A compound telmisartan-levamlodipine tablet and its preparation method

Abstract

This invention belongs to the field of pharmaceutical formulation technology, specifically relating to a bilayer tablet preparation process, and more specifically to a compound telmisartan-levamlodipine tablet and its preparation method. The process includes: dissolving telmisartan raw material in a solution containing meglumine and sodium hydroxide as alkaline reagents, then adding a binder and mixing thoroughly to obtain an alkaline solution of telmisartan raw material; preheating the telmisartan layer filler in a fluidized bed, spraying the telmisartan raw material alkaline solution onto it, drying and granulating it, then adding a lubricant for the telmisartan layer and mixing to obtain telmisartan layer granules; mixing levamlodipine besylate raw material and the excipients of the levamlodipine layer thoroughly, performing dry granulation and granulation sequentially, then adding a lubricant for the levamlodipine layer and mixing to obtain levamlodipine layer granules; and finally, bilayer tableting. The compound telmisartan-levamlodipine tablets prepared by this invention exhibit excellent uniformity, higher similarity in in vitro dissolution curves, and better stability.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical formulation technology, and relates to a process for preparing bilayer tablets, specifically to a compound telmisartan-levoamlodipine tablet and its preparation method. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Clinical studies have confirmed that telmisartan effectively lowers and controls blood pressure. It is a specific angiotensin II receptor (AT I type). Telmisartan binds with high affinity to the ATI receptor subtype (the known site of action of angiotensin II) instead of the angiotensin II receptor. Telmisartan has no site-specific agonist effect at the ATI receptor site; it selectively binds to the ATI receptor, and this binding is long-lasting, thus resulting in a significant antihypertensive effect.

[0004] Amlodipine is a commonly used dihydropyridine calcium channel blocker in clinical practice. Its characteristics include a slow binding and dissociation rate with receptors, resulting in a long duration of action. In patients with myocardial ischemia, it can increase cardiac output and coronary blood flow, increase myocardial oxygen supply and reduce oxygen consumption, and improve exercise capacity. Amlodipine has two enantiomers, levo-amlodipine and dextro-amlodipine. Levo-amlodipine is a newer generation product of amlodipine, obtained through chiral resolution technology; it is non-toxic and has a hypotensive effect. Dextro-amlodipine is highly toxic and has no hypotensive effect. Therefore, levo-amlodipine is more effective and safer than amlodipine for hypertension. Levo-amlodipine is characterized by a slow onset of action, long duration of action, and a high trough-to-peak ratio, and is widely used clinically in the treatment of cardiovascular and cerebrovascular diseases such as hypertension and angina pectoris.

[0005] If a patient's blood pressure is not adequately controlled after using amlodipine or telmisartan alone, the treatment can be switched to a combination of telmisartan and amlodipine tablets. The indication for this combination is primarily for the treatment of essential hypertension and for patients whose blood pressure cannot be adequately controlled by monotherapy.

[0006] However, the inventors discovered through research that telmisartan raw material and levamlodipine besylate raw material would interact, so directly mixing telmisartan and levamlodipine besylate to make a combination drug would result in poor stability. Summary of the Invention

[0007] To minimize contact between telmisartan and levamlodipine besylate, the inventors conducted a detailed study of bilayer tablets. This study revealed that the vacuum cleaner remained on throughout the tableting process, easily removing fine powder. This posed a risk of stratification of the levamlodipine layer during tableting, resulting in poor uniformity of the active pharmaceutical ingredient content. Furthermore, the telmisartan layer was unstable in the raw material solution during granulation, and telmisartan sodium salt solution easily precipitated out, leading to poor uniformity and stability. Therefore, the purpose of this invention is to provide a compound telmisartan-levamlodipine tablet and its preparation method. The compound telmisartan-levamlodipine tablet prepared by this invention exhibits excellent uniformity, and its in vitro dissolution curve is comparable to that of the reference drug telmisartan tablets produced by Boehringer Ingelheim Hellas Single Member SA. Amlodipine besylate tablets manufactured by Pfizer Pharmaceuticals Co., Ltd. It exhibits better similarity and greater stability during the stability assessment period.

[0008] To achieve the above objectives, the technical solution of the present invention is as follows:

[0009] On one hand, a method for preparing compound telmisartan-levamlodipine tablets includes:

[0010] The preparation process of telmisartan layer particles involves dissolving telmisartan raw material in a solution containing meglumine and sodium hydroxide as alkaline reagents, then adding a binder and mixing evenly to obtain an alkaline solution of telmisartan raw material; preheating the telmisartan layer filler in a fluidized bed, spraying the alkaline solution of telmisartan raw material onto it, drying and granulating it, then adding a lubricant for the telmisartan layer and mixing it to obtain telmisartan layer particles;

[0011] The preparation process of levamlodipine layer granules involves mixing levamlodipine benzylsulfonic acid raw material with levamlodipine layer excipients evenly, performing dry granulation and granulation in sequence, and then adding levamlodipine layer lubricant for total mixing to obtain levamlodipine granules.

[0012] Furthermore, the preparation process of the bilayer tablet involves compressing the telmisartan granules and levamlodipine granules into a bilayer tablet to obtain the compound telmisartan-levamlodipine tablet.

[0013] This invention first uses a mixture of two alkaline reagents (sodium hydroxide and meglumine) to increase the dissolution rate of telmisartan raw material, forming telmisartan sodium. A binder is added to the solution to improve the stability of the alkaline solution and prevent telmisartan precipitation during granulation. Based on this, fluidized bed granulation is employed, which significantly improves the uniformity and stability of telmisartan. Secondly, in preparing levamlodipine granules, this invention first mixes the ingredients and then granulates them using a dry method, resulting in a uniform levamlodipine besylate content. Simultaneously, the excipients are compressed together with levamlodipine besylate, reducing the risk of stratification caused by dust collection during tableting and thus improving the uniformity of the active pharmaceutical ingredient content.

[0014] Experiments have shown that the compound telmisartan-levoamlodipine tablets prepared by this invention have better uniformity and superior stability.

[0015] On the other hand, a compound telmisartan-levoamlodipine tablet is obtained by the above preparation method.

[0016] The beneficial effects of this invention are as follows:

[0017] This application employs fluidized bed granulation for the telmisartan layer, which has low equipment requirements, high production efficiency, and improves product stability. Sodium hydroxide and meglumine are added as alkaline reagents during the preparation of the telmisartan alkaline solution, ensuring rapid dissolution of telmisartan to form telmisartan sodium. Additionally, a binder is added to the raw material solution to improve its stability and prevent telmisartan precipitation during granulation. The levamlodipine layer is prepared using a dry granulation method after mixing, resulting in granules with uniform active pharmaceutical ingredient content. Combining the excipients and active pharmaceutical ingredient reduces the risk of separation caused by dust collection during tableting. Finally, the two granule layers are compressed into a double-layer tablet using a double-layer tablet press, avoiding large-area contact between the two active pharmaceutical ingredients. The telmisartan-levamlodipine double-layer tablets prepared by the process described in this invention exhibit superior stability, better uniformity of telmisartan and levamlodipine besylate content, and a dissolution curve similar to the control drug telmisartan tablets. Amlodipine besylate tablets Closer. Detailed Implementation

[0018] It should be noted that the following detailed descriptions are exemplary and intended to provide further illustration of the invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0019] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of exemplary embodiments according to the invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0020] In order to avoid the risk of delamination of the levamlodipine layer and the easy precipitation of telmisartan raw material when making bilayer tablets by large-area contact between telmisartan raw material and levamlodipine besylate raw material, resulting in poor uniformity and stability, this invention proposes a compound telmisartan-levamlodipine tablet and its preparation method.

[0021] A typical embodiment of the present invention provides a method for preparing compound telmisartan-levamlodipine tablets, comprising:

[0022] The preparation process of telmisartan layer particles involves dissolving telmisartan raw material in a solution containing meglumine and sodium hydroxide as alkaline reagents, then adding a binder and mixing evenly to obtain an alkaline solution of telmisartan raw material; preheating the telmisartan layer filler in a fluidized bed, spraying the alkaline solution of telmisartan raw material onto it, drying and granulating it, then adding a lubricant for the telmisartan layer and mixing it to obtain telmisartan layer particles;

[0023] The preparation process of levamlodipine layer granules involves mixing levamlodipine benzylsulfonic acid raw material with levamlodipine layer excipients evenly, performing dry granulation and granulation in sequence, and then adding levamlodipine layer lubricant for total mixing to obtain levamlodipine granules.

[0024] Furthermore, the preparation process of the bilayer tablet involves compressing the telmisartan granules and levamlodipine granules into a bilayer tablet to obtain the compound telmisartan-levamlodipine tablet.

[0025] In some embodiments, the mass ratio of telmisartan raw material, alkaline reagent, binder, filler, and lubricant in the telmisartan layer particles is 80:25-35:20-30:300-360:6-10.

[0026] In some embodiments, the mass ratio of meglumine to sodium hydroxide is 23–26:1–12.

[0027] In some embodiments, the binder in the telmisartan layer particles is povidone, preferably povidone K25.

[0028] In some embodiments, the filler in the telmisartan layer particles is sorbitol.

[0029] In some embodiments, the lubricant in the telmisartan layer particles is magnesium stearate.

[0030] In some embodiments, the excipients in the levamlodipine layer particles include a filler, a colorant, and a flow aid. Specifically, the mass ratio of levamlodipine besylate, filler, colorant, and flow aid is 3.47:160-220:1-5:1-5. Specifically, the filler is microcrystalline cellulose or a combination of microcrystalline cellulose and corn starch, or a combination of microcrystalline cellulose, corn starch, and pregelatinized starch, wherein the microcrystalline cellulose is preferably microcrystalline cellulose 102. Specifically, the colorant is a combination of yellow iron oxide and black iron oxide. Specifically, the flow aid is colloidal silica.

[0031] In some embodiments, the mass ratio of levamlodipine benzylsulfonic acid to lubricant in the levamlodipine layer particles is 3.47:1 to 5.

[0032] In some embodiments, the lubricant in the levamlodipine layer particles is magnesium stearate.

[0033] In some embodiments, levamlodipine besylate raw material is premixed with a colorant, a flow aid, and a portion of a filler to obtain a premix, which is then mixed with the remaining filler. This method enables better and more uniform mixing of the levamlodipine besylate raw material with the excipients of the levamlodipine layer.

[0034] In one or more embodiments, during premixing, the weight of the added filler is 1 / 4 to 1 / 2 of the total weight of the filler.

[0035] In some embodiments, the mass ratio of telmisartan raw material to levamlodipine besylate raw material is 79–81:3.0–4.0.

[0036] Another embodiment of the present invention provides a compound telmisartan-levoamlodipine tablet, which is obtained by the above preparation method.

[0037] In some embodiments, the hardness of the double-layer core is 150-250 N.

[0038] In some embodiments, the weight ratio of telmisartan layer to levamlodipine layer is 470–490:190–210.

[0039] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0040] Example 1

[0041] Telmisartan granules were prepared using spray drying and direct mixing; amlodipine powder was prepared using a powder mixing and direct mixing method, with a batch size of 1500 tablets. The formulation is shown in Table 1.

[0042] Table 1. Prescription for Example 1

[0043]

[0044]

[0045] Preparation process

[0046] 1. Preparation

[0047] Telmisartan layer:

[0048] (1) Weigh out meglumine, sodium hydroxide, povidone, and telmisartan for later use.

[0049] (2) Preparation of telmisartan alkaline solution

[0050] Weigh an appropriate amount of purified water. First, dissolve the prescribed amount of meglumine and sodium hydroxide in the purified water. After clarification, slowly add telmisartan while stirring. After the raw materials are completely dissolved, add povidone and stir until completely clear to obtain an alkaline telmisartan solution (solid content concentration of about 30%).

[0051] (3) Spray drying

[0052] An LPG-5 spray dryer was used, with the induced draft frequency set to 40–50 Hz, the atomization frequency to 340–380 Hz, the heating temperature to 200–220 ℃, the peristaltic pump speed to 8–18 rpm, the inlet air temperature to be controlled at 190–220 ℃, and the outlet air temperature to be controlled at 75–100 ℃, to obtain telmisartan spray-dried granules.

[0053] (5) Mixing

[0054] Calculate and weigh the amount of sorbitol and magnesium stearate based on the yield of spray-dried particles. Add the spray-dried particles and sorbitol to a three-dimensional mixer and mix for 10 minutes. Then add magnesium stearate and mix for another 5 minutes to obtain the telmisartan intermediate product.

[0055] Levoamlodipine layer:

[0056] (1) Pretreatment of raw and auxiliary materials

[0057] Microcrystalline cellulose, pregelatinized starch, corn starch, and levamlodipine benzylsulfonate are passed through a 40-mesh sieve, while yellow ferric oxide and black ferric oxide are passed through a 60-mesh sieve.

[0058] (2) Weighing

[0059] Weigh out the following ingredients according to the prescription: microcrystalline cellulose, pregelatinized starch, corn starch, colloidal silica, magnesium stearate, and levamlodipine benzylsulfonate.

[0060] (3) Premixing

[0061] Half the prescribed amount of microcrystalline cellulose, half the prescribed amount of pregelatinized starch, and half the prescribed amount of corn starch, along with the prescribed amounts of colloidal silica, amlodipine benzenesulfonate, yellow iron oxide, and black iron oxide, were added to a three-dimensional mixer. The mixing speed was set to 10 rpm and the mixing time to 15 min. The mixture was then mixed to obtain the premix.

[0062] (4) Mixing

[0063] The remaining microcrystalline cellulose, remaining pregelatinized starch, and remaining corn starch were added to a three-dimensional mixer, and the mixing speed was set to 10 rpm and the mixing time to 10 min to obtain a mixture.

[0064] (5) Total Mixing

[0065] Magnesium stearate was added to a three-dimensional mixer, the mixing speed was set to 10 rpm, the mixing time was 5 min, and the mixture was mixed. After the mixing was completed, the material was discharged to obtain levamlodipine layer granules.

[0066] 2. Tableting

[0067] A rotary tablet press is used, with a 16.3*8.0mm elliptical shallow concave die to press double-layer tablets. The tablet core hardness is controlled at 150-250N, and the tablet weight difference is controlled within ±5.0%.

[0068] Example 2

[0069] Telmisartan granules were prepared using spray drying and dry granulation processes; levamlodipine granules were prepared using a direct mixing method, with a batch size of 1500 tablets. The formulation is shown in Table 2.

[0070] Table 2 Prescription for Example 2

[0071]

[0072] Preparation process

[0073] 1. Preparation

[0074] Telmisartan layer:

[0075] (1) Weigh out meglumine, sodium hydroxide, povidone, and telmisartan for later use.

[0076] (2) Preparation of telmisartan alkaline solution

[0077] Weigh an appropriate amount of purified water. First, dissolve the prescribed amount of meglumine and sodium hydroxide in the purified water. After clarification, slowly add telmisartan while stirring. After the raw materials are completely dissolved, add povidone and stir until completely clear to obtain an alkaline telmisartan solution (solid content concentration of about 30%).

[0078] (3) Spray drying

[0079] An LPG-5 spray dryer was used, with the induced draft frequency set to 40–50 Hz, the atomization frequency to 340–380 Hz, the heating temperature to 200–220 ℃, the peristaltic pump speed to 8–18 rpm, the inlet air temperature to be controlled at 190–220 ℃, and the outlet air temperature to be controlled at 75–100 ℃, to obtain telmisartan spray-dried granules.

[0080] (4) Premix

[0081] Telmisartan spray-dried granules and sorbitol 1 were separately added into a three-dimensional mixer. The mixing speed was set to 10 rpm, and the mixture was mixed for 15 minutes. The mixture was then discharged to obtain a premix.

[0082] (5) Dry granulation

[0083] The premixed material was fed into a GL4-50 dry granulator for dry granulation (0.8mm sieve). The feeding frequency was set to 5Hz, the tableting frequency to 18Hz, and the granulation frequency to 18-25Hz. Telmisartan dry granules were obtained by passing the material through a 20-mesh sieve.

[0084] (6) Total Mixing

[0085] Calculate and weigh the amount of sorbitol 2 and magnesium stearate added based on the dry granulation yield. First, put the dry granulated particles and sorbitol 2 into a three-dimensional mixer and mix for 10 minutes. Then, add magnesium stearate and mix for 5 minutes to obtain telmisartan layer particles.

[0086] The preparation process of the levamlodipine layer is the same as in Example 1.

[0087] 2. Tableting

[0088] A rotary tablet press is used, with a 16.3*8.0mm elliptical shallow concave die to press double-layer tablets. The tablet core hardness is controlled at 150-250N, and the tablet weight difference is controlled within ±5.0%.

[0089] Example 3

[0090] Telmisartan granules were prepared using a fluidized bed top-spray granulation process; levamlodipine granules were prepared using a direct mixing method, with a batch size of 1500 tablets. The formulation is shown in Table 3.

[0091] Table 3. Prescription for Example 3

[0092]

[0093] Preparation process

[0094] 1. Preparation

[0095] Telmisartan layer:

[0096] (1) Weigh out meglumine, sodium hydroxide, povidone, and telmisartan for later use.

[0097] (2) Preparation of telmisartan alkaline solution

[0098] Weigh an appropriate amount of purified water. First, dissolve the prescribed amount of meglumine and sodium hydroxide in the purified water. After clarification, slowly add telmisartan while stirring. After the raw materials are completely dissolved, add povidone and stir until completely clear to obtain an alkaline telmisartan solution (solid content concentration of about 30%).

[0099] (3) Granulation

[0100] The prescribed amount of sorbitol was added to a fluidized bed. The inlet air temperature was set to 60°C, the peristaltic pump speed to 5-10 rpm, the atomization pressure to 0.50 bar, and the air volume to 25.0-42.0 Hz. Telmisartan alkaline solution was sprayed in, and the mixture was dried. The moisture content of the granules was controlled to be ≤2.0%, thus obtaining dried telmisartan granules.

[0101] (4) Granulation

[0102] The dried granules are fed into a high-speed granulator, using a 1397μm sieve and a rotation speed of 1750rpm to obtain dry granules of appropriate size.

[0103] (5) Total Mixing

[0104] Calculate the amount of magnesium stearate to be added based on the dry particle yield and weigh it. Put the dry particles and magnesium stearate into a three-dimensional mixer and mix for 5 minutes to obtain telmisartan layer particles.

[0105] The preparation process of the levamlodipine layer is the same as in Example 1.

[0106] 2. Tableting

[0107] A rotary tablet press is used, with a 16.3*8.0mm elliptical shallow concave die to press double-layer tablets. The tablet core hardness is controlled at 150-250N, and the tablet weight difference is controlled within ±5.0%.

[0108] Example 4

[0109] Telmisartan granules were prepared using a fluidized bed top-spray granulation process; levamlodipine granules were prepared using a dry granulation method, with a batch size of 1500 tablets. The formulation is shown in Table 4.

[0110] Table 4. Prescription for Example 4

[0111]

[0112] Preparation process

[0113] 1. Preparation

[0114] Telmisartan layer:

[0115] (1) Weigh out meglumine, sodium hydroxide, povidone, and telmisartan for later use.

[0116] (2) Preparation of telmisartan alkaline solution

[0117] Weigh an appropriate amount of purified water. First, dissolve the prescribed amount of meglumine and sodium hydroxide in the purified water. After clarification, slowly add telmisartan while stirring. After the raw materials are completely dissolved, add povidone and stir until completely clear to obtain an alkaline telmisartan solution (solid content concentration of about 30%).

[0118] (3) Granulation

[0119] The prescribed amount of sorbitol was added to the fluidized bed, and the inlet air temperature was set to 60℃, the peristaltic pump speed to 5-10 rpm, the atomization pressure to 0.50 bar, and the air volume to 25.0-42.0 Hz. Telmisartan alkaline solution was added, and the mixture was dried to control the moisture content of the granules to ≤2.0%, thus obtaining dried telmisartan granules.

[0120] (4) Granulation

[0121] The dried granules are fed into a high-speed granulator, using a 1397μm sieve and a rotation speed of 1750rpm to obtain dry granules of appropriate size.

[0122] (4) Total Mixing

[0123] Calculate the amount of magnesium stearate to be added based on the dry particle yield and weigh it. Put the dry particles and magnesium stearate into a three-dimensional mixer and mix for 5 minutes to obtain telmisartan layer particles.

[0124] Levoamlodipine layer:

[0125] (1) Pretreatment of raw and auxiliary materials

[0126] Microcrystalline cellulose, pregelatinized starch, corn starch, and levamlodipine benzylsulfonate are passed through a 40-mesh sieve, while yellow ferric oxide and black ferric oxide are passed through a 60-mesh sieve.

[0127] (2) Weighing

[0128] Weigh out the following ingredients according to the prescription: microcrystalline cellulose, pregelatinized starch, corn starch, colloidal silica, magnesium stearate, and levamlodipine benzylsulfonate.

[0129] (3) Premixing

[0130] Half the prescribed amount of microcrystalline cellulose, half the prescribed amount of pregelatinized starch, and half the prescribed amount of corn starch, along with the prescribed amounts of colloidal silica, amlodipine benzenesulfonate, yellow iron oxide, and black iron oxide, were added to a three-dimensional mixer. The mixing speed was set to 10 rpm and the mixing time to 15 min. The mixture was then mixed to obtain the premix.

[0131] (4) Mixing

[0132] The remaining microcrystalline cellulose, remaining pregelatinized starch, and remaining corn starch were added to a three-dimensional mixer, and the mixing speed was set to 10 rpm and the mixing time to 10 min to obtain a mixture.

[0133] (5) Dry granulation

[0134] The mixture is fed into a GL4-50 dry granulator for dry granulation (0.8mm sieve). The feeding frequency is set to 5Hz, the tableting frequency to 20Hz, and the granulation frequency to 22-30Hz. The levamlodipine dry granules are obtained by passing through a 20-mesh sieve.

[0135] (6) Total Mixing

[0136] The amount of magnesium stearate used was calculated and weighed based on the dry granulation yield. The dry granulation particles and magnesium stearate were then put into a three-dimensional mixer. The mixing speed was set to 10 rpm and the mixing time to 5 min. After mixing, the material was discharged to obtain levamlodipine layer particles.

[0137] 2. Tableting

[0138] A rotary tablet press is used, with a 16.3*8.0mm elliptical shallow concave die to press double-layer tablets. The tablet core hardness is controlled at 150-250N, and the tablet weight difference is controlled within ±5.0%.

[0139] The quality data of the products obtained by different processes in Examples 1 to 4 are shown in Tables 5 to 8.

[0140] Table 5. Results of uniformity of telmisartan and levamlodipine content in products prepared by different methods.

[0141]

[0142] Table 6. Dissolution results of telmisartan in various media for products prepared by different methods.

[0143]

[0144] Table 7. Dissolution results of levamlodipine benzylsulfonate in various media for products prepared by different methods.

[0145]

[0146]

[0147] Table 8 Results of the investigation into factors affecting the stability of products prepared by different methods

[0148]

[0149]

[0150] Table 1 shows that the uniformity is better when telmisartan is granulated using a fluidized bed. The comparison results of Examples 1-2 and 3-4 show that the active pharmaceutical ingredient content of the granules is more uniform when levamlodipine is granulated using a dry granulation method after mixing.

[0151] Tables 2 and 3 show the cumulative dissolution rates of the product prepared using the process in Example 4 at each time point compared to the control drug telmisartan tablets. Amlodipine besylate tablets Closer; that is, the dissolution curve is closer to that of the control drug.

[0152] Table 4 shows that the two active pharmaceutical ingredients prepared by the processes used in Examples 3 and 4 have better stability. Specifically, the product prepared by the process used in Example 4 has better stability than the product prepared by the process used in Example 3.

[0153] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for preparing compound telmisartan-levamlodipine tablets, characterized in that, include: The preparation process of telmisartan layer particles involves dissolving telmisartan raw material in a solution containing meglumine and sodium hydroxide as alkaline reagents, then adding a binder and mixing evenly to obtain an alkaline solution of telmisartan raw material with a solid content concentration of approximately 30%. The telmisartan layer filler is preheated in a fluidized bed, and an alkaline solution of the telmisartan raw material is sprayed on. After drying and granulation, the telmisartan layer lubricant is added and mixed to obtain telmisartan layer particles. In the telmisartan layer particles, the mass ratio of telmisartan raw material, alkaline reagent, binder, filler, and lubricant is 80:25~35:20~30:300~360:6~10; the mass ratio of meglumine to sodium hydroxide is 23~26:1~12. In the telmisartan layer particles, the binder is povidone K25, the filler is sorbitol, and the lubricant is magnesium stearate; The preparation process of levamlodipine layer granules involves premixing levamlodipine benzylsulfonic acid raw material with colorant, flow aid and a portion of filler to obtain a premix, and then mixing the premix with the remaining filler. During premixing, the weight of the added filler is 1 / 4 to 1 / 2 of the total weight of the filler. Dry granulation and granulation are carried out in sequence, and then the lubricant of the levamlodipine layer is added for total mixing to obtain levamlodipine granules. In the levamlodipine layer particles, the mass ratio of levamlodipine besylate, filler, colorant, and flow aid is 3.47:160~220:1~5:1~5; the filler is microcrystalline cellulose or a combination of microcrystalline cellulose and corn starch, or a combination of microcrystalline cellulose, corn starch, and pregelatinized starch; the microcrystalline cellulose is microcrystalline cellulose 102; the colorant is a combination of yellow iron oxide and black iron oxide; the flow aid is colloidal silica; the mass ratio of levamlodipine besylate and lubricant is 3.47:1~5; in the levamlodipine layer particles, the lubricant is magnesium stearate; Furthermore, the preparation process of the bilayer tablet involves compressing the telmisartan granules and levamlodipine granules into a bilayer tablet to obtain the compound telmisartan-levamlodipine tablet.

2. The preparation method of compound telmisartan-levamlodipine tablets as described in claim 1, characterized in that, The mass ratio of telmisartan raw material to amlodipine besylate raw material is 79~81:3.0~4.

0.

3. A compound telmisartan-levamlodipine tablet, characterized in that, Obtained by the preparation method described in any one of claims 1 to 2.

4. The compound telmisartan-levoamlodipine tablets as described in claim 3, characterized in that, The hardness of the double-layer core is 150~250N.

5. The compound telmisartan-levoamlodipine tablets as described in claim 3, characterized in that, The weight ratio of telmisartan to amlodipine is 470-490:190-210.

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