A stirring device and a high-speed centrifugal device using the same

Abstract

The application relates to the technical field of pharmaceutical preparation mixing processes, in particular to a stirring device and a high-speed centrifugal device adopting the stirring device, which comprises a stirring paddle and a directional rotor, the stirring paddle and the directional rotor are coaxially and oppositely arranged, and are used for providing opposite shearing forces when rotating. Compared with the prior art, the application has the advantages that when two or more materials with large particle size difference and large proportion difference are mixed, the materials can reach a uniform and stable state in a short time under the action of high shearing force, the RSD value of content detection of random sampling in the tank is at a low level, and the mixed materials can meet the tanking requirements of powder for inhalation preparations.

Description

Technical Field

[0001] This invention relates to the field of dry powder mixing technology for pharmaceutical preparations, and more specifically to a stirring device and a high-speed centrifuge device using the stirring device. Background Technology

[0002] Commonly used mixing equipment on the market includes V-type mixers, double cone mixers, three-dimensional mixers, and high-shear mixers. Materials are mixed by gravity-driven tumbling inside the drum, and the speed at the end of the impeller is relatively low. When there is a large difference in the proportion of two or more components, the mixing is not uniform and the mixing time is relatively long. The materials near the stirring paddle can achieve a uniform mixing state, but the powder floating on the upper surface of the container and hanging around the container cannot participate in the mixing, resulting in uneven product mixing. Summary of the Invention

[0003] The purpose of this invention is to overcome the shortcomings of the prior art and provide a device that can solve the problem of uneven mixing when the API and excipients of inhaled formulations have large differences in particle size and content percentage.

[0004] To achieve the above objectives, a stirring device is designed, including a stirring paddle and a directional rotor, wherein the stirring paddle and the directional rotor are coaxially arranged in opposite directions to provide shearing forces in opposite directions when rotating.

[0005] Preferably, the directional rotor is disposed inside the circumference of the rotating trajectory of the stirring paddle.

[0006] Preferably, the angle between the directional rotor and the horizontal plane is 15° to 65°, with the optimal range being 40° to 50°. During rotation, a downward airflow is generated, guiding the powder that rises during stirring back to the stirring blades.

[0007] Preferably, the stirring paddle includes several blades, which are inclined clockwise along the circumferential direction, and the directional rotor includes several rotors, which are inclined counterclockwise along the circumferential direction.

[0008] Preferably, the angle between the stirring blade and the horizontal plane is 15° to 65°, with the optimal range being 40° to 50°. During rotation, it generates an upward thrust and airflow, which lifts the powder at the bottom into the container.

[0009] A high-speed centrifugal device for mixing raw materials and excipients of dry powder inhalers using the aforementioned stirring device includes a high-speed power unit; a pot body, the bottom of which is provided with a drive shaft, the pot body being connected to the high-speed power unit via the drive shaft, the top of which is provided with a sealing cover, and the interior of which is provided with a sealed cavity; and at least one stirring device, which is sleeved on the top of the drive shaft.

[0010] Preferably, it also includes a discharge device, which is connected to the sealed cavity inside the pot, and the discharge device has a discharge port at its bottom.

[0011] Preferably, the discharge device further includes a discharge control rod, which moves in a limited position in the horizontal direction, and the starting position of the discharge control rod is located on the inner wall of the pot.

[0012] Preferably, it also includes a cooling water inlet and a cooling water outlet, wherein the cooling water inlet and the cooling water outlet are located on one side of the pot body, and the cooling water outlet is located above the cooling water inlet.

[0013] Preferably, it also includes a temperature probe, which is disposed on one side of the pot body to monitor the temperature of the sealed cavity inside the pot.

[0014] Preferably, it also includes a temperature control jacket, which is disposed on the outer wall of the pot body.

[0015] Compared with existing technologies, the advantages of this invention are as follows: when mixing two or more materials with large differences in particle size and proportion, a uniform and stable state can be achieved in a short time under the action of high shear force. The RSD value of random sampling and content detection in the tank is at a low level, ensuring that the mixed material can meet the powder packaging requirements of inhalation preparations. Compared with traditional high shear mixers, the rotation speed range of this novel experimental mixer is 100-3000 rpm, and the blade tip linear velocity can reach 20 m / s, which is at least twice the blade tip linear velocity of HSG. The higher energy input can make the material mix more uniformly, and the mixing uniformity RSD is usually less than 2%, or even less than 1% (the specific mixing uniformity varies depending on the product characteristics and mixing ratio). Attached Figure Description

[0016] Figure 1 This is an overall structural diagram of the present invention;

[0017] Figure 2 This is a top view of the stirring device of the present invention;

[0018] Figure 3 This is a front view of the stirring device of the present invention;

[0019] Figure 4 This is a diagram showing the adaptation of the pot body and the high-speed rotating power device of the present invention.

[0020] Figure 5 This is a structural diagram of the dual stirring device of the present invention;

[0021] In the diagram: 1. Sealing cover, 2. Pot body, 3. Temperature control jacket, 4. Feeding control rod, 5. Discharge port, 6. High-speed power unit, 7. Cooling water outlet, 8. Temperature probe, 9. Directional rotor, 10. Main stirring paddle, 11. Cooling water inlet, 12. Drive shaft, 13. Stirring device. Detailed Implementation

[0022] See Figure 1 , Figure 2 and Figure 3 A stirring device and a high-speed centrifuge using the stirring device are disclosed, comprising: a high-speed power unit and a pot body. The pot body is connected to the high-speed power unit via a drive shaft, which is located at the bottom of the pot body. A sealing cover is provided on the top of the pot body, and a sealed cavity is located inside the pot body. A stirring device is provided at the bottom of the sealed cavity. The stirring device includes a stirring paddle and a directional rotor. The stirring paddle includes several blades arranged clockwise along the circumference. The directional rotor includes several rotors arranged counterclockwise along the circumference. The stirring paddle and the directional rotor are coaxially arranged in opposite directions and sequentially fitted onto the top of the drive shaft, providing shearing forces in opposite directions during rotation.

[0023] One side of the pot body also includes a discharge device, which communicates with the sealed cavity inside the pot body. The discharge device has a discharge port at its bottom and a discharge control rod, which can move horizontally and is initially positioned on the inner wall of the pot body. The other side of the pot body also includes a cooling water outlet and a cooling water inlet, and a temperature probe to monitor the temperature of the sealed cavity inside the pot body in real time. A temperature control jacket is also included on one side of the pot body.

[0024] After mixing, adjust the centrifugal agitator to a low speed and drag the discharge control lever outward. The mixed product will leave the pot under the push of the agitator and be collected from the discharge port.

[0025] See Figure 4 and Figure 5 The pot body is available in various sizes, including 1L, 5L, 10L, 20L, 30L and 50L. Every three adjacent pot body models can share a high-speed power unit. When the volume of the pot body increases, the stirring device can be equipped with multiple stirring paddles and directional rotors to achieve a better mixing effect. The number of stirring paddles and directional rotors increases proportionally with the increase of the pot body volume.

[0026] Example 1

[0027] Lactose monohydrate (99.0g) and inhalation raw material A (1.0g) were mixed in the device of the present invention for 10 minutes and allowed to stand for an appropriate time to prepare a uniformly mixed powder 1. Three sites were taken from the upper, middle and lower layers, and one site was taken from the center for content detection.

[0028] Lactose monohydrate (99.5g) and inhalation raw material B (0.5g) were mixed in the device of the present invention for 10 minutes and allowed to stand for an appropriate time to prepare a uniformly mixed powder 2. Three sites were taken from the upper, middle and lower layers, and one site was taken from the center for content detection.

[0029] Lactose monohydrate (98.5g) and inhalation raw material B (1.5g) were mixed in the device of the present invention for 10 minutes and allowed to stand for an appropriate time to prepare a uniformly mixed powder 3. Three sites were taken from the upper, middle and lower layers, and one site was taken from the center for content detection.

[0030] The RSD values ​​of the contents of the three powders were calculated using a high-performance liquid chromatography system. The results are as follows: the RSD% (n=10) values ​​of the contents of mixed powder 1, mixed powder 2 and mixed powder 3 are 1.62, 2.49 and 1.54, respectively.

[0031] Example 2

[0032] Lactose monohydrate (293.54g) and ferric oxide (1.6g) were mixed and placed in a mixer using a sandwich method. The bottom layer was 96.56g of lactose, the first layer was 0.73g of ferric oxide, the middle layer was 105.63g of lactose, the second layer was 0.73g of ferric oxide, and the third layer was 91.35g of lactose. The mixing speed was set to 2000rpm. At mixing times of 1, 3, 5, 7, and 9 minutes, detection sites were taken from the top, middle, and bottom layers of the container, and one site was taken from the center for content detection.

[0033] Iron content was determined using inductively coupled plasma optical emission spectrometry (IPC-OES). The equipment settings were as follows: RF power: 1.3 kW, plasma gas flow rate: 10 L / min, auxiliary gas flow rate: 0.5 L / min, nebulizer flow rate: 0.55 L / min, peristaltic pump flow rate: 1.5 L / min. The test results are shown in the table below.

[0034]

[0035]

[0036] The iron oxide content measured after mixing for 9 minutes was 4.86 mg / g, which is very close to the theoretical content. The relative standard deviation (RSD) was 2.21%, indicating that the material was mixed evenly.

[0037] When mixing two or more materials with significantly different particle sizes and proportions, a homogeneous and stable state can be achieved in a short time under high shear force. The RSD value of random sampling and content detection in the tank is at a low level, ensuring that the mixed material can meet the powder packaging requirements of inhaled preparations. Compared with traditional high-shear mixers, the rotation speed range of this novel mixer is 100-3000 rpm, and the blade tip linear velocity can reach 20 m / s, which is at least twice that of the HSG blade tip linear velocity. The higher energy input can make the material mix more uniformly, and the mixing uniformity RSD is usually less than 2%, or even less than 1% (the specific mixing uniformity varies depending on the product characteristics and mixing ratio).

[0038] The above description is merely a specific embodiment of the invention, but the scope of protection of the invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the technical scope disclosed in the invention, based on the technical solutions and novel concepts of the invention, should be covered within the scope of protection of the invention.

Claims

1. A stirring device, comprising a stirring paddle, characterized in that... It also includes directional rotors, The stirring paddle and the directional rotor are arranged coaxially and in opposite directions to provide shearing forces in opposite directions when rotating; The directional rotor is disposed inside the circumference of the rotation trajectory of the stirring paddle; The stirring paddle includes several blades, which are inclined clockwise along the circumference. The directional rotor includes several rotors, which are inclined counterclockwise along the circumference.

2. The stirring device as described in claim 1, characterized in that... The angle between the directional rotor and the horizontal plane is 15°~65°, and the angle between the blade and the horizontal plane is 15°~65°.

3. A high-speed centrifugal device for mixing raw materials and excipients of dry powder inhalers, employing the stirring device as described in any one of claims 1-2, characterized in that... include High-speed power unit; The pot body has a drive shaft at the bottom and is connected to a high-speed power device via the drive shaft. The top of the pot body has a sealing cover and the inside of the pot body has a sealing cavity. At least one stirring device is fitted onto the top of the drive shaft.

4. The high-speed centrifuge device for mixing raw materials and excipients in dry powder inhalers as described in claim 3, characterized in that... It also includes a discharge device, which is connected to the sealed cavity inside the pot, and the discharge device has a discharge port at the bottom.

5. The high-speed centrifuge device for mixing raw materials and excipients in dry powder inhalers as described in claim 4, characterized in that... The discharge device also includes a discharge control rod, which moves in a limited position in the horizontal direction, and the starting position of the discharge control rod is located on the inner wall of the pot.

6. The high-speed centrifuge device for mixing raw materials and excipients in dry powder inhalers as described in claim 3, characterized in that... It also includes a cooling water inlet and a cooling water outlet, which are located on one side of the pot body, with the cooling water outlet located above the cooling water inlet.

7. The high-speed centrifuge device for mixing raw materials and excipients of dry powder inhalers as described in claim 3, characterized in that... It also includes a temperature probe, which is set on one side of the pot body to monitor the temperature of the sealed cavity inside the pot.

8. The high-speed centrifuge device for mixing raw materials and excipients of dry powder inhalers as described in claim 3, characterized in that... It also includes a temperature control jacket, which is located on the outside of the pot body and controls the temperature of the pot body through circulating constant temperature water or refrigerant.

Images