Metformin empagliflozin tablet and fluidized bed preparation process thereof
By employing fluidized bed preparation technology and precise control of process parameters, the problem of uneven mixing of metformin empagliflozin tablets under differences in active ingredients at high and low doses was solved, achieving stable large-scale production and consistent quality, and ensuring the bioequivalence of the product.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- SHANDONG SBOND PHARMA
- Filing Date
- 2026-06-09
- Publication Date
- 2026-07-10
AI Technical Summary
Existing technologies for preparing metformin empagliflozin tablets face the problem of uneven mixing caused by the difference between high-dose and low-dose active ingredients, and the process parameter control window is narrow, making it difficult to achieve stable large-scale production and consistent quality.
By employing a fluidized bed preparation process and combining precise control of process parameters such as binder formulation, fluidized granulation, total mixing, and coating, the problem of mixing uniformity between high-dose metformin and low-dose empagliflozin is solved through fluidized bed granulation. Furthermore, the complete process window from mixing to tableting and coating is clearly defined, ensuring consistent product quality.
A robust and controllable preparation process was achieved, ensuring a smooth transition from laboratory-scale trials to pilot-scale and commercial production. The product's content uniformity, hardness, brittleness, and coating weight gain met the standards, guaranteeing bioequivalence with the reference formulation.
Smart Images
Figure CN122351184A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of metformin empagliflozin tablets, specifically to a metformin empagliflozin tablet and its fluidized bed preparation process. Background Technology
[0002] Metformin and empagliflozin are both commonly used drugs for treating type 2 diabetes, and their combined use has a synergistic effect. In existing technologies, metformin and empagliflozin tablets are typically prepared using wet or dry granulation processes. However, existing processes often face the following two technical problems when dealing with the significant differences between high-dose and low-dose active ingredients: First, in the traditional wet granulation process, due to the significant differences between metformin and empagliflozin in terms of particle size, density, and flowability, it is difficult to achieve uniform particle growth in fluidized bed granulation. This results in uneven particle size distribution and large differences in bulk density, which in turn affects the stability of subsequent tableting processes, making it difficult to scale up the process from laboratory pilot to pilot and commercial production scale.
[0003] Second, during the scale-up process, the existing process has a narrow control window for key process parameters (such as inlet air temperature, material temperature, spraying speed, and drying endpoint determination), resulting in poor batch-to-batch reproducibility. This makes it difficult for the final product to maintain quality consistency with the reference formulation (original drug) in key quality attributes such as content uniformity and dissolution behavior, thereby affecting the bioequivalence of the drug. Summary of the Invention
[0004] To solve the above-mentioned technical problems, the present invention provides the following technical solution: A metformin empagliflozin tablet, comprising raw materials, wherein the raw materials, by parts, include: 900-1100 parts metformin hydrochloride, 10-15 parts empagliflozin, 1-3 parts corn starch, 10-15 parts copovidone, 4-6 parts magnesium stearate, 1-5 parts silica, 120-130 parts first purified water, 25-35 parts film coating premix (gastric-soluble type), and 120-130 parts second purified water.
[0005] A fluidized bed-based preparation process for metformin empagliflozin tablets includes the following steps: S1, Weighing and mixing ingredients: Weigh metformin hydrochloride, empagliflozin, corn starch, copovidone, magnesium stearate, silicon dioxide, first purified water, film coating premix, and second purified water; S2, Adhesive preparation: Copovidone is added to the first purified water to prepare an aqueous solution of copovidone; S3, Premixing: Metformin hydrochloride, empagliflozin, and corn starch are added to a mixing device and mixed to obtain a premixed material; S4, Fluidized bed granulation: The premixed material is transferred into a fluidized bed equipment for fluidization, while a copovidone aqueous solution is sprayed in for granulation and dried to the target moisture content to obtain dry granules; S5, Total Mixture: The dry granules are mixed with magnesium stearate and silicon dioxide to obtain the total mixture. S6, tableting: compressing the total mixture into tablets; S7, Coating: Coating the unprocessed tablets with a film coating premix to obtain metformin empagliflozin tablets.
[0006] As a preferred embodiment of the fluidized bed preparation process for metformin empagliflozin tablets described in this invention, the specific steps of S3 are as follows: S31, Metformin hydrochloride, Empagliflozin and corn starch are sequentially added to a wet granulation mixer for mixing; S32, after mixing, discharge the material and transfer the premixed material to the fluidized bed dryer granulator using a PE bag.
[0007] As a preferred embodiment of the fluidized bed preparation process for metformin empagliflozin tablets described in this invention, the stirring speed of the wet mixing granulator in S31 is set to 100-200 rpm, the shearing speed is set to 1500-2000 rpm, and the mixing time is set to 15-30 min.
[0008] As a preferred embodiment of the fluidized bed preparation process for metformin empagliflozin tablets described in this invention, the specific steps of S4 are as follows: S41, after the premixed material is transferred in, adjust the inlet air temperature and exhaust frequency converter to preheat the material to the preset value; S42, after the material is preheated, adjust the atomization pressure and spraying speed of the copovidone aqueous solution, start the spraying and granulation by the exhaust frequency converter, control the material temperature during the granulation process, and spray until granulation is completed. S43, sample and test the moisture content. When the moisture content of the material reaches the standard, stop drying and discharge the material.
[0009] As a preferred embodiment of the fluidized bed preparation process for metformin empagliflozin tablets described in this invention, wherein: the inlet air temperature in S41 is set to 50-70℃, and the preset value is set to 30-50℃; the atomization pressure in S42 is set to 1.5-3.0 bar, and the spraying speed is set to 50-200 g / min.
[0010] As a preferred embodiment of the fluidized bed preparation process for metformin empagliflozin tablets described in this invention, the specific steps of S5 are as follows: S51, the dry-granulated granules, magnesium stearate, and silica are added sequentially to the three-dimensional motion high-efficiency mixer; S52, set the mixing speed to 25-45 rpm and the mixing time to 15-20 min for mixing.
[0011] As a preferred embodiment of the fluidized bed preparation process for metformin empagliflozin tablets described in this invention, the specific steps of S6 are as follows: S61, Calculate the required tablet weight based on the total mixed intermediate product content determination results; S62, Formal Tableting: Set the tableting speed to 30-60 tablets / minute. During the tableting process, monitor the tablet weight difference of the sample by ±5.0%, hardness (10-20kg), and friability (weight loss ≤1.0%, and no broken, cracked, or pulverized tablets should be detected).
[0012] As a preferred embodiment of the fluidized bed preparation process for metformin empagliflozin tablets described in this invention, the specific steps of S7 are as follows: S71, add the second purified water to the mixing tank, start stirring, and slowly add the film coating premix for later use; S72, install spray gun, peristaltic pump, etc., put qualified raw tablets into the coating pan, control the tablet bed temperature, and preheat the raw tablets; S73, set the atomization pressure and adjust the coating pan speed to a suitable range to ensure the material flows evenly; S74, begin coating, control the inlet air temperature and spray speed, maintain the tablet bed temperature until coating is complete, and control the coating weight gain of the coated tablets to reach 2%-4%; S75, maintain the bed temperature, dry for 15-20 minutes, turn off the heating, and let the sheet temperature drop to room temperature before discharging.
[0013] As a preferred embodiment of the fluidized bed preparation process for metformin empagliflozin tablets according to the present invention, wherein: the tablet bed temperature in S72 is set to 30-50℃; the atomization pressure in S73 is set to 1.0-2.0 bar, and the coating pan rotation speed is set to 3-8 rpm; the inlet air temperature in S74 is set to 50-70℃, the liquid spraying speed is set to 5-20 g / min, and the tablet bed temperature is set to 30-50℃; and the tablet bed temperature in S75 is set to 30-50℃.
[0014] Compared with existing technologies: 1. By employing fluidized bed granulation and precisely controlling the process parameters throughout the entire process, including premixing, binder preparation, fluidized bed granulation, total mixing, and coating, a robust, controllable, and scalable manufacturing process can be achieved. This invention combines wet mixing with fluidized bed granulation, solving the problem of mixing uniformity between high-dose metformin and low-dose empagliflozin due to differences in physical properties. It also clarifies the complete process window from mixing and granulation to tableting and coating, avoiding process interruptions or product scrap due to parameter fluctuations, and ensuring a smooth transition from laboratory-scale trials to pilot-scale and commercial batch production. 2. By controlling the material temperature, drying endpoint, and total mixing parameters during the fluidized bed granulation process, and dynamically adjusting the tablet weight based on the content determination results of the intermediate product, this invention achieves the effect of ensuring the product meets quality standards and is essentially consistent with the quality of the reference formulation. Through standardized process parameter control, this invention can stably prepare tablets with content uniformity, hardness, friability, and coating weight gain that all meet preset standards. Simultaneously, by controlling the microstructure of the particles and tablets, it ensures a high degree of consistency with the reference formulation in dissolution behavior and physical stability, providing a reliable guarantee for subsequent bioequivalence studies and clinical use. Attached Figure Description
[0015] Figure 1 This is a schematic diagram of the overall process of the present invention. Detailed Implementation
[0016] To make the objectives, technical solutions, and advantages of the present invention clearer, the embodiments of the present invention will be described in further detail below. Example
[0017] This invention provides a metformin empagliflozin tablet, comprising raw materials, wherein the raw materials, by weight, include: 900 parts metformin hydrochloride, 10 parts empagliflozin, 1 part corn starch, 10 parts copovidone, 4 parts magnesium stearate, 1 part silica, 120 parts first purified water, 25 parts film coating premix (gastric-soluble type), and 120 parts second purified water.
[0018] A fluidized bed-based preparation process for metformin empagliflozin tablets includes the following steps: S1, Weighing and mixing ingredients: Weigh metformin hydrochloride, empagliflozin, corn starch, copovidone, magnesium stearate, silicon dioxide, first purified water, film coating premix, and second purified water; S2, Adhesive preparation: Copovidone is added to the first purified water to prepare an aqueous solution of copovidone; S3, Premixing: Metformin hydrochloride, empagliflozin, and corn starch are added to a mixing device and mixed to obtain a premixed material; The specific steps of S3 are as follows: S31, Metformin hydrochloride, Empagliflozin, and corn starch are sequentially added to a wet granulation mixer for mixing; wherein, the stirring speed of the wet granulation mixer is set to 100 rpm, the shearing speed is set to 1500 rpm, and the mixing time is set to 15 min. S32, after mixing, discharge the material and transfer the premixed material to the fluidized bed dryer granulator using a PE bag; S4, Fluidized bed granulation: The premixed material is transferred into a fluidized bed equipment for fluidization, while a copovidone aqueous solution is sprayed in for granulation and dried to the target moisture content to obtain dry granules; The specific steps of S4 are as follows: S41, after the premixed material is transferred in, adjust the inlet air temperature and exhaust frequency converter to preheat the material to the preset value; wherein, the inlet air temperature is set to 50℃ and the preset value is set to 30℃. S42, after the material is preheated, adjust the atomization pressure and spraying speed of the copovidone aqueous solution, start the spraying and granulation by the frequency converter of the exhaust air, control the material temperature during the granulation process, and spray until granulation is completed; wherein, the atomization pressure is set to 1.5 bar and the spraying speed is set to 50 g / min; S43, sample and test the moisture content. When the moisture content of the material reaches the standard, stop drying and discharge the material. S5, Total Mixture: The dry granules are mixed with magnesium stearate and silicon dioxide to obtain the total mixture. The specific steps of S5 are as follows: S51, the dry-granulated granules, magnesium stearate, and silica are added sequentially to the three-dimensional motion high-efficiency mixer; S52, set the mixing speed to 25 rpm and the mixing time to 15 min for mixing; S6, tableting: compressing the total mixture into tablets; The specific steps of S6 are as follows: S61, Calculate the required tablet weight based on the total mixed intermediate product content determination results; S62, Formal Tableting: Set the tableting speed to 30 tablets / minute. During the tableting process, monitor the tablet weight difference of the sample by ±5.0%, hardness (10kg), and friability (weight loss ≤1.0%, and no broken, cracked, or pulverized tablets should be detected). S7, Coating: Coating the uncoated tablets with a film coating premix to obtain metformin empagliflozin tablets; The specific steps of S7 are as follows: S71, add the second purified water to the mixing tank, start stirring, and slowly add the film coating premix for later use; S72, install spray gun, peristaltic pump, etc., put qualified raw tablets into the coating pan, control the tablet bed temperature, and preheat the raw tablets; wherein, the tablet bed temperature is set to 30℃; S73, set the atomization pressure and adjust the coating pan speed to a suitable range to ensure the material flows evenly; wherein, the atomization pressure is set to 1.0 bar and the coating pan speed is set to 3 rpm; S74, start coating, control the inlet air temperature and spraying speed, maintain the tablet bed temperature until coating is finished, and control the coating weight gain of the coated tablets to reach 2%; wherein, the inlet air temperature is set to 50℃, the spraying speed is set to 5g / min, and the tablet bed temperature is set to 30℃. S75, maintain the tablet bed temperature, dry for 15 minutes, turn off the heating, reduce the tablet temperature to room temperature, and discharge the material; wherein, the tablet bed temperature is set to 30℃. Example
[0019] This invention provides a metformin empagliflozin tablet, comprising raw materials, which by weight include: 1000 parts metformin hydrochloride, 12.5 parts empagliflozin, 2 parts corn starch, 12.5 parts copovidone, 5 parts magnesium stearate, 3 parts silica, 125 parts first purified water, 30 parts film coating premix (gastric-soluble type), and 125 parts second purified water.
[0020] A fluidized bed-based preparation process for metformin empagliflozin tablets includes the following steps: S1, Weighing and mixing ingredients: Weigh metformin hydrochloride, empagliflozin, corn starch, copovidone, magnesium stearate, silicon dioxide, first purified water, film coating premix, and second purified water; S2, Adhesive preparation: Copovidone is added to the first purified water to prepare an aqueous solution of copovidone; S3, Premixing: Metformin hydrochloride, empagliflozin, and corn starch are added to a mixing device and mixed to obtain a premixed material; The specific steps of S3 are as follows: S31, Metformin hydrochloride, Empagliflozin, and corn starch are sequentially added to a wet granulation mixer for mixing; wherein, the stirring speed of the wet granulation mixer is set to 150 rpm, the shearing speed is set to 1750 rpm, and the mixing time is set to 22.5 min. S32, after mixing, discharge the material and transfer the premixed material to the fluidized bed dryer granulator using a PE bag; S4, Fluidized bed granulation: The premixed material is transferred into a fluidized bed equipment for fluidization, while a copovidone aqueous solution is sprayed in for granulation and dried to the target moisture content to obtain dry granules; The specific steps of S4 are as follows: S41, after the premixed material is transferred in, adjust the inlet air temperature and exhaust frequency converter to preheat the material to the preset value; wherein, the inlet air temperature is set to 60℃ and the preset value is set to 40℃. S42, after the material is preheated, adjust the atomization pressure and spraying speed of the copovidone aqueous solution, start the spraying and granulation by the frequency converter of the exhaust air, control the material temperature during the granulation process, and spray until granulation is completed; wherein, the atomization pressure is set to 2.25 bar and the spraying speed is set to 125 g / min; S43, sample and test the moisture content. When the moisture content of the material reaches the standard, stop drying and discharge the material. S5, Total Mixture: The dry granules are mixed with magnesium stearate and silicon dioxide to obtain the total mixture. The specific steps of S5 are as follows: S51, the dry-granulated granules, magnesium stearate, and silica are added sequentially to the three-dimensional motion high-efficiency mixer; S52, set the mixing speed to 35 rpm and the mixing time to 17.5 min for mixing; S6, tableting: compressing the total mixture into tablets; The specific steps of S6 are as follows: S61, Calculate the required tablet weight based on the total mixed intermediate product content determination results; S62, Formal Tableting: Set the tableting speed to 45 tablets / minute. During the tableting process, monitor the tablet weight difference of the sample by ±5.0%, hardness (15kg), and friability (weight loss ≤1.0%, and no broken, cracked, or pulverized tablets should be detected). S7, Coating: Coating the uncoated tablets with a film coating premix to obtain metformin empagliflozin tablets; The specific steps of S7 are as follows: S71, add the second purified water to the mixing tank, start stirring, and slowly add the film coating premix for later use; S72, install spray gun, peristaltic pump, etc., put qualified raw tablets into the coating pan, control the tablet bed temperature, and preheat the raw tablets; the tablet bed temperature is set to 40℃. S73, set the atomization pressure and adjust the coating pan speed to a suitable range to ensure the material flows evenly; the atomization pressure is set to 1.5 bar and the coating pan speed is set to 5.5 rpm. S74, start coating, control the inlet air temperature and spraying speed, maintain the tablet bed temperature until coating is finished, and control the coating weight gain of the coated tablets to reach 3%; wherein, the inlet air temperature is set to 60℃, the spraying speed is set to 12.5g / min, and the tablet bed temperature is set to 40℃. S75, maintain the tablet bed temperature, dry for 17.5 minutes, turn off the heating, reduce the tablet temperature to room temperature, and discharge the material; wherein, the tablet bed temperature is set to 40℃. Example
[0021] This invention provides a metformin empagliflozin tablet, comprising raw materials, wherein the raw materials, by weight, include: 1100 parts metformin hydrochloride, 15 parts empagliflozin, 3 parts corn starch, 15 parts copovidone, 6 parts magnesium stearate, 5 parts silica, 130 parts first purified water, 35 parts film coating premix (gastric-soluble type), and 130 parts second purified water.
[0022] A fluidized bed-based preparation process for metformin empagliflozin tablets includes the following steps: S1, Weighing and mixing ingredients: Weigh metformin hydrochloride, empagliflozin, corn starch, copovidone, magnesium stearate, silicon dioxide, first purified water, film coating premix, and second purified water; S2, Adhesive preparation: Copovidone is added to the first purified water to prepare an aqueous solution of copovidone; S3, Premixing: Metformin hydrochloride, empagliflozin, and corn starch are added to a mixing device and mixed to obtain a premixed material; The specific steps of S3 are as follows: S31, Metformin hydrochloride, Empagliflozin, and corn starch are sequentially added to a wet granulation mixer for mixing; wherein, the stirring speed of the wet granulation mixer is set to 200 rpm, the shearing speed is set to 2000 rpm, and the mixing time is set to 30 min. S32, after mixing, discharge the material and transfer the premixed material to the fluidized bed dryer granulator using a PE bag; S4, Fluidized bed granulation: The premixed material is transferred into a fluidized bed equipment for fluidization, while a copovidone aqueous solution is sprayed in for granulation and dried to the target moisture content to obtain dry granules; The specific steps of S4 are as follows: S41, after the premixed material is transferred in, adjust the inlet air temperature and exhaust frequency converter to preheat the material to the preset value; wherein, the inlet air temperature is set to 70℃ and the preset value is set to 50℃. S42, after the material is preheated, adjust the atomization pressure and spraying speed of the copovidone aqueous solution, start the spraying and granulation by the frequency converter of the exhaust air, control the material temperature during the granulation process, and spray until granulation is completed; wherein, the atomization pressure is set to 3.0 bar and the spraying speed is set to 200 g / min; S43, sample and test the moisture content. When the moisture content of the material reaches the standard, stop drying and discharge the material. S5, Total Mixture: The dry granules are mixed with magnesium stearate and silicon dioxide to obtain the total mixture. The specific steps of S5 are as follows: S51, the dry-granulated granules, magnesium stearate, and silica are added sequentially to the three-dimensional motion high-efficiency mixer; S52, set the mixing speed to 45 rpm and the mixing time to 20 min for mixing; S6, tableting: compressing the total mixture into tablets; The specific steps of S6 are as follows: S61, Calculate the required tablet weight based on the total mixed intermediate product content determination results; S62, Formal Tableting: Set the tableting speed to 60 tablets / minute. During the tableting process, monitor the tablet weight difference of the sample by ±5.0%, hardness (20kg), and friability (weight loss ≤1.0%, and no broken, cracked, or pulverized tablets should be detected). S7, Coating: Coating the uncoated tablets with a film coating premix to obtain metformin empagliflozin tablets; The specific steps of S7 are as follows: S71, add the second purified water to the mixing tank, start stirring, and slowly add the film coating premix for later use; S72, install spray gun, peristaltic pump, etc., put qualified raw tablets into the coating pan, control the tablet bed temperature, and preheat the raw tablets; wherein, the tablet bed temperature is set to 50℃; S73, set the atomization pressure and adjust the coating pan speed to a suitable range to ensure the material flows evenly; the atomization pressure is set to 2.0 bar and the coating pan speed is set to 8 rpm. S74, start coating, control the inlet air temperature and spray speed, maintain the tablet bed temperature until coating is finished, and control the coating weight gain of the coated tablets to reach 4%; wherein, the inlet air temperature is set to 70℃, the spray speed is set to 20g / min, and the tablet bed temperature is set to 50℃. S75, maintain the tablet bed temperature, dry for 20 minutes, turn off the heating, reduce the tablet temperature to room temperature, and discharge the material; wherein, the tablet bed temperature is set to 50℃.
[0023] Example 1 Example 2 Example 3 Single batch production pass rate 96.2% 99.5% 97.8% Process scale-up adaptability Fine-tuning of spray parameters is required. Directly enlarged without adjustment The intake air temperature needs to be adjusted. As shown in the table above, the metformin empagliflozin tablets prepared in Examples 1-3 all showed good performance in terms of single-batch production qualification rate and process scale-up adaptability. After use, Example 2 showed the best results.
[0024] Although the present invention has been described above with reference to embodiments, various modifications can be made and components can be replaced with equivalents without departing from the scope of the invention. In particular, as long as there is no structural conflict, the features in the disclosed embodiments can be combined with each other in any manner. The lack of an exhaustive description of these combinations in this specification is merely for the sake of brevity and resource conservation. Therefore, the present invention is not limited to the specific embodiments disclosed herein, but includes all technical solutions falling within the scope of the claims.
Claims
1. A metformin empagliflozin tablet, comprising raw materials, characterized in that, The raw materials, by weight, include: 900-1100 parts metformin hydrochloride, 10-15 parts empagliflozin, 1-3 parts corn starch, 10-15 parts copovidone, 4-6 parts magnesium stearate, 1-5 parts silica, 120-130 parts first purified water, 25-35 parts film coating premix, and 120-130 parts second purified water.
2. A fluidized bed preparation process for metformin empagliflozin tablets, characterized in that, Includes the following steps: S1, Weighing and mixing ingredients: Weigh metformin hydrochloride, empagliflozin, corn starch, copovidone, magnesium stearate, silicon dioxide, first purified water, film coating premix, and second purified water; S2, Adhesive preparation: Copovidone is added to the first purified water to prepare an aqueous solution of copovidone; S3, Premixing: Metformin hydrochloride, empagliflozin, and corn starch are added to a mixing device and mixed to obtain a premixed material; S4, Fluidized bed granulation: The premixed material is transferred into a fluidized bed equipment for fluidization, while a copovidone aqueous solution is sprayed in for granulation and dried to the target moisture content to obtain dry granules; S5, Total Mixture: The dry granules are mixed with magnesium stearate and silicon dioxide to obtain the total mixture. S6, tableting: compressing the total mixture into tablets; S7, Coating: Coating the unprocessed tablets with a film coating premix to obtain metformin empagliflozin tablets.
3. The fluidized bed preparation process for metformin empagliflozin tablets according to claim 2, characterized in that, The specific steps of S3 are as follows: S31, Metformin hydrochloride, Empagliflozin and corn starch are sequentially added to a wet granulation mixer for mixing; S32, after mixing, discharge the material and transfer the premixed material to the fluidized bed dryer granulator using a PE bag.
4. The fluidized bed preparation process for metformin empagliflozin tablets according to claim 3, characterized in that, The stirring speed of the wet mixing granulator in S31 is set to 100-200 rpm, the shearing speed is set to 1500-2000 rpm, and the mixing time is set to 15-30 min.
5. The fluidized bed preparation process for metformin empagliflozin tablets according to claim 2, characterized in that, The specific steps of S4 are as follows: S41, after the premixed material is transferred in, adjust the inlet air temperature and exhaust frequency converter to preheat the material to the preset value; S42, after the material is preheated, adjust the atomization pressure and spraying speed of the copovidone aqueous solution, start the spraying and granulation by the exhaust frequency converter, control the material temperature during the granulation process, and spray until granulation is completed. S43, sample and test the moisture content. When the moisture content of the material reaches the standard, stop drying and discharge the material.
6. The fluidized bed preparation process for metformin empagliflozin tablets according to claim 5, characterized in that, The air inlet temperature in S41 is set to 50-70℃, and the preset value is set to 30-50℃; the atomization pressure in S42 is set to 1.5-3.0 bar, and the spraying speed is set to 50-200 g / min.
7. The fluidized bed preparation process for metformin empagliflozin tablets according to claim 2, characterized in that, The specific steps of S5 are as follows: S51, the dry-granulated granules, magnesium stearate, and silica are added sequentially to the three-dimensional motion high-efficiency mixer; S52, set the mixing speed to 25-45 rpm and the mixing time to 15-20 min for mixing.
8. The fluidized bed preparation process for metformin empagliflozin tablets according to claim 2, characterized in that, The specific steps of S6 are as follows: S61, Calculate the required tablet weight based on the total mixed intermediate product content determination results; S62, Formal Tableting: Set the tableting speed to 30-60 tablets / minute, and monitor the tablet weight difference, hardness, and brittleness of the samples during the tableting process.
9. The fluidized bed preparation process for metformin empagliflozin tablets according to claim 2, characterized in that, The specific steps of S7 are as follows: S71, add the second purified water to the mixing tank, start stirring, and slowly add the film coating premix for later use; S72, put the qualified uncoated tablets into the coating pan, control the temperature of the tablet bed, and preheat the uncoated tablets; S73, set the atomization pressure and adjust the coating pan speed to a suitable range to ensure the material flows evenly; S74, begin coating, control the inlet air temperature and spray speed, maintain the tablet bed temperature until coating is complete, and control the coating weight gain of the coated tablets to reach 2%-4%; S75, maintain the bed temperature, dry for 15-20 minutes, turn off the heating, and let the sheet temperature drop to room temperature before discharging.
10. The fluidized bed preparation process for metformin empagliflozin tablets according to claim 9, characterized in that, The tablet bed temperature in S72 is set to 30-50℃; the atomization pressure in S73 is set to 1.0-2.0 bar, and the coating pan rotation speed is set to 3-8 rpm; the inlet air temperature in S74 is set to 50-70℃, the liquid spraying speed is set to 5-20 g / min, and the tablet bed temperature is set to 30-50℃; the tablet bed temperature in S75 is set to 30-50℃.