Method for determining particle size of salbutamol sulfate

Abstract

The present invention discloses a salbutamol sulfate particle size determination method, and relates to the field of particle size determination methods, the salbutamol sulfate and a dispersion medium form a mixed liquid for salbutamol sulfate particle size detection, the dispersion medium can disperse salbutamol sulfate particles therein, the salbutamol sulfate is difficult to dissolve in the dispersion medium. According to the invention, the salbutamol sulfate particles can be dispersed in the dispersion medium, and the salbutamol sulfate and the dispersion medium form a mixed liquid to carry out particle size detection on the salbutamol sulfate, so that the salbutamol sulfate is uniformly dispersed; therefore, the purpose of improving the particle size and particle size distribution determination accuracy and repeatability of salbutamol sulfate is achieved.

Description

Technical Field

[0001] The invention relates to the field of particle size determination methods, and in particular to a salbutamol sulfate particle size determination method. Background Art

[0002] Salbutamol sulfate is a β2 receptor agonist that stimulates the β2 receptors on the respiratory smooth muscle to relax the bronchial smooth muscle, thereby dilating the bronchi, increasing respiratory ventilation, and improving respiratory function. As a drug, salbutamol sulfate can effectively relieve symptoms such as dyspnea and wheezing caused by bronchospasm, especially for patients with acute attacks of bronchial asthma, and can quickly improve their respiratory conditions.

[0003] In aerosol and powder spray, salbutamol sulfate exists in solid form, and the control of its particle size is particularly critical. The difference in particle size may affect the release effect and clinical efficacy of the drug, so the particle size and particle size distribution of salbutamol sulfate are key evaluation indicators of the product, and strict quality control of its particle size is required. Usually, salbutamol sulfate needs to be crushed before use, and in actual research, the crushed salbutamol sulfate is prone to agglomeration and is not easy to disperse. This phenomenon greatly affects the determination of particle size and particle size distribution, and the data obtained are highly volatile, and accurate and reliable test results cannot be obtained, which is unfavorable for the quality control of medicines. Therefore, it is of great significance to develop a salbutamol sulfate particle size detection method with high accuracy and good repeatability.

[0004] In view of this, this application is hereby filed. Summary of the invention

[0005] The object of the present invention is to provide a method for measuring the particle size of salbutamol sulfate. The method comprises the following steps: using a dispersion medium to disperse salbutamol sulfate therein, and forming a mixed liquid with the dispersion medium to detect the particle size of salbutamol sulfate, so as to solve the problem that the pulverized salbutamol sulfate in the prior art is prone to agglomeration and is difficult to disperse, thus affecting the measurement of the particle size and particle size distribution.

[0006] The embodiment of the present invention is achieved through the following technical scheme: The embodiment of the present invention provides a method for measuring the particle size of salbutamol sulfate, comprising forming a mixed liquid with salbutamol sulfate and a dispersion medium to detect the particle size of salbutamol sulfate, wherein the dispersion medium can disperse salbutamol sulfate particles therein, and the salbutamol sulfate is insoluble in the dispersion medium.

[0007] Optionally, the dispersion medium includes at least one of isopropanol, n-hexane, cyclohexane, and cycloheptane.

[0008] Specifically, the embodiments of the present invention select specific dispersion media, such as isopropanol, n-hexane, cyclohexane, cycloheptane, etc., which are poor solvents for salbutamol sulfate and can effectively disperse salbutamol sulfate therein. Since salbutamol sulfate is poorly soluble in these dispersion media, this incompatibility forces the particles to remain dispersed, avoiding agglomeration, thereby making particle size detection more accurate.

[0009] Optionally, the dispersion medium is isopropanol.

[0010] Optionally, the mass of the salbutamol sulfate accounts for 0.05% to 0.5% of the total mass of the mixed liquid.

[0011] Specifically, in particle size detection technologies such as laser particle size analysis, there needs to be sufficient particle scattered light signals to ensure that the instrument can accurately detect the particles. Each time the test is performed, the amount of salbutamol sulfate in the sample pool needs to be fixed. If the concentration of salbutamol sulfate is too low, the scattering signal may be too weak, resulting in inaccurate test results; however, at lower concentrations, the possibility of contact and agglomeration between particles is reduced, which helps to maintain the dispersed state of the particles, thereby obtaining more accurate particle size measurements. Therefore, if the concentration of salbutamol sulfate is too high, it may cause an increase in measurement errors, because the complex scattering and overlapping scattering signals of the particles may interfere with the measurement results. In an embodiment of the present invention, ensuring that the concentration of the sample is within the range of 0.05% to 0.5% can ensure that the sample is representative, that is, the particle size distribution of the sample can reflect the particle size distribution of the entire batch, and can improve the accuracy and repeatability of particle size detection.

[0012] Optionally, the mass of the salbutamol sulfate accounts for 0.05% to 0.1% of the total mass of the mixed liquid.

[0013] Optionally, before the mixed liquid is subjected to particle size detection of salbutamol sulfate, the mixed liquid is dispersed using an ultrasonic instrument.

[0014] Specifically, the ultrasonic wave generated by the ultrasonic instrument forms a pressure change in the liquid, produces tiny bubbles, and these bubbles produce strong shock waves when they collapse, thereby breaking up the agglomerates of the salbutamol sulfate particles and realizing the uniform dispersion of the particles. When the ultrasonic wave propagates in the liquid at the same time, it can also produce high-speed micro-flow and shearing force, and these shearing forces can further help to break up the agglomerates of the particles and promote the uniform dispersion of the particles. Therefore, in an embodiment of the present invention, by ultrasonic dispersion, it can be further ensured that the salbutamol sulfate particles are evenly distributed in the dispersion medium, reducing the possibility of the particle size detection error caused by agglomeration, thereby improving the accuracy of the test result. Compared with traditional methods such as manual stirring, ultrasonic dispersion can disperse particles more quickly and thoroughly, reducing the loss of the sample in the process.

[0015] Optionally, before forming the mixed liquid, the salbutamol sulfate particles are placed in an environment with a relative humidity of 50% to 90% for 0.5 to 10 hours.

[0016] Specifically, high humidity treatment can reduce the surface energy of salbutamol sulfate particles and improve dispersibility. In an embodiment of the present invention, the salbutamol sulfate particles pretreated with high humidity can be more evenly dispersed in the dispersion medium during the subsequent dispersion process due to the reduction in surface energy and improvement in dispersibility, which can further improve the accuracy of the detection results.

[0017] At the same time, too low relative humidity may lead to electrostatic aggregation between salbutamol sulfate particles, while too high relative humidity may lead to excessive moisture absorption or deliquescence. Therefore, choosing a relative humidity range of 50% to 90% can avoid extreme moisture absorption or water loss and maintain the stability of particle properties. Similarly, the placement time also needs to be controlled within an appropriate range.

[0018] Optionally, the relative humidity of the environment where the salbutamol sulfate particles are placed is 70% to 90%.

[0019] Optionally, the salbutamol sulfate particles are placed in an environment with a relative humidity of 50% to 90% for 4 to 6 hours.

[0020] Optionally, the detector for detecting the particle size of salbutamol sulfate is a Synpatek HEILSIBR laser particle size analyzer, and the Synpatek HEILSIBR laser particle size analyzer includes a sample pool. The conditions for detecting salbutamol sulfate include setting the optical concentration of the sample pool to 5% to 20% and the stirring speed to 500 to 1500 rpm.

[0021] Specifically, the Synpatec HEILSIBR laser particle size analyzer is an instrument for measuring particle size distribution, including a sample pool, which can detect the particle size of granular samples such as salbutamol sulfate. The optical concentration refers to the light shielding rate of particles in the sample pool. For the detection of salbutamol sulfate, the optical concentration is set to 5% to 20%. This range of optical concentration can ensure that the laser can effectively pass through the sample pool and scatter, while ensuring that the intensity of the scattered signal is sufficient for accurate measurement.

[0022] The stirring speed refers to the speed at which the dispersed medium flows in the sample pool. For the detection of salbutamol sulfate, the stirring speed is set at 500-1500rpm. An appropriate stirring speed helps to maintain a uniform distribution of particles in the sample pool, prevent particles from settling or agglomerating, and thus obtain more accurate particle size measurement results. A stirring speed range of 500-1500rpm can ensure that the particles are fully dispersed while avoiding particle breakage or excessive turbulence of the liquid in the sample pool that may be caused by excessive stirring speed.

[0023] Compared with the prior art, the embodiments of the present invention have the following advantages and beneficial effects:

[0024] 1. A kind of salbutamol sulfate particle size determination method provided by an embodiment of the present invention, salbutamol sulfate and a dispersion medium form a mixed liquid, wherein the selection of the dispersion medium is based on the poor solvent properties of the salbutamol sulfate and the salbutamol sulfate, i.e., salbutamol sulfate is insoluble in these dispersion media. By using a poor solvent as a dispersion medium, the salbutamol sulfate particles can be uniformly dispersed in the medium, and agglomeration is avoided, thereby improving the accuracy of the particle size and particle size distribution determination, and the method can ensure that the dispersion state of the salbutamol sulfate particles in each experiment is consistent on the basis of the type and conditions (such as ultrasonic power and time) of the control dispersion medium, and enhances the repeatability of the experimental results.

[0025] 2. In the embodiment of the present invention, isopropyl alcohol is preferably used as the dispersion medium because isopropyl alcohol has a stronger affinity for salbutamol sulfate than n-hexane, cyclohexane, and cycloheptane, and can better disperse salbutamol sulfate particles and maintain the dispersed state of the particles even at a lower concentration. In addition, compared with other solvents, isopropyl alcohol is relatively safe and has less impact on the environment.

[0026] 3. Before mixing the liquid in the mixed liquid of the embodiment of the present invention, the salbutamol sulfate particles are placed in an environment with high relative humidity, because the high humidity treatment can reduce the surface energy of the salbutamol sulfate particles. For salbutamol sulfate, this treatment of reducing the surface energy helps to reduce the cohesion between the particles, making it easier to disperse in the dispersion medium. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0028] Figure 1 This is a schematic diagram of multiple detection results of Example 3 of the present invention;

[0029] Figure 2 It is a schematic diagram of the results of multiple tests on the particle size of salbutamol sulfate without relative humidity;

[0030] Figure 3 This is a schematic diagram comparing the test results of Examples 1-4;

[0031] Figure 4 It is a schematic diagram comparing the test results of Example 3 and Examples 5-7;

[0032] Figure 5 This is a schematic diagram comparing the test results of Example 3, Example 8 and Example 9;

[0033] Figure 6 It is a schematic diagram comparing the test results of Example 3 and Examples 10-12. DETAILED DESCRIPTION

[0034] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Generally, the components of the embodiments of the present invention described and shown in the drawings here can be arranged and designed in various different configurations.

[0035] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the invention claimed for protection, but merely represents selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0036] It should be noted that similar reference numerals and letters denote similar items in the following drawings, and therefore, once an item is defined in one drawing, further definition and explanation thereof is not required in subsequent drawings.

[0037] In the description of the present invention, it should be noted that the terms "first", "second", "third", etc. are only used to distinguish the description and cannot be understood as indicating or implying relative importance.

[0038] Example

[0039] Generally speaking, the crushed salbutamol sulfate raw material has a higher surface energy and greater viscosity, making it easy to aggregate and difficult to disperse. This phenomenon greatly affects the determination of particle size and particle size distribution. The data obtained is highly volatile, and accurate and reliable test results cannot be obtained.

[0040] In order to solve this problem, an embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate, comprising the following steps:

[0041] Step 1: Sample processing

[0042] (1) Environmental adjustment: The solid powder of salbutamol sulfate is placed in a test chamber with a relative humidity controlled at 50% to 90%. The purpose of this step is to adjust the surface moisture of the salbutamol sulfate particles to reduce their surface energy and the adhesion between the particles, thereby improving their dispersibility in the dispersion medium;

[0043] (2) Storage time: The salbutamol sulfate granules are placed in the above environment for 0.5 to 10 hours. This period of time is sufficient for the granules to reach moisture equilibrium, while avoiding changes in the properties of the granules that may be caused by placing them for too long.

[0044] Step 2: Sample preparation

[0045] (1) Weighing: Accurately weigh the salbutamol sulfate particles and the dispersion medium, with the mass of salbutamol sulfate accounting for 0.05% to 0.5% of the total mass of the mixed liquid;

[0046] (2) Mixing: Add the weighed salbutamol sulfate and isopropanol (or n-hexane, cyclohexane, cycloheptane) into a reagent bottle;

[0047] (3) Ultrasonic dispersion: Use an ultrasonic instrument to disperse the mixed solution. Set the power of the Biosafer900 ultrasonic instrument to 540W-900W, use a Φ6mm amplitude rod, and the dispersion time is 1-10 minutes. This step breaks up the particle agglomerates through mechanical action and cavitation effect to achieve uniform dispersion of the particles.

[0048] Step 3: Sample testing

[0049] (1) Sample transfer: Pipette the dispersed sample mixture and add it to the sample pool of the Synpatec HEILSIBR laser particle size analyzer;

[0050] (2) Optical density adjustment: adjust the optical density of the sample in the sample cell to 5% to 20%, preferably 10%;

[0051] (3) Stirring speed setting: Set the stirring speed of the sample pool to 500-1500 rpm, preferably 1000 rpm. An appropriate stirring speed helps maintain the uniformity of the sample during the detection process and prevent particle sedimentation;

[0052] (4) Particle size detection: Start the laser particle size analyzer to detect the particle size of the sample. The instrument will analyze and provide particle size distribution data based on the scattering of laser and particles.

[0053] In the embodiment of the present invention, the crushed salbutamol sulfate is placed in an environment with a relative humidity of 50% to 90% for 0.5 to 10 hours, and then a poor solvent for salbutamol sulfate such as isopropanol, n-hexane, cyclohexane, cycloheptane, etc. is used as a dispersion medium, so that the salbutamol sulfate can be evenly dispersed in the medium, which is suitable for particle size and particle size distribution detection, and the detection result is accurate and stable. In order to improve the persuasiveness of the embodiment of the present invention, the embodiment of the present invention will be experimentally verified as follows:

[0054] Example 1

[0055] The embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate, comprising the following steps:

[0056] Step 1: Sample processing

[0057] (1) Environmental adjustment: placing salbutamol sulfate solid powder in a test chamber where the relative humidity is controlled at 50%;

[0058] (2) Storage time: Place the salbutamol sulfate granules in the above environment for 4 hours;

[0059] Step 2: Sample preparation

[0060] (1) Weighing: Accurately weigh the salbutamol sulfate granules and isopropyl alcohol, with the mass of salbutamol sulfate accounting for 0.1% of the total mass of the mixed liquid;

[0061] (2) Mixing: Add the weighed salbutamol sulfate and isopropyl alcohol into a reagent bottle;

[0062] (3) Ultrasonic dispersion: The mixed solution was dispersed using an ultrasonic instrument, Biosafer900 with a power of 540 W and a Φ6 mm amplitude rod, and the dispersion time was 10 min.

[0063] Step 3: Sample testing

[0064] (1) Sample transfer: Pipette the dispersed sample mixture and add it to the sample pool of the Synpatec HEILSIBR laser particle size analyzer;

[0065] (2) Optical density adjustment: adjust the optical density of the sample in the sample pool to 10%;

[0066] (3) Stirring speed setting: Set the stirring speed of the sample cell to 1000 rpm;

[0067] (4) Particle size detection: Start the laser particle size analyzer to detect the particle size of the sample.

[0068] Example 2

[0069] The embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate. The difference from Embodiment 1 is that the solid powder of salbutamol sulfate is placed in a test box with a relative humidity controlled at 70%, and the other steps are the same.

[0070] Example 3

[0071] The embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate. The difference from Embodiment 1 is that the solid powder of salbutamol sulfate is placed in a test box with a relative humidity controlled at 80%, and the other steps are the same.

[0072] The test results of Example 3 were repeated several times. Figure 1 As shown, Figure 2 Based on Example 3, the test results of multiple repetitions with "Step 1" removed, that is, the sample treatment step removed and other steps remaining unchanged, are obtained by Figure 1 and Figure 2 By comparison, Figure 2 The particle size test results of salbutamol sulfate without relative humidity are unstable, the test results vary greatly each time, and the repeatability is poor. The test results of the test sample are D 10 , D 50 , D 90 The relative standard deviations of the results were 5.4%, 22.1% and 37.3% respectively. The multiple test results of Example 3 of the present invention are stable, accurate and reproducible. 10 , D 50 , D 90 The relative standard deviations are 1.2%, 1.6% and 1.9% respectively. It can be seen that the high humidity treatment of the salbutamol sulfate raw material reduces the surface energy of the salbutamol sulfate, makes the salbutamol sulfate easier to disperse, and improves the accuracy and repeatability of the detection.

[0073] Example 4

[0074] The embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate. The difference from Embodiment 1 is that the solid powder of salbutamol sulfate is placed in a test box with a relative humidity controlled at 90%, and the other steps are the same.

[0075] Example 5

[0076] The embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate, which is different from the embodiment 3 in that the salbutamol sulfate particles are placed for 0.5 hours, and the other steps are the same.

[0077] Example 6

[0078] The embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate, which is different from the embodiment 3 in that the salbutamol sulfate particles are placed for 6 hours, and the other steps are the same.

[0079] Example 7

[0080] The embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate, which is different from the embodiment 3 in that the salbutamol sulfate particles are placed for 10 hours, and the other steps are the same.

[0081] Example 8

[0082] The embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate, which is different from the embodiment 3 in that the mass of salbutamol sulfate accounts for 0.05% of the total mass of the mixed liquid, and the remaining steps are the same.

[0083] Example 9

[0084] The embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate, which is different from the embodiment 3 in that the mass of salbutamol sulfate accounts for 0.5% of the total mass of the mixed liquid, and the remaining steps are the same.

[0085] Example 10

[0086] The embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate, which is different from Example 3 in that salbutamol sulfate particles and cyclohexane are accurately weighed, and the weighed salbutamol sulfate and cyclohexane are added to a reagent bottle, and the remaining steps are the same.

[0087] Embodiment 11

[0088] The embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate, which is different from Example 3 in that salbutamol sulfate particles and n-hexane are accurately weighed, and the weighed salbutamol sulfate and n-hexane are added to a reagent bottle, and the remaining steps are the same.

[0089] Example 12

[0090] The embodiment of the present invention provides a method for detecting the particle size of salbutamol sulfate, which is different from Example 3 in that salbutamol sulfate particles and cycloheptane are accurately weighed, and the weighed salbutamol sulfate and cycloheptane are added to a reagent bottle, and the remaining steps are the same.

[0091] The parameters of Examples 1-12 are sorted and compared, as shown in Table 1 below.

[0092] Table 1

[0093]

[0094] The test results of Examples 1-12 are shown in Table 2 below.

[0095] Table 2

[0096]

[0097] From Table 2, Figure 3 , Figure 4 , Figure 5 and Figure 6 Combined, we can see that:

[0098] (1) By comparing Examples 1-4, it can be seen that the relative humidity of the test box cannot be too low. When the relative humidity is too low, the salbutamol sulfate particles will agglomerate, resulting in a particle size test result of D 50 Therefore, the relative humidity of the environment where the salbutamol sulfate particles are placed is preferably 70%-90%.

[0099] (2) By comparing Example 3 with Examples 5-7, the placement time cannot be too short or too long. If the time is too short, the surface of the salbutamol sulfate particles can cause the particles to aggregate, resulting in a particle size test result of D 50 The particle size test results showed no significant difference when the time was prolonged, indicating that the high humidity treatment time was not too long. Therefore, the time for the salbutamol sulfate particles to be placed in a high humidity environment is preferably 4 to 6 hours.

[0100] (3) By comparing Example 3 with Examples 8-9, it can be seen that when the concentration of salbutamol sulfate in the mixed liquid is in the range of 0.05% to 0.5%, there is no significant difference in the particle size detection results. However, the higher the concentration of salbutamol sulfate in the mixed liquid, the more difficult it is for the operator to transfer the mixed liquid, resulting in an increase in measurement error, which in turn interferes with the measurement results. Therefore, the concentration of salbutamol sulfate in the mixed liquid is preferably 0.05% to 0.1%.

[0101] (4) By comparing Examples 3 and 10-12, it can be seen that when isopropyl alcohol, cyclohexane, n-hexane, and cycloheptane are used as dispersion media, there is no significant difference in the particle size detection results. Compared with cyclohexane, n-hexane, and cycloheptane as dispersion media, isopropyl alcohol is safer to use and has less impact on operators and the environment. Therefore, isopropyl alcohol is preferably used as the dispersion medium.

[0102] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included in the protection scope of the present invention. It should be noted that the structures or components illustrated in the accompanying drawings are not necessarily drawn to scale, and the present invention omits the description of known components and processing technologies and processes to avoid unnecessary limitations on the present invention.

Claims

1. A method for measuring the particle size of salbutamol sulfate, characterized in that: The method comprises forming a mixed liquid with salbutamol sulfate and a dispersion medium to detect the particle size of the salbutamol sulfate, wherein the dispersion medium can disperse the salbutamol sulfate particles therein, and the salbutamol sulfate is poorly soluble in the dispersion medium.

2. A method for measuring the particle size of salbutamol sulfate according to claim 1, characterized in that: The dispersion medium includes at least one of isopropanol, n-hexane, cyclohexane and cycloheptane.

3. A method for measuring the particle size of salbutamol sulfate according to claim 2, characterized in that: The dispersion medium is isopropanol.

4. A method for measuring the particle size of salbutamol sulfate according to any one of claims 1 to 3, characterized in that: The mass of the salbutamol sulfate accounts for 0.05% to 0.5% of the total mass of the mixed liquid.

5. A method for measuring the particle size of salbutamol sulfate according to claim 4, characterized in that: The mass of the salbutamol sulfate accounts for 0.05% to 0.1% of the total mass of the mixed liquid.

6. A method for measuring the particle size of salbutamol sulfate according to claim 1, characterized in that: Before the particle size of salbutamol sulfate is detected on the mixed liquid, the mixed liquid is dispersed using an ultrasonic instrument.

7. A method for measuring the particle size of salbutamol sulfate according to claim 1, characterized in that: Before forming the mixed liquid, the salbutamol sulfate particles are placed in an environment with a relative humidity of 50% to 90% for 0.5 to 10 hours.

8. A method for measuring the particle size of salbutamol sulfate according to claim 7, characterized in that: The relative humidity of the environment where the salbutamol sulfate particles are placed is 70% to 90%.

9. A method for measuring the particle size of salbutamol sulfate according to claim 7, characterized in that: The salbutamol sulfate particles are placed in an environment with a relative humidity of 50% to 90% for 4 to 6 hours.

10. A method for measuring the particle size of salbutamol sulfate according to claim 1, characterized in that: The detector for detecting the particle size of salbutamol sulfate is a Synpatek HEILSIBR laser particle size analyzer, which includes a sample pool. The conditions for detecting salbutamol sulfate include setting the optical concentration of the sample pool to 5% to 20% and the stirring speed to 500-1500rpm.

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