Calcium citrate tablet composition for improving surface smoothness as well as preparation method and application of calcium citrate tablet composition

Abstract

The invention belongs to the technical field of pharmacy, and particularly relates to a calcium citrate tablet composition for improving surface smoothness and a preparation method and application thereof. The calcium citrate tablet composition is prepared from the following raw materials in parts by weight: 58-65 parts of calcium citrate, 4.5-6 parts of casein phosphopeptides, 0.1-1 part of vitamin D3 powder, 14-28 parts of a filling agent, 12-20 parts of an adhesive, 3-5 parts of a disintegrating agent, 1-2 parts of a lubricating agent and 0.4-2 parts of a flavoring agent, the adhesive comprises polyvinyl alcohol, microcrystalline cellulose and pullulan, and the filling agent comprises D-mannitol, isomaltitol and sorbitol. By optimizing the raw material ratio, introducing a novel adhesive composition and adjusting a preparation process, the surface quality of the tablet is remarkably improved.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of pharmacy, and particularly relates to a calcium citrate tablet composition for improving surface smoothness, a preparation method thereof and application. BACKGROUND

[0002] Calcium is the most abundant mineral element in the human body. Basically, all life processes require the participation of calcium. The human body cannot synthesize calcium itself and must obtain it from the outside. Calcium intake for a long time will produce various symptoms due to various factors, which will affect normal growth and development. Calcium deficiency may have adverse effects on growth and development before it is discovered and lay the foundation for certain chronic metabolic diseases in adulthood.

[0003] Calcium citrate, also known as calcium citrate, is a kind of organic calcium, which is commonly used in the food field and often used as calcium fortifier, chelating agent, buffer and tissue coagulant, etc. Especially as a calcium fortifier, it is often added to infant formula, beverages, milk and various health products due to its mild taste and high calcium content.

[0004] As a common dietary supplement form, the appearance and texture of calcium citrate tablets are crucial to consumer acceptance. The conventional production technology in the industry generally has problems such as rough tablet surface, poor gloss and edge defects. These problems are mainly caused by the following reasons: (1) Material itself: The calcium citrate raw material itself has small density and small particle size, and has a high proportion in the formula. In the tabletting process, the adhesion is low, the powder is easy to fall off, and the stress distribution is uneven, thereby affecting the forming quality of the tablet surface.

[0005] (2) Defects of traditional formula: Traditional binders such as starch, hydroxypropyl methyl cellulose (HPMC), etc. are commonly used in conventional formulas, which can provide certain binding force, but their film-forming property and plasticity are poor, and it is difficult to form a dense and smooth surface layer in the tabletting process. Chinese patent application CN119523107A discloses a compound preparation of calcium citrate casein phosphopeptide calcium tablets, which comprises the following components by weight percentage: calcium citrate granules 90-96%, casein phosphopeptide 0.68-1.84%, vitamin D3 powder 0.08-0.16%, vitamin K2 powder 0.7-1.5%, carboxymethyl starch sodium 0.5-1.5%, magnesium stearate 0.6-1.0%, and coating premix 2-4%. Although the application focuses on the proportioning of nutritional ingredients, it does not effectively optimize the appearance quality of the tablets, resulting in defects such as powder falling off and rough surface in actual use.

[0006] (3) Traditional process limitations: The existing preparation process does not control the key parameters such as granulation particle size, drying temperature and tabletting pressure finely, and the particle flowability is poor, which further aggravates the surface defects of the tablet after tabletting. In some cases, the tabletting pressure is increased to enhance the hardness of the tablet, which may cause "top cracking" or "delamination" on the tablet surface.

[0007] Therefore, the current calcium citrate tablets generally have unstable surface quality, insufficient aesthetic degree and poor user experience in production, and need to be solved by formula optimization and process improvement. SUMMARY

[0008] In view of the deficiencies of the prior art, the present application provides a calcium citrate tablet composition for improving surface smoothness and a preparation method and application thereof. By optimizing the ratio of raw materials, introducing a new binder group and adjusting the preparation process, the surface quality of the tablet is significantly improved.

[0009] In order to achieve the above-mentioned purposes of the present application, the specific technical scheme adopted by the present application is as follows: A calcium citrate tablet composition for improving surface smoothness, the raw materials of the calcium citrate tablet composition include, by weight fraction: calcium citrate 58-65 parts, casein phosphopeptide 4.5-6 parts, vitamin D3 powder 0.1-1 part, filler 14-28 parts, binder 12-20 parts, disintegrant 3-5 parts, lubricant 1-2 parts and flavoring agent 0.4-2 parts. The binder includes polyvinyl alcohol, microcrystalline cellulose and pullulan, and the filler includes D-mannitol, isomalt and sorbitol.

[0010] Preferably, the binder includes, by weight fraction: polyvinyl alcohol 2-4 parts, microcrystalline cellulose 8-11 parts and pullulan 2-4 parts.

[0011] Preferably, the filler includes, by weight fraction: D-mannitol 5-8 parts, isomalt 1-7 parts and sorbitol 8-13 parts.

[0012] Preferably, the disintegrant is cross-linked sodium carboxymethyl cellulose; and the lubricant is magnesium stearate.

[0013] Preferably, the flavoring agent includes, by weight fraction: citric acid 0.2-1 part and essence 0.2-1 part.

[0014] The present application also relates to a preparation method of the above-mentioned calcium citrate tablet composition, comprising the following steps: (1) uniformly mixing calcium citrate, casein phosphopeptide and D-mannitol to obtain a mixture 1; (2) uniformly mixing polyvinyl alcohol and pullulan to obtain a mixture 2; (3) taking the mixture 2, adding water to make pulp, and obtaining a wetting agent; (4) spraying the wetting agent into the mixture 1, sieving, drying, and sieving again to obtain dry granules; (5) uniformly mixing isomalt, sorbitol, vitamin D3 powder, microcrystalline cellulose, disintegrating agent, flavoring agent, and the dry granules, and then adding a lubricant to obtain a mixture 3; (6) compressing the mixture 3 to obtain the calcium citrate tablet composition.

[0015] Preferably, the mass concentration of the wetting agent in step (3) is 7%-9%.

[0016] Preferably, the sieving in step (4) is sieving through a 12-16 mesh sieve, and the drying temperature is 70-75℃, and the drying is performed until the moisture content is 4%-5%.

[0017] The application also relates to the use of the calcium citrate tablet composition prepared by the above method in the preparation of a calcium citrate tablet product.

[0018] Compared with the prior art, the application has the following beneficial effects: (1) The tablet smoothness of the calcium citrate tablet composition is significantly improved, the discomfort of swallowing is reduced, and the product appearance grade is improved.

[0019] (2) The tablet hardness and friability are optimized, the shelf life is prolonged, and the damage during transportation is reduced.

[0020] (3) The disintegration time of the tablet is shortened, and the requirement of swallowing the tablet is met.

[0021] (4) The preparation process is stable, suitable for industrial production, and the cost is controllable. DETAILED DESCRIPTION

[0022] The application will be further described in detail below in combination with specific examples, and the following examples are not used to limit the application, but only to illustrate the application. Unless otherwise specified, the experimental methods in the following examples are generally performed under conventional conditions, and the materials and reagents used in the following examples are commercially available unless otherwise specified.

[0023] Calcium citrate B05, purchased from Zhengzhou Ruipu Biological Engineering Co., Ltd.; casein phosphopeptide, purchased from Hangzhou Kangyuan Food Technology Co., Ltd.; vitamin D3 powder, purchased from Xinchang Xinhewecheng Vitamin Co., Ltd.; polyvinyl alcohol 8805, purchased from Sichuan Laitex Polysciences Pharmaceutical Auxiliary Co., Ltd.; microcrystalline cellulose PH102, purchased from Huzhou Linghu Xiwang Chemical Co., Ltd.; pullulan, purchased from Shaanxi Baichuan Kangze Biological Technology Co., Ltd.; sodium carboxymethyl cellulose, purchased from Shanghai Changguang Enterprise Development Co., Ltd.; cross-linked sodium carboxymethyl cellulose, pregelatinized starch and low-substituted hydroxypropyl cellulose SH-LH21, all purchased from Anhui Shanhe Yao Yong Auxiliary Co., Ltd.

[0024] Example 1 A calcium citrate tablet composition for improving surface smoothness, the raw materials of which are as follows in parts by weight: Calcium citrate 60 parts, casein phosphopeptide 5 parts, vitamin D3 powder 0.5 part; Filling agent: D-mannitol 7 parts, isomalt 4 parts and sorbitol 10 parts; Flavoring agent: citric acid 0.5 part and kaman orange flavor 0.4 part; Binder: polyvinyl alcohol 3 parts, microcrystalline cellulose 9 parts and pullulan 3 parts; Disintegrant: cross-linked sodium carboxymethyl cellulose 4 parts; Lubricant: magnesium stearate 1.5 parts.

[0025] The preparation method of the above calcium citrate tablet composition is as follows: (1) Mix calcium citrate, casein phosphopeptide and D-mannitol in proportion to obtain mixture 1; (2) Mix polyvinyl alcohol and pullulan in proportion to obtain mixture 2; (3) Take mixture 2, add purified water to prepare a solution with a mass concentration of 8% to obtain a wetting agent; (4) Spray the wetting agent into mixture 1, pass through a 14-mesh sieve, dry at 72°C until the moisture content is 4.5%, pass through a 14-mesh sieve to obtain dry granules; (5) Mix isomalt, sorbitol, vitamin D3 powder, cross-linked sodium carboxymethyl cellulose, microcrystalline cellulose, citric acid, kaman orange flavor and dry granules uniformly, then add magnesium stearate and mix to obtain mixture 3; (6) Compress mixture 3 into tablets using a tablet press to obtain the product with a hardness of 14 kg.

[0026] Example 2 A calcium citrate tablet composition for improving surface smoothness, the raw materials of which are as follows in parts by weight: Calcium citrate 58 parts, casein phosphopeptide 4.5 parts, vitamin D3 powder 0.1 part; Filling agent: D-mannitol 5 parts, isomalt 1 part and sorbitol 8 parts; Flavoring agent: citric acid 0.2 parts and kaman orange essence 0.2 parts; Binder: polyvinyl alcohol 2 parts, microcrystalline cellulose 8 parts and pullulan 2 parts; Disintegrant: croscarmellose sodium 3 parts; Lubricant: magnesium stearate 1 part.

[0027] The preparation method of the above-mentioned calcium citrate tablet composition is as follows: (1) Mix calcium citrate, casein phosphopeptide and D-mannitol uniformly according to the proportion to obtain mixture 1; (2) Mix polyvinyl alcohol and pullulan uniformly according to the proportion to obtain mixture 2; (3) Take mixture 2, add purified water to prepare a solution with a mass concentration of 7% to obtain a wetting agent; (4) Spray the wetting agent into mixture 1, pass through a 14-mesh sieve, and dry at 75°C until the moisture content is 4%, then pass through a 14-mesh sieve to obtain dry granules; (5) Mix isomalt, sorbitol, vitamin D3 powder, croscarmellose sodium, microcrystalline cellulose, citric acid, kaman orange essence and the dry granules uniformly, then add magnesium stearate and mix to obtain mixture 3; (6) Compress mixture 3 into tablets using a tablet press, with a hardness of 12 kg, and the calcium citrate tablets are obtained.

[0028] Example 3 A calcium citrate tablet composition for improving surface smoothness, the raw materials of which are as follows in parts by weight: Calcium citrate 65 parts, casein phosphopeptide 6 parts, vitamin D3 powder 1 part; Filling agent: D-mannitol 8 parts, isomalt 7 parts and sorbitol 13 parts; Flavoring agent: citric acid 1 part and essence 1 part; Binder: polyvinyl alcohol 4 parts, microcrystalline cellulose 11 parts and pullulan 4 parts; Disintegrant: croscarmellose sodium 5 parts; Lubricant: magnesium stearate 2 parts.

[0029] The preparation method of the above-mentioned calcium citrate tablet composition is as follows: (1) Mix calcium citrate, casein phosphopeptide and D-mannitol uniformly according to the proportion to obtain mixture 1; (2) Mix polyvinyl alcohol and pullulan uniformly according to the proportion to obtain mixture 2; (3) Take mixture 2, add purified water to prepare a solution with a mass concentration of 9% to obtain a wetting agent; (4) The wetting agent is sprayed into the mixture 1, sieved, dried at 70°C until the moisture content is 5%, sieved, and dry granules are obtained; (5) The isomalt, sorbitol, vitamin D3 powder, croscarmellose sodium, microcrystalline cellulose, citric acid, kamen orange flavor and dry granules are mixed uniformly, and then magnesium stearate is added and mixed to obtain a mixture 3; (6) The mixture 3 is compressed by a tablet machine to obtain the product.

[0030] Comparative Example 1 The difference between this comparative example and Example 1 is only that the type of binder is different, specifically: 19 parts of sodium carboxymethyl cellulose.

[0031] The preparation method is as follows: (1) The calcium citrate, casein phosphopeptide and D-mannitol are mixed uniformly to obtain a mixture 1; (2) The sodium carboxymethyl cellulose is taken and mixed with purified water to prepare a sodium carboxymethyl cellulose slurry with a mass concentration of 2% to obtain a wetting agent; (3) The wetting agent is sprayed into the mixture 1, sieved, dried at 72°C until the moisture content is 4.5%, sieved, and dry granules are obtained; (4) The isomalt, sorbitol, vitamin D3 powder, croscarmellose sodium, citric acid, kamen orange flavor and dry granules are mixed uniformly, and then magnesium stearate is added and mixed to obtain a mixture 2; (5) The mixture 2 is compressed by a tablet machine to obtain the product.

[0032] Comparative Example 2 The difference between this comparative example and Example 1 is only that the type of binder is different, specifically: 0.5 parts of sodium carboxymethyl cellulose, 3.5 parts of pregelatinized starch and 7 parts of microcrystalline cellulose.

[0033] The preparation method is as follows: (1) The calcium citrate, casein phosphopeptide and D-mannitol are mixed uniformly to obtain a mixture 1; (2) The sodium carboxymethyl cellulose is taken and mixed with purified water to prepare a sodium carboxymethyl cellulose slurry with a mass concentration of 0.5% to obtain a wetting agent; (3) The wetting agent is sprayed into the mixture 1, sieved, dried at 72°C until the moisture content is 4.5%, sieved, and dry granules are obtained; (4) The isomalt, sorbitol, vitamin D3 powder, pregelatinized starch, microcrystalline cellulose, citric acid, kamen orange flavor and dry granules are mixed uniformly, and then magnesium stearate is added and mixed to obtain a mixture 2; (5) The mixture 2 is compressed by a tablet machine to obtain the product.

[0034] Comparative Example 3 The difference between this comparative example and Example 1 is only in the binder, specifically: sodium carboxymethyl cellulose 0.5 parts, low-substituted hydroxypropyl cellulose 3.5 parts, and microcrystalline cellulose 15 parts.

[0035] The preparation method is as follows: (1) Mix calcium citrate, casein phosphopeptide, and D-mannitol uniformly to obtain a mixture 1; (2) Take sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose, and add purified water to prepare a 1% sodium carboxymethyl cellulose slurry to obtain a wetting agent; (3) Spray the wetting agent into the mixture 1, sieve, and dry at 72°C until the moisture content is 4.5%, sieve, and obtain dry granules; (4) Mix isomalt, sorbitol, vitamin D3 powder, microcrystalline cellulose, citric acid, and Camman orange flavor with the dry granules uniformly, and then add magnesium stearate, mix, to obtain a mixture 2; (5) The mixture 2 is compressed into tablets by a tablet press, with a hardness of 14 kg, to obtain the product.

[0036] Comparative Example 4 The difference between this comparative example and Example 1 is only in the raw material ratio, specifically: The raw materials are as follows in parts by weight: Calcium citrate 60 parts, casein phosphopeptide 5 parts, and vitamin D3 powder 0.5 part; Filling agent: D-mannitol 10 parts, isomalt 5 parts, and sorbitol 15 parts; Flavoring agent: citric acid 0.5 part and Camman orange flavor 0.4 part; Binder: polyvinyl alcohol 5 parts, microcrystalline cellulose 4 parts, and pullulan 6 parts; Disintegrant: cross-linked sodium carboxymethyl cellulose 4 parts; Lubricant: magnesium stearate 1.5 parts.

[0037] Comparative Example 5 The difference between this comparative example and Example 1 is only in the binder, specifically: polyvinyl alcohol 7.5 parts, microcrystalline cellulose 0 part, and pullulan 7.5 parts.

[0038] Comparative Example 6 The difference between this comparative example and Example 1 is only in the binder, specifically: polyvinyl alcohol 0 part, microcrystalline cellulose 15 parts, and pullulan 0 part.

[0039] Comparative Example 7 The difference between this comparative example and Example 1 is only in the binder, specifically: polyvinyl alcohol 6 parts, microcrystalline cellulose 9 parts, and pullulan 0 part.

[0040] Comparative Example 8 The difference between this comparative example and Example 1 is only that the binder is different, specifically: polyvinyl alcohol 0 parts, microcrystalline cellulose 9 parts, and pullulan 6 parts.

[0041] Effect test The tablet surface, chewable effect, friability, and disintegration time of the calcium citrate tablet composition of Examples 1-3 and Comparative Examples 1-8 were investigated, and the results are shown in Table 1 below.

[0042] Method for measuring friability: The product was tested according to the Friability Test Method (ChP 2020 Edition General Chapter 0923). The powder that fell off the tablet was blown away with a hair dryer, weighed accurately, and placed in a cylinder, which was rotated 100 times. It was removed and the powder was removed in the same way, weighed accurately, and the weight loss should not exceed 1%, and no broken, cracked, or crushed tablets should be detected. This test is usually only done once. If the weight loss exceeds 1%, it should be retested twice, and the average weight loss of three times should not exceed 1%, and no broken, cracked, or crushed tablets should be detected.

[0043] Method for measuring disintegration time: The product was tested according to the Disintegration Time Test Method (ChP 2020 Edition General Chapter 0921). The basket was suspended on the support by the upper end of the stainless steel shaft, immersed in a 1000 mL beaker, and the basket position was adjusted so that the screen was 25 mm from the bottom of the beaker when it was lowered to the low point. The beaker contained water at a temperature of 37°C or 1°C, and the water level was adjusted so that the basket rose to the high point when the screen was 15 mm below the water surface. The top of the basket should not be immersed in the solution. Unless otherwise specified, 6 tablets of the test product were placed in the glass tube of the basket, and the disintegration tester was started to check. Each tablet should disintegrate completely within 15 minutes. If one tablet does not disintegrate completely, another 6 tablets should be tested, and all should meet the requirements.

[0044]

[0045] The above detailed description is a specific description of one of the feasible embodiments of the present application, which is not intended to limit the patent scope of the present application. Any equivalent implementation or modification that does not deviate from the present application should be included within the scope of the technical solutions of the present application.

Claims

1. A calcium citrate tablet composition for improving the smoothness of a surface, characterized by, The raw materials of the calcium citrate tablet composition include, by weight fraction, calcium citrate 58-65 parts, casein phosphopeptide 4.5-6 parts, vitamin D3 powder 0.1-1 part, filler 14-28 parts, binder 12-20 parts, disintegrant 3-5 parts, lubricant 1-2 parts, and flavoring agent 0.4-2 parts; The binder includes polyvinyl alcohol, microcrystalline cellulose, and pullulan, and the filler includes D-mannitol, isomalt, and sorbitol.

2. The calcium citrate tablet composition according to claim 1, characterized by, The binder includes, by weight fraction, polyvinyl alcohol 2-4 parts, microcrystalline cellulose 8-11 parts, and pullulan 2-4 parts.

3. The calcium citrate tablet composition according to claim 1, wherein The filler includes, by weight fraction, D-mannitol 5-8 parts, isomalt 1-7 parts, and sorbitol 8-13 parts.

4. The calcium citrate tablet composition according to claim 1, wherein The disintegrant is cross-linked sodium carboxymethyl cellulose, and the lubricant is magnesium stearate.

5. The calcium citrate tablet composition according to any one of claims 1-4, wherein, The flavoring agent includes, by weight fraction, citric acid 0.2-1 part and essence 0.2-1 part.

6. A method of preparing the calcium citrate tablet composition according to any one of claims 1 to 5, characterized in that, The method includes the following steps: (1) uniformly mixing calcium citrate, casein phosphopeptide, and D-mannitol to obtain mixture 1; (2) uniformly mixing polyvinyl alcohol and pullulan to obtain mixture 2; (3) taking mixture 2, adding water to prepare a slurry, and obtaining a wetting agent; (4) spraying the wetting agent into mixture 1, sieving, drying, and sieving again to obtain dry granules; (5) uniformly mixing isomalt, sorbitol, vitamin D3 powder, microcrystalline cellulose, disintegrant, flavoring agent, and dry granules, and then adding lubricant and mixing to obtain mixture 3; (6) compressing mixture 3 to form the calcium citrate tablet composition.

7. The preparation method according to claim 6, characterized in that, The mass concentration of the wetting agent in step (3) is 7%-9%.

8. The preparation method according to claim 6, characterized in that, In step (4), sieving is performed through a 12-16 mesh sieve, and the drying temperature is 70-75°C, and the moisture content is 4%-5% after drying.

9. Use of the calcium citrate tablet composition of any one of claims 1-5 or prepared by the method of any one of claims 6-8 in the preparation of a calcium citrate tablet product.

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