Vitamin mineral double-layer tablet and preparation method

Abstract

The invention discloses a vitamin-mineral double-layer tablet and a preparation method thereof, comprising a vitamin layer, a mineral layer and a coating. The invention adopts an adhesive solution of appropriate concentration to wrap white to off-white powder vitamins in isomalt powder which is easy to granulate, and utilizes the characteristics of isomalt powder that is extremely easy to granulate and the polymer adhesive forming a liquid bridge on the surface of the particles to coat the vitamins, thereby solving the problem that the mineral layer is easy to be stained due to powder falling off due to friction of the tablet surface during the coating process of the double-layer tablet; and adopts a double-head punching tablet, and through the optimization of the tableting process, significantly improves the problems of slow tableting speed, unstable tablet weight and low production efficiency during the tableting process of the double-layer tablet, thereby improving product quality and production efficiency.

Description

Technical Field

[0001] The invention relates to the technical field of medicine and health food, and in particular to a vitamin and mineral double-layer tablet and a preparation method thereof. Background Art

[0002] Nutrients refer to various substances needed to maintain human health and ensure human growth, development and activities, including seven categories: sugar, fat, protein, vitamins, minerals, dietary fiber and water. Based on the dietary structure and eating habits of Chinese people, there is a widespread problem of dietary imbalance, and vitamins and mineral nutrients are often insufficient. The "Scientific Research Report on the Dietary Guidelines for Chinese Residents" (2022) issued by the Chinese Nutrition Society pointed out this problem. The report emphasized that the problem of insufficient intake of micronutrients (vitamins and minerals, etc.) by Chinese residents is widespread. Vitamins and minerals are closely related to human health. For example, a lack of vitamin A can lead to slow growth, weakened dark adaptation ability, and may even develop into night blindness. A lack of vitamin B2 can lead to stomatitis, conjunctivitis and various inflammatory diseases. Because food can easily destroy vitamins or affect the absorption of minerals during processing, storage, and cooking, it is essential to supplement complex vitamins and minerals on the basis of a reasonable diet to ensure that the body's nutrient intake meets daily needs, which is crucial to maintaining the body's health.

[0003] At present, there are many medicines and health foods for supplementing vitamins and minerals on the market. Multivitamin and multimineral compound products are the first choice for consumers because they can supplement various trace elements and vitamins in a comprehensive way. However, scientific research shows that there are many interactions between different nutrients, especially many vitamins and minerals that affect each other's biological activity. For example, iron, selenium, and copper are chemically active and will react with vitamin C, thereby affecting the stability of vitamin C. The reaction of iron and vitamin C will produce black spots that affect the appearance of the product. Multivitamin and multimineral tablets on the market mostly use the method of mixing minerals and vitamins and then pressing them into tablets, and reduce the mutual influence between vitamins and minerals through technical means such as raw material embedding and preparation process control. However, the above process method adds a pre-treatment process for vitamin components, and cannot completely avoid the mutual reaction between vitamins and minerals. In actual production, the feed of some vitamins will be increased to make up for the loss in the stability process, and the color coating will be used to cover the possible discoloration during the process.

[0004] A double-layer tablet is a tablet with two layers, each layer containing different drugs or excipients, which can avoid the compatibility changes between different components in multi-component preparations, or achieve the effect of sustained release or controlled release. Multivitamin tablets are prepared as double-layer tablets, with one layer of minerals and one layer of vitamins, which can effectively solve the loss of activity of vitamins caused by the influence of minerals. However, in actual applications, the double-layer tablet press needs to be filled twice and only one side is discharged, so the production speed is slow, less than half of that of a single-layer tablet press, and the hardness and weight of the double-layer tablets often fluctuate abnormally. In addition, multivitamin and multi-mineral compound products usually have larger product specifications because they supplement various trace elements and vitamins at the same time. If they are eaten directly after tableting, they are not smooth to swallow. In addition, vitamins and minerals have their own unique smell, which is difficult for consumers to accept. Taking all factors into consideration, multivitamin and multi-mineral compound products usually choose to be wrapped with a transparent or translucent film coating, which can not only improve the swallowing compliance, but also cover up their unique smell. However, in actual development, it was found that during the coating process, the tablets were turned over in the coating pan, causing the mineral layer and the vitamin layer to rub against each other, resulting in the vitamin layer easily falling off and the mineral layer being stained, among other related problems. Summary of the invention

[0005] In order to overcome the shortcomings and deficiencies of the prior art, the primary purpose of the present invention is to provide a vitamin-mineral double-layer tablet, which, on the one hand, effectively solves the loss of activity of vitamins caused by the influence of minerals, and on the other hand, effectively eliminates the problem of powdering and staining caused by the friction between the mineral layer and the vitamins during the coating process, and has good appearance and stable quality.

[0006] The present invention is achieved through the following technical solutions:

[0007] A vitamin-mineral double-layer tablet, comprising a stacked vitamin layer, a mineral layer, and a coating, wherein the vitamin layer comprises vitamins and auxiliary materials, and the mineral layer comprises minerals and auxiliary materials;

[0008] The vitamins include white to off-white vitamins and colored vitamins; the white to off-white vitamins include white to off-white powder vitamins and white to off-white granular vitamins;

[0009] The minerals include calcium, magnesium, iron, zinc, manganese, and / or selenium;

[0010] The auxiliary materials include fillers and adhesives;

[0011] The filler is one or more of isomalt powder, microcrystalline cellulose, lactose, resistant dextrin or maltodextrin; the binder is one or more of povidone K30, copovidone, hydroxypropyl cellulose or hydroxypropyl methylcellulose;

[0012] The white to off-white powder vitamins are wrapped in particles formed by isomalt powder.

[0013] The coating includes coating materials, plasticizers, film formers, lubricants and the like.

[0014] In the present invention, particles are small particles with certain regular shapes, relatively dispersed, and strong self-weight, generally with a size between 0.1-1000 microns. Powder is a collection of fine particles, generally refers to fine granular substances with a size between 0.001-0.1 mm.

[0015] The white to off-white vitamin powder has 100% of the powder between 10 meshes and 200 meshes, and more than 70% of the powder passes 80 meshes.

[0016] The white to off-white vitamin particles are 100% between 10 meshes and 200 meshes, and no more than 15% are past 80 meshes.

[0017] Preferably, the white to off-white powder vitamins include one or more of vitamin B1, vitamin B6, biotin, niacinamide, vitamin C or pantothenic acid;

[0018] The white to off-white granular vitamins include one or more of vitamin A, vitamin D, vitamin E or vitamin K;

[0019] The colored vitamins include vitamin B2, vitamin B 12 Or one or more of folic acid.

[0020] The vitamin-mineral double-layer tablet provided by the present invention separates minerals from vitamins, and can effectively solve the loss of activity of vitamins caused by the influence of minerals. For example, it can effectively block the contact between iron and selenium elements and vitamin C, avoiding the situation that vitamin C is oxidized and blackened when it encounters iron and selenium, and can effectively block the contact between vitamin K and magnesium elements, significantly improving the stability of vitamin K.

[0021] The vitamin-mineral double-layer tablet provided by the present invention has white to off-white powder vitamins wrapped in isomalt powder that is easy to granulate, thereby ensuring the tightness between the vitamin layer materials and effectively eliminating the problem of powder loss and staining caused by friction between the mineral layer and the vitamins during the coating process.

[0022] Preferably, the mineral layer accounts for 50-80% by weight of the whole tablet, and the vitamin layer accounts for 20-50% by weight of the whole tablet.

[0023] The auxiliary materials of the present invention also include disintegrants and / or lubricants, etc. Applicable disintegrants may be low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, etc. Applicable lubricants may be silicon dioxide, magnesium stearate, etc. The dosage of the above auxiliary materials is the conventional dosage for granulation in the art, and the weight percentage of each auxiliary material component may be 10-40% of filler, 2-5% of binder, 2-8% of disintegrant, 0.5-1.5% of silicon dioxide, and 0.5-1.5% of magnesium stearate.

[0024] The present invention also provides a method for preparing the above vitamin and mineral double-layer tablet, comprising the following steps:

[0025] (I) Preparation of mineral mixture

[0026] (a) Granulation I: After mixing the mineral and the filler, a binder solution is prepared, the binder solution is sprayed into the granules, and the mineral granules are obtained by drying to control the moisture content;

[0027] (b) Total mixing I: adding mineral particles and other auxiliary materials into a mixer and mixing them evenly to obtain a mineral total mixture;

[0028] 2. Preparation of Vitamin Total Mixture

[0029] (1) Granulation I: Mix white to off-white powder vitamins with fillers, prepare a binder solution, spray the binder solution into granules, and dry to control moisture to obtain vitamin granules;

[0030] (2) Total mixing II: adding vitamin granules, white to off-white granular vitamins, colored vitamins, and other auxiliary materials into a mixer and mixing evenly to obtain a vitamin total mixture;

[0031] 3. Preparation of Vitamin and Mineral Bilayer Tablets

[0032] The double-head punching tablet is adopted to press the vitamin total mixture into the upper layer and the mineral total mixture into the lower layer, and the vitamin-mineral double-layer tablet is made by pressing the tablet.

[0033] 4. Preparation of Vitamin and Mineral Double-Layer Coated Tablets

[0034] The film coating premix is ​​used for coating to obtain vitamin and mineral double-layer coated tablets.

[0035] The present invention adds white to off-white powder vitamins (vitamin B1, vitamin B6, biotin, nicotinamide, vitamin C or pantothenic acid) into granules, and the white to off-white powder vitamins are coated in isomalt powder which is easy to granulate, thereby reducing fine powder of the total mixed material and solving the problem that the mineral layer is easily stained due to powder falling off due to friction of the tablet surface during the double-layer tablet coating process.

[0036] Vitamin B2, Vitamin B12 Folic acid is a colorful water-soluble vitamin. If it is added to the granules, the water may not be completely dried. During the accelerated stability test, the water remaining in the granules migrates to the surface of the tablets, causing the color of the tablets to deepen locally and form spots. 12 , folic acid) is added to avoid the contact between colored water-soluble vitamins and water during the preparation of vitamin premixes, which can effectively reduce the problem of tablet surface color spots caused by the migration of colored water-soluble vitamins during the accelerated stability test of tablets.

[0037] Preferably, in step (a), the mineral is calcium; and in step (1), the filler is isomalt powder.

[0038] The present invention can improve the coating of vitamins during granulation, improve the powder loss of one side, and help improve dyeing by selecting a binder of appropriate concentration and an auxiliary material with good granulation properties. However, the binder concentration is too high, and the production efficiency is reduced. Preferably, in step (1), the mass concentration of the binder solution is 10-20%.

[0039] Preferably, in step (1), the moisture content of the particles after drying is controlled to be less than 1.5%.

[0040] The present invention has found through research that the tableting speed can be improved by controlling the amount of fine powder in the vitamin total mixture. Preferably, in step (2), the fine powder exceeding 100 mesh in the vitamin total mixture is less than 15%, preferably the fine powder exceeding 100 mesh in the vitamin total mixture is less than 10%.

[0041] Preferably, in step (a), the mass concentration of the binder solution is 5-15%, and the moisture content of the calcium particles after drying is controlled to be 0.8-2.0%.

[0042] The present invention uses a double-head punching tablet, which can significantly improve the problems of slow tableting speed, unstable tablet weight and low production efficiency in the tableting process of double-layer tablets.

[0043] As a preferred method, the pre-compression pressure of the lower layer is controlled to be 1-3KN during tableting, and the hardness of the whole tablet is 16-30kg / cm 2 When tableting, the tableting speed is controlled to be 100,000-150,000 tablets / h.

[0044] Compared with the prior art, the present invention has the following beneficial effects:

[0045] (1) The present invention uses a binder solution of appropriate concentration to encapsulate white to off-white powder vitamins in isomalt powder that is easy to granulate, and utilizes the characteristics of isomalt powder that is very easy to granulate and the polymer binder that forms a liquid bridge on the particle surface to encapsulate the colorless powder vitamins, thereby reducing the amount of fine powder in the total mixed material and solving the problem of easy staining of the mineral layer due to powder loss caused by friction on the tablet surface during the double-layer tablet coating process;

[0046] (2) The present invention adds colored vitamins and mixes them, thereby avoiding the colored water-soluble vitamins from contacting water during the pre-tabletting process, and can effectively reduce the problem of one-sided color spots on the tablets caused by the colored water-soluble vitamins during the stability placement process;

[0047] (3) The present invention adopts double-head punching tablets, and through the optimization of the tableting process, significantly improves the slow tableting speed, unstable tablet weight and low production efficiency in the double-layer tableting process, thereby improving product quality and production efficiency. DETAILED DESCRIPTION

[0048] The present invention is further described below by means of specific implementation methods. The following examples are preferred implementation methods of the present invention, but the implementation methods of the present invention are not limited to the following examples.

[0049] The raw materials or auxiliary materials used in the examples and comparative examples of the present invention can be purchased from the market.

[0050] Embodiment 1:

[0051] The formula of the vitamin and mineral double-layer tablets of this embodiment is as shown in Table 1 by weight:

[0052] Table 1

[0053]

[0054] The process is as follows:

[0055] Preparation of mineral mix:

[0056] (1) Granulation I: Mix calcium carbonate and maltodextrin evenly. Prepare 10% concentration of povidone K30, spray the slurry on the surface of the mixture for granulation, and dry to control the moisture content to 0.8-2.0% to obtain calcium granules;

[0057] (2) Total mixing I: Add calcium particles, other minerals (magnesium, iron, zinc, manganese, selenium), microcrystalline cellulose, low-substituted hydroxypropyl cellulose, povidone K30 and silicon dioxide into a mixer and mix evenly, then add magnesium stearate and mix evenly to obtain a mineral layer mixed powder;

[0058] Preparation of vitamin mix:

[0059] (1) Granulation II: isomalt powder, microcrystalline cellulose, white to off-white powder vitamins (vitamin C, vitamin B1, B6, niacinamide, pantothenic acid, biotin, 100% of the above vitamins are between 10 mesh and 200 mesh, and more than 70% are above 80 mesh) are mixed evenly, povidone K30 is prepared into a 15% solution, the slurry is sprayed on the surface of the mixture for granulation, and the moisture content is controlled to be less than 1.5% during drying to obtain vitamin granules;

[0060] (2) Total Mixing II: Mix the vitamin granules, colored vitamins (vitamin B2, vitamin B 12 , folic acid), white to off-white granular vitamins (vitamin A, vitamin D, vitamin E, vitamin K, 100% of the above vitamins are between 10 mesh and 200 mesh, and no more than 15% are above 80 mesh), low-substituted hydroxypropyl cellulose, copovidone and silicon dioxide are added into a mixer, mixed evenly, and then magnesium stearate is added and mixed evenly to obtain a vitamin layer mixed powder;

[0061] Tablet pressing: Minerals are pressed on the lower layer, vitamins are pressed on the upper layer, the pre-pressed hardness of the lower layer is controlled to be 1-3KN, and the hardness of the whole tablet is 16-30kg / cm 2 ;

[0062] Coating: Plain tablets are coated with a transparent film coating, and the coating weight gain is 1.0%.

[0063] Embodiment 2:

[0064] The formula of the vitamin and mineral tablets in this embodiment is as shown in Table 2 by weight:

[0065] Table 2

[0066]

[0067]

[0068] The process is as follows:

[0069] Preparation of mineral mix:

[0070] (1) Granulation I: Mix calcium carbonate and maltodextrin evenly. Prepare 10% concentration of povidone K30, spray the slurry on the surface of the mixture for granulation, and dry to control the moisture content to 0.8-2.0% to obtain calcium granules;

[0071] (2) Total mixing I: Add calcium particles, other minerals (magnesium, iron, zinc, manganese, selenium), microcrystalline cellulose, low-substituted hydroxypropyl cellulose, povidone K30 and silicon dioxide into a mixer and mix well. Then add magnesium stearate and mix well to obtain a mineral layer mixed powder.

[0072] Preparation of vitamin mix:

[0073] (1) Granulation II:

[0074] Isomalt powder, microcrystalline cellulose, white to off-white powder vitamins (vitamin C, vitamin B1, B6, niacinamide, pantothenic acid, biotin, 100% of the above vitamins are between 10 mesh and 200 mesh, and more than 70% are above 80 mesh) are mixed evenly, and hydroxypropyl methylcellulose is prepared into a 10% solution, and the slurry is sprayed on the surface of the mixture for granulation, and the moisture is controlled to be less than 1.5% during drying to obtain vitamin granules;

[0075] (2) Total Mixing II: Mix the vitamin granules, colored vitamins (vitamin B2, vitamin B 12 , folic acid), white to off-white granular vitamins (vitamin A, vitamin D, vitamin E, vitamin K, 100% of the above vitamins are between 10 mesh and 200 mesh, and no more than 15% are above 80 mesh), low-substituted hydroxypropyl cellulose, copovidone and silicon dioxide are added into a mixer, mixed evenly, and then magnesium stearate is added and mixed evenly to obtain a vitamin layer mixed powder;

[0076] Tablet pressing: Minerals are pressed on the lower layer, vitamins are pressed on the upper layer, the pre-pressed hardness of the lower layer is controlled to be 1-3KN, and the hardness of the whole tablet is 16-30kg / cm 2 ;

[0077] Coating: Plain tablets are coated with a transparent film coating, and the coating weight gain is 1.0%.

[0078] Comparative Example 1:

[0079] The formula of the vitamin and mineral tablets in this embodiment is as shown in Table 3 by weight:

[0080] Table 3

[0081]

[0082]

[0083] The process is as follows:

[0084] Preparation of mineral mix:

[0085] (1) Granulation I: Mix calcium carbonate and maltodextrin evenly. Prepare 10% concentration of povidone K30, spray the slurry on the surface of the mixture for granulation, and dry to control the moisture content to 0.8-2.0% to obtain calcium granules;

[0086] (2) Total mixing I: Add calcium particles, other minerals (magnesium, iron, zinc, manganese, selenium), microcrystalline cellulose, low-substituted hydroxypropyl cellulose, povidone K30 and silicon dioxide into a mixer and mix well. Then add magnesium stearate and mix well to obtain a mineral layer mixed powder.

[0087] Preparation of vitamin mix:

[0088] (1) Granulation II:

[0089] Isomalt powder, microcrystalline cellulose, white to off-white powder vitamins (vitamin C, vitamin B1, vitamin B6, niacinamide, pantothenic acid, biotin, 100% of the above vitamins are between 10 mesh and 200 mesh, and more than 70% are above 80 mesh) are mixed evenly, and povidone K30 is prepared into an 8% solution, and the slurry is sprayed on the surface of the mixture for granulation, and the moisture is controlled to be less than 1.5% during drying to obtain vitamin granules;

[0090] (2) Total Mixing II: Mix the vitamin granules, colored vitamins (vitamin B2, vitamin B 12 , folic acid), white to off-white granular vitamins (vitamin A, vitamin D, vitamin E, vitamin K, 100% of the above vitamins are between 10 mesh and 200 mesh, and no more than 15% are above 80 mesh), low-substituted hydroxypropyl cellulose, copovidone and silicon dioxide are added into a mixer, mixed evenly, and then magnesium stearate is added and mixed evenly to obtain a vitamin layer mixed powder;

[0091] Tablet pressing: Minerals are pressed on the lower layer, vitamins are pressed on the upper layer, the pre-pressed hardness of the lower layer is controlled to be 1-3KN, and the hardness of the whole tablet is 16-30kg / cm 2 ;

[0092] Coating: Plain tablets are coated with a transparent film coating, and the coating weight gain is 1.0%.

[0093] Comparative Example 2:

[0094] The formula of the vitamin and mineral tablets in this embodiment is as shown in Table 4 by weight:

[0095] Table 4

[0096]

[0097]

[0098] The process is as follows:

[0099] Preparation of mineral mix:

[0100] (1) Granulation I: Mix calcium carbonate and maltodextrin evenly. Prepare 10% concentration of povidone K30, spray the slurry on the surface of the mixture for granulation, and dry to control the moisture content to 0.8-2.0% to obtain calcium granules;

[0101] (2) Total mixing I: Add calcium particles, other minerals (magnesium, iron, zinc, manganese, selenium), microcrystalline cellulose, low-substituted hydroxypropyl cellulose, povidone K30 and silicon dioxide into a mixer and mix well. Then add magnesium stearate and mix well to obtain a mineral layer mixed powder.

[0102] Preparation of vitamin mix:

[0103] (1) Granulation II:

[0104] Isomalt powder, microcrystalline cellulose, white to off-white powder vitamins (vitamin C, vitamin B1, vitamin B6, niacinamide, pantothenic acid, biotin, 100% of the above vitamins are between 10 mesh and 200 mesh, and more than 70% pass 80 mesh), colored vitamins (vitamin B2, vitamin B 12 , folic acid) are mixed evenly, povidone K30 is prepared into a 15% solution, the slurry is sprayed on the surface of the mixture for granulation, and the moisture content is controlled to be less than 1.5% during drying to obtain vitamin granules;

[0105] (2) Total mixing II: Add vitamin granules, white to off-white granular vitamins (vitamin A, vitamin D, vitamin E, vitamin K, 100% of the above vitamins are between 10 mesh and 200 mesh, and no more than 15% pass 80 mesh), low-substituted hydroxypropyl cellulose, copovidone and silicon dioxide into a mixer, mix well, then add magnesium stearate and mix well to obtain a vitamin layer mixed powder;

[0106] Tablet pressing: Minerals are pressed on the lower layer, vitamins are pressed on the upper layer, the pre-pressed hardness of the lower layer is controlled to be 1-3KN, and the hardness of the whole tablet is 16-30kg / cm 2 ;

[0107] Coating: Plain tablets are coated with a transparent film coating, and the coating weight gain is 1.0%.

[0108] Comparative Example 3:

[0109] The formula of the vitamin and mineral tablets in this embodiment is as shown in Table 5 by weight:

[0110] Table 5

[0111]

[0112]

[0113] The process is as follows:

[0114] Preparation of mineral mix:

[0115] (1) Granulation I: Mix calcium carbonate and maltodextrin evenly. Prepare 10% concentration of povidone K30, spray the slurry on the surface of the mixture for granulation, and dry to control the moisture content to 0.8-2.0% to obtain calcium granules;

[0116] (2) Total mixing I: Add calcium particles, other minerals (magnesium, iron, zinc, manganese, selenium), microcrystalline cellulose, low-substituted hydroxypropyl cellulose, povidone K30 and silicon dioxide into a mixer and mix well. Then add magnesium stearate and mix well to obtain a mineral layer mixed powder.

[0117] Preparation of Vitamin Layer Master Mix:

[0118] (1) Granulation II:

[0119] Isomalt powder, microcrystalline cellulose, white to off-white powder vitamins (vitamin C, vitamin B1, vitamin B6, niacinamide, pantothenic acid, biotin, 100% of the above vitamins are between 10 mesh and 200 mesh, and more than 70% are above 80 mesh) are mixed evenly, povidone K30 is prepared into a 15% solution, the slurry is sprayed on the surface of the mixture for granulation, and the moisture is controlled to be less than 1.5% during drying to obtain vitamin granules;

[0120] (2) Total Mixing II: Mix the vitamin granules, colored vitamins (vitamin B2, vitamin B 12 , folic acid), white to off-white granular vitamins (vitamin A, vitamin D, vitamin E, vitamin K, 100% of the above vitamins are between 10 mesh and 200 mesh, and no more than 15% are above 80 mesh), low-substituted hydroxypropyl cellulose, copovidone and silicon dioxide are added into a mixer, mixed evenly, and then magnesium stearate is added and mixed evenly to obtain a vitamin layer mixed powder;

[0121] Tablet pressing: Minerals are pressed on the lower layer, vitamins are pressed on the upper layer, the pre-pressed hardness of the lower layer is controlled to be 1-3KN, and the hardness of the whole tablet is 16-30kg / cm 2 ;

[0122] Coating: Plain tablets are coated with a transparent film coating, and the coating weight gain is 1.0%.

[0123] Comparative Example 4:

[0124] The formula of the vitamin and mineral tablets in this embodiment is as shown in Table 6 by weight:

[0125] Table 6

[0126]

[0127]

[0128] The process is as follows:

[0129] Preparation of mineral mix:

[0130] (1) Granulation I: Mix calcium carbonate and maltodextrin evenly. Prepare 10% concentration of povidone K30, spray the slurry on the surface of the mixture for granulation, and dry to control the moisture content to 0.8-2.0% to obtain calcium granules;

[0131] (2) Total mixing I: Add calcium particles, other minerals (magnesium, iron, zinc, manganese, selenium), microcrystalline cellulose, low-substituted hydroxypropyl cellulose, povidone K30 and silicon dioxide into a mixer and mix well. Then add magnesium stearate and mix well to obtain a mineral layer mixed powder.

[0132] Preparation of vitamin mix:

[0133] (1) Granulation II:

[0134] Isomalt powder, microcrystalline cellulose, sodium ascorbate, white to off-white powder vitamins (vitamin B1, B6, niacinamide, pantothenic acid, biotin, 100% of the above vitamins are between 10 mesh and 200 mesh, and more than 70% are above 80 mesh) are evenly mixed, povidone K30 is prepared into a 15% solution, the slurry is sprayed on the surface of the mixture for granulation, and the moisture is controlled to be less than 1.5% during drying to obtain vitamin granules.

[0135] (2) Total Mixing II: Mix the vitamin granules, colored vitamins (vitamin B2, vitamin B 12 , folic acid), white to off-white granular vitamins (vitamin A, vitamin D, vitamin E, vitamin K, 100% of the above vitamins are between 10 mesh and 200 mesh, and no more than 15% are above 80 mesh), low-substituted hydroxypropyl cellulose, copovidone and silicon dioxide are added into a mixer, mixed evenly, and then magnesium stearate is added and mixed evenly to obtain a vitamin layer mixed powder;

[0136] Tablet pressing: Minerals are pressed on the lower layer, vitamins are pressed on the upper layer, the pre-pressed hardness of the lower layer is controlled to be 1-3KN, and the hardness of the whole tablet is 16-30kg / cm 2 ;

[0137] Coating: Plain tablets are coated with a transparent film coating, and the coating weight gain is 1.0%.

[0138] Comparative Example 5:

[0139] The formula of the vitamin and mineral tablets in this embodiment is shown in Table 7 by weight:

[0140] Table 7

[0141]

[0142]

[0143] The process is as follows:

[0144] Preparation of mineral mix:

[0145] (1) Granulation I: Mix calcium carbonate and maltodextrin evenly. Prepare 10% concentration of povidone K30, spray the slurry on the surface of the mixture for granulation, and dry to control the moisture content to 0.8-2.0% to obtain calcium granules;

[0146] (2) Total mixing I: Add calcium particles, other minerals (magnesium, iron, zinc, manganese, selenium), microcrystalline cellulose, low-substituted hydroxypropyl cellulose, povidone K30 and silicon dioxide into a mixer and mix well. Then add magnesium stearate and mix well to obtain a mineral layer mixed powder.

[0147] Preparation of vitamin mix:

[0148] (1) Granulation II:

[0149] The isomalt powder and microcrystalline cellulose are mixed evenly, and a 15% solution of povidone K30 is prepared. The slurry is sprayed on the surface of the mixture to granulate, and the moisture content is controlled to be less than 1.5% during drying to obtain vitamin granules.

[0150] (2) Total Mixing II: Mix vitamin granules, white to off-white powder vitamins (vitamin C, vitamin B1, vitamin B6, niacinamide, pantothenic acid, biotin, 100% of the above vitamins are between 10 mesh and 200 mesh, and more than 70% pass 80 mesh), colored vitamins (vitamin B2, vitamin B 12 , folic acid), white to off-white granular vitamins (vitamin A, vitamin D, vitamin E, vitamin K, 100% of the above vitamins are between 10 mesh and 200 mesh, and no more than 15% are above 80 mesh), low-substituted hydroxypropyl cellulose, copovidone and silicon dioxide are added into a mixer, mixed evenly, and then magnesium stearate is added and mixed evenly to obtain a vitamin layer mixed powder;

[0151] Tablet pressing: Minerals are pressed on the lower layer, vitamins are pressed on the upper layer, the pre-pressed hardness of the lower layer is controlled to be 1-3KN, and the hardness of the whole tablet is 16-30kg / cm 2 ;

[0152] Coating: Plain tablets are coated with a transparent film coating, and the coating weight gain is 1.0%.

[0153] Comparative Example 6:

[0154] The formula of the vitamin and mineral tablets in this embodiment is shown in Table 8 by weight:

[0155] Table 8

[0156]

[0157]

[0158] The process is as follows:

[0159] Preparation of mineral mix:

[0160] (1) Granulation I: Mix calcium carbonate and maltodextrin evenly. Prepare 10% concentration of povidone K30, spray the slurry on the surface of the mixture for granulation, and dry to control the moisture content to 0.8-2.0% to obtain calcium granules;

[0161] (2) Total mixing I: Add calcium particles, other minerals (magnesium, iron, zinc, manganese, selenium), microcrystalline cellulose, low-substituted hydroxypropyl cellulose, povidone K30 and silicon dioxide into a mixer and mix well. Then add magnesium stearate and mix well to obtain a mineral layer mixed powder.

[0162] Preparation of vitamin mix:

[0163] (1) Granulation II:

[0164] Isomalt powder, microcrystalline cellulose, white to off-white powder vitamins (vitamin C, vitamin B1, vitamin B6, niacinamide, pantothenic acid, biotin, 100% of the above vitamins are between 10 mesh and 200 mesh, and more than 70% are above 80 mesh) are mixed evenly, povidone K30 is prepared into a 30% solution, the slurry is sprayed on the surface of the mixture for granulation, and the moisture content is controlled to be less than 1.5% during drying to obtain dry granules;

[0165] (2) Total Mixing II: Mix dry granules, colored vitamins (vitamin B2, vitamin B 12 , folic acid), white to off-white granular vitamins (vitamin A, vitamin D, vitamin E, vitamin K, 100% of the above vitamins are between 10 mesh and 200 mesh, and no more than 15% are above 80 mesh), low-substituted hydroxypropyl cellulose, copovidone and silicon dioxide are added into a mixer, mixed evenly, and then magnesium stearate is added and mixed evenly to obtain a vitamin layer mixed powder;

[0166] Tablet pressing: Minerals are pressed on the lower layer, vitamins are pressed on the upper layer, the pre-pressed hardness of the lower layer is controlled to be 1-3KN, and the hardness of the whole tablet is 16-30kg / cm 2 ;

[0167] Coating: Plain tablets are coated with a transparent film coating, and the coating weight gain is 1.0%.

[0168] Test process:

[0169] The samples prepared in different embodiments and comparative examples were evaluated, and the evaluation indicators were the powder properties of the total mixed II material, the product performance during tableting, the appearance of the coated tablets, and the stability.

[0170] 1. Powder properties of mixed II materials

[0171] 1. Test methods

[0172] The bulk density is measured according to the method specified in ASTM D 7481; the tap density is measured according to the method specified in GB 5162; Carr's coefficient = (tap density – bulk density) / tap density × 100%

[0173] The particle size distribution was determined by sieving method. No. 20 (0.85 mm), No. 40 (0.425 mm), No. 60 (0.25 mm), No. 80 (0.18 mm), and No. 100 (0.15 mm) sieves were used. The sieves were installed on the oscillating sieve in order from small to large apertures. About 100 g of the total mixed II granules were taken and accurately weighed. The granules were placed on the top sieve and oscillated at an amplitude of 0.6 mm for 10 minutes. After the test, the mass of the granules retained on each layer of the sieve was accurately weighed, and the retention percentage of the granules on each layer of the sieve was calculated.

[0174] 2. Test results

[0175] From the results, after the vitamin layer total mixture is granulated, the powder fluidity of each embodiment and comparative example is good and suitable for tableting. The particle size distribution of embodiments 1 and 2 is similar to that of comparative examples 1, 2, 4, and 6, and the fine powder of comparative examples 3 and 5 is more. The specific data is shown in Table 9 below:

[0176] Table 9

[0177]

[0178] 2. Product performance during tableting

[0179] The double-layer tablet press was used to compress each embodiment and comparative example, and the tablet weight, hardness, disintegration and friability of the product under the tableting speed were examined. The results showed that when the tableting speed of Examples 1 and 2 and Comparative Examples 1, 2, 4 and 6 was 140,000 tablets / h, the quality of each item was stable, while Comparative Examples 3 and 5 could only support a tableting speed of 80,000 tablets / h. The specific results are shown in Table 10 below:

[0180] Table 10

[0181]

[0182] 3. Appearance of coated tablets

[0183] Each embodiment and comparative example was coated respectively to examine the coating process, and the specific results are shown in Table 11 below. The results show that the coating process of embodiments 1, 2 and comparative examples 2, 4, and 6 was normal, with the appearance of the lower layer being colorless and the upper layer being yellow; comparative examples 1, 3, and 5 all showed dyeing during coating.

[0184] Table 11

[0185]

[0186] The stability of each embodiment and comparative example was investigated respectively, and the appearance change of the coated tablet during the stability placement process was investigated. The specific results are shown in Table 12 below. The results show that the product appearance of both layers of Embodiments 1 and 2 and Comparative Example 6 after 1 month and 2 months of acceleration had no obvious change, the mineral layer had no obvious change after 3 months of acceleration, and the color of the vitamin layer was slightly deepened. Comparative Examples 1, 3, and 5 began to change color after 2 months of acceleration. Comparative Examples 2 and 4 had color spots on the vitamin layer after 1 month of acceleration, and obvious color spots after 3 months of acceleration.

[0187] Table 12

[0188]

[0189] 4. Stability

[0190] The product was placed at 37°C ± 2°C and 75% ± 5% humidity for 3 months. The results showed that the stability of vitamin A and vitamin K in the embodiments and comparative examples with double-layer tablet design was good for 3 months, while the stability of ordinary tablets decreased significantly. See Tables 13-14 below for details:

[0191] Table 13 Accelerated changes of vitamin A

[0192]

[0193]

[0194] Table 14 Accelerated changes of vitamin K

[0195] Group 0 month Add 1 Add 2 Add 3 Degradation rate Example 1 13.75 13.42 13.18 12.16 11.56％ Example 2 13.98 13.56 13.24 11.98 14.31％ Comparative Example 1 13.58 13.22 12.88 11.48 15.46％ Comparative Example 2 13.7 13.29 12.96 11.84 13.58％ Comparative Example 3 13.69 13.08 12.76 11.13 18.70％ Comparative Example 4 13.36 13.13 12.87 12.11 9.36％ Comparative Example 5 13.73 13.44 13.02 12.33 10.20％ Comparative Example 6 13.73 13.52 13.23 12.44 9.40％ Ordinary film 13.86 11.58 9.98 6.84 50.65％

[0196] From the above test results, it can be seen that the vitamin and mineral double-layer tablets according to the embodiment of the present invention have good appearance and stable quality, and well solve the problem of easy staining of the mineral layer due to powder loss caused by friction on the tablet surface during the coating process of the double-layer tablets, and are significantly better than the product appearance and quality of other comparative examples.

[0197] The concentration of the binder solution used in Comparative Example 1 is relatively low, and the sheet is dyed during coating. The concentration of the binder solution used in Comparative Example 6 is relatively high, and the production efficiency is reduced. The present invention controls the binder concentration to 10-20%, which can improve the coating of vitamins during granulation, improve the powder loss of the sheet, and help improve dyeing.

[0198] In comparative example 2, colored vitamins (vitamin B2, vitamin B12, folic acid) were mixed with white to off-white powder vitamins for granulation, and spots appeared on the vitamin layer during the acceleration process. The present invention adds and mixes water-soluble colored vitamins, which can avoid the colored water-soluble vitamins from contacting water during the pre-tabletting process, and can effectively reduce the problem of one-sided spots on the tablets caused by the colored water-soluble vitamins during the stability placement process, which helps to improve the one-sided sensory perception during the stability placement process.

[0199] In Comparative Example 5, all vitamins were added and blended, and staining occurred during coating.

[0200] In comparative examples 3 and 5, the fine powder exceeding 100 mesh in the vitamin mixture is greater than 30%, the fine powder is too much, the tableting speed is slow, and the tablets are stained during coating. The present invention can improve the tableting speed by controlling the amount of fine powder in the vitamin mixture.

[0201] Comparative Example 4 uses sodium ascorbate, and spots appear on the vitamin layer during the acceleration process. The present invention uses powdered vitamin C, which helps to improve the one-sided sensory perception during the stability process.

[0202] The stability of vitamin A and vitamin K in ordinary tablets is poor. The present invention adopts a double-layer tablet design to effectively improve the stability of some vitamins.

Claims

1. A vitamin-mineral double-layer tablet, the double-layer tablet comprising a stacked vitamin layer, a mineral layer and a coating, the vitamin layer comprising vitamins and auxiliary materials, the mineral layer comprising minerals and auxiliary materials; The vitamins include white to off-white vitamins and colored vitamins; the white to off-white vitamins include white to off-white powder vitamins and white to off-white granular vitamins; The minerals include calcium, magnesium, iron, zinc, manganese, and / or selenium; The auxiliary materials include fillers and adhesives; The filler includes one or more of isomalt powder, microcrystalline cellulose, lactose, resistant dextrin or maltodextrin; The binder includes one or more of povidone K30, copovidone, hydroxypropyl cellulose or hypromellose; It is characterized in that The white to off-white powder vitamins are encapsulated in particles formed by isomalt powder; The method for preparing the vitamin and mineral double-layer tablet comprises the following steps:

1. Preparation of mineral mixture (a) Granulation I: After mixing the mineral and the filler, a binder solution is prepared, the binder solution is sprayed into the granules, and the mineral granules are obtained by drying to control the moisture content; (b) Total mixing I: adding mineral particles and other auxiliary materials into a mixer and mixing them evenly to obtain a mineral total mixture; 2. Preparation of Vitamin Total Mixture (1) Granulation II: Mix the white to off-white powder vitamins with the filler, prepare a binder solution, spray the binder solution into the granules, dry and control the moisture content to obtain vitamin granules; (2) Total mixing II: Add vitamin granules, white to off-white granular vitamins, colored vitamins, and other auxiliary materials into a mixer and mix evenly to obtain a vitamin total mix; 3. Preparation of Vitamin and Mineral Bilayer Tablets The double-head punching tablet is used to press the vitamin total mixture on the upper layer and the mineral total mixture on the lower layer to form a vitamin-mineral double-layer tablet; In step (1), the mass concentration of the binder solution is 10-20%; In step (2), the content of fine powder passing 100 mesh in the total vitamin mixture is less than 15%.

2. The vitamin and mineral double-layer tablet according to claim 1, characterized in that: The mineral layer accounts for 50-80% of the mass of the whole tablet, and the vitamin layer accounts for 20-50% of the mass of the whole tablet.

3. The vitamin and mineral double-layer tablet according to claim 1, characterized in that: The white to off-white powder vitamins include one or more of vitamin B1, vitamin B6, biotin, niacinamide, vitamin C or pantothenic acid; the white to off-white granular vitamins include one or more of vitamin A, vitamin D, vitamin E or vitamin K; the colored vitamins include vitamin B2, vitamin B 12 Or one or more of folic acid.

4. The method for preparing the vitamin and mineral double-layer tablet according to any one of claims 1 to 3, characterized in that: The steps include:

1. Preparation of mineral mixture (a) Granulation I: After mixing the mineral and the filler, a binder solution is prepared, the binder solution is sprayed into the granules, and the mineral granules are obtained by drying to control the moisture content; (b) Total mixing I: Add mineral particles and other auxiliary materials into the mixer and mix evenly to obtain the total mineral Mixing; 2. Preparation of Vitamin Total Mixture (1) Granulation II: Mix the white to off-white powder vitamins with the filler, prepare a binder solution, spray the binder solution into the granules, dry and control the moisture content to obtain vitamin granules; (2) Total mixing II: Add vitamin granules, white to off-white granular vitamins, colored vitamins, and other auxiliary materials into a mixer and mix evenly to obtain a vitamin total mix; 3. Preparation of Vitamin and Mineral Bilayer Tablets The double-head punching tablet is adopted to press the vitamin total mixture into the upper layer and the mineral total mixture into the lower layer, and the vitamin-mineral double-layer tablet is made by pressing the tablet.

5. The method for preparing the vitamin and mineral double-layer tablet according to claim 4, characterized in that: In step (a), the mineral is calcium; in step (1), the filler is isomalt powder.

6. The method for preparing the vitamin and mineral double-layer tablet according to claim 4, characterized in that: In step (1), the mass concentration of the adhesive solution is 10-20%.

7. The method for preparing the vitamin and mineral double-layer tablet according to claim 4, characterized in that: In step (1), the moisture content of the particles after drying is controlled to be less than 1.5%.

8. The method for preparing the vitamin and mineral double-layer tablet according to claim 4, characterized in that: In step (2), the content of fine powder passing 100 mesh in the total vitamin mixture is less than 15%.

9. The method for preparing the vitamin and mineral double-layer tablet according to claim 8, characterized in that: In step (2), the content of fine powder passing 100 mesh in the total vitamin mixture is less than 10%.

10. The method for preparing the vitamin and mineral double-layer tablet according to claim 4, characterized in that: In step (a), the mass concentration of the binder solution is 5-15%, and the moisture content of the calcium particles after drying is controlled to be 0.8-2.0%.

11. The method for preparing the vitamin and mineral double-layer tablet according to claim 4, characterized in that: When tabletting, the pre-pressing pressure of the lower layer is controlled to be 1-3KN, and the hardness of the whole tablet is 16-30 kg / cm 2 When tableting, the tableting speed is controlled to be 100,000-150,000 tablets / h.

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