A method for preparing blocky glimepiride crystals

Abstract

The invention discloses a preparation method of blocky glimepiride crystals, and relates to the technical field of drug crystallization. The method specifically comprises the following steps: preparing a glimepiride solution, preparing a dissolving agent for a polyvinyl pyrrolidone aqueous solution, and performing two-stage dissolving crystallization. The blocky glimepiride crystals of the invention use ethyl cellulose and polyvinyl pyrrolidone at the same time, and adopt low-temperature crystal growing and then high-temperature crystal growing to obtain the blocky glimepiride crystals. The crystal particles have uniform size and blocky structure, are not easy to agglomerate in a subsequent pharmaceutical process, have good fluidity and dispersibility, and are beneficial to the subsequent pharmaceutical process.

Description

Technical Field

[0001] The invention relates to the technical field of drug crystallization, in particular to a method for preparing blocky glimepiride crystals. Background Art

[0002] Glimepiride, chemically known as 1-[4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxamido)-ethyl]-benzenesulfonyl]-3-(trans-4-methylcyclohexyl)-urea, has a therapeutic mechanism of binding to the sulfonylurea receptor on the surface of pancreatic β-cells. This receptor binds to the ATP-sensitive K + (KATP) channels, causing the KATP channels to close, leading to the depolarization of the cell membrane and the opening of voltage-dependent calcium channels. 2+ Glimepiride can also increase cardiac glucose uptake through non-insulin-dependent pathways and is widely used because it has few adverse cardiovascular reactions.

[0003] Although glimepiride has a wide range of uses, due to its large molecular weight and low water solubility, it is difficult to control the particle size and shape of its API during the crystallization process. The glimepiride crystals currently prepared by pharmaceutical companies are needle-shaped or elongated rod-shaped crystals, which are easy to agglomerate during the pharmaceutical process, and have poor fluidity and dispersibility, making subsequent drug preparation and preparation steps such as mixing, tableting, and granulation difficult. Therefore, it is urgent to develop a glimepiride API suitable for pharmaceutical companies. Summary of the invention

[0004] To solve the above problems, the object of the present invention is to provide a method for preparing blocky glimepiride crystals.

[0005] In order to achieve the above object, the present invention is implemented through the following technical solutions:

[0006] A method for preparing blocky glimepiride crystals comprises the following steps:

[0007] ① Preparation of glimepiride solution: adding glimepiride and ethyl cellulose to an amide organic solvent, stirring and dissolving them, filtering them through a 0.45 μm organic filter membrane to obtain a glimepiride solution for later use; wherein the mass ratio of glimepiride, ethyl cellulose and amide organic solvent is 1:0.001-0.005:10-15;

[0008] ②Preparation of solvent: Add polyvinyl pyrrolidone into deionized water, stir thoroughly to dissolve through a 0.45 μm organic filter membrane, and obtain a polyvinyl pyrrolidone aqueous solution for later use; wherein the mass ratio of polyvinyl pyrrolidone to deionized water is 0.001-0.005:100;

[0009] ③ Dissolution crystallization: the polyvinyl pyrrolidone aqueous solution obtained in step ② is transferred to a crystallization kettle, stirring and thermostat are turned on, the temperature is controlled at 20-25° C., the glimepiride solution obtained in step ① is added to the crystallization kettle, and the crystals are grown at a constant temperature of 20-25° C. for 5-10 hours, and then the temperature of the crystallization kettle is increased to 50-55° C., and the crystals are grown at a constant temperature for 5-8 hours, hot filtration is performed, the filter cake is washed with deionized water, and vacuum dried at 35-45° C. for 20-30 hours to obtain blocky glimepiride crystals;

[0010] The mass ratio of the polyvinyl pyrrolidone aqueous solution obtained in step ② to the glimepiride solution obtained in step ① is 6 to 10:1.

[0011] Preferably, the amide organic solvent is N,N-dimethylacetamide or N,N-dimethylformamide.

[0012] Preferably, the mass ratio of glimepiride, ethyl cellulose and organic solvent is 1:0.004:12.

[0013] Preferably, the mass ratio of polyvinyl pyrrolidone to deionized water is 0.003:100.

[0014] Preferably, the mass ratio of the polyvinyl pyrrolidone aqueous solution obtained in step ② to the glimepiride solution obtained in step ① is 8:1.

[0015] Preferably, the temperature and time of the two constant temperature crystal growing in step ③ are respectively 22° C. crystal growing for 8 hours and 52° C. crystal growing for 6 hours.

[0016] Preferably, the polyvinyl pyrrolidone is K30, K60 or K90.

[0017] Compared with the prior art, the present invention has the following advantages:

[0018] The blocky glimepiride crystals of the present invention use ethyl cellulose and polyvinyl pyrrolidone at the same time, and adopt low-temperature crystal growing and then high-temperature crystal growing to obtain the blocky glimepiride crystals; the crystal particles have uniform size and block structure, are not easy to agglomerate in the subsequent pharmaceutical process, have good fluidity and dispersibility, and are beneficial to the subsequent pharmaceutical process. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is a microscope image of the bulk glimepiride crystals obtained in Example 5;

[0020] Figure 2 This is a scanning electron microscope image of the bulk glimepiride crystals obtained in Example 5;

[0021] Figure 3 This is the particle size distribution diagram of the blocky glimepiride crystals obtained in Example 5;

[0022] Figure 4 This is a microscope image of the glimepiride crystals obtained in Comparative Example 1;

[0023] Figure 5 This is a scanning electron microscope image of the glimepiride crystals obtained in Comparative Example 1;

[0024] Figure 6 This is the particle size distribution diagram of the glimepiride crystals obtained in Comparative Example 1;

[0025] Figure 7 This is a microscope image of the glimepiride crystals obtained in Comparative Example 2;

[0026] Figure 8 This is a scanning electron microscope image of the glimepiride crystals obtained in Comparative Example 2;

[0027] Fig. 9 This is the particle size distribution diagram of the glimepiride crystals obtained in Comparative Example 2;

[0028] Fig.10 This is a microscope image of the glimepiride crystals obtained in Comparative Example 3;

[0029] Fig.11 This is a microscope image of the glimepiride crystals obtained in Comparative Example 4;

[0030] Figure 3 , Figure 6 and Fig. 9 In the particle size distribution diagram, the horizontal axis is the particle size classification (μm) and the vertical axis is the volume density (%). DETAILED DESCRIPTION

[0031] The object of the present invention is to provide a method for preparing blocky glimepiride crystals, which is achieved by the following technical scheme:

[0032] A method for preparing blocky glimepiride crystals comprises the following steps:

[0033] ① Preparation of glimepiride solution: adding glimepiride and ethyl cellulose to an amide organic solvent, stirring and dissolving them, filtering them through a 0.45 μm organic filter membrane to obtain a glimepiride solution for later use; wherein the mass ratio of glimepiride, ethyl cellulose and amide organic solvent is 1:0.001-0.005:10-15;

[0034] ②Preparation of solvent: Add polyvinyl pyrrolidone into deionized water, stir thoroughly to dissolve through a 0.45 μm organic filter membrane, and obtain a polyvinyl pyrrolidone aqueous solution for later use; wherein the mass ratio of polyvinyl pyrrolidone to deionized water is 0.001-0.005:100;

[0035] ③ Dissolution crystallization: the polyvinyl pyrrolidone aqueous solution obtained in step ② is transferred to a crystallization kettle, stirring and thermostat are turned on, the temperature is controlled at 20-25° C., the glimepiride solution obtained in step ① is added to the crystallization kettle, and the crystals are grown at a constant temperature of 20-25° C. for 5-10 hours, and then the temperature of the crystallization kettle is increased to 50-55° C., and the crystals are grown at a constant temperature for 5-8 hours, hot filtration is performed, the filter cake is washed with deionized water, and vacuum dried at 35-45° C. for 20-30 hours to obtain blocky glimepiride crystals;

[0036] The mass ratio of the polyvinyl pyrrolidone aqueous solution obtained in step ② to the glimepiride solution obtained in step ① is 6 to 10:1.

[0037] Preferably, the amide organic solvent is N,N-dimethylacetamide or N,N-dimethylformamide.

[0038] Preferably, the mass ratio of glimepiride, ethyl cellulose and organic solvent is 1:0.004:12.

[0039] Preferably, the mass ratio of polyvinyl pyrrolidone to deionized water is 0.003:100.

[0040] Preferably, the mass ratio of the polyvinyl pyrrolidone aqueous solution obtained in step ② to the glimepiride solution obtained in step ① is 8:1.

[0041] Preferably, the temperature and time of the two constant temperature crystal growing in step ③ are respectively 22° C. crystal growing for 8 hours and 52° C. crystal growing for 6 hours.

[0042] Preferably, the polyvinyl pyrrolidone is K30, K60 or K90.

[0043] The present invention is further described below in conjunction with specific embodiments.

[0044] Example 1

[0045] A method for preparing blocky glimepiride crystals comprises the following steps:

[0046] ① Preparation of glimepiride solution: Add 1 kg of glimepiride and 1 g of ethyl cellulose into 10 kg of N,N-dimethylacetamide, stir thoroughly to dissolve, filter through a 0.45 μm organic filter membrane to obtain a glimepiride solution for later use;

[0047] ②Prepare the solvent: add 1g polyvinyl pyrrolidone K30 into 100kg deionized water, stir thoroughly to dissolve through a 0.45μm organic filter membrane to obtain a polyvinyl pyrrolidone aqueous solution for later use;

[0048] ③ Dissolution and crystallization: 66 kg of the polyvinyl pyrrolidone aqueous solution obtained in step ② was transferred to a crystallization kettle, stirring and thermostat were turned on, the temperature was controlled at 20 ° C, 11 kg of the glimepiride solution obtained in step ① was added to the crystallization kettle, and the crystals were grown at a constant temperature of 20 ° C for 5 hours, and then the temperature of the crystallization kettle was increased to 50 ° C, and the crystals were grown at a constant temperature for 5 hours, hot filtered, and the filter cake was washed with deionized water, and vacuum dried at 35 ° C for 30 hours to obtain 0.93 kg of blocky glimepiride crystals.

[0049] Example 2

[0050] A method for preparing blocky glimepiride crystals comprises the following steps:

[0051] ① Preparation of glimepiride solution: Add 1 kg of glimepiride and 5 g of ethyl cellulose into 15 kg of N,N-dimethylformamide, stir thoroughly to dissolve, filter through a 0.45 μm organic filter membrane to obtain a glimepiride solution for later use;

[0052] ②Prepare the solvent: add 8g polyvinyl pyrrolidone K60 into 160kg deionized water, stir thoroughly to dissolve through a 0.45μm organic filter membrane to obtain a polyvinyl pyrrolidone aqueous solution for later use;

[0053] ③ Dissolution crystallization: 160 kg of the polyvinyl pyrrolidone aqueous solution obtained in step ② was transferred to a crystallization kettle, stirring and thermostat were turned on, the temperature was controlled at 25 ° C, 16 kg of the glimepiride solution obtained in step ① was added to the crystallization kettle, and the crystals were grown at a constant temperature of 25 ° C for 10 hours, and then the temperature of the crystallization kettle was increased to 55 ° C, and the crystals were grown at a constant temperature for 8 hours, hot filtered, and the filter cake was washed with deionized water, and vacuum dried at 45 ° C for 20 hours to obtain 0.94 kg of blocky glimepiride crystals.

[0054] Example 3

[0055] A method for preparing blocky glimepiride crystals comprises the following steps:

[0056] ① Preparation of glimepiride solution: Add 1 kg glimepiride and 3 g ethyl cellulose into 12 kg N,N-dimethylacetamide, stir thoroughly to dissolve, filter through a 0.45 μm organic filter membrane to obtain a glimepiride solution for later use;

[0057] ②Prepare the solvent: add 2g polyvinyl pyrrolidone K90 into 100kg deionized water, stir thoroughly to dissolve through a 0.45μm organic filter membrane to obtain a polyvinyl pyrrolidone aqueous solution for later use;

[0058] ③ Dissolution crystallization: 91 kg of the polyvinylpyrrolidone aqueous solution obtained in step ② was transferred to a crystallization kettle, the stirring and thermostat were turned on, the temperature was controlled at 22 ° C, 13 kg of the glimepiride solution obtained in step ① was added to the crystallization kettle, and the crystals were grown at a constant temperature of 22 ° C for 6 hours, and then the temperature of the crystallization kettle was increased to 52 ° C, and the crystals were grown at a constant temperature for 6 hours, hot filtered, and the filter cake was washed with deionized water, and vacuum dried at 38 ° C for 22 hours to obtain 0.93 kg of blocky glimepiride crystals.

[0059] Example 4

[0060] A method for preparing blocky glimepiride crystals comprises the following steps:

[0061] ① Preparation of glimepiride solution: Add 1 kg glimepiride and 2 g ethyl cellulose into 14 kg N,N-dimethylformamide, stir thoroughly to dissolve, filter through a 0.45 μm organic filter membrane to obtain a glimepiride solution for later use;

[0062] ②Prepare the solvent: add 4g polyvinyl pyrrolidone K60 into 100kg deionized water, stir thoroughly to dissolve through a 0.45μm organic filter membrane to obtain a polyvinyl pyrrolidone aqueous solution for later use;

[0063] ③ Dissolution crystallization: 95 kg of the polyvinylpyrrolidone aqueous solution obtained in step ② was transferred to a crystallization kettle, the stirring and thermostat were turned on, the temperature was controlled at 24 ° C, 15 kg of the glimepiride solution obtained in step ① was added to the crystallization kettle, and the crystals were grown at a constant temperature of 24 ° C for 8 hours, and then the temperature of the crystallization kettle was increased to 54 ° C, and the crystals were grown at a constant temperature for 7 hours, hot filtered, and the filter cake was washed with deionized water, and vacuum dried at 42 ° C for 28 hours to obtain 0.95 kg of blocky glimepiride crystals.

[0064] Example 5

[0065] A method for preparing blocky glimepiride crystals comprises the following steps:

[0066] ① Preparation of glimepiride solution: Add 1 kg glimepiride and 4 g ethyl cellulose into 12 kg N,N-dimethylacetamide, stir thoroughly to dissolve, filter through a 0.45 μm organic filter membrane to obtain a glimepiride solution for later use;

[0067] ②Prepare the solvent: add 3g polyvinyl pyrrolidone K60 into 100kg deionized water, stir thoroughly to dissolve through a 0.45μm organic filter membrane to obtain a polyvinyl pyrrolidone aqueous solution for later use;

[0068] ③ Dissolution crystallization: 100 kg of the polyvinylpyrrolidone aqueous solution obtained in step ② was transferred to a crystallization kettle, the stirring and thermostat were turned on, the temperature was controlled at 22 ° C, 13 kg of the glimepiride solution obtained in step ① was added to the crystallization kettle, and the crystals were grown at a constant temperature of 22 ° C for 8 hours, and then the temperature of the crystallization kettle was increased to 52 ° C, and the crystals were grown at a constant temperature for 6 hours, hot filtered, and the filter cake was washed with deionized water, and vacuum dried at 40 ° C for 25 hours to obtain 0.96 kg of blocky glimepiride crystals.

[0069] Comparative Example 1

[0070] A method for preparing glimepiride crystals comprises the following steps:

[0071] ① Preparation of glimepiride solution: Add 1 kg of glimepiride into 12 kg of N,N-dimethylacetamide, stir thoroughly to dissolve, filter through a 0.45 μm organic filter membrane to obtain a glimepiride solution for later use;

[0072] ②Prepare the solvent: add 3g polyvinyl pyrrolidone K60 into 100kg deionized water, stir thoroughly to dissolve through a 0.45μm organic filter membrane to obtain a polyvinyl pyrrolidone aqueous solution for later use;

[0073] ③ Dissolution crystallization: 95 kg of the polyvinylpyrrolidone aqueous solution obtained in step ② was transferred to a crystallization kettle, the stirring and thermostat were turned on, the temperature was controlled at 22 ° C, 13 kg of the glimepiride solution obtained in step ① was added to the crystallization kettle, and the crystals were grown at a constant temperature of 22 ° C for 8 hours, and then the temperature of the crystallization kettle was increased to 52 ° C, and the crystals were grown at a constant temperature for 6 hours, and hot filtered. The filter cake was washed with deionized water and vacuum dried at 40 ° C for 25 hours to obtain 0.78 kg of fine flaky glimepiride crystals.

[0074] Comparative Example 2

[0075] A method for preparing glimepiride crystals comprises the following steps:

[0076] ① Preparation of glimepiride solution: Add 1 kg glimepiride and 4 g ethyl cellulose into 12 kg N,N-dimethylacetamide, stir thoroughly to dissolve, filter through a 0.45 μm organic filter membrane to obtain a glimepiride solution for later use;

[0077] ②Prepare the solvent: Pass 100 kg of deionized water through a 0.45 μm organic filter membrane to obtain a deionized water solvent for later use;

[0078] ③ Dissolution and crystallization: 90 kg of the deionized water solvent obtained in step ② was transferred to the crystallization kettle, the stirring and thermostat were turned on, the temperature was controlled at 22 ° C, 13 kg of the glimepiride solution obtained in step ① was added to the crystallization kettle, and the crystals were grown at a constant temperature of 22 ° C for 8 hours, and then the temperature of the crystallization kettle was increased to 52 ° C, and the crystals were grown at a constant temperature for 6 hours, hot filtered, and the filter cake was washed with deionized water, and vacuum dried at 40 ° C for 25 hours to obtain 0.84 kg of glimepiride crystals agglomerated into blocks and needles.

[0079] Comparative Example 3

[0080] A method for preparing glimepiride crystals comprises the following steps:

[0081] ① Preparation of glimepiride solution: Add 1 kg of glimepiride into 12 kg of N,N-dimethylacetamide, stir thoroughly to dissolve, filter through a 0.45 μm organic filter membrane to obtain a glimepiride solution for later use;

[0082] ②Prepare the solvent: Pass 100 kg of deionized water through a 0.45 μm organic filter membrane to obtain a deionized water solvent for later use;

[0083] ③ Dissolution and crystallization: 90 kg of the deionized water solvent obtained in step ② was transferred to the crystallization kettle, the stirring and thermostat were turned on, the temperature was controlled at 22 ° C, 13 kg of the glimepiride solution obtained in step ① was added to the crystallization kettle, and the crystals were grown at a constant temperature of 22 ° C for 8 hours, and then the temperature of the crystallization kettle was increased to 52 ° C, and the crystals were grown at a constant temperature for 6 hours, and hot filtration was performed. The filter cake was washed with deionized water and vacuum dried at 40 ° C for 25 hours to obtain 0.82 kg of fine particles of glimepiride crystals.

[0084] Comparative Example 4

[0085] A method for preparing glimepiride crystals comprises the following steps:

[0086] ① Preparation of glimepiride solution: Add 1 kg glimepiride and 4 g ethyl cellulose into 12 kg N,N-dimethylacetamide, stir thoroughly to dissolve, filter through a 0.45 μm organic filter membrane to obtain a glimepiride solution for later use;

[0087] ②Prepare the solvent: add 3g polyvinyl pyrrolidone K60 into 100kg deionized water, stir thoroughly to dissolve through a 0.45μm organic filter membrane to obtain a polyvinyl pyrrolidone aqueous solution for later use;

[0088] ③ Dissolution crystallization: 91 kg of the polyvinylpyrrolidone aqueous solution obtained in step ② was transferred to a crystallization kettle, the stirring and thermostat were turned on, the temperature was controlled at 22°C, 13 kg of the glimepiride solution obtained in step ① was added to the crystallization kettle, the crystals were grown at a constant temperature of 22°C for 14 hours, hot filtered, the filter cake was washed with deionized water, and vacuum dried at 40°C for 25 hours to obtain 0.81 kg of filamentous glimepiride crystals with an average particle size of 28 μm, but the particle size range distribution was wide.

[0089] The particle sizes of the blocky glimepiride crystals obtained in Examples 1 to 5 and Comparative Examples 1 to 4 were detected, and the results are shown in Table 1.

[0090] Table 1 Particle size and fluidity results of glimepiride crystals obtained in Examples 1 to 5 and Comparative Examples 1 to 4

[0091]

[0092]

[0093] The particle size distribution of the crystal is concentrated or dispersed, which can be represented by the span. The smaller the span, the narrower the peak of the particle size, and the more concentrated the distribution. It can be seen from the results of Table 1 that the particle size distribution of the glimepiride crystal obtained by the preparation method of the present invention is concentrated, so that the particle size of the crystal is uniform and the fluidity is better, which can alleviate the nesting problem of small particles in large particles, and the properties such as bulk density will also be affected accordingly. In addition, the uniform particle size is conducive to the tableting process operation of the tablet, reduces the problems of cracking and disintegration caused by uneven particle size, and can also reduce the color difference of the tablet surface caused by the particle size of the raw material. In general, the drug release rate of particles with uniform particle size is easier to guarantee.

[0094] The fluidity of the crystal is reflected by the angle of repose. The smaller the angle of repose, the better the fluidity. When the aspect ratio of the particles is small, the fluidity is generally good. The more uniform the particle size distribution, the better the fluidity. By adopting the preparation method of the present invention, block crystals are obtained, and the particle size distribution is narrow, so the crystal has good fluidity, which is convenient for subsequent preparation into pharmaceutical preparations.

[0095] The glimepiride crystals obtained in Example 5 and Comparative Examples 1 to 4 were observed under a microscope for their microscopic morphology, scanning electron microscope images and particle size distribution at the same magnification.

[0096] Depend on Figure 1 to Figure 3 It can be seen that the blocky glimepiride crystal particles obtained by the preparation method of the present invention are uniform and dispersed, the particle size distribution is concentrated, the particle size is uniform, and the average particle size is about 70 μm; Figures 4 to 6 It can be seen that when only polyvinyl pyrrolidone aqueous solution is used as the solvent, the product is fine flake crystals with an average particle size of 26 μm. Figure 7 to Figure 9It can be seen that when only ethyl cellulose is used as a crystal promoter in the preparation process, the product is short rod-shaped crystals with an average particle size of 80 μm. Fig.10 It can be seen that when no polymer additive is used, the product is fine granular crystals with an average particle size of 20 μm, and there is agglomeration between the particles; Fig.11 It can be seen that when ethyl cellulose and polyvinyl pyrrolidone are used simultaneously but the temperature is not raised for crystal growth, the product is filamentous crystals with a wide particle size distribution and more prominent agglomeration of the filamentous crystals. The agglomeration phenomenon is not conducive to the dispersion and flow of the glimepiride product and will bring difficulties to the operation of preparing the preparation.

Claims

1. A method for preparing blocky glimepiride crystals, characterized in that: The following steps are involved: ① Preparation of glimepiride solution: adding glimepiride and ethyl cellulose to an amide organic solvent, stirring and dissolving them, filtering them through a 0.45 μm organic filter membrane to obtain a glimepiride solution for later use; wherein the mass ratio of glimepiride, ethyl cellulose and amide organic solvent is 1:0.001-0.005:10-15; ②Preparation of solvent: Add polyvinyl pyrrolidone into deionized water, stir thoroughly to dissolve through a 0.45 μm organic filter membrane, and obtain a polyvinyl pyrrolidone aqueous solution for later use; wherein the mass ratio of polyvinyl pyrrolidone to deionized water is 0.001-0.005:100; ③ Dissolution crystallization: the polyvinyl pyrrolidone aqueous solution obtained in step ② is transferred to a crystallization kettle, stirring and thermostat are turned on, the temperature is controlled at 20-25° C., the glimepiride solution obtained in step ① is added to the crystallization kettle, and the crystals are grown at a constant temperature of 20-25° C. for 5-10 hours, and then the temperature of the crystallization kettle is increased to 50-55° C., and the crystals are grown at a constant temperature for 5-8 hours, hot filtration is performed, the filter cake is washed with deionized water, and vacuum dried at 35-45° C. for 20-30 hours to obtain blocky glimepiride crystals; The mass ratio of the polyvinyl pyrrolidone aqueous solution obtained in step ② to the glimepiride solution obtained in step ① is 6 to 10:

1.

2. A method for preparing a blocky glimepiride crystal according to claim 1, characterized in that: The amide organic solvent is N,N-dimethylacetamide or N,N-dimethylformamide.

3. The method for preparing a blocky glimepiride crystal according to claim 1, characterized in that: The mass ratio of glimepiride, ethyl cellulose and organic solvent is 1:0.004:

12.

4. The method for preparing a blocky glimepiride crystal according to claim 1, characterized in that: The mass ratio of polyvinyl pyrrolidone to deionized water is 0.003:

100.

5. The method for preparing a blocky glimepiride crystal according to claim 1, characterized in that: The mass ratio of the polyvinyl pyrrolidone aqueous solution obtained in step ② to the glimepiride solution obtained in step ① is 8:

1.

6. The method for preparing a blocky glimepiride crystal according to claim 1, characterized in that: The temperature and time of the two constant temperature crystal growing in step ③ are respectively 22° C. for 8 hours and 52° C. for 6 hours.

7. The method for preparing a blocky glimepiride crystal according to claim 1, characterized in that: The polyvinyl pyrrolidone is K30, K60 or K90.

Images