Blade-free planetary mixer

Abstract

The present disclosure relates to blade-free planetary mixers (200) including a container holder (207a,b) comprising a heating element (208) and a power unit (209) fixedly mounted on the second rotary shaft (205) for providing electricity to the heating element. The disclosure also relates to methods for compounding active pharmaceutical ingredients using the blade-free planetary mixers.

Description

[0001] Blade-free planetary mixer

[0002] FIELD

[0003] The present disclosure relates to blade-free planetary mixers, in particular to heatable blade-free planetary mixers for compounding active pharmaceutical ingredients. The disclosure also relates to methods for compounding pharmaceutical formulations using the blade-free planetary mixers.

[0004] BACKGROUND

[0005] Blade-free planetary mixers (BFPMs) are mainly constituted of a cylindrical container with no obstacles nor agitators. The container is subjected to two rotational movements: one is a rotation around its geometric axis, the second is a revolution around an axis located at a given distance (Ro) as shown in Fig. 1. The cylinder is usually inclined at an angle a to improve mixing.

[0006] The BFPM technique is known since the 1970s. The BFPMs are usually used in industry to mix, synthesize, and aerate high viscosity products such as colloids, resins, pastes, creams, and paints.

[0007] WO201808592 disclosed that the friction occurring during the mixing by BFPM enables compounding certain pharmaceutical compositions simply by the material flow friction action without requiring the addition of external heat. As disclosed therein the superimposed revolution and rotation movement produces the desired melt.

[0008] The method disclosed in WO201808592 is formulation dependent. Although the melting without heating is achievable e.g., with gelatin-based materials, some other materials such as those including significant amounts of polyethylene glycol or sorbitol do not absorb heat but only dissipate heat.

[0009] Accordingly, there is still a need for further mixing methods for active pharmaceutical ingredients.

[0010] SUMMARY

[0011] It is an object of the present disclosure to provide a blade-free planetary mixer comprising a drive unit such as an electric motor; a first rotary shaft rotatably driven by the drive unit; a rotary arm fixedly mounted on the first rotary shaft, the rotary arm provided with a raised oblique or inclined portion at its distal end; a second rotary shaft positioned on the raised oblique or inclined portion of the rotary arm, the second rotary shaft being rotatably driven by a rotary drive mechanism; a container holder mounted on the second rotary shaft, the container holder comprising an electric resistance heating element; and a power unit mounted on the second rotary shaft for providing electricity to the electric resistance heating element.

[0012] It is also an object of the present disclosure to provide a method for preparing a compounded pharmaceutical composition using the blade-free planetary mixer of claim 1.

[0013] A number of exemplifying and non-limiting embodiments of the invention are described in accompanied dependent claims.

[0014] Various exemplifying and non-limiting embodiments of the invention and methods of operation, together with additional objects and advantages thereof, are best understood from the following description of specific exemplifying embodiments, when read in connection with the accompanying figures.

[0015] The verbs “to comprise” and “to include” are used in this document as open limitations that neither exclude nor require the existence of further unrecited 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", i.e., a singular form, throughout this document does not exclude a plurality.

[0016] BRIEF DESCRIPTION OF FIGURES

[0017] Figure 1 shows the principle of a blade-free planetary mixer. The curved arrows show direction of rotation.

[0018] Figures 2-4 show blade-free planetary mixers according to exemplary non-limiting embodiments of the present disclosure. The curved arrows show direction of rotation.

[0019] DESCRIPTION

[0020] 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.

[0021] In one aspect the present disclosure concerns a blade-free planetary mixer. A planetary mixer 200 according to an exemplary non-limiting embodiment is shown in figure 2. The mixer comprises a first rotary shaft 202 rotatably driven by a drive unit 201 such an electric motor, and a rotary arm 203 fixedly mounted on the first rotary shaft. The rotary arm is provided with a raised oblique or inclined portion 204 at its distal end. The mixer includes a second rotary shaft 205 positioned on the raised oblique of inclined portion of the rotary arm. The second rotary shaft is rotatably driven by a rotary drive 206 mechanism such as belts, pulleys and / or gear wheels. By adjusting gear or pulley size or number of teeth a desired gear ratio can be achieved. Rotary drive mechanisms are well known in the art. The rotary drive mechanism is omitted from the figures 2A, 3, and 4 for clarity. The second rotary shaft may also have a drive unit such as an electronic motor of its own.

[0022] The mixer 200 includes a container holder 207a mounted on the second rotary shaft for material to be mixed and heated.

[0023] The inclination enhances the mixing efficiency by allowing a more thorough and uniform distribution of the contents within a container. This inclination helps in creating a complex flow pattern improving the interaction between different layers of the mixture, thus ensuring homogeneous mixing. A particular inclination angle a is 45°. Decreasing the angle below 45° generally means that the flow dynamics become less intense in terms of axial deviation, potentially leading to a flow that resembles more closely a solid body rotation, which is less effective for mixing. If the inclination angle is increased beyond 45°, the mixer might experience more pronounced axial and radial flows. These intensified flows could potentially enhance mixing under certain conditions by increasing the interaction between different fluid layers. However, too steep an angle might also lead to inefficient mixing near the edges or top of the mixer, as the material might not circulate as effectively throughout the entire volume. This could result in uneven mixing or more significant separation of components, especially for fluids with varying densities or viscosities.

[0024] The container holder includes an electric resistance heating element 208, such as a resistance wire or a ceramic heater.

[0025] The mixer also includes a power unit 209 mounted on the second rotary shaft for providing electricity to the heating element. The mounting ensures that the power unit spins with the second rotary shaft. The mounting can be done using a coupler 210, which can be, for example, a quick-release coupler or a threaded coupler, allowing for easy attachment and detachment of the power unit.

[0026] In an embodiment the power unit comprises a generator such as an on-axis generator, configured to convert rotational energy generated by the second rotary shaft to electricity for heating the electric resistance heating element. Since all electronic components of the generator are mounted directly on the rotating axis, the need of complicated electrical connections between stationary and rotating parts is eliminated. Thus, the generator can be mechanically simple which reduces maintenance needs and increases reliability. Figure 3A shows section view of another exemplary blade-free planetary mixer 300 of the present disclosure. The power unit 309 of the blade-free planetary mixer includes a generator comprising a coil 311 and a permanent magnet 312 positioned around the coil. The coil and the permanent magnet are rotatable independently from each other. The blade- free planetary mixer also includes a mechanism 313 mounted on the raised oblique or inclined portion 304 of the rotary arm 303. The mechanism is configured to be pressed against the permanent magnet. This allows the permanent magnet to be rotated by a speed difference between the second rotation axis 305 and the rotary arm 303. The generated rotating magnetic field is able to provide electric field that can be transformed into electric current for heating the container. Figure 3B and 3C exemplifies situations where the mechanism allows and restricts the rotation of the permanent magnet, respectively.

[0027] Figure 4 shows a section view of still another exemplary blade-free planetary mixer 400 of the present disclosure. The power unit 409 of the blade-free planetary mixer includes a generator comprising a coil 411 and a permanent magnet 412 positioned around the coil. The coil is configured to rotate with the second rotary shaft 405, but the rotation of the permanent magnet is prevented by a mechanism 413 fixedly mounted on the raised oblique or inclined portion 404 of the rotary arm 403 and on the permanent magnet 412. This configuration allows for generating rotating magnetic field for providing electric field that can be transformed into electric current for heating the container when the mixer is in operation.

[0028] In another embodiment the power unit comprises a battery.

[0029] The container holder may have different sizes and shapes. The container holder 207a shown in figure 2A is for mixing and heating jars, whereas the container holder 207b of figure 2B is for mixing and heating various reservoirs such as syringe barrels 214. By using a blade-free mixer, the contents loaded in the syringe barrel can be mixed without risks of damage to the barrel. If using blades those can easily result in non-homogeneous mixing or scraping the barrel walls.

[0030] In an embodiment the container holder is exchangeable. Accordingly, the same blade-free mixer is suitable for mixing and heating materials positioned e.g., in jars and syringe barrels simply by selecting the size and shape of the container holder.

[0031] In an embodiment the blade-free planetary mixer includes temperature controlling means 215 such as one or more sensors and thermometers to control temperature of the container holder.

[0032] In an embodiment the temperature controlling means is coupled to the power unit or to the container holder so that it spins with the second rotary shaft, the container holder, and the power unit. This simplifies the electrical connections requirements drastically, since there is no need to transfer electric current or signals through high-speed rotating axis.

[0033] In an embodiment the temperature controlling means is a standalone unit configured to receive signals via wireless, optical and / or sonar means from control electronics 216 of the mixer.

[0034] In an embodiment the temperature controlling means is configured for setting mixing and / or preheating temperatures so that the container can achieve optimal temperature conditions while mixing.

[0035] The blade-free planetary mixer can be customized for specific pharmaceutical applications by adjusting the rotational speed and the heating element temperature. For instance, different types of active pharmaceutical ingredients (APIs) may require varying mixing durations and temperatures to achieve optimal compounding results. The design of the container holder can also be adapted to fit various container shapes and sizes, allowing for greater flexibility in the types of pharmaceutical compositions that can be prepared.

[0036] Additionally, the blade-free design of the mixer minimizes the risk of contamination and ensures that the APIs are evenly distributed throughout the mixture. This is particularly important for pharmaceutical applications where uniformity and purity are critical. The heating element's efficiency can be enhanced through the use of advanced materials such as high-temperature ceramics or metal alloys, which provide consistent and controlled heating.

[0037] The ability to control both the rotational movement and the heating process allows for precise adjustment of the mixing parameters, enabling the preparation of complex pharmaceutical formulations. This flexibility makes the blade-free planetary mixer an invaluable tool in pharmaceutical manufacturing, research, and development.

[0038] In another aspect the present disclosure concerns a method for preparing a compounded pharmaceutical composition using the blade-free planetary mixer, the method comprising the following steps: a)providing a blade-free planetary mixer 200 comprising a drive unit 201 such as an electric motor; a first rotary shaft 202 rotatably driven by the drive unit; a rotary arm 203 fixedly mounted on the first rotary shaft, the rotary arm provided with a raised oblique or inclined portion 204 at its distal end; a second rotary shaft 205 positioned on the raised oblique of inclined portion of the rotary arm, the second rotary shaft being rotatably driven by a rotary drive mechanism 206, and a container holder 207a mounted on the second rotary shaft, the container holder comprising an electric resistance heating element 208 and a power unit 209 mounted on the second rotary shaft for providing electricity to the heating element. b) providing a container 217 including at least one active pharmaceutical ingredient (API) and a pharmaceutical excipient base; c) positioning the container into the container holder; d) obtaining pre-determined or determining dispersing pattern parameters to obtain a melt, and e) subjecting the least one API and the pharmaceutical excipient to superimposed revolution and rotation movement and to heating on the container by said blade-free planetary mixer based on the pre-determined or determined parameters to obtain the melt.

[0039] A temperature range for the heating element is typically 30-100°C, depending on the specific requirements of the pharmaceutical ingredients being compounded.

[0040] In an embodiment the superimposed revolution and rotation movements is performed for less than 60 seconds to avoid over-processing.

[0041] It is known that G forces plays a big role depending on material and could be even up to 35 G for some resins, but for gels maybe 25 G maximum.

[0042] In an embodiment, the melt comprises 0.1-25 wt.-% API and 99.9-75 wt.-% a pharmaceutical excipient base. The pharmaceutical excipient base comprises typically one or more gelling agents, fillers, solvents, thickeners, preservatives, surfactants, pH adjusting agents, and / or sweeteners.

Claims

What is claimed is1 . A blade-free planetary mixer (200, 300, 400) comprising a drive unit (201 ) such as an electric motor; a first rotary shaft (202) rotatably driven by the drive unit; a rotary arm (203, 303, 403) fixedly mounted on the first rotary shaft, the rotary arm provided with a raised oblique or inclined portion (204, 304, 404) at its distal end; a second rotary shaft (205, 305, 405) positioned on the raised oblique or inclined portion of the rotary arm, the second rotary shaft being rotatably driven by a rotary drive mechanism (206) and a container holder (207a, 207b) mounted on the second rotary shaft, characterized in that the container holder comprises an electric resistance heating element (208) and that the blade-free planetary mixer comprises a power unit (209, 309, 409) mounted on the second rotary shaft for providing electricity to the electric resistance heating element.

2. The blade-free planetary mixer according to claim 1 , wherein the power unit comprises a generator configured to convert rotational energy of the second rotary shaft to electricity.

3. The blade-free planetary mixer according to claim 2, wherein the power unit (309) comprises a generator comprising a rotatable coil (311 ) and a rotatable permanent magnet (312) positioned around the coil, and wherein the blade-free planetary mixer comprises a mechanism (313) mounted to the raised oblique or inclined portion (304) of the rotary arm (303), wherein the mechanism is configured to be pressed against the permanent magnet to allow the permanent magnet to be rotated by a speed difference between the second rotary shaft (305) and the rotary arm (303).

4. The blade-free planetary mixer (400) according to claim 2, wherein the power unit (409) comprises a generator comprising a coil (411 ) and a permanent magnet (412) positioned around the coil, wherein the coil is configured to rotate with the second rotary shaft (405) and wherein the blade-free planetary mixer comprises a mechanism (413) fixedly mounted on raised oblique or inclined portion (404) of the rotary arm (403) and on the permanent magnet (412) for preventing the permanent magnet for rotating with the second rotary shaft.

5. The blade-free planetary mixer according to claim 1 , wherein the power unit comprises a battery.

6. The blade-free planetary mixer according to any one of claims 1 to 5, wherein the container holder is exchangeable.

7. The blade-free planetary mixer according to any one of claims 1 to 6 comprising a coupler (210) for attaching and detaching the power unit from and to the secondary rotary shaft.

8. The blade-free planetary mixer according to any one of claims 1 to 7 comprising means (215) for controlling temperature of the container holder.

9. The blade-free planetary mixer according to any one of claims 1 to 8, wherein the rotary drive mechanism is an electric motor.

10. A method for preparing a compounded pharmaceutical composition, the method comprising the following steps: a) providing a blade-free planetary mixer according to any one of claims 1 to 9; b) providing a container including at least one active pharmaceutical ingredient (API) and a pharmaceutical excipient base; c) positioning the container into the container holder; d) obtaining pre-determined or determining dispersing pattern parameters to obtain a melt, and e) said blade-free planetary mixer subjecting the least one API and the pharmaceutical excipient to superimposed revolution and rotation movement and to heating on the container based on the pre-determined or determined parameters to obtain the melt.11 . The method according to claim 10, wherein the heating is up to 100 °C.

12. The method according to claim 10 or 11 , wherein the superimposed revolution and rotation movements is performed for less than 60 seconds.

13. The method according to any one of claims 10 to 12 wherein the superimposed revolution and rotation movements include a maximal G force value of less than 35 g.

14. The method according to any one of claims 10 to 13, wherein the melt comprises 0.1- 25 wt.-% API and 99.9-75 wt.-% a pharmaceutical excipient base.

15. The method according to claim 10 to 14, wherein the pharmaceutical excipient base comprises one or more gelling agents, fillers, solvents, thickeners, preservatives, surfactants, pH adjusting agents, and / or sweeteners.

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