Candesartan cilexetil amlodipine oral tablet and preparation method thereof

Abstract

The invention discloses an oral tablet of candesartan cilexetil amlodipine and a preparation method thereof, the tablet is composed of three layers: an amlodipine layer I with a groove, a candesartan cilexetil layer II filled in the groove, and an amlodipine layer III covering the groove, the weight of the amlodipine layer I with the groove is 280-320 mg, the weight of the amlodipine layer II with the groove is 200-300 mg, and the weight of the amlodipine layer III with the groove is 200-300 mg. The weight of the amlodipine layer III covering the groove is 180-220 mg, and the weight of the candesartan cilexetil layer is 40 mg. According to the tablet, the candesartan cilexetil layer is filled in the groove of the amlodipine layer, the candesartan cilexetil layer is almost not extruded by external force or is only extruded by small external force and is kept in a loose state, meanwhile, the candesartan cilexetil layer and the amlodipine layer are relatively separated, and the stability of the candesartan cilexetil preparation in the long-term storage process is improved.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical preparations, and particularly relates to an oral tablet of candesartan cilexetil and amlodipine and a preparation method thereof. Background Art

[0002] Candesartan is a new type of angiotensin II receptor antagonist that directly acts on ATⅠ receptors to exert a blood pressure-lowering effect. It was first launched in Sweden in 1997 and was approved by the US FDA in 1998 for the treatment of hypertension. Its trade name is Amias. The main ingredient is Candesartan Cilexetil, which is converted into active candesartan after taking it and exerts its therapeutic effect.

[0003] Amlodipine besylate is a new generation of calcium ion antagonist and a third-generation dihydropyridine long-acting calcium ion channel blocker. It can block the influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, moderate the long-term dilation of peripheral blood vessels and coronary blood vessels, and reduce vascular resistance. It is used to treat various degrees of hypertension and variant angina pectoris and stable angina pectoris.

[0004] Candesartan cilexetil has multiple crystal forms, among which Crystal Form I has the advantages of high bioavailability and is widely used in commercial preparations. However, Crystal Form I is easily subjected to external force compression (such as crushing), which leads to an increase in related substances during storage.

[0005] Chinese patent CN102670604B discloses a composition of candesartan cilexetil and amlodipine and a preparation method thereof. The composition contains mannitol or lactose, cross-linked carboxymethyl cellulose sodium or cross-linked carboxymethyl cellulose calcium, etc., and the preparation method is wet granulation, and is prepared into tablets, etc. When prepared into tablets, it is squeezed by external force, which may cause the crystal structure of candesartan cilexetil to change. In addition, amlodipine besylate and lactose may undergo Maillard reaction, resulting in browning of the preparation color.

[0006] Chinese patents CN102688236B, CN103705513A, CN102764258A, CN102688236B, etc. all disclose a composition of candesartan cilexetil and amlodipine, in which PEG6000 is added as a stabilizer. PEG6000 is an oily substance, and is prone to sticking during high-speed tableting. In addition, PEG6000 is not a single component, and the physical and chemical properties of PEG6000 in different batches may have certain differences, thereby affecting the quality of the preparation. In addition, the improper use of PEG6000 in the preparation prescription will also affect the stability of the sample, which brings certain difficulties to the preparation development.

[0007] Therefore, it is necessary to develop a candesartan cilexetil and amlodipine oral tablet with stable quality and a preparation method thereof. Summary of the invention

[0008] The purpose of the present invention is to provide an oral tablet containing candesartan cilexetil and amlodipine and a preparation method thereof. The oral tablet consists of three parts: 1. an amlodipine layer I with a groove, 2. a candesartan cilexetil layer II filling the groove, and 3. an amlodipine layer III covering the groove.

[0009] The following embodiments are provided to achieve the purpose of the present invention.

[0010] In one embodiment, the oral tablet of candesartan cilexetil and amlodipine of the present invention consists of three layers: an amlodipine layer I with a groove, a candesartan cilexetil layer II filling the groove, and an amlodipine layer III covering the groove.

[0011] Preferably, in the oral tablets of the present invention, the weight of the amlodipine layer I with the groove is 280-320 mg, the weight of the amlodipine layer III covering the groove is 180-220 mg, and the weight of the candesartan cilexetil layer filling the groove is 40 mg.

[0012] In some embodiments, the above-mentioned oral tablet of the present invention, amlodipine layer I or amlodipine layer III, comprises amlodipine besylate, mannitol, microcrystalline cellulose, sodium starch glycolate and magnesium stearate.

[0013] Preferably, in the oral tablet of the present invention, the amlodipine layer I or the amlodipine layer III comprises by weight 1-2% of amlodipine besylate, 45.5-50% of mannitol, 45-49% of microcrystalline cellulose, 1.5-3% of sodium starch glycolate and 0.5-1.5% of magnesium stearate.

[0014] Preferably, the amlodipine layer I or amlodipine layer III of the oral tablet of the present invention comprises 1.39% by weight of amlodipine besylate, 48.00% by weight of mannitol, 47.60% by weight of microcrystalline cellulose, 2.00% by weight of sodium starch glycolate and 1.01% by weight of magnesium stearate.

[0015] In some embodiments, in the oral tablet of the present invention, the candesartan cilexetil layer II filling the groove comprises candesartan cilexetil, mannitol and microcrystalline cellulose.

[0016] Preferably, in the oral tablet of the present invention, the candesartan cilexetil layer II filling the groove contains 18-25% by weight of candesartan cilexetil, 50-60% by weight of mannitol and 20-32% by weight of microcrystalline cellulose, more preferably contains 20% by weight of candesartan cilexetil, 55% by weight of mannitol and 25% by weight of microcrystalline cellulose.

[0017] In some embodiments, the oral tablet of the present invention contains 8 mg of candesartan cilexetil and 5 mg of amlodipine.

[0018] In another embodiment, the present invention provides a method for preparing the above-mentioned oral tablet of the present invention, comprising the following steps:

[0019] 1) Preparation of Amlodipine Layer Mixture

[0020] The prescribed amount of amlodipine besylate, mannitol, microcrystalline cellulose and sodium starch glycolate are placed in a mixer and mixed, and the prescribed amount of magnesium stearate is added and mixed to obtain a mixture I;

[0021] 2) Preparation of candesartan cilexetil layer mixture

[0022] Prescribed amounts of candesartan cilexetil, mannitol and microcrystalline cellulose were placed in a mixer and mixed to obtain mixture II;

[0023] 3) Tablet pressing

[0024] Take the mixture I of step 1) and press it into an amlodipine layer I with a groove, then fill the mixture II of step 2) into the groove of the amlodipine layer I to obtain the candesartan cilexetil layer II filling the groove, then take the mixture I of step 1) and fill it on top of the amlodipine layer 1 and the candesartan cilexetil layer II, and press into shape to obtain the amlodipine layer III with a sealing groove and the candesartan cilexetil amlodipine tablets.

[0025] In some embodiments, a method for preparing an oral tablet containing candesartan cilexetil and amlodipine of the present invention comprises the following steps:

[0026] 1) Preparation of Amlodipine Layer Mixture

[0027] Mix the prescribed amount of amlodipine besylate, mannitol, microcrystalline cellulose and sodium starch glycolate in a three-dimensional mixer, add the prescribed amount of magnesium stearate, and mix to obtain mixture I;

[0028] 2) Preparation of candesartan cilexetil layer mixture

[0029] Mix the prescribed amounts of candesartan cilexetil, mannitol and microcrystalline cellulose in a three-dimensional mixer to obtain mixture II;

[0030] 3) Tablet pressing

[0031] First, take the mixture I and press it into an amlodipine layer I with a groove, then fill the mixture II into the groove of the amlodipine layer I to obtain a candesartan cilexetil layer II with the groove filled, then take the mixture I and fill it on top of the amlodipine layer 1 and the candesartan cilexetil layer II, and press into shape to obtain candesartan cilexetil amlodipine tablets.

[0032] Preferably, in the method for preparing the oral tablets of the present invention, the weight of the amlodipine layer I in step 3) is 280 mg / tablet to 320 mg / tablet.

[0033] Preferably, in the method for preparing the oral tablets of the present invention, the weight of the amlodipine layer III in step 3) is 180 mg / tablet to 220 mg / tablet.

[0034] The beneficial effects of the present invention are as follows: the present invention is ingeniously conceived, the candesartan cilexetil layer is filled in the groove of the amlodipine layer, the candesartan cilexetil layer is hardly squeezed by external force or is only squeezed by a small external force, and maintains a relatively loose state, while the materials of the candesartan cilexetil layer and the amlodipine layer are relatively separated, which is beneficial to improving the stability of the candesartan cilexetil preparation during long-term storage. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is a schematic diagram of the hierarchical structure of candesartan cilexetil and amlodipine oral tablets;

[0036] Among them, 1 is the amlodipine layer I, 2 is the candesartan cilexetil layer II, and 3 is the amlodipine layer III. DETAILED DESCRIPTION

[0037] The following examples are typical and are used to further understand the spirit of the present invention, but are not intended to limit the scope of the present invention in any way.

[0038] Example 1 Candesartan cilexetil and amlodipine tablets prescription

[0039] (1) Prescription: Composition of each tablet

[0040] Components weight Amlodipine besylate layer (Mixture I) Amlodipine Besylate 6.93mg Mannitol 240mg Microcrystalline Cellulose 238mg Sodium starch glycolate 10mg Magnesium Stearate 5.07mg Candesartan cilexetil layer (mixture II) Candesartan cilexetil 8mg Mannitol 22mg Microcrystalline Cellulose 10mg

[0041] (2) Oral tablet composition:

[0042] It consists of three parts: 1. Amlodipine layer I with grooves (1), 2. Candesartan cilexetil layer II (2) filling the grooves, and 3. Amlodipine layer III (3) covering the grooves. Tablet layer structure see Figure 1 Schematic diagram of the invention. The weight of the amlodipine layer I (1) with the groove is 280-320 mg, the weight of the candesartan cilexetil layer II (2) filling the groove is 40 mg, and the weight of the amlodipine layer III (3) covering the groove is 180-220 mg.

[0043] Example 2 Preparation of samples for comparative test of candesartan cilexetil tablets subjected to external force compression

[0044] (1) Preparation of candesartan cilexetil layer mixture

[0045] 24 g of candesartan cilexetil, 66 g of mannitol and 30 g of microcrystalline cellulose were mixed in a three-dimensional mixer at 10 rpm for 20 minutes to obtain mixture II.

[0046] (2) Preparation of sample 1 for comparison test of candesartan cilexetil under external force extrusion

[0047] Take 3 g of mixture II as comparative test sample 1.

[0048] (3) Preparation of sample 2 for comparison test of candesartan cilexetil under external force extrusion

[0049] Take an appropriate amount of mixture II and press it into tablets with an average hardness of 15N as comparative test sample 2.

[0050] (4) Preparation of sample 3 for comparison test of candesartan cilexetil extrusion under external force

[0051] Take an appropriate amount of mixture II and press it into tablets with an average hardness of 30N as comparative test sample 3.

[0052] (5) Preparation of sample 4 for comparison test of candesartan cilexetil extrusion under external force

[0053] Take an appropriate amount of mixture II and press it into tablets with an average hardness of 45N as comparative test sample 4.

[0054] Example 3 Influencing Factors Test

[0055] Test samples: comparative test sample 1, comparative test sample 2, comparative test sample 3, comparative test sample 4 prepared in Example 2.

[0056] Test conditions: high temperature 60℃, high humidity 92.5%, light 4500lx±500lx

[0057] Test results: see Table 1

[0058] Table 1. Test results of influencing factors

[0059]

[0060]

[0061] As can be seen from the results in Table 1, the properties and related substances of the comparative test sample 1 which was not pressed into tablets and not subjected to external force extrusion at high temperature of 60°C, high humidity of 92.5%, and illumination of 4500lx±500lx for 10 days did not change significantly, and the properties and related substances of the comparative test sample 2 which was pressed into tablets with a hardness of 15N at high temperature of 60°C, high humidity of 92.5%, and illumination of 4500lx±500lx for 10 days did not change significantly. The properties and related substances of the comparative test sample 3 which was pressed into tablets with a hardness of 30N at high temperature of 60°C, high humidity of 92.5%, and illumination of 4500lx±500lx for 10 days increased, and the properties and related substances of the comparative test sample 4 which was pressed into tablets with a hardness of 45N at high temperature of 60°C, high humidity of 92.5%, and illumination of 4500lx±500lx for 10 days increased significantly. It can be seen from this that when a mixture containing candesartan cilexetil is squeezed by a large external force, the content of related substances may increase during the storage process, while when the external force is small, the content of related substances will not change significantly during the storage process.

[0062] Example 4 Preparation of Amlodipine Tablet Layer Mixture and Candesartan Cilexetil Layer Mixture

[0063] (1) Preparation of mixture I of amlodipine layer

[0064] 41.58 g of amlodipine besylate, 1440 g of mannitol, 1428 g of microcrystalline cellulose and 60 g of sodium starch glycolate were mixed in a three-dimensional mixer at 10 rpm for 20 minutes, 30.42 g of magnesium stearate was added, and mixed at 10 rpm for 10 minutes to obtain mixture I;

[0065] (2) Preparation of Mixture II of Candesartan Cilexetil Layer

[0066] 48 g of candesartan cilexetil, 132 g of mannitol and 60 g of microcrystalline cellulose were mixed in a three-dimensional mixer at 10 rpm for 20 minutes to obtain mixture II.

[0067] The prepared mixture I and mixture II were also used for the preparation of candesartan cilexetil and amlodipine tablets in the following Examples 5-7.

[0068] Example 5 Preparation of Candesartan Cilopenem and Amlodipine Tablets

[0069] First, take a proper amount of the mixture I to compress an amlodipine layer I (1) with a groove, wherein the weight of the amlodipine layer I (1) is 280 mg / tablet; then, fill a proper amount of the mixture II into the groove of the amlodipine layer I (1) to obtain a candesartan cilexetil layer II (2) filling the groove, wherein the weight of the candesartan cilexetil layer II (2) is 40 mg / tablet; then, take a proper amount of the mixture I to fill the top of the amlodipine layer I and the candesartan cilexetil layer II, and compress them into shape to obtain an amlodipine layer III (3) covering the groove, and candesartan cilexetil amlodipine tablets, wherein the weight of the amlodipine layer III (3) is 220 mg / tablet.

[0070] Example 6 Preparation of Candesartan Cilopenem and Amlodipine Tablets

[0071] First, take a proper amount of the mixture I to compress an amlodipine layer I (1) with a groove, wherein the weight of the amlodipine layer I (1) is 300 mg / tablet; then, fill a proper amount of the mixture II into the groove of the amlodipine layer I (1) to obtain a candesartan cilexetil layer II (2) filling the groove, wherein the weight of the candesartan cilexetil layer II (2) is 40 mg / tablet; then, take a proper amount of the mixture I to fill the top of the amlodipine layer I and the candesartan cilexetil layer II, and compress them into shape to obtain an amlodipine layer III (3) covering the groove, and candesartan cilexetil amlodipine tablets, wherein the weight of the amlodipine layer III (3) is 200 mg / tablet.

[0072] Example 7 Preparation of Candesartan Ciloxane Amlodipine Tablets

[0073] First, take a proper amount of the mixture I to compress an amlodipine layer I (1) with a groove, wherein the weight of the amlodipine layer I (1) is 320 mg / tablet; then, fill a proper amount of the mixture II into the groove of the amlodipine layer I (1) to obtain a candesartan cilexetil layer II (2) filling the groove, wherein the weight of the candesartan cilexetil layer II (2) is 40 mg / tablet; then, take a proper amount of the mixture I to fill the top of the amlodipine layer I and the candesartan cilexetil layer II, and compress them into shape to obtain an amlodipine layer III (3) covering the groove, and candesartan cilexetil amlodipine tablets, wherein the weight of the amlodipine layer III (3) is 180 mg / tablet.

[0074] Example 8 Preparation of Candesartan Cilopenem and Amlodipine Tablets

[0075] (1) Prescription: Composition of each tablet

[0076]

[0077]

[0078] (2) 6 g of amlodipine besylate, 273 g of mannitol, 294 g of microcrystalline cellulose and 18 g of sodium starch glycolate were mixed in a three-dimensional mixer at 10 rpm for 20 minutes, 9 g of magnesium stearate was added, and the mixture was mixed at 10 rpm for 10 minutes to obtain mixture I;

[0079] (3) 43.2 g of candesartan cilexetil, 120 g of mannitol, and 76.8 g of microcrystalline cellulose were mixed in a three-dimensional mixer at 10 rpm for 20 minutes to obtain a mixture II.

[0080] (4) First, take an appropriate amount of the mixture I and compress it into an amlodipine layer I (1) with a groove, wherein the weight of the amlodipine layer I (1) is 300 mg / tablet; then, fill an appropriate amount of the mixture II into the groove of the amlodipine layer I (1) to obtain a candesartan cilexetil layer II (2) filling the groove, wherein the weight of the candesartan cilexetil layer II (2) is 40 mg / tablet; then, take an appropriate amount of the mixture I and fill it on top of the amlodipine layer I and the candesartan cilexetil layer II, and compress them into shape to obtain an amlodipine layer III (3) covering the groove and candesartan cilexetil amlodipine tablets, wherein the weight of the amlodipine layer III (3) is 200 mg / tablet.

[0081] Example 9 Preparation of Candesartan Cilopenem and Amlodipine Tablets

[0082] (1) Prescription: Composition of each tablet

[0083]

[0084]

[0085] (2) 12 g of amlodipine besylate, 300 g of mannitol, 270 g of microcrystalline cellulose and 9 g of sodium starch glycolate were mixed in a three-dimensional mixer at 10 rpm for 20 minutes, 9 g of magnesium stearate was added, and the mixture was mixed at 10 rpm for 10 minutes to obtain mixture I;

[0086] (3) 60 g of candesartan cilexetil, 132 g of mannitol, and 48 g of microcrystalline cellulose were mixed in a three-dimensional mixer at 10 rpm for 20 minutes to obtain a mixture II.

[0087] (4) First, take an appropriate amount of the mixture I and compress it into an amlodipine layer I (1) with a groove, wherein the weight of the amlodipine layer I (1) is 300 mg / tablet; then, fill an appropriate amount of the mixture II into the groove of the amlodipine layer I (1) to obtain a candesartan cilexetil layer II (2) filling the groove, wherein the weight of the candesartan cilexetil layer II (2) is 40 mg / tablet; then, take an appropriate amount of the mixture I and fill it on top of the amlodipine layer I and the candesartan cilexetil layer II, and compress them into shape to obtain an amlodipine layer III (3) covering the groove and candesartan cilexetil amlodipine tablets, wherein the weight of the amlodipine layer III (3) is 200 mg / tablet.

[0088] Example 10 Preparation of Candesartan Cilopenem and Amlodipine Tablets

[0089] (1) Prescription: Composition of each tablet

[0090] Components weight Amlodipine besylate layer (Mixture I) Amlodipine Besylate 10mg Mannitol 227.5mg Microcrystalline Cellulose 245mg Sodium starch glycolate 15mg Magnesium Stearate 2.5mg Candesartan cilexetil layer (mixture II) Candesartan cilexetil 8mg Mannitol 24mg Microcrystalline Cellulose 8mg

[0091] (2) 12 g of amlodipine besylate, 273 g of mannitol, 294 g of microcrystalline cellulose and 18 g of sodium starch glycolate were mixed in a three-dimensional mixer at 10 rpm for 20 minutes, 3 g of magnesium stearate was added, and the mixture was mixed at 10 rpm for 10 minutes to obtain mixture I;

[0092] (3) 48 g of candesartan cilexetil, 144 g of mannitol, and 48 g of microcrystalline cellulose were mixed in a three-dimensional mixer at 10 rpm for 20 minutes to obtain mixture II.

[0093] (4) First, take an appropriate amount of the mixture I and compress it into an amlodipine layer I (1) with a groove, wherein the weight of the amlodipine layer I (1) is 300 mg / tablet; then, fill an appropriate amount of the mixture II into the groove of the amlodipine layer I (1) to obtain a candesartan cilexetil layer II (2) filling the groove, wherein the weight of the candesartan cilexetil layer II (2) is 40 mg / tablet; then, take an appropriate amount of the mixture I and fill it on top of the amlodipine layer I and the candesartan cilexetil layer II, and compress them into shape to obtain an amlodipine layer III (3) covering the groove and candesartan cilexetil amlodipine tablets, wherein the weight of the amlodipine layer III (3) is 200 mg / tablet.

[0094] The tablet samples of Examples 5-10 were carefully cut along the junction of amlodipine layer I (1) and amlodipine layer III (3). It can be seen that the candesartan cilexetil layer II (2) filling the groove is in a relatively loose state and breaks when touched lightly, indicating that the candesartan cilexetil layer II (2) is only squeezed by a small external force.

[0095] Example 11 Preparation of Candesartan Ciloxane Amlodipine Tablets Containing PEG6000 in the Prescription

[0096] (1) Prescription: Composition of each tablet

[0097] Components weight Amlodipine besylate layer Amlodipine Besylate 6.93mg Mannitol 240mg Microcrystalline Cellulose 238mg Sodium starch glycolate 10mg Magnesium Stearate 5.07mg Candesartan cilexetil layer Candesartan cilexetil 8mg Mannitol 21mg Microcrystalline Cellulose 9.8mg Polyethylene glycol 6000 1.2mg

[0098] (2) Preparation of Amlodipine Layer Mixture

[0099] 20.79 g of amlodipine besylate, 720 g of mannitol, 714 g of microcrystalline cellulose, and 30 g of sodium starch glycolate were mixed in a three-dimensional mixer at 10 rpm for 20 minutes, 15.21 g of magnesium stearate was added, and the mixture was mixed at 10 rpm for 10 minutes to obtain mixture I;

[0100] (3) Preparation of Candesartan Cilexetil Layer Mixture

[0101] 24 g of candesartan cilexetil, 63 g of mannitol, 29.4 g of microcrystalline cellulose and 3.6 g of polyethylene glycol 6000 were placed in a three-dimensional mixer and mixed at 10 rpm for 20 minutes to obtain mixture II.

[0102] (4) Tableting

[0103] First, take a proper amount of the mixture I to compress an amlodipine layer I (1) with a groove, wherein the weight of the amlodipine layer I (1) is 320 mg / tablet; then, fill a proper amount of the mixture II into the groove of the amlodipine layer I (1) to obtain a candesartan cilexetil layer II (2) filling the groove, wherein the weight of the candesartan cilexetil layer II (2) is 40 mg / tablet; then, take a proper amount of the mixture I to fill the amlodipine layer 1 and the candesartan cilexetil layer II, and compress them into shape to obtain an amlodipine layer III (3) with a groove covered and a candesartan cilexetil amlodipine tablet, wherein the weight of the amlodipine layer III (3) is 180 mg / tablet.

[0104] Stability test

[0105] The tablet samples of Examples 5-11 were respectively placed in oral solid pharmaceutical high-density polyethylene bottles and sealed with caps, and an accelerated stability test was performed to examine the stability of the samples.

[0106] Test method: Place at a temperature of 40±2℃ and a relative humidity of 75±5% for 6 months. Take samples once in the 0th, 1st, 2nd, 3rd, 4th, 5th and 6th month of the experiment, and determine the content and total impurities by HPLC. Compare with the results in 0th month. The results are shown in Table 2.

[0107] Table 2. Accelerated stability test results

[0108]

[0109]

[0110] As can be seen from the results in Table 2, the samples of Examples 5-10 were accelerated for 6 months, and the content did not decrease significantly, and the total impurities increased slightly, but the increase was small and within the allowable limit. This shows that the sample quality of the candesartan cilexetil and amlodipine tablets of the present invention is stable, and its stability is not lower than that of the sample of Example 11 containing polyethylene glycol 6000 in the prescription and prepared by the same method. On the contrary, adding polyethylene glycol 6000 to the prescription may introduce more impurities.

[0111] The above embodiments are only representative of the present invention. Any simple variation, combination, modification, etc. of the present invention without departing from the spirit and purpose of the present invention shall fall within the scope of the present invention.

Claims

1. An oral tablet of candesartan cilexetil and amlodipine, the tablet consisting of three layers: An amlodipine layer I having a groove, a candesartan cilexetil layer II filling the groove, and an amlodipine layer III covering the groove.

2. The oral tablet according to claim 1, wherein the weight of the amlodipine layer I with the groove is 280-320 mg, and the weight of the amlodipine layer III with the sealing groove is 180-220 mg.

3. The oral tablet according to claim 1, wherein the weight of the candesartan cilexetil layer is 40 mg.

4. The oral tablet according to claim 1, wherein the amlodipine layer I or the amlodipine layer III comprises amlodipine besylate, mannitol, microcrystalline cellulose, sodium starch glycolate and magnesium stearate.

5. The oral tablet according to claim 4, wherein the amlodipine layer I or the amlodipine layer III comprises by weight 1-2% amlodipine besylate, 45.5-50% mannitol, 45-49% microcrystalline cellulose, 1.5-3% sodium starch glycolate and 0.5-1.5% magnesium stearate.

6. The oral tablet according to claim 5, wherein the amlodipine layer I or the amlodipine layer III comprises 1.39% by weight of amlodipine besylate, 48.00% by weight of mannitol, 47.60% by weight of microcrystalline cellulose, 2.00% by weight of sodium starch glycolate and 1.01% by weight of magnesium stearate.

7. The oral tablet according to claim 1, wherein the candesartan cilexetil layer II comprises candesartan cilexetil, mannitol and microcrystalline cellulose.

8. The oral tablet according to claim 7, wherein the candesartan cilexetil layer II comprises 18-25% by weight of candesartan cilexetil, 50-60% by weight of mannitol and 20-32% by weight of microcrystalline cellulose, preferably 20% by weight of candesartan cilexetil, 55% by weight of mannitol and 25% by weight of microcrystalline cellulose.

9. The oral tablet according to claim 1, comprising 8 mg of candesartan cilexetil and 5 mg of amlodipine.

10. A method for preparing the oral tablet of claims 1-9, comprising the following steps: 1) Preparation of Amlodipine Layer Mixture The prescribed amount of amlodipine besylate, mannitol, microcrystalline cellulose and sodium starch glycolate are placed in a mixer and mixed, and the prescribed amount of magnesium stearate is added and mixed to obtain a mixture I; 2) Preparation of candesartan cilexetil layer mixture Prescribed amounts of candesartan cilexetil, mannitol and microcrystalline cellulose are placed in a mixer and mixed to obtain mixture II; 3) Tablet pressing Take the mixture I of step 1) and press it into an amlodipine layer I with a groove, then fill the mixture II of step 2) into the groove of the amlodipine layer I to obtain a candesartan cilexetil layer II with a filled groove, then take the mixture I of step 1), fill it on top of the amlodipine layer I and the candesartan cilexetil layer II, and press it into a tablet.

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