or a rigid material reinforced by at least one O-ring (1). As in the previous alternative, this plug is located at the proximal end of the proximal cylindrical body (24) of the housing (13), serving as its base.The mixing paddle (14) is inserted into the formulation equipment and enters the proximal cylindrical section (24) of the housing (13) during the formulation process, agitating the materials being formulated. In this alternative, the mixing paddle (14) may or may not be complemented by an additional piece that functions as a closing cap for the distal end of the proximal cylindrical section (24) of the housing (13). In this alternative version, the formulation process ends with the removal of the mixing paddle (14), the attachment of the distal conical section (25) of the housing (13), and its venting through the outlet nozzle (17). After this operation, the finished cartridge (8) can be operated identically to the original version.

[0248] In any of its alternatives, the cartridge and its parts are designed to operate and fulfill their functions in the context of the formulating equipment (3) and extruding equipment (4).

[0249] In another alternative, shown in Figure 10, the mixing paddle (14) has a turbine-like shape, with at least two blades, preferably more than three. In this alternative, the housing (13) is formed by two pieces, or parts, coupled together. Likewise, the piston plug (16) and the mixing paddle (14) are integrated into a single, complementary unit, as shown in Figure 11.

[0250] In this example shown in Figures 10 and 11, the mixing paddle (15) is a solid body that rotates freely inside the piston plug (16). The mixing paddle or turbine body (14) comprises blades or vanes that agitate the molten material and takes the conical shape of the distal body (25) of the housing (13), where the paddle will be housed after extrusion is complete. This mixing paddle (14) has a specific morphology at its proximal end, opposite the conical distal body (25), to couple with the system element that allows rotation in the formulating equipment. The piston plug (16) has a body that integrates the mixing paddle (14), allowing it to rotate freely during the manufacturing process. When this piston plug (16) is pushed into the extruder, it moves within the housing (13), and as it integrates with the mixing paddle, it displaces the paddle, ultimately housing it in the conical distal body (25) of the housing (13).This distal body (25) of the housing (13) may be entirely elastomeric or not. If it is not elastomeric, it will have an O-ring and / or a seal to prevent leakage of the ingredients or ink during agitation or extrusion.

[0251] As in previous constructions, each unit (mixing paddle (14) integrated into the piston plug (16) may include an NFC (Near Field Communication - short-range wireless communication technology) code or similar technology, which notifies the equipment / system of the cartridge identity in order to avoid errors and ensure traceability.

[0252] i- Hoppers (6, 7): These are devices, generally shaped like a truncated pyramid or inverted cone, used to precisely dose into the empty cartridges (5) some of the components or raw materials that give rise to the inks.

[0253] These hoppers (6, 7) have specially adapted loading nozzles to dispense raw materials into empty or pre-filled cartridges (5). They will not necessarily be identical, as they are designed to maintain (for a certain time) and dispense different components of active ingredients (AI), pure excipients (EX), and pre-formulated excipients (EX), which may have different properties and can be liquid, solid, semi-solid, or dispersed systems.

[0254] These hoppers (6, 7) operate in the context of equipment that, following the guidelines loaded into the data processing unit (software) (1), connects to the empty or pre-filled cartridge (5), using the cartridge access ports (19, 20), and deposits the right and necessary amount of active ingredient (AI) and / or excipients (EX) according to the designed formulation, the prescribed dose and the frequency of use.

[0255] Like the empty or prefilled cartridge (5), the hoppers (6, 7) include an NFC (Near Field Communication - short-range wireless communication technology) code that allows data exchange between compatible devices at a distance of a few centimeters (or other similar technology that allows identification and traceability).

[0256] C) At least one automated equipment that uses information provided by processing units and devices, executes filling, mixing and extrusion orders to produce customized products (PP) in their primary packaging without human intervention and with quality assured by the process.

[0257] These machines are designed according to GMP (Good Manufacturing Practices) standards, which are a series of rules and guidelines that ensure products are manufactured to the appropriate quality under specific conditions. They operate using arms or movement units equipped with a specially designed head to: 1) house the cartridge, 2) enable connection to the hoppers, 3) perform the actions to manufacture the cartridges (heating / homogenizing / venting / capping), and 4) precisely extrude the manufactured ink to reach the required dose specified in the recipe.

[0258] As additional features, this system includes:

[0259] • A dedicated processing unit to interpret the preparation orders (OP) and the extrusion order (OE) / printing order (OE) and block the use of the equipment if necessary.

[0260] • Extrusion beds (11) prepared to be loaded with the primary packaging or capsules in order to avoid cross-contamination.

[0261] • Hoppers (6, 7) specially provided to connect with the empty or pre-filled cartridge (5) in the head and deposit the raw materials into the cartridge.

[0262] • A body-shell (13) that isolates it from environmental conditions that may affect the process.

[0263] This equipment is divided into two operationally related units: a preparation / formulation unit (equipped with hoppers and which interprets the preparation order) and an extrusion unit (which is fed with the formulated cartridges and primary containers, and which interprets the extrusion / printing commands). In the two-unit model, an operator or a third technology (e.g., a robotic arm) is required to take the formulated cartridge from the preparation unit and feed it into the extrusion unit. The units may be located in the same facility, or there may be one facility that prepares the cartridges and another that performs the extrusion.

[0264] The system of the present invention generates a method for the automated and personalized production of medicines, supplements and / or functional foods.

[0265] This method exists to the extent that there is first a personalized treatment for a patient (P). Based on information specific to each person, such as their pathologies, history, preferences, metabolism, renal function, microbiota, etc., patients are prescribed a treatment that includes at least one inhibitor (AI) at a specific dose, frequency of use, and duration of treatment.

[0266] EXAMPLES

[0267] A patient (P) was prescribed 3 active ingredients (AI):

[0268] • IA No. 1, 5 mg, twice a day (once in the morning and once at night), for 60 days.

[0269] • IA No. 2, 80 mg (which in this example the industry markets in commercial tablets of 20 mg), once a day (in the morning), for 60 days.

[0270] • IA No. 3, 40 mg, twice a day (once in the morning and once at night), for 60 days. Therefore, the patient (P) must take 6 tablets in the morning and two at night, which with the method described here can be reduced to at least one tablet per shift. The method begins when the patient's (P) personalized treatment is uploaded to the data processing unit (1), either directly by a physician (M) or a prescribing professional, or by the patient or the pharmacy using the provided indication or prescription. This data processing unit (1) connects to the cloud (2) where, through a validation process with the database, a preparation order (PO) is generated (which instructs the operation of the compounding-formulating equipment (3)) and an extrusion order (EO) / printing order (OI) (which instructs the operation of the extruder equipment (4)), which is then sent to a production location.

[0271] In the case of the example described here, the system first calculates the minimum number of milligrams that should be used for the patient's treatment.

[0272] TABLE 1

[0273]

[0274] The system identifies that two finished cartridges (8) are required: one cartridge loaded with IA No. 1 and IA No. 3 (Cartridge No. 1) and another with IA No. 2 (Cartridge No. 2). IA No. 1 and No. 3 are compatible with each other and can be loaded into an ink containing 89% of excipient No. 1, 6% of excipient No. 2, and 5% of excipient No. 3. IA No. 2 can also be loaded into this same ink, which supports up to 40% of these IAs without altering its extrusion properties.

[0275] The system also indicates that this ink results in a loss of 450 mg per cartridge during the printing process (primarily due to adhesion to cartridge components). Based on this information, the preparation order for cartridge #1 and cartridge #2 is generated.

[0276] Cartridge No. 1 must contain at least 5400 mg of IA (between IA No. 1 and IA No. 3), which is equivalent to 40% of the total weight of the material, that is, between IA and excipient (EX) would total 13500 mg.

[0277] Considering the ink loss that adheres to the cartridge, the system generates a preparation order for 14000 mg of ink, distributed as follows:

[0278]

[0279] The preparation order (PO), in addition to defining the quantities, indicates the order in which the components should be added and whether any processing is required before adding another. Example: Add excipient (EX), heat to 50°C, stir for 10 minutes, and add active ingredient (AI). In this example, the AI ​​and excipients from both cartridges can be mixed, the order in which they are added is irrelevant, and then melted simultaneously.

[0280] Therefore, the preparation order for cartridge No. 1 is as follows:

[0281] a. Load an empty cartridge into the equipment (5)

[0282] b. Connect cartridge to excipient hopper No. 1

[0283] c. Add 7476 mg

[0284] d. Connect cartridge to excipient hopper No. 2

[0285] e. Add 504 mg

[0286] f. Connect cartridge to excipient hopper No. 3

[0287] g. Add 420 mg

[0288] h. Connect cartridge to IA hopper No. 1

[0289] i. Add 622.2 mg

[0290] j. Connect cartridge to IA hopper No. 3

[0291] k. Add 4977.8

[0292] l. Seal cartridge. Heat thermostatically controlled jacket to 55°C

[0293] n. Shake at 100 rpm for 15 minutes.

[0294] This same logic applies to cartridge #2, which must contain a minimum of 4800 mg of IA #2, equivalent to 40% of the total material weight. Therefore, the IAs and excipient together would total 12000 mg. Considering the ink loss that adheres to the cartridge, the system generates a preparation order for 12500 mg of ink distributed as follows:

[0295]

[0296] Therefore, the preparation order for cartridge No. 2 is as follows:

[0297] a. Load an empty cartridge into the machine

[0298] b. Connect cartridge to excipient hopper No. 1

[0299] c. Add 6675 mg

[0300] d. Connect cartridge to excipient hopper No. 2

[0301] e. Add 450 mg

[0302] f. Connect cartridge to excipient hopper No. 3

[0303] g. Add 375 mg

[0304] h. Connect cartridge to IA hopper No. 2

[0305] i. Add 5000 mg

[0306] j. Seal cartridge

[0307] k. Heat thermostated jacket to 55°C

[0308] l. Shake at 100 rpm for 15 minutes.

[0309] In the pharmacy, automated equipment or compounding-formulating equipment (3) is used, where many hoppers (6, 7) with different (IA) and excipients (EX) are housed.

[0310] If the necessary hoppers (6, 7) and empty or pre-filled cartridges (5) are not already loaded, the preparation order (PO) will additionally instruct the operator to perform these steps, that is, to load the necessary cartridges and hoppers into the equipment according to the preparation order. Once this has been done, the automated equipment, following the guidelines of the preparation order, deposits the necessary quantities of active ingredient (AI) and / or excipients into each empty or pre-filled cartridge (5), in a predetermined order and sequence, for the preparation of the ink(s) that will produce the patient's or user's primary pigment (PP).

[0311] In this preparation, the excipients (EX) can be heated and stirred, with the temperatures, stirring speeds, times, and order of component deposition being key to obtaining the formulation. Once the preparation is complete, the equipment notifies that the process has finished and that the extrusion order (OE) should begin.

[0312] When dealing with two machines in the same facility, the system notifies the operator of the completion of the process, so that they can move the finished cartridge(s) and insert the containers, if they are not loaded automatically.

[0313] Alternatively, and only where the ink allows, the compounding-formulating equipment (3) can be operated in a location other than the pharmacy, with the preparation and extrusion processes completely separate. In all cases, the NFC code (or similar technology) notifies the equipment of the cartridge's identity to prevent errors and ensure traceability. In the example case, the extrusion order (EO) or print order (OI) indicates the following:

[0314] 1. Load the cartridge identified (via NFC) as “Cartridge No. 1” and “Cartridge No. 2” into the extruder (or extruder module).

[0315] 2. Load two blisters (primary packaging 12) of 60 alveoli into the extrusion bed (11) of the extruder (or extruder module), 30 for daytime tablets and 30 for nighttime tablets.

[0316] 3. Using “Cartridge No. 1”, use g.code No. 1 (which tells the extruder the extrusion speed and movements, in stroke and speed, to accurately deposit 112.5 mg of ink) in the 120 cells

[0317] 4. Using “Cartridge No. 2”, use g.code No. 2 (which tells the extruder the extrusion speed and movements, in stroke and speed, to accurately deposit 200 mg of ink) in the 60 “night cells”

[0318] 5. Remove blisters or packaging.

[0319] The difference between OE and OI lies in the nature of the g-code. In OE, the g-code instructs the machine to move the print head to position the cartridge nozzle in the center of the mold and then precisely extrude the material, possibly heated to a specific temperature. In OI, the g-code instructs the machine to perform precise and coordinated movements to extrude the material as the print head moves along the three axes (X, Y, Z), ultimately forming a solid, three-dimensional geometry.

[0320] As can be seen in the example, in order for the extrusion / printing order (OE / OI) to be executed, the equipment needs (in addition to the ink-loaded cartridge(s)) the primary containers (12) where the extrusion will be deposited to be loaded (or configured).

[0321] In certain cases, the bed may require temperature regulation (hot or cold), and instead of using primary containers, a disposable surface may be used to prevent cross-contamination. The extrusion bed parameters (11) and / or the primary containers (12) (or disposable surface) can be loaded automatically or manually. When using the extruder (4), the operator selects the order, the primary containers (12) (or surfaces), and the finished cartridge(s) (8), which will be identified with its NFC code to prevent errors.

[0322] The extruder unit (4) working together with the data processing unit (1), reads the extrusion order (EO) and uses the required manufactured cartridge(s) (8) (a PP can use more than one cartridge) to produce the required PP by additive manufacturing or by molding onto the primary packaging (12) (or disposable surface).

[0323] Finally, the operator removes the PP for subsequent quality control and sealing of the container, issues that can be automated in the future.

[0324] In summary, the method involves the following steps:

[0325] 1- Loading the patient's personalized treatment into the data processing unit. 2- Generating the preparation and extrusion / printing orders, based on the treatment information and the raw material study stored in the database. 3- Loading (manually or automatically) the cartridge(s) into the single automated equipment or processing equipment.

[0326] 4- Loading (manual or automatic) of the hoppers in single automated equipment or processing equipment

[0327] 5- Preparation of inks in cartridges, based on the raw materials from the hoppers and the work of the printhead of the equipment that follows the instructions contained in the preparation order, filling, heating and agitating the contents of the cartridges

[0328] 6- Loading (manual or automatic) of ink cartridges and primary containers (or disposable surface) into single automated equipment or extruder equipment

[0329] 7- Production of personalized products, based on the cartridge(s) loaded with the ink(s) produced in step 5 and the work of the printhead of the equipment that follows the instructions contained in the extrusion / printing order, depositing the inks in a controlled and orderly manner in the primary containers (or disposable surface) until reaching the final product intended for the patient.

[0330] The things described and exemplified are included within the scope of protection of this patent application, which is established, in essence, by the text of the claims that follow.

Claims

CLAIMS 1. Cartridge for mixing and extruding ingredients for the production of medicines, supplements, cosmetics and / or functional foods, characterized in that it comprises: a body-housing (13) with a proximal end (EP) and a distal end (D), a plug-piston (16) disposed inside the proximal end (EP), an outlet nozzle (17) with a connection at the distal end (D), and a mixing paddle (14) for mixing the ingredients housed inside said body-housing (13).

2. Cartridge, according to claim 1, characterized in that said body-housing (13) comprises two parts with coupling means between them, a first part consisting of a proximal cylindrical body (24) and a second part consisting of a conical distal body (25) with an outlet nozzle (17) or a connection.

3. Cartridge, according to claim 1, characterized in that said body-housing (13) is a single part, having a proximal cylindrical end (24) and a conical distal end (25).

4. Cartridge, according to any of the preceding claims, characterized in that the mixing paddle (14) is arranged in the plug-piston (16) at its proximal end (EP) with a coupling connection to an external rotation shaft.

5. Cartridge, according to claim 4, characterized in that between the mixing paddle (14) and the piston plug (16) it comprises a shaft (15) coupled to the piston plug (16) with a coupling connection to the external rotation shaft.

6. Cartridge, according to any of the preceding claims, characterized in that said plug-piston (16) has an external shape similar to that of the internal distal end of the body-housing (13) and at least one access opening (19, 20) at its proximal end.

7. Cartridge, according to claim 6, characterized in that said access opening (19, 20) has an independent closing piece (23) that seals the cartridge after loading the ingredients.

8. Cartridge, according to claim 6, characterized in that said access opening (19, 20) has an elastic membrane that seals the cartridge after loading the ingredients.

9. Cartridge, according to any of the preceding claims, characterized in that it comprises at least one O-ring (21) between the plug-piston (16) and the body-housing (13).

10. Cartridge, according to any of claims 4 or 5, characterized in that the coupling connection of the plug-piston (16) to the external rotation shaft comprises a central retainer (22).

11. System for the automated and personalized production of medicines, supplements, cosmetics and / or functional foods, characterized in that it comprises: at least one data processing unit (1) connected to a cloud (2) of databases of ingredients, excipients (EX) and active ingredients (IA) and ink formulations based on said ingredients, configured to receive information related to a patient's treatment (P) and to create, based on the information received, preparation orders (OP) and / or extrusion / printing orders (OE / OI), at least one formulator-manufacturer (3), which manufactures the inks in at least one cartridge (5), according to any of claims 1 to 10, from the preparation orders (OP) and with at least one hopper (6) containing the active ingredients (IA) and / or a hopper (7) containing the excipients (EX), at least one extruder unit (4) with a formulating arm head (9) and a printing arm head (10), which automatically produces the customized final product (PP) from the extrusion / printing order (OE / OI) and at least one prepared cartridge (8) with ingredients, the contents of which are poured onto an extrusion bed (11) to provide a finished product in a primary container (12) intended for the patient (P), having operational linking means between said at least two units (3, 4) and said at least one data processing unit (1) by means of said database cloud (2).

12. System, according to claim 11, characterized in that said processing equipment has a shaft complementary to the shaft of the paddle in order to execute the rotation of the mixing paddle (14) of the cartridge.

13. System, according to claim 11, characterized in that said at least one empty or pre-filled cartridge (5) and said at least two hoppers (6, 7) include an NFC code (Near Field Communication - short-range wireless communication technology or similar technology).

14. System, according to any of claims 11 to 13, characterized in that the formulating equipment and the extruding equipment are separate.

15. System, according to any of claims 11 to 13, characterized in that the formulating equipment and the extruding equipment form a single integrated automated unit, with a formulating component and an extruding component.

16. Method for the automated and personalized production of medicines, supplements, cosmetics and / or functional foods, employed in the system according to any of claims 11 to 15, characterized in that it comprises the following steps: a) loading the patient's personalized treatment (P) into said at least one data processing unit (1), b) prepare the preparation orders (PO) and the extrusion / printing orders (OE / OI), based on the information from the treatment and the study of the ingredients stored in the database, c) manually or automatically load at least one empty cartridge (5) into said at least one formulating unit (3) or formulating component of the integrated automated equipment, d) manually or automatically load said at least two hoppers (6, 7) into said at least one formulating equipment (3) or formulating component (3) of the integrated equipment, d) execute the preparation orders (PO) comprising preparing the inks in said at least one empty cartridge (5), based on the ingredients in said at least two hoppers (6, 7), and execute the preparation orders, obtaining the prepared cartridge (8) with ink, e) manually or automatically load said at least one prepared cartridge (8) with ink and some primary containers, or disposable surface, into the extruder equipment (4) or extruder component of the integrated automated equipment, and f) produce the personalized products (PP), based on said at least one prepared cartridge (8) loaded with the ink(s) prepared in step d) and the work of the printheads of the extruder equipment (4), or extruder component of the integrated automated equipment, which follow the instructions contained in the extrusion / printing orders (OE / OI), depositing in a controlled and orderly manner the inks in the primary packaging, or disposable surface, until reaching the final product intended for the patient (P).

17. Method employed in the system according to any of claims 11 to 15, characterized in that it comprises the following steps: a) load the patient's personalized treatment (P) into said at least one data processing unit (1), b) prepare the preparation orders (PO) and the extrusion / printing orders (EO / OI), based on the information on the treatment and the study of the raw materials stored in the database, c) manually or automatically load at least one pre-filled cartridge (5) with ingredients into said at least one formulating equipment (3) or formulating component, d) manually or automatically load said at least one hopper (6,7) into said at least one formulating equipment (3) or formulating component of the integrated automated equipment, d) execute the preparation orders (PO) comprising preparing the inks in said at least one pre-filled cartridge (5), based on the ingredients of said at least one hopper (6,7), and execute the preparation orders, obtaining the prepared cartridge (8) with ink, e) manually or automatically load said at least one prepared cartridge (8) with ink and primary packaging, or disposable surface, into the extruder equipment (4) or extruder component of the integrated automated equipment, and f) prepare the personalized products (PP), based on said at least one prepared cartridge (8) loaded with the ink(s) prepared in step d) and the work of the printheads of the extruder equipment (4), or extruder component of the integrated automated equipment, which follow the instructions contained in the extrusion / printing orders (OE / OI), depositing in a controlled and orderly manner the inks in the primary containers, or disposable surface, until reaching the final product intended for the patient (P).

18. Method, employed in the system according to any of claims 11 to 15, characterized in that it comprises the following steps: a) load the patient's personalized treatment (P) into said at least one data processing unit (1), b) prepare the preparation orders (PO) and the extrusion / printing orders (OE / OI), based on the treatment information and the information stored in the database regarding cartridges pre-filled with ingredients, c) manually or automatically load said at least one pre-filled cartridge (5) into said at least one formulating equipment (3) or formulating component of the integrated automated equipment, d) execute the preparation orders (PO) which include preparing the inks in said at least one pre-filled cartridge (5) with ingredients, and execute the preparation orders, obtaining the prepared cartridge (8) with ingredients that make up the ink, (e) manually or automatically load said at least one cartridge (8) made with ink and the primary packaging, or disposable surface, into extruder equipment (4) or extruder component of integrated automated equipment, and f) manufacturing the personalized products (PP), based on said at least one manufactured cartridge (8) loaded with the ink(s) manufactured in step d) and the work of the printheads of the extruder equipment (4), or extruder component of the integrated automated equipment, which follow the instructions contained in the extrusion / printing orders (OE / OI), depositing in a controlled and orderly manner the inks in the primary containers or disposable surface, until reaching the final product intended for the patient (P).

19. Method, according to any of claims 16 or 17, characterized in that the manufacturing orders comprise the filling, heating and agitation of the cartridge, and subsequent venting of the air.

20. Method, according to claim 18, characterized in that the manufacturing orders comprise heating and agitation of the cartridge and subsequent venting to the air.

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