Angiotensin converting enzyme inhibitor tablet and preparation method thereof

Abstract

The invention discloses an angiotensin converting enzyme inhibitor tablet and a preparation method thereof, the tablet comprises benazepril hydrochloride as an active component, lactose as an auxiliary material, pregelatinized starch, microcrystalline cellulose, polyvinylpolypyrrolidone, colloidal silicon dioxide and hydrogenated castor oil as a lubricant, and the tablet is prepared by wet granulation and coating treatment. In the preparation process, the comprehensive optimization of the tablet quality is realized by accurately controlling the key steps of raw material sieving, premixing, granulating process, fluidized bed drying, total mixing, tabletting, coating and the like. The benazepril hydrochloride tablet is uniform in component and stable in quality, and provides a more reliable and efficient treatment choice for patients.

Description

Technical Field

[0001] This application belongs to the field of pharmaceutical formulation technology, and specifically relates to an angiotensin-converting enzyme inhibitor tablet and its preparation method. Background Technology

[0002] Benazepril hydrochloride, chemically known as 3-{[(1-ethoxycarbonyl)-3-phenyl-(1s)-propyl]amino}-2,3,4,5-tetrahydro-2-oxo-1-hydro-1-(3s)-benzodiazepine-1-acetic acid monohydrochloride, is an angiotensin-converting enzyme inhibitor (ACEI) primarily used to treat hypertension and congestive heart failure. It works by inhibiting angiotensin-converting enzyme, preventing the conversion of angiotensin I into angiotensin II, which has a strong vasoconstrictive effect, thereby reducing vascular resistance and decreasing aldosterone secretion, thus achieving the effects of lowering blood pressure and improving cardiac function.

[0003] The following problems may be encountered during the preparation of benazepril hydrochloride tablets:

[0004] (1) Drug stability: As a drug that is susceptible to environmental influences, the stability of benazepril hydrochloride needs to be carefully monitored during preparation and storage.

[0005] (2) Drug dissolution: The dissolution of a drug directly affects its bioavailability, and thus its therapeutic effect. Therefore, improving the dissolution of benazepril hydrochloride tablets is an important direction for optimizing the preparation process. Summary of the Invention

[0006] The purpose of this application is to provide an angiotensin-converting enzyme inhibitor tablet and its preparation method. By optimizing the preparation process parameters, such as selecting appropriate types and dosage ranges of disintegrants and adjusting the particle size distribution, an angiotensin-converting enzyme inhibitor tablet and an optimal preparation method are obtained. This product not only ensures excellent dissolution performance but also exhibits excellent stability, thereby ensuring the stability and effectiveness of the drug during storage and use.

[0007] On one hand, this application provides a benazepril hydrochloride tablet, the components of which, by weight percentage, are: 5.56% benazepril hydrochloride, 80%-85% filler, 4.44% binder, 1.67%-3.8% disintegrant, 0.56% glidant, and 4.44% lubricant. Further, the tablet is coated, with the coating gaining 2%-4%.

[0008] In one embodiment of benazepril hydrochloride tablets, the filler is one or a mixture of microcrystalline cellulose and lactose.

[0009] Furthermore, the filler comprises 10%-16.7% microcrystalline cellulose and 66.7%-73.3% lactose.

[0010] In one embodiment of benazepril hydrochloride tablets, the lactose may be lactose monohydrate, such as flowlac100, T80, or G200.

[0011] In one embodiment of benazepril hydrochloride tablets, the binder is pregelatinized starch.

[0012] In one embodiment of benazepril hydrochloride tablets, the disintegrant is one or a mixture of several of sodium carboxymethyl starch, crospovidone (PVPP), crospovidone carboxymethyl cellulose, and low-substituted hydroxypropyl cellulose.

[0013] In one embodiment of benazepril hydrochloride tablets, the lubricant is one or more of hydrogenated castor oil and silicon dioxide.

[0014] In one embodiment of benazepril hydrochloride tablets, the flow aid is colloidal silica.

[0015] In one embodiment of benazepril hydrochloride tablets, the components of the benazepril hydrochloride tablets, by weight percentage, are as follows:

[0016] 5.56% benazepril hydrochloride, 73.3% lactose, 4.44% pregelatinized starch, 10.0% microcrystalline cellulose, 1.67% crospovidone, 0.56% colloidal silica, and 4.44% hydrogenated castor oil.

[0017] In one embodiment of the present invention, the particle size D90 of benazepril hydrochloride is <70 μm.

[0018] On the other hand, the present invention provides a method for preparing benazepril hydrochloride tablets, comprising the following steps:

[0019] A method for preparing benazepril hydrochloride tablets includes the following steps:

[0020] Premix: Benazepril hydrochloride, lactose, and pregelatinized starch are premixed for 2-3 minutes;

[0021] Granulation: Add water for granulation, stirring: 150-300, shearing: 600-800, time: 2-6 min; wet granules are sieved through an 18-mesh sieve for granulation; fluidized bed drying: air inlet 60℃±5℃; 20-mesh dry granulation;

[0022] Total mixture: Microcrystalline cellulose, crospovidone, colloidal silica, and hydrogenated castor oil are added according to the prescription ratio and then mixed.

[0023] Tablets: 180mg Shallow concave round stamped sheet;

[0024] Coating: Coating solution concentration 15%, coating temperature 50-60℃, coating weight gain 2-4%.

[0025] In some embodiments, before premixing, benazepril hydrochloride, lactose, and pregelatinized starch are passed through a 60-mesh sieve; microcrystalline cellulose, cross-linked polyvinyl chloride, and colloidal silica are passed through a 40-mesh sieve respectively, and set aside for later use.

[0026] In the implementation of the premixing step, the process parameters are: stirring speed 200 rpm; shearing speed 800 rpm; time: 2 min.

[0027] In the granulation step, the prescribed amount of purified water is added by spraying or rinsing, with the spraying time controlled within 4 minutes. Under the same parameters, the granulation time is 4-6 minutes. The process parameters are: stirring speed 200 rpm and shearing speed 800 rpm.

[0028] In some embodiments, the amount of water added in the granulation step does not exceed 13.9%.

[0029] In some embodiments, the drying time in the drying step is 20-60 minutes, preferably 30 minutes, 45 minutes, or 60 minutes.

[0030] In some embodiments, the moisture content in the drying step is controlled within the range of 4 to 5.5%.

[0031] In some implementations, the total homogeneity is controlled at 5%, the content is 52.8-58.3 mg / g, and the moisture content is 4-5.5%.

[0032] In some implementations, the coating weight gain is controlled at 2-4%, and the moisture content is controlled at 4-5.5%.

[0033] Compared with the prior art, the present invention has the following beneficial effects:

[0034] By controlling the dosage of disintegrants within an appropriate range and avoiding the use of magnesium stearate, a lubricant that may interact with the drug components, benazepril hydrochloride tablets can release the drug more rapidly and stably after administration, thereby improving the drug's bioavailability and efficacy. This adjustment not only benefits the patient's treatment outcome but also helps improve the drug's safety and stability. Attached Figure Description

[0035] Figure 1 This is a process flow diagram for benazepril hydrochloride tablets. Detailed Implementation

[0036] The technical solutions of the embodiments of this application will be clearly described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this application. All other embodiments obtained by those skilled in the art based on the embodiments of this application are within the scope of protection of this application.

[0037] Unless otherwise defined, all technical terms and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the embodiments of this invention pertain. If any definition stated in this section is contrary to or otherwise inconsistent with a definition stated in a patent, patent application, published patent application, or other publication incorporated herein by reference, the definitions listed here shall prevail over those incorporated herein by reference.

[0038] Furthermore, the mass of the relevant components mentioned in the specification of the embodiments of this invention can refer not only to the specific content of each component, but also to the proportional relationship between the masses of the components. Therefore, any scaling up or down of the content of the relevant components according to the specification of the embodiments of this invention is within the scope disclosed in the specification of the embodiments of this invention. Specifically, the mass described in the specification of the embodiments of this invention can be a mass unit known in the chemical industry, such as μg, mg, g, or kg.

[0039] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods. Unless otherwise specified, the materials and reagents used in the following embodiments are commercially available. This application will now be described in detail with reference to specific embodiments.

[0040] This application provides a benazepril hydrochloride tablet, the components of which, by weight percentage, are: 5.56% benazepril hydrochloride, 80%-85% filler, 4.44% binder, 1.67%-3.8% disintegrant, 0.56% glidant, and 4.44% lubricant. Further, the tablet is coated, with the coating gain being 2%-4%. The amount of filler added can be 82%, 83.3%, or 85%; the disintegrant can be 1.67%, 2.7%, or 3.8%.

[0041] In one embodiment of benazepril hydrochloride tablets, the filler is one or a mixture of microcrystalline cellulose and lactose.

[0042] Preferably, the filler comprises 10%-16.7% microcrystalline cellulose and 66.7%-73.3% lactose; more preferably, the filler comprises 10% microcrystalline cellulose and 73.3% lactose.

[0043] In one embodiment of benazepril hydrochloride tablets, the lactose may be lactose monohydrate, such as flowlac100, T80, or G200.

[0044] In one embodiment of benazepril hydrochloride tablets, the binder is pregelatinized starch.

[0045] In one embodiment of benazepril hydrochloride tablets, the disintegrant is one or a mixture of several of sodium carboxymethyl starch, crospovidone (PVPP), crospovidone carboxymethyl cellulose, and low-substituted hydroxypropyl cellulose. Preferably, the disintegrant is crospovidone.

[0046] In one embodiment of benazepril hydrochloride tablets, the lubricant is one or more of hydrogenated castor oil and silicon dioxide. Preferably, the lubricant is hydrogenated castor oil.

[0047] In one embodiment of benazepril hydrochloride tablets, the flow aid is colloidal silica.

[0048] In one embodiment of benazepril hydrochloride tablets, the components of the benazepril hydrochloride tablets, by weight percentage, are as follows:

[0049] 5.56% benazepril hydrochloride, 73.3% lactose, 4.44% pregelatinized starch, 10.0% microcrystalline cellulose, 1.67% crospovidone, 0.56% colloidal silica, and 4.44% hydrogenated castor oil.

[0050] In one embodiment of the present invention, the particle size D90 of benazepril hydrochloride is <70 μm.

[0051] A method for preparing benazepril hydrochloride tablets includes the following steps:

[0052] Premix: Benazepril hydrochloride, lactose, and pregelatinized starch are premixed for 2-3 minutes;

[0053] Granulation: Add water for granulation, stirring: 150-300, shearing: 600-800, time: 2-6 min; wet granules are sieved through an 18-mesh sieve for granulation; fluidized bed drying: inlet air temperature 60℃±5℃; 20-mesh dry granulation;

[0054] Total mixing: Microcrystalline cellulose, crospovidone, colloidal silica and hydrogenated castor oil are added and mixed according to the formula ratio; the mixing time can be 3-20 minutes, preferably 15 minutes.

[0055] Tablets: 180mg Shallow concave round stamped sheet;

[0056] Coating: Coating solution concentration 15%, coating temperature 50-60℃, coating weight gain 2-4%.

[0057] In some embodiments, before premixing, benazepril hydrochloride, lactose, and pregelatinized starch are passed through a 60-mesh sieve; microcrystalline cellulose, cross-linked polyvinyl chloride, and colloidal silica are passed through a 40-mesh sieve respectively, and set aside for later use.

[0058] In the implementation of the premixing step, the process parameters are: stirring speed 200 rpm; shearing speed 800 rpm; time: 2 min.

[0059] The mixing uniformity of this process is RSD≤10%, and the content is 63.3-70.0mg / g. The content of the premixed powder is detected by HPLC and data from 10 different sampling points are statistically analyzed.

[0060] In the granulation step, the prescribed amount of purified water is added by spraying or rinsing, with the spraying time controlled within 4 minutes, and granulation is carried out for 4-6 minutes under the same parameters. The process parameters are: stirring speed 200 rpm and shearing speed 800 rpm.

[0061] In some embodiments, the amount of water added in the granulation step does not exceed 13.9%.

[0062] In the implementation of the wet granulation step, wet granulation is carried out using a high-speed granulator with a 3mm screen and a rotation speed of 15-20Hz.

[0063] In this drying process, the wet particles are placed in a fluidized bed for drying. The process parameters are: inlet air temperature 60±5℃, drying time 20min~60min; the moisture content is required to be controlled within the range of 4~5.5%. A rapid moisture determination method is used to measure the moisture content of the dried particles, with measurements taken every 10min after 20min.

[0064] In some embodiments, the drying time in the drying step is 30 minutes, 45 minutes, or 60 minutes.

[0065] In the dry granulation implementation, the dry granules are granulated by a high-speed granulator with a screen size of 1 mm and a rotation speed of 15-20 Hz.

[0066] In the implementation of the total mixing step, the process parameters are: rotation speed 20±5 Hz, mixing time 15 min. Samples were taken at different locations at 5, 10, and 15 min to determine the content.

[0067] The overall mixing uniformity of this process is controlled at 5%, with a content of 52.8-58.3 mg / g and a moisture content of 4-5.5%. The mixing uniformity is determined by HPLC to detect the particle content after granulation and to collect data from 10 different sampling points (10 samples taken at each time point). The moisture content is determined by a rapid moisture analyzer on random samples after discharge.

[0068] In the tableting process, the die: Shallow concave punching is used to compress the total mixed granules into tablets with a pressure of 4-8 kg.

[0069] During the tableting process, 10 tablets were taken every 15 minutes to measure the total weight and the weight of each tablet, and the tablet weight difference was calculated and controlled within ±5%, with a friability of ≤1%.

[0070] Record detailed tableting parameters: tableting speed, rolling pressure, etc.

[0071] In the coating step, the coating solution is prepared as follows: the solid content of the coating solution is 15%, and it is stirred for 45 minutes before use.

[0072] Preheat the core: Set the inlet air temperature to 50-60℃, preheat for 10-20 minutes, and rotate at 2-8 rpm;

[0073] Spraying: Control the spray pressure to 0.2-0.5MPa, adjust the pot speed to 2-8rpm; the inlet air temperature to 50-60℃, so that the tablet bed temperature is 40±5℃, and adjust the exhaust fan frequency to maintain the negative pressure between 0 and 20Pa.

[0074] Drying: After the slurry is sprayed, set the air inlet temperature to 50-60℃, dry for 60 minutes, and stop drying when the moisture content is measured to be 4-5.5%. Cool to room temperature and discharge.

[0075] This process controls the coating weight gain and tablet moisture content. The coating weight gain is controlled at 2-4%, and the moisture content is controlled at 4-5.5%, measured using a rapid moisture analyzer.

[0076] Furthermore, for the inner packaging, double aluminum blister packaging can be used: polyamide / aluminum / polyvinyl chloride cold-stamped solid pharmaceutical composite hard sheet and pharmaceutical aluminum foil.

[0077] The features and performance of this application will be further described in detail below with reference to the embodiments.

[0078] Content detection method - HPLC method.

[0079] Reference formulation

[0080] Table 1 Basic Information of Reference Preparation

[0081] Product Name Loding New Manufacturer Novartis Pharmaceuticals Beijing Co., Ltd. Properties A round, thin-film coated sheet, yellowish-brown in color, with letters on both sides. batch number X2603 Production date 2017.08 Validity period July 2020 (36 months) Specification 10mg Average tablet weight (mg) 187mg Scratches None, letter Coating film coat diameter 8.2mm thick 3.5mm Hardness (kP) 6.52kg

[0082] The inactive ingredients listed in the new US labeling for Lotin are: colloidal silica, cropovidone, hydrogenated castor oil (10 mg and 20 mg tablets), hydroxypropyl methylcellulose, iron oxide, lactose, magnesium stearate (40 mg tablets), microcrystalline cellulose, polysorbate 80, propylene glycol (40 mg tablets), starch, talc, and titanium dioxide.

[0083] Example 1: Benazepril Hydrochloride Tablets (10mg)

[0084] The formulation of benazepril hydrochloride tablets is shown in Table 1.

[0085] Table 1

[0086]

[0087]

[0088] Note 1: Water is ultimately removed during the process; Note 2: Excessive preparation of coating solution results in a coating weight gain of approximately 2-4%.

[0089] Double aluminum blister packaging is proposed, and the coating materials are as shown in Table 2 below:

[0090] Table 2 Packaging Materials

[0091]

[0092] Preparation process of benazepril hydrochloride tablets:

[0093] Premix: Benazepril hydrochloride, lactose, and pregelatinized starch are premixed for 2-3 minutes;

[0094] Granulation: Add water to granulate, stirring: 400, shearing: 800, time: 6min; wet granules are sieved through an 18-mesh sieve for granulation;

[0095] Fluidized bed drying: air inlet temperature 60℃; 20-mesh dry granulation;

[0096] Total Mixture: Add microcrystalline cellulose, crospovidone, colloidal silica and hydrogenated castor oil according to the prescription ratio and mix for 3-15 minutes;

[0097] Tablets: 180mg Shallow concave round stamped sheet;

[0098] Coating: Coating increases weight by 2-4%.

[0099] Example 2

[0100] Prescription dosage: see Table 3.

[0101] Table 3 Prescription dosage for Example 2

[0102]

[0103] The preparation process of benazepril hydrochloride tablets is the same as that in Example 1.

[0104] Example 3:

[0105] The prescription quantities are shown in Table 4.

[0106] Table 4 Prescription dosage for Example 3

[0107]

[0108] The preparation process of benazepril hydrochloride tablets is the same as that in Example 1.

[0109] Example 4:

[0110] The prescription quantities are shown in Table 5.

[0111] Table 5 Prescription dosage for Example 4

[0112]

[0113] The preparation process of benazepril hydrochloride tablets is the same as that in Example 1. Comparative Example 1:

[0114] The prescription quantities are shown in Table 6.

[0115] Table 6 Comparative Example 1 Prescription Quantity

[0116]

[0117]

[0118] The preparation process of benazepril hydrochloride tablets is the same as that in Example 1. Comparative Example 2:

[0119] The prescription quantities are shown in Table 7.

[0120] Table 7. Prescription quantity for Comparative Example 2

[0121]

[0122] The preparation process of benazepril hydrochloride tablets is the same as that in Example 1. Comparative Example 3:

[0123] The prescription quantities are shown in Table 8.

[0124] Table 8. Prescription quantity for Comparative Example 3

[0125]

[0126] The preparation process of benazepril hydrochloride tablets is the same as that in Example 1. Comparative Example 4:

[0127] The prescription quantities are shown in Table 9.

[0128] Table 9. Prescription quantity for Comparative Example 4

[0129]

[0130] Preparation process of benazepril hydrochloride tablets:

[0131] Premix: Benazepril hydrochloride, lactose, and pregelatinized starch are premixed for 3 minutes;

[0132] Granulation: Add water for granulation, stirring: 400, shearing: 800, time: 6min; wet granules are sieved through an 18-mesh sieve for granulation; fluidized bed drying: air inlet 60℃; 20-mesh dry granulation;

[0133] Total Mixture: Add microcrystalline cellulose, crospovidone, colloidal silica, and magnesium stearate according to the prescription ratio, and mix for 3-15 minutes;

[0134] Tablets: 180mg Shallow concave round stamped sheet;

[0135] Coating: Coating increases weight by 2-4%.

[0136] A: The dissolution performance of benazepril hydrochloride tablets prepared in Examples 1-4 and Comparative Examples 1-4 was investigated.

[0137] The dissolution and release rate were determined according to the method of determination (Chinese Pharmacopoeia 2020 Edition, Part IV, General Chapter 0931, Method II). Water, 0.1 mol / L HCl solution, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer were used as dissolution media, respectively. The dissolution speed was 100 rpm. The procedure was followed, and samples were taken at 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, and 60 min. The f2 factor of the dissolution curves of benazepril hydrochloride tablets prepared in Examples 1-3 and Comparative Examples 1-4 and the reference reagent (Lotensin) were detected. The results are shown in Table 10.

[0138] Table 10

[0139]

[0140]

[0141] As can be seen from Examples 1-3, the f2 factor is above 50% in all cases, and the increase in the amount of disintegrant leads to an increase in dissolution rate, but the amount of disintegrant needs to be controlled within a certain range. The f2 factor of the dissolution curves of Comparative Examples 1-4 is unstable in different media, and in some media, the f2 factor is below 50%. It is evident that the dissolution curves of Examples 1-3 in various media are consistent with the dissolution curves of the reference formulation in the same media, while the dissolution curves of Comparative Examples 1-4 differ significantly from the reference formulation in the same media, with the dissolution factor below 50% in some media, resulting in dissimilar dissolution curves. Therefore, when the disintegrant dosage is between 1.67% and 3.8%, the dissolution curves of the prepared benazepril hydrochloride tablets are more similar to those of the reference formulation.

[0142] The comparison between Example 3 and Comparative Example 4 shows that when the amount of disintegrant is the same (3.8%), the f2 factor of Example 3 is >70% when the lubricant is hydrogenated castor oil, while the f2 factor is less than 50% when the lubricant is magnesium stearate. Therefore, this application can obtain a higher f2 factor and better dissolution performance by using hydrogenated castor oil as a lubricant than by using magnesium stearate.

[0143] B: Stability Study of Small-Scale Trial Batch in Example 1

[0144] batch number Production date batch 20181026 2018.10.26 10,000 20181108 2018.11.08 100,000

[0145] The pilot production process flow is as follows: Figure 1 As shown in Table 11, the dissolution comparison results of the above batches with the reference formulation are as follows:

[0146] Table 11

[0147]

[0148]

[0149] Experimental results show that the small-scale formulation of the present invention maintained good content stability under all test conditions, approaching or slightly exceeding 100%, indicating that its preparation process is stable and reliable. Furthermore, the benazepril hydrochloride tablets of the present invention exhibited excellent dissolution under the aforementioned test conditions, especially under commercial packaging, 40°C, and RH 92.5%, where the dissolution rate approached or reached 100%. Although the dissolution rates of both the small-scale formulation and the reference formulation decreased significantly under high temperature (60°C), the overall performance of the small-scale formulation of the present invention was relatively better, especially in terms of long-term storage stability, where it outperformed the reference formulation.

[0150] 1: Investigation on the moisture control of intermediates in the fluidized bed drying step of the preparation process

[0151] Using the same preparation steps as in Example 1, the intermediates were dried in an oven for different times, then tableted according to the prescription, coated, sealed in a composite film bag, and placed at 80°C for 6 days to detect changes in benazeprilat.

[0152]

[0153]

[0154] Experimental data show that:

[0155] The intermediate of lactose monohydrate was fluidized bed dried for 30 minutes, with a moisture content of 5.9% (approximately 1.5% free water). After being stored at 80°C for 60 days, the degradation degree of benazeprilat was comparable to that of the reference formulation.

[0156] After drying for 45 minutes, the intermediate moisture content was 4.8% (approximately 0.4% free water); after drying for 60 minutes, the intermediate moisture content was 5.4% (approximately 1.0% free water). After being stored at 80°C for 60 days, the degradation degree of benazeprilat was comparable to that of the reference formulation.

[0157] After drying for 60 minutes, the intermediate moisture content was 5.4% (approximately 1.0% free water). After being stored at 80°C for 60 days, the degradation of benazeprilat was less than that of the reference formulation.

[0158] These experimental results, combined with oven drying data, show that when the intermediate moisture content is reduced to less than 5.9% (approximately 1.5% free water), the degradation rate of benazeprilat remains comparable to or slightly better than that of the reference formulation. This indicates that moisture is one of the key factors affecting drug stability and degradation rate. Reducing moisture content can slow down the degradation process of benazeprilat by decreasing the rate of hydrolysis or other water-required chemical reactions.

[0159] In conclusion, by precisely controlling the moisture content during the oven drying process, the degradation rate of benazeprilat can be significantly improved, making it comparable to or better than the reference formulation.

[0160] The embodiments of this application have been described above with reference to the accompanying drawings. However, this application is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of this application without departing from the spirit and scope of the claims, and all of these forms are within the protection scope of this application.

Claims

1. A benazepril hydrochloride tablet, wherein the components of the tablet, by weight percentage, are: 5.56% benazepril hydrochloride, 80%-85% filler, 4.44% binder, 1.67%-3.8% disintegrant, 0.56% glidant, and 4.44% lubricant.

2. The benazepril hydrochloride tablets according to claim 1, characterized in that, The tablets are coated, and the coating increases the weight by 2%-4%.

3. The benazepril hydrochloride tablets according to claim 1, characterized in that, The filler comprises 10%-16.7% microcrystalline cellulose and 66.7%-73.3% lactose.

4. The benazepril hydrochloride tablets according to claim 1, characterized in that, The lactose can be lactose monohydrate, such as flowlac100, T80, or G200.

5. The benazepril hydrochloride tablets according to claim 1, characterized in that, The adhesive is pregelatinized starch; The lubricant is hydrogenated castor oil; The flow aid is colloidal silica.

6. The benazepril hydrochloride tablets according to claim 1, characterized in that, The components of the benazepril hydrochloride tablets, by weight percentage, are as follows: 5.56% benazepril hydrochloride, 73.3% lactose, 4.44% pregelatinized starch, 10.0% microcrystalline cellulose, 1.67% crospovidone, 0.56% colloidal silica, and 4.44% hydrogenated castor oil.

7. The benazepril hydrochloride tablets according to claim 1, wherein the preparation method of the benazepril hydrochloride tablets comprises the following steps: Premix: Benazepril hydrochloride, lactose, and pregelatinized starch are premixed for 2-3 minutes; Granulation: Add water for granulation, stirring: 150-300, shearing: 600-800, time: 2-6 min; wet granules are sieved through an 18-mesh sieve for granulation; fluidized bed drying: air inlet 60℃±5℃; 20-mesh dry granulation; Total Mixture: Add microcrystalline cellulose, crospovidone, colloidal silica and hydrogenated castor oil according to the prescription ratio and mix for 3-15 minutes; Tableting: 180mg tablets, φ8mm shallow concave round punch; Coating: Coating increases weight by 2-4%.

8. The method for preparing benazepril hydrochloride tablets according to claim 7, characterized in that, Before premixing, benazepril hydrochloride, lactose, and pregelatinized starch were sieved through a 60-mesh sieve; microcrystalline cellulose, crospovidone, and colloidal silica were sieved through a 40-mesh sieve.

9. The method for preparing benazepril hydrochloride tablets according to claim 7, characterized in that, The premixing process parameters are: stirring speed 200 rpm; shearing speed 800 rpm; time: 2 min; The amount of water added in the granulation step shall not exceed 13.9%; The granulation time is 4-6 minutes; the stirring process parameters are: stirring speed 200 rpm, shearing speed 800 rpm; The drying time in the drying step is 20 minutes to 60 minutes, preferably 30 minutes, 45 minutes, or 60 minutes; Furthermore, the moisture content during the drying step is controlled within the range of 4% to 5.5%. The overall uniformity was controlled at 5%, the content was 52.8-58.3 mg / g, and the moisture content was 4-5.5%. The weight gain of the coating is controlled at 2-4%, and the moisture content is controlled at 4-5.5%.

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