A magnesium stearate and sodium dodecyl sulfate co-treated product and its preparation method

Abstract

This invention discloses a co-treated product of magnesium stearate and sodium dodecyl sulfate and its preparation method, belonging to the field of pharmaceutical excipient technology. The co-treated product is composed of magnesium stearate and sodium dodecyl sulfate in a mass ratio of 94:6, with a drying loss ≤5%, a particle size D50 of 5-30 μm, and a bulk density of 0.05-0.30 g / cm³. 3 The preparation method includes: first, synthesizing magnesium stearate with specific physicochemical properties; then, mixing it with sodium dodecyl sulfate in an ethanol-water solution in a certain proportion to form a slurry; and finally, spray drying after dispersion treatment. This co-treated compound solves the problems of uneven physical mixing and poor batch stability. In tablet applications, it exhibits excellent lubricity and significantly promotes tablet disintegration and drug dissolution, effectively mitigating the "over-lubricating" effect of magnesium stearate. The overall performance of tablet hardness and disintegration time is superior to that of magnesium stearate alone and its physical mixtures.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical excipient synthesis technology, and in particular to a magnesium stearate sodium dodecyl sulfate co-treated compound and its preparation method. Background Technology

[0002] Currently, in the direct compression process of pharmaceutical tablets, lubricants are key excipients ensuring smooth tableting. Their main functions are to reduce friction between the granules and the die, prevent sticking, improve the yield rate of tablet weight variation, and enhance the flowability and compressibility of the material. Commonly used lubricants in the industry include magnesium stearate, talc, hydrogenated vegetable oil, and polyethylene glycol compounds. Among these, magnesium stearate is the most popular choice due to its excellent lubrication properties, good chemical stability, and relatively low cost, with a typical addition amount of 0.2%–5.0% (by total tablet weight). In practical applications, magnesium stearate is usually added directly to the mixing process in commercially available powder form, or used after simple sieving.

[0003] However, in the actual production process of direct compression tablets, although excessive addition of magnesium stearate can improve flowability, it significantly prolongs the disintegration time of tablets, causing delayed dissolution and affecting clinical efficacy. Magnesium stearate is prone to "migration and enrichment" during tableting, forming a continuous hydrophobic film on the particle surface, further inhibiting water penetration and exacerbating disintegration difficulties. Fourth, a single component cannot simultaneously meet the dual requirements of "strong lubricity" and "high dispersibility," and there is an urgent need for a new type of composite lubricant that can maintain excellent lubrication effects while improving mixing uniformity and disintegration performance.

[0004] Sodium lauryl sulfate, as a surfactant, reduces the interfacial tension between the tablet and gastrointestinal fluids, helping water to penetrate the tablet core more quickly, thus rapidly disintegrating the tablet into granules. Simultaneously, it can increase the solubility of poorly soluble drugs in body fluids, promoting the release and absorption of drug molecules. However, the combined use of magnesium stearate and sodium lauryl sulfate may result in uneven mixing and inconsistent tablet compression quality.

[0005] In existing technologies, to address the problem of slow tablet disintegration caused by magnesium stearate as a lubricant, some solutions have proposed combining magnesium stearate with the surfactant sodium dodecyl sulfate. For example, Chinese patent CN201810521111A discloses a mercaptopurine composition that effectively improves the disintegration and sticking problems of mercaptopurine tablets by physically mixing magnesium stearate and sodium dodecyl sulfate before tableting. However, this on-site physical mixing method has inherent drawbacks: the two powders have different physical properties such as density and particle size, which easily lead to separation during mixing and subsequent processing, resulting in poor mixing uniformity and batch-to-batch stability. This inhomogeneity may cause fluctuations in the lubrication effect and disintegration performance of different parts of the tablet, affecting the uniformity and reliability of the final drug quality.

[0006] Existing physical mixing methods for magnesium stearate and sodium dodecyl sulfate are prone to separation due to differences in their physical properties, resulting in poor mixing uniformity and batch stability, and cannot effectively solve the problem of tablet performance fluctuations caused by excessive lubrication. Summary of the Invention

[0007] The purpose of this invention is to provide a magnesium stearate co-treated with sodium dodecyl sulfate, which effectively improves the problem of delayed tablet disintegration caused by excessive lubrication of magnesium stearate, and enhances mixing uniformity and tablet disintegration and dissolution performance.

[0008] The above-mentioned objective of the present invention is achieved by the following technical solution: a magnesium stearate and sodium dodecyl sulfate co-treated product, comprising, by mass parts: 94 parts magnesium stearate and 6 parts sodium dodecyl sulfate; The magnesium stearate and sodium dodecyl sulfate co-treated product has a particle size D50 of 5-30 μm, a drying loss of ≤5%, and a bulk density of 0.05-0.30 g / cm³. 3 ; The magnesium stearate sodium dodecyl sulfate co-treated compound is used for direct tableting of the drug.

[0009] Preferably, the magnesium stearate and sodium dodecyl sulfate co-treated product is obtained by slurrying magnesium stearate and sodium dodecyl sulfate in a ≥60% ethanol aqueous solution and then spray drying.

[0010] Preferably, the particle size D of the magnesium stearate is... 50 ≤30 μm, specific surface area ≥3.0 m² 2 / g, loose density ≤0.18g / mL.

[0011] A method for preparing the magnesium stearate-sodium dodecyl sulfate co-treated product includes the following steps: S1. Synthesis of magnesium stearate: Purified water was added to a reaction vessel and the temperature was raised to 75°C. Stearic acid was added at a mass ratio of 1.0:(0.05–0.2), and the temperature was further raised to 95°C. A 35–45% (w / w) sodium hydroxide aqueous solution preheated to 75°C was uniformly sprayed in, and the pH of the reaction system was controlled at 8.0–11.0, and the temperature at 85–100°C for saponification. Deionized water preheated to 75°C was added to the saponification solution for dilution, and then a pipeline pump was turned on to uniformly spray a 4.5–5.5% (w / w) magnesium chloride aqueous solution preheated to 75°C was added, and the reaction was stirred at 75–80°C. After the reaction was completed, the solution was centrifuged, washed, dried, and sieved to obtain magnesium stearate with a D50 ≤30 μm and a specific surface area ≥3.0 m². 2 / g, loose density ≤0.18 g / mL; S2. Pulping: The magnesium stearate obtained in S1 and sodium dodecyl sulfate are added to an ethanol aqueous solution at a mass ratio of 94:6, wherein the mass percentage of ethanol in the ethanol aqueous solution is ≥60%, and the mixture is stirred at 250–500 rpm for 15–30 min to obtain a uniform slurry with suitable solid content. S3. Spray drying: The slurry obtained in S2 is subjected to pre-spray dispersion treatment, and then dried in a spray drying tower to obtain the co-treated product.

[0012] Preferably, the pre-spray dispersion treatment is selected from any one of ball milling, ultrasonic treatment, high-pressure homogenization, or emulsification.

[0013] Preferably, the ethanol aqueous solution contains 60–85% ethanol by mass.

[0014] Preferably, in step S1, the sodium hydroxide aqueous solution is added at a time of 5–15 min, and the magnesium chloride aqueous solution is sprayed at a time of 8–20 min, while maintaining the system temperature fluctuation within ±2℃ throughout the process.

[0015] Preferably, the operating parameters of the spray drying tower in step S3 are: inlet air temperature 80-180 ℃, outlet air temperature 50-120 ℃, atomizer speed 25-40 Hz, and feed flow rate 1-3 m³ / h. 3 / h, system negative pressure 500-1300 Pa.

[0016] Preferably, the atomizer rotation speed is negatively correlated with the product particle size, bulk density, and loose density.

[0017] A tablet containing the aforementioned magnesium stearate sodium dodecyl sulfate co-processed compound, wherein the content of the magnesium stearate sodium dodecyl sulfate co-processed compound is 0.1% to 3.0% based on the total weight of the tablet.

[0018] The beneficial effects of this invention are: Magnesium stearate and sodium dodecyl sulfate were co-treated in a 94:6 ratio to achieve a synergistic effect between lubricant and surfactant. Magnesium stearate provided the dominant lubrication function, while sodium dodecyl sulfate offset the negative impact of magnesium stearate on dissolution, thereby improving drug bioavailability while ensuring smooth tablet compression.

[0019] The co-treatment process enables sodium dodecyl sulfate to achieve a molecular-level uniform distribution on the surface of magnesium stearate, thereby effectively reducing the solid-liquid interfacial energy and promoting water penetration. In tablet applications, the magnesium stearate-sodium dodecyl sulfate co-treated compound can accelerate disintegration and significantly improve drug dissolution rate, providing an advantage for improving the bioavailability of poorly soluble drugs.

[0020] The magnesium stearate and sodium dodecyl sulfate co-treated compound not only improves the flow and filling behavior of the powder, but also gives it superior compressibility during tableting, making it easier to form strong tablets. Particularly beneficial is that, while providing efficient lubrication, the co-treated compound does not significantly reduce tablet hardness like conventional magnesium stearate, achieving a good balance between lubricity and compressibility / hardness. This contributes to the production of tablets with a smooth appearance, high mechanical strength, and stable performance. Attached Figure Description

[0021] Figure 1 This is the particle size distribution diagram of Embodiment 1 of the present invention. Figure 2 This is the particle size distribution diagram of embodiment 2 of the present invention. Figure 3 This is the particle size distribution diagram of Comparative Example 1 of the present invention. Figure 4 This is the particle size distribution diagram of Comparative Example 2 in this invention. Figure 5 This is an SEM electron microscope image from Embodiment 1 of the present invention. Table 1: Physicochemical properties of the samples Table 2: Tablet performance obtained by preparing different samples as lubricants Detailed Implementation

[0022] The present invention will now be described in further detail with reference to the accompanying drawings.

[0023] To facilitate understanding, the terminology used in this article will be explained first: Magnesium stearate sample: refers to a single magnesium stearate substance not bound to sodium dodecyl sulfate, prepared by the method step S1 described in claim 5 and this part. It possesses specific physicochemical properties (e.g., particle size D50 ≤ 25 μm, specific surface area ≥ 3.0 m²). 2 / g, loose density ≤0.18 g / cm³ 3 ), which is a key raw material for preparing subsequent co-processed products.

[0024] Magnesium stearate and sodium dodecyl sulfate co-processed product: This refers to the final product obtained by co-processing the above-mentioned magnesium stearate sample and sodium dodecyl sulfate at a mass ratio of 94:6, including pulping, dispersion, and spray drying. This product is not a simple physical mixture of the two, but rather a homogeneous and stable composite formed through the process, exhibiting a synergistic effect. Its final physicochemical properties must meet the following characteristics: loss on drying ≤5%, particle size D50 of 5-30 μm, and bulk density of 0.05-0.30 g / cm³. 3 A loss on drying of ≤5% indicates a low content of moisture and volatile substances in the magnesium stearate-sodium dodecyl sulfate co-treated product. This helps prevent hydrolysis, oxidation, or microbial growth during storage, thereby extending the product's shelf life. Low moisture content reduces powder stickiness, preventing clumping and agglomeration, improving powder flowability and compressibility, and ensuring uniformity in tablet weight and content.

[0025] D50 ranges from 5 to 30 μm. 5 μm particles facilitate uniform mixing with other ingredients, such as the active pharmaceutical ingredient, reducing separation; while 30 μm particles improve overall flowability and prevent dust dispersion. This range balances flowability and mixability, making it suitable for direct compression or dry granulation processes. The uniform particle size distribution ensures consistent filling during compression, resulting in good reproducibility of tablet weight and hardness, and reducing tablet defects.

[0026] The density of loose material is 0.05-0.30 g / cm³. 3 This indicates that the powder is fluffy and has high porosity, making it easy to compress during tableting and forming porous tablets. The porous structure of the tablets facilitates water penetration, accelerating tablet disintegration and drug dissolution.

[0027] This invention obtains a high-performance "co-treated product" by controlling the quality of magnesium stearate samples and employing a specific co-processing technique. The preparation process and performance are specifically demonstrated in the following examples.

[0028] This specific embodiment is merely an explanation of the present invention and is not intended to limit the invention. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they are within the scope of the claims of the present invention.

[0029] Example: The examples in this section are intended to illustrate the specific preparation process and parameter changes of the magnesium stearate sodium dodecyl sulfate co-treated product described in this invention.

[0030] Preparation of magnesium stearate samples 100 kg of deionized water was added to a reaction vessel and the temperature was raised to 75 °C. 6 kg of stearic acid was added, and the temperature was raised to 95 °C. A 40% sodium hydroxide aqueous solution, preheated to 75 °C, was sprayed in at a uniform rate. The pH of the reaction system was controlled at 9.5 ± 0.5, and the saponification reaction was carried out at 95 °C for 3 hours. 15 kg of preheated deionized water (preheated to 75 °C) was added to the reaction solution for dilution. While stirring, 68 kg of a 5.0% magnesium chloride aqueous solution, preheated to 75 °C, was sprayed in at a uniform rate. The temperature was controlled at 78 ± 2 °C, and the reaction continued for 1.5 hours. After the reaction, the slurry was centrifuged, and the solids were washed with deionized water until the filtrate was neutral. The filtrate was then vacuum dried at 80 °C for 12 hours and passed through a 200-mesh sieve to obtain the magnesium stearate sample.

[0031] Example 1: 94.0 g of the prepared magnesium stearate and 6.0 g of sodium dodecyl sulfate were initially mixed in a mixer. A 70% (w / w) aqueous ethanol solution was added to prepare a homogeneous slurry with a solid content of 25%, and the mixture was continuously stirred at 400 rpm for 20 minutes. The slurry was homogenized three times under 50 MPa pressure using a high-pressure homogenizer, and then spray-dried. The operating parameters of the spray drying tower were: inlet air temperature 160℃, outlet air temperature 90℃, atomizer speed 30 Hz, and feed flow rate 1.6 m³ / s. 3 / h, system negative pressure 1000 Pa. Collect the dried powder to obtain magnesium stearate and sodium dodecyl sulfate co-treated sample A (repeat the experimental steps three times).

[0032] Keeping all other conditions unchanged, only the atomizer speed was adjusted to 25 Hz, and the dried powder was collected to obtain sample A2 of magnesium stearate and sodium dodecyl sulfate co-treated material (the experimental steps were repeated three times).

[0033] Keeping all other conditions unchanged, only the atomizer speed was adjusted to 35 Hz, and the dried powder was collected to obtain magnesium stearate sodium dodecyl sulfate co-treated sample A3 (the experimental steps were repeated three times).

[0034] The particle size D50 of magnesium stearate before pulping was 15.5 μm, and the specific surface area was 3.5 m². 2 / g, loose density 0.13 g / mL.

[0035] Example 2: The preparation process is the same as in Example 1, except that the spray drying parameters are changed: inlet air temperature 180 ℃, outlet air temperature 100 ℃, atomizer speed 30 Hz, and feed flow rate 1.7 m³ / s. 3 / h, system negative pressure 1020 Pa. The resulting product is co-processed sample B.

[0036] Keeping all other conditions unchanged, only the atomizer speed was adjusted to 25 Hz, and the dried powder was collected to obtain magnesium stearate sodium dodecyl sulfate co-treated sample B2 (the experimental steps were repeated three times).

[0037] Keeping all other conditions unchanged, only the atomizer speed was adjusted to 35 Hz, and the dried powder was collected to obtain magnesium stearate sodium dodecyl sulfate co-treated sample B3 (the experimental steps were repeated three times).

[0038] The particle size (D50) of magnesium stearate before pulping was 17.0 μm, and the specific surface area was 3.0 m². 2 / g, with a density of 0.15g / mL.

[0039] Comparative Example 1: 100 kg of water was added to the reactor and heated to 75 °C. 6000 g of stearic acid was added, and the temperature was raised to 95 °C. Then, a 45% sodium hydroxide aqueous solution preheated to 75 °C was evenly sprayed in. The pH was maintained at 10.3, and the reaction was carried out at 95 °C for 3 hours. 15 kg of deionized water preheated to 75 °C was added to the saponified solution. A pipeline pump was started to evenly spray 61.5 kg of a 5.5% magnesium chloride aqueous solution preheated to 75 °C into the saponified solution. The reaction was then stirred for 1.5 hours, with the temperature controlled at 80 °C. The material was then centrifuged, washed, dried, and sieved to obtain magnesium stearate sample C (the experimental steps were repeated three times). Comparative Example 2: The magnesium stearate and sodium dodecyl sulfate prepared above were mixed in a three-dimensional motion mixer at a mass ratio of 94:6 for 2 hours to obtain physical mixture sample D.

[0040] Co-processing physicochemical property detection Key physicochemical indicators were tested on the samples obtained in Examples 1 and 2 and Comparative Examples 1 and 2. Table 1 like Figure 1 , Figure 2 As shown, the particle sizes of Sample A in Example 1 and Sample B in Example 2 exhibit a normal distribution and are uniform and stable. Figure 3 As shown, the pure magnesium stearate sample C of Comparative Example 1 showed slight signs of uneven mixing or beginning to agglomerate, such as... Figure 4 As shown, the particle size distribution of physical mixture sample D in Comparative Example 2 is uneven, indicating poor mixing uniformity.

[0041] As shown in Table 1, under the same inlet / outlet air temperature conditions (such as samples A, A2, and A3 in Example 1): As the atomizer speed increased, the particle size D50 decreased significantly (A2: 23–25 μm → A: 17–19 μm → A3: 8–9 μm), and the bulk density decreased. Comparative Example 2, which used a simple three-dimensional mixing method to physically mix magnesium stearate and sodium dodecyl sulfate, exhibited large fluctuations in bulk density (0.15–0.19 g / cm³). 3 The samples exhibited by Examples 1 and 2, with a wide particle size distribution (12–20 μm) and the highest moisture content (3.7–3.9%), indicate that the components did not form an effective bond, making them prone to moisture absorption and exhibiting poor flowability. In contrast, the samples obtained through the "co-processing" process of slurry blending + high-pressure homogenization + spray drying in Examples 1 and 2 (series A and B) showed more uniform particle size, lower moisture content, and a denser structure, demonstrating that this process can achieve effective composite composition of the two components at the microscopic level, improving physical stability and functionality.

[0042] II. Tablet Preparation and Application Examples The examples in this section are intended to illustrate the performance of the magnesium stearate sodium dodecyl sulfate co-treated product of the present invention as a lubricant in tablet preparation.

[0043] Example 3: Low-dosage, short-time mixing 995 g of microcrystalline cellulose (pH 102) was mixed with 5 g of samples A, B, C, and D as lubricants. The mixture was then mixed in a cubic mixer for 2 minutes. Tableting was performed using a single-punch tablet press with a target tablet weight of 350 mg, a press speed of 30 rpm, and a preset pressure of 10 kN.

[0044] Tablets made using samples A, C, and D as lubricants are numbered Tablet A-1, Tablet B-1, Tablet C-1, and Tablet D-1, respectively.

[0045] Example 4: Low dosage, long-term mixing The preparation process is the same as in Example 3, except that the mixing time is extended to 10 minutes.

[0046] The resulting tablets were numbered as tablet A-2, tablet B-2, tablet C-2, and tablet D-2, respectively.

[0047] Example 5: High dosage, short time mixing Microcrystalline cellulose (pH 102) 980 g, lubricant 20 g.

[0048] The preparation process is the same as in Example 3, with a mixing time of 2 minutes.

[0049] The resulting tablets were numbered as tablet A-3, tablet B-3, tablet C-3, and tablet D-3, respectively.

[0050] Example 6: High dosage and long duration of mixing Take 980 g of microcrystalline cellulose 102 and 20 g of lubricant. The preparation process is the same as in Example 3, with a mixing time of 10 min.

[0051] The resulting tablets were numbered A-4, B-4, C-4, and D-4, respectively.

[0052] Tablet performance testing Key performance tests were performed on the tablets prepared in Examples 3-5. Table 2 As shown in Table 2, tablets A-1 and B-1, which use co-treated samples A and B as lubricants under conventional processes (i.e., low dosage and short mixing time), have higher hardness than tablets C-1, which uses pure magnesium stearate as a lubricant, or tablet D-1, which uses a physical mixture as a lubricant, under the same processes. Furthermore, their disintegration time is significantly shorter compared to tablets using pure magnesium stearate or a physical mixture as a lubricant.

[0053] As shown in Examples 4 and 6, the hardness and disintegration properties of all tablets were adversely affected when the mixing time was prolonged (simulating over-lubrication) or the amount of lubricant was increased. However, tablets using co-treated samples A and B as lubricants showed better tolerance under the same process compared to tablets using pure magnesium stearate or physical mixtures as lubricants, exhibiting the smallest decrease in tablet hardness and the least extension of disintegration time.

[0054] Under all test conditions, the magnesium stearate and sodium dodecyl sulfate co-treated product prepared in this invention provides effective lubrication while achieving higher tablet hardness and faster disintegration rate, effectively mitigating the "over-lubrication" effect of magnesium stearate, and exhibiting superior overall performance compared to pure magnesium stearate and its physical mixture with sodium dodecyl sulfate.

[0055] The performance of the co-treated samples obtained in Examples 1 and 2 of this invention and the comparative sample were tested. Their loss on drying was ≤5%, particle size D50 was in the range of 5-20 μm, and bulk density was 0.05-0.30 g / cm³. 3 Within the scope of this invention, it conforms to the features described in claims 1-4. The co-treated compound exhibits superior lubricity, disintegration-promoting effect, and dissolution performance in tablet applications.

Claims

1. A magnesium stearate-sodium dodecyl sulfate co-treated product, characterized in that, By mass, it includes: 94 parts magnesium stearate and 6 parts sodium dodecyl sulfate; The magnesium stearate and sodium dodecyl sulfate co-treated product has a particle size D50 of 5-30 μm, a drying loss of ≤5%, and a bulk density of 0.05-0.30 g / cm³. 3 ; The magnesium stearate-sodium dodecyl sulfate co-treated product adheres to magnesium stearate after co-treatment.

2. The magnesium stearate and sodium dodecyl sulfate co-treated product according to claim 1, characterized in that, The magnesium stearate and sodium dodecyl sulfate co-processed product is obtained by slurrying magnesium stearate and sodium dodecyl sulfate in a ≥60% ethanol aqueous solution and then spray drying.

3. The magnesium stearate and sodium dodecyl sulfate co-treated product according to claim 2, characterized in that, The particle size D of the magnesium stearate 50 ≤30 μm, specific surface area ≥3.0 m² 2 / g, loose density ≤0.18 g / mL.

4. A method for preparing the magnesium stearate-sodium dodecyl sulfate co-treated product as described in any one of claims 1-3, characterized in that, Includes the following steps: S1. Synthesis of magnesium stearate: Purified water was added to a reaction vessel and the temperature was raised to 75°C. Stearic acid was added at a mass ratio of 1.0:(0.05–0.2), and the temperature was further raised to 95°C. A 35–45% (w / w) sodium hydroxide aqueous solution preheated to 75°C was uniformly sprayed in, and the pH of the reaction system was controlled at 8.0–11.0, and the temperature at 85–100°C for saponification. Deionized water preheated to 75°C was added to the saponification solution for dilution, and then a pipeline pump was turned on to uniformly spray a 4.5–5.5% (w / w) magnesium chloride aqueous solution preheated to 75°C was added, and the reaction was stirred at 75–80°C. After the reaction was completed, the solution was centrifuged, washed, dried, and sieved to obtain magnesium stearate with a D50 ≤ 30 μm and a specific surface area ≥ 3.0 m². 2 / g, loose density ≤0.18 g / mL; S2. Pulping: The magnesium stearate obtained in S1 and sodium dodecyl sulfate are added to an ethanol aqueous solution at a mass ratio of 94:6, wherein the mass percentage of ethanol in the ethanol aqueous solution is ≥60%, and the mixture is stirred at 250–500 rpm for 15–30 min to obtain a uniform slurry with suitable solid content. S3. Spray drying: The slurry obtained in S2 is subjected to pre-spray dispersion treatment and then dried in a spray drying tower to obtain the co-treated product.

5. The method according to claim 4, characterized in that, The pre-spray dispersion treatment is selected from any one of ball milling, ultrasonic treatment, high-pressure homogenization, or emulsification.

6. The preparation method according to claim 4, characterized in that, The ethanol aqueous solution contains ≥60% ethanol by mass.

7. The method according to claim 4, characterized in that, In step S1, the sodium hydroxide aqueous solution is added over a period of 5–15 min, and the magnesium chloride aqueous solution is sprayed over a period of 8–20 min, while the temperature fluctuation of the system is kept within ±2℃ throughout the process.

8. The preparation method according to claim 4, characterized in that, The operating parameters of the spray drying tower in step S3 are: inlet air temperature 80-180℃, outlet air temperature 50-120℃, atomizer speed 25-40 Hz, and feed flow rate 1-3 m³ / h. 3 / h, system negative pressure 500-1300 Pa.

9. The preparation method according to claim 4, characterized in that, The atomizer rotation speed is negatively correlated with the product particle size and bulk density.

10. A tablet containing the magnesium stearate and sodium dodecyl sulfate co-treated product as described in any one of claims 1-2, characterized in that, The content of the magnesium stearate sodium dodecyl sulfate co-processed product is 0.1% to 3.0% based on the total weight of the tablets.

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