Amlodipine benazepril capsule and preparation method thereof

Abstract

The preparation method comprises the following steps: preparing raw materials, namely preparing amlodipine besylate and benazepril hydrochloride as main materials, taking a filling agent, a disintegrating agent and a lubricating agent as auxiliary materials, adding starch into powdered sugar, then adding purified water, heating while mixing and stirring, and uniformly mixing, so as to obtain the amlodipine besylate benazepril capsule. The preparation method comprises the following steps: preparing a gelatinized starch slurry as an adhesive solution for later use, mixing, putting amlodipine besylate and benazepril hydrochloride raw materials into a mixer according to a ratio of 1: 4, carrying out primary mixing, adding the adhesive solution into the uniformly mixed material, and stirring while adding to prepare a soft material. The composition of amlodipine besylate and benazepril hydrochloride is adopted, and amlodipine can selectively inhibit calcium ions from transmembrane entry into smooth muscle cells and myocardial cells, so that vascular smooth muscles are relaxed, peripheral vascular resistance is reduced, blood pressure is reduced, and angiotensin I is inhibited from being converted into angiotensin II.

Description

Technical Field

[0001] The invention relates to the technical field of amlodipine benazepril capsule preparation, in particular to an amlodipine benazepril capsule and a preparation method thereof. Background Art

[0002] Amlodipine Benazepril Capsules are a compound antihypertensive drug. The main ingredients are amlodipine besylate and benazepril hydrochloride. Among them, amlodipine besylate belongs to the calcium channel blocker class of drugs, and benazepril hydrochloride belongs to the angiotensin converting enzyme inhibitor class of drugs. The two drugs are combined in one capsule to exert a synergistic antihypertensive effect. It mainly selectively blocks the calcium ion channels on the vascular smooth muscle cell membrane and reduces the influx of calcium ions. When the intracellular calcium ions decrease, the smooth muscle cells relax. This causes the peripheral blood vessels to dilate, reducing peripheral vascular resistance, thereby lowering blood pressure. Benazepril inhibits the conversion of angiotensin I to angiotensin II in the body. Angiotensin II is a strong vasoconstrictor and can stimulate the secretion of aldosterone. Aldosterone can cause water and sodium retention, which increases blood pressure. Benazepril inhibits this process, reduces the generation of angiotensin II, reduces peripheral vascular resistance, and reduces aldosterone secretion, producing a hypotensive effect. The capsule itself may limit the dissolution rate of the drug. Compared with solution and other dosage forms, amlodipine besylate and benazepril hydrochloride need to disintegrate first after taking, so that the drug decomposes slowly in the body, resulting in insufficient drug dissolution, affecting drug absorption and efficacy. The few amlodipine besylate and benazepril hydrochloride tablets containing disintegrating elements have an unsuitable disintegration rate, either too slow or too fast, resulting in the drug being unable to reach an effective position for disintegration and release. For this reason, we provide an amlodipine benazepril capsule and a preparation method thereof. Summary of the invention

[0003] The purpose of the present invention is to provide an amlodipine benazepril capsule and a preparation method thereof in view of the above technical problems, which has the advantages of rapid water absorption, swelling, disintegration and promoting the dissolution of the drug.

[0004] To achieve this object, the present invention provides an amlodipine benazepril capsule and a preparation method thereof, which adopts the following technical embodiments:

[0005] An amlodipine-benazepril capsule comprises a tablet core and a capsule shell, wherein the tablet core comprises amlodipine besylate, benazepril hydrochloride, a filler, a binder, a disintegrant, and a lubricant;

[0006] The content of amlodipine besylate is 15%-17%, the content of benazepril hydrochloride is 60%-65%, the content of filler is 20%-25%, the content of disintegrant is 3%-8%, and the content of lubricant is 0.5%-1%.

[0007] A preparation method of amlodipine benazepril capsules, the preparation method comprising the following steps:

[0008] S1: Raw material preparation: prepare amlodipine besylate and benazepril hydrochloride as main materials, and filler, disintegrant and lubricant as auxiliary materials;

[0009] S2: Add starch to powdered sugar and then add purified water, mix and stir while heating to obtain gelatinized starch slurry as an adhesive solution for later use;

[0010] S3: Mixing: putting the raw materials of amlodipine besylate and benazepril hydrochloride into a mixer at a ratio of 1:4 for preliminary mixing;

[0011] S4: adding the above-mentioned adhesive solution to the uniformly mixed material, stirring while adding, to make a soft material;

[0012] S5: Adding excipients and remixing: adding disintegrants, lubricants and fillers to the preliminarily mixed materials;

[0013] S6: The soft material is made into wet granules by a swing granulator;

[0014] S7: Place the wet granules in an oven for drying to avoid excessive temperature causing drug decomposition, so that the granules are dried evenly and the drying is completed;

[0015] S8: Select a capsule shell of appropriate specifications according to the required drug filling amount, and use a capsule filler to fill the mixed drug material into the capsule shell;

[0016] S9: Perform a visual inspection on the filled capsules to check whether the capsules are intact and have no cracks;

[0017] S10: Pack with suitable packaging materials and label them.

[0018] Preferably, the filler is any one of starch and dextrin, the disintegrant is sodium carboxymethyl starch, and the lubricant is magnesium stearate.

[0019] Preferably, in step S2, the mixing time of the mixer is 15-20 minutes, and the mixing ratio of starch to sugar water is 1:1.

[0020] Preferably, in step S3, the rotation speed of the preliminary mixing is 20-30 rpm, and the mixing time is 15-30 minutes.

[0021] Preferably, in step S5, the auxiliary materials are mixed and stirred again, and the stirring time is 5-10 minutes.

[0022] Preferably, in step S6, the mesh size of the oscillating granulator is 80-100 mesh.

[0023] Preferably, in step S7, the drying temperature of the oven is 40-60° C., and the drying time is 3-5 hours.

[0024] Preferably, in step S8, the filling volume inside the capsule shell is 1.37-1.45 ml.

[0025] Preferably, in step S8, the filling speed of the capsule filling agent is 3000-7000 capsules / minute.

[0026] The present invention has at least the following beneficial effects:

[0027] In the present invention, a combination of amlodipine besylate and benazepril hydrochloride is used. Amlodipine can selectively inhibit calcium ions from entering smooth muscle cells and cardiomyocytes across the membrane, thereby relaxing vascular smooth muscle, reducing peripheral vascular resistance, lowering blood pressure, and inhibiting the conversion of angiotensin I to angiotensin II. Angiotensin II is a strong vasoconstrictor and can stimulate the secretion of aldosterone. By inhibiting this process, benazepril can reduce peripheral vascular resistance, reduce aldosterone secretion, and produce a hypotensive effect;

[0028] In the present invention, starch or dextrin is used as a filler, which is relatively cheap and has good compressibility and fluidity, and is conducive to particle forming. Dextrin is a product of starch hydrolysis, which can increase the viscosity of capsule particles and make the capsule particles more compact;

[0029] In the present invention, sodium carboxymethyl starch is used as a disintegrant, which can rapidly absorb water and swell after contacting water.

[0030] The tablets can be disintegrated and the dissolution of the drug can be promoted. The addition of lubricant magnesium stearate can reduce the friction in the capsule granule preparation process and ensure a smooth surface.

[0031] In the present invention, a binder solution is added to the amlodipine besylate and benazepril hydrochloride tablets, and an adhesive layer is formed on the surface of the material particles, which can fill the gaps between the material particles, connect the particles to each other, and enhance the forming rate of the particles. In the granulation process, the binder can increase the strength of the particles, and sufficient binder can form a skeleton-like structure inside the particles, so that the particles can remain intact in the subsequent drying and granulation processes.

[0032] Other advantages, objectives and features of the present invention will be embodied in part through the following description, and in part will be understood by those skilled in the art through study and practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 The present invention is a flow chart of an amlodipine benazepril capsule and a preparation method thereof. DETAILED DESCRIPTION

[0034] In order to make the purpose, technical embodiments and advantages of the present invention more clear, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0035] The application principle of the present invention is described in detail below in conjunction with the accompanying drawings.

[0036] An amlodipine-benazepril capsule comprises a tablet core and a capsule shell, wherein the tablet core comprises amlodipine besylate, benazepril hydrochloride, a filler, a binder, a disintegrant, and a lubricant;

[0037] The content of amlodipine besylate is 15%-17%, the content of benazepril hydrochloride is 60%-65%, the content of filler is 20%-25%, the content of disintegrant is 3%-8%, and the content of lubricant is 0.5%-1%.

[0038] A preparation method of amlodipine benazepril capsules, the preparation method comprising the following steps:

[0039] S1: Raw material preparation: prepare amlodipine besylate and benazepril hydrochloride as main materials, and filler, disintegrant and lubricant as auxiliary materials;

[0040] S2: Add starch to powdered sugar and then add purified water, mix and stir while heating to obtain gelatinized starch slurry as an adhesive solution for later use;

[0041] S3: Mixing: putting the raw materials of amlodipine besylate and benazepril hydrochloride into a mixer at a ratio of 1:4 for preliminary mixing;

[0042] S4: adding the above-mentioned adhesive solution to the uniformly mixed material, stirring while adding, to make a soft material;

[0043] S5: Adding excipients and remixing: adding disintegrants, lubricants and fillers to the preliminarily mixed materials;

[0044] S6: The soft material is made into wet granules by a swing granulator;

[0045] S7: Place the wet granules in an oven for drying to avoid excessive temperature causing drug decomposition, so that the granules are dried evenly and the drying is completed;

[0046] S8: Select a capsule shell of appropriate specifications according to the required drug filling amount, and use a capsule filler to fill the mixed drug material into the capsule shell;

[0047] S9: Perform a visual inspection on the filled capsules to check whether the capsules are intact and have no cracks;

[0048] S10: Pack with suitable packaging materials and label them.

[0049] The filler is any one of starch and dextrin, the disintegrant is sodium carboxymethyl starch, and the lubricant is magnesium stearate.

[0050] Wherein, in step S2, the mixing time of the mixer is 15-20 minutes, and the mixing ratio of starch and sugar water is 1:1.

[0051] Wherein, in step S3, the rotation speed of the preliminary mixing is 20-30 rpm, and the mixing time is 15-30 minutes.

[0052] Wherein, in step S5, the auxiliary materials are mixed and stirred again, and the stirring time is 5-10 minutes.

[0053] Wherein, in step S6, the mesh size of the oscillating granulator is 80-100 mesh.

[0054] Wherein, in step S7, the drying temperature of the oven is 40-60° C., and the drying time is 3-5 hours.

[0055] Wherein, in step S8, the filling volume inside the capsule shell is 1.37-1.45 ml.

[0056] Wherein, in step S8, the filling speed of the capsule filling agent is 3000-7000 capsules / minute.

[0057] Example 1

[0058] In the present embodiment, amlodipine benazepril capsules and preparation method thereof are as follows:

[0059] S1: Raw material preparation: prepare amlodipine besylate and benazepril hydrochloride as main materials, and filler, disintegrant and lubricant as auxiliary materials;

[0060] S2: Add starch to powdered sugar and then add purified water, mix and stir while heating to obtain gelatinized starch slurry as an adhesive solution for later use;

[0061] S3: Mixing: putting the raw materials of amlodipine besylate and benazepril hydrochloride into a mixer at a ratio of 1:4 for preliminary mixing;

[0062] S4: adding the above-mentioned adhesive solution to the uniformly mixed material, stirring while adding, to make a soft material;

[0063] S5: Adding excipients and remixing: adding disintegrants, lubricants and fillers to the preliminarily mixed materials;

[0064] S6: The soft material is made into wet granules by a swing granulator;

[0065] S7: Place the wet granules in an oven for drying to avoid excessive temperature causing drug decomposition, so that the granules are dried evenly and the drying is completed;

[0066] S8: Select a capsule shell of appropriate specifications according to the required drug filling amount, and use a capsule filler to fill the mixed drug material into the capsule shell;

[0067] S9: Perform a visual inspection on the filled capsules to check whether the capsules are intact and have no cracks;

[0068] S10: Pack with suitable packaging materials and label them.

[0069] Example 2

[0070] In the present embodiment, amlodipine benazepril capsules and preparation method thereof are as follows:

[0071] S1: Raw material preparation: prepare amlodipine besylate and benazepril hydrochloride as main materials, and filler, disintegrant and lubricant as auxiliary materials;

[0072] S2: Mixing: putting the raw materials of amlodipine besylate and benazepril hydrochloride into a mixer at a ratio of 1:4 for preliminary mixing;

[0073] S3: adding the above-mentioned adhesive solution to the uniformly mixed material, stirring while adding, to make a soft material;

[0074] S4: The soft material is made into wet granules by a swing granulator;

[0075] S5: Place the wet granules in an oven for drying to avoid excessive temperature causing drug decomposition, so that the granules are dried evenly and the drying is completed;

[0076] S6: Select a capsule shell of appropriate specifications according to the required drug filling amount, and use a capsule filler to fill the mixed drug material into the capsule shell;

[0077] Example 3

[0078] In the present embodiment, amlodipine benazepril capsules and preparation method thereof are as follows:

[0079] S1: Raw material preparation: prepare amlodipine besylate and benazepril hydrochloride as main materials, and filler, disintegrant and lubricant as auxiliary materials;

[0080] S2: Add starch to powdered sugar and then add purified water, mix and stir while heating to obtain gelatinized starch slurry as an adhesive solution for later use;

[0081] S3: Mixing: putting the raw materials of amlodipine besylate and benazepril hydrochloride into a mixer at a ratio of 1:4 for preliminary mixing;

[0082] S4: adding the above-mentioned adhesive solution to the uniformly mixed material, stirring while adding, to make a soft material;

[0083] S5: The soft material is made into wet granules by a swing granulator;

[0084] S6: Place the wet granules in an oven for drying to avoid excessive temperature causing drug decomposition, so that the granules are dried evenly and the drying is completed;

[0085] S7: Select a capsule shell of appropriate specifications according to the required drug filling amount, and use a capsule filler to fill the mixed drug material into the capsule shell.

[0086] Comparing Examples 1-3, it can be seen that the dissolution rate of amlodipine besylate and benazepril hydrochloride capsules containing disintegrants is large, and in the process of comparing Examples 1-3, it is found that the greater the content of disintegrant, the faster the dissolution rate, and there are no other adverse reactions and no effect on the efficacy. The content of 6% disintegrant in Example 1 is most appropriate.

[0087] The above embodiments are only used to illustrate rather than limit the technical embodiments of the present invention. Relevant technical personnel in the field may make reasonable modifications or equivalent substitutions to the present invention, but any modifications and partial substitutions that do not depart from the spirit and scope of the present invention should be included in the scope of the claims of the present invention.

[0088] The contents not described in detail in this specification belong to the prior art known to professional and technical personnel in this field.

Claims

1. An amlodipine benazepril capsule, comprising a tablet core and a capsule shell, characterized in that: The tablet core comprises amlodipine besylate, benazepril hydrochloride, a filler, a binder, a disintegrant, and a lubricant; The content of amlodipine besylate is 15%-17%, the content of benazepril hydrochloride is 60%-65%, the content of filler is 20%-25%, the content of disintegrant is 3%-8%, and the content of lubricant is 0.5%-1%.

2. A method for preparing amlodipine benazepril capsules, characterized in that: The preparation method comprises the following steps: S1: Raw material preparation: prepare amlodipine besylate and benazepril hydrochloride as main materials, and filler, disintegrant and lubricant as auxiliary materials; S2: Add starch to powdered sugar and then add purified water, mix and stir while heating to obtain gelatinized starch slurry as an adhesive solution for later use; S3: Mixing: putting the raw materials of amlodipine besylate and benazepril hydrochloride into a mixer at a ratio of 1:4 for preliminary mixing; S4: adding the above-mentioned adhesive solution to the uniformly mixed material, stirring while adding, to make a soft material; S5: Adding excipients and remixing: adding disintegrants, lubricants and fillers to the preliminarily mixed materials; S6: The soft material is made into wet granules by a swing granulator; S7: Place the wet granules in an oven for drying to avoid excessive temperature causing drug decomposition, so that the granules are dried evenly and the drying is completed; S8: Select a capsule shell of appropriate specifications according to the required drug filling amount, and use a capsule filler to fill the mixed drug material into the capsule shell; S9: Perform a visual inspection on the filled capsules to check whether the capsules are intact and have no cracks; S10: Pack with suitable packaging materials and label them.

3. An amlodipine benazepril capsule according to claim 1, characterized in that: The filler is any one of starch and dextrin, the disintegrant is sodium carboxymethyl starch, and the lubricant is magnesium stearate.

4. The method for preparing an amlodipine benazepril capsule according to claim 2, characterized in that: In step S2, the mixing time of the mixer is 15-20 minutes, and the mixing ratio of starch to sugar water is 1:

1.

5. The method for preparing an amlodipine benazepril capsule according to claim 2, characterized in that: In step S3, the rotation speed of the preliminary mixing is 20-30 rpm, and the mixing time is 15-30 minutes.

6. The method for preparing amlodipine benazepril capsules according to claim 2, characterized in that: In step S5, the auxiliary materials are mixed and stirred again, and the stirring time is 5-10 minutes.

7. The method for preparing amlodipine benazepril capsules according to claim 2, characterized in that: In step S6, the mesh size of the oscillating granulator is 80-100 mesh.

8. The method for preparing amlodipine benazepril capsules according to claim 2, characterized in that: In step S7, the drying temperature of the oven is 40-60° C., and the drying time is 3-5 hours.

9. The method for preparing amlodipine benazepril capsules according to claim 2, characterized in that: In step S8, the filling volume inside the capsule shell is 1.37-1.45 ml.

10. The method for preparing amlodipine benazepril capsules according to claim 2, characterized in that: In step S8, the filling speed of the capsule filling agent is 3000-7000 capsules / minute.

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