A glimepiride tablet and a method for preparing the same

Abstract

This invention relates to a glimepiride tablet and its preparation method. The glimepiride tablet, by weight, comprises: 2.0 parts glimepiride, 150-160 parts diluent, 8-15 parts disintegrant, 0.8-1.2 parts binder, and 0.8-1.2 parts lubricant. The diluent is selected from any one or more of the following: lactose, microcrystalline cellulose, or combinations thereof. This invention optimizes the product formulation and preparation process of glimepiride tablets, reducing the impurity content in the tablets and significantly improving the product's stability and dissolution performance.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical formulation technology, and in particular to a glimepiride tablet and its preparation method. Background Technology

[0002] Glimepiride is a new generation of sulfonylurea hypoglycemic drugs that mainly exerts its effect by stimulating the release of insulin from pancreatic β cells. Its chemical name is 1-[[4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrrolino-1-carboxamido)ethyl]phenyl]sulfonyl]-3-(trans-4-methylcyclohexyl)urea, and its molecular structure is as follows:

[0003]

[0004] Glimepiride regulates insulin secretion through its interaction with ATP-dependent potassium channels in the pancreatic β-cell membrane. Glimepiride specifically binds to a 65 kDa protein in the β-cell membrane, and this interaction determines the opening or closing of the ATP-dependent potassium channels. Glimepiride closes the potassium channels, inducing β-cell depolarization, while simultaneously opening voltage-sensitive calcium channels, leading to calcium ion influx into the cell. Ultimately, the increased intracellular calcium concentration stimulates insulin release through exocytosis.

[0005] Glimepiride is a new generation of sulfonylurea drugs developed by the German company Hoechest Marion Roussel. It was first launched in Sweden in September 1995 under the brand name Amary. In 1996, it was approved by the FDA for the treatment of type 2 diabetes in patients whose blood sugar cannot be adequately controlled by diet, exercise therapy and weight loss.

[0006] CN102416004A discloses a glimepiride tablet and its preparation method, which is prepared by directly compressing glimepiride with lactose, microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate into tablets; its formulation composition differs from that of the reference preparation (the reference preparation contains the excipient povidone), and the different formulation composition may lead to dissimilarity in BE (bioequivalence) with the reference preparation.

[0007] CN111135150A discloses a glimepiride tablet and its preparation method, which involves mixing micronized glimepiride, lactose, and povidone, using a certain amount of water or ethanol aqueous solution as a wetting agent, and increasing the mixing shear time to achieve a solubilizing effect. In this product, lactose acts as a filler and povidone acts as a binder. If water is used as a wetting agent, both lactose and povidone can act as binders, which is not conducive to the dissolution of the active pharmaceutical ingredient.

[0008] CN109481408A discloses a glimepiride tablet and its preparation method, which utilizes the hydrogen bonding between povidone and glimepiride and adopts a powder direct pressing preparation technology. However, the dissolution curves of the prepared sample are not similar to those of the reference preparation, which is not conducive to in vivo absorption.

[0009] The aforementioned methods for preparing glimepiride tablets suffer from drawbacks such as cumbersome processes and low production efficiency. Therefore, there is an urgent need to provide a glimepiride tablet with high stability, good dissolution performance, and a simple preparation process, along with its preparation method. Summary of the Invention

[0010] To address the deficiencies and shortcomings in the aforementioned technical problems, this application provides a glimepiride tablet and its preparation method. The glimepiride tablet is prepared by thoroughly mixing glimepiride and lactose, adding other excipients, using a binder solution, and then performing wet granulation, drying, mixing, and tableting. The glimepiride tablets prepared by the formulation and method of this invention reduce the impurity content in the tablets and significantly improve the stability and dissolution performance of the formulation.

[0011] This invention is achieved through the following means:

[0012] A glimepiride tablet, by weight, comprises: 2.0g glimepiride, 150-160g diluent, 8-15g disintegrant, 0.8-1.2g binder, and 0.8-1.2g lubricant;

[0013] The diluent is selected from any one or more of the following: lactose, microcrystalline cellulose, or a combination thereof;

[0014] Preferably, the diluent is a composition of lactose and microcrystalline cellulose;

[0015] More preferably, the lactose type is selected as: regular lactose.

[0016] In some embodiments, the particle size of lactose is 80-200 mesh; preferably, the ordinary lactose is 200 mesh.

[0017] In some embodiments, the weight ratio of the diluent lactose to microcrystalline cellulose is (120-150):(10-30); preferably, the weight ratio of lactose to microcrystalline cellulose is 137.2:14.0.

[0018] In some embodiments, the weight parts of the diluent and the disintegrant are controlled at 160 to 175 parts by weight; preferably 165.2 parts by weight.

[0019] In some embodiments, the disintegrant is selected from any one or more of the following: sodium carboxymethyl starch or crospovidone; preferably, the disintegrant is sodium carboxymethyl starch.

[0020] In some embodiments, the adhesive is selected from any one or more of the following: povidone K25 or povidone K30; preferably, the adhesive is povidone K30.

[0021] In some embodiments, the amount of povidone K30 used is 0.8 to 1.2 parts by weight; preferably, the amount of povidone K30 used is 1.0 parts by weight.

[0022] In some embodiments, the lubricant is selected from any one or more of the following: magnesium stearate or silicon dioxide; preferably, the lubricant is magnesium stearate.

[0023] In some embodiments, the amount of magnesium stearate is 0.8 to 1.2 parts by weight; preferably, the amount of magnesium stearate is 1.0 parts by weight.

[0024] In some embodiments, the tablets further include 0.1 to 2.0 parts by weight of a pigment; in some preferred embodiments, the pigment is used in an amount of 0.5 to 1.0 parts by weight.

[0025] In some embodiments, the pigment is selected from any one or more of the following: yellow iron oxide, indigo aluminum lake, or combinations thereof; in some preferred embodiments, the pigment is a combination of yellow iron oxide and indigo aluminum lake.

[0026] In some embodiments, the amount of the yellow iron oxide and indigo aluminum lake composition is 0.5 to 1 part by weight; preferably, the amount is 0.8 parts by weight.

[0027] In some preferred embodiments, the drug is used to treat type 2 diabetes.

[0028] In some preferred embodiments, the drug is administered orally.

[0029] This invention also provides a method for preparing glimepiride tablets, comprising the following steps:

[0030] (1) Weigh out glimepiride, diluent, disintegrant and optional pigment and mix them in a mixer;

[0031] (2) Wet particles were prepared using a binder solution and dried in a fluidized bed.

[0032] (3) Add lubricant to the dried material and mix thoroughly; preferably, mix thoroughly.

[0033] (4) Tableting, packaging, and preparation of glimepiride tablets; preferably, packaging is also included after tableting.

[0034] In some implementations, step (1) of the mixing process is as follows:

[0035] First, add glimepiride and lactose, and mix for 3-5 minutes.

[0036] Then add microcrystalline cellulose, sodium carboxymethyl starch, and optionally yellow iron oxide and indigo, and mix for 5–7 minutes.

[0037] In some preferred embodiments, the particle size D90 of glimepiride in step (1) is 1.0 to 10.0 μm; preferably, the particle size D90 of glimepiride is 1.0 to 3.0 μm.

[0038] In some preferred embodiments, the fluidized bed drying temperature in step (2) is 55-65°C and the moisture content is controlled to be within 6.0%.

[0039] In some preferred embodiments, step (3) is performed using a cone mixer for a mixing time of 10 to 15 minutes.

[0040] In some preferred embodiments, the tableting process in step (4) controls the tablet hardness to be 130-160 N.

[0041] In addition, the present invention provides the use of glimepiride tablets in the preparation of a medicament for the treatment of type 2 diabetes.

[0042] In some preferred embodiments, the drug is administered orally.

[0043] The beneficial effects of this invention are as follows:

[0044] This invention provides a glimepiride tablet and its preparation method, optimizing its formulation and preparation process. Compared with tablet products obtained by other formulations and / or preparation processes, the glimepiride tablets obtained by this invention reduce the impurity content in the tablets and significantly improve the product's stability and dissolution performance.

[0045] Specifically:

[0046] 1. The product formulation and preparation process of the present invention produce tablets with good uniformity. Compared with tablet products obtained by other formulations and / or preparation processes, the formulation and method of the present invention significantly reduce the impurity content in glimepiride tablets, improve the stability of drug tablets under high temperature and high humidity conditions, and significantly improve the dissolution performance of tablets.

[0047] 1) By using the lactose type of this invention, the impurity content in the finished tablets is significantly reduced, and the stability of the drug tablets under accelerated conditions such as high temperature and high humidity is improved;

[0048] Compared to other types of lactose, tablets made with regular lactose have the lowest impurity content and the best stability.

[0049] 2) Changing the diluent ratio significantly reduced the impurity content in the finished tablets and improved the stability of the drug tablets under high temperature conditions;

[0050] Compared to other diluent formulations, using a mixture of lactose and microcrystalline cellulose as a diluent, and controlling the weight ratio of lactose to microcrystalline cellulose to (120–150): (10–30), can significantly reduce impurity content while ensuring stability; when lactose to microcrystalline cellulose to (137.2): 14.0, the impurity content is the lowest and the stability is the best.

[0051] 3) By changing the amount of binder, the impurity content in the finished tablets was significantly reduced, the stability of the tablets under high temperature conditions was improved, and the dissolution performance of the tablets was also significantly improved.

[0052] Compared to other ranges of binder formulation dosages, when the weight parts of povidone K30 are 0.8 to 1.2, the resulting glimepiride tablets have low impurity content, good stability under high temperature conditions, and excellent dissolution performance; when the weight parts of povidone K30 are controlled at 1.0, the tablets have the best impurity content, stability, and dissolution performance.

[0053] 4) Changing the amount of lubricant significantly improves the dissolution performance of tablets;

[0054] Compared to other ranges of lubricant formulations, magnesium stearate exhibits good dissolution performance when used as a lubricant; the best dissolution performance is achieved when 0.8 to 1.2 parts by weight of magnesium stearate is added, especially 1.0 parts by weight of magnesium stearate.

[0055] 2. In the formulation of this application, lactose can be fully and evenly mixed with glimepiride and other excipients, which significantly improves the stability and safety of the product, thereby improving the quality of the product, ensuring the stability of product quality, ensuring clinical treatment effect, and the prescription is simple and easy to use, saving production costs. Attached Figure Description

[0056] Figure 1 This is a comparison of the dissolution curves of glimepiride tablets prepared by methods 1 and 2 in Example 1 of the present invention and a reference formulation in phosphate buffer at pH 6.8.

[0057] Figure 2 This is a comparison of the dissolution curves of the glimepiride tablets prepared by method 1 in Example 4 of the present invention and the reference formulation in phosphate buffer at pH 6.8.

[0058] Figure 3This is a comparison of the dissolution curves of the glimepiride tablets prepared by method 2 in Example 4 of the present invention and the reference formulation in phosphate buffer at pH 6.8.

[0059] Figure 4 This is a comparison of the dissolution curves of the glimepiride tablets prepared by method 3 in Example 4 of the present invention and the reference formulation in phosphate buffer at pH 6.8.

[0060] Figure 5 This is a comparison of the dissolution curves of the glimepiride tablets prepared by method 4 of Example 4 of the present invention and the reference formulation in phosphate buffer at pH 6.8.

[0061] Figure 6 This is a comparison of the dissolution curves of the glimepiride tablets prepared by method 1 in Example 5 of the present invention and the reference formulation in phosphate buffer at pH 6.8.

[0062] Figure 7 This is a comparison of the dissolution curves of the glimepiride tablets prepared by method 2 in Example 5 of the present invention and the reference formulation in phosphate buffer at pH 6.8.

[0063] Figure 8 This is a comparison of the dissolution curves of the glimepiride tablets prepared by method 3 in Example 5 of the present invention and the reference formulation in phosphate buffer at pH 6.8.

[0064] Figure 9 This is a comparison of the dissolution curves of the glimepiride tablets prepared by method 4 in Example 5 of the present invention and the reference formulation in phosphate buffer at pH 6.8. Detailed Implementation

[0065] The following embodiments further describe the technical solution of the present invention. These embodiments are for illustrative purposes only and are not intended to limit the invention. Therefore, any modifications or equivalent substitutions to the technical solution of the present invention based on the method described herein are within the scope of protection of the present invention.

[0066] Example 1

[0067] Example 1 Method 1

[0068] A glimepiride tablet uses lactose and microcrystalline cellulose as diluents, sodium carboxymethyl starch as a disintegrant, povidone K30 as a binder, and magnesium stearate as a lubricant. The product formulation is shown in Table 1-1.

[0069] Table 1-1 Product Prescription

[0070]

[0071]

[0072] The preparation method is as follows:

[0073] (1) Weighing: Weigh glimepiride, 200 mesh regular lactose, microcrystalline cellulose, sodium carboxymethyl starch, povidone K30 and magnesium stearate according to the product prescription in Table 1, and set aside.

[0074] Among them, the particle size D90 of glimepiride is less than 3.0 μm;

[0075] Place the prescribed amount of glimepiride and 200-mesh regular lactose in a wet granulation mixer and mix for 3 minutes. Then add microcrystalline cellulose and sodium carboxymethyl starch and mix for 5 minutes.

[0076] (2) Wet granulation was performed using povidone K30 solution for 3 min; the wet granules were then placed in a fluidized bed for drying at 60°C for 30 min, and the resulting formulation granules contained 5.2% moisture.

[0077] (3) After drying, add magnesium stearate and mix for 10 min at a mixing frequency of 15 Hz;

[0078] (4) Finally, glimepiride tablets are obtained by compression and packaging; during compression, the hardness of the tablets is controlled to be 150N.

[0079] Example 1 Method 2

[0080] A glimepiride tablet uses lactose and microcrystalline cellulose as diluents, sodium carboxymethyl starch as a disintegrant, povidone K30 as a binder, and magnesium stearate as a lubricant. The product formulation is shown in Table 1-2.

[0081] Table 1-2 Product Prescriptions

[0082]

[0083] The preparation method is as follows:

[0084] (1) Weighing: Weigh glimepiride, 200 mesh regular lactose, microcrystalline cellulose, sodium carboxymethyl starch, yellow iron oxide, indigo aluminum lake, povidone K30 and magnesium stearate according to the product prescription in Table 1, and set aside.

[0085] Among them, the particle size D90 of glimepiride is less than 3.0 μm;

[0086] Place the prescribed amount of glimepiride and 200-mesh regular lactose in a wet granulation mixer and mix for 3 minutes. Then add microcrystalline cellulose, sodium carboxymethyl starch, yellow iron oxide and indigo aluminum lake and mix for 5 minutes.

[0087] (2) Wet granulation was performed using povidone K30 solution for 3 min; the wet granules were then placed in a fluidized bed for drying at 60°C for 30 min, and the resulting formulation granules contained 5.2% moisture.

[0088] (3) After drying, add magnesium stearate and mix for 10 min at a mixing frequency of 15 Hz;

[0089] (4) Finally, glimepiride tablets are obtained by compression and packaging; during compression, the hardness of the tablets is controlled to be 150N.

[0090] No pigment is added to the formulation of Method 1 in Example 1 above, while pigment is added to the formulation of Method 2 in Example 1. All other formulation components and preparation methods remain consistent. The pigment is used solely for coloring and does not affect the stability or dissolution properties of the tablets. The tablets produced by Method 1 and Method 2 in Example 1 have the same properties.

[0091] Example 2 Different types of lactose

[0092] Referring to the preparation method of Method 1 in Example 1, different types of lactose were used, i.e., the lactose in step (2) was changed from the ordinary lactose (200 mesh) in Example 1 to:

[0093] Method 1: Regular lactose (120 mesh);

[0094] Method 2: Regular lactose (80 mesh);

[0095] Method 3: Spray drying type (80 mesh);

[0096] The dosage and procedures for other ingredients are the same as in Example 1, Method 1.

[0097] Example 3 Different diluent ratios

[0098] Referring to the preparation method of Method 1 in Example 1, the total amount of lactose, microcrystalline cellulose (diluent), and sodium carboxymethyl starch (disintegrant) was 165.2 parts by weight, wherein the weight ratio of lactose to microcrystalline cellulose was (120-150):(10-30). The ratio of lactose to microcrystalline cellulose in Example 1 was changed to 137.2:14.0, and the specific ratio and amount are shown in Table 2.

[0099] Table 2

[0100]

[0101] The dosage and procedures for other ingredients are the same as in Example 1, Method 1.

[0102] Example 4: Different Adhesive Doses

[0103] In the formulation, the weight of the adhesive is controlled between 0.8 and 1.5. Referring to the preparation method of Method 1 in Example 1, the amount of povidone K30 (1.0) in Method 1 of Example 1 is changed. The specific amounts are shown in Table 3.

[0104] Table 3

[0105] serial number Parts by weight of povidone K30 Povidone K30 mass / mg Method 1 0.8 0.8 Method 2 1.2 1.2 Method 3 0.5 0.5 Method 4 1.5 1.5

[0106] The dosage and procedures for other ingredients are the same as in Example 1, Method 1.

[0107] Example 5: Different Lubricant Doses

[0108] In the formulation, the amount of lubricant is controlled at 0.8 to 1.2 parts by weight. Referring to the preparation method of Method 1 in Example 1, the amount of magnesium stearate (1.0 parts by weight) in Method 1 of Example 1 is changed. The specific amounts are shown in Table 4.

[0109] Table 4

[0110] serial number Parts by weight of magnesium stearate Magnesium stearate dosage / mg Method 1 0.8 0.8 Method 2 1.2 1.2 Method 3 0.5 0.5 Method 4 1.5 1.5

[0111] The dosage and procedures for other ingredients are the same as in Example 1, Method 1.

[0112] Comparative Example 1:

[0113] The main difference between Comparative Example 1 and Method 2 of Example 1 is that the formulation is the same, but the preparation methods are different.

[0114] Comparative Example 1 uses the formulation of Method 2 in Example 1, except that: glimepiride tablets are prepared according to the preparation process of patent CN111603453A.

[0115] The preparation process is as follows:

[0116] (1) The particle size D90 of glimepiride is less than 3.0 μm;

[0117] (2) Glimepiride and regular lactose were mixed and passed through a 100-mesh sieve, and then mixed with 70% of the sodium carboxymethyl starch in a wet granulator for 25 minutes to obtain a premixed powder.

[0118] (3) The soft material was prepared by using polyvinyl ketone K30 solution, granulated by 20-mesh sieve, and dried in a fluidized bed with moisture content controlled at 0.2% to 3.5%;

[0119] (4) Add the dried granules to the remaining 30% of sodium carboxymethyl starch, microcrystalline cellulose, yellow iron oxide, indigo aluminum lake and magnesium stearate and mix and compress into tablets.

[0120] (5) When compressing tablets, control the tablet hardness to 150N.

[0121] The other methods and steps are the same as those in Method 2 of Example 1.

[0122] Comparative Examples 2-3:

[0123] The difference between the formulation and preparation process of Comparative Example 1 is as follows:

[0124] In step (1) of the preparation process, the particle size D90 of glimepiride was changed from less than 3.0 μm to:

[0125] Comparative Example 2: 5.0 μm;

[0126] Comparative Example 3: 10.0 μm.

[0127] The other steps are the same as in Comparative Example 1.

[0128] The stability of the drug tablets was evaluated by measuring the content of various impurities in the drug tablets prepared by the methods of the examples and comparative examples and the reference preparation.

[0129] Experiment Example 1: Stability Evaluation

[0130] The impurity content of glimepiride tablets was determined under the following experimental conditions to investigate the stability of the drug tablets.

[0131] Experimental conditions:

[0132] Acceleration conditions: Placed for 6 months at a temperature of 40℃±2℃ and a humidity of 75%±5%;

[0133] High temperature conditions: Place at 60℃ for 30 days.

[0134] Glimepiride is sensitive to high temperatures, and under high-temperature conditions, it degrades to generate impurity III as shown below:

[0135] Impurity III has the following structural formula:

[0136]

[0137] 1-1. Effect of acceleration conditions (temperature 40℃±2℃, humidity 75%±5%) on stability

[0138] Example 1, Comparative Example 1, and the reference preparation were placed under accelerated conditions (temperature 40℃±2℃, humidity 75%±5%) for 6 months. Samples were taken at 0, 1, 3, and 6 months to examine the content of each impurity. The results were compared with those at month 0. The limit standard for impurity III was ≤1.0%, the limit standard for other single impurities was ≤0.5%, and the limit standard for other total impurities was ≤1.0%. The results are shown in Table 5.

[0139] Table 5 Comparison of impurity content in Example 1, Comparative Example 1, and reference formulation under accelerated conditions.

[0140]

[0141]

[0142] Results analysis:

[0143] In Example 1, the tablets prepared by Method 1 showed lower levels of all impurities than the reference formulation: stability at 0 months was superior to the reference formulation; after 1 month of accelerated storage, no other single impurities or total impurities were detected; at 3 months, no other single impurities were detected, and the total impurity content was 0.01%; at 6 months, the impurity III content was controlled at 0.09%, an increase of only 0.04% compared to 0 months, and significantly lower than the impurity content of the reference formulation under the same conditions (0.25%). No other single impurities were detected, and the total impurity content was controlled at 0.02%, with no significant change, and all were significantly lower than the impurity limits (Impurity III limit ≤ 1.0%, other single impurity limit ≤ 0.5%, other total impurity limit ≤ 1.0%), indicating good stability.

[0144] As the storage time increased, the content of each impurity in the glimepiride tablets prepared by method 1 of Example 1 was significantly lower than that in the reference preparation under the same conditions, indicating that the stability of the glimepiride tablets prepared by the method of the present invention is better than that of the reference preparation.

[0145] The tablets prepared in Comparative Example 1 had an impurity III content of 0.10% at month 0, which was significantly higher than the impurity III content (0.05%) in Method 1 of Example 1 from the initial preparation stage. During accelerated storage, the impurity III content in Comparative Example 1 was also significantly higher than that in Method 1 of Example 1; in particular, the impurity III content in Comparative Example 1 exceeded that in Method 1 of Example 1 by more than 50%. Furthermore, after 6 months of accelerated storage, the total impurity content in Comparative Example 1 increased from 0 to 0.08%, indicating that tablets prepared using the method of Comparative Example 1 are prone to increased impurity content and poor stability during storage.

[0146] The impurity content of the tablets prepared by method 1 in Example 1 was significantly lower than that of Comparative Example 1. The preparation process used in method 1 of Example 1 effectively reduced the impurity content of the tablets: the impurity III content of the tablets prepared by method 1 of Example 1 was much lower than that of Comparative Example 1 and the reference formulation, indicating that the stability of the tablets prepared by method 1 of Example 1 was better than that of Comparative Example 1 in the early stage of preparation.

[0147] After being placed under accelerated conditions for 6 months, the content of each impurity in Example 1, Method 1 was significantly lower than that in Comparative Example 1, indicating that the stability of the glimepiride tablets prepared by Method 1 of Example 1 of the present invention is still significantly better than that of Comparative Example 1 after being placed under accelerated conditions (temperature 40℃±2℃, humidity 75%±5%).

[0148] The only difference between Method 2 and Method 1 in Example 1 is whether or not pigment is added for coloring, which has no effect on the dissolution properties of the formulation product.

[0149] Therefore, the finished tablets prepared by method 2 in Example 1 and method 1 in Example 1 show that the types of impurities, the content of each impurity, and the total impurity content are roughly the same in the stability test results of impurity content, which is consistent with the above comparison conclusion.

[0150] summary:

[0151] The present invention significantly improves the stability of tablets by improving the preparation process. Compared with tablets prepared by other processes (e.g., Comparative Example 1 and reference formulation), the tablets of this application show a significant reduction in impurity content and good stability after being stored for 0 months and 6 months under accelerated conditions (temperature 40℃±2℃, humidity 75%±5%).

[0152] 1-2. The effect of different types of lactose on stability

[0153] The stability of glimepiride tablets prepared with different lactose formulations was investigated using the following methods:

[0154] Example 1, Method 1: 200-mesh regular lactose;

[0155] Example 1, Method 2: 200-mesh regular lactose;

[0156] Example 2, Method 1: 120-mesh regular lactose;

[0157] Example 2, Method 2: 80-mesh regular lactose;

[0158] Example 2, Method 3: 80-mesh spray-dried lactose;

[0159] Finished tablets were prepared and placed at a high temperature of 60°C. The impurity content of the finished tablets after 0 days and 30 days was analyzed and compared with the impurity content in the reference preparation. The results are shown in Table 6.

[0160] Table 6 Comparison of impurity content in Examples 1 and 2 and the reference formulation under high temperature conditions.

[0161]

[0162]

[0163] Results analysis:

[0164] The finished tablets prepared using 200-mesh ordinary lactose in Example 1, after being placed at 60°C for 30 days, had an impurity III content of 1.35%, which was much lower than that in Example 2, Method 3 (1.65%) and the reference preparation (1.59%). The contents of other single impurities and other total impurities remained unchanged at 0, indicating the best stability.

[0165] In Example 2, the finished tablets prepared using 120-mesh and 80-mesh ordinary lactose were placed at 60°C for 30 days. The increase in impurity III was lower than that in the reference preparation (1.42%) and much smaller than that in Example 2, Method 3 (1.59%). The increase in other single impurities and total impurities was controlled below 0.02%, indicating good stability.

[0166] The finished tablets prepared using spray-dried lactose in Example 2 and Method 3, after being placed at 60°C for 30 days, showed a significant increase in the content of impurity III to 1.65%, which was higher than that of the reference formulation (1.59%). The contents of other single impurities and other total impurities were 0.02% and 0.03%, respectively, which were higher than those of the reference formulation under the same conditions (0.01% and 0.02%). The tablets exhibited poor stability and did not meet the formulation standards.

[0167] The only difference between Method 2 and Method 1 in Example 1 is whether or not pigment is added for coloring, which has no effect on the dissolution properties of the formulation product.

[0168] Therefore, the finished tablets prepared by method 2 in Example 1 and method 1 in Example 1 show that the types of impurities, the content of each impurity, and the total impurity content are roughly the same in the stability test results of impurity content, which is consistent with the above comparison conclusion.

[0169] summary:

[0170] The results of changes in various impurities under a high temperature of 60°C show that the type of lactose significantly affects tablet stability. In Examples 1, Methods 1-2 and Examples 2, Methods 1-2, using ordinary lactose, the increase in impurity III content was not significant, and other single impurities and total impurities showed no significant changes, indicating excellent stability. In contrast, tablets prepared with spray-dried lactose exhibited poor stability and did not meet formulation standards, resulting in unusable finished products. Therefore, the tablets prepared using ordinary lactose in this application demonstrate significantly better stability than those prepared with spray-dried lactose.

[0171] 1-3. Effect of different diluent ratios on stability

[0172] The stability of glimepiride tablets prepared with different weight proportions of diluents in the formulation was investigated, using lactose and microcrystalline cellulose in different weight proportions as diluents as examples:

[0173] Example 1, Method 1: Lactose: Microcrystalline cellulose = 137.2:14.0;

[0174] Example 1, Method 2: Lactose: Microcrystalline cellulose = 137.2:14.0;

[0175] Example 3, Method 1: Lactose: Microcrystalline cellulose = 127.2:30;

[0176] Example 3, Method 2: Lactose: Microcrystalline cellulose = 137.2:20;

[0177] Example 3, Method 3: Lactose: Microcrystalline cellulose = 147.2:10;

[0178] Example 3, Method 4: Lactose: Microcrystalline cellulose = 117.2:40;

[0179] Example 3, Method 5: Lactose = 157.2;

[0180] The finished tablets prepared under the above-mentioned different diluent dosage conditions were placed at a high temperature of 60°C, and the impurity content at 0 days and 30 days was analyzed and compared with the impurity content in the reference preparation. The results are shown in Table 7.

[0181] Table 7. Comparison of impurities in Examples 1 and 3 and the reference formulation under high-temperature conditions.

[0182]

[0183]

[0184] Results analysis:

[0185] In Example 1, Method 1, finished tablets were prepared using lactose and microcrystalline cellulose in a weight ratio of 137.2:14.0. After being placed at a high temperature of 60°C for 30 days, the content of impurity III was 1.35%, which was much lower than the content of impurity III in the reference preparation under the same conditions (1.59%). Other single impurities and other total impurities were still not detected. Furthermore, after 30 days of high-temperature placement, the change in the content of impurity III was controlled at 1.30%, which was also much lower than the increase in impurity III in the reference preparation (1.42%), indicating the best stability.

[0186] In Examples 3, the tablets prepared using methods 1-3 with lactose and microcrystalline cellulose weight ratios of 127.2:30, 137.2:20, and 147.2:10, after being stored at 60°C for 30 days, showed that the content of impurity III was controlled within the range of 1.41% to 1.47%, lower than the impurity III content in the reference formulation (1.59%). The content of other single impurities and total impurities increased by only 0.01%, with no significant change. Furthermore, in terms of the increase rate, the increase of impurity III in the tablets prepared using methods 1-3 in Examples 3 (1.35%, 1.37%, 1.40%) was far lower than the increase of impurity III in the reference formulation (1.42%), indicating good stability.

[0187] In Example 3, Method 4 used lactose and microcrystalline cellulose in a weight ratio of 117.2:40, and Method 5 used 157.2 parts by weight of lactose alone as a diluent. After the finished tablets were placed at a high temperature of 60°C, the content of impurity III in Method 4 increased from 0.10% to 1.64% (an increase of 1.54%), and the content of impurity III in Method 5 increased from 0.14% to 1.71% (an increase of 1.57%). After 30 days of high-temperature placement, the content and increase of impurity III in both methods were significantly higher than those in the reference formulation (content of 1.59% and increase of 1.42%). The increase in impurity content was significant, the stability was poor, and it did not meet the formulation standards.

[0188] The only difference between Method 2 and Method 1 in Example 1 is whether or not pigment is added for coloring, which has no effect on the dissolution properties of the formulation product.

[0189] Therefore, the finished tablets prepared by method 2 in Example 1 and method 1 in Example 1 show that the types of impurities, the content of each impurity, and the total impurity content are roughly the same in the stability test results of impurity content, which is consistent with the above comparison conclusion.

[0190] summary:

[0191] The results of changes in various impurities under high temperature conditions of 60℃ show that the proportion of diluent significantly affects tablet stability. Tablets prepared using a lactose and microcrystalline cellulose weight ratio of (120–150):(10–30) exhibited minimal changes in impurity III content under high temperature conditions of 60℃, while the contents of other single impurities and total impurities remained essentially unchanged, demonstrating good stability significantly superior to other tablets in the prior art.

[0192] Among them, the tablets prepared when the weight ratio of lactose to microcrystalline cellulose was 137.2:14.0 had the lowest variation in impurity content and the best tablet stability.

[0193] Conversely, formulations prepared using other diluent ratios (e.g., tablets obtained by method 4 in Example 3) do not meet formulation standards and cannot be used.

[0194] 1-4. Effect of different adhesive dosages on stability

[0195] The stability of glimepiride tablets prepared with different amounts of binder in the formulation was investigated, using povidone K30 as a binder as an example:

[0196] Example 1, Method 1: The amount of povidone K30 used was 1.0 part by weight;

[0197] Example 1, Method 2: The amount of povidone K30 used was 1.0 part by weight;

[0198] Example 4, Method 1: The amount of povidone K30 used was 0.8 parts by weight;

[0199] Example 4, Method 2: The amount of povidone K30 used was 1.2 parts by weight;

[0200] Example 4, Method 3: The amount of povidone K30 used was 0.5 parts by weight;

[0201] Example 4, Method 4: The amount of povidone K30 used was 1.5 parts by weight;

[0202] The finished tablets prepared under the above-mentioned different weight parts of binder conditions were placed at a high temperature of 60°C, and the impurity content at 0 days and 30 days was analyzed and compared with the impurity content in the reference preparation. The results are shown in Table 8.

[0203] Table 8. Comparison of impurities in Examples 1 and 4 with the reference formulation under high-temperature conditions.

[0204]

[0205] Results analysis:

[0206] In Example 1, Method 1, 1.0 part by weight of povidone K30 tablets were placed at 60°C for 30 days. The content of impurity III was 1.35%, which was much lower than the content of impurity III in the reference preparation under the same conditions (1.59%). Other single impurities and other total impurities were still not detected. Furthermore, after 30 days of high-temperature placement, the change in the content of impurity III was controlled at 1.30%, which was also much lower than the increase in impurity III in the reference preparation (1.42%), indicating the best stability.

[0207] In Example 4, Methods 1 and 2 used tablets with 0.8 and 1.2 parts by weight of povidone K30, respectively. Under high temperature conditions of 60°C, the content of impurity III was 1.49% and 1.46%, respectively, which was lower than the reference preparation of 1.59%. The content of other single impurities and other total impurities changed by 0.01%, which remained basically unchanged, indicating good stability.

[0208] In Examples 4, Methods 3 and 4 used tablets with 0.5 and 1.5 parts by weight of povidone K30, respectively. Under high temperature conditions of 60°C, impurity III increased by 1.55% and 1.51%, respectively. The content change was higher than the increase value of the reference preparation (1.42%), indicating poor stability and failure to meet the formulation standards.

[0209] The only difference between Method 2 and Method 1 in Example 1 is whether or not pigment is added for coloring, which has no effect on the dissolution properties of the formulation product.

[0210] Therefore, the finished tablets prepared by method 2 in Example 1 and method 1 in Example 1 show that the types of impurities, the content of each impurity, and the total impurity content are consistent in the stability test results, which is also in line with the above comparison conclusion.

[0211] summary:

[0212] The results of changes in various impurities under high temperature conditions of 60℃ show that the amount of binder significantly affects tablet stability. Tablets using 0.8–1.2 parts by weight of povidone K30 exhibited minimal change in the content of impurity III under 60℃ conditions, while the contents of other single impurities and total impurities remained unchanged, demonstrating good stability significantly superior to other tablet products.

[0213] Among them, tablets with a povidone K30 dosage of 1.0 part by weight showed the least variation in impurity content and the best tablet stability.

[0214] Conversely, formulations prepared using other amounts of binder (e.g., tablets prepared using methods 3-4 in Example 4) do not meet formulation standards and cannot be used.

[0215] Experimental Example 2: Dissolution Analysis

[0216] Dissolution is a key factor in evaluating drug release behavior and formulation performance. Among these methods, the paddle method offers high precision and reproducibility, making it a better fit for evaluating the in vitro release of common oral formulations by simulating the actual release via oral administration.

[0217] This product is a common oral tablet, and the dissolution test was conducted using the paddle method.

[0218] Based on in vivo and in vitro correlation, a universal dissolution analyzer (UDT-812A-12) was used. The dissolution conditions were as follows: paddle method was adopted, with 900 mL of phosphate buffer (pH 6.8) as the dissolution medium, temperature of 37±0.5℃, and rotation speed of 50 r / min. 10 mL samples were taken at 5 min, 10 min, 15 min, 30 min, 45 min, 60 min, and 90 min, and 10 mL of the same medium at the same temperature was added. The dissolution solution was filtered through a 0.45 μm polyethersulfone filter membrane. The initial filtrate was discarded, and the subsequent filtrate was analyzed by high performance liquid chromatography to detect the dissolved substances and their content.

[0219] Dissolution tests were conducted on different formulations, and the dissolution curve results and similarity factor f2 were compared with those of the reference formulation.

[0220] The formula for calculating the similarity factor f2 is:

[0221]

[0222] Among them, R t T represents the average dissolution rate of the reference sample at time t; t t represents the average dissolution amount of the test sample at time t; n represents the number of sampling time points.

[0223] Compared with the reference formulation, the closer the similarity factor f2 value of the prepared formulation is to 100, the better the dissolution effect. The formulation dissolution standard stipulates that f2 > 50; f2 below 50 indicates poor dissolution and the formulation product is unqualified.

[0224] 2-1. Effect of binder dosage on dissolution

[0225] The dissolution rate of glimepiride tablets prepared with different amounts of binder in the formulation was investigated, using povidone K30 as a binder as an example:

[0226] Example 1, Method 1: The amount of povidone K30 used was 1.0 part by weight;

[0227] Example 1, Method 2: The amount of povidone K30 used was 1.0 part by weight;

[0228] Example 4, Method 1: The amount of povidone K30 used was 0.8 parts by weight;

[0229] Example 4, Method 2: The amount of povidone K30 used was 1.2 parts by weight;

[0230] Example 4, Method 3: The amount of povidone K30 used was 0.5 parts by weight;

[0231] Example 4, Method 4: The amount of povidone K30 used was 1.5 parts by weight;

[0232] The finished tablets prepared under the above-mentioned different binder dosage conditions were tested for dissolution within 90 min in phosphate buffer at pH 6.8, and compared with the reference formulation. The dissolution curve results and similarity factor f2 comparison are shown in Table 9.

[0233] Table 9. Dissolution rates and similarity factors of Examples 1, 4, and the reference formulation in pH 6.8 medium.

[0234]

[0235]

[0236] Results analysis:

[0237] In Example 1 of this application, Method 1 uses 1.0 part by weight of povidone K30. Figure 1 The tablets of Example 1 showed that the average cumulative dissolution rate in phosphate buffer at pH 6.8 within 90 min was close to that of the reference formulation, and the similarity factor f2 of the dissolution curves of the two was 80, with the similarity factor being closest to 100. This indicates that the dissolution curve of Method 1 in Example 1 is highly consistent with the reference formulation and has the best dissolution behavior.

[0238] The only difference between Method 2 and Method 1 in Example 1 is whether or not a pigment is added for coloring; it has no effect on the dissolution properties of the formulation. The finished tablets prepared by Method 2 in Example 1 showed an average cumulative dissolution rate close to the reference formulation within 90 minutes in phosphate buffer at pH 6.8. Furthermore, the similarity factor f2 of their dissolution curves was 79, slightly lower than that of Method 1 in Example 1, but the similarity factor of Method 2 in Example 1 was close to 100, indicating that the dissolution curve of Method 2 in Example 1 was highly consistent with the reference formulation, and the dissolution behavior was significant.

[0239] In Example 4, methods 1 and 2 each used 0.8 parts by weight of povidone K30. Figure 2 ) and 1.2 parts by weight ( Figure 3 The tablets of the above formulation showed an average cumulative dissolution rate close to that of the reference formulation within 90 min in phosphate buffer at pH 6.8. The similarity factors f2 of the dissolution curves of the two formulations were 73 and 65, respectively, and both were close to 100. This indicates that the dissolution behavior of the dissolution curves of methods 1-2 in Example 1 was significantly better than that of the reference formulation.

[0240] In Example 4, methods 3 and 4 used 0.5 parts by weight of povidone K30 respectively. Figure 4 ) and 1.5 parts by weight ( Figure 5The tablets, when dissolved in phosphate buffer at pH 6.8, showed a significant difference in average cumulative dissolution rate within 90 minutes compared to the reference formulation. Furthermore, the similarity factor f2 of the dissolution curves of methods 3-4 in Example 4 was only 49, with all similarity factors < 50, which was significantly lower than that of methods 1-2 in Example 1 (f2 = 80 and 79). The dissolution curves of the tablets did not show similarity to the reference formulation, exhibited poor dissolution behavior, did not meet the formulation standards, and could not produce qualified formulation products.

[0241] summary:

[0242] The average cumulative dissolution rate over 90 minutes in phosphate buffer at pH 6.8 showed that the amount of binder significantly affects the dissolution performance of tablets. Compared with finished tablets prepared with other formulation amounts, tablets using 0.8–1.2 parts by weight of povidone K30 binder exhibited superior dissolution performance.

[0243] Among them, tablets with a binder content of 1.0 part by weight of povidone K30 showed the best dissolution performance.

[0244] Conversely, formulations prepared using other amounts of binder (e.g., methods 3-4 in Example 4) do not meet the formulation standards in terms of dissolution performance and cannot be used.

[0245] 2-2. Effect of Lubricant Dosage on Dissolution

[0246] The dissolution rate of glimepiride tablets prepared with different weight parts of lubricant in the formulation was investigated, taking magnesium stearate as an example:

[0247] Example 1, Method 1: Magnesium stearate dosage: 1.0 part by weight;

[0248] Example 1, Method 2: Magnesium stearate dosage 1.0 part by weight;

[0249] Example 5, Method 1: The amount of magnesium stearate used was 0.8 parts by weight;

[0250] Example 5, Method 2: The amount of magnesium stearate used was 1.2 parts by weight;

[0251] Example 5, Method 3: The amount of magnesium stearate used was 0.5 parts by weight;

[0252] Example 5, Method 4: The amount of magnesium stearate used was 1.5 parts by weight;

[0253] The finished tablets prepared under the above different lubricant dosage conditions were tested for dissolution within 90 min in phosphate buffer at pH 6.8, and compared with the reference formulation. The dissolution curve results and similarity factor f2 comparison are shown in Table 10.

[0254] Table 10. Dissolution rates and similarity factors of Examples 1, 5, and the reference formulation in pH 6.8 medium.

[0255]

[0256]

[0257] Results analysis:

[0258] In Example 1, Method 1 used tablets with 1.0 parts by weight of magnesium stearate. The average cumulative dissolution rate in phosphate buffer at pH 6.8 within 90 minutes was close to that of the reference formulation, and the similarity factor f2 of the dissolution curves of the two was 80, with the similarity factor being closest to 100. This indicates that the dissolution curve of Example 1, Method 1 is highly consistent with the reference formulation, and the dissolution behavior is optimal.

[0259] The only difference between Method 2 and Method 1 in Example 1 is whether or not a pigment is added for coloring; it has no effect on the dissolution properties of the formulation. The finished tablets prepared by Method 2 in Example 1 showed an average cumulative dissolution rate close to the reference formulation within 90 minutes in phosphate buffer at pH 6.8. The similarity factor f2 of their dissolution curves was 78, slightly lower than that of Method 1 in Example 1, but the similarity factor of Method 2 in Example 1 was close to 100, indicating that the dissolution curve of Method 2 in Example 1 was highly consistent with the reference formulation, and the dissolution behavior was significant.

[0260] In Example 5, methods 1 and 2 used magnesium stearate in an amount of 0.8 parts by weight. Figure 6 ) and 1.2 parts by weight ( Figure 7 The tablets of the formulation showed an average cumulative dissolution rate close to that of the reference formulation within 90 min in phosphate buffer at pH 6.8, and the similarity factors f2 of the dissolution curves of the two formulations were 69 and 71, respectively. The similarity factors were >50 and close to 100, indicating that the dissolution behavior of methods 1-2 in Example 5 was excellent.

[0261] In Example 5, methods 3-4 used magnesium stearate in an amount of 0.5 parts by weight. Figure 8 ) and 1.5 parts by weight ( Figure 9 The tablets from Example 5 showed a significantly different average cumulative dissolution rate compared to the reference formulation within 90 minutes in phosphate buffer at pH 6.8. Furthermore, the similarity factors f2 of the dissolution curves from methods 3 and 4 in Example 5 were 33 and 30, respectively, both far below 50. Moreover, the similarity factors (f2 = 33, f2 = 30) of the dissolution curves from methods 3 and 4 in Example 5 were significantly different from those from method 1 in Example 1 (f2 = 80 and 78), indicating a lack of similarity to the reference formulation dissolution curves, poor dissolution behavior, and failure to meet formulation standards, making it impossible to produce a qualified formulation product.

[0262] summary:

[0263] The average cumulative dissolution rate over 90 minutes in phosphate buffer at pH 6.8 showed that the amount of lubricant significantly affected the dissolution performance of the tablets. Compared with finished tablets prepared with other formulation amounts, tablets using 0.8–1.2 parts by weight of magnesium stearate as lubricant showed significantly better dissolution performance.

[0264] Among them, the tablets using 1.0 part by weight of magnesium stearate as a lubricant exhibited the best dissolution performance.

[0265] Conversely, formulations prepared using other amounts of lubricant (e.g., methods 3-4 in Example 5) do not meet the formulation standards in terms of dissolution performance and cannot be used.

[0266] 2-3. Effect of different preparation processes on dissolution

[0267] Finished formulations were prepared using the best-performing preparation process of the present invention (Example 1), the least effective preparation process (Example 2, Method 1), and the preparation processes of reference patents CN111603453A (Comparative Example 1, less than 3.0 μm), CN111603453A (Comparative Example 2, less than 5.0 μm), and CN111603453A (Comparative Example 3, less than 10.0 μm). Dissolution curves were detected in phosphate buffer solutions at different pH values ​​(4.5, 6.8). The similarity factor f2 of multiple dissolution curves of the reference formulation was compared. The results are shown in Table 11.

[0268] Table 11 Similarity factors of Examples 1, Comparative Examples 1-3 and the reference formulation in different dissolution media.

[0269]

[0270] Results analysis:

[0271] Example 1 represents the best performance of the present invention. The finished tablets prepared using methods 1 and 2 of Example 1 showed similarity factors f2 of 66 and 81 with the reference formulation in phosphate buffer solutions at pH 4.5 and 6.8, respectively. After 6 months of accelerated storage, the similarity factor f2 of the dissolution curve with the reference formulation was 65. Both maintained the standard of similarity factor > 50, indicating the best dissolution behavior.

[0272] In addition, the finished tablets prepared using the preparation process of Method 1 of Example 2 of the present invention, which had poorer results, had dissolution curve similarity factors f2 of 65 and 80 with the reference formulation in phosphate buffer solutions at pH 4.5 and 6.8, respectively; after accelerated storage for 6 months, the dissolution curve similarity factors f2 with the reference formulation were 62 and 64, respectively. Although the dissolution curve similarity factor f2 was slightly lower than that of Methods 1-2 of Example 1, it still maintained the standard of similarity factor > 50, and the dissolution behavior was significantly improved.

[0273] Comparative Example 1 adopted the preparation process of patent CN111603453A, in which, in step (1), the particle size D90 of glimepiride was less than 3.0 μm. The prepared finished tablets, in phosphate buffer solutions at pH 4.5 and 6.8, had dissolution similarity factors f2 of 60 and 65 with the reference formulation, respectively. The initial (0 months) f2 was lower than that of Method 2 in Example 1 (f2 = 66, f2 = 81). After 6 months of accelerated storage, the similarity factor f2 showed a significant decreasing trend, decreasing to f2 = 48 (pH = 4.5) and f2 = 49 (pH = 6.8), respectively. The similarity factor f2 was less than 50, and the dissolution curves were not similar to those of the reference formulation, indicating poor dissolution behavior and failure to meet the formulation standards.

[0274] Comparative Example 2 adopted the preparation process of patent CN111603453A, in which the particle size D90 of glimepiride in step (1) was less than 5.0 μm. The prepared finished tablets had dissolution curve similarity factors f2 of 58 and 55 with the reference preparation in phosphate buffer at pH 4.5 and 6.8. The initial f2 was significantly lower than that of Method 2 in Example 1 (f2 = 66, f2 = 81). After 6 months of accelerated storage, the similarity factor f2 showed a significant decreasing trend, decreasing to f2 = 46 (pH = 4.5) and f2 = 47 (pH = 6.8) respectively. The similarity factor f2 was less than 50. The dissolution curves were not similar to those of the reference preparation, the dissolution behavior was poor, and it did not meet the preparation standards.

[0275] Comparative Example 3 adopted the preparation process of patent CN111603453A, wherein in step (1), the particle size D90 of glimepiride was less than 10.0 μm. The prepared finished tablets, in phosphate buffer at pH 4.5 and 6.8, had dissolution curve similarity factors of 51 and 53 with the reference formulation, respectively. The initial f2 was significantly lower than that of Method 2 in Example 1 (f2 = 66, f2 = 81). After 6 months of accelerated storage, the similarity factor f2 showed a significant decreasing trend, decreasing to f2 = 44 (pH = 4.5) and f2 = 45 (pH = 6.8), respectively. The similarity factor f2 was less than 50. The dissolution curves were not similar to those of the reference formulation, the dissolution behavior was poor, and it did not meet the formulation standards.

[0276] The only difference between Method 2 and Method 1 in Example 1 is whether or not pigment is added for coloring, which has no effect on the dissolution properties of the formulation product.

[0277] Therefore, the finished tablets prepared by method 2 in Example 1 and method 1 in Example 1 show consistent dissolution behavior in the dissolution curve results, which is also consistent with the above comparison conclusion.

[0278] summary:

[0279] By comparing the dissolution process of finished tablets obtained from different preparation processes in phosphate buffer solutions at pH 4.5 and 6.8, it was shown that the preparation process significantly affects dissolution performance. Compared with Comparative Examples 1-3, the tablets exhibited poor dissolution behavior after 6 months of accelerated dissolution, failing to meet the formulation standards. The glimepiride tablets prepared by methods 1-2 of Example 1 (the best performing example) and method 1 of Example 2 (the least performing example) showed good dissolution performance in both the initial state and after 6 months of accelerated dissolution in phosphate buffer solutions at pH 4.5 and 6.8, significantly exceeding the formulation standards.

[0280] In summary, the glimepiride tablets and their preparation method provided by this invention optimize the formulation and preparation process, reduce the impurity content in the tablets, significantly improve the stability of the product, and improve the dissolution performance of the tablets with significant dissolution effect.

Claims

1. A glimepiride tablet, comprising, by weight: 2.0g glimepiride, 150-160g diluent, 14g sodium carboxymethyl starch, 0.8-1.2g povidone K30, and 0.8-1.2g magnesium stearate; wherein the diluent is lactose and microcrystalline cellulose, the weight ratio of lactose to microcrystalline cellulose being (120-150):(10-30), and the lactose being 80-200 mesh ordinary lactose; the preparation method of the glimepiride tablet includes the following steps: (1) Weigh glimepiride, diluent, and sodium carboxymethyl starch and mix them in a mixer. First, add glimepiride and lactose and mix for 3-5 minutes. Then add microcrystalline cellulose and sodium carboxymethyl starch and mix for 5-7 minutes. (2) Prepare wet granules using povidone K30 solution and dry them in a fluidized bed. (3) Add magnesium stearate to the dried material and mix it. (4) Compress the material to make glimepiride tablets.

2. The glimepiride tablet according to claim 1, wherein the lactose is 200-mesh ordinary lactose.

3. The glimepiride tablet according to claim 1 or 2, wherein the weight ratio of lactose to microcrystalline cellulose is 137.2:14.

0.

4. The glimepiride tablets according to claim 1, wherein the amount of povidone K30 is 1.0 part by weight.

5. The glimepiride tablet according to claim 1, wherein the amount of magnesium stearate is 1.0 parts by weight.

6. The glimepiride tablet according to claim 1, wherein the glimepiride tablet further comprises 0.1 to 2.0 parts by weight of a pigment.

7. The glimepiride tablet according to claim 6, wherein the amount of pigment used is 0.5 to 1.0 parts by weight.

8. The glimepiride tablet according to claim 6, wherein the pigment is selected from any one or more of the following: yellow iron oxide, indigo aluminum lake, or a combination thereof.

9. The glimepiride tablet according to claim 8, wherein the pigment is a composition of yellow iron oxide and indigo aluminum lake.

10. The glimepiride tablet according to claim 9, wherein the amount of the yellow iron oxide and indigo aluminum lake composition is 0.5 to 1.0 parts by weight.

11. The glimepiride tablet according to claim 10, wherein the amount of the yellow iron oxide and indigo aluminum lake composition is 0.8 parts by weight.

12. The glimepiride tablet according to claim 1, wherein the preparation method further includes a packaging step after tableting.

13. The glimepiride tablet according to claim 1, wherein the particle size D90 of the glimepiride in step (1) is 1.0 to 10.0 μm.

14. The glimepiride tablet according to claim 13, wherein the particle size D90 of the glimepiride is 1.0 to 3.0 μm.

15. The glimepiride tablets according to claim 1, wherein the fluidized bed drying temperature in step (2) is 55-65°C and the moisture content is controlled within 6.0%.

16. The glimepiride tablets according to claim 1, wherein step (3) is performed by mixing with a square cone mixer for a mixing time of 10 to 15 minutes.

17. The glimepiride tablet according to claim 1, wherein in step (4) the tableting process, the tablet hardness is controlled to be 130-160 N.

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