Benazepril hydrochloride and hydrochlorothiazide tablet and preparation method thereof

Abstract

The invention provides benazepril hydrochloride and hydrochlorothiazide tablets and a preparation method thereof, and relates to the technical field of pharmaceutical preparations. The benazepril hydrochloride and hydrochlorothiazide tablet is prepared from the following raw material components: benazepril hydrochloride, hydrochlorothiazide, lactose, hydroxypropyl methylcellulose, polyvinylpolypyrrolidone, hydrogenated castor oil and opadry coating powder. The weight content of the lactose in the benazepril hydrochloride and hydrochlorothiazide tablet is 50 wt%-82 wt%. In the coating process of preparing the tablets, the drying temperature is 30-60 DEG C. The prepared benazepril hydrochloride and hydrochlorothiazide tablet compound preparation is high in stability, high in release rate and low in impurity content. According to the benazepril hydrochloride hydrochlorothiazide tablet, the stability of the product is improved, and the problem that the impurity content of the benazepril hydrochloride hydrochlorothiazide tablet is easy to greatly increase during long-term storage is solved.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a benazepril hydrochloride and hydrochlorothiazide tablet and a preparation method thereof. Background Art

[0002] Hypertension is an important risk factor for cardiovascular and cerebrovascular diseases, and its direct complications include stroke, heart failure, renal failure, coronary heart disease, etc. Lowering blood pressure can significantly reduce the incidence of vascular diseases such as coronary heart disease and stroke. Angiotensin-converting enzyme inhibitors (ACEI) and diuretics are two types of hypertension drugs that are currently widely used in clinical practice. The antihypertensive mechanisms of these two classic antihypertensive drugs, ACEI and diuretics, complement each other, acting on different links that lead to increased blood pressure, achieving dual blocking of the hypertension pressure mechanism and volume mechanism, and synergistically lowering blood pressure.

[0003] Benazepril hydrochloride can inhibit the activity of angiotensin converting enzyme, reduce the level of angiotensin II, dilate small arteries, and has a significant antihypertensive effect on various types of hypertension. It can also improve the cardiac function of patients with congestive heart failure. Hydrochlorothiazide is a diuretic that mainly inhibits the cortical part of the ascending limb of the loop of Henle to Na + and Cl - Benazepril and hydrochlorothiazide are used together to reduce the reverse regulatory effect of hydrochlorothiazide on the renin-angiotensin system, thereby enhancing the antihypertensive effect of diuretics.

[0004] Chinese invention patent CN1827110A discloses a pharmaceutical composition with hydrochlorothiazide and benazepril hydrochloride as active ingredients, and its preparation method and use. Hydrochlorothiazide and benazepril hydrochloride are used as raw materials, and some specific types and proportions of auxiliary materials are added to prepare the preparation, wherein the tablet auxiliary materials include microcrystalline cellulose, pregelatinized starch, lactose, sodium carboxymethyl cellulose, talcum powder and micro-powder silica gel. Although the invention prepares benazepril hydrochlorothiazide compound tablets, the storage stability of the tablets is low. As the storage time increases, the impurity content exceeds the limit, resulting in unqualified products.

[0005] Chinese invention patent CN102579346A discloses a liposome solid preparation of a benazepril / hydrochlorothiazide pharmaceutical composition, wherein the auxiliary ingredients include soybean lecithin, octadecylamine, cholesterol acetyl ester, microcrystalline cellulose, lactose, sodium carboxymethyl starch, povidone K30, hydroxypropyl cellulose and micro-powder silica gel; the prepared liposome preparation has high encapsulation efficiency and high bioavailability, and the total impurity content is above 0.45%, and there is still room for improvement.

[0006] Currently, there are few compound preparations of pril drugs and hydrochlorothiazide on the market. The original formulation of benazepril hydrochlorothiazide tablets is Loten sin HCT. Since benazepril hydrochloride is weakly acidic and magnesium stearate is weakly alkaline, if benazepril hydrochloride and other suitable excipients and magnesium stearate are simply mixed during the production process, benazepril hydrochloride may slowly react with magnesium stearate during storage, resulting in the increase of benazeprilat and other impurities. In order to solve this problem, hydrogenated castor oil is used instead of magnesium stearate to lubricate benazepril hydrochlorothiazide tablets (Loten sin HCT). However, the chemical structure of benazepril contains ester bonds and amide bonds, which is structurally unstable and easily produces by-products during long-term storage; it is unstable during storage, resulting in an increase in impurities, reduced efficacy or increased side effects.

[0007] In view of this, it is necessary to develop a compound preparation of hydrochlorothiazide and benazepril hydrochloride with high stability, low impurity content and high solubility. Summary of the invention

[0008] The invention aims at the problems existing in the prior art and provides a benazepril hydrochloride and hydrochlorothiazide tablet and a preparation method thereof. The benazepril hydrochloride and hydrochlorothiazide tablet is prepared by using auxiliary materials with specific components and dosages and improving process parameters, thereby improving the stability and dissolution release of the drug preparation, reducing the impurity content and improving the quality of the preparation.

[0009] The present invention has found in the early stage of research that the impurity content of the original preparation of benazepril hydrochlorothiazide tablets (Loten sin HCT) still increases to a certain extent during long-term storage, and the measure of using hydrogenated castor oil instead of magnesium stearate as a lubricant cannot well ensure the stability of benazepril hydrochloride in the preparation.

[0010] The present invention unexpectedly found in the study of the composition and preparation method of benazepril hydrochlorothiazide tablets that benazepril hydrochlorothiazide tablets use no more than 80.2wt% of lactose as a filler, preferably no more than 62wt% of lactose as a filler in the tablets, the impurity content of the preparation increases lower and the stability is better. At the same time, it is unexpectedly found that the temperature in the drying process is controlled not to exceed 60°C, preferably the drying process temperature does not exceed 48°C, the impurity content of the preparation increases lower, the stability is better, and the release is higher.

[0011] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0012] In one aspect, the present invention provides a benazepril hydrochloride and hydrochlorothiazide tablet, the raw materials of which include components: benazepril hydrochloride, hydrochlorothiazide, lactose, hypromellose, crospovidone, hydrogenated castor oil and Opadry coating powder;

[0013] The weight content of the lactose in the benazepril hydrochloride and hydrochlorothiazide tablets is 50wt%-82wt%.

[0014] Preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of lactose is 55wt%-80.2wt%.

[0015] Further preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of lactose is 57.5wt%-62wt%.

[0016] More preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of lactose is 62 wt %.

[0017] Preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of benazepril hydrochloride is 3wt%-11wt%.

[0018] Further preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of benazepril hydrochloride is 4wt%-10wt%.

[0019] More preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of benazepril hydrochloride is 10 wt %.

[0020] Preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of hydrochlorothiazide is 4wt%-14wt%.

[0021] Further preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of hydrochlorothiazide is 5wt%-12.5wt%.

[0022] More preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of hydrochlorothiazide is 12.5 wt %.

[0023] Preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of hypromellose is 1wt%-3wt%.

[0024] Further preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of hypromellose is 1.2wt%-3wt%.

[0025] More preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of hypromellose is 2 wt %.

[0026] Preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of cross-linked polyvinylpyrrolidone is 3wt%-8wt%.

[0027] Further preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of cross-linked polyvinylpyrrolidone is 4wt%-8wt%.

[0028] More preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of cross-linked polyvinylpyrrolidone is 7 wt %.

[0029] Preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of hydrogenated castor oil is 1wt%-4wt%.

[0030] Further preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of hydrogenated castor oil is 2.4wt%-4wt%.

[0031] More preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of hydrogenated castor oil is 3 wt %.

[0032] Preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of Opadry coating powder is 1wt%-5wt%.

[0033] Further preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of Opadry coating powder is 3.2wt%-5wt%.

[0034] More preferably, in the benazepril hydrochloride and hydrochlorothiazide tablets, the weight content of Opadry coating powder is 3.5 wt %.

[0035] Preferably, the raw materials of the benazepril hydrochloride and hydrochlorothiazide tablets include the following components, measured by weight: 3-11 parts of benazepril hydrochloride, 4-14 parts of hydrochlorothiazide, 50-82 parts of lactose, 1-3 parts of hydroxypropyl methylcellulose, 3-8 parts of cross-linked polyvinylpyrrolidone, 1-4 parts of hydrogenated castor oil and 1-5 parts of Opadry coating powder.

[0036] Further preferably, the raw materials of the benazepril hydrochloride and hydrochlorothiazide tablets include the following components, measured by weight: 4-10 parts of benazepril hydrochloride, 5-12.5 parts of hydrochlorothiazide, 55-80.2 parts of lactose, 1.2-3 parts of hydroxypropyl methylcellulose, 4-8 parts of cross-linked polyvinylpyrrolidone, 2.4-4 parts of hydrogenated castor oil and 3.2-5 parts of Opadry coating powder.

[0037] More preferably, the raw materials of the benazepril hydrochloride and hydrochlorothiazide tablets include the following components, measured by weight: 4-10 parts of benazepril hydrochloride, 5-12.5 parts of hydrochlorothiazide, 57.5-62 parts of lactose, 1.2-3 parts of hydroxypropyl methylcellulose, 4-8 parts of cross-linked polyvinylpyrrolidone, 2.4-4 parts of hydrogenated castor oil and 3.2-5 parts of Opadry coating powder.

[0038] More preferably, the raw materials of the benazepril hydrochloride and hydrochlorothiazide tablets include the following components, measured by weight: 10 parts of benazepril hydrochloride, 12.5 parts of hydrochlorothiazide, 57.5-62 parts of lactose, 2-3 parts of hydroxypropyl methylcellulose, 7-8 parts of cross-linked polyvinylpyrrolidone, 3-4 parts of hydrogenated castor oil and 3.5-5 parts of Opadry coating powder.

[0039] More preferably, the raw materials of the benazepril hydrochloride and hydrochlorothiazide tablets include the following components, measured by weight: 10 parts of benazepril hydrochloride, 12.5 parts of hydrochlorothiazide, 62 parts of lactose, 2 parts of hydroxypropyl methylcellulose, 7 parts of cross-linked polyvinylpyrrolidone, 3 parts of hydrogenated castor oil and 3.5 parts of Opadry coating powder.

[0040] Preferably, the Opadry coating powder is a gastric soluble Opadry coating powder.

[0041] Preferably, the raw materials of the benazepril hydrochloride and hydrochlorothiazide tablets also include water, the water is purified water, and the weight portion of water is 30-70 parts; more preferably, the weight portion of water is 40-50 parts; further preferably, the weight portion of water is 45 parts.

[0042] In the present invention, water is dried and removed during the preparation process of the benazepril hydrochloride and hydrochlorothiazide tablets.

[0043] On the other hand, the present invention provides a method for preparing the above-mentioned benazepril hydrochloride and hydrochlorothiazide tablets, comprising the steps of:

[0044] (1) Granulation: Wet granulation of benazepril hydrochloride, hydrochlorothiazide, lactose, carboxypropyl methylcellulose and water to obtain wet granules;

[0045] (2) Drying: Drying and granulating the wet granules in a fluidized bed to obtain dry granules;

[0046] (3) mixing: mixing the dry granules, crospovidone and hydrogenated castor oil to obtain mixed granules;

[0047] (4) tableting: tableting the mixed granules to obtain plain tablets;

[0048] (5) Coating: The plain tablets are coated with Opadry coating powder and dried at a temperature of 30-60°C.

[0049] Preferably, in step (1), the wet granulation is a conventional granulation method; illustratively: the material is added to a granulation pot, the stirring blade speed is set to 150-250 rpm, the shear speed is set to 1000-2000 rpm, purified water is added, and granulation is performed for 60-120 seconds.

[0050] Further preferably, the wet granulation is specifically as follows: adding the material into a granulation pot, setting the stirring blade speed to 150-160 rpm, the shear speed to 1400-1500 rpm, adding purified water, and granulating for 90 seconds.

[0051] Preferably, in step (2), the drying temperature is 35-50°C.

[0052] More preferably, in step (2), the drying temperature is 40°C.

[0053] Preferably, in step (2), the process parameters of the fluidized bed are: setting the fan frequency to 15-30 Hz, performing drying, and ending when the drying loss is ≤1.0%.

[0054] Further preferably, the process parameters of the fluidized bed are: setting the fan frequency to 20 Hz.

[0055] Preferably, in step (4), the process parameters of tableting are: setting the feed shoe speed to 30-50 rpm, the tableting pre-pressure to 0.5-2 KN, the tableting main pressure to 2-5 KN, and the tableting speed to 2-5 thousand tablets / hour for tableting.

[0056] Further preferably, the process parameters of tableting are: setting the feed shoe speed to 40 rpm, the tableting pre-pressure to 1.0 KN, the tableting main pressure to 3.0 KN, and the tableting speed to 3,000 tablets / hour for tableting.

[0057] Preferably, the coating in step (5) is specifically as follows: Opadry coating powder is prepared into a 12% (w / w) coating solution, the air inlet temperature is set to 50-70°C, the main engine speed is 6-10 rpm, and the air volume is 100-200m 3 / h, peristaltic pump speed 2-8rpm, atomization pressure 1-3bar, for coating.

[0058] Further preferably, the coating in step (5) is specifically as follows: Opadry coating powder is prepared into a 12% (w / w) coating solution, the air inlet temperature is set to 60°C, the main engine speed is 8 rpm, and the air volume is 150m 3 / h, peristaltic pump speed 5rpm, atomization pressure 1bar, and coating was carried out.

[0059] Preferably, in step (5), the drying temperature is 40-48°C; further preferably, in step (5), the drying temperature is 42-48°C.

[0060] Compared with the prior art, the present invention has the following beneficial effects:

[0061] The benazepril hydrochloride and hydrochlorothiazide tablets of the present invention are prepared by selecting auxiliary materials with specific contents and components, controlling the drying temperature of the preparation process, improving the storage stability of the benazepril hydrochloride and hydrochlorothiazide tablets, and also improving the release of active ingredients hydrochlorothiazide and benazepril hydrochloride. The technical solution of the present invention solves the problem that the benazepril hydrochloride and hydrochlorothiazide tablets are unstable and the impurity content increases during long-term storage. DETAILED DESCRIPTION

[0062] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is merely an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of the present invention.

[0063] When the embodiments give numerical ranges, it should be understood that, unless otherwise specified in the present invention, both endpoints of each numerical range and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used in the present invention have the same meanings as those generally understood by those of ordinary skill in the art to which the present invention belongs.

[0064] The present invention is further described below by way of specific examples. Unless otherwise specified, the various chemical reagents used in the examples of the present invention are obtained through conventional commercial channels.

[0065] In the following examples, the hydroxypropyl methylcellulose (LV) was purchased from Danisco Biotechnology (Shanghai) Co., Ltd., with the product number E5 Prium LV; the cross-linked polyvinylpyrrolidone was purchased from Anhui Shanhe Pharmaceutical Excipients Co., Ltd., with the product number SH-SL10; the hydrogenated castor oil was purchased from BASF (China) Co., Ltd., with the product number HCO; the Opadry coating powder was purchased from Shanghai Colorcon Coating Technology Co., Ltd., with the product number 00F540011-CN. The above components, products from different manufacturers have no significant effect on the effect.

[0066] Example 1

[0067] A benazepril hydrochloride and hydrochlorothiazide tablet, the raw material formula of which is as follows:

[0068]

[0069]

[0070] The preparation method of benazepril hydrochloride hydrochlorothiazide tablets is as follows:

[0071] (1) Granulation: Add lactose, benazepril hydrochloride, hydrochlorothiazide and hypromellose into a wet granulator, add purified water, set the stirring speed to 160 rpm, the shear speed to 1460 rpm, and granulate for 90 s.

[0072] (2) Drying: Add the wet granules into a fluidized bed and set the fan frequency to 20 Hz; dry at 45 ± 3 °C to size the granules.

[0073] (3) Mixing: Add dry granules, crospovidone and hydrogenated castor oil into a mixing bucket and mix until uniform.

[0074] (4) Tabletting: Add the mixed granules into the tablet press, set the feed shoe speed to 40 rpm, pre-compression to 1.0 KN, main pressure to 3 KN, tableting speed to 3,000 tablets / hour, and tablet press.

[0075] (5) Coating: Add the plain tablets into the coating machine, set the air inlet temperature to 60°C, the main machine speed to 8 rpm, and the air volume to 150 m 3 / h, peristaltic pump speed 5rpm, atomization pressure 1bar, coating, control the product temperature not to exceed 48℃ during drying; the specific drying temperature is 45±3℃.

[0076] Example 2

[0077] The difference from Example 1 is that the dosage ratio of each raw material in the benazepril hydrochloride and hydrochlorothiazide tablets is different, specifically:

[0078]

[0079]

[0080] The rest is the same as in Example 1.

[0081] Example 3

[0082] The difference from Example 1 is that the dosage ratio of each raw material in the benazepril hydrochloride and hydrochlorothiazide tablets is different, specifically:

[0083]

[0084] The rest is the same as in Example 1.

[0085] Comparative Example 1

[0086] The license holder in the "Catalogue of Reference Preparations of Generic Drugs" (54th batch) is Validus Pharmaceuticals LLC, and the original formulation of benazepril hydrochlorothiazide tablets with the trade name Loten sin HCT.

[0087] The raw material formula is as follows:

[0088]

[0089]

[0090] The preparation method of the benazepril hydrochlorothiazide tablets is as follows: benazepril hydrochloride, hydrochlorothiazide, hydroxypropyl methylcellulose and lactose are mixed, purified water is added, a stirring speed of 200 rpm and a shearing speed of 2000 rpm are set, and granulation is performed for 60 seconds; a fan frequency of 20 Hz is set, drying is performed, and the dry granules are granulated at a granulation speed of 500 rpm, and then the granules are mixed with cross-linked polyvinylpyrrolidone and hydrogenated castor oil, and then the mixed granules are added to a tablet press, a feed shoe speed of 40 rpm is set, a pre-compression of 1.0 KN, a main pressure of 3 KN, a tableting speed of 3,000 tablets / hour, tableting is performed, and then a plain tablet is added to a coating machine, the coating liquid is a 12% (w / w) film coating material, and the air inlet temperature is set to 60°C, the main engine speed is 8 rpm, and the air volume is 150 m 3 / h, peristaltic pump speed 5rpm, atomization pressure 1bar, coating. Purified water is dried and removed during the process.

[0091] Comparative Example 2

[0092] The difference from Example 1 is that the dosage ratio of each raw material in the benazepril hydrochloride and hydrochlorothiazide tablets is different, specifically:

[0093]

[0094]

[0095] The rest are the same as in Example 1.

[0096] Comparative Example 3

[0097] The difference from Example 1 is that in the preparation method of benazepril hydrochloride and hydrochlorothiazide tablets, the temperature of the dried product in step (5) exceeds 60° C., specifically 65±3° C. The rest is the same as Example 1.

[0098] Comparative Example 4

[0099] The difference from Example 1 is that the dosage ratio of each raw material in the benazepril hydrochloride and hydrochlorothiazide tablets is different, specifically:

[0100]

[0101] The rest are the same as in Example 1.

[0102] Test 1 Drying loss detection

[0103] The determination was carried out according to the loss on drying method (General Rules 0831 of Part IV of the Chinese Pharmacopoeia 2020 Edition).

[0104] The benazepril hydrochloride and hydrochlorothiazide tablets of each embodiment and comparative example were placed in an accelerated test chamber (40° C., 75% RH) for 6 months, and the drying loss was detected. The weight loss rate (%) results are shown in Table 1.

[0105] Table 1

[0106]

[0107] Test 2: Detection of related substances

[0108] The determination was carried out according to high performance liquid chromatography (General Rules 0512 of Part IV of the Chinese Pharmacopoeia 2020 Edition).

[0109] The benazepril hydrochloride and hydrochlorothiazide tablets of the examples and comparative examples were placed in an accelerated test chamber (40° C., 75% RH) for 6 months, and the contents (%) of related substances were detected at 6 months. The results are shown in Table 2:

[0110] Table 2

[0111]

[0112]

[0113] Among the related substances, impurity C is benazepril impurity C, (3S)-3-[[(1S)-1-carboxy-3-phenylpropyl]amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine ]-1-acetic acid; single impurity is an unknown single impurity; total impurity is the sum of the peak areas of each impurity (excluding benazepril impurity C).

[0114] From Table 2 we can see that:

[0115] ① In Example 1, during the 6-month accelerated process, the growth rate of impurities was small;

[0116] ② In Example 2, during the 6-month accelerated process, the growth rate of impurities was small;

[0117] ③ In Example 3, during the 6-month acceleration process, the growth rate of impurities was small;

[0118] ④ In comparative example 1, during the 6-month acceleration process, the impurities increased significantly, and the single impurity exceeded the upper limit;

[0119] ⑤ In comparative example 2, during the 6-month acceleration process, the impurities increased significantly, and the single impurity exceeded the upper limit;

[0120] ⑥ In comparative example 4, during the 6-month accelerated process, impurities increased significantly, and a single impurity exceeded the upper limit.

[0121] The benazepril hydrochloride and hydrochlorothiazide tablets of the present invention have a high drying loss ratio, but the increase in the content of related substances is still very small, indicating that the product obtained by the preparation method of the present invention has a small change in impurity content and stable quality.

[0122] Test 3: Dissolution test

[0123] Detection method: The basket method was adopted, with 0.1N HCl as the dissolution medium, the medium volume was 500mL, the rotation speed was 75 revolutions per minute, and 5mL of the solution was taken as the test solution after 5min, 10min, 15min, and 30min respectively. The cumulative dissolution amount (%) of hydrochlorothiazide and benazepril hydrochloride was calculated respectively according to the high performance liquid chromatography method (General Rule 0512).

[0124] The dissolution results of hydrochlorothiazide are shown in Table 3, and the dissolution results of benazepril hydrochloride are shown in Table 4.

[0125] Table 3

[0126]

[0127] Table 4

[0128]

[0129] It can be seen from Table 3 and Table 4 that the dissolution results of hydrochlorothiazide and benazepril hydrochloride in Comparative Example 3 are significantly different from those in the Examples.

[0130] Result analysis:

[0131] Comparing Example 1, Comparative Example 1 and Comparative Example 2, although the drying loss of the preparation of the present invention is relatively high, the increase in impurities is still very small.

[0132] Comparing Example 1 and Comparative Example 3, it can be seen that by increasing the drying temperature to reduce the drying loss of the preparation, although the increase in the amount of related substances is very small, the release (dissolution amount) of hydrochlorothiazide and benazepril hydrochloride will be reduced.

[0133] Comparing Example 1 to Example 3 and Comparative Example 3 to Comparative Example 4, the hydrochlorothiazide and benazepril hydrochloride compound preparation prepared by controlling the lactose content and the drying temperature has good stability and high release (dissolution amount).

[0134] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A benazepril hydrochloride and hydrochlorothiazide tablet, characterized in that: The raw materials include components: benazepril hydrochloride, hydrochlorothiazide, lactose, hypromellose, crospovidone, hydrogenated castor oil and Opadry coating powder; The weight content of the lactose in the benazepril hydrochloride and hydrochlorothiazide tablets is 50wt%-82wt%.

2. The benazepril hydrochloride and hydrochlorothiazide tablet according to claim 1, characterized in that: The weight content of the lactose is 55wt%-80.2wt%.

3. The benazepril hydrochloride and hydrochlorothiazide tablet according to claim 2, characterized in that: The weight content of the lactose is 57.5wt%-62wt%.

4. The benazepril hydrochloride and hydrochlorothiazide tablet according to any one of claims 1 to 3, characterized in that: The weight content of the benazepril hydrochloride is 3wt%-11wt%; the weight content of the hydrochlorothiazide is 4wt%-14wt%; the weight content of the hypromellose is 1wt%-3wt%; the weight content of the cross-linked polyvinylpyrrolidone is 3wt%-8wt%; the weight content of the hydrogenated castor oil is 1wt%-4wt%; and the weight content of the Opadry coating powder is 1wt%-5wt%.

5. The benazepril hydrochloride and hydrochlorothiazide tablet according to claim 1, characterized in that: The raw materials include components in parts by weight: 3-11 parts of benazepril hydrochloride, 4-14 parts of hydrochlorothiazide, 50-82 parts of lactose, 1-3 parts of hydroxypropyl methylcellulose, 3-8 parts of cross-linked polyvinylpyrrolidone, 1-4 parts of hydrogenated castor oil and 1-5 parts of Opadry coating powder.

6. The benazepril hydrochloride and hydrochlorothiazide tablet according to claim 5, characterized in that: The raw materials include components in parts by weight: 4-10 parts of benazepril hydrochloride, 5-12.5 parts of hydrochlorothiazide, 55-80.2 parts of lactose, 1.2-3 parts of hydroxypropyl methylcellulose, 4-8 parts of cross-linked polyvinylpyrrolidone, 2.4-4 parts of hydrogenated castor oil and 3.2-5 parts of Opadry coating powder.

7. The benazepril hydrochloride and hydrochlorothiazide tablet according to claim 6, characterized in that: The raw materials include components in parts by weight: 4-10 parts of benazepril hydrochloride, 5-12.5 parts of hydrochlorothiazide, 57.5-62 parts of lactose, 1.2-3 parts of hydroxypropyl methylcellulose, 4-8 parts of cross-linked polyvinylpyrrolidone, 2.4-4 parts of hydrogenated castor oil and 3.2-5 parts of Opadry coating powder.

8. The benazepril hydrochloride and hydrochlorothiazide tablet according to claim 7, characterized in that: The raw materials include components in parts by weight: 10 parts of benazepril hydrochloride, 12.5 parts of hydrochlorothiazide, 57.5-62 parts of lactose, 2-3 parts of hydroxypropyl methylcellulose, 7-8 parts of cross-linked polyvinylpyrrolidone, 3-4 parts of hydrogenated castor oil and 3.5-5 parts of Opadry coating powder.

9. The method for preparing the benazepril hydrochloride and hydrochlorothiazide tablets according to any one of claims 1 to 8, characterized in that: Includes steps: (1) Granulation: Wet granulation of benazepril hydrochloride, hydrochlorothiazide, lactose, carboxypropyl methylcellulose and water to obtain wet granules; (2) Drying: Drying and granulating the wet granules in a fluidized bed to obtain dry granules; (3) mixing: mixing the dry granules, crospovidone and hydrogenated castor oil to obtain mixed granules; (4) tableting: tableting the mixed granules to obtain plain tablets; (5) Coating: The plain tablets are coated with Opadry coating powder and dried at a temperature of 30-60°C.

10. The preparation method according to claim 9, characterized in that: In step (5), the drying temperature is 40-48°C.

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