Benidipine hydrochloride tablet and preparation method thereof

Abstract

The invention discloses a benidipine hydrochloride tablet. The benidipine hydrochloride tablet is a preparation formed by coating a tablet core with a coating solution, the tablet core is formed by mixing and pressing material particles with the following particle sizes in proportion: gt; 0.8%-8% of 20 meshes, 5%-20% of 20-40 meshes, 9%-21% of 40-60 meshes, 15%-48% of 60-80 meshes and 20%-51% of 80-100 meshes; 3-21% of 100 mesh; the material particles comprise the following raw and auxiliary materials in parts by weight: 2-5 parts of benidipine hydrochloride, 76-99 parts of a diluent, 1-2 parts of an adhesive and 0.5-1.5 parts of a lubricant. According to the invention, a specific process of stirring, cutting and atomizing is adopted, so that the raw and auxiliary materials in the tablet are uniformly mixed, material particles with specific granularity are easily prepared for tabletting, the preparation process is simple, and the obtained tablet has the advantages of low content of related substances, stable property, quick dissolution and quick effect, and has practical popularization and application values.

Description

Technical Field

[0001] The present invention specifically relates to a benidipine hydrochloride tablet and a preparation method thereof. Background Art

[0002] The chemical name of benidipine hydrochloride is 3-[(3RS)-1-benzylpiperidin-3-yl]5-methyl(4RS)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid monohydrochloride. It is a new type of dihydropyridine calcium ion antagonist. It binds to dihydropyridine receptors that block cell membrane potential-dependent calcium ion channels, preventing calcium ions from flowing into cells and causing vasodilation. It has the characteristics of stable blood pressure reduction, lasting efficacy, good safety and compliance. It is a very core drug for elderly patients with primary hypertension and angina pectoris, and is widely used because of its safety and effectiveness.

[0003] According to the literature "Effects of Renin-Angiotensin System Blockers and Dihydropyridine Calcium Antagonists on Parathyroid Hormone Levels in Hypertensive Patients, Journal of China Prescription Drug Vol.18No.6", the use of dihydropyridine calcium ion antagonists tends to increase PTH, which is consistent with the results of small-scale population studies abroad. The literature "Biological Research and Osteogenesis of Parathyroid Hormone, ChinJ Osteoporos, December 2017, Vol 23, No.12" reports that PTH has a dual effect on bone formation and bone resorption. Continuous high-dose PTH promotes bone resorption, and intermittent low-dose PTH promotes bone formation. The serum PTH level is negatively correlated with bone density, which can be used as a good diagnostic indicator for osteoporosis and early detection of osteoporosis. It can be inferred that dihydropyridine calcium ion antagonists have a certain effect on bone formation and bone resorption.

[0004] The study "Wang B, Bi M, Zhu Z, et al. Effects of the antihypertensive drug benidipine on osteoblast function in vitro. Exp Ther Med, 2014, 7(3): 649-653" revealed that benidipine concentration was 10 -7 -10 -8 Within the M range, benidipine can significantly promote the proliferation and differentiation of osteoblasts and inhibit the differentiation of osteoclasts; higher concentrations of benidipine inhibit the proliferation of osteoblasts, while lower concentrations of benidipine have no effect on the proliferation of osteoblasts.

[0005] Patent application CN201911116310.9 discloses a benidipine hydrochloride tablet, and its background technology discloses that the rapid dissolution and rapid metabolism of benidipine hydrochloride will cause an increase in parathyroid hormone in the blood. This instantaneous increase helps promote bone formation; while the slow dissolution of benidipine hydrochloride will lead to a long-term increase in blood drug concentration in the body, and the concentration of parathyroid hormone in the blood will also increase for a long time, thereby inhibiting bone synthesis.

[0006] Patent application CN201911116310.9 discloses a benidipine hydrochloride tablet, which has a short disintegration time and rapid drug dissolution through specific excipients, but its disintegration time of 3 minutes still limits the benefits to the target population. It is necessary to develop a benidipine hydrochloride tablet with higher dissolution efficiency and more stable quality. Summary of the invention

[0007] In order to solve the above problems, the present invention provides a benidipine hydrochloride tablet, which is a preparation formed by coating a tablet core with a coating liquid; the tablet core is formed by mixing and pressing material particles of the following particle sizes in proportion:

[0008] >20 mesh 0.8-8%, 20-40 mesh 5-20%, 40-60 mesh 9-21%, 60-80 mesh 15-48%, 80-100 mesh 20-51%;, <100 mesh 3-21%;

[0009] The material particles include the following raw materials and auxiliary materials in parts by weight:

[0010] 2-5 parts of benidipine hydrochloride, 76-99 parts of diluent, 1-2 parts of adhesive, and 0.5-1.5 parts of lubricant.

[0011] Furthermore, the tablet core is formed by mixing and pressing material particles of the following particle sizes in proportion:

[0012] >20 mesh 5-8%; 20-40 mesh 12-20%; 40-60 mesh 9-14%; 60-80 mesh 15-17%; 80-100 mesh 25-50%; <100 mesh 3-21%.

[0013] Furthermore, the tablet core is formed by mixing and pressing material particles of the following particle sizes in proportion:

[0014] >20 mesh 7~8%; 20-40 mesh 13~14%; 40-60 mesh 10~11%; 60-80 mesh 15~16%; 80-100 mesh 32~33%; <100 mesh 20~21%.

[0015] Further, the diluent is a mixture of 6-9 parts of corn starch and 70-90 parts of lactose;

[0016] The lubricant is one or more of talc, stearic acid, magnesium stearate, calcium stearate, sodium stearate, polyethylene glycol, and sodium lauryl sulfate;

[0017] The adhesive is one or more of dextrin, polyvinyl pyrrolidone and polyvinyl alcohol.

[0018] Furthermore, the coating solution is Opadry film coating solution with a concentration of 6-10%.

[0019] The present invention also provides a method for preparing the aforementioned benidipine hydrochloride tablets, which comprises the following steps:

[0020] S1, taking 70-85% of the adhesive in the formula, adding water to dissolve, and obtaining an adhesive solution;

[0021] S2, mixing and shearing the diluent, benidipine hydrochloride and the remaining binder to obtain a mixture, and then adding water and the binder solution obtained in step S1 in sequence by atomization, stirring, and granulating to obtain wet granules;

[0022] S3, drying the wet granules obtained in step S2, granulating, sieving, mixing with a lubricant, screening according to the particle size, and then mixing according to the particle size ratio to obtain material granules;

[0023] S4, taking the material particles obtained in step S3 and pressing them into tablet cores, coating them with a coating liquid, drying them, and cooling them to obtain tablet cores.

[0024] Furthermore, in step S1, the temperature of the water is 50-60° C.; and the concentration of the adhesive solution is 5-20%.

[0025] Furthermore, in step S2, the stirring speed of the mixed shear is 200-210rpm, the cutting speed is 2000-2050rpm, and the stirring time is 3-5min; the amount of water added is 5-8% of the mixture, the water is stirred for 30-60s after being added, and the adhesive solution is stirred for 1-3min after being added.

[0026] Furthermore, the moisture content of the material particles in step S3 is 3-4%.

[0027] Furthermore, the design pressure of the pressing in step S4 is 4-6 kgf, the main pressure is 14.0-18.0 KN, and the tablet weight of the tablet core is 126.0-136.0 mg.

[0028] The present invention discloses a benidipine hydrochloride tablet. The tablet core is made of material particles of a specific particle size. After being coated, the tablet core has good uniformity of main drug content, fast dissolution rate, short disintegration time, can quickly release the main drug benidipine hydrochloride, and avoid the side effects of benidipine hydrochloride tablets. The preparation method of the benidipine hydrochloride tablet of the present invention adopts a specific process of stirring + knife cutting + atomization to mix the raw and auxiliary materials in the tablet evenly, and is easy to be made into material particles of a specific particle size for tableting. The preparation process is simple, the obtained tablet has a small content of related substances, stable properties, can be quickly dissolved, and has a fast onset of effect, and has practical promotion and application value.

[0029] Obviously, according to the above contents of the present invention, in accordance with common technical knowledge and customary means in the art, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change may be made.

[0030] The above contents of the present invention are further described in detail below through specific implementation methods in the form of embodiments. However, this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. All technologies realized based on the above contents of the present invention belong to the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 Dissolution

[0032] Figure 2 Sampling diagram DETAILED DESCRIPTION

[0033] Example 1 Preparation of Benidipine Hydrochloride Tablets

[0034] Tablet formula:

[0035] Main drug: 3 parts of benidipine hydrochloride

[0036] Diluent: 7.3 parts corn starch, 87.4 parts lactose

[0037] Adhesive: 1.5 parts polyvinyl alcohol

[0038] Lubricant: 0.8 parts of magnesium stearate;

[0039] Tablet preparation:

[0040] S1. Slowly add 75% of the formula amount of polyvinyl alcohol into purified water at a constant temperature of 55°C, stir until completely dissolved, stop stirring, and let it stand to obtain an adhesive solution with a mass concentration of 20%;

[0041] S2, corn starch, lactose, 25% polyvinyl alcohol, and benidipine hydrochloride were placed in a wet mixing granulator, stirred for 3 min at a stirring speed of 204 rpm and a cutting speed of 2040 rpm to obtain a mixture, and then 5.59% of the mixture by weight of purified water was added by atomization and continued to stir for 30 s; then the binder solution obtained in step S1 was added by atomization, and continued to stir for 1 min, then the stirring was stopped, the material was collected, and the material was placed in a container The high-speed crushing and granulating machine with a screen is used to granulate to obtain wet granules;

[0042] S3, drying, granulating, sieving, and mixing the wet granules obtained in step S2 with magnesium stearate, screening according to the following particle sizes, and mixing according to the proportions to obtain material granules with a moisture content of 3-4%;

[0043] The proportion of each particle size is: >20 mesh 5.09%; 20-40 mesh 19.80%; 40-60 mesh 13.91%; 60-80 mesh 16.36%; 80-100 mesh 41.51%; <100 mesh 3.33%;

[0044] S4, taking the material particles obtained in step S3 and pressing them under the conditions of a design pressure of 4-6 kgf and a main pressure of 14.0-18.0 KN to obtain a tablet core of 126.0-136.0 mg per tablet;

[0045] Tablet preparation

[0046] The tablet cores were coated with 9% mass concentration of Opadry film coating solution, dried and cooled to obtain tablets, wherein the coating increased the weight of the tablets by 2-4% relative to the tablet cores.

[0047] Example 2 Preparation of Benidipine Hydrochloride Tablets

[0048] The specific details are the same as Example 1, except that the proportions of various particle sizes in the material particles in step S3 during tablet core preparation are: >20 mesh 7.11%; 20-40 mesh 13.77%; 40-60 mesh 10.98%; 60-80 mesh 15.27%; 80-100 mesh 32.55%; <100 mesh 20.32%.

[0049] Example 3 Preparation of Benidipine Hydrochloride Tablets

[0050] The specific details are the same as Example 1, except that the proportions of various particle sizes in the material particles in step S3 during the preparation of the tablet core are: >20 mesh 5.88%; 20-40 mesh 12.15%; 40-60 mesh 9.12%; 60-80 mesh 15.19%; 80-100 mesh 50.69%; <100 mesh 6.97%.

[0051] Example 4 Preparation of Benidipine Hydrochloride Tablets

[0052] The specific details are the same as Example 1, except that the mass concentration of the binder solution in step S1 during the preparation of the tablet core is 5.88%; the proportions of various particle sizes in the material particles in step S3 are: >20 mesh 1.64%; 20-40 mesh 5.47%; 40-60 mesh 20.18%; 60-80 mesh 36.49%; 80-100 mesh 25.79%; <100 mesh 10.44%.

[0053] Example 5 Preparation of Benidipine Hydrochloride Tablets

[0054] The specific details are the same as Example 1, except that the mass concentration of the binder solution in step S1 during tablet core preparation is 5.88%; the proportion of each particle size in the material particles in step S3 is: >20 mesh 0.84%; 20-40 mesh 6.06%; 40-60 mesh 10.69%; 60-80 mesh 47.48%; 80-100 mesh 31.05%; <100 mesh 3.88%.

[0055] Example 6 Preparation of Benidipine Hydrochloride Tablets

[0056] The specific details are the same as Example 1, except that the mass concentration of the binder solution in step S1 during tablet core preparation is 5.88%; the proportions of various particle sizes in the material particles in step S3 are: >20 mesh 2.19%; 20-40 mesh 9.54%; 40-60 mesh 12.79%; 60-80 mesh 41.60%; 80-100 mesh 21.67%; <100 mesh 12.20%.

[0057] Example 7 Preparation of Benidipine Hydrochloride Tablets

[0058] The specific details are the same as in Example 1, except that:

[0059] Tablet formula:

[0060] Main drug: 5 parts of benidipine hydrochloride

[0061] Diluent: 6 parts corn starch, 70 parts lactose

[0062] Binder: 2 parts dextrin

[0063] Lubricant: 1.5 parts calcium stearate

[0064] Tablet core preparation: The mass concentration of the adhesive solution in step S1 is 5.88%; the proportion of each particle size in the material particles in step S3 is: >20 mesh 2.19%; 20-40 mesh 9.54%; 40-60 mesh 12.79%; 60-80 mesh 41.60%; 80-100 mesh 21.67%; <100 mesh 12.20%.

[0065] Tablet preparation: The mass concentration of Opadry film coating solution is 6%.

[0066] Example 8 Preparation of Benidipine Hydrochloride Tablets

[0067] The specific details are the same as in Example 1, except that:

[0068] Tablet formula:

[0069] Main drug: 2 parts of benidipine hydrochloride

[0070] Diluent: 9 parts corn starch, 90 parts lactose

[0071] Binder: 1 part polyvinyl pyrrolidone

[0072] Lubricant: 0.5 parts of polyethylene glycol

[0073] Tablet core preparation: The mass concentration of the adhesive solution in step S1 is 5.88%; the proportion of each particle size in the material particles in step S3 is: >20 mesh 2.19%; 20-40 mesh 9.54%; 40-60 mesh 12.79%; 60-80 mesh 41.60%; 80-100 mesh 21.67%; <100 mesh 12.20%.

[0074] Tablet preparation: The mass concentration of Opadry film coating solution is 10%.

[0075] The beneficial effects of the present invention are further illustrated by test examples below.

[0076] Test Example: Quality Determination of Benidipine Hydrochloride Tablets

[0077] 1. Physical performance test

[0078] 1. Methods

[0079] The benidipine hydrochloride tablets prepared in Examples 1 to 6 were taken respectively, and their physical properties such as friability, weight difference, tablet thickness, disintegration time, hardness, tablet weight, average content, content uniformity and cumulative dissolution were tested; the intermediate material particles prepared in Examples 1 to 6 were taken respectively, and their average content and mixing uniformity were measured. The specific method for the physical properties of the intermediate material particles is as follows:

[0080] ① Average content: The average value of the content of each sampling point measured under the following mixing uniformity item is taken as the content determination result.

[0081] ② Mixing uniformity: Figure 2 Sampling diagram, sampling at 10 different positions of the three-dimensional swing mixer (points 1, 2, and 3 are the average three points of the charging surface; point 4 is the charging surface close to the corner of the barrel wall; points 6 and 7 are two points on a straight line at the lower corner of the barrel wall; points 5 and 8 are two points in the center of the mixed powder; points 9 and 10 are near the discharge port).

[0082] After sampling, mix and determine according to high performance liquid chromatography (Chinese Pharmacopoeia 2020 Edition Part IV General Rules 0512).

[0083] Test solution: Take about 262 mg of benidipine hydrochloride tablets, weigh accurately, place in a 100 ml volumetric flask, add about 60 ml of diluent (methanol-diluted phosphoric acid (1→500) (1:1)), shake thoroughly to dissolve the benidipine hydrochloride, dilute to the scale with the diluent, shake well, filter with a 0.45 μm filter membrane, and take the filtrate.

[0084] Reference solution: Take an appropriate amount of benidipine hydrochloride reference substance dried at 105°C for 2 hours, weigh it accurately, add diluent to dissolve it and quantitatively dilute it to make a solution containing about 80 μg per 1 ml.

[0085] System suitability solution: Take 6 mg of benidipine hydrochloride reference substance and 5 mg of benzoin, place in a 200 ml volumetric flask, add an appropriate amount of methanol-water (1:1), shake thoroughly to dissolve, dilute to the scale with methanol-water (1:1), and shake well.

[0086] The chromatographic conditions are as follows: octadecylsilane bonded silica gel is used as a filler (CAPCELL PAK C18, 100×4.6 mm, 3 μm or a chromatographic column of equivalent performance); 0.05 mol / L potassium dihydrogen phosphate buffer (take 6.8 g of potassium dihydrogen phosphate, add 1000 ml of water to dissolve, and adjust the pH value to 3.0 with phosphoric acid)-methanol-tetrahydrofuran (65:27:8) is used as the mobile phase; the detection wavelength is 237 nm; the column temperature is 25°C; the injection volume is 10 μl; and the flow rate is adjusted so that the retention time of the benidipine hydrochloride peak is about 20 minutes.

[0087] System suitability requirements: In the system suitability solution chromatogram, the separation between the benidipine hydrochloride peak and the benzoin peak should be no less than 8.0; in the reference solution chromatogram, the theoretical plate number calculated based on the benidipine hydrochloride peak should be no less than 3000.

[0088] Determination method: Accurately measure the test solution and the reference solution, inject them into the liquid chromatograph respectively, record the chromatogram, and calculate by peak area according to the external standard method.

[0089] The limit of each sampling point is benidipine hydrochloride (C 28 H 31 N3O6·HCl) should be 92.0% to 108.0% of the labeled amount. The measured values ​​at each sampling point should be within ±10% (absolute) of the average value, and the RSD should not be greater than 5.0%.

[0090] Benidipine Hydrochloride Tablets Physical Properties Test:

[0091] ① Friability test: refer to the 0923 Tablet Friability Test Method in Part IV of the 2020 edition of the Chinese Pharmacopoeia. The limit requirement is: the weight loss should be less than 1.0%, and no broken, cracked or crushed tablets should be detected.

[0092] ② Detection of weight difference: refer to the weight difference inspection method of the general rules for preparations in the 2020 edition of the "Chinese Pharmacopoeia", with a limit of ±7.5%.

[0093] ③ Detection of sheet thickness: Use vernier caliper for detection, limit: 3.10~3.40mm.

[0094] ④ Disintegration time detection: Refer to the disintegration time limit regulations in the 2020 edition of the "Chinese Pharmacopoeia". All tablets should be completely disintegrated within 15 minutes (through the hanging basket sieve).

[0095] ⑤Hardness testing method: Use intelligent hardness tester for testing.

[0096] ⑥ Tablet weight: weighed using an electronic balance.

[0097] ⑦Content uniformity: Take 1 benidipine hydrochloride tablet, place it in a 50ml volumetric flask, add about 30ml of diluent (methanol-diluted phosphoric acid (1→500) (1:1)), shake thoroughly to dissolve the benidipine hydrochloride, dilute to the scale with the diluent, shake well, filter, and take the filtrate as the test solution. The content should be determined according to the method under the item of content determination of benidipine hydrochloride tablets in the fourth general rule of the 2020 edition of the Chinese Pharmacopoeia (0512) (0941 of the fourth general rule of the 2020 edition of the Chinese Pharmacopoeia), A+2.2S≤15.0.

[0098] ⑧ Detection of average content: The average value of the above content uniformity is taken as the content determination result.

[0099] ⑨Dissolution test

[0100] The dissolution of the tablets of Examples 1 to 3 and the commercially available tablets (from Kyowa Hakko Kirin Co., Ltd.) was tested with reference to the Japanese Orange Book / JP17 by the following method, specifically: Dissolution medium: 17.91 g of disodium hydrogen phosphate dodecahydrate was weighed, dissolved in degassed purified water and fixed to 1000 ml to obtain a 0.05 mol / L disodium hydrogen phosphate solution; 5.25 g of citric acid monohydrate was taken, dissolved in degassed purified water and fixed to 1000 ml to obtain a 0.025 mol / L citric acid solution; the disodium hydrogen phosphate solution was then adjusted to pH 4.0 with the citric acid solution to obtain; the dissolution conditions were: paddle method, sinker, 900 mL medium, 50 r / min.

[0101] Since SDS is not added in the dissolution determination method in the Japanese Orange Book / JP17, in order to make the tablets dissolve more fully, the dissolution of the tablets of Examples 4 to 6 and the commercially available tablets (from Kyowa Hakko Kirin Co., Ltd.) was tested by the following method, specifically: using pH 6.8 phosphate solution + 0.02% SDS medium: weighing 0.2g of SDS, using pH 6.8 buffer (weighing 1.9488g of sodium dihydrogen phosphate (dihydrate), 3.34922g of disodium hydrogen phosphate (heptahydrate), adding degassed purified water to dissolve and set to 1000ml, adjusting pH=6.8 with phosphoric acid) 1000ml to dissolve (ultrasonic dissolution if necessary). Dissolution conditions: paddle method, adding sinker, 900mL medium, 50r / min.

[0102] 2. Results

[0103] The weight difference of the tablets prepared in Examples 1 to 6: single tablet weight difference 131 mg ± 7.5%; friability: ≤ 1%; tablet thickness: 3.10 to 3.40 mm; disintegration time: each tablet completely disintegrated in water within 1.5 min and passed through the hanging basket screen.

[0104] Dissolution Figure 1 , Tables 1~2.

[0105] Table 1 Dissolution of Tablets of Examples 1-3

[0106]

[0107] from Figure 1 As shown in Table 1, the cumulative dissolution rate of the benidipine hydrochloride tablets of the present invention is greater than that of the commercial product, and the dissolution equilibrium can be reached in less than 15 minutes; the commercial product reaches the dissolution equilibrium in about 30 minutes; at the same time, the content uniformity is better than the commercial product, the difference in the amount of the main drug per tablet of the product is small, and the quality is better than the commercial product. The bulk density of the material particles obtained in Examples 1-3 is 0.6245g / ml, 0.6381g / ml, and 0.6196g / ml respectively; the tap density of the obtained material particles is 0.7373g / ml, 0.7451g / ml, and 0.7286g / ml.

[0108] Table 2 Dissolution of tablets obtained in Examples 4-6

[0109]

[0110] As can be seen from Table 2, the cumulative dissolution rate of the tablets of the present invention in a pH 6.8 phosphate solution + 0.02% SDS environment is comparable to that of the commercial product; in the first 45 minutes, the cumulative dissolution rate is greater than that of the commercial product, indicating rapid dissolution.

[0111] In summary, compared with commercially available products, the content uniformity of the present invention is better, the content of the main drug is more uniform, the dissolution rate is higher, and its instantaneous dissolution has potential benefits for bone formation.

[0112] 2. Chemical performance test

[0113] The physical property test determined that the dissolution rate of the benidipine hydrochloride tablets prepared in Example 2 was the highest, the difference between the proportion of 40-100 mesh particles and the maximum and minimum particle sizes was the smallest, and the amount of binder was appropriate, so the tablets prepared in Example 2 were selected for further testing of their chemical stability.

[0114] The tablets obtained in Example 2 were subjected to high temperature, high humidity, light or accelerated tests, and the results are shown in Table 3. The dissolution test conditions are: 900 mL of sodium chloride hydrochloric acid solution (weighing 2 g of sodium chloride, adding 7 ml of hydrochloric acid, and adding water to 1000 ml) is used as the dissolution medium, the rotation speed is 50 revolutions per minute, and the operation is carried out according to the law, and sampling is taken after 30 minutes.

[0115] Table 3 Degradation results of the tablets obtained in Example 2 and commercially available products

[0116]

[0117] As can be seen from Table 3, the benidipine hydrochloride tablets of the present invention are more stable than commercial products, and the impurity content is low regardless of high temperature, high humidity or light degradation. In particular, in the accelerated test of packaged tablets, the impurity content of the benidipine hydrochloride tablets of the present invention is much less than that of the commercial products, indicating that the benidipine hydrochloride tablets of the present invention are stable and not easy to decompose, further proving that the drug quality is excellent and the safety is high.

[0118] In summary, the tablet cores pressed from material particles of a specific particle size in the present invention have good uniformity of the main drug content after coating, fast dissolution rate, short disintegration time, and can quickly release the main drug benidipine hydrochloride, thereby avoiding the side effects of benidipine hydrochloride tablets. The preparation method of benidipine hydrochloride tablets of the present invention adopts a specific process of stirring + knife cutting + atomization to mix the raw and auxiliary materials in the tablets evenly, and is easy to make material particles of a specific particle size for tableting, the preparation process is simple, the obtained tablets have a small content of related substances, stable properties, can be quickly dissolved, and take effect quickly.

Claims

1. A benidipine hydrochloride tablet, characterized in that: It is a preparation formed by coating the tablet core with a coating liquid; the tablet core is formed by mixing and pressing material particles of the following particle sizes in proportion: >20 mesh 0.8-8%, 20-40 mesh 5-20%, 40-60 mesh 9-21%, 60-80 mesh 15-48%, 80-100 mesh 20-51%;, <100 mesh 3-21%; The material particles include the following raw materials and auxiliary materials in parts by weight: 2-5 parts of benidipine hydrochloride, 76-99 parts of diluent, 1-2 parts of adhesive, and 0.5-1.5 parts of lubricant.

2. The benidipine hydrochloride tablet according to claim 1, characterized in that: The tablet core is formed by mixing and pressing material particles of the following particle sizes in proportion: >20 mesh 5-8%; 20-40 mesh 12-20%; 40-60 mesh 9-14%; 60-80 mesh 15-17%; 80-100 mesh 25-50%; <100 mesh 3-21%.

3. The benidipine hydrochloride tablet according to claim 2, characterized in that: The tablet core is formed by mixing and pressing material particles of the following particle sizes in proportion: >20 mesh 7~8%; 20-40 mesh 13~14%; 40-60 mesh 10~11%; 60-80 mesh 15~16%; 80-100 mesh 32~33%; <100 mesh 20~21%.

4. The benidipine hydrochloride tablet according to any one of claims 1 to 3, characterized in that: The diluent is a mixture of 6-9 parts of corn starch and 70-90 parts of lactose; The lubricant is one or more of talc, stearic acid, magnesium stearate, calcium stearate, sodium stearate, polyethylene glycol, and sodium lauryl sulfate; The adhesive is one or more of dextrin, polyvinyl pyrrolidone and polyvinyl alcohol.

5. The benidipine hydrochloride tablet according to claim 1, characterized in that: The coating liquid is Opadry film coating liquid with a concentration of 6-10%.

6. A method for preparing the benidipine hydrochloride tablets according to claim 1, characterized in that: It includes the following steps: S1, taking 70-85% of the adhesive in the formula, adding water to dissolve, and obtaining an adhesive solution; S2, mixing and shearing the diluent, benidipine hydrochloride and the remaining binder to obtain a mixture, and then adding water and the binder solution obtained in step S1 in sequence by atomization, stirring, and granulating to obtain wet granules; S3, drying the wet granules obtained in step S2, granulating, sieving, mixing with a lubricant, screening according to the particle size, and then mixing according to the particle size ratio to obtain material granules; S4, taking the material particles obtained in step S3 and pressing them into tablet cores, coating them with a coating liquid, drying them, and cooling them to obtain tablet cores.

7. The method according to claim 6, characterized in that: In step S1, the temperature of the water is 50-60° C.; the concentration of the adhesive solution is 5-20%.

8. The method according to claim 6, characterized in that: In step S2, the mixing and shearing stirring speed is 200-210rpm, the cutting knife speed is 2000-2050rpm, and the stirring time is 3-5min; the amount of water added is 5-8% of the mixture, and the mixture is stirred for 30-60s after the water is added, and the adhesive solution is stirred for 1-3min after the addition.

9. The method according to claim 6, characterized in that: The moisture content of the material particles in step S3 is 3-4%.

10. The method according to claim 6, characterized in that: The design pressure of the pressing in step S4 is 4-6 kgf, the main pressure is 14.0-18.0 KN, and the tablet weight of the tablet core is 126.0-136.0 mg.

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