A benidipine hydrochloride tablet composition and its preparation method and application

Abstract

The present invention belongs to the field of medical technology, and specifically relates to a benidipine hydrochloride tablet composition, a preparation method thereof and an application thereof. The benidipine hydrochloride tablet composition is composed of a tablet core and a coating, and the raw materials of the tablet core include, by mass percentage: 21%-32% of benidipine hydrochloride raw material composition, 64%-73% of filler, 3.6%-4.8% of adhesive, 0.4%-1.5% of lubricant and 0-1.5% of flow aid. The present invention loosens and calcisfies the raw materials, so that the granulation using a high-viscosity adhesive can also be uniformly granulated, and the equipment does not require very high requirements, which is suitable for large-scale production; the obtained product has good repeatability, a small RSD of the dissolution curve, good content uniformity, and small quality difference.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and specifically relates to a benidipine hydrochloride tablet composition and a preparation method and application thereof. Background Art

[0002] Benidipine hydrochloride tablets are a calcium channel blocker that works mainly by inhibiting the L-type calcium ion channel on the vascular endothelial cell membrane. The drug can reduce myocardial contractility and peripheral resistance, and dilate the microcirculation around the coronary arteries, brain and renal tubules. It is mainly used for: (1) Acting on the heart: When treating hypertension, benidipine hydrochloride can effectively dilate peripheral blood vessels, reduce afterload, and thus reduce the burden on the heart; (2) Improving kidney function: Due to its vasodilatory effect, it is often used in clinical practice to treat edema symptoms and positive urine protein caused by chronic kidney disease; (3) Protecting the cardiovascular system: Studies have shown that long-term use of benidipine hydrochloride can significantly lower blood pressure levels, and can also prevent or delay the occurrence and development of atherosclerosis, which has a positive impact on the patient's heart health. In short, benidipine hydrochloride is a commonly used antihypertensive drug and is highly favored due to its unique efficacy.

[0003] Benidipine hydrochloride is slightly soluble in methanol and ethanol (99.5%), and almost insoluble in water. It is classified as BCS class II (low solubility and high osmotic pressure) and has large in vivo variability. Therefore, the formulation process has a greater impact on the body. The differences between and within batches also pose a great challenge to clinical safety.

[0004] After studying the control preparation of the existing product, benidipine hydrochloride tablets (licensed manufacturer: Kyowa Hakko Kirin Co., Ltd., specification: 8mg), it was found that the process was a wet granulation process through analytical reference. At the same time, after a large number of tests and studies, the in vitro dissolution RSD of the control preparation was relatively large, and the batch differences were also large. Since the study found that the control preparation added a high-viscosity adhesive, which led to uneven granulation during the granulation process, it put forward very high requirements on the equipment, which can easily cause the uneven granulation adhesive to lead to the final product content uniformity is not very ideal, and the in vitro dissolution RSD is very large, which leads to certain risks in the clinical drug safety of the product.

[0005] Chinese invention patent application CN102166212A discloses a method for rapidly dissolving benidipine hydrochloride from a tablet, wherein in a tablet containing benidipine hydrochloride, the volume average particle size of benidipine hydrochloride crystals is 4.5-30.0 μm, or the volume average particle size and number average particle size of benidipine hydrochloride crystals are 4.5-30.0 μm. This method mainly involves the control of the particle size of the raw materials, and does not solve the problem of large dissolution RSD and the risk of content uniformity.

[0006] Chinese invention patent application CN112807284A discloses a benidipine hydrochloride tablet and a preparation method thereof, wherein the benidipine hydrochloride tablet is composed of the following components by weight: 1-20% benidipine hydrochloride, 20-60% hydrophilic filler, 0.5-6.0% wetting agent, 25-50% disintegrant, 2.5-4.0% binder, 1%-3% glidant, and the balance is a solid dispersion carrier. The solid aqueous dispersion technology is mainly used to solve the technical problems of low dissolution and low dissolution rate of the existing benidipine hydrochloride tablets, and no explanation is given for the problem of large dissolution RSD and the risk of content uniformity. Summary of the invention

[0007] In view of the deficiencies in the prior art, the present invention provides a benidipine hydrochloride tablet composition and a preparation method and application thereof. After extensive research, the inventors found that in order to achieve bioequivalence with a control preparation, the same wet granulation process is adopted, but the viscosity of the binder is very large during the granulation process, and the reduced amount cannot achieve in vitro equivalence with the control preparation, so it will be difficult to mix the binder solution during granulation, the dissolution RSD is large, and the risk of exceeding the content uniformity limit is large. The raw material benidipine hydrochloride is loosened and calcified by calcium chloride and lactose monohydrate through special means. The process of adding a binder during granulation can improve the granulation effect, avoid uneven binders, and improve the problems of large dissolution RSD and large content uniformity.

[0008] In order to achieve the above-mentioned purpose of the present invention, the specific technical solution adopted by the present invention is:

[0009] A benidipine hydrochloride tablet composition consists of a tablet core and a coating. The raw materials of the tablet core include, by mass percentage, 21%-32% of benidipine hydrochloride raw material composition, 64%-73% of a filler, 3.6%-4.8% of a binder, 0.4%-1.5% of a lubricant, and 0-1.5% of a glidant.

[0010] Preferably, the benidipine hydrochloride raw material composition consists of benidipine hydrochloride, calcium chloride and lactose monohydrate in a mass ratio of 1:1.5-2.5:3-5.

[0011] Further preferably, the method for preparing the benidipine hydrochloride raw material composition comprises the following steps:

[0012] (1) benidipine hydrochloride and calcium chloride are mixed and crushed to obtain a mixture 1;

[0013] (2) After the lactose monohydrate is loosened and calcified by a grinder, it is added to the mixture 1 and ground to obtain the benidipine hydrochloride raw material composition.

[0014] Preferably, the particle sizes of the mixture 1 in step (1) and the benidipine hydrochloride raw material composition in step (2) are both D90≤30 μm.

[0015] Preferably, the filler is a mixture of starch and lactose monohydrate, the binder is polyvinyl alcohol 4-88, the lubricant is magnesium stearate, the glidant is micropowdered silica gel, and the coating is a gastric soluble coating premix.

[0016] Further preferably, the mass ratio of the starch to lactose monohydrate is 1-1.5:1-2.8.

[0017] The present invention also relates to a method for preparing the above-mentioned benidipine hydrochloride tablet composition, comprising the following steps:

[0018] S1. The benidipine hydrochloride raw material composition is mixed with a filler, sheared, a binder is added, granulated, wet granulated, dried, dry granulated, to obtain granules 1;

[0019] S2. Mix the lubricant and the glidant with the granules 1, compress the granules, and apply coating to obtain the benidipine hydrochloride tablet composition.

[0020] Preferably, the mixing time in step S1 is 4-6 min, the mixing speed is 80-100 rpm, the shearing knife speed is 1400-1600 rpm, the adhesive is added by atomizing and adding the adhesive aqueous solution, the mass concentration of the adhesive aqueous solution is 22%-24%, the slurry pressure of the pressure tank during the atomization process is 0.14-0.16 MPa, preferably 0.15±0.05 MPa, and the atomization pressure is 0.14-0.16 MPa, preferably 0.15±0.05 MPa.

[0021] Preferably, the granulation time in step S1 is 1.5-2.5 min, the wet granulation adopts a 15-17 mesh screen, the moisture after drying is ≤3%, and the dry granulation adopts a 0.9-1.1 mm screen; the mixing speed in step S2 is 7-9 rpm, the mixing time is 7-9 min, the hardness after tableting is 30-80 N, and the coating weight gain is 4.0%-7.0%.

[0022] The present invention also relates to the use of the above-mentioned benidipine hydrochloride tablet composition or the benidipine hydrochloride tablet composition prepared by the above-mentioned preparation method in the preparation of drugs for lowering blood pressure levels.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] (1) The present invention loosens and calcitrate the raw materials, so that even granulation with a high-viscosity binder can be uniform, and the equipment does not require very high requirements, which is suitable for large-scale production;

[0025] (2) The product obtained by the present invention has good reproducibility, small RSD of in vitro dissolution amount, good content uniformity and small quality difference;

[0026] (3) The clinical safety risk of the benidipine hydrochloride tablet composition prepared by the present invention is greatly increased. DETAILED DESCRIPTION

[0027] The present invention will be further described in detail below in conjunction with specific examples. The following examples are not intended to limit the present invention but are only intended to illustrate the present invention. The experimental methods used in the following examples are generally based on conventional conditions unless otherwise specified.

[0028] The purchase information of raw materials and auxiliary materials involved in the present invention is shown in Table 1.

[0029] Table 1 Raw material and auxiliary material information

[0030]

[0031] Example 1

[0032] A benidipine hydrochloride tablet composition, raw materials and auxiliary materials and added amounts are shown in Table 2.

[0033] Table 2 Raw materials and additive amounts

[0034]

[0035] The preparation method of the above-mentioned benidipine hydrochloride tablet composition comprises the following steps:

[0036] (1) Benidipine hydrochloride and calcium chloride are mixed evenly, and the mixture is crushed in a pulverizer until the particle size D90 is 15.8 μm. Lactose monohydrate (for calcification treatment) is added, the mixture is mixed evenly, and the mixture is crushed in a pulverizer until the particle size D90 is 25.2 μm to obtain a benidipine hydrochloride raw material composition.

[0037] (2) placing the benidipine hydrochloride raw material composition, lactose monohydrate and starch in a wet mixing granulator, starting stirring and shearing, mixing time for 5 min, setting the stirring speed to 90 rpm, the cutting speed to 1500 rpm, adding a 23% mass concentration of polyvinyl alcohol (4-88) aqueous solution by atomization, the pressure tank slurry pressure to 0.15 MPa, the atomization pressure to 0.15 MPa, and granulation after liquid addition, the granulation time is 2 min;

[0038] Then, the oscillating granulator was used to perform wet granulation using a 16-mesh nylon screen. The wet granules were placed in a boiling dryer for drying until the moisture content was 2.5%. The dried granules were then placed in a granulator for granulation using a 1.0 mm screen to obtain granules 1.

[0039] (3) Magnesium stearate and granules 1 were mixed at 8 rpm for 8 min, tableted to obtain plain tablets (hardness 56 N), and then coated (prepared with 10% gastric soluble coating premix suspension aqueous solution, coating weight gain 4.5%) to obtain benidipine hydrochloride tablet composition.

[0040] Example 2

[0041] A benidipine hydrochloride tablet composition, raw materials and auxiliary materials and added amounts are shown in Table 3.

[0042] Table 3 Raw materials and additive amounts

[0043]

[0044] The preparation method of the above-mentioned benidipine hydrochloride tablet composition comprises the following steps:

[0045] (1) Benidipine hydrochloride and calcium chloride are mixed evenly, and the mixture is crushed in a pulverizer to a particle size D90 of 10.5 μm. Lactose monohydrate (for calcification treatment) is added, the mixture is mixed evenly, and the mixture is crushed in a pulverizer to a particle size D90 of 18.6 μm to obtain a benidipine hydrochloride raw material composition.

[0046] (2) placing the benidipine hydrochloride raw material composition, lactose monohydrate and starch in a wet mixing granulator, starting stirring and shearing, mixing time for 5 min, setting the stirring speed to 90 rpm, the cutting speed to 1500 rpm, adding a 23% mass concentration of polyvinyl alcohol (4-88) aqueous solution by atomization, the pressure tank slurry pressure to 0.15 MPa, the atomization pressure to 0.15 MPa, and granulation after liquid addition, the granulation time is 2 min;

[0047] Then, the oscillating granulator was used to perform wet granulation using a 16-mesh nylon screen. The wet granules were placed in a boiling dryer for drying until the moisture content was 2.8%. The dried granules were then placed in a granulator for granulation using a 1.0 mm screen to obtain granules 1.

[0048] (3) Magnesium stearate and granules 1 were mixed at 8 rpm for 8 min, tableted to obtain plain tablets (hardness 32N), and then coated (prepared with 10% gastric soluble coating premix suspension aqueous solution, coating weight gain 4.2%) to obtain benidipine hydrochloride tablet composition.

[0049] Example 3

[0050] A benidipine hydrochloride tablet composition, raw materials and auxiliary materials and added amounts are shown in Table 4.

[0051] Table 4 Raw materials and additive amounts

[0052]

[0053] The preparation method of the above-mentioned benidipine hydrochloride tablet composition comprises the following steps:

[0054] (1) Benidipine hydrochloride and calcium chloride are mixed evenly, and the mixture is crushed in a pulverizer until the particle size D90 is 15.5 μm. Lactose monohydrate (for calcification treatment) is added, the mixture is mixed evenly, and the mixture is crushed in a pulverizer until the particle size D90 is 20.1 μm to obtain a benidipine hydrochloride raw material composition.

[0055] (2) placing the benidipine hydrochloride raw material composition, lactose monohydrate and starch in a wet mixing granulator, starting stirring and shearing, mixing time for 5 min, setting the stirring speed to 90 rpm, the cutting speed to 1500 rpm, adding a 23% mass concentration of polyvinyl alcohol (4-88) aqueous solution by atomization, the pressure tank slurry pressure to 0.15 MPa, the atomization pressure to 0.15 MPa, and granulation after liquid addition, the granulation time is 2 min;

[0056] Then, the oscillating granulator was used to perform wet granulation using a 16-mesh nylon screen. The wet granules were placed in a boiling dryer for drying until the moisture content was 2.5%. The dried granules were then placed in a granulator for granulation using a 1.0 mm screen to obtain granules 1.

[0057] (3) Magnesium stearate and granules 1 were mixed at 8 rpm for 8 min, tableted to obtain plain tablets (hardness 78 N), and then coated (prepared with 10% gastric soluble coating premix suspension aqueous solution, coating weight gain 6.8%) to obtain benidipine hydrochloride tablet composition.

[0058] Example 4

[0059] A benidipine hydrochloride tablet composition, raw materials and auxiliary materials and added amounts are shown in Table 5.

[0060] Table 5 Raw materials and additive amounts

[0061]

[0062] The preparation method of the above-mentioned benidipine hydrochloride tablet composition comprises the following steps:

[0063] (1) Benidipine hydrochloride and calcium chloride are mixed evenly, and the mixture is crushed in a pulverizer to a particle size D90 of 25.4 μm. Lactose monohydrate (for calcification treatment) is added, the mixture is mixed evenly, and the mixture is crushed in a pulverizer to a particle size D90 of 8.5 μm to obtain a benidipine hydrochloride raw material composition.

[0064] (2) placing the benidipine hydrochloride raw material composition, lactose monohydrate and starch in a wet mixing granulator, starting stirring and shearing, the mixing time is 4 minutes, the stirring speed is set to 100 rpm, the cutting speed is set to 1400 rpm, and a 22% mass concentration of polyvinyl alcohol (4-88) aqueous solution is added by atomization, the pressure tank slurry pressure is 0.14 MPa, the atomization pressure is 0.14 MPa, and granulation is carried out after the addition of liquid is completed, and the granulation time is 2.5 minutes;

[0065] Then, the 17-mesh nylon screen was used in the swing granulator for wet granulation, and the wet granules were placed in a boiling dryer for drying until the moisture content was 2.0%. The dried granules were then placed in a granulator for granulation with a screen of 0.9 mm to obtain granules 1.

[0066] (3) Magnesium stearate and granules 1 were mixed at 9 rpm for 7 min, tableted to obtain plain tablets (hardness 57N), and then coated (prepared with 10% gastric soluble coating premix suspension aqueous solution, coating weight gain 5.5%) to obtain benidipine hydrochloride tablet composition.

[0067] Example 5

[0068] A benidipine hydrochloride tablet composition, raw materials and auxiliary materials and added amounts are shown in Table 6.

[0069] Table 6 Raw materials and additive amounts

[0070]

[0071] The preparation method of the above-mentioned benidipine hydrochloride tablet composition comprises the following steps:

[0072] (1) Benidipine hydrochloride and calcium chloride are mixed evenly, and the mixture is crushed in a pulverizer to a particle size D90 of 5.8 μm. Lactose monohydrate (for calcification treatment) is added, the mixture is mixed evenly, and the mixture is crushed in a pulverizer to a particle size D90 of 29.6 μm to obtain a benidipine hydrochloride raw material composition.

[0073] (2) placing the benidipine hydrochloride raw material composition, lactose monohydrate and starch in a wet mixing granulator, starting stirring and shearing, mixing time for 6 min, setting the stirring speed to 80 rpm, the cutting speed to 1600 rpm, adding a 24% mass concentration of polyvinyl alcohol (4-88) aqueous solution by atomization, the pressure tank slurry pressure to 0.16 MPa, the atomization pressure to 0.16 MPa, and granulation after liquid addition, the granulation time is 2 min;

[0074] Then, the swung granulator was used to perform wet granulation using a 15-mesh nylon screen. The wet granules were placed in a boiling dryer for drying until the moisture content was 2.0%. The dried granules were then placed in a granulator for granulation using a 1.1 mm screen to obtain granules 1.

[0075] (3) Magnesium stearate and granules 1 were mixed at 7 rpm for 9 min, tableted to obtain plain tablets (hardness 52N), and then coated (prepared with 10% gastric soluble coating premix suspension aqueous solution, coating weight gain 5.5%) to obtain benidipine hydrochloride tablet composition.

[0076] Example 6

[0077] A benidipine hydrochloride tablet composition, wherein the raw materials, auxiliary materials, addition amounts and preparation method are consistent with those in Example 1.

[0078] Comparative Example 1

[0079] The difference between this comparative example and Example 1 is that benidipine hydrochloride is not subjected to calcification and pulverization treatment, but is directly mixed and then mixed and granulated; the specific steps are as follows:

[0080] (1) benidipine hydrochloride, calcium chloride, lactose monohydrate and starch were placed in a wet mixing granulator, stirring and shearing were started, the mixing time was 5 min, the stirring speed was set to 90 rpm, the cutting speed was set to 1500 rpm, and a 23% mass concentration of polyvinyl alcohol (4-88) aqueous solution was added by atomization. The pressure tank slurry pressure was 0.15 MPa, the atomization pressure was 0.15 MPa, and granulation was carried out after the addition of liquid. The granulation time was 2 min;

[0081] Then, the oscillating granulator was used to perform wet granulation using a 16-mesh nylon screen. The wet granules were placed in a boiling dryer for drying until the moisture content was 2.5%. The dried granules were then placed in a granulator for granulation using a 1.0 mm screen to obtain granules 1.

[0082] (2) Magnesium stearate and granules 1 were mixed at 8 rpm for 8 min, tableted to obtain plain tablets (hardness 56 kN), and then coated (prepared with 10% gastric soluble coating premix suspension aqueous solution, coating weight gain 4.5%) to obtain benidipine hydrochloride tablet composition.

[0083] Comparative Example 2

[0084] The difference between this comparative example and Example 1 is only that calcium chloride is replaced by magnesium chloride.

[0085] Comparative Example 3

[0086] The difference between this comparative example and Example 1 is only that calcium chloride is replaced with calcium sulfate.

[0087] Comparative Example 4

[0088] The only difference between this comparative example and Example 1 is that benidipine hydrochloride, calcium chloride and lactose monohydrate (for calcification treatment) are pulverized together for loose calcification treatment.

[0089] Comparative Example 5

[0090] The difference between this comparative example and Example 1 is that benidipine hydrochloride is firstly pulverized together with lactose monohydrate (for calcification treatment) and then treated with calcium chloride, and the only difference is the order.

[0091] Comparative Example 6

[0092] The only difference between this comparative example and Example 1 is that the particle size D90 of benidipine hydrochloride and calcium chloride after pulverization is 32.2 μm.

[0093] Comparative Example 7

[0094] The only difference between this comparative example and Example 1 is that lactose monohydrate (for calcification treatment) is added and the particle size D90 after loose calcification treatment is 32.8 μm.

[0095] Comparative Example 8

[0096] The only difference between this comparative example and Example 4 is that the amount of calcium chloride used is 11 mg / tablet, and the weight ratio of benidipine hydrochloride to calcium chloride is 8:11.

[0097] Comparative Example 9

[0098] The only difference between this comparative example and Example 4 is that the amount of calcium chloride used is 22 mg / tablet, and the weight ratio of benidipine hydrochloride to calcium chloride is 8:22.

[0099] Comparative Example 10

[0100] The only difference between this comparative example and Example 4 is that the amount of lactose monohydrate (for calcification treatment) is 23 mg / tablet, and the weight ratio of benidipine hydrochloride to lactose monohydrate (for calcification treatment) is 8:23.

[0101] Comparative Example 11

[0102] The only difference between this comparative example and Example 3 is that the amount of lactose monohydrate (for calcification treatment) is 41 mg / tablet, and the weight ratio of benidipine hydrochloride to lactose monohydrate (for calcification treatment) is 8:41.

[0103] Comparative Example 12

[0104] The only difference between this comparative example and Example 1 is that the particle size D90 of benidipine hydrochloride and calcium chloride after mixed and pulverized is 32.4 μm.

[0105] Effect test

[0106] The benidipine hydrochloride tablet compositions (tablets) obtained in Examples 1-6 and Comparative Examples 1-10, and a marketed control preparation (benidipine hydrochloride tablets, specification: 8 mg, batch number: 681AAF, manufacturer Kyowa Hakko Kirin Co., Ltd.) were subjected to in vitro dissolution comparison and content uniformity test in pH 1.2 hydrochloric acid solution. The in vitro dissolution test results of Examples 1-6 and the control preparation are shown in Table 7, the in vitro dissolution test results of Comparative Examples 1-10 and the control preparation are shown in Table 8, and the content uniformity test results are shown in Table 9.

[0107] In vitro evaluation method: refer to the second method (paddle method) in the general chapter 0931 dissolution and release determination method of the 2020 edition of the "Chinese Pharmacopoeia" for detection, medium: pH 1.2 hydrochloric acid solution, volume 900mL, rotation speed: 50rpm; detection method: high performance liquid chromatography, wavelength: 237nm, chromatographic column: C18, 4.6mm×100mm, 3μm.

[0108] Evaluation method for content and content uniformity: Refer to the content uniformity inspection method of the 2020 edition of the Chinese Pharmacopoeia General Chapter 0941, determine the content of 10 tablets, calculate A+2.2S, A+2.2S≤15 is in compliance with the requirements, otherwise it does not meet the requirements. Detection method: high performance liquid chromatography, wavelength: 237nm, chromatographic column: C18, 4.6mm×100mm, 3μm.

[0109] Table 7 In vitro dissolution test results

[0110]

[0111] Table 8 In vitro dissolution test results

[0112]

[0113] Note: F2 represents the similarity factor with the control preparation, which is calculated at time points of 5min, 10min, 15min, and 20min. If F2 is greater than 50, it indicates that the dissolution conditions are similar in vitro to those of the control preparation.

[0114] Table 9 Content uniformity results

[0115]

[0116] Note: According to the general rules for preparations in Part IV of the 2020 edition of the Chinese Pharmacopoeia, the content uniformity judgment standard is: A+2.2S≤L, then the content uniformity of the test sample meets the requirements, L is the specified value, L=15.0.

[0117] Among Examples 1-5, Example 1 is the best example, and Example 6 is a reproduction of Example 1. The dissolution is similar to the control preparation, the content uniformity also meets the requirements, and the risk is lower than that of the control preparation; the reproducibility of Examples 1 and 6 is also good. For Comparative Examples 1-12, the RSD of the points after 10 minutes of dissolution is large and the content uniformity is not good.

[0118] The above results show that the dissolution of the benidipine hydrochloride tablet composition of the present invention can be similar to that of the control preparation, the dissolution RSD is also relatively small, the content uniformity can meet the requirements and is significantly better than the control preparation, while the RSD of the comparative example 1-12 after 10 minutes of dissolution is large, and the content uniformity does not meet the requirements.

[0119] The above detailed description is a specific description of one feasible embodiment of the present invention. The embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or modification that does not deviate from the present invention should be included in the scope of the technical solution of the present invention.

Claims

1. A benidipine hydrochloride tablet composition, consisting of a tablet core and a coating, characterized in that: The raw materials of the tablet core include, by mass percentage: 21%-32% of benidipine hydrochloride raw material composition, 64%-73% of filler, 3.6%-4.8% of binder, 0.4%-1.5% of lubricant and 0-1.5% of glidant; The benidipine hydrochloride raw material composition is composed of benidipine hydrochloride, calcium chloride and lactose monohydrate in a mass ratio of 1:1.5-2.5:3-5; The preparation method of the benidipine hydrochloride raw material composition comprises the following steps: (1) benidipine hydrochloride and calcium chloride are mixed and crushed to obtain a mixture 1; (2) After the lactose monohydrate is pulverized by a pulverizer, the mixture is added to the mixture 1 and pulverized to obtain the benidipine hydrochloride raw material composition; Wherein, the particle sizes of the mixture 1 in step (1) and the benidipine hydrochloride raw material composition in step (2) are both D90≤30 μm.

2. The benidipine hydrochloride tablet composition according to claim 1, characterized in that: The filler is a mixture of starch and lactose monohydrate, the binder is polyvinyl alcohol 4-88, the lubricant is magnesium stearate, the glidant is micro-powder silica gel, and the coating is a gastric soluble coating premix.

3. The benidipine hydrochloride tablet composition according to claim 2, characterized in that: The mass ratio of the starch to lactose monohydrate is 1-1.5:1-2.

8.

4. A method for preparing the benidipine hydrochloride tablet composition according to any one of claims 1 to 3, characterized in that: The following steps are involved: S1. The benidipine hydrochloride raw material composition is mixed with a filler, sheared, a binder is added, granulated, wet granulated, dried, dry granulated, to obtain granules 1; S2. Mix the lubricant and the glidant with the granules 1, compress the granules, and coat the granules to obtain the benidipine hydrochloride tablet composition.

5. The preparation method according to claim 4, characterized in that: The mixing time in step S1 is 4-6 minutes, the mixing speed is 80-100 rpm, the shearing knife speed is 1400-1600 rpm, the adhesive is added by atomizing the adhesive aqueous solution, the mass concentration of the adhesive aqueous solution is 22%-24%, the slurry pressure of the pressure tank during the atomization process is 0.14-0.16 MPa, and the atomization pressure is 0.14-0.16 MPa.

6. The preparation method according to claim 4, characterized in that: The granulation time in step S1 is 1.5-2.5min, the wet granulation adopts a 15-17 mesh screen, the moisture after drying is ≤3%, and the dry granulation adopts a 0.9-1.1mm screen; the mixing speed in step S2 is 7-9rpm, the mixing time is 7-9min, the hardness after tableting is 30-80N, and the coating weight gain is 4.0%-7.0%.

7. Use of the benidipine hydrochloride tablet composition according to any one of claims 1 to 3 in the preparation of a drug for lowering blood pressure levels.

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