Calcium carbonate D3 chewable tablet and preparation method thereof

Abstract

The invention discloses a calcium carbonate D3 chewable tablet and a preparation method, and the chewable tablet comprises the following components in parts by mass: 100-120 parts of calcium carbonate, 30-40 parts of mannitol, 0.5-1 part of vitamin D3, 8-12 parts of pectin, 10-15 parts of lactulose, 1-3 parts of magnesium stearate, and 1-5 parts of citric acid. The preparation method comprises the following steps: adding water into pectin to prepare a pectin solution, adding water into calcium carbonate to prepare a calcium carbonate suspension, mixing the calcium carbonate suspension with the pectin solution, and freeze-drying to obtain pectin-embedded calcium carbonate dry powder; the preparation method comprises the following steps: mixing calcium carbonate dry powder, mannitol, vitamin D3, magnesium stearate and citric acid, adding lactulose, carrying out wet granulation to obtain particles, drying to obtain calcium carbonate particles, and tabletting to obtain the product. According to the invention, the variety and dosage of auxiliary materials are reduced, and the prepared calcium carbonate D3 chewable tablet is appropriate in hardness, good in taste and stable in product quality.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, relates to chewable tablets and a preparation method thereof, and in particular to a calcium carbonate D3 chewable tablet and a preparation method thereof. Background Art

[0002] Calcium carbonate is an important regulator of bone metabolism, which can maintain normal excitability of nerves and muscles and reduce capillary permeability. It is clinically used to prevent and treat calcium deficiency diseases such as osteoporosis, tetany, bone dysplasia, rickets, and calcium supplementation for children, pregnant and lactating women, menopausal women, and the elderly.

[0003] Calcium carbonate is a raw material for calcium supplementation. It has high calcium content, low price and good absorption in the body. In order to promote absorption, vitamin D3 is often added to the components to prepare calcium carbonate D3 compound preparations, such as calcium carbonate D3 chewable tablets. However, calcium carbonate has poor fluidity and is difficult to directly compress into tablets. It is necessary to add adhesives to increase viscosity. At the same time, calcium carbonate has a poor taste, astringency and a strong sense of gravel, so other auxiliary materials such as flavors need to be added to the components to improve the taste and aroma.

[0004] However, as people pay more attention to the safety and health issues of additives, products containing multiple additives are increasingly questioned, so it is necessary to optimize the components of calcium carbonate D3 chewable tablets and reduce the amount of additives without affecting its taste and product quality. Summary of the invention

[0005] The purpose of the present invention is to optimize the components of calcium carbonate D3 chewable tablets, study a suitable preparation process, and reduce the amount of additives without affecting the taste and product quality.

[0006] The technical solution adopted by the present invention provides a calcium carbonate D3 chewable tablet, the key point is that, measured by weight, the components of the chewable tablet include: 100 to 120 parts of calcium carbonate, 30 to 40 parts of mannitol, 0.5 to 1 part of vitamin D3, 8 to 12 parts of pectin, 10 to 15 parts of lactulose, 1 to 3 parts of magnesium stearate, and 1 to 5 parts of citric acid.

[0007] Preferably, the components of the above-mentioned chewable tablet include, by weight: 110 parts of calcium carbonate, 35 parts of mannitol, 0.8 parts of vitamin D3, 10 parts of pectin, 12 parts of lactulose, 2 parts of magnesium stearate, and 3 parts of citric acid.

[0008] Specifically, the mass ratio of the calcium carbonate to pectin is 8 to 15:1.

[0009] Furthermore, the components of the above-mentioned chewable tablets also include 0.1 to 0.3 parts of flavor.

[0010] A preparation method of a calcium carbonate D3 chewable tablet, the key of which is to prepare a pectin solution by adding pectin to water, prepare a calcium carbonate suspension by adding calcium carbonate to water, mix the suspension with the pectin solution, and obtain pectin-encapsulated calcium carbonate dry powder by freeze-drying; mix the calcium carbonate dry powder, mannitol, vitamin D3, magnesium stearate and citric acid, add lactulose, obtain granules by wet granulation, obtain calcium carbonate granules after drying, and obtain calcium carbonate D3 chewable tablets by tableting.

[0011] Specifically, the mass concentration of pectin in the pectin solution is 8% to 12%, and the mass concentration of the calcium carbonate suspension is 70% to 80%.

[0012] Furthermore, the specific operation of the above freeze drying is: spread the material on a tray with a thickness of 0.4 cm to 0.6 cm, put it into a freeze dryer, control the cold trap temperature to -50°C to -40°C, the vacuum degree of the drying chamber to 2Pa to 4Pa, and dry it for 20h to 28h.

[0013] Furthermore, the calcium carbonate dry powder, mannitol, vitamin D3, magnesium stearate and citric acid are mixed at a rotation speed of 10 rpm to 15 rpm, and the mixing time is 10 min to 15 min.

[0014] Preferably, the tabletting pressure is 4 kN to 6 kN.

[0015] Compared with the prior art, the present invention has the following beneficial effects:

[0016] The components of the calcium carbonate D3 chewable tablet of the present invention include calcium carbonate and vitamin D3 as raw materials, mannitol as a filler, magnesium stearate as a lubricant, lactulose as a binder, and also as a flavoring agent together with citric acid to adjust the acidity and sweetness of the sample. In the present invention, no flavoring is required, and the smell and taste can still meet the requirements.

[0017] The present invention uses pectin to embed calcium carbonate, and prepares pectin-embedded calcium carbonate dry powder through freeze drying, which greatly reduces the astringency and grittiness of calcium carbonate itself, improves the mouthfeel, and improves the stability of calcium carbonate. This is because pectin loses water quickly during freeze drying, long chains break and form a microporous structure, which not only does not produce a sticky feeling when taken, but also its microporous structure helps to improve the dissolution of the sample, making the sample easier to absorb. Pectin itself also has a certain viscosity, so it also helps to reduce the amount and type of adhesive used, therefore, the particles obtained by the present invention are easier to agglomerate into sheets, and it is not necessary to use excessive pressure during tableting to obtain a product with moderate hardness and standard brittleness. DETAILED DESCRIPTION

[0018] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0019] If no specific conditions are specified in the examples, the experiments can be carried out under conventional conditions; if no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0020] Embodiment 1

[0021] A calcium carbonate D3 chewable tablet comprises, by weight, 110 parts of calcium carbonate, 35 parts of mannitol, 0.8 parts of vitamin D3, 10 parts of pectin, 12 parts of lactulose, 2 parts of magnesium stearate and 3 parts of citric acid.

[0022] The specific preparation steps of the above-mentioned calcium carbonate D3 chewable tablets are as follows:

[0023] S1. Weigh 10 parts of pectin, add deionized water, and prepare a pectin solution with a mass concentration of 10%;

[0024] S2, 110 parts of calcium carbonate, add deionized water to prepare a calcium carbonate suspension with a mass concentration of 78%;

[0025] S3, the above pectin solution and calcium carbonate suspension were mixed, stirred, the stirring speed was controlled to be 15 rpm, the stirring time was 15 min, and the calcium carbonate pectin feed solution was obtained;

[0026] S4, spread the calcium carbonate pectin liquid on the tray of the freeze dryer, control the liquid thickness to 0.5 cm, put it into the freeze dryer, control the cold trap temperature to -45 ° C, the vacuum degree of the drying chamber to 3 Pa, dry for 24 hours, obtain pectin-embedded calcium carbonate dry powder, and pass through a 60-mesh sieve to size the particles;

[0027] S5, mixing the prepared calcium carbonate dry powder, 35 parts of mannitol, 0.8 parts of vitamin D3, 2 parts of stearic acid and 3 parts of citric acid, controlling the mixing speed to 12 rpm and the mixing time to 12 min;

[0028] S6. Add 12 parts of lactulose to the uniformly mixed material. Lactulose is liquid. Deionized water can be added appropriately. Wet granules are obtained by wet granulation. Calcium carbonate particles are obtained after drying. The tableting pressure is controlled to be 5 kN. Calcium carbonate D3 chewable tablet sample 1 is obtained by tableting.

[0029] Embodiment 2

[0030] A calcium carbonate D3 chewable tablet comprises, by weight, 100 parts of calcium carbonate, 30 parts of mannitol, 1 part of vitamin D3, 12 parts of pectin, 10 parts of lactulose, 3 parts of magnesium stearate and 5 parts of citric acid.

[0031] The specific preparation steps of the above calcium carbonate D3 chewable tablets are:

[0032] S1. Weigh 12 parts of pectin, add deionized water, and prepare a pectin solution with a mass concentration of 8%;

[0033] S2, 100 parts of calcium carbonate, add deionized water to prepare a calcium carbonate suspension with a mass concentration of 80%;

[0034] S3, the pectin solution and the calcium carbonate suspension were mixed, stirred, the stirring speed was controlled to 18 rpm, the stirring time was 10 min, and the calcium carbonate pectin liquid was obtained;

[0035] S4, spread the calcium carbonate pectin liquid on the tray of the freeze dryer, control the liquid thickness to 0.4 cm, put it into the freeze dryer, control the cold trap temperature to -50 ° C, the vacuum degree of the drying chamber to 2 Pa, dry for 26 hours, obtain pectin-embedded calcium carbonate dry powder, and pass it through a 60-mesh sieve to size the particles;

[0036] S5, mixing the prepared calcium carbonate dry powder, 30 parts of mannitol, 1 part of vitamin D3, 3 parts of stearic acid and 5 parts of citric acid, controlling the mixing speed to 11 rpm and the mixing time to 14 min;

[0037] S6. Add 10 parts of lactulose to the uniformly mixed material. Lactulose is liquid. Deionized water can be added appropriately. Wet granules are obtained by wet granulation. Calcium carbonate particles are obtained after drying. The tableting pressure is controlled to 6 kN. Calcium carbonate D3 chewable tablet sample 2 is obtained by tableting.

[0038] Embodiment 3

[0039] A calcium carbonate D3 chewable tablet comprises, by weight, 120 parts of calcium carbonate, 40 parts of mannitol, 0.5 parts of vitamin D3, 8 parts of pectin, 15 parts of lactulose, 1 part of magnesium stearate and 1 part of citric acid.

[0040] The specific preparation steps of the above-mentioned calcium carbonate D3 chewable tablets are as follows:

[0041] S1. Weigh 8 parts of pectin, add deionized water, and prepare a pectin solution with a mass concentration of 12%;

[0042] S2, 120 parts of calcium carbonate, add deionized water to prepare a calcium carbonate suspension with a mass concentration of 70%;

[0043] S3, the pectin solution and the calcium carbonate suspension were mixed, stirred, and the stirring speed was controlled to be 15 rpm, and the stirring time was 12 min to obtain a calcium carbonate pectin liquid;

[0044] S4, spread the calcium carbonate pectin liquid on the tray of the freeze dryer, control the liquid thickness to 0.6 cm, put it into the freeze dryer, control the cold trap temperature to -50 ° C, the vacuum degree of the drying chamber to 4 Pa, dry for 22 hours, obtain pectin-embedded calcium carbonate dry powder, and pass through a 60-mesh sieve to size particles;

[0045] S5, mixing the prepared calcium carbonate dry powder, 40 parts of mannitol, 0.5 parts of vitamin D3, 1 part of stearic acid and 1 part of citric acid, controlling the mixing speed to 10 rpm and the mixing time to 15 min;

[0046] S6. Add 15 parts of lactulose to the uniformly mixed material. Lactulose is liquid. Deionized water can be added appropriately. In this embodiment, no water is added. Wet granules are obtained by wet granulation. Calcium carbonate particles are obtained after drying. The tableting pressure is controlled to 4 kN. Calcium carbonate D3 chewable tablet sample 3 is obtained by tableting.

[0047] Embodiment 4

[0048] A calcium carbonate D3 chewable tablet comprises, by weight, 108 parts of calcium carbonate, 32 parts of mannitol, 0.8 parts of vitamin D3, 10 parts of pectin, 12 parts of lactulose, 2 parts of magnesium stearate, 3 parts of citric acid and 0.1 part of flavor.

[0049] The specific preparation steps of the above-mentioned calcium carbonate D3 chewable tablets are as follows:

[0050] S1. Weigh 10 parts of pectin, add deionized water, and prepare a pectin solution with a mass concentration of 10%;

[0051] S2, 108 parts of calcium carbonate, add deionized water to prepare a calcium carbonate suspension with a mass concentration of 75%;

[0052] S3, the pectin solution and the calcium carbonate suspension were mixed, stirred, and the stirring speed was controlled to be 15 rpm, and the stirring time was 10 min to obtain a calcium carbonate pectin liquid;

[0053] S4, spread the calcium carbonate pectin liquid on the tray of the freeze dryer, control the liquid thickness to 0.4 cm, put it into the freeze dryer, control the cold trap temperature to -40 ° C, the vacuum degree of the drying chamber to 2 Pa, dry for 28 hours, obtain pectin-embedded calcium carbonate dry powder, and pass it through a 60-mesh sieve to size the particles;

[0054] S5, the prepared calcium carbonate dry powder, 32 parts of mannitol, 0.8 parts of vitamin D3, 2 parts of stearic acid and 3 parts of citric acid are mixed, the mixing speed is controlled to be 15 rpm, and the mixing time is 10 min;

[0055] S6. Add 12 parts of lactulose to the uniformly mixed material. Lactulose is liquid. Deionized water can be added appropriately. Wet granules are obtained by wet granulation. Calcium carbonate particles are obtained after drying. The tableting pressure is controlled to 5 kN. Sample 4 of calcium carbonate D3 chewable tablets containing flavor is obtained by tableting.

[0056] Embodiment 5

[0057] A calcium carbonate D3 chewable tablet comprises, by weight, 115 parts of calcium carbonate, 38 parts of mannitol, 0.8 parts of vitamin D3, 10 parts of pectin, 11 parts of lactulose, 1 part of magnesium stearate, 1 part of citric acid and 0.3 parts of flavor.

[0058] The specific preparation steps of the above-mentioned calcium carbonate D3 chewable tablets are as follows:

[0059] S1. Weigh 10 parts of pectin, add deionized water, and prepare a pectin solution with a mass concentration of 12%;

[0060] S2, 115 parts of calcium carbonate, add deionized water to prepare a calcium carbonate suspension with a mass concentration of 78%;

[0061] S3, the above pectin solution and calcium carbonate suspension were mixed, stirred, the stirring speed was controlled to be 14 rpm, the stirring time was 13 min, and the calcium carbonate pectin feed solution was obtained;

[0062] S4, spread the calcium carbonate pectin liquid on the tray of the freeze dryer, control the liquid thickness to 0.5 cm, put it into the freeze dryer, control the cold trap temperature to -45 ° C, the vacuum degree of the drying chamber to 4 Pa, dry for 20 hours, obtain pectin-embedded calcium carbonate dry powder, and pass it through a 60-mesh sieve to size the particles;

[0063] S5, mixing the prepared calcium carbonate dry powder, 38 parts of mannitol, 0.8 parts of vitamin D3, 1 part of stearic acid and 1 part of citric acid, controlling the mixing speed to 11 rpm and the mixing time to 13 min;

[0064] S6. Add 11 parts of lactulose to the uniformly mixed material. Lactulose is liquid. Deionized water can be added appropriately. Wet granules are obtained by wet granulation. Calcium carbonate particles are obtained after drying. The tableting pressure is controlled to be 5 kN. Sample 5 of calcium carbonate D3 chewable tablets containing flavor is obtained by tableting.

[0065] Analysis and testing

[0066] 1. Dissolution, hardness and friability testing

[0067] The dissolution (30 min), hardness and friability of the calcium carbonate D3 chewable tablet samples prepared in the examples and the comparative examples (commercially available reference products 1 and 2) were tested. The test results are shown in Table 1.

[0068] Table 1: Dissolution and hardness test results

[0069]

[0070] It can be seen from the results in Table 1 that the hardness of the samples of the present invention is smaller than that of the commercially available samples, but the friability test results thereof still meet the requirements of the relevant standards. At the same time, the solubility of the samples of the present invention is higher, while the solubility of the commercially available samples is poor.

[0071] 2. Sensory test

[0072] The sensory evaluation table is as follows:

[0073] Table 2: Sensory evaluation table

[0074] Evaluation score odor hardness taste Taste 5 Nice smell Suitable hardness, easy to chew Sweet taste No grit 4 Good smell Moderate hardness, easy to chew Good taste Almost no grit 3 No odor, normal smell Too hard, difficult to chew No odor, average taste Slightly gritty 2 There is a strange smell Too soft, slightly chewy There is a strange smell Gritty 1 Severe odor Very low hardness, no chewing sensation Severe odor Severe grittiness

[0075] Ten subjects were randomly selected, with an average age of 33.1 years old, including 4 males and 6 females, and the calcium carbonate D3 chewable tablet samples prepared in the examples and the comparative examples (commercially available reference products 1 and 2) were subjected to sensory evaluation and scoring. The results are shown in Table 3.

[0076] Table 3: Sensory evaluation results

[0077] Samples to be tested odor hardness taste Taste Total score Sample 1 4.7 4.9 4.8 4.7 19.1 Sample 2 4.5 4.5 4.9 4.8 18.7 Sample 3 4.6 4.8 4.7 4.8 18.9 Sample 4 5.0 4.7 4.8 4.7 19.2 Sample 5 4.9 4.7 4.8 4.8 19.2 Reference 1 4.9 3.7 4.8 3.6 17.0 Reference 2 5.0 3.9 4.9 3.8 17.6

[0078] As can be seen from the results in Table 3, among the samples prepared by the present invention, the evaluation score of the sample without flavor is not as high as that of the commercially available samples and the sample with flavor, but its taste and mouthfeel are very good, and even the taste score is better than that of the commercially available samples. This may be because the auxiliary materials such as lactulose and citric acid added in the present invention cooperate with each other to form a good aroma, improve the taste, and cover up the astringency of calcium carbonate. At the same time, the present invention embeds calcium carbonate with pectin, which greatly reduces the grittiness produced by calcium carbonate, so the mouthfeel is better.

[0079] 3. Sample stability test

[0080] The samples were tested under accelerated stability test conditions (temperature 40° C., relative humidity 75%). The results are shown in Table 4.

[0081] Table 4: Stability test results

[0082]

[0083] It can be seen from the results in Table 4 that the product of the present invention is stable. Under the accelerated test conditions, the loss of the main component calcium carbonate is about 5%, the loss of vitamin D3 is about 30%, and the dissolution rate of the product is not greatly affected after 6 months of testing.

Claims

1. A calcium carbonate D3 chewable tablet, characterized in that: Calculated by weight, the components of the chewable tablet include: 100 to 120 parts of calcium carbonate, 30 to 40 parts of mannitol, 30.5 to 1 part of vitamin D, 8 to 12 parts of pectin, 10 to 15 parts of lactulose, 1 to 3 parts of magnesium stearate, and 1 to 5 parts of citric acid.

2. A calcium carbonate D3 chewable tablet according to claim 1, characterized in that: Calculated by weight, the components of the chewable tablet include: 110 parts of calcium carbonate, 35 parts of mannitol, 0.8 parts of vitamin D3, 10 parts of pectin, 12 parts of lactulose, 2 parts of magnesium stearate, and 3 parts of citric acid.

3. A calcium carbonate D3 chewable tablet according to claim 1, characterized in that: The mass ratio of the calcium carbonate to pectin is 8-15:

1.

4. A calcium carbonate D3 chewable tablet according to claim 1, characterized in that: Calculated by weight, the components of the chewable tablet also include 0.1 to 0.3 parts of flavor.

5. The method for preparing a calcium carbonate D3 chewable tablet according to any one of claims 1 to 5, characterized in that: Pectin is added with water to prepare a pectin solution, calcium carbonate is added with water to prepare a calcium carbonate suspension, the suspension is mixed with the pectin solution, and pectin-encapsulated calcium carbonate dry powder is obtained by freeze-drying; calcium carbonate dry powder, mannitol, vitamin D3, magnesium stearate and citric acid are mixed, lactulose is added, and granules are obtained by wet granulation, calcium carbonate granules are obtained after drying, and calcium carbonate D3 chewable tablets are obtained by tabletting.

6. The method for preparing a calcium carbonate D3 chewable tablet according to claim 5, characterized in that: The mass concentration of pectin in the pectin solution is 8% to 12%, and the mass concentration of the calcium carbonate suspension is 70% to 80%.

7. The method for preparing a calcium carbonate D3 chewable tablet according to claim 5, characterized in that: The specific operation of the freeze drying is: spread the material on a tray with a thickness of 0.4cm to 0.6cm, put it into a freeze dryer, control the cold trap temperature to -50℃ to -40℃, the vacuum degree of the drying chamber to 2Pa to 4Pa, and dry it for 20h to 28h.

8. The method for preparing a calcium carbonate D3 chewable tablet according to claim 5, characterized in that: The calcium carbonate dry powder, mannitol, vitamin D3, magnesium stearate and citric acid are mixed at a rotation speed of 10 rpm to 15 rpm, and the mixing time is 10 min to 15 min.

9. The method for preparing a calcium carbonate D3 chewable tablet according to claim 5, characterized in that: The tablet pressing pressure is 4kN to 6kN.

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