阅读说明：本技术 一种铝碳酸镁咀嚼片及其制备方法 (Hydrotalcite chewable tablet and preparation method thereof ) 是由 周红建 李俊霞 刘振民 田广林 芦钦伟 李丽 危雪平 王美玲 王升 刘松 王志杰 于 2021-01-12 设计创作，主要内容包括：本发明提供了一种铝碳酸镁咀嚼片及其制备方法,本发明提供的方法通过高剪切湿法制粒工艺,将经过微粉化处理的铝碳酸镁原料药与稀释剂制备成颗粒,将得到的颗粒与润滑剂及矫味剂混合后制备成片剂,得到铝碳酸镁咀嚼片；本发明可提高铝碳酸镁咀嚼片的制酸速度,提高产品质量；配合处方及制粒工艺,得到口感较好的铝碳酸镁咀嚼片,增强患者顺应性；采用本发明得到的产品,质量稳定,且该制备方法适用于放大生产。(The invention provides a hydrotalcite chewable tablet and a preparation method thereof, the method provided by the invention prepares micronized hydrotalcite bulk drug and diluent into granules by a high-shear wet granulation process, and prepares tablets after mixing the obtained granules with lubricant and flavoring agent to obtain the hydrotalcite chewable tablet; the invention can improve the acid making speed of the hydrotalcite chewable tablet and improve the product quality; the hydrotalcite chewable tablet with good taste is obtained by matching with a prescription and a granulating process, so that the compliance of a patient is enhanced; the product obtained by the invention has stable quality, and the preparation method is suitable for large-scale production.)

1. A hydrotalcite chewable tablet is characterized in that: the raw materials comprise 50 percent of micronized hydrotalcite, 47.5 to 49.5 percent of diluent, 0.5 to 2.0 percent of lubricant and 0 to 0.5 percent of flavoring agent.

2. The hydrotalcite chewable tablet of claim 1, wherein: the treatment method of the micronized hydrotalcite comprises the following steps: the particle diameter D of the crushed raw material medicine is obtained by adopting a jet mill through crushing equipment₉₀The thickness is controlled to be 15-10 μm.

3. The hydrotalcite chewable tablet of claim 1, wherein: the diluent is one or the combination of more than two of mannitol, lactose and corn starch.

4. The hydrotalcite chewable tablet of claim 1, wherein: the lubricant is one of magnesium stearate or calcium stearate.

5. The hydrotalcite chewable tablet of claim 1, wherein: the flavoring agent is one or more of saccharin sodium, peppermint essence and orange essence.

6. A preparation method of a hydrotalcite chewable tablet is characterized in that: comprises the following steps

(1) According to specification D₉₀50 percent of aluminum magnesium carbonate micronized at 15 mu m to 10 mu m, 47.5 to 49.5 percent of diluent, 0.5 to 2.0 percent of lubricant and 0 to 0.5 percent of flavoring agent are weighed according to the proportion;

(2) premixing: putting the magnesium aluminocarbonate subjected to micronization in the step (1) and a diluent into a high-shear wet-process granulator for mixing;

(3) and (3) granulating: preparing the raw materials prepared in the step (2) into wet granules by using purified water as a wetting agent through a high-shear wet granulator;

(4) wet granulation: granulating the wet granules obtained in the step (3) by using a swinging granulator;

(5) and (3) drying: drying the wet and granulated particles obtained in the step (4) by using a fluidized bed, wherein the drying air inlet temperature is 50-70 ℃;

(6) dry granulation: finishing the dried granules obtained in the step (5) by using a swinging granulator;

(7) total mixing: putting the granules obtained in the step (6) and the lubricant and the flavoring agent weighed in the step (1) into a multidirectional motion mixer for mixing;

(8) tabletting: and (4) preparing tablets from the mixed raw materials obtained in the step (7) by using a high-speed tabletting machine.

7. The method for preparing the hydrotalcite chewable tablet according to claim 6, wherein the step of: the premixing time in the step (2) is 5-15 minutes, and the total mixing time in the step (7) is 5-10 minutes.

8. The method for preparing the hydrotalcite chewable tablet according to claim 6, wherein the step of: the purified water in the step (3) is added in an atomized manner.

9. The method for preparing the hydrotalcite chewable tablet according to claim 6, wherein the step of: the mesh number of the wet whole grain screen used in the step (4) is 10-20 meshes, and the mesh number of the dry whole grain screen used in the step (6) is 14-24 meshes.

Technical Field

The invention relates to the technical field of medicinal preparations, in particular to an aluminum magnesium carbonate chewable tablet and a preparation method thereof.

Background

Magnesium aluminocarbonate (Hydrotalcite), chemical name: basic magnesium aluminocarbonate tetrahydrate, molecular formula: al (Al)₂Mg₆(OH)₁₆CO_3·4H₂O。

The chemical formula is as follows:

the hydrotalcite chewable tablet is suitable for acute and chronic gastritis, reflux esophagitis, peptic ulcer, heartburn and stomach discomfort related to gastric acid, can relieve symptoms such as heartburn, acid regurgitation, nausea, emesis and abdominal distention caused by hyperchlorhydria, and can prevent gastric mucosa injury of non-steroidal drugs.

The hydrotalcite chewable tablet belongs to antacid drugs, and when the quality of the drugs is evaluated, the antacid capacity index of the drugs not only comprises the acid making capacity item in pharmacopeia standard, but also needs to be examined for the acid making speed; at present, chewable tablets prepared by using domestic magnesium aluminate bulk drugs have the phenomenon of slow acid preparation speed to different degrees, and the quality is inferior to that of the originally ground product; in addition to this, the taste of chewable tablets is an important item to be focused on in order to improve patient compliance, and various solutions have been developed to address the above problems.

The Chinese patent CN200710093165.8 micronizes the hydrotalcite raw material and mannitol, the preparation process is firstly granulated by a high-shear wet method and then granulated by one step, the process is complex, the consumed time is long, the preparation is not suitable for large-scale flow line production, the preparation has the effect taking time of 10min, and the effect taking time is still long.

The Chinese patent CN201010584531.1 adopts a powder direct pressing process, and combines microcrystalline cellulose and crosslinked carboxymethyl starch sodium as a disintegrating agent, so that the acid making speed can be increased, but the improvement effect on the acid making speed is not stable.

The Chinese patent CN201210001044.7 uses micronized bulk drug to increase the disintegration speed by adding sodium dodecyl sulfate in the prescription, but the tablet prepared by the proposal can generate gas in the acid making process and can aggravate abdominal distension.

Chinese patent CN201610610562.7 adopts a wet granulation tabletting process to prepare the hydrotalcite chewable tablet, and does not pay attention to the acid making speed of the product.

The Chinese patent CN201811603597.3 adopts a direct powder tabletting process to prepare the hydrotalcite chewable tablet, only pays attention to the acidity and taste of the product, and does not pay attention to the acidity preparation speed of the product.

Chinese patents CN201810022721.0 and CN202010321155.0 improve the disintegration rate by selecting and proportioning the filler and the disintegrating agent, thereby improving the acid making rate, but the taste is still not ideal.

Based on the problems in the prior art, the hydrotalcite chewable tablet which has high acidification speed, stable quality and good taste and is suitable for industrial mass production and the preparation process thereof need to be developed.

Disclosure of Invention

The invention aims to overcome the defects in the prior art and provides a hydrotalcite chewable tablet and a preparation method thereof.

The invention is realized by the following technical scheme: a hydrotalcite chewable tablet comprises the following raw materials: micronized hydrotalcite, diluent, lubricant and flavoring agent.

Preferably, the raw materials are in the following ratio: 50% of micronized hydrotalcite, 47.5-49.5% of diluent, 0.5-2.0% of lubricant and 0-0.5% of flavoring agent.

Preferably, the treatment method of the micronized hydrotalcite comprises the following steps: the particle diameter D of the crushed raw material medicine is obtained by adopting a jet mill through crushing equipment₉₀The thickness is controlled to be 15-10 μm.

Preferably, the diluent is one or the combination of more than two of mannitol, lactose and corn starch.

Preferably, the lubricant is one of magnesium stearate or calcium stearate.

Preferably, the flavoring agent is one or a combination of more than two of saccharin sodium, mint essence and orange essence.

A preparation method of a hydrotalcite chewable tablet comprises the following steps:

(1) the raw materials are weighed according to the proportion of 50 percent of micronized hydrotalcite, 47.5 to 49.5 percent of diluent, 0.5 to 2.0 percent of lubricant and 0 to 0.5 percent of flavoring agent.

(2) Premixing: and (2) putting the magnesium aluminocarbonate subjected to micronization in the step (1) and a diluent into a high-shear wet-process granulator for mixing.

(3) And (3) granulating: preparing the raw material prepared in step (2) into wet granules by a high shear wet granulator using purified water as a wetting agent.

(4) Wet granulation: and (4) granulating the wet granules obtained in the step (3) by using a swinging granulator.

(5) And (3) drying: and (3) drying the wet-sized particles obtained in the step (4) by using a fluidized bed, wherein the drying air inlet temperature is 50-70 ℃.

(6) Dry granulation: and (5) finishing the dried granules obtained in the step (5) by using a swing granulator.

(7) Total mixing: and (3) putting the granules obtained in the step (6) and the lubricant and the flavoring agent weighed in the step (1) into a multidirectional motion mixer for mixing.

(8) Tabletting: and (4) preparing tablets from the mixed raw materials obtained in the step (7) by using a high-speed tabletting machine.

Preferably, the premixing time in the step (2) is 5-15 minutes, and the total mixing time in the step (7) is 5-10 minutes.

Preferably, the purified water in step (3) is added by atomization.

Preferably, the mesh number of the wet whole grain sieve used in the step (4) is 10 to 20 meshes, and the mesh number of the dry whole grain sieve used in the step (6) is 14 to 24 meshes.

The functions and characteristics of the raw materials in the technical scheme are as follows:

aluminum magnesium carbonate: powder; the pharmacological effects include: neutralizing gastric acid: the product can maintain the pH value of gastric juice between 3 and 5, neutralize 99 percent of gastric acid, inactivate 80 percent of pepsin and has rapid, mild and lasting antacid effect; protecting gastric mucosa: the product can increase synthesis of prostaglandin E2, enhance barrier function of gastric mucosa, promote release of epidermal growth factor in gastric mucosa, increase content of phospholipid in hydrophobic layer of lower layer of mucus, and prevent gastric mucosa damage caused by H + reverse osmosis; ③ the product can absorb and bind pepsin, directly inhibit the activity of pepsin, is beneficial to the restoration of ulcer surfaces, and can also bind bile acid and absorb lysophosphatidylcholine to prevent the substances from damaging and destroying gastric mucosa.

Mannitol: has a chemical formula of C₆H₁₄O₆Is a sugar alcohol; is easily soluble in water, is white crystalline powder, and has sweet taste similar to sucrose; as excipient for tablet, mannitol has no hygroscopicity, quick drying, good chemical stability, good taste, and good granulation propertyAnd the like, and is used for most of tablets such as anticancer drugs, antibacterial drugs, antihistamines, vitamins and the like. In addition, it is also used for chewable tablets such as sobering drugs and mouth coolants.

Lactose: has a chemical formula of C₁₂H₂₂O₁₁Is disaccharide composed of glucose and galactose, white crystal or crystalline powder; is mainly used for preparing infant food and preparing medicines, such as tablets and medicinal powder, and is used as diluent.

Corn starch: also known as cornstarch, is an important excipient of medicines, and corn starch is mostly used as a filler and a binder in tablets produced by pharmaceutical factories in various countries in the early days.

Magnesium stearate: has a chemical formula of C₃₆H₇₀MgO₄Is an organic compound, which is white non-gritty fine powder; mainly used as lubricant, anti-sticking agent and glidant; can be used as glidant in direct compression, filter aid, clarifier and foam-dropping agent, and suspending agent and thickening agent for liquid preparation.

Calcium stearate: is an organic compound with a molecular formula of C₃₆H₇₀CaO₄White powder, insoluble in water, can be used as a water repellent, a lubricant, a plastic additive and the like.

Sodium saccharin: has a chemical formula of C₇H₅NO₃SNa is an organic chemical synthetic product and is a food additive; in sweetness, the anion decomposed from saccharin sodium has strong sweetness, but has no sweetness in molecular state; the saccharin sodium has high solubility and dissociation degree, so the saccharin sodium has strong sweet taste.

Mint essence: oily liquid with mint characteristic fragrance is a food additive; has pure mint flavor, strong cool feeling, fresh and clear aroma and is refreshing.

Orange essence: is an essence which mainly imitates the fragrance characteristic of orange pulp. The key components for forming the orange fragrance are aldehydes, alcohols and esters; wherein the trace components for generating the fresh and sweet fruity flavor are ethyl butyrate, ethyl 2-methylbutyrate, sinenseal and the like.

The invention has the beneficial effects that: the method provided by the invention adopts a high-shear wet granulation process, the magnesium aluminum carbonate bulk drug subjected to micronization and a diluent are prepared into granules, and the obtained granules are mixed with a lubricant and a flavoring agent to prepare tablets so as to obtain the magnesium aluminum carbonate chewable tablets; the invention can improve the acid making speed of the hydrotalcite chewable tablet and improve the product quality; the hydrotalcite chewable tablet with good taste is obtained by matching with a prescription and a granulating process, so that the compliance of a patient is enhanced; the product obtained by the invention has stable quality, and the preparation method is suitable for large-scale production.

Detailed Description

In the description of the present invention, it is also to be noted that, unless explicitly stated or limited otherwise; the specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art.

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments; all other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

A hydrotalcite chewable tablet comprises the following raw materials: micronized hydrotalcite, diluent, lubricant and flavoring agent.

The treatment method of the micronized hydrotalcite comprises the following steps: the particle diameter D of the crushed raw material medicine is obtained by adopting a jet mill through crushing equipment₉₀The thickness is controlled to be 15-10 μm.

The diluent is one or two or three of mannitol, lactose and corn starch.

The lubricant is one of magnesium stearate or calcium stearate.

The flavoring agent is one or two or three of saccharin sodium, peppermint essence and orange essence.

Examples 1-4 were prepared using the following wet granulation process:

a preparation method of a hydrotalcite chewable tablet comprises the following steps:

(1) the raw materials are weighed according to the proportion of 50 percent of micronized hydrotalcite, 47.5 to 49.5 percent of diluent, 0.5 to 2.0 percent of lubricant and 0 to 0.5 percent of flavoring agent.

(2) Premixing: and (2) putting the magnesium aluminocarbonate subjected to micronization in the step (1) and a diluent into a high-shear wet-process granulator for mixing.

(3) And (3) granulating: preparing the raw material prepared in step (2) into wet granules by a high shear wet granulator using purified water as a wetting agent.

(4) Wet granulation: and (4) granulating the wet granules obtained in the step (3) by using a swinging granulator.

(5) And (3) drying: and (3) drying the wet-sized particles obtained in the step (4) by using a fluidized bed, wherein the drying air inlet temperature is 50-70 ℃.

(6) Dry granulation: and (5) finishing the dried granules obtained in the step (5) by using a swing granulator.

(7) Total mixing: and (3) putting the granules obtained in the step (6) and the lubricant and the flavoring agent weighed in the step (1) into a multidirectional motion mixer for mixing.

(8) Tabletting: and (4) preparing tablets from the mixed raw materials obtained in the step (7) by using a high-speed tabletting machine.

The premixing time in the step (2) is 5-15 minutes, and the total mixing time in the step (7) is 5-10 minutes.

The purified water in the step (3) is added in an atomized manner.

The mesh number of the wet whole grain screen used in the step (4) is 10-20 meshes, and the mesh number of the dry whole grain screen used in the step (6) is 14-24 meshes.

Example 1

The formulation is shown in table 1:

table 1:

in the preparation process, the crushing degree of the hydrotalcite raw material used in the step (1) is below 10 mu m; in the step (2), the premixing time is 5 min; in the step (4), the mesh number of the wet whole grain screen is 16 meshes; in the step (5), the air inlet temperature of the fluidized bed is 60 ℃, and in the step (6), the mesh number of the dry whole-grain screen is 18 meshes; in the step (7), the total mixing time is 5 min.

Preparing into granule by the above preparation process, and further preparing into tablet; and (3) detecting the powder chemical properties of the intermediate after the total mixing in the step (7), the acid making capacity and the acid making curve of the tablet, comparing the acid making curve with the Daxi tablet (approval document: Chinese medicine standard H20013410, production enterprise: Bayer medicine health-care Co., Ltd.) of the original product, and obtaining a detection result shown in Table 2.

Table 2:

from the above comparative data, it can be seen that the pharmaceutical formulation prepared according to the present technology can achieve approximately the same antacid effect as the "darxi" tablet under the same conditions.

Example 2

The formulation is shown in table 3:

table 3:

in the preparation process, the crushing degree of the hydrotalcite raw material used in the step (1) is below 15 mu m; in the step (2), the premixing time is 10 min; in the step (4), the mesh number of the wet whole grain screen is 10 meshes; in the step (5), the air inlet temperature of the fluidized bed is 70 ℃; in the step (6), the mesh number of the dry whole granule screen is 16 meshes; in the step (7), the total mixing time is 5 min.

Preparing into granule by the above preparation process, and further preparing into tablet; and (3) detecting the powder chemical properties of the intermediate after the total mixing in the step (7), the acid making capacity and the acid making curve of the tablet, comparing the acid making curve with the Daxi tablet (approval document: Chinese medicine standard H20013410, production enterprise: Bayer medicine health-care Co., Ltd.) of the original product, and obtaining a detection result shown in Table 4.

Table 4:

from the above comparative data, it can be seen that the pharmaceutical formulation prepared according to the present technology can achieve approximately the same antacid effect as the "darxi" tablet under the same conditions.

Example 3

The formulation is shown in table 5:

table 5:

in the preparation process, the crushing degree of the hydrotalcite raw material used in the step (1) is below 12 mu m; in the step (2), the premixing time is 10 min; in the step (4), the mesh number of the wet whole grain screen is 16 meshes; in the step (5), the air inlet temperature of the fluidized bed is 60 ℃; in the step (6), the mesh number of the dry whole grain sieve is 20 meshes; in the step (7), the total mixing time is 8 min.

Preparing into granule by the above preparation process, and further preparing into tablet; and (3) detecting the powder chemical properties of the intermediate after the total mixing in the step (7), the acid making capacity and the acid making curve of the tablet, comparing the acid making curve with the Daxi tablet (approval document: Chinese medicine standard H20013410, production enterprise: Bayer medicine health-care Co., Ltd.) of the original product, and obtaining a detection result shown in Table 6.

Table 6:

from the above comparative data, it can be seen that the pharmaceutical formulation prepared according to the present technology can achieve approximately the same antacid effect as the "darxi" tablet under the same conditions.

Example 4

The formulation is shown in table 7:

table 7:

in the preparation process, the crushing degree of the hydrotalcite raw material used in the step (1) is below 10 mu m; in the step (2), the premixing time is 8 min; in the step (5), the mesh number of the wet whole grain screen is 18 meshes; in the step (6), the air inlet temperature of the fluidized bed is 70 ℃; in the step (7), the mesh number of the dry whole grain sieve is 20 meshes; in the step (8), the total mixing time is 5 min.

Preparing into granule by the above preparation process, and further preparing into tablet; the powder properties of the intermediate after the final mixing in the step (7) and the acid making power and acid making curve of the tablet are detected, the acid making curve is compared with the original grinding product Daxi tablet (approval document: Chinese medicine standard H20013410, production enterprise: Bayer medicine health Limited company), and the detection results are shown in Table 8.

Table 8:

from the above comparative data, it can be seen that the pharmaceutical formulation prepared according to the present technology can achieve approximately the same antacid effect as the "darxi" tablet under the same conditions.

Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments or portions thereof without departing from the spirit and scope of the invention.