Mixing device

Abstract

The present invention relates to a mixing device (1), more particularly to a mixing device (1) for producing nanoparticles by mixing of at least two fluids, the mixing device (1) comprising a mixing chamber (2), two inlet conduits (3, 4) and an outlet (5).

Description

[Technical field]

[0001] The present invention is in the pharmaceutical field and relates to a mixing device, more specifically a mixing device for producing nanoparticles. [Background technology]

[0002] A problem that exists in the scaling of nanoparticles in industrial manufacturing, both in the chemical and pharmaceutical drug production sectors, is the need to maintain the physicochemical properties of the nanoparticles and their reproducibility from batch to batch during production.

[0003] In certain cases of clinical and preclinical trials at early stages of development, small amounts of product may be sufficient, and such small-scale production allows for great reproducibility to be achieved with appropriately characterized nanoparticles.

[0004] However, when large-scale production is required, the batch-to-batch reproducibility and polydispersity of nanoparticles can be difficult to control, leading to large variations in the physicochemical properties of nanoparticles in different batches, which may result in batch rejection and increased manufacturing costs.

[0005] Variations in the physicochemical properties of nanoparticles may induce undesirable effects in users or patients, so further testing is required before large-scale industrial production can be achieved.

[0006] In general, there are two approaches to nanoparticle fabrication: "top-down" and "bottom-up" approaches. Top-down approaches involve the creation of nanometre-sized entities from larger structures by techniques such as milling, whereas bottom-up approaches use smaller components that assemble to form larger functional structures, such as in monomer polymerisation.

[0007] The formulation of nano-drugs may require various processes such as high-speed homogenization, ultrasonication, milling, emulsification, reticulation, organic solvent evaporation, centrifugation, filtration, and / or freeze-drying. Therefore, the manufacture of nano-drug products does not simply involve the addition and mixing of individual components. Instead, it requires well-defined industrial production processes, precise analysis of the obtained products, and strict quality control, which results in very high manufacturing costs. Summary of the Invention

[0008] The present invention solves the aforementioned problem by a mixing device according to claim 1 and a method for producing nanoparticles according to claim 15. The dependent claims define preferred embodiments of the invention.

[0009] In a first inventive aspect, the present invention provides a mixing device for producing nanoparticles by mixing of at least two fluids, comprising: a mixing chamber comprising a base and at least one wall; two inlet conduits configured to supply fluid into the mixing chamber, each inlet conduit comprising an inlet portion with a plurality of inlet openings, the inlet portions being disposed inside the mixing chamber, spaced apart from one another, and oriented by the inlet openings to supply fluid into the mixing chamber in a substantially tangential direction relative to an inner surface of the wall; an outlet conduit having an outlet opening, the outlet conduit being configured to be positioned such that the outlet opening is located within the mixing chamber at a higher position than the position of the inlet opening; The present invention provides a mixing device comprising:

[0010] Each of the inlet conduits of the mixing device of the present invention is configured to be connected to a fluid source to supply fluid into the mixing chamber, the inner surface of the base and the inner surface of the at least one wall of the mixing chamber defining an internal volume for receiving the fluid.

[0011] In use, various fluids are fed into the mixing chamber via the inlet conduits. The insertion of the fluids into the mixing chamber through the multiple inlet openings, substantially tangential to the inner surface of the wall, creates gentle fluid agitation inside the mixing chamber that promotes mixing, and is therefore particularly suitable for preparing nanoparticles by nanoprecipitation without the need for additional stirring means. This has the advantage of obtaining a simpler device than prior art devices that require the action of additional elements to move the fluids.

[0012] By substantially tangential, it is understood that the fluid is inserted into the mixing chamber in a direction such that the tangential component is greater than the other two perpendicular components. In embodiments in which at least one wall of the mixing chamber is substantially shaped as a surface of revolution, the other two perpendicular components of the direction are radial and axial. By tangential to the inner surface of the wall, it is understood that the tangential direction is at the point on the inner surface of the wall closest to the inlet opening.

[0013] When the liquid level inside the mixing chamber containing the desired product exceeds the outlet opening, the formed nanoparticles enter the outlet conduit and exit the mixing chamber, thus allowing the nanoparticles to be obtained in a continuous process where the fluid inlet is maintained while the formed product is provided through the outlet, where the process flow for both the raw materials entering the mixing chamber and the final product can also be controlled when the required reactants are produced.

[0014] Overflowing the outlet opening allows the extraction of nanoparticles without applying any force to the nanoparticles, which is advantageous, especially for porous nanoparticles, since applying force to the nanoparticles, such as by pumping, can dramatically affect the nanoparticle properties, and overflowing the outlet opening allows the production of nanoparticles in any quantity, from small to large, depending on the time the production process is maintained in the mixing device of the present invention.

[0015] The size of the nanoparticles can be adjusted by controlling the pressure and flow rate of the fluid fed into the mixing chamber. When a larger nanoparticle size is required, a lower flow rate and pressure is used for the fluid compared to when a smaller nanoparticle size is desired. Such adjustment occurs through the configuration of the inlet conduit that feeds the primary fluid into the mixing chamber.

[0016] The mixing device of the present invention is suitable for both laboratory and industrial scale production, since it allows the production of nanoparticles by nanoprecipitation in a continuous process, which is achieved by the aforementioned configuration with separate inlets for the required fluids as well as suitable outlets for the obtained products, said outlets being configured to extract said products from the inner space of the mixing chamber, where the mixing of the raw materials from the inlets takes place, the products being the nanoparticles obtained by the aforementioned nanoprecipitation procedure.

[0017] In one embodiment, two miscible solvents are used to prepare nanoparticles by nanoprecipitation using the mixing device of the present invention, a first solvent being a good solvent for the material forming the nanoparticles and a second solvent being an anti-solvent for the aforementioned material. The material forming the matrix of the nanoparticles (e.g., a polymer, a protein, or any other compound or combination thereof) is dissolved in a first solvent (e.g., an organic solvent) to form a solvent phase. The first solvent and the second solvent are each fed into the mixing chamber through one inlet conduit. When the solvent phase is mixed with the anti-solvent (e.g., water), the solvent tends to diffuse into the anti-solvent, causing desolvation of the material and subsequent disintegration of the material to form nanoparticles. If the solvent phase contains an active ingredient, the active ingredient is encapsulated in the nanoparticles.

[0018] The mixing apparatus of the present invention enables cost-effective and reliable industrial production of nanoparticles by nanoprecipitation as described above, where batches of various nanoparticle sizes can be produced with batch-to-batch reproducibility in a continuous process.

[0019] In one embodiment, the inlet conduits are arranged to feed the fluids into the mixing chamber in the same direction, i.e., clockwise or counterclockwise. Advantageously, the agitating motion of the fluids is generated by including fluids inside the mixing chamber that do not induce excessive turbulence in the space available for the formation of nanoparticles. Thus, the motion generated by the orientation of the inlet conduits directing the flow of fluids inside the mixing chamber is sufficient to promote the formation of nanoparticles without resulting in fluid motion that would degrade the resulting product.

[0020] In one embodiment, at least a portion of the outlet conduit is disposed along the longitudinal axis of the mixing chamber, i.e. along the direction of the longest dimension of the mixing chamber, which advantageously allows for optimization of the space available inside the chamber for controlling the movement of the fluid introduced therein and for the formation of nanoparticles by said fluid movement.

[0021] In one embodiment, the longitudinal axis of the mixing chamber is aligned in the direction of gravity.

[0022] In one embodiment, the outlet conduit is located in a central position within the mixing chamber. According to this embodiment, the inlet conduit is arranged to feed the fluid into the mixing chamber tangentially to the inner surface of the wall, thus surrounding the outlet conduit. This embodiment allows for improved mixing of the fluids introduced inside the mixing chamber by the stirring required to induce the formation of nanoparticles and the subsequent overflow of the outlet, which is located in the mixing chamber at an equal distance from the inner surface of the wall.

[0023] In one embodiment, each inlet conduit is arranged such that the multiple inlet openings are distributed along a direction generally parallel to the longitudinal axis of the mixing chamber.

[0024] In one embodiment, the inner surface of at least one wall of the mixing chamber is shaped substantially as a surface of revolution. Preferably, the inner surface of the wall of the mixing chamber is shaped substantially as a cylinder, thus resulting in a cylindrical chamber integral with the base.

[0025] In one embodiment the outlet conduit is positioned along or parallel to the axis of rotation of the surface of rotation, preferably in this embodiment the axis of rotation is the longitudinal axis of the mixing chamber.

[0026] In embodiments in which the inner surface of at least one wall of the mixing chamber is substantially shaped as a surface of revolution, the inlet conduits are arranged such that the inlet openings are distributed along a direction generally parallel to the axis of rotation of the surface of revolution, which in this embodiment is preferably the longitudinal axis of the mixing chamber.

[0027] In one embodiment, the distance from the outlet opening to the base of the mixing chamber is adjustable. Adjustment of the distance from the outlet opening to the base can be achieved in various ways. In one embodiment, the outlet conduit is movable relative to the mixing chamber to adjust the position of the outlet opening inside the mixing chamber. Alternatively or additionally, in one embodiment, the outlet conduit has an adjustable length, allowing the outlet opening to be positioned at a desired distance relative to the base of the mixing chamber. Adjusting the distance of the outlet opening from the base of the mixing chamber allows for precise positioning of the outlet opening relative to the inlet opening, which has an effect on the movement of fluids inside the mixing chamber as well as the overflow of the resulting product to control the manufacturing process and the batch size produced. Additionally, the volume available inside the mixing chamber depends on the volume occupied by the outlet conduit, which affects the physicochemical properties of the nanoparticles.

[0028] In one embodiment, the inlet conduit is spaced apart from the wall.

[0029] In one embodiment, one inlet conduit is located behind the other inlet conduit when the mixer is in operation, such that each inlet conduit impedes the flow of fluids introduced into the mixing chamber through the other inlet conduit, thereby improving mixing of both fluids.

[0030] In one embodiment, each inlet opening comprises a spray nozzle having a nozzle opening.

[0031] In one embodiment, each spray nozzle comprises size adjustment means for adjusting the size of the nozzle opening. Advantageously, the size adjustment of the nozzle opening makes it possible to control the stirring effect caused inside the mixing chamber by the pressure with which the fluid is introduced inside the mixing chamber, as well as to adapt the size of the nozzle opening to the particular flow rate and / or fluid used. This embodiment also makes it possible to close one or some of the inlet openings of the inlet conduit, thereby allowing the fluid to enter the mixing chamber only through selected inlet openings, thus allowing a better control of the parameters defining the nanoparticle manufacturing process.

[0032] In one embodiment, each inlet conduit is equipped with a flow meter.

[0033] In one embodiment, the mixing device comprises a cover configured to mate with a top of the mixing chamber and close an interior volume defined by the mixing chamber.

[0034] In one embodiment, the mixing device comprises a support structure configured to support the mixing chamber, the support structure allowing for positioning the mixing chamber in a suitable position for collecting the produced nanoparticles. In one embodiment, the support structure comprises a plurality of support legs. Preferably, the support legs comprise levelling means for improving the stability of the mixing device.

[0035] The present invention also provides a mixing system comprising a mixing device according to any of the embodiments according to the first inventive aspect.

[0036] In one embodiment, the mixing system comprises a collection chamber in fluid communication with the mixing chamber via the outlet conduit. Preferably, the collection chamber is disposed below the mixing chamber for receiving the nanoparticles produced therein from the mixing chamber.

[0037] In one embodiment, the mixing system comprises a bend portion coupled to the outlet conduit and configured to provide fluid communication with the collection chamber.

[0038] In one embodiment, the mixing device comprises a sealing means configured to seal the junction of the outlet conduit and the bend so that the product flow from the mixing chamber is accurately directed to the collection chamber.

[0039] In one embodiment, the mixing system comprises two reservoirs, each connected to an inlet conduit, in which the required fluids are stored to be fed to the mixing chamber by the aforementioned inlet conduit. Further control of the manufacturing process can be performed by controlling the height of the reservoirs and providing the fluids in the mixing chamber.

[0040] In one embodiment, the mixing system comprises pumping means for supplying at least one fluid to the mixing chamber, in a particular embodiment, the pumping means is provided such that the flow rate of such fluid towards the mixing chamber can be controlled by drawing the fluid from the reservoir and passing it through the inlet conduit at a predetermined pressure and velocity.

[0041] In a second inventive aspect, the present invention provides a method for producing nanoparticles using a mixing device according to any of the embodiments of the present invention or a mixing system according to any of the embodiments of the present invention, comprising: (a) obtaining a first solvent containing nanoparticle-forming material and an active ingredient; (b) obtaining a second solvent that is an anti-solvent for the material that will form the nanoparticles; (c) supplying a first solvent into the mixing chamber via a first inlet conduit and a second solvent into the mixing chamber via a second inlet conduit; (d) allowing the liquid level within the mixing chamber to exceed the exit orifice such that the formed nanoparticles enter the exit conduit and exit the mixing chamber; The method includes:

[0042] In one embodiment, the first solvent and / or the second solvent are fed into the mixing chamber using a pumping means.

[0043] In one embodiment, the material forming the nanoparticles is or includes any other compound such as a polymer, a protein, or a combination thereof.

[0044] In one embodiment, the first solvent is an organic solvent.

[0045] In one embodiment, the second solvent is water.

[0046] All features described in this specification (including the claims, specification, and drawings), and / or all steps of the methods described, may be combined in any combination, except for such mutually exclusive combinations of features and / or steps.

[0047] These and other features and advantages of the present invention will be clearly understood from a consideration of the detailed description of the invention which is given by way of example only and is not intended to be limiting, and which is made clear from preferred embodiments of the invention, given with reference to the drawings, in which: [Brief description of the drawings]

[0048] [Figure 1] 1 shows a front view and a detailed view of a mixing device according to one embodiment of the present invention. [Diagram 2] 2 shows a partial cross-sectional side view of the mixing device of FIG. 1. [Diagram 3] FIG. 2 shows a front view of the mixing device of FIG. 1 with the cover removed. [Figure 4] 2 shows a cross-sectional plan view of the mixing chamber of the mixing device of FIG. 1. [Diagram 5] 2 shows a detailed view of an inlet conduit according to one embodiment of the present invention. [Figure 6] FIG. 2 shows a plan view of the mixing device of FIG. [Figure 7] 1 shows a block diagram of a mixing system according to the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0049] 1 and 2 respectively show a front view and a partially cutaway side view of a mixing device according to one embodiment of the present invention. The mixing device (1) comprises a mixing chamber (2), two inlet conduits (3, 4) and an outlet conduit (5).

[0050] The mixing chamber (2) comprises a base (12) and at least one wall (13). The inner surface of the base (12) and the inner surface of the at least one wall (13) of the mixing chamber (2) define an internal volume configured to receive fluids entering from the two inlet conduits (3, 4). In the embodiment shown, the mixing chamber (2) comprises one wall (13) having an inner surface substantially shaped as a surface of revolution, i.e., substantially cylindrical, thereby configuring the mixing chamber (2) as a substantially cylindrical chamber. However, in other embodiments, the mixing chamber (2) may have several wall portions and / or be configured in a different shape. In this embodiment, the mixing chamber (2) is open at its upper end, i.e., the end facing the base (12), so that the internal volume of the mixing chamber (2) is accessible.

[0051] The inlet conduits (3, 4) are configured to be connected to a fluid source, such as a reservoir or storage location (22, 23) as depicted diagrammatically in FIG. 7, to supply fluid into the mixing chamber (2). Each inlet conduit (3, 4) comprises an inlet portion with a number of inlet openings (11). As shown in FIG. 2, in this embodiment, the inlet openings (11) are aligned substantially along a portion of the inlet conduits (3, 4). During use of the mixing device (1), the inlet portions of the inlet conduits (3, 4) containing the inlet openings (11) are spaced apart from one another within the mixing chamber (2) and are oriented by the inlet openings (11) to supply fluid into the mixing chamber (2) in a substantially tangential direction with respect to the inner surface of the wall (13). In this embodiment, the inlet conduits (3, 4) are arranged to supply fluid into the mixing chamber (2) in the same direction, i.e. counterclockwise. Also in this embodiment, the inlet conduits (3, 4) are arranged such that the inlet openings (11) are distributed along a direction substantially parallel to the axis of rotation of the substantially cylindrical mixing chamber, which is also the longitudinal axis of the mixing chamber (2) and which, in use, is substantially aligned in the direction of gravity. In this embodiment, the inlet conduits (3, 4) are arranged at a distance from the wall (13).

[0052] Such an arrangement of inlet conduits (3, 4) is shown diagrammatically in FIG. 4, which shows a plan cross-sectional view of a mixing chamber (2) having an inlet conduit (3, 4) configuration of the present invention.

[0053] The outlet conduit (5) comprises an outlet opening (6) and is configured to be arranged in the mixing chamber (2) such that the outlet opening (6) is located at a higher position than the inlet openings (11), i.e. higher than the position of the highest inlet opening (11). In this embodiment, the outlet conduit (5) is arranged along the central longitudinal axis of the mixing chamber (2), which corresponds to the axis of rotation of the substantially cylindrical mixing chamber, and is movable along this longitudinal axis. This is shown diagrammatically in FIG. 2, where the outlet conduit (5) is depicted in two different positions, namely a first (upper) position, in which the outlet opening (6) is located at a higher position in the mixing chamber (2) than the inlet openings (11), and a second (lower) position, in which the outlet opening (6) is located at a lower height compared to the first position. In FIG. 2, the second position of the outlet conduit (5) is depicted with dashed lines to distinguish it from the first position. Various positions other than those depicted are also possible for the outlet conduit (5), for example intermediate positions of the outlet conduit (5).

[0054] In this embodiment, the base (12) of the mixing chamber (2) has an opening that allows the insertion of a portion of the outlet conduit (5). By longitudinally moving the outlet conduit (5), the length of the outlet conduit (5) inserted inside the mixing chamber (2) and therefore the position where the produced nanoparticles are extracted from the mixing chamber (2) after acquisition can be adjusted. Once the desired length of the outlet conduit (5) is inside the mixing chamber (2), the outlet conduit (5) is removably fixed and remains connected to the mixing chamber (2) until it is later necessary to remove the outlet conduit (5). Sealing means are preferably provided to ensure a seal at the connection between the outlet conduit (5) and the base (12) of the mixing chamber (2). The end of the outlet conduit (5) opposite the outlet opening (6) is located outside the mixing chamber (2), thus allowing the product to be discharged from the mixing chamber (2). The mixing device (1) may include a bent portion (9) coupled to the end of the outlet conduit (5) to enhance discharge of the product, such as by providing fluid communication with a collection chamber (21). In other embodiments, discharge of the product occurs directly through the end of the outlet conduit (5) or by other means.

[0055] Instead of or in addition to the outlet conduit (5) being movable relative to the mixing chamber (2) to adjust the position of the outlet opening (6) inside the mixing chamber (2), in one embodiment the outlet conduit (5) has a telescopic section whose length is adjustable, so that by adjusting the length of the telescopic section the outlet opening (6) can be positioned at a desired distance relative to the base of the mixing chamber (2).

[0056] In one embodiment, each inlet opening (11) of the inlet conduits (3, 4) comprises a spray nozzle having a nozzle opening. The spray nozzle comprises a size adjustment means for adjusting the size of the nozzle opening. Figure 5 shows a detailed view of an inlet conduit according to this embodiment of the invention.

[0057] In the embodiment shown, the mixing device (1) comprises a cover (10) configured to couple to the top of the mixing chamber (2) to close the mixing chamber. The cover (10) is visible in Figures 1, 2 and 6, while Figure 3 shows the mixing device with the cover (10) removed. In this embodiment, the cover (10) is removably coupled to the mixing chamber (2) by a fastening bolt (15). The fastening bolt (15) is rotatably fixed to a corresponding lug (18) located on the top of the mixing chamber (2). By rotating the fastening bolt (15) from a non-coupled position (shown in Figure 3) to a coupled position (shown in Figures 1 and 6), the fastening bolt (15) is received in a slot (19) provided in the cover (10) and the cover (10) is coupled to the mixing chamber (2). The coupling position of the fastening bolt (15) is shown in the enlarged detail view of Figure 1. Additional or alternative fastening means between the cover (10) and the top of the mixing chamber (2) are also possible.

[0058] Sealing means (not shown) may be provided to seal the connection between the cover (10) and the mixing chamber (2). In Figure 4, an annular groove (17) is visible located at the top of the mixing chamber (2) for receiving the sealing means.

[0059] In this embodiment, the cover (10) comprises two openings through which the inlet conduits (3, 4) are introduced into the mixing chamber (2) such that their inlet portions are located inside the mixing chamber (2). Additional portions of the inlet conduits (3, 4) remain outside the mixing chamber (2) and have a connection portion (16) for coupling with a fluid source and receiving fluid therefrom. Sealing means may be provided to seal the connection between the inlet conduits (3, 4) and the openings implemented in the cover (10).

[0060] In this embodiment, the cover (10) also comprises a window (26) through which the interior of the mixing chamber (2) can be observed even when closed by the cover (10).

[0061] As shown in Figures 1-3, in this embodiment, the mixing device (1) comprises a support structure configured to support the mixing chamber (2). The support structure comprises a number of support legs (7) with leveling means (8) for improving the stability of the mixing device (1) and placing it in a suitable location. The mixing device (1) also comprises a bent portion (9) connected to the end of the outlet conduit (5) located outside the mixing chamber to improve the guiding of the resulting product, i.e., nanoparticles, from the mixing chamber (2) to a collection chamber (21) where the nanoparticles can be stored or further processed.

[0062] In this embodiment, the mixing device comprises a vent pipe (14) for venting gas from the mixing chamber (2).

[0063] In one embodiment, the mixing device comprises an outlet port (27) located at the bottom of the mixing chamber (2). The outlet port (27) comprises a closing means for opening and closing the outlet port (27) as required. The outlet port (27) allows for easy extraction of contents remaining inside the mixing chamber (2) at the end of the process, such as nanoparticles or fluids that were not discharged through the outlet conduit (5) by overflow of the outlet opening (6). The outlet port (27) also allows for the collection of samples during the production process. Furthermore, the outlet port (27) allows for the extraction of contents from the mixing chamber (2) in case of overpressure. This can happen, for example, when the velocity of the inlet flow is higher than the velocity of the outlet flow through the outlet conduit (5).

[0064] FIG. 7 shows a block diagram of a mixing system (20) according to the present invention.

[0065] Figure 7 shows a schematic representation of a mixing system (20) according to the invention, comprising a mixing device (1), a collection chamber (21), a first reservoir (22) and a second reservoir (23), and a pumping system (24, 25). Each reservoir (22, 23) is in fluid communication with one inlet conduit (3, 4) of the mixing device (1), and the collection chamber (21) is in fluid communication with the mixing chamber (2) via an outlet conduit (5). The pumping system (24, 25) is arranged to supply fluid from the reservoirs (22, 23) to the mixing chamber (2) via the inlet conduits (3, 4).

[0066] To prepare nanoparticles using the mixing device of the present invention, two miscible solvents are used, namely a first solvent and a second solvent. The first solvent is a good solvent for the material forming the nanoparticles and contains the material forming the nanoparticles and the active ingredient. The second solvent is an anti-solvent for the material forming the nanoparticles.

[0067] The first step is to introduce a first solvent and a second solvent into a first reservoir (22) and a second reservoir (23), respectively, which are connected to the mixing chamber by inlet conduits (3, 4). The solvents contained in the first reservoir (22) and the second reservoir (23) are then pumped into the mixing chamber at flow rates suitable for the formation of nanoparticles with the desired physicochemical properties. For this purpose, a pumping system (24, 25) is arranged between each reservoir (22, 23) and the mixing chamber (2).

[0068] The flow of the first and second solvents is controlled by adjusting the pressure and velocity. After adjusting the appropriate flow rate of each solvent, the pumping system (24, 25) is activated and the solvents are introduced into the mixing chamber (2) through different inlet conduits (3, 4).

[0069] The inlet conduits (3, 4) are positioned with their inlet portions inside the mixing device (1) to feed the fluids in the same direction (e.g., counterclockwise) into the mixing chamber (2). The agitating motion of the fluids is created by including enough fluid inside the mixing chamber (2) that does not induce excessive turbulence to promote the formation of nanoparticles without creating fluid motion that would degrade the resulting product.

[0070] When the liquid level inside the mixing chamber (2) containing the desired product exceeds the outlet opening (6), the formed nanoparticles enter the outlet conduit (6) and leave the mixing chamber (2), thus being extracted without the application of any force.

[0071] Finally, the formed nanoparticles are delivered to a collection chamber (21) where they can be stored or further processed.

Claims

1. A mixing device (1) for producing nanoparticles by mixing at least two fluids, comprising: a mixing chamber (2) having a base (12) and at least one wall (13); two inlet conduits (3, 4) configured to supply fluids into the mixing chamber (2), each inlet conduit (3, 4) having an inlet portion with a plurality of inlet openings (11), the inlet portion being disposed inside the mixing chamber (2), spaced apart from each other, and the inlet openings (11) being oriented to supply fluids into the mixing chamber (2) in a substantially tangential direction with respect to the inner surface of the wall (13); an outlet conduit (5) having an outlet opening (6), the outlet conduit (5) being configured such that the outlet opening (6) is positioned inside the mixing chamber (2) at a position higher than the position of the inlet openings (11); The mixing device (1) comprising.

2. The mixing device (1) according to claim 1, wherein at least a part of the outlet conduit (5) is arranged along the longitudinal axis of the mixing chamber (2).

3. The mixing device (1) according to claim 1, wherein the distance from the outlet opening (6) of the outlet conduit (5) to the base (12) of the mixing chamber (2) is adjustable.

4. The mixing device (1) according to claim 1, wherein one inlet conduit (3) is arranged behind the other inlet conduit (4) when the mixing device (1) is in an operating state.

5. The mixing device (1) according to claim 1, wherein the inner surface of the wall (13) of the mixing chamber (2) is shaped substantially as a rotating surface, preferably substantially as a cylindrical shape.

6. The mixing device (1) according to claim 5, wherein the rotation axis of the rotating surface is the longitudinal axis of the mixing chamber.

7. The mixing device (1) according to claim 1, wherein each inlet conduit (3, 4) is arranged such that the plurality of inlet openings are distributed along a direction substantially parallel to the longitudinal axis of the mixing chamber (2).

8. The mixing device (1) according to claim 1, wherein each inlet opening (11) comprises a spray nozzle having a nozzle opening, preferably the spray nozzle comprises size adjusting means for adjusting the size of the nozzle opening.

9. The mixing device (1) according to claim 1, further comprising a cover (10) configured to be coupled to the upper part of the mixing chamber (2).

10. The mixing device (1) according to claim 1, wherein at least one inlet conduit (3, 4) comprises a flow meter.

11. A mixing system (20) comprising the mixing device according to claim 1 and a collection chamber (21) in fluid communication with the mixing chamber (2) via the outlet conduit (5).

12. The mixing system (20) according to claim 11, further comprising a bent portion (9) configured to be coupled to the outlet conduit (5) and provide fluid communication with the collection chamber.

13. The mixing system (20) according to claim 11, further comprising two reservoirs (22, 23) each connected to one of the inlet conduits (3, 4).

14. The mixing system (20) according to claim 11, further comprising pumping means (24, 25) for supplying at least one fluid to the mixing chamber (2).

15. A method for producing nanoparticles using the mixing device (1) according to any one of claims 1 to 10 or the mixing system according to any one of claims 11 to 14, comprising: (a) obtaining a first solvent containing a material and an active ingredient for forming the nanoparticles; (b) obtaining a second solvent which is an anti-solvent for the material for forming the nanoparticles; (c) supplying the first solvent into the mixing chamber (2) via a first inlet conduit (3) and the second solvent via a second inlet conduit (4); and (d) enabling the liquid level inside the mixing chamber (2) to exceed the outlet opening (6) such that the formed nanoparticles penetrate into the outlet conduit (6) and exit the mixing chamber (2). A method comprising the steps.

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