Methods and systems for the preparation of pharmaceutical dosage forms

Abstract

According to an example aspect of the present invention, there is provided a method for preparing pharmaceutical dosage forms, the method comprising: inserting a dispenser into a thermal end; wherein the dispenser comprises a first tag and a dispensable dispersion comprising an active pharmaceutical ingredient (API), wherein the thermal end is detachably attachable to a liquid handling device, reading the first tag with a first reader to obtain a dispenser identification code, sending, by the liquid handling apparatus, the obtained dispenser identification code to a server comprising a database comprising at least one previously obtained dispenser identification code, verifying, by the server, the obtained dispenser identification code against the at least one previously obtained dispenser identification code to confirm the identity of the dispenser, and dispensing, by the liquid handling apparatus, at least some of the dispensable dispersion onto a dispensing target to form one or more dosage forms.

Description

METHODS AND SYSTEMS FOR THE PREPARATION OF PHARMACEUTICALDOSAGE FORMSFIELD

[0001] The present invention relates to methods and systems for the preparation of pharmaceutical dosage forms comprising active pharmaceutical ingredients (APIs), in particular in the field of personalized medicine.BACKGROUND

[0002] Extrusion-based dispensing is a technology which gives the possibility to manufacture personalized dosage forms of medicaments. One main benefit of the technology for personalized medicine is the ability to produce small batches with carefully tailored dosages, shapes, sizes, and release characteristics. It also allows flavors to be incorporated into a dosage form without the need of a film coating, entirely masking the taste of chemical compounds. Systems for preparing pharmaceutical dosage forms can be installed in pharmacies, hospitals, clinics, and remote locations, enabling on-demand production of drugs, particularly those with poor stability or that have cold chain storage requirements. For pharmaceutical companies and pharmacists, extrusion-based dispensing can significantly reduce costs, waste, and environmental burden as dispensers only deposit the exact amounts of raw materials required.

[0003] Any discussion, including discussion of problems and solutions, set forth in this section has been included in this disclosure solely for the purpose of providing a context for the present disclosure. Such discussion should not be taken as an admission that any or all of the information was known at the time the invention was made or otherwise constitutes prior art.SUMMARY OF THE INVENTION

[0004] This summary is provided to introduce a selection of concepts in a simplified form. These concepts are described in further detail in the detailed description of example embodiments of the disclosure below. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter.

[0005] The invention is defined by the features of the independent claims. Some specific embodiments are defined in the dependent claims.

[0006] According to a first aspect of the present invention, there is provided a method for preparing pharmaceutical dosage forms the method comprising:- inserting a dispenser into a thermal end; wherein the dispenser comprises a first tag and a dispensable dispersion comprising an active pharmaceutical ingredient (API), wherein the thermal end:- is detachably attachable to a liquid handling device,- is configured to accept the dispenser,- reading the first tag with a first reader, wherein the first reader: is configured to obtain a dispenser identification code by reading the first tag, is connected to the liquid handling apparatus,- sending, by the liquid handling apparatus, the obtained dispenser identification code to a server comprising a database, the database comprising at least one previously obtained dispenser identification code,- verifying, by the server, the obtained dispenser identification code against the at least one previously obtained dispenser identification code to confirm the identity of the dispenser, indicating, by the server, responsive to a positive verification, to the liquid handling apparatus that the inserted dispenser is acceptable,- dispensing, by the liquid handling apparatus, at least some of the dispensable dispersion onto a dispensing target to form one or more dosage forms,- recording, by the liquid handling apparatus while dispensing, parameters relating to the formed one or more dosage forms, and- sending, by the liquid handling apparatus, the recorded parameters to the server, the server being configured to store the recorded parameters in the database.

[0007] According to a second aspect of the present invention, there is provided a system for preparing pharmaceutical dosage forms, the system comprising- a server comprising at least one processing core, at least one memory including computer program code, the server comprising or connected to a database,- a dispenser thermal end, said thermal end configured to accept a dispenser comprising a first tag and a dispensable dispersion comprising an active pharmaceutical ingredient (API) and to adjust the temperature of the dispensable dispersion,- a first reader, said first reader configured to obtain a dispenser identification code by reading the first tag,- a liquid handling apparatus connected to the server, wherein the liquid handling apparatus is configured to:- send, to the server, the obtained dispenser identification code, the server being configured to verify the obtained dispenser identification code against at least one previously obtained dispenser identification code, and responsive to a positive verification, indicate to the liquid handling apparatus that the inserted dispenser is acceptable,- optionally adjust the temperature of the dispensable dispersion by controlling the thermal end,- dispense, using said dispenser, at least some of the dispensable dispersion to a dispensing target to form one or more dosage forms, record, while dispensing, parameters relating to the formed one or more dosage forms, and- send the recorded parameters to the server, the server being configured to store the recorded parameters in the database.

[0008] According to a third aspect of the present invention, there is provided a server comprising at least one processing core, at least one memory including computer program code, the server comprising or connected to a database, the at least one memory and the computer program code being configured to, with the at least one processing core, cause the server at least to:- receive, from a liquid handling apparatus, at least one dispenser identification code, DIC,- verify the obtained DIC against at least one previously obtained DIC to confirm the identity of a dispenser associated with the obtained DIC, wherein the at least one previously obtained DIC is retrieved from a database comprised in or connected to the server,- indicate, if the verification result is positive, to the liquid handling apparatus that the inserted dispenser is acceptable,- receive, from the liquid handling apparatus, recorded dispensing parameters, and- store the received recorded dispensing parameters in the server.

[0009] According to a fourth aspect of the present invention, there is provided a liquid handling apparatus comprising at least one processing core, at least one memory including computer program code, the at least one memory and the computer program code being configured to, with the at least one processing core, cause the liquid handling apparatus at least to:- read a first tag with a first reader, wherein the first reader:- is configured to obtain a dispenser identification code by reading the first tag,- is connected to the liquid handling apparatus,- send, the obtained dispenser identification code to a server comprising a database, the database comprising at least one previously obtained dispenser identification code,- receive from the server, if the verification result is positive, to the liquid handling apparatus that the inserted dispenser is acceptable,- begin dispensing and record dispensing parameters, and- send the recorded dispensing parameters to the server.

[0010] Various embodiments of the first, second, third or fourth aspect may comprise at least one feature from the following bulleted list:• the first tag is an RFID tag, in particular an NFC tag, and wherein the first reader is an RFID reader;• the first tag is a barcode and wherein the first reader is a barcode reader;• the first tag is a machine-readable label, for example a QR code, and wherein the first reader is a camera.• the dispensing target comprises a second tag, the method further comprising:- reading the second tag with a second reader to obtain a target identification code,- sending, by the liquid handling apparatus, the obtained target identification code to the server comprising a database, the database comprising at least one previously obtained target identification code,- verifying, by the server, the obtained target identification code against the at least one previously obtained target identification code to confirm the identity of the dispensing target, and- indicating, by the server, responsive to a positive verification, to the liquid handling apparatus that the dispensing target identity is acceptable;• the first and / or second reader is positioned on or within the thermal end.BRIEF DESCRIPTION OF THE DRAWINGS

[0011] FIGURE 1 shows an exemplary syringe suitable for the method of the present disclosure.

[0012] FIGURE 2 shows an exemplary arrangement for use in weighting an active pharmaceutical ingredient and a pharmaceutical excipient base into a barrel of a syringe.

[0013] FIGURE 3 shows a representative part of an exemplary blade-free planetary mixer suitable for use in the method of the present disclosure.

[0014] FIGURE 4 shows an exemplary dispenser suitable for use in the method of the present disclosure.

[0015] FIGURE 5 shows an exemplary system for use in method of the present disclosure for producing packages including one or more traceable solid dosage forms of active pharmaceutical ingredients.

[0016] FIGURE 6 shows an exemplary method in accordance with the present disclosure,

[0017] FIGURE 7 shows an exemplary method in accordance with the present disclosure,

[0018] FIGURE 8 shows an exemplary method in accordance with the present disclosure,

[0019] FIGURE 9 shows an exemplary method in accordance with the present disclosure,

[0020] FIGURE 10 shows an exemplary method in accordance with the present disclosure,

[0021] FIGURE 11 shows an exemplary liquid handling apparatus in accordance with the present disclosure,

[0022] FIGURE 12 shows an exemplary data structure in accordance with the present disclosure,

[0023] FIGURE 13 shows an exemplary flowchart in accordance with the present disclosure, and

[0024] FIGURES 14A and 14B show an exemplary apparatuses in accordance with the present disclosure.

[0025] It will be appreciated that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions of some of the elements in the figures may be exaggerated relative to other elements to help improve understanding of illustrated embodiments of the present disclosure.EMBODIMENTS

[0026] The present disclosure provides apparatuses and methods for manufacturing products such as pharmaceutical products in a distributed and / or personalized manner. In the disclosure, a liquid handling apparatus may be used to precisely dispense formulations, such as medical formulations, and a server apparatus may be used in connection with the liquid handling apparatus and optionally other equipment to ensure that the manufacturing complies with the manufacturing order, that is to say that the manufacturing has been properly performed. After manufacturing, a data structure with the relevant information may be provided to stakeholders. Such a structure may be provided for each individual dosage form and it may precisely describe the manufacturing and content of the individual dosage form.

[0027] Further, the methods and systems herein are suitable for 3D printing, in particular of pharmaceutical products. 3D printing refers to a manufacturing process that creates three-dimensional objects, for example by successively adding material layer by layer to fabricate items, in particular items with precise geometries and complex structures.

[0028] DEFINITIONS

[0029] A dosage form (also known as a dose) refers to a physical form of a pharmaceutical composition. A dosage form comprises at least one active ingredient. Typically, it further comprises at least one carrier or excipient. A dosage form may be any one of a tablet, a capsule, a powder, a granule, a pellet, a liquid, a gel, a suspension, a emulsion, an ointment, a suppository. The term “dosage form” may describe both the format (such as “tablet”) and the product (“a manufactured tablet”).

[0030] A dispenser, for example a syringe, refers to a device used to draw in, contain, and dispense liquids, viscous fluids or other materials in various applications. A dispenser may be used to dispense for example liquids, semi-solids, viscous fluids, or formulations such as a base formulation, or a medical formulation, which can comprise a pharmaceutical excipient base, which can be admixed with active pharmaceutical ingredients (API) to produce dispensable dispersions in precise volumes for applications such as laboratory procedures, industrial processes, or medical applications. A dispenser may be of different sizes depending on the intended use of the dispenser and the material to be dispensed. A cartridge is another example of dispenser that can be used for controlled dispensing of various formulations. Such a cartridge is typically pre-filled and designed for use in a dispensing system, ensuring precise and sterile delivery of for example liquids, semi-solids, viscous fluids, or formulations in pharmaceutical, industrial, and laboratory applications.

[0031] For example, a dispenser, such as a syringe or a cartridge, may have a volume capacity from 0.001 ml to 1000 ml, for example from 0.1 ml to 500 ml, or from 1 ml to 100 ml, or from 1 to 50 ml, or from 5 ml to 20 ml.

[0032] A dispenser, such as a syringe may be associated with a dispenser identification code, DIC. A DIC identifies a single dispenser. A DIC may comprise or correspond to at least one of: an indication of the dispenser type, manufacturer, and / or production date. A server may look up the information associated with the DIC from a database, when provided with the DIC. A DIC may be used to verify that the dispenser is the same dispenser throughout the process, for example. A DIC may be used, for example, to identify and / or verify the dispenser is of a correct type. At least one DIC may be provided in advance of manufacturing to a database, for example by uploading a list of DIC’s to the database or by reading, using a reader, at least one DIC. Any DIC provided in advance is a previously obtained DIC when discussed below. A DIC may be read by a suitable from a tag attached to or printed on the dispenser. For example, the tag may be an RFID tag, in particular an NFC tag, and the reader may be an RFID reader; or the tag may be a barcode and the reader may a barcode reader; or the tag may be a machine-readable label, for example a QR code, and the reader may be a camera.

[0033] A syringe may comprise a barrel, a barrel flange, a piston, a piston flange, a seal, a luer lock, and a luer slip with a centric tip.

[0034] A syringe barrel may comprise a cylindrical main body for the material, for example liquid, which is to be dispensed. The barrel further may comprise barrel flanges located on the barrel. The barrel flanges are "wings" that protrude from the sides of the barrel and provide a surface or area which aids in aspiration or liquid administration by providing a surface to hold when the syringe is operated.

[0035] A syringe piston is a shaft that connects the piston flange to the syringe seal. The pressure applied to the plunger goes through to the seal and presses the liquid down towards the luer lock.

[0036] A piston flange is a protruding feature at the rear end of the barrel that provides a gripping surface and easier application of pressure. The piston flange bears the load of the pressure applied to the piston.

[0037] A syringe seal is a flexible component positioned at the distal end of the piston that forms a fluid-tight interface with the barrel's inner surface, preventing leakage and ensuring efficient fluid transfer. The seal slides up and down the barrel in response to the pressure applied to the piston (similar to the motion of a piston in a cylinder).

[0038] A luer lock is a standardized screw fitting for attaching fittings to the syringe that will not ‘blow off when the liquid is under pressure. The luer lock ensures a leakresistant interface. There are three different styles of luer lock; luer lock tip, luer slip centric tip, and luer slip eccentric tip. A syringe as used in the present disclosure may have any type of luer lock, preferably a luer slip centric tip. A luer slip centric tip is a luer lock with the tip centrally located. Reference is made to the ISO 80369 standard, for example part 7, with respect to the luer lock and luer slip.

[0039] A thermal end refers to an apparatus comprising a docking component and a hollow, elongated multilayered body, into which a dispenser can be inserted to control the temperature of the dispenser, in particular the contents of the dispenser. In other words, the thermal end receives the dispenser. The thermal end comprises controllable thermoelements, which may be controlled to raise and / or lower the temperature. The term hollow refers to the elongated body being empty on the inside when no dispenser is present. Elongated means that the body extends further in one dimension than in the others.

[0040] A docking component refers to an integral or attached part of the thermal end used to attach the thermal end to a counterpart docking component. The dockingcomponent may comprise pins, pin holes, magnets, and / or guide features to aid in attaching the apparatus via the docking component to a counterpart docking component.

[0041] A counterpart docking component refers to a complementary structure designed to engage with the docking component of the thermal end, thereby securing the thermal end to an external device, for example to a liquid handling apparatus.

[0042] Heating refers to the process of increasing the temperature of a dispenser, or its contents, by transferring thermal energy from the thermal end to the dispenser through conduction, convection, radiation, or a combination thereof.

[0043] Cooling refers to the process of decreasing the temperature of a dispenser, or its contents, by transferring thermal energy away from the dispenser to the thermal end or another heat sink through conduction, convection, radiation, or a combination thereof.

[0044] Temperature control refers to regulation of a dispenser’s, or its content’s, temperature within a desired range, including active heating, active cooling, or passive maintenance of a desired temperature, as enabled by the thermal end.

[0045] A liquid handling apparatus refers to an apparatus which is configured to dispense liquids, semi-solids, viscous fluids, or formulations which can be admixed with active pharmaceutical ingredients (API) to produce dispensable dispersions, by using a dispenser, for example a syringe. In such an apparatus, at least one motor is used to actuate the dispenser. Beneficially, such an apparatus further allows for moving the dispenser in at least two dimensions (X and Y dimensions), in particular in three dimensions (X, Y and Z) dimensions. This allows the apparatus to dispense to multiple locations, for example to one or more cavities of a container, to one or more blisters of a blister pack, or to a flat surface, for example a glass surface. A thermal end may be attached to a liquid handling apparatus. Additionally or alternatively, a thermal end may form a part of a liquid handling apparatus, allowing the dispenser to be heated or cooled to any suitable temperature.

[0046] A manufacturing order refers to a digital or physical instruction or directive for the production of a pharmaceutical product. The manufacturing order specifies the composition, form, quantity, mass, dosage form (dose), quantity of active agent, and packaging. The manufacturing order may comprise patient-specific information for the production of personalized medicine. The manufacturing order may comprise process parameters, for example mixing and / or dispensing parameters such as temperature. Themanufacturing order may comprise batch parameters, for example in the production of bulk drugs. The manufacturing order may originate from a pharmacy, automated prescription system, an internal scheduling system, or any other suitable provider. The manufacturing order may serve as the trigger for initiating the production process of the pharmaceutical product. The manufacturing order may govern the process throughout. Examples of a manufacturing order include: a personalized prescription drug for a single patient, or a bulk drug order of for example ibuprofen.

[0047] The manufacturing order may comprise a plurality of dosage forms, with at least some of the dosage forms having different characteristics, for example mass, than others within the plurality. For example, the manufacturing order may comprise a first dose with a first quantity of active ingredient, and a second dose with a second quantity of the active ingredient, where the first quantity is larger than the second quantity. This is achieved by reducing (or increasing, as the case may be) the total mass of the dosage form. This can be continued with third, fourth, fifth doses, etc. This has the advantage of providing personalized medicine, as the patient will have gradually decreasing amounts of the active ingredient in doses on the same package (blister). This allows for different dosage regimens and / or treatment regiments to be provided to the patient with only a single package.

[0048] A blend refers to a physical admixture of two or more components, for example of a pharmaceutical excipient base and at least one active pharmaceutical ingredient (API), that have been weighed and combined. The blend may be heterogeneous, and provides the material to form the dispensable dispersion, which can be achieved by mixing.

[0049] A dispensable dispersion refers to a composition in which the components of a blend have been mixed to form a homogeneous or substantially homogeneous mixture. The dispensable dispersion may comprise suitable rheological and structural properties to be suitable for dispensing, or 3D printing, of a pharmaceutical product. Alternatively, the dispensable dispersion may require an adjustment in temperature, in order to achieve suitable rheological and structural properties.

[0050] An RFID reader and an RFID tag refer to components of a radio-frequency identification (RFID) system. An RFID tag is a device that stores data and communicates said data wirelessly via radio waves when energized by an electromagnetic field generatedby the reader. An RFID reader is a device configured to emit radio-frequency signals to power and communicate with one or more RFID tags, thereby enabling reading or updating of data stored on the tags. The RFID tag and reader may utilize various frequency ranges, including high-frequency protocols such as Near Field Communication (NFC), and may be used for identification, tracking, authentication, and / or data logging in connection with the production of pharmaceutical products.

[0051] Users may log into a system disclosed herein using user credentials. The credential may be one or more of the following types: username and password, one time password, time-based one-time password, shared secret, public key certificate, hardware token, smart card, biometric data, facial recognition, voice recognition. Each user has a user identification code, UIC, which is a unique identifier usable to distinguish the user from other users. The UIC allows the user to be identified by apparatuses without necessarily transmitting the credentials to said apparatuses.

[0052] A dispensing target refers to at least one object suitable for dispensing a dispensable dispersion in or on, for example a blister pack or a plate surface, such as a glass plate or silicone mat. The dispensing target may reflect the dosage form of the dispensed substance. A dispensing target may comprise cavities to which the dispensable dispersion is dispensed to. Alternatively or additionally, a dispensing target may comprise a flat smooth surface to which the dispensable dispersion is dispensed to. A dispensing target may be associated with a target identification code, TIC. A TIC identifies a single dispensing target, for example a blister or a plate surface. A TIC may comprise or correspond to at least one of an indication of the dispensing target type, manufacturer, and / or production date. A server may look up the information associated with the TIC from a database, when provided with the TIC. In particular, a TIC may be used to identify and / or verify the dispensing target is of a correct type. At least one TIC may be provided in advance of manufacturing to a database, for example by uploading a list of TIC’s to the database or by reading, using a reader, at least one TIC. Any TIC provided in advance is a previously obtained TIC when discussed below. A TIC may be read by a suitable from a tag attached to or printed on the dispensing target. For example, the tag may be an RFID tag, in particular an NFC tag, and the reader may be an RFID reader; or the tag may be a barcode and the reader may be a barcode reader; or the tag may be a machine-readable label, for example a QR code, and the reader may be a camera.

[0053] Process data may be collected and / or recorded from equipment such as liquid handling apparatuses, balances, mixers, sealers, labellers. In particular, data from table 4 below, table 5 below, and / or table 6 below may be recorded. Such data collection is advantageous for ensuring that the dosage form has been produced correctly, for example according to predefined parameters. Such data may be recorded at predefined intervals, for example at intervals between 1ms to 1 second, in particular at a 5 ms interval. The data may be stored locally and uploaded to a server later, or uploaded directly after recording.

[0054] Via the embodiments, manufacturing of several different dosage forms is possible. In particular, pills, i.e. tablets or capsules, may be manufactured by dispensing into a blister pack form. The same applies to orally disintegrating tablets, lozenges or electuaries. Thin films may also be produced in accordance with the present disclosure. Any of suppositories, pastes, drops, lotions, emulsions and ointments are also within the scope of the present disclosure.

[0055] The specific examples provided in the description given below should not be construed as limiting the scope and / or the applicability of the appended claims. Lists and groups of examples provided in the description given below are not exhaustive unless otherwise explicitly stated.

[0056] In one aspect the present disclosure concerns method for producing one or more solid dosage forms of an active pharmaceutical ingredient. The method comprises the following steps: a) weighting at least an active pharmaceutical ingredient (API) and a pharmaceutical excipient base into a reservoir thereby producing a mixture of weighted materials; b) mixing and heating the mixture of the weighted materials in the reservoir until the mixture of the weighted materials is in the form of a dispensable dispersion; c) dispensing one or more doses of the dispensable dispersion from the reservoir onto a dispensing base a.k.a. a dispensing surface or dispensing target; d) cooling the one or more doses on the dispensing base to a temperature wherein the one or more doses are in a solid state thereby forming one or more solid dosage forms of an active pharmaceutical ingredient.

[0057] Exemplary reservoirs suitable for the method are a cartridge and a barrel of a syringe.

[0058] An exemplary syringe 100 suitable for the method is shown in figure 1. The syringe includes a piston 101 and a barrel 102 including a first opening 102a for the piston and a second opening 102b for allowing forcing the dispensable dispersion from the barrel. In an embodiment the syringe also includes a piston flange 103 and a barrel flange 104. In an embodiment the syringe includes a RFID code 105 for traceability. Exemplary syringes include ISO 11040-4: glass syringes ready for filling and ISO 11040-6: plastic syringes ready for filling.

[0059] The weighting step is illustrated in figure 2. For weighting, the barrel 102 is placed in a substantially vertical position on a balance 106 in the aid of a holder 107. Exemplary holders include containers such as a flask which is configured to support the side walls of the barrel, and statives. The second opening of the barrel is preferably closed by a plug 108 prior to weighting. The weighting produces a mixture of known amounts of the API, the pharmaceutical excipient base, and other ingredients if present.

[0060] In an embodiment the API is weighted as a crushed tablet including a known amount of API. If the tablet includes film coating, it is preferably removed e.g., by sieving the crushed mass.

[0061] The mixture should be homogenized before dispensing. For homogenizing the weighted materials are mixed and heated in the reservoir until a dispensable dispersion is formed. The required heating temperature is dependent predominantly on the properties of the pharmaceutical excipient base.

[0062] In an embodiment the homogenizing, i.e., mixing and heating, is performed using a mixer, preferably a blade-free planetary mixer. Representative part of an exemplary blade-free planetary mixer 109 equipped with a barrel holder 110 is shown in figure 3. Blade-free planetary mixers are well known in the art.

[0063] For mixing and heating the first end 102a of the barrel is preferably closed with a plug 111 to avoid the materials escaping from the mixer during mixing. Accordingly, the plugged barrel inducing the mixture of the weighted materials is positioned in the barrel holder 110 and the mixture of the weighted materials in the barrel is mixed and heated until a dispensable dispersion is formed. When the mixing is performed using a blade-free planetary mixer, the friction occurring during the mixing enables certain materials to be heated by the material flow friction action. Such materialsmay be for example pharmaceutical excipient bases including significant amounts of gelatin. Some other materials such as polyethylene glycol and sorbitol do not absorb heat but only dissipate heat. Thus, additional heating may be required.

[0064] When the desired dispersion is formed, the barrel is removed from the barrel holder, the plugs 108 and 110 are removed, and the piston 101 is positioned into the barrel 102.

[0065] For dispensing, the dispensable dispersion is forced from the barrel of the syringe through the opening 102b by pressing the piston 101 to produce one or more doses on a dispensing base. An exemplary dispensing base is a blister base including plurality of cavities for doses. Blisters are typically made of plastic.

[0066] The one or more doses are allowed to solidify upon cooling thereby producing one or more solid dosage forms of the API. The solidification temperature is dependent on the dispersion.

[0067] An exemplary dispensing apparatus 200 (which also may be termed a dispenser by some) for dispensing the dispensable dispersion produced is shown in figure 4. The dispensing apparatus includes a dispenser fixture arrangement 201, and a motor 202 comprising a threaded rod 203 engaged to the dispenser fixture arrangement. For operation, the syringe 100 filled with the dispensable dispersion prepared as disclosed above is attached to the dispenser fixture arrangement in such a way that the piston flange 103 and the barrel flange 104 of the syringe are arranged to the dispenser fixture by the first clamp 204 and the second clamp 205, respectively. When the fixing is completed, the dispensable dispersion is forced from the barrel through the opening 104a by pressing the piston using the motor 202 engaged to the first clamp.

[0068] In an embodiment the dispensing base comprising a desired number of solid dosage forms is sealed by a sealant. An exemplary sealant is a heat sealable foil.

[0069] In an embodiment the method includes printing a QR code positioned on top of the seal of each dose. The QR code comprises preferably one or more of: time of manufacture, batch info, dose, prescription in general, patient info, expiry date.

[0070] A preferable pharmaceutical excipient base used in the method includes the following properties- it is thermoreversible,- its viscosity at the dispensing temperature enables dispensing at temperature such as at 35-90 °C, or at 35-55 °C while it is solid at room temperature, and- it is suitable for use with a wide range of APIs.

[0071] A pharmaceutical excipient base suitable for the method comprises typically one or more of the following: gelling agents, fillers, solvents, thickeners, preservatives, surfactants, pH adjusting agents, and sweeteners.

[0072] Gelling agents are for creating the structural matrix of the dosage form; fillers provide bulk and can affect the release profile of the API; solvents are for dissolving and mixing the ingredients; thickeners assist achieving the desired consistency of the dispersion; preservatives ensure the stability and shelf-life of the product; surfactants aid in the uniform dispersion of the API within the excipient base; pH adjusting agents maintain the desired pH level for stability and compatibility; and sweeteners are for improving the taste of the final product, which can be important for patient compliance. These components are for ensuring the formulation's stability, efficacy, and patient acceptability. Other ingredients like flavoring agents or colorants may be added based on specific formulation requirements.

[0073] An exemplary pharmaceutical excipient base suitable for the method comprises5 - 30 wt.-% of one or more gelling agents selected from a group consisting of gelatin, agar, and combinations thereof;0.5 - 5 wt.-% silica;10 - 35 wt.-% of one or more lipid-based excipients selected from one or more hydrated vegetable fats, wherein the melting point of the one or more hydrated vegetable fats is from 35 °C to 55 °C;10- 30 wt.-% of one or more carbohydrates and / or sugar alcohols;40 - 70 wt.-% of one or more solvents preferably selected from water, glycerol and mixtures thereof.

[0074] In some embodiments, the pharmaceutical excipient base also includes one or more excipients selected from a group consisting of preservatives, pH-adjusting agents,chelating agents, sweeteners, surfactants, and flavoring agents. Chelating agents, such as EDTA, are known to increase stability of certain drugs, such as captopril. Surfactants, in turn, assist in stabilizing oil-in water emulsions by reducing the interfacial tension between oil and water phases, and by forming a protective layer around oil droplets to prevent them from coalescing. Exemplary surfactants include polysorbates.

[0075] Exemplary pH adjusting agents include citric acid, sodium citrate, and malic acid. Exemplary preservatives include sorbic acid, potassium sorbate, and parabens. Exemplary flavoring agents include marshmallow flavour, molasses flavor, vanilla flavour, peanut butter flavour, fruit flavour, and berry flavour. Exemplary sweeteners include the above-mentioned glucose, fructose, and xylitol. Also, artificial sweeteners, such as sucralose, and polyol sugars, such as erythritol which are not metabolized in the same way as normal carbohydrates, can be used.

[0076] According to a particular embodiment, the pharmaceutical excipient base includes 10-15 wt.-% gelatin as a gelling agent, 1-2 wt.% silicon dioxide as a thickening agent, 10-15 wt.-% of cocoa butter as a lipid-based excipient, and 20 wt.-% xylitol as a filler and a sweetener. A particular pharmaceutical excipient base is disclosed in Table 1.Table 1.

[0077] The viscosity of the pharmaceutical excipient base of Table 1 is ca 2.1 Pa s at50 °C.

[0078] Exemplary non-limiting APIs suitable for the method of the present disclosure are disclosed in Table 2.Table 2.a. Class I: high permeability, high solubility; Class II: high permeability, low solubility; Class III: low permeability, high solubility; Class IV: low permeability, low solubility (M9_Guideline_Step4_2019_l 116.pdf (ich.org)).

[0079] The pharmaceutical excipient base disclosed above is suitable for dispensing a wide range of active pharmaceutical ingredients (API), independent of the properties of the API. Accordingly, dispensable dispersions could be achieved when the pharmaceutical excipient base is admixed with 0.1-5 wt.-% one or more Class I, Class II, Class III, and / or Class IV APIs, wherein the wt.-% is the total weight of the APIs in the dispersion. When the one or more APIs were of Class I or III, the wt.-% range may be broader, i.e., 0.1-25 wt.-%. For example, a dispersion including 25 wt.-% propranolol and 75 wt.-% of a formulation as disclosed herein could be used for producing a solid dosage formulation of the API, whereas in the case of ramipril and quetiapine, the maximum amount of the API was 5 wt.-%.

[0080] For providing a dispensable dispersion using the pharmaceutical excipient base disclosed above, the total wt.-% of the one or more APIs in the dispersion is 0.1-25 wt.-% for APIs of Class I and Class III. When one or more of the APIs is of Class II or Class IV, the total wt.-% of the one or more APIs in the dispersion is 0.1-5 wt.-% for APIs of Class II and Class IV.

[0081] The dispensable dispersions disclosed above can also be used for dispensing APIs derived from crushed tablets, provided that the tablets include at least 50 wt.-% API.

[0082] According to another aspect the present disclosure concerns a method for producing a package comprising one or more traceable solid dosage forms of an active pharmaceutical ingredient. An exemplary system suitable for the method is shown in figure 5. The method comprises the following steps:a) providing a system comprising a reservoir 102 comprising a RFID sticker 105, a first dispenser 301 comprising a first balance 302 and a first RFID reader 303, a mixer 304 comprising a second RFID reader 305, a second dispenser 306 comprising a heating means, a second balance 307, and a third RFID reader 308, a dispensing base 309, a sealer 310 comprising a printer, and a batch record 311; b) providing dose description; c) for producing one or more solid dosage forms i. the first dispenser scanning the RFID code; dispensing and weighting, based on the dose prescription, at least an API and a pharmaceutical excipient base into the reservoir thereby producing a mixture of weighted materials; and sending weights of the weighted materials into the batch record; ii. transferring the reservoir comprising the weighted materials into the mixer, iii. the mixer scanning the RFID code; mixing and heating the mixture of the weighted materials in the reservoir until a dispensable dispersion is formed; and sending one or more of time of mixing and heating and temperature of heating to the batch record; iv. transferring the reservoir into the second dispenser; v. the second dispenser scanning the RFID code; dispensing and weighting one or more doses of the dispensable dispersion from the reservoir into the dispensing base; cooling the one or more doses to a temperature wherein the one or more doses are in a solid state thereby forming one more solid dosage forms of the API; andsending one or more of: number of doses dispensed, weight of the one or more doses dispense to the batch record, vi. transferring the dispensing base comprising the one or more solid dosage forms of the API into the sealer; vii. the sealer sealing the dispensing base by a sealant and printing a QR code on the sealant, the QR code comprising one or more of: time of manufacture, batch info, dose amount, prescription, patient info, and expiry date on the package, thereby providing a package comprising one or more traceable solid dosage forms an active pharmaceutical ingredient.Preferably, the method further includes d) printing the batch record.

[0083] In an embodiment, a dose prescription is inputted into the system. A barrel 102 of a syringe 100, equipped with an RFID sticker 105, is scanned at the first dispenser 301, and the information is logged into batch record 311. Then the ingredients required for the prescription are weighed in the barrel at the first dispenser. This initiates the creation of a digital batch record. Following this, the pharmaceutical excipient base is weighted into the barrel, and the batch record is updated.

[0084] Once all materials are weighted into the barrel, the barrel is transferred to the mixer 304. The mixer reads the RFID on the barrel and updates the batch record accordingly. The barrel undergoes mixing and heating in the mixer, preparing it for the next dispensing stage.

[0085] The next step involves installing the piston 101 into barrel syringe and installing the syringe including the dispensable dispersion into the second dispenser 306. The second dispenser reads the RFID and continues to update the batch record with the necessary data. The second dispenser dispenses desired number of doses on a dispensing base 309, such as a blister base by forcing the dispersion from the barrel by pressing the piston. The dispensing process may include Near-Infrared (NIR) checks to ensure quality. The doses are allowed to cool for solidification.

[0086] Finally, the dispensing base including desired number of doses is inserted into a sealer 310. The sealer seals the dispensing base to form a package comprising thedesired number of doses. An exemplary seal is a heat sealable foil 312. Preferably, the sealer also prints a QR code positioned on top of the seal on each dose. The digital batch record is then finalized in the app and can also be printed out. This results in a ready prescription that can be dispensed to the patient, ensuring that all steps have been tracked and recorded accurately throughout the process.

[0087] Conclusions. The method of the present disclosure has the following benefits. i) Reduced contamination risk. By minimizing the transfer of the formulation between different containers, the process significantly decreases the exposure to potential contaminants. This is especially crucial in pharmaceutical manufacturing where maintaining sterility is paramount. ii) Increased Efficiency. Streamlining the process to use one syringe for all steps reduces the time and labor involved in preparing the formulation. This efficiency gain lead to faster production cycles and potentially lower labor costs. iii) Enhanced Precision. Handling the formulation less frequently reduces the risk of human error during transfers. With the formulation prepared and dispensed from the same syringe, there is better control over dosage accuracy, which is critical for maintaining consistent drug efficacy. iv) Reduced Waste. Using a single syringe limits the amount of residual formulation left in multiple containers, thereby reducing product waste. This can lead to cost savings and more environmentally friendly practices by minimizing the disposal of unused pharmaceutical substances. v) Simplified Training and Operations. The process simplification makes it easier to train staff, as there are fewer steps and equipment involved. This can lead to quicker mastery of the manufacturing process, reduced errors, and more consistent product quality. vi) Improved Product Integrity. Fewer transfers and manipulations of the formulation help preserve its physical and chemical integrity, ensuring that the final product retains its intended properties and effectiveness. vii) Enhanced Management and Traceability. Eliminating the uses of mixing jars makes it easier to track and manage pieces of equipment that are involved in the production process. Hence, enables convenient batch record. viii) Cost Savings. Reducing the number of tools and equipment needed for the process can lower capital and maintenance costs. Additionally, the decrease in waste andimproved efficiency can contribute to overall cost reductions in the manufacturing process.

[0088] FIGURE 6 illustrates an exemplary embodiment of a method for forming a blend. In the first phase 402 of method 451, a dispenser and a manufacturing order are obtained. The dispenser, for example syringe 100, comprises a first tag. The first tag may comprise an RFID tag, for example an NFC tag, or a barcode, or a machine-readable label, for example a QR code. The manufacturing order may comprise process parameters.

[0089] In the second phase 403, the dispenser and the manufacturing order are paired together in a database. The pairing 403 may comprise reading the first tag of the dispenser with a reader to obtain a dispenser identification code (DIC), sending the DIC to a server for storing in a database, and causing, for example by the server, the DIC and the manufacturing order to be associated with one another within the database.

[0090] In phase 404, the dispenser is placed on a balance, for example balance 106. On, within, or nearby the balance is a reader associated with the balance. The reader may be, for example, an RFID reader, a barcode reader, or a camera, depending on what type of tag is used. For an RFID tag, an RFID reader may be used. For a barcode, a barcode reader may be used. For a QR code, a camera may be used. In some embodiments, the reader of the balance may be the same reader used in phase 403. In some embodiments, the reader of the balance may be a separate reader from the reader used in phase 403.

[0091] In phase 406, the first tag of the dispenser is read with the reader of the balance or an apparatus associated with the balance. By reading the tag in phase 406, a DIC is obtained in phase 407.

[0092] Further, still in phase 407, the obtained DIC is sent to the server comprising the database by the balance or an apparatus associated with the balance. The database comprises at least one previously obtained dispenser identification code, which allows the server to verify the obtained dispenser identification code against the at least one previously obtained dispenser identification code to confirm the identity of the dispenser. The previously obtained DIC may be the DIC read in phase 403. The verification may comprise checking, by the server, that the previously obtained DIC is identical to the obtained DIC (positive verification), so that it is clear that the dispenser has not been changed during the method. If the DIC’s are not identical, this is a negative verification.Responsive to a negative verification, at least one of the following actions may be performed by the server: indicating a negative result to the balance, or indicating a negative result to a user.

[0093] Still further in phase 407, responsive to a positive verification, the server may indicate to the balance that the placed dispenser is acceptable. Weighing parameters regarding the amount of API and of a pharmaceutical excipient base to be placed in the dispenser may be received by the balance from the server.

[0094] The weighing parameters may be preset parameters stored within the database for each API, pharmaceutical base, and other ingredients. Additionally or alternatively, the parameters may be derived, by the server using mathematical formulas, from the manufacturing order. The weighing parameters may comprise, for example: the mass of each ingredient, the form of each ingredient, and / or the weighing order of each ingredient.

[0095] In phase 408, the ingredients are weighed to form a blend in the dispenser, for example in the reservoir 102 of the syringe 100, based on the weighing parameters. After weighing in phase 408, parameters associated with the weighing are optionally sent by the balance or by an apparatus associated with the balance, to the server comprising the database in phase 409, wherein the server is configured to store the parameters in the database. The parameters associated with the weighing may comprise the actual mass of each weighed ingredient.

[0096] The verification may comprise checking, by the server, that the parameters associated with the weighing are within a preset tolerance with respect to the weighing parameters. A preset tolerance may be, for example below 10%, below 7%, below 5%, below 4%, below 2%, below 1%, below 0.5%, below 0.2%, below 0.1%, or preferably below 0.05% weight percent for each ingredient. If any parameters, for example the mass of an ingredient, are not within the preset tolerance, this will result in a negative verification. Responsive to a negative verification, at least one of the following actions may be performed by the server: indicating a negative result to the balance, or indicating a negative result to a user.

[0097] During method 451, for example during phase 402 or 404, the method may comprise obtaining a user identification code (UIC) of a user using the balance. Apreliminary phase of obtaining the UIC may comprise logging into, by a user, the server or an apparatus connected to the server using user credentials of that user, authenticating, by the server, the user credentials, and obtaining, by the server, a previously obtained UIC corresponding to the user. Obtaining the UIC may then comprise at least one of the following: checking the user is logged in to an apparatus associated with the balance, or reading, by a reader of the balance or associated with the balance, the UIC. The obtained UIC is sent, to the server comprising the database, by the balance or an apparatus associated with the balance. The database comprises at least one previously obtained UIC, which allows the server to verify the obtained UIC against the at least one previously obtained UIC to confirm the identity of the user. The previously obtained UIC may be prestored in the server. The verification may comprise checking, by the server, that the previously obtained UIC is identical to the obtained UIC and that the user has the correct permissions related to the balance and the manufacturing order, specifically the APIs in the manufacturing order (positive verification). In other words, the user must be recognized by the server, the user must have preset permissions to operate the balance and the user must have preset permission to work with the contents of the dispenser. If any of the above criteria are not met, the result of the verification is negative (negative verification). Responsive to a negative verification, at least one of the following actions may be performed by the server: indicating a negative result to the balance, or indicating a negative result to a user.

[0098] FIGURE 7 illustrates an exemplary embodiment of a method for forming a dispensable dispersion. In the first phase 410 of method 452, the dispenser, for example syringe 100, is placed on a mixer. The mixer may be, for example, a planetary blade-free mixer.

[0099] Method 452 may be performed directly after method 451. By “directly”, it is meant that no intervening process steps are performed between the methods. The dispenser comprises a blend, for example the blend form in phase 408 of method 451, illustrated in figure 6.

[0100] In phase 412, the first tag of the dispenser is read with a reader of the mixer or an apparatus associated with the mixer. The reader may be, for example, an RFID reader, a barcode reader, or a camera, depending on what type of tag is used. For an RFID tag, an RFID reader may be used. For a barcode, a barcode reader may be used. For a QRcode, a camera may be used. By reading the tag in phase 412, a DIC is obtained in phase 411.

[0101] Further, still in phase 411, the obtained DIC is sent to the server comprising the database by the mixer or an apparatus associated with the mixer. The database comprises at least one previously obtained dispenser identification code, which allows the server to verify the obtained dispenser identification code against the at least one previously obtained dispenser identification code to confirm the identity of the dispenser. The previously obtained DIC may be the DIC read in phase 403, and / or DIC read in phase 407. The verification may comprise checking, by the server, that the previously obtained DIC is identical to the obtained DIC (positive verification), so that it is clear that the dispenser has not been changed during the method. If the DIC’s are not identical, this is a negative verification. Responsive to a negative verification, at least one of the following actions may be performed by the server: indicating a negative result to the mixer, or indicating a negative result to a user.

[0102] Still further in phase 411, responsive to a positive verification, the server may indicate to the mixer that the placed dispenser is acceptable, and mixing parameters regarding the blend may be received by the mixer from the server.

[0103] The mixing parameters may be preset parameters stored to the database for each API, pharmaceutical base, and other ingredients. The parameters may be obtained, by the server, from the manufacturing order, wherein the manufacturing order comprises the mixing parameters. Additionally or alternatively, the parameters may be derived, by the server using mathematical formulas, from the manufacturing order. The mixing parameters may comprise, for example, mixing time and mixing speed / rate.

[0104] In phase 414, the blend is mixed based on the mixing parameters to form the dispensable dispersion. After mixing, recorded parameters associated with the mixing are optionally sent by the mixer or by an apparatus associated with the mixer, to the server comprising the database in phase 415, wherein the server is configured to store the recorded parameters in the database. The parameters associated with the weighing may comprise the actual mixing time and / or actual mixing speed / rate.

[0105] Mixing may be performed by a user or automated device. The mixing time and / or speed / rate may be set manually, semi-automatically, or automatically. By manually,it is meant that the user may select the parameters. By semi-automatically, it is meant that the user may confirm a proposed temperature set by the system. By automatically, it is meant that the user may not be able to influence the mixing.

[0106] FIGURE 8 illustrates an exemplary embodiment of a method for dispensing to form one or more dosage forms. Before the first phase 416 of method 453, method 451 and / or method 452 illustrated in figures 6 and 7 may be performed or may have been performed. In the first phase 416, the dispenser, for example syringe 100, comprises a dispensable dispersion, and is inserted into a thermal end, for example into thermal end 474 illustrated in figure 11. After inserting the dispenser into the thermal end, the thermal end may be attached and thereby electrically connected to a liquid handling apparatus. Alternatively, the thermal end may be attached to the liquid handling apparatus before the dispenser is inserted into the thermal end.

[0107] In phase 418, the first tag of the dispenser is read with a reader of the thermal end, for example reader 476 of thermal end 474 in figure 11. The reading may occur automatically when the dispenser is inserted into the thermal end, if the thermal end is attached to the liquid handling apparatus. If the thermal end is detached from the liquid handling apparatus, the reading may occur when the thermal end is attached to the liquid handling apparatus. By reading the tag in phase 418, a DIC is obtained in phase 417.

[0108] Further, still in phase 417, the obtained DIC is sent to the server comprising a database by the liquid handling apparatus to which the thermal end is attached. The database comprises at least one previously obtained dispenser identification code, which allows the server to verify the obtained dispenser identification code against the at least one previously obtained dispenser identification code to confirm the identity of the dispenser. The previously obtained DIC may be the DIC read in phase 403, 407, or 411. The verification may comprise checking, by the server, that the previously obtained DIC is identical to the obtained DIC (positive verification), so that it is clear that the dispenser has not been changed during the method. If the DIC’s are not identical, this is a negative verification. Responsive to a negative verification, at least one of the following actions may be performed by the server: indicating a negative result to the balance, or indicating a negative result to a user.

[0109] Still further in phase 417, responsive to a positive verification, the server may indicate to the liquid handling apparatus that the inserted dispenser is acceptable, anddispensing instructions regarding the dispensable dispersion may be received by the liquid handling apparatus, from the server.

[0110] The dispensing instructions may be stored within the database for the dispensable dispersion. Additionally or alternatively, the dispensing instructions may be stored within the database for each dosage form within the manufacturing order. The dispensing instructions may comprise, for example, any of the information of table 3, below.Table 3. Dispensing instructionsSuitable machine typeSuitable temperature ranges for at least one temperature sensor in thermal endMachine operating ranges (for example, maximum acceleration ranges) Acceptable range of weight of dispensing target throughout the process Acceptable duration of dispensing

[0111] In phase 426, the dispensable dispersion is dispensed onto a dispensing target to form one or more dosage forms. During dispensing 426, the dispenser is fixedly attached inside the thermal end, and the piston flange is pushed downwards in a vertical direction to dispense a suitable amount (i.e., one dosage) of the dispensable dispersion to one or more cavities or other dispensing locations of the dispensing target. After dispensing to one location, the thermal end and dispenser may be moved, for example by liquid handling apparatus 460, in the X, Y, and / or Z direction to the next location, in order to dispenser a suitable amount to the next location, for example the next cavity of a blister pack. This process (dispensing to a cavity, moving, dispensing to another cavity, moving, and so on) may then be repeated until all of the cavities or other dispensing locations of the dispensing target have been filled. After dispensing, the liquid handling apparatus is configured to weigh the dispensed dosage form. This is done by weighing the mass of the dispensingtarget before and after the dispensing of the dosage form and calculating the mass of the dosage form based on the difference in the masses. The calculation and verification of the dispensed dosage form may be performed by the server connected to the liquid handling apparatus. This is advantageous as it allows the mass of each dosage form to be verified.

[0112] After dispensing, dosage form information may be sent by the liquid handling apparatus to the server comprising the database in phase 428, wherein the server is configured to store the dosage form information in the database.

[0113] The dosage form information may comprise the dosage form location on the dispensing target, for example the specific location of the dosage form on a blister (for example “A” or “B2”). The dose information may further comprise at least one of: user id for dispensing process (UIC), process data for dispensing process, dispenser id (DIC), target id (TIC), or any of the data provided in data 833 as discussed below.

[0114] Method 453 may further comprise optional phases. In optional phase 420, the temperature of the dispensable dispersion is adjusted by controlling the thermal end. The thermal end comprises controllable thermoelements, which the liquid handling apparatus may control to raise and / or lower the temperature.

[0115] In some embodiments, the dispensable dispersion may need to be heated. In some embodiments, the dispensable dispersion may need to be cooled. In some embodiments, the temperature of the dispensable dispersion may need to be adjusted to 25 °C to 95 °C, or 35 °C to 95 °C, or 35 °C to 70 °C, or 35 °C to 55 °C, or 40 °C to 50 °C. In some embodiments, the dispensable dispersion may be suitable for dispensing at room temperature.

[0116] In optional phase 422, a dispensing target comprising a second tag is placed. The dispensing target may be placed, for example, in any position of the dispensing area, for example the dispensing area defined by working distances 480 and 481 of liquid handling apparatus 460, illustrated in figure 11. In optional phase 424, the second tag of the dispensing target is read with a second reader of the thermal end, for example with reader 475 of thermal end 474, illustrated in figure 11. By reading the tag in optional phase 424, a target identification code (TIC) is obtained in optional phase 423.

[0117] Further, still in phase 423, the obtained TIC is sent to the server comprising a database by the liquid handling apparatus to which the thermal end is attached. Thedatabase comprises at least one previously obtained target identification code, which allows the server to verify the obtained target identification code against the at least one previously obtained target identification code to confirm the identity of the dispensing target. Still further in optional phase 423, responsive to a positive verification, the server may indicate to the liquid handling apparatus that the placed dispensing target is acceptable. The verification may comprise checking, by the server, that the TIC is of the correct type with respect to the manufacturing order. If the TIC indicates the dispensing target type is suitable, the result is a positive verification, whereby the process may continue. If the TIC indicates the dispensing target type is not suitable, this is a negative verification. Responsive to a negative verification, at least one of the following actions may be performed by the server: indicating a negative result to the liquid handling apparatus, or indicating a negative result to a user.

[0118] FIGURE 9 illustrates an exemplary embodiment of a method 454 for sealing one or more dosage forms. Before the first phase 430 of method 454, methods 451, 452, and / or 453 illustrated in figures 6, 7, and 8 may be performed or may have been performed. In the first phase 430, the dispensing target comprises one or more dispensed dosage forms, and is inserted into a sealer. For example, the dispensing target may be dispensing target 477 comprising dispensed dosage forms in dispensing locations (cavities) 478 illustrated in figure 11.

[0119] In the sealer, the one or more dosage forms are sealed by a sealant in phase 432. An exemplary sealant is a heat sealable foil, for example an aluminum foil.

[0120] In phase 434, one or more labels are printed. The labels comprise information from the database, for example information comprising at least one of time of manufacture, batch info, dose, prescription information, patient information, and expiry date. Further, still in phase 434, the label(s) are attached to the dose(s). In some embodiments, the labeling may comprise attaching one label to each dosage form, wherein each attached label corresponds to the dosage form in question. Labelling may be done by the sealer or when the product is within the sealer, or the labelling may be done by a distinct labelling machine. Labels may be verified, for example by the server and a camera system configured to scan the labels and provide the scanned information to the server.

[0121] FIGURE 10 illustrates an exemplary embodiment of a method 450 for preparing pharmaceutical dosage forms. In the first phase, method 451 is performed. In thesecond phase, method 452 is performed. In the third phase, method 453 is performed. In the fourth phase, method 454 is performed.

[0122] In some embodiments, method 451 may be considered optional. In some embodiments, method 452 may be considered optional. In some embodiments, method 454 may be considered optional.

[0123] FIGURE 11 illustrates an isometric top view of a liquid handling apparatus capable of supporting at least some embodiments of the present disclosure. The liquid handling apparatus 460 comprises a bridge assembly 471 and a drive mechanism 472. The liquid handling apparatus 460 further comprises a leadscrew, an actuator, a linear guide block, and a linear guide rail. At least some of the components of apparatus 460 may be located within the drive mechanism 472 of the apparatus. Thermal end 474 is detachably attached to counterpart docking component 482 of drive mechanism 472. This means that the thermal end, when attached, is configured to move in the Z-direction when drive mechanism 472 moves along the bridge assembly 471 in the Z-direction. Thermal end 474 is configured to accept a dispenser, for example syringe 100. Configured to accept, as used herein, means that the syringe can be inserted inside a hollow body of the thermal end. While inside, the dispenser is in an interlocked position, meaning that the dispenser cannot be moved vertically or horizontally with respect to the thermal end.

[0124] Further, dispensing target 477 and its dispensing locations (cavities) 478, are illustrated. Dispensing target 477 may be positioned anywhere within the area defined by working distances 480 and 481, and the liquid handling apparatus 460 is configured to dispense accurately to the dispensing locations (cavities) 478 of the dispensing target 477.

[0125] Additionally, liquid handling apparatus 460 comprises an end-effector 473, for example a gripping apparatus, configured to grip a dispenser, for example syringe 100. In the embodiment of figure 11, the end-effector 473 is gripping syringe 100, of which only piston 101 is visible. Liquid handling apparatus 460 is configured so that the endeffector is movable in XYZ directions, i.e. the horizontal, vertical and depth directions. The end-effector may be moved the Y-direction with respect to drive mechanism 472. In the X- and Z-directions, the end-effector moves together with the drive mechanism, and does not move with respect to its position to the drive mechanism. Liquid handing apparatus 460 is also programmable to operate autonomously. Consequently, the liquid handling apparatus is a cartesian coordinate robot.

[0126] Vertical movement of the end-effector is provided by the leadscrew, the actuator and the linear guide block, which in the embodiment of Figure 11 are hidden inside drive mechanism 472. The leadscrew is an elongated threaded shaft configured to convert rotational motion into linear motion. The leadscrew is configured to drive and / or position the end-effector of the liquid handling apparatus in a vertical direction. The actuator is a device configured to provide controlled rotational motion for driving a mechanical element or system with precise positioning, for example a stepper motor. The actuator is configured to actuate the end-effector of the liquid handling apparatus along a vertical axis via the leadscrew. The linear guide block is configured to move linearly along a guide rail, wherein the linear guide block comprises a housing having rolling elements, such as balls or rollers, arranged to facilitate linear motion with minimal friction between the guide block and the guide rail. The linear guide block serves as the part connecting the apparatus to the linear guide rail. The linear guide rail comprises an elongated, rigid structural member having at least one guide surface or raceway, configured to guide and support the linear guide block during linear motion. The linear guide block / rail combination may be used together with the leadscrew to provide smooth movement of the end-effector.

[0127] Horizontal movement (Z-axis) of the end-effector is provided by moving the drive mechanism 472 along the bridge assembly 471. Liquid handling apparatus 4600 may be configured to use a further leadscrew, further actuator and a further linear guide block / rail combination to move the entire drive mechanism 472 in either direction along the bridge 471. The further leadscrew, further actuator, and further linear guide block / rail combination may be located within the bridge assembly 471 of the apparatus. Thereby, the drive mechanism 472 may be moved in either direction along working distance 481.

[0128] A third axis, i.e., the depth axis, of movement (X-axis) is provided by moving bridge assembly 471, and thereby the drive mechanism 472, along the length of the working distance 480. Liquid handling apparatus 460 may be configured to use a further leadscrew, further actuator and a further a linear guide block / rail combination to move the bridge assembly 471 in either direction along working distance 997.

[0129] Further illustrated are two readers (475, 476) of the thermal end 474. Reader 475 is configured to read tag 479 of the dispensing target, to obtain a target identificationcode (TIC). Reader 476 is configured to read a tag of the dispenser, for example RFID sticker 105 of syringe 100, to obtain a dispenser identification code (DIC).

[0130] The readers of the thermal end may be positioned anywhere within or on the thermal end. In some embodiments, the reader configured to obtain a TIC is positioned near the bottom of the thermal end. In some embodiments, the reader configured to obtain a DIC is positioned in the middle, or near the top of the thermal end, and the reader may be wrapped around the thermal end to provide reliable reading of the dispenser’s tag. In general, reader 476 is positioned above reader 475 with respect to the thermal end, with a gap in-between. The gap may be, for example, at least 0.5 cm, at least 1 cm, at least 2 cm, at least 3 cm, at least 4 cm, at least 5 cm, at least 6 cm, or at least 7 cm. This arrangement ensures that there is no interference between the readers, and minimizes the risk of the readers reading the wrong tag.

[0131] FIGURE 12 illustrates an example data structure 800 usable with at least some of the embodiments disclosed herein. Data structure 800 may be provided as a tree data type, where each data is a node. Each node may be connected to several children, but may have only one parent (with the exception of node 841, which is the root node in exemplary figure 12). Alternatively, data structure 800 may be provided as multiple tree data types, which are linked hierarchically or listed sequentially. Alternatively, data structure 800 may be provided in a list format, where the data is listed sequentially. In data structure 800, a parent node comprises the data of the child node. In other words, data 841 comprises all data from the nodes within data structure 800.

[0132] Figure 12 shows for illustrative purposes only the stages of a corresponding process on the left-hand side of the figure. Starting from the bottom, typically first is the initialization stage, where the manufacturing order comprising the recipe is received. Also during initialization, a dispenser id is read into the system from at least one dispenser. After initialization, at least one formulation is typically added into the dispenser and weighed to obtain accurate information of the dispenser content. The contents of the dispenser are then mixed. After mixing, the dispenser and a dispensing target, for example a blister, are inserted into a liquid handling machine configured to dispense the contents of the dispenser into the dispensing target. The contents are then dispensed, and the dispensing target is sealed and labelled, typically in a different machine from the dispensing liquid handling machine.

[0133] Data structure 800 may be generated by a server. A server may comprise at least one processing core, at least one memory including computer program code, the server comprising or connected to a database, the at least one memory and the computer program code being configured to, with the at least one processing core, cause the server at least to receive and transmit information from equipment such as: a liquid handling apparatus, and optionally at least one of RFID reader, a balance, a mixer, a sealer, a labeller, and to receive and transmit information from the database based on the received and transmitted information from the equipment, wherein the server may be configured to verify the received and transmitted information from the equipment based on the information within the database, and wherein the server is configured to generate data structure 800. The server may be configured to generate data structure 800 after a predetermined phase, for example after the labelling is complete, and / or after each phase (for example weighing, mixing, dispensing, sealing, labelling) is complete.

[0134] The server may be configured to verify the contents of the data structure, upon receipt of said contents and / or upon generation of the data structure. The contents of the data structure may be verified against the contents of the manufacturing order. For example, if the manufacturing order states that the dosage form shall comprise 10%-wt ibuprofen, and the weighing data 813 indicates the dosage form only comprises 9,5 %-wt ibuprofen, then the verification would have a negative result. In another example, should a certain dispenser be paired with the manufacturing order, and later another dispenser is provided (unexpectedly) to a machine during the same manufacturing order, this would result in a negative verification. The contents of the data structure may be verified against user permissions. Such permissions may be made accessible to the server via a distinct database, for example. The verification of the user permission may comprise checking, by the server, that the user is allowed to operate a certain equipment. If the user is not allowed to operate the equipment, then the verification would have a negative result.

[0135] The data structure 800 comprises data 841 relating to a manufactured pharmaceutical product. As can be seen from the data structure, data 841 comprises all of the connected nodes within data structure 800. Thus, when data 841 is provided, along with the product corresponding to said data, all of the process data within data structure 800 may be made available, for example to a user or a regulatory authority.

[0136] The product associated with data 841 is labelled, to provide the required information to the end-user of the product. Data 841 comprises user id 836, identifying the user who has labelled the product or caused the product to be labelled. Data 841 comprises labelling process information data 837, which is a record, obtained from the labelling machine, of the labelling process. Labelling process information data 837 may comprise: machine id, labelling process information as measured by the machine during the process, for example process 454. Data 841 comprises data 839 relating to the sealed, but yet unlabelled, package. Any of data 836, 837, 839 may be verified, by the server, to ensure that the manufacturing order is correctly performed.

[0137] Data 839 comprises user id 835, identifying the user who has sealed the product or caused the product to be sealed. It is noted that user id 835 may be distinct from user id 836, and the other user id’s within data structure 800. This is due to the fact that the manufacturing process may utilize several distinct users. The user id’s within data structure 800 may be used to verify the user is allowed to operate the machine, or manufacture the product. User ID’s correspond to the user identification codes, UIC’s discussed within this document. Data 839 comprises sealing process information data 834, which is a record, obtained from the sealing machine, of the sealing process. Sealing process information data 834 may comprise: machine id, labelling process information as measured by the machine during the process, for example process 454. Data 839 comprises data 833 relating to each dispensed dosage form in the unsealed product. Any of data 833, 834, 835 may be verified, by the server, to ensure that the manufacturing order is correctly performed.

[0138] Data 833 relates to a dosage form, for example a pharmaceutical dosage form, which has been manufactured, for example a pill. Thus, a plurality of data 833 are shown in the data structure 833, each instance of data 833 corresponding to a manufactured dose. Data 833 may comprise all of the connected nodes within data structure 800. Thus, when data 833 is provided along with the dosage form corresponding to said data, all of the process data within data structure 800 may be made available, for example to a user or regulator.

[0139] Data structure 800 comprises dosage form location data 831, which details the location of the dosage form (dosage form related to data 833), for example on a blister pack. For example, the dosage form location may be location A, or location B2.

[0140] Data structure 800 comprises dispensing process data 829, which is a record of the dispensing process received from a liquid handling apparatus dispensing the dosage form related to data 841. Such data may be obtained, for example, during process 453. For example, the dispensing data may comprise any of the information of table 4.Table 4. Dispensing process dataMachine IDThermal end IDTemperature values, for example from thermal end, throughout the processMachine process history (for example electrical current values during process) Weight of dispensing target throughout the process (in particular, before and after dispensing each dosage form)Time stamp (for example start and end time of dispensing)

[0141] The weight of the dispensing target may be measured before, after, and during the dispensing. The measuring may be performed by a balance arranged within the liquid handling apparatus, wherein the dispensing target may be arranged on the balance. The balance may be connected to the liquid handling apparatus and / or the server. Alternatively, the liquid handling apparatus may comprise the balance. As discussed herein, recording the measured weight before and after dispensing allows calculation, for example by the server, of the mass of each dispensed dosage form.

[0142] Photographic and / or videographic recording of the dispensing may be performed by at least one camera apparatus. The camera apparatus may be arranged within or nearby the liquid handling apparatus. The camera may be connected to the liquid handling apparatus and / or the server. Alternatively, the liquid handling apparatus may comprise the camera.

[0143] Data structure 800 comprises user id 827, which is a record of the user operating the dispensing machine. Any of data 827, 829, 831 may be verified, by the server, to ensure that the manufacturing order is correctly performed. Such verification may be performed against the contents of table 3, for example.

[0144] Data structure 800 comprises pre-dispensing data 821. Data 821 may be used, for example, to verify that the correct dispenser is being used with the correct blister and vice versa. Data 821 may comprise target identification data 825, which may be read from the RFID tag attached to or otherwise related to the dispensing target which is within the liquid handling apparatus for dispensing purposes. Target identification datas within data structure 800 correspond to the target identification codes, TICs, discussed in this disclosure. Data record 821 may comprise dispenser identification data 823, which may be read from the RFID tag attached to or otherwise related to the dispenser which is within the liquid handling apparatus for dispensing purposes. In at least some embodiments, 825 and 823 are read by different (distinct) RFID readers connected to thermal end. Dispenser identification datas within data structure 800 correspond to the dispenser identification codes, DICs, discussed in this disclosure. Data 821 may comprise user identification data 822 which is a record of the user inserting the dispensing target and the dispenser into the liquid handling machine performing the dispensing process. Data 821 may comprise liquid handling apparatus identification data 824, which is a record of the liquid handling apparatus being used to perform the dispensing process. Any of data 824, 822, 823 and 825 may be verified, by the server, to ensure that the manufacturing order is correctly performed.

[0145] Data structure 800 comprises mixing data 817. Data 817 may comprise user identification data 815, which is a record of the user operating the mixing machine. Data 817 may comprise dispenser identification data 814, which is a record of the dispenser used in the mixing process.

[0146] Data structure 800 comprises mixing data 816, which is a record of the mixing process received from mixer mixing a formulation related to data 841. For example, the mixing data may comprise any of the information of table 5.Table 5. Mixing dataMachine IDTemperature values of mixing environment throughout the processMachine process history (for example motor current values, RPM, torque, acceleration, during process)Weight of dispenser throughout the processTime stamp (for example start and end time of mixing)

[0147] The temperature values of the mixing environment may be beneficial to measure to ensure the formulation is correctly mixed.

[0148] Any of data 815, 816, 813 and 814 may be verified, by the server, to ensure that the manufacturing order is correctly performed.

[0149] Data structure 800 comprises weighing data 813. Data 813 may comprise user identification data 812, which is a record of the user operating the mixing machine. Data 817 may comprise dispenser identification data 809, which is a record of the dispenser used in the weighing process.

[0150] Data structure 800 comprises weighing process data 811, which is a record of the weighing process data received from balance weighing a formulation related to data 841. For example, the weighing data may comprise any of the information of table 6.Table 6. Weighing dataMachine IDTemperature values throughout the processMachine process history (for example electrical values such as voltage during process)Weight of dispensing target throughout the processTime stamp (for example start and end time of weighing)

[0151] Any of data 812, 811, 807 and 809 may be verified, by the server, to ensure that the manufacturing order is correctly performed.

[0152] Data structure 800 comprises batch data 807. Data 807 may comprise dispenser identification data 805, which is a record of the dispenser used in the process. For example, data 805 may correspond to an unused dispenser, which is selected, by a user, for the process. Data 805 may comprise or correspond to at least one of: an indication of the dispenser type, manufacturer, and / or production date. For example, the server may look up the information from a database, when provided with data 805. Once data 805 isverified with respect to the process, by the server, it may be used to verify the read dispenser id’s at all following phases, for example it may be used to verify data 814, 823, and / or 809.

[0153] Data 807 may comprise manufacturing order data 803. The manufacturing order comprises recipe 801 comprising information regarding the end product, for example: the composition, form, quantity, for example dose or dosage form, quantity of active agent, and packaging. The manufacturing order may comprise process parameters, for example mixing and / or dispensing parameters such as temperature. These process parameters may be used by the server to verify the measured parameters during the processes. The manufacturing order 803 may comprise an indication of the equipment, for example a liquid handling apparatus, which is suitable for producing said order.

[0154] As seen in figure 12, the data structure 800 may comprise a complete record of the manufacturing process from the manufacturing order to the final single dose. Such a record allows troubleshooting throughout the entire process. For example, if the dosage form corresponding to data 833 does not pass customer quality control, the data structure may be analysed to find a root cause of the issue. Such analysis may be done based only on data structure 833, for example.

[0155] FIGURE 13 is exemplary sequence diagrams illustrating communication between a liquid handling apparatus, the readers connected to the liquid handling apparatus, a server and a database. A data structure is also shown in the figure for the sake of clarity. Each entity within the figures has a vertical line which is a so-called lifeline. Data transmission is illustrated with arrows that extend between these lifelines. After each transmission is performed, the response or next transmission is located beneath the previous one.

[0156] Figure 13 shows database 861, server 860, liquid handling apparatus 850, and readers 851 and 852. Server 860 may be configured to provide data structure 800 based on database 861, wherein the providing may comprise generating, editing or transmitting the data structure in whole or in part. Server 860 may be configured to communicate with equipment such as liquid handling apparatus 850. Such communication is illustrated with the arrows linking the server to the apparatus 850.

[0157] In the figure 13, phase 870 (as indicated on the left-hand side of the figure) is the pre-dispensing process. Phase 870 may be started manually by a user, or automatically, for example when apparatus 850 is powered on. Phase 870 may comprise the transmittal of messages 871 - 878 as discussed below. In the phase, the liquid handling apparatus transmits, to the server 860, a message 871 comprising an indication that the liquid handling apparatus is ready for operation. Upon receiving message 871, the server requests, by message 872, a manufacturing order from the database. The manufacturing order may specify the particular apparatus 850, or the server may check the database for suitable manufacturing orders usable with apparatus 850. The manufacturing order is obtained in message 873. Then, the server communicates the order to the apparatus 850 in message 874. Next, the user is verified. The apparatus communicates a user identification code, UIC, in message 875. The server checks the database for user permissions, as discussed elsewhere in this disclosure, via message 876, and receives the permissions from the database in message 877. The server determines a positive or negative verification and indicates it to the apparatus in message 878. Should the verification be negative, the phase 870 may be repeated. Should the verification be positive, the system may move on to phase 880.

[0158] Phase 880 (as indicated on the left-hand side of the figure) is the dispenser check. Apparatus 850 reads the dispenser identification code, DIC, using a first reader 851 connected to the apparatus 850. Reader 851 may be any suitable reader as indicated elsewhere in this disclosure, in particular a RFID reader. Reader 851 is operated directly by the apparatus 850, but for the sake of clarity it (and reader 852) are shown having their own lifelines. The DIC is provided in message 881, which the apparatus forwards to the server in message 882. The server checks the database for previously stored and / or obtained DIC’s, as discussed elsewhere in this disclosure, in message 883, and receives the results from the database in message 884. The server determines a positive or negative verification and indicates it to the apparatus in message 878. Should the verification be negative, the phase 880 may be repeated. Should the verification be positive, the system may move on to phase 890.

[0159] Phase 890 is the target check. Apparatus 850 reads the target identification code, TIC, using a second reader 852 connected to the apparatus 850. Reader 852 may be any suitable reader as indicated elsewhere in this disclosure, in particular a RFID reader. Reader 852 is operated directly by the apparatus 850. The TIC is provided in message 891,which the apparatus forwards to the server in message 892. The server checks the database for previously stored and / or obtained TIC’s, as discussed elsewhere in this disclosure, in message 893, and receives the results from the database in message 884. The server determines a positive or negative verification and indicates it to the apparatus in message 895. Should the verification be negative, the phase 890 may be repeated. Should the verification be positive, the system may move on to phase 900, and the server is configured to add the data from phases 870, 880 and 890 to a data structure such as data structure 800. Phase 890 may be performed before phase 880 in at least some embodiments, whereby the sequence would then be 870-890-880-900.

[0160] Phase 900 is the dispensing. The server sends the dispensing parameters (as discussed elsewhere in this disclosure) to the liquid handling apparatus in message 901. The parameters may be retrieved, by the server, from the database based on the manufacturing order prior to the sending, in a process not shown by Fig. 13. The apparatus 850 then begins the dispensing process of a single dosage form (a single dose, such as a tablet). The apparatus 850 is configured to periodically read the DIC and the TIC, using the readers, and obtain the results via messages 902, 903. The dispensing data from the process (with reference to Table 4, above) is also periodically sent to the server in message 904. Message 904 may also comprise the read DIC 902 and the read TIC 903. Message 904 may comprise the measured mass of the dispensing target before and after the dispensing of the single dosage form. This is advantageously done so that the mass of the dispensed dosage form may be calculated, for example by the server, and verified, by the server. The server checks the database for previously stored and / or obtained DIC’s, TIC’s, and reference dispensing parameters, as discussed elsewhere in this disclosure, in message 904, and receives the results from the database in message 905. The server determines a positive or negative verification of the contents of message 904 (verifying against data 905) and indicates it to the apparatus in message 907. Should the verification be negative, the dispensing process may be halted. In the event the determination is positive, the apparatus is configured to add the data from phase 900 to the database and the data structure 800.

[0161] Phase 900 may be repeated for each dosage form being dispensed for the target in question. Advantageously, both the DIC and TIC may be checked for each dosage form, for example before starting dispensing, to ensure that the correct dispenser and target are in use at all times. Monitoring the process parameters for each individual dosage form, as seen in phase 900 of Figure 13, provides improving tracking and less waste, asacceptable dosage forms need not be thrown away if subsequent dosage forms are defective.

[0162] Additional apparatuses and middleware programs may optionally be used to facilitate communication. Equipment such as liquid handling apparatus 850 may be configured to communicate with other apparatuses, for example via server 860. Server 860 may comprise an application layer configured to interact with at least one database, for example database 861. Server 860 may comprise a user interface layer (also known as a presentation layer) connected to the application layer. Server 860 may be configured to add data, for example manufacturing orders, to database 861. When such manufacturing orders are added, the server may be configured to cause the corresponding processes to be performed. Human approval may be required for some processes.

[0163] The server as discussed herein may comprise a user interface. The user interface may be provided as a web portal, for example (“web app”). The user interface may be configured so that user credentials, manufacturing orders, and information relating to formulations and / or equipment may be provided to the server and / or the database via the user interface.

[0164] The server as discussed herein may provide a centralized manufacturing order management system. Organizations operating in a plurality of geographical locations may manage the various manufacturing orders across the different sites. User credentials may be managed in a similar manner. This improves the utility of distributed manufacturing.

[0165] Connections between, for example, equipment such as liquid handling apparatuses and a server may be facilitated via Ethernet, CANBUS, or other suitable technologies. Equipment connected to the server may be configured to autonomously upload data to the server. The server, for example server 860, may be configured to populate data into data structure 800 as such data is received by the server. For the sake of clarity, data here refers to at least any data within data structure 800. The server may be configured to provide data structure 800 in whole or in part. The providing may comprise providing access to data structure 800, for example via the HTTP protocol. The providing may comprise providing a copy of data structure 800, preferably in a machine-readable format. Data structure 800 may be provided, for example, in at least one of: a JavaScript Object Notation, JSON, file format, a comma-separated value format, a PDF format.

[0166] The server may be configured to finalize the data structure 220 in phase 385. The finalizing (or “signing”) may comprise calculating a message digest code using the content of the data structure 800 as an input for the calculation, and adding the calculated message digest code to the data structure 800. Suitable algorithms include at least SHA- 512. The finalized data structure may be provided by the server, for example to stakeholders such as patients or users. Finalization provides the benefit of ensuring data integrity.

[0167] FIGURES 14A and 14B illustrate example apparatuses capable of supporting at least some embodiments of the present disclosure. Figure 14A illustrates an example server apparatus 920 capable of supporting at least some embodiments of the present disclosure. Server 920 may be used to at least participate in any of the methods disclosed herein. The apparatus may comprise a processing core 921, at least one memory 922 including computer program code, the at least one memory 922 and the computer program code being configured to, with the at least one processing core, cause the apparatus at least to participate in providing a database, for example database 861. The apparatus may comprise database 861, as seen in the figure. Database 861 may be provided by a single apparatus 920, or several such apparatuses may act in concert to provide the database.

[0168] Connections between server 920 and other devices may be provided by a communications unit 923 that is comprised in or connected to apparatus 920, for example a network interface. The server 920 may be configured to provide access to database 861. The server may be connected to other devices using TCP / IP, for example. In embodiments, the server is connected to the Internet.

[0169] The memory 922 is capable of storing instructions, such as at least one of operating system, various applications, models, neural networks and / or, preprocessing sequences. Furthermore, the memory may include a storage that may be used to store, e.g., the database 861 and / or at least some of the information and data used in the disclosed embodiments. The memory 922 may be embodied as one or more volatile memory devices, one or more non-volatile memory devices, and / or a combination of one or more volatile memory devices and non-volatile memory devices. For example, the memory may be embodied as semiconductor memories (such as mask ROM, PROM (programmable ROM), EPROM (erasable PROM), flash ROM, RAM (random access memory), etc ).

[0170] Although the apparatus 920 is depicted as including one processor, the apparatus 920 may include several processors. Furthermore, the processor 921 is capable of executing the stored instructions. The processor 921 may be embodied as a multi-core processor, a single core processor, or a combination of one or more multi-core processors and one or more single core processors. For example, the processor may be embodied as one or more of various processing devices, such as a coprocessor, a microprocessor, a controller, a digital signal processor (DSP), a processing circuitry with or without an accompanying DSP, or various other processing devices including integrated circuits such as, for example, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a microcontroller unit (MCU), a hardware accelerator, a specialpurpose computer chip, or the like. In an embodiment, the processor may be configured to execute hard-coded functionality. In an embodiment, the processor is embodied as an executor of software instructions, wherein the instructions may specifically configure the processor to perform at least one of the methods and / or operations described herein when the instructions are executed.

[0171] A UI apparatus is shown within figure 14A. A UI apparatus may comprise at least one processing core, at least one memory including computer program code, the at least one memory and the computer program code being configured to, with the at least one processing core, cause the UI apparatus at least to be connected to at least one equipment, for example a liquid handling apparatus, and a server such as server 860, 920. UI apparatus may serve as a user interface for a user using the equipment. UI apparatus may be configured to transmit and / or receive data from the server, for example commands and informational messages. For example, UI apparatus may be configured to display a message indicating a positive or negative verification result. The UI apparatus may be or comprise any of: a smart phone, a tablet, a laptop computer, or a personal computer. The UI apparatus may comprise a reader suitable for reading tags as discussed within this disclosure. UI apparatus may be configured to serve as a gateway between the server and the other apparatuses (equipment), for example to retransmit information. UI apparatus may be distinct from the UI of the server, or from the UI of the liquid handling apparatus 940. Several UI apparatuses may be in communication with the server, for example a first UI apparatus could be connected to a balance (and the server) and a second UI apparatus could be connected to a mixer (and the server).

[0172] Figure 14B illustrates an example liquid handling apparatus 940 capable of supporting at least some embodiments of the present disclosure. Liquid handling apparatus 940 may be used to at least participate in any of the methods disclosed herein. The apparatus may comprise a controller 941 comprising at least one processing core 942, at least one memory 943 including computer program code, the at least one memory 943 and the computer program code being configured to, with the at least one processing core, cause the apparatus at least to participate in dispensing a dispensable dispersion.

[0173] Connections between apparatus 940 and other devices may be provided by a communications unit 944 that is comprised in or connected to apparatus 940, for example a network interface. The apparatus may be connected to other devices using TCP / IP or CANBUS, for example. As seen in the figure 14B, the apparatus is also connected to the scale (balance) apparatus, the mixing apparatus, the UI apparatus. Apparatus 944 may be configured to serve as a gateway between the server and the other apparatuses (equipment), for example to retransmit information. In embodiments, the apparatus is connected to the Internet.

[0174] The memory 943 is capable of storing instructions, such as at least one of: operating system, various applications, models, neural networks and / or, preprocessing sequences. Furthermore, the memory may include a storage that may be used to store, e.g., the data received from a server, and / or from readers attached to the apparatus and / or at least some of the information and data used in the disclosed embodiments. The memory 943 may be embodied as one or more volatile memory devices, one or more non-volatile memory devices, and / or a combination of one or more volatile memory devices and nonvolatile memory devices. For example, the memory may be embodied as semiconductor memories (such as mask ROM, PROM (programmable ROM), EPROM (erasable PROM), flash ROM, RAM (random access memory), etc.).

[0175] Although the apparatus 940 is depicted as including one processor, the apparatus 940 may include several processors. Furthermore, the processor 942 is capable of executing the stored instructions. The processor 942 may be embodied as a multi-core processor, a single core processor, or a combination of one or more multi-core processors and one or more single core processors. For example, the processor may be embodied as one or more of various processing devices, such as a coprocessor, a microprocessor, a controller, a digital signal processor (DSP), a processing circuitry with or without anaccompanying DSP, or various other processing devices including integrated circuits such as, for example, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a microcontroller unit (MCU), a hardware accelerator, a specialpurpose computer chip, or the like. In an embodiment, the processor may be configured to execute hard-coded functionality. In an embodiment, the processor is embodied as an executor of software instructions, wherein the instructions may specifically configure the processor to perform at least one of the methods and / or operations described herein when the instructions are executed.

[0176] The liquid handling apparatus as discussed herein may comprise a user interface. The user interface may be provided as an application (“printer app”) on a touch screen connected to or comprised in the liquid handling apparatus, for example. The user interface may be configured so that the user may log in via the user interface. The user interface may be configured to display a message indicating a positive or negative verification result. The user interface may comprise a reader suitable for reading tags as discussed within this disclosure.

[0177] Apparatus 940 may be configured to: read a first tag with a first reader connected to apparatus 940, wherein the first reader is configured to obtain a dispenser identification code by reading the first tag, and is connected to the liquid handling apparatus; send the obtained dispenser identification code to a server comprising a database, the database comprising at least one previously obtained dispenser identification code; receive an indication from the server, responsive to a positive verification, that the inserted dispenser is acceptable; dispense at least some of the dispensable dispersion onto a dispensing target to form one or more dosage forms; and record, while dispensing, parameters relating to the formed one or more dosage forms; and send, by the liquid handling apparatus, the recorded parameters to the server, the server being configured to store the recorded parameters in the database.

[0178] It is contemplated that, unless stated otherwise, any of the embodiments and / or features of the embodiments described herein may be combined to form additional embodiments. Such combinations are understood within the scope of this description.

[0179] Further, it is understood that embodiments of the disclosure described above do not limit the scope of the invention, since these embodiments are merely examples of the embodiments of the invention, which are defined by the appended claims and theirlegal equivalents. Any equivalent embodiments are intended to be within the scope of this invention. Still further, various modifications of the disclosure, in addition to those described, such as alternative useful combinations of the embodiments described, may become apparent to those skilled in the art from the description. Such modifications and embodiments are also intended to fall within the scope of the appended claims.

[0180] In this disclosure, several elements, parts, or assemblies are attached to each other. Such attachment may be facilitated by any of the following solutions singly or jointly: adhesive, hook-or-loop fastener, screws, bolts, clasps, locks, nails, snap-fits, pins, snap-fasteners, spring elements such as ball plungers, zip-ties, magnets, electro-magnets.

[0181] In this disclosure, parts may be actuated manually or automatically. Manual movement may be performed directly by the hand of an operator. Manual or automatic movement may also be performed using equipment comprising: a pushbutton, a handle, a lever, a pedal, a control apparatus, a hydraulic cylinder, a leadscrew, a bearing, a magnet, an electro-magnet, an actuator, an electric motor, a pneumatic cylinder, a linear variable differential transformer.

[0182] Several benefits are provided by the present disclosure. The apparatuses and methods disclosed herein allow for manufacturing of products, for example pharmaceutical products, in a distributed and / or personalized manner. Distributed means that the products may be produced in various locations, ideally close to the consumer or patient. This minimizes shipping delay, or overreliance on a single production facility. Personalized means that the products may comprise one or more formulations adjusted to the patient’s needs. Some pharmaceutical products may be combined into a single dosage form, for example, which reduces the amount of dosage forms the patient needs to consume. Another example is that a treatment regime may be adjusted to meet a single patient’s needs, for example by reducing the active ingredient amount gradually over the course of several dosage forms. The present disclosure further ensures that production is done in a safe and quality controlled manner, and that the production is fully traceable. Production details may be provided on a single dosage form basis to stakeholders, so that each dosage form is individually traceable to the machine and user (operator) level.

[0183] It is to be understood that the embodiments of the invention disclosed are not limited to the particular structures, process steps, or materials disclosed herein, but are extended to equivalents thereof as would be recognized by those ordinarily skilled in therelevant arts. It should also be understood that terminology employed herein is used for the purpose of describing particular embodiments only and is not intended to be limiting.

[0184] Reference throughout this specification to one embodiment or an embodiment means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Where reference is made to a numerical value using a term such as, for example, about or substantially, the exact numerical value is also disclosed.

[0185] As used herein, a plurality of items, structural elements, compositional elements, and / or materials may be presented in a common list for convenience. However, these lists should be construed as though each member of the list is individually identified as a separate and unique member. Thus, no individual member of such list should be construed as a de facto equivalent of any other member of the same list solely based on their presentation in a common group without indications to the contrary. In addition, various embodiments and example of the present invention may be referred to herein along with alternatives for the various components thereof. It is understood that such embodiments, examples, and alternatives are not to be construed as de facto equivalents of one another, but are to be considered as separate and autonomous representations of the present invention.

[0186] Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. In this description, numerous specific details are provided, such as examples of lengths, widths, shapes, etc., to provide a thorough understanding of embodiments of the invention. One skilled in the relevant art will recognize, however, that the invention can be practiced without one or more of the specific details, or with other methods, components, materials, etc. In other instances, well-known structures, materials, or operations are not shown or described in detail to avoid obscuring aspects of the invention.

[0187] For the purposes of the present disclosure, the phrases “A or B” and “A and / or B” means (A), (B), or (A and B). For the purposes of the present disclosure, the phrase “A, B, and / or C” means (A), (B), (C), (A and B), (A and C), (B and C), or (A, B, and C).

[0188] While the forgoing examples are illustrative of the principles of the present invention in one or more particular applications, it will be apparent to those of ordinary skill in the art that numerous modifications in form, usage and details of implementation can be made without the exercise of inventive faculty, and without departing from the principles and concepts of the invention. Accordingly, it is not intended that the invention be limited, except as by the claims set forth below.

[0189] The verbs “to comprise” and “to include” are used in this document as open limitations that neither exclude nor require the existence of also un-recited features. The features recited in depending claims are mutually freely combinable unless otherwise explicitly stated. Furthermore, it is to be understood that the use of "a" or "an", that is, a singular form, throughout this document does not exclude a plurality.

[0190] The invention can also be utilized via the following clauses:

[0191] Clause 1. A method for preparing pharmaceutical dosage forms, the method comprising: inserting a dispenser into a thermal end;- wherein the dispenser comprises a first RFID tag and a dispensable dispersion comprising an active pharmaceutical ingredient (API),- wherein the thermal end: comprises at least two RFID readers, is detachably attachable to a liquid handling device, is configured to accept the dispenser, is configured to obtain information by reading at least the first and / or a second RFID tag, is configured to allow the obtained information to be sent to the liquid handling apparatus, wherein the liquid handling apparatus is configured to check the obtained information against a database to confirm the identity of the dispenser and the identity of a dispensing target comprising the second RFID tag, optionally adjusting the temperature of the dispensable dispersion by controlling the dispenser thermal end, and dispensing at least some of the dispensable dispersion onto the dispensing target to form one or more dosage forms by controlling the liquid handling apparatus, andrecording weight and / or composition of the one or more dosage forms in the database.

[0192] Clause 2. A method for producing one or more solid dosage forms of an active pharmaceutical ingredient (API), the method comprising the following steps:- weighting at least an API and a pharmaceutical excipient base into a reservoir thereby producing a mixture of weighted materials;- mixing and heating the mixture of the weighted materials in the reservoir until the mixture of the weighted materials is in a form of a dispensable dispersion; dispensing one or more doses of the dispensable dispersion from the reservoir onto a dispensing base; and cooling the one or more doses to a temperature wherein the one or more doses are in solid state thereby forming one or more solid dosage forms of an API.

[0193] Clause 3. The method according to clause 2, wherein the reservoir includes a RFID sticker.

[0194] Clause 4. The method according to clause 2 or 3, wherein the reservoir is a barrel of a syringe, and wherein step c) includes- installing a piston into the syringe, and- forcing the dispensable dispersion from the barrel of the syringe by pressing the piston.

[0195] Clause 5. The method according to any one of clauses 2 to 4 wherein the mixing and heating of step b) is performed using a mixer, preferably a blade-free planetary mixer.

[0196] Clause 6. The method according to any one of claims 1 to 4 further comprising e) sealing the dispensing base.

[0197] Clause 7. The method according to any one of clauses 2 to 6 wherein the pharmaceutical excipient base includes one or more gelling agents, fillers, solvents, thickeners, preservatives, surfactants, pH adjusting agents, and / or sweeteners.

[0198] Clause 8. The method according to any one of clauses 2 to 7 wherein heating of step b) is to 35-90 °C, such as to 35-55 °C; the dispensing of step c) is at 35- 90 °C,35-55 °C, and the cooling of step d) is to 25 °C or below.

[0199] Clause 9. The method according to any one of clauses 2 to 8, wherein pharmaceutical excipient base includes:- 5 - 30 wt.-% of one or more gelling agents selected from a group consisting of gelatin, agar, and combinations thereof;- 0.5 - 5 wt.-% silica;- 10 - 35 wt.-% of one or more hydrated vegetable fats, wherein the melting point of the one or more hydrated vegetable fats is from 35 °C to 55 °C;- 10 - 30 wt.-% of one or more carbohydrates and / or sugar alcohols;- 40 - 70 wt.-% of one or more solvents, and optionally one or more surfactants, preservatives, pH adjusting agents, flavoring agents, or sweeteners.

[0200] Clause 10. The method according to any one of clauses 2 to 9, comprising 75-99.9 wt.-% pharmaceutical excipient base and 0.1-25 wt.-% API.

[0201] Clause 11. A method for producing a package comprising one or more traceable solid dosage forms of an active pharmaceutical ingredient (API), the method comprising the following steps: a) providing a system comprising a reservoir (102) comprising a RFID sticker (105), a first dispenser (301) comprising a first balance (302) and a first RFID reader (303), a mixer (304) comprising a second RFID reader (305), a second dispenser (306) comprising a heating means a second balance (307), and a third RFID reader (308), a dispensing base (309), a sealer (310) comprising a printer, and a batch record (311);b) providing a dose description; c) for producing one or more solid dosage forms i. positioning the reservoir onto the first balance; ii. the first dispenser scanning the RFID code; dispensing and weighting, based on the dose prescription, at least an API and a pharmaceutical excipient base into the reservoir thereby producing a mixture of weighted materials; and sending weights of the weighted materials to the batch record; iii. transferring the reservoir into the mixer, iv. the mixer scanning the RFID code; mixing and heating the mixture of the weighted materials in the reservoir until a dispensable dispersion is formed; and sending one or more of: time of mixing and heating and temperature of heating to the batch record; v. transferring the reservoir into the second dispenser; vi. the second dispenser scanning the RFID code; dispensing and weighting one or more doses of the dispensable dispersion from the reservoir to the dispensing base; cooling the one or more doses to a temperature wherein the one or more doses are in solid state thereby forming one or more solid dosages of an API; sending at least number of doses dispensed, weight of the one or more doses dispensed to the batch record; vii. transferring the dispensing base comprising the one or more solid dosages of the API into the sealer; viii. the sealer sealing the dispensing base comprising the one or more solid dosages of the API by a sealant and printing one or more QR codes comprising one or more of: time of manufacture, batch info, dose, prescription in general, patient info, expiry date, on the sealant,thereby providing a package comprising one or more traceable solid dosage forms of an active pharmaceutical ingredient.

[0202] Clause 12. The method according to clause 11, comprising d) printing the batch record.

[0203] Clause 13. The method according to clause 11 or 12, wherein the reservoir is a barrel of a syringe (100), and wherein step vi. includes a. installing a piston (101) into a barrel (102) of the syringe, and b. forcing the dispensable dispersion from the barrel by pressing the piston.

[0204] Clause 14. The method according to any one of clauses 11 to 13, wherein the pharmaceutical excipient base includes one or more gelling agents, fillers, solvents, thickeners, preservatives, surfactants, pH adjusting agents, and / or sweeteners.

[0205] Clause 15. The method according to any one of clauses 11 to 14 wherein the pharmaceutical excipient base includes5 - 30 wt.-% of one or more gelling agents selected from a group consisting of gelatin, agar, and combinations thereof;0.5 - 5 wt.-% silica;10 - 35 wt.-% of one or more hydrated vegetable fats, wherein the melting point of the one or more hydrated vegetable fats is from 35 °C to 55 °C;10 - 30 wt.-% of one or more carbohydrates and / or sugar alcohols;40 - 70 wt.-% of one or more solvents, and optionally one or more surfactants, preservatives, pH adjusting agents, flavoring agents, or sweeteners.

[0206] Clause 16. The method according to any one of clauses 11 to 15, comprising 75-99.9 wt.-% pharmaceutical excipient base and 0.1-25 wt.-% API.INDUSTRIAL APPLICABILITY

[0207] At least some embodiments of the present invention find industrial application in producing products such as pharmaceutical products.ACRONYMS LISTAPI Active pharmaceutical ingredient DIC Dispenser identification codeTIC Target identification codeUIC User identification codeREFERENCE SIGNS LIST

Claims

CLAIMS:

1. A method for preparing pharmaceutical dosage forms, the method comprising: inserting a dispenser into a thermal end;- wherein the dispenser comprises a first tag and a dispensable dispersion comprising an active pharmaceutical ingredient (API),- wherein the thermal end: is detachably attachable to a liquid handling device, is configured to accept the dispenser, reading the first tag with a first reader, wherein the first reader: is configured to obtain a dispenser identification code by reading the first tag, is connected to the liquid handling apparatus, sending, by the liquid handling apparatus, the obtained dispenser identification code to a server comprising a database, the database comprising at least one previously obtained dispenser identification code, verifying, by the server, the obtained dispenser identification code against the at least one previously obtained dispenser identification code to confirm the identity of the dispenser, indicating, by the server, responsive to a positive verification, to the liquid handling apparatus that the inserted dispenser is acceptable, dispensing, by the liquid handling apparatus, at least some of the dispensable dispersion onto a dispensing target to form one or more dosage forms, recording, by the liquid handling apparatus while dispensing, process data relating to the formed one or more dosage forms, and sending, by the liquid handling apparatus, the recorded process data to the server, the server being configured to store the recorded process data in the database.

2. The method according to claim 1, wherein the first tag is an RFID tag, in particular an NFC tag, and wherein the first reader is an RFID reader; or wherein the first tag is a barcode and wherein the first reader is a barcode reader; or wherein the first tag is a machine-readable label, for example a QR code, and wherein the first reader is a camera.

3. The method according to claim 1 or 2, wherein the dispensing target comprises a second tag, the method further comprising:- reading the second tag with a second reader to obtain a target identification code,- sending, by the liquid handling apparatus, the obtained target identification code to the server comprising a database, the database comprising at least one previously obtained target identification code,- verifying, by the server, the obtained target identification code against the at least one previously obtained target identification code to confirm the identity of the dispensing target, and- indicating, by the server, responsive to a positive verification, to the liquid handling apparatus that the dispensing target identity is acceptable.

4. The method according to any one of the preceding claims, further comprising- checking, by the server, the obtained target identification code against information associated with the obtained target identification code within the database in order to confirm the type of the dispensing target,- verifying, by the server, the confirmed type of the dispensing target against a manufacturing order comprising an acceptable dispensing target type,- indicating, by the server, responsive to a positive verification, to the liquid handling apparatus that the dispensing target type is acceptable.

5. The method according to any one of the preceding claims, wherein the first and / or second reader is positioned on or within the thermal end.

6. The method according to any one of the preceding claims, wherein the first reader is arranged on the thermal end and configured to read at least one tag on the dispenser within the thermal end, and wherein the second reader is arranged on the thermal end and configured to read at least one tag outside the thermal end, for example on a dispensing target.

7. The method according to any one of the preceding claims, wherein the second tag is an RFID tag, in particular an NFC tag, and wherein the second reader is an RFID reader;or wherein the second tag is a barcode and wherein the second reader is a barcode reader; or wherein the second tag is a machine-readable label, for example a QR code, and wherein the second reader is a camera.

8. The method according to any one of the preceding claims, wherein the recorded process data comprises at least one of the following: the weight of the dispensing target before and after dispensing each dosage form, temperature values of the dispensable dispersion during the dispensing process, time stamp information relating to the dispensing, and / or image and / or video recording of the dispensed dosage form.

9. The method according to any one of the preceding claims, further comprising, prior to inserting the dispenser into the thermal end: placing the dispenser onto a mixer, reading the first tag with a reader of the mixer to obtain a dispenser identification code,- sending, by the mixer or an apparatus associated with the mixer, the obtained dispenser identification code to the server comprising a database, the database comprising at least one previously obtained dispenser identification code,- verifying, by the server, the obtained dispenser identification code against the at least one previously obtained dispenser identification code to confirm the identity of the dispenser,- indicating, by the server, responsive to a positive verification, to the mixer that the placed dispenser is acceptable, mixing, by the mixer, a blend in the dispenser to form the dispensable dispersion, and optionally sending, by the mixer or an apparatus associated with the mixer, recorded mixing parameters to the server comprising a database, the server configured to store the mixing parameters within the database and associate, in the database, the parameters with the dispenser identification code.

10. The method according to any one of the preceding claims, wherein the thermal end is configured to adjust the temperature of the dispensable dispersion, wherein the temperature of the dispersion is adjusted to 35-95 °C, for example to 35-55 °C.

11. The method according to any one of the preceding claims, wherein the method further comprises cooling the one or more dosage forms after the dispensing.

12. The method according to claim 9, wherein the blend comprises the API and a pharmaceutical excipient base, the pharmaceutical excipient base comprising:- 5 - 30 wt.-% of one or more gelling agents selected from the group consisting of gelatin, agar, and combinations thereof;- 0.5 - 5 wt.-% silica;- 10 - 35 wt.-% of one or more hydrated vegetable fats, wherein the melting point of the one or more hydrated vegetable fats is from 35 °C to 55 °C;- 10 - 30 wt.-% of one or more carbohydrates and / or sugar alcohols;- 40 - 70 wt.-% of one or more solvents, and optionally one or more surfactants, preservatives, pH adjusting agents, flavoring agents, or sweeteners.

13. The method according to claim 9, wherein the blend comprises 0.1-25 wt.-% of the API and 75-99.9 wt-% of a pharmaceutical excipient base.

14. The method according to any one of the preceding claims, the method further comprising:- sealing the one or more dosage forms, and- printing one or more labels, wherein the labels comprise information from the database, for example information comprising at least one of: time of manufacture, batch info, dose, prescription information, patient information, expiry date; and- attaching at least one label to the one or more dosage forms, in particular attaching one label to each dosage form wherein said attached one label corresponds to the dosage form in question.

15. The method according to any one of the preceding claims, further comprising, prior to inserting the dispenser into the thermal end:- placing the dispenser on a balance,- reading the first tag, by a reader of the balance or an apparatus associated with the balance, to obtain a dispenser identification code, and- sending, by the balance or an apparatus associated with the balance, the obtained dispenser identification code to the server comprising a database, the database comprising at least one previously obtained dispenser identification code,- verifying, by the server, the obtained dispenser identification code against the at least one previously obtained dispenser identification code to confirm the identity of the dispenser,- indicating, by the server, responsive to a positive verification, to the balance that the placed dispenser is acceptable,- receiving, by the balance from the server, weighing parameters regarding the amount of API and of a pharmaceutical excipient base to be placed in the dispenser,- weighing, based on the weighing parameters, an amount of the API and of a pharmaceutical excipient base to form the blend, sending, by the balance or an apparatus associated with the balance, parameters associated with the weighing to the server comprising a database, wherein the server is configured to store the parameters in the database.

16. A system for preparing pharmaceutical dosage forms, the system comprising:- a server comprising at least one processing core, at least one memory including computer program code, the server comprising or connected to a database, a dispenser thermal end, said thermal end configured to: accept a dispenser comprising a first tag and a dispensable dispersion comprising an active pharmaceutical ingredient (API), adjust the temperature of the dispensable dispersion, a first reader, said first reader configured to: obtain a dispenser identification code by reading the first tag, a liquid handling apparatus connected to the server, wherein the liquid handling apparatus is configured to:- send, to the server, the obtained dispenser identification code, the server being configured to verify the obtained dispenser identification code against at least one previously obtained dispenser identification code, and responsive to a positive verification, indicate to the liquid handling apparatus that the inserted dispenser is acceptable,optionally adjust the temperature of the dispensable dispersion by controlling the thermal end, dispense, using said dispenser, at least some of the dispensable dispersion to a dispensing target to form one or more dosage forms,- record, while dispensing, dispensing data relating to the formed one or more dosage forms, and- send the recorded dispensing data to the server, the server being configured to store the recorded dispensing data in the database.

17. The system according to claim 16, wherein the server is configured to verify the recorded dispensing data against stored acceptable dispensing data, and responsive to a positive verification, indicate to the liquid handling apparatus that the recorded dispensing data are acceptable.

18. The system according to claim 17 or claim 18, further comprising a second reader, wherein the second reader is configured to:- obtain a target information code by reading a second tag attached to a dispensing target, and wherein the liquid handling apparatus is configured to send, to the server, the obtained target identification code, the server being configured to verify the obtained target identification code against at least one previously obtained target identification code, and responsive to a positive verification, indicate to the liquid handling apparatus that the inserted target is acceptable.

19. The system according to any one of claims 16 to 18, further comprising a mixer, wherein the mixer comprises or is associated with a reader; wherein the mixer is configured to: read the first tag by the reader of the mixer; mix a blend comprising the active pharmaceutical ingredient (API) in the dispenser to form the dispensable dispersion.

20. A server comprising at least one processing core, at least one memory including computer program code, the server comprising or connected to a database, the at least onememory and the computer program code being configured to, with the at least one processing core, cause the server at least to:- receive, from a liquid handling apparatus, at least one dispenser identification code, DIC,- verify the obtained DIC against at least one previously obtained DIC to confirm the identity of a dispenser associated with the obtained DIC, wherein the at least one previously obtained DIC is retrieved from a database comprised in or connected to the server,- indicate, if the verification result is positive, to the liquid handling apparatus that the inserted dispenser is acceptable,- receive, from the liquid handling apparatus, recorded dispensing data, and- store the received recorded dispensing data in the server.

21. The system according to claim 20, wherein the server is configured to verify the recorded dispensing data against stored acceptable dispensing data, and indicate, if the verification result is positive, to the liquid handling apparatus that the recorded data are acceptable.

22. The system according to claim 20 or claim 21, wherein the server is further configured to:- receive, from a liquid handling apparatus, at least one dispensing target identification code, TIC,- check the obtained target identification code against information associated with the obtained target identification code within the database in order to confirm the type of the dispensing target,- indicate, if the check result is positive, to the liquid handling apparatus that the inserted dispensing target is acceptable.

23. A liquid handling apparatus comprising at least one processing core, at least one memory including computer program code, the at least one memory and the computer program code being configured to, with the at least one processing core, cause the liquid handling apparatus at least to:- read a first tag with a first reader, wherein the first reader: is configured to obtain a dispenser identification code by reading the first tag, is connected to the liquid handling apparatus,- send the obtained dispenser identification code to a server comprising a database, the database comprising at least one previously obtained dispenser identification code, the server configured to verify the obtained dispenser identification code against the at least one previously obtained dispenser identification code,- receive, from the server, if the verification result is positive, an indication that the inserted dispenser is acceptable,- begin dispensing, record dispensing process data while dispensing, and- send the recorded dispensing process data to the server.

24. The apparatus of claim 23, wherein the server is configured to verify the recorded dispensing process data against stored acceptable dispensing process data, wherein the apparatus is configured to receive, if the verification result is positive, an indication that the recorded dispensing process data is acceptable.

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