Microcapsule, tablet and preparation method and application thereof

Abstract

The invention provides a microcapsule, a tablet and a preparation method and application thereof, the microcapsule comprises the following components in parts by weight: 70-83 parts of magnesium oxide, 1-2.5 parts of stearic acid and 3.5-5.5 parts of a composite adhesive, the particle size D90 of the magnesium oxide is 15-150 [mu] m, the composite adhesive is a composition of HPMC and PVP, and PVP is PVP-K30. The tablets include magnesium oxide microcapsules. The preparation method of the tablet comprises the following steps: S1, uniformly mixing magnesium oxide and stearic acid according to a formula ratio to obtain a mixture, granulating the mixture by using a composite adhesive solution, and then drying and sieving the granules to obtain microcapsules; and S2, tabletting the microcapsules by using a tablet press to obtain the tablets. Through the specific material composition and the specific magnesium oxide particle size range, the effects of uniform granulation particles, improvement of product compressibility, improvement of the product friction black problem, improvement of the product yield and production stability and prolonging of the service life of equipment to a certain extent are achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of dietary supplements, and particularly relates to a microcapsule, a tablet, and a preparation method and application thereof. Background Art

[0002] Magnesium oxide is a white or grayish-white powder, odorless, tasteless, and non-toxic, and is a typical alkaline earth metal oxide. The melting point of magnesium oxide is 2852 °C, the boiling point is 3600 °C, and the density at room temperature is 3.58 g / cm 3 . Magnesium oxide is soluble in acids and ammonium salt solutions, hardly soluble in water, insoluble in alcohol, and its solubility in water is 0.00062 g / 100 mL (0 °C), 0.0086 g / 100 mL (30 °C). Magnesium oxide is prone to absorbing moisture and carbon dioxide in the air and generating basic magnesium carbonate, and can combine with water to generate magnesium hydroxide under certain conditions, showing a slightly alkaline reaction, and the pH of the saturated aqueous solution is 10.3.

[0003] Magnesium oxide tablets are mainly composed of magnesium oxide, fillers, binders, and disintegrants. Due to the relatively high hardness of magnesium oxide, with a Mohs hardness of 5.5 - 6.6, in the production of existing magnesium oxide tablets, when the magnesium oxide content is greater than 40%, it is very easy to have the problem of blackening due to mutual friction between the material and the metal parts of the tablet press, and the use of metal parts is unavoidable in the current production process of magnesium oxide tablets. Therefore, many current magnesium oxide tablets with a high magnesium oxide content are prone to having blackened patches on the tablet surface, and a non-transparent coating powder can be coated on the outside of the magnesium oxide tablets in the form of coating to cover the blackening. When the magnesium oxide content is greater than 70%, the compressibility of the product becomes poor, and problems such as lamination or insufficient hardness will occur during the tableting process, seriously affecting the production of the product. Although it can be improved by adding binders, the addition of binders is very likely to result in coarser and harder granules after granulation, thus leading to the waste of coarse granules and affecting the yield. Moreover, the higher hardness will further exacerbate the blackening situation and also affect the service life of the tablet press.

[0004] All in all, in the production process of current high-content magnesium oxide tablets, it is very easy to have problems such as poor granule uniformity after granulation, poor compressibility of the product, low yield of the granulated product, difficult normal and stable operation of production, blackening on the surface of magnesium oxide tablets, and damage to the tablet press. Summary of the Invention

[0005] In order to solve the problems and deficiencies existing in the prior art, the present invention provides a microcapsule, a tablet, and a preparation method and application thereof, which achieve uniform granulation particles, improved compressibility of the product, improved blackening problem of the product, increased product yield and production stability, and to a certain extent, improved service life of the equipment through specific material composition and specific magnesium oxide particle size range.

[0006] The first aspect of the present invention provides a microcapsule, which comprises the following components in parts by weight: 70 to 83 parts of magnesium oxide, 1 to 2.5 parts of stearic acid, and 3.5 to 5.5 parts of a composite binder, wherein the particle size D90 of the magnesium oxide is 15 to 150 μm, the composite binder is a composition of HPMC and PVP, and the PVP is PVP-K30.

[0007] The present invention is dedicated to preparing microcapsules with high magnesium oxide content and uniform granulated particles, and the specific means are: first, magnesium oxide with a specific particle size range is selected, and the present invention selects magnesium oxide with a particle size D90 of 15 to 150 μm, i.e., 100 to 800 meshes as the main material; second, a suitable adhesive is added, and the present invention selects a composition of HPMC and PVP (preferably PVP-K30) as a composite adhesive to wrap the magnesium oxide; third, stearic acid is added to achieve the purpose of lubrication, so as to reduce the friction between granulated particles and between particles and metal parts, and reduce the proportion of coarse particles generated during the granulation process; fourth, a specific ratio of magnesium oxide, stearic acid, and composite adhesive is limited, i.e., (70 to 83):(1 to 2.5):(3.5 to 5.5). Thus, the present invention adds stearic acid and magnesium oxide in a specific particle size range for granulation, adds a composition of two adhesives (a composition of HPMC and PVP-K30), wraps the magnesium oxide with a composite adhesive, and lubricates it with stearic acid, thereby reducing the friction between the granulated particles and between the particles and metal parts, and reducing the proportion of coarse particles produced during the granulation process, thereby improving the yield of the product and simultaneously improving the blackening problem of high-content magnesium oxide microcapsules.

[0008] Preferably, the particle size D90 of magnesium oxide is 15 to 150 μm, 20 to 140 μm or 20 to 135 μm.

[0009] Preferably, the weight ratio of PVP to HPMC in the composite adhesive is 7: 1 to 11: 1, 7: 1 to 10: 1, 8: 1 to 10: 1 or 9: 1 to 10: 1. Within this ratio range, the granulated particles have good uniformity and a high granulation yield.

[0010] The second aspect of the present invention provides a tablet, comprising: the above-mentioned microcapsule.

[0011] The weight parts of magnesium oxide in the microcapsules of the tablets are 70 to 83 parts, aiming to prepare tablets with a high magnesium oxide content and uniform granulation particles. The specific means are as follows: First, magnesium oxide with a specific particle size range is selected. In the present invention, magnesium oxide with a D90 particle size of 15 to 150 μm, that is, 100 to 800 mesh, is selected as the main material; Second, a suitable binder is added. In the present invention, a composition of HPMC and PVP-K30 is selected as the composite binder to coat the magnesium oxide; Third, stearic acid is added to achieve the purpose of lubrication, so as to reduce the friction between granulation particles and between particles and metal components, and reduce the generation ratio of coarse particles during the granulation process; Fourth, the specific ratio of magnesium oxide, stearic acid, and the composite binder is defined as (70 to 83):(1 to 2.5):(3.5 to 5.5). Thus, in the present invention, granulation is carried out by adding stearic acid and magnesium oxide with a specific particle size range, and a composition of two binders (a composition of HPMC and PVP-K30) is added. The magnesium oxide is coated with the composite binder, and stearic acid is used for lubrication, so as to reduce the friction between granulation particles and between particles and metal components, and reduce the generation ratio of coarse particles during the granulation process, thereby improving the product yield and simultaneously improving the problem of blackening due to friction of high-content magnesium oxide tablets.

[0012] All in all, in the present invention, the ratio of stearic acid + HPMC + PVP-K30 to magnesium oxide with a specific particle size range achieves uniform granulation particles, improves the compressibility of the product, improves the problem of blackening due to friction of the product, improves the product yield and production stability, and to a certain extent improves the service life of the equipment.

[0013] Preferably, the microcapsules are 74.5 to 91 parts.

[0014] Preferably, the tablets further include at least one of a filler, a disintegrant, a glidant, a release agent, and a functional ingredient. The addition of the filler, disintegrant, glidant, and release agent is more conducive to improving the uniformity of granulation particles, granulation yield, and blackening due to friction of magnesium oxide tablets, and can improve the compressibility of the product and the service life of the equipment. The addition of plant extracts and vitamins can endow the magnesium oxide microcapsules with corresponding effects.

[0015] Preferably, the filler is 5 to 20 parts, 5 to 18 parts, or 5 to 15 parts, and the filler includes at least one of microcrystalline cellulose, sorbitol, mannitol, and lactose.

[0016] Preferably, the disintegrant is 1 to 6 parts, 2 to 5 parts, or 2 to 4 parts, and the disintegrant includes at least one of cross-linked carboxymethylcellulose sodium, sodium carboxymethyl starch, and cross-linked polyvinylpyrrolidone.

[0017] Preferably, the glidant is 0.1 to 1.5 parts or 0.3 to 1.0 parts, and the glidant includes silicon dioxide.

[0018] Preferably, the release agent is 1.0 to 2.0 parts or 1.2 to 2.0 parts, and the release agent includes magnesium stearate.

[0019] Preferably, the functional component is 0 to 5 parts, and the functional component includes plant extract and / or vitamin.

[0020] More preferably, the plant extract includes at least one of fennel, citrus extract, and licorice extract, and the vitamin includes at least one of vitamin A, vitamin C, vitamin D, vitamin E, and B vitamins.

[0021] Preferably, the surface of the tablet is coated with a coating layer, and the mass of the coating layer makes R 0 to 5%, where R = mass of the coating layer / (mass of the tablet - mass of the coating layer). The raw materials for preparing the coating layer include at least one of ethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, and polyethylene glycol. The setting of the coating layer is beneficial to covering defects such as rubbing black on the surface of the tablet to ensure the good appearance of the tablet. The mass of the coating layer affects the disintegration time and the concealer effect of the tablet. When the value of R satisfies the range of 0 to 5%, the coating layer can achieve a good covering effect and ensure the disintegration of the tablet within the specified time. When R is greater than 5%, the disintegration time of the tablet is prolonged, affecting the efficacy of the tablet. Theoretically, the surface of the tablet prepared by the present invention has no defects such as rubbing black, so the coating layer may not be coated.

[0022] The third aspect of the present invention provides a method for preparing microcapsules. This preparation method is used to prepare the microcapsules provided in the first aspect of the present invention, and this preparation method includes the following steps:

[0023] Mix the formulated amounts of magnesium oxide and stearic acid evenly to obtain a mixture, granulate the mixture using a composite binder solution, and then dry and screen and size the granules to obtain microcapsules.

[0024] Preferably, the method for preparing the composite binder solution is to add the formulated amounts of solid powders of HPMC and PVP to ethanol to prepare a composite binder solution with a concentration of 20 to 25%.

[0025] Preferably, the granulation is wet granulation.

[0026] The fourth aspect of the present invention provides a method for preparing tablets. This preparation method is used to prepare the tablets provided in the second aspect of the present invention, and this preparation method includes the following steps:

[0027] S1. Mix the formulated amounts of magnesium oxide and stearic acid evenly to obtain a mixture, granulate the mixture using a composite binder solution, and then dry and screen and size the granules to obtain microcapsules;

[0028] S2. Use a tableting machine to tablet the microcapsules to obtain magnesium oxide tablets.

[0029] The preparation method of the present invention is mainly used for producing tablet products, including but not limited to health foods and dietary supplements, and the daily dosage is determined according to the limited amount of efficacy materials. The tablets of the present invention are granulated by adding stearic acid and magnesium oxide within a specific particle size range, and adding a composition of two binders (a composition of HPMC and PVP-K30). The magnesium oxide is coated with the composite binder, and lubricated with stearic acid, so as to reduce the friction between granulated particles and between particles and metal components, and reduce the generation ratio of coarse particles during the granulation process, thereby improving the product yield and simultaneously improving the problem of blackening due to friction of tablets with high content of magnesium oxide.

[0030] Preferably, in S1, the formulated amounts of solid powders of HPMC and PVP are added to ethanol to prepare a composite binder solution with a concentration of 20-25%.

[0031] Preferably, the granulation is wet granulation.

[0032] Preferably, in S2, the microcapsules are mixed with the formulated amounts of filler, disintegrant, glidant, mold release agent and functional components to obtain a mixed material, and then the mixed material is tabletted using a tabletting machine to obtain tablets.

[0033] Preferably, the preparation method further includes S3. Coating the surface of the tablets with a coating layer to obtain tablets with a coating layer. Theoretically, the surface of the tablets prepared by the present invention has no defects such as blackening due to friction and does not need to be coated with a coating layer. If defects such as blackening due to friction occur during the production process due to improper operation of some steps, a coating layer can be set, but the quality of the coating layer needs to be controlled to avoid affecting the normal disintegration of the tablets.

[0034] The fifth aspect of the present invention provides an application of microcapsules and / or tablets in foods and / or pharmaceuticals. Specific Embodiments

[0035] The technical features in the technical solutions provided by the present invention will be further clearly and completely described below in conjunction with specific embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative efforts fall within the protection scope of the present invention.

[0036] The materials used in the examples and comparative examples of the present invention are all commercially available. Among them, HPMC is carboxymethylpropyl cellulose, and PVP-K30 is a kind of polyvinylpyrrolidone.

[0037] The following examples and comparative examples involve the following test methods:

[0038] Instruments used: electronic balance, friability tester, disintegration tester.

[0039] Test items:

[0040] (1) Granule uniformity of granulation: Screen the granulated granules, calculate the proportion of granules in the range of 20 - 80 mesh, denoted as q; calculate the proportion of granules in the range < 20 mesh, denoted as w. Among them, if q ≥ 75% and w < 12%, it indicates that the granules meet the requirements, have high uniformity, and a low proportion of coarse granules; if w ≥ 12%, it indicates a high proportion of coarse granules.

[0041] (2) Granulation yield a: The mass M of the granules after granulation and drying through a 20 - mesh sieve 1 and the mass M of the material before granulation 2 The percentage value: a = M 1 * 100% / M 2 .

[0042] (3) Quality assessment of tablets

[0043] Pressure: Directly read the value displayed on the tablet press during tableting, unit KN.

[0044] Hardness: Place the tablets after tableting on a friability and hardness tester, click start to test, measure the hardness value of the corresponding tablets, and read and record it, unit N.

[0045] Pressure & Hardness: The lower the pressure and the higher the hardness, the better the compressibility of the product; conversely, it indicates worse compressibility of the product.

[0046] Friability: Determine according to the requirements of the tablet friability test method in the General Chapter of Preparations, Part III of the Pharmacopoeia of the People's Republic of China (2020 Edition), unit %. Friability can reflect the friability and strength of the product to a certain extent, and is used to evaluate the risks in subsequent film coating, packaging, and transportation processes. Under normal circumstances, the required friability is < 1%.

[0047] (4) Disintegration time limit: Determine the tablets prepared according to the requirements of the disintegration time limit test method in the General Chapter of Preparations, Part III of the Pharmacopoeia of the People's Republic of China (2020 Edition), unit min, the requirement is ≤ 60 min, and the normal internal control requirement is ≤ 45 min.

[0048] (5) Tablet rubbing blackness degree: Use a GODA standard stain card to judge the rubbing blackness degree of the tablets pressed out. Judgment criteria: A. No rubbing blackness seen: No rubbing blackness seen with the naked eye; B. Slight rubbing blackness: The length or diameter of the black dots < 1.0 mm; C. Partial rubbing blackness: The length or diameter of the black dots is between 1.0 - 1.5 mm; D. Obvious rubbing blackness: The length or diameter of the black dots ≥ 1.5 mm.

[0049] (6) Evaluation of tableting operation stability (relative standard deviation of tablet weight RSD)

[0050] After the tablet press runs normally, continuously take out 40 tablets from the tablet outlet, weigh the tablets respectively, record and calculate the RSD value of the tablet weight during the operation of the equipment under this formula. Generally, it is required that RSD ≤ 5%, which represents stable operation. The larger the RSD, the worse the operation stability. Relative standard deviation (RSD) = standard deviation (SD) / arithmetic mean (X) of the calculation result.

[0051] (7) Mold wear assessment: According to daily use experience, the greater the production pressure, the more obvious the rubbing blackening situation, and the greater the wear on the mold.

[0052] (8) Test of the mesh number of magnesium oxide: Use a laser scattering particle size distribution analyzer to measure the average particle size of magnesium oxide twice.

[0053] Example 1

[0054] This example explores the effects of the particle size and content of magnesium oxide. A total of 8 treatment groups, namely implementation treatment groups 1 - 5 and comparison treatment groups 1 - 3, are set up. The formula, related parameters, and performance results of each treatment group are shown in Table 1.

[0055] In this example, the preparation method of the tablets in each treatment group is as follows: S1. Mix the formulated amount of magnesium oxide and stearic acid evenly to obtain a mixture. Add solid powders of HPMC and PVP - K30 with a weight ratio of 1:10 to ethanol to prepare a composite binder solution with a concentration of 20 - 25%. Use the composite binder solution to granulate the mixture, then dry and screen and size - reduce to obtain micro - capsules; S2. Mix the micro - capsules with the formulated amount of filler, disintegrant, glidant, and lubricant to obtain a mixed material, and then use a tablet press to press the mixed material to obtain tablets.

[0056] Table 1. Formulas, related parameters, and performance results of each treatment group in Example 1

[0057]

[0058]

[0059]

[0060] Note: The compound binder is calculated by the number of parts according to the solute, and the calculation method in subsequent examples is the same.

[0061] As can be seen from Table 1:

[0062] A. When the number of parts of magnesium oxide is between 70 - 83 parts, the granulation particle uniformity is good, the granulation yield is relatively high, the compressibility of the product is good, under the condition of relatively small pressure, better hardness can be achieved, the friability is qualified, the tablet - pressing operation process is stable (RSD < 5%), the disintegration time limit is qualified, no rubbing blackening situation is seen, and the impact on mold wear assessment is also small.

[0063] B. When the amount of magnesium oxide is less than 70 parts, due to the larger space for product excipients, the product formability is better, etc.

[0064] C. When the amount of magnesium oxide is higher than 83 parts, the uniformity of granulation particles is poor, there are more coarse particles, the granulation yield is too low, the compressibility of the product is poor, a larger pressure is required to form the product, and the hardness is also relatively low, and the friability is relatively high. The stability during the tablet pressing process is poor (RSD>5%), the disintegration time limit is long, and there are some problems of rubbing black. It is evaluated that it has an impact on die wear.

[0065] D. When the particle size of magnesium oxide is relatively coarse (320um), due to the relatively coarse magnesium oxide particles, the uniformity of granulation particles is poor, the proportion of coarse particles is high, the compressibility of the product is poor, the friability is high, the disintegration time limit is long, and there are obvious problems of rubbing black. It is evaluated that it has a greater impact on die wear. When the particle size of magnesium oxide is relatively fine (11um), there is a problem that the disintegration time limit is relatively long. The reason is that the material is too fine, the specific surface area is larger, and more water can be adsorbed; and the entire production process is more cumbersome, the sieving time is longer, and the material is more difficult to disperse. Therefore, for the production timeliness, it is not adopted.

[0066] In summary, due to the relatively high hardness of magnesium oxide itself, too high content of magnesium oxide will affect the molding, disintegration and appearance and other indicators of the product. Therefore, the appropriate range of high content of magnesium oxide in the present invention is 70-83 parts, and the D90 particle size is most suitable at 150um-15um.

[0067] Example 2

[0068] This example explores the influence of the ratio of HPMC and PVP-K30 in the composite binder. A total of 5 treatment groups are set, including implementation treatment groups 6-8 and comparative treatment groups 4-5. The formulations, related parameters and performance results of each treatment group are shown in Table 2.

[0069] The preparation method of the tablets in each treatment group of this example is as follows: S1. Mix the formulated amount of magnesium oxide and stearic acid evenly to obtain a mixture. Add a total of 4.5 parts of solid powders of HPMC and PVP-K30 to ethanol to prepare a composite binder solution with a concentration of 20-25%. Use the composite binder solution to granulate the mixture, then dry and sieve and size the granules to obtain microcapsules; S2. Mix the microcapsules with the formulated amount of filler, disintegrant, glidant and lubricant to obtain a mixed material, and then use a tableting machine to press the mixed material to obtain tablets.

[0070] Table 2. Formulations, related parameters and performance results of each treatment group in Example 2

[0071]

[0072] From Table 2, we can see that:

[0073] A. When the ratio of PVP-K30:HPMC in the composite adhesive is between 7:1 and 10:1, the uniformity of the granulated particles is good, the granulation yield is high, the compressibility of the product is good, and under low pressure, better hardness can be achieved, the friability is also qualified, the tableting process is stable (RSD <5%), the disintegration time is qualified, no blackening is observed, and the impact on mold wear is also small.

[0074] B. When PVP-K30:HPMC in the composite adhesive is 6:1<7:1, the uniformity of the granulated particles is poor, there are more coarse particles, the granulation yield is too low, the compressibility of the product is poor, and a larger pressure is required to form the product. The hardness is relatively low, the friability is relatively high, the stability of the tableting process is poor (RSD>5%), the disintegration time is long, and some blackening problems occur. It is evaluated that there is an impact on mold wear.

[0075] C. When PVP-K30:HPMC in the compound adhesive is 11:1>10:1, the granulated particles contain more fine powder, the compressibility of the product is poor, and a larger pressure is required to form the product. The hardness is relatively low, the friability is relatively high, the stability of the tableting process is poor (RSD>5%), and the disintegration time is long.

[0076] In summary, the viscosity of HPMC is greater than that of PVP-K30, so a higher proportion of HPMC will produce more coarse particles during granulation, which will affect the relevant indicators; but when the proportion of HPMC is too low, the granulated particles will be powdery, which will affect the relevant indicators. Therefore, the appropriate ratio of PVP-K30:HPMC in the composite adhesive of the present invention is 7:1 to 10:1.

[0077] Example 3

[0078] This example explores the effect of stearic acid content. A total of 5 treatment groups, including implementation treatment groups 9 to 10 and comparison treatment groups 6 to 8, are set up. The formula of each treatment group, related parameters, and performance results are shown in Table 3.

[0079] The preparation methods of tablets in each treatment group of this embodiment are: S1. The formulated amounts of magnesium oxide and stearic acid are uniformly mixed to obtain a mixture, HPMC and PVP-K30 solid powders in a weight ratio of 1:10 are added to ethanol to prepare a composite adhesive solution with a concentration of 20-25%, the composite adhesive solution is used to granulate the mixture, and then the granules are dried and sieved to obtain microcapsules; S2. The microcapsules are mixed with the formulated amounts of fillers, disintegrants, glidants and release agents to obtain a mixed material, and then the mixed material is compressed using a tablet press to obtain tablets.

[0080] Table 3. Formulations, related parameters, and performance results of each treatment group in Example 3

[0081]

[0082]

[0083] As can be seen from Table 3:

[0084] A. When the number of parts of stearic acid is between 1 and 2.5 parts, the granulation particles have good uniformity, the granulation yield is relatively high, the compressibility of the product is good, and under relatively small pressure, better hardness can be achieved, the friability is also qualified, the tablet pressing operation process is stable (RSD < 5%), the disintegration time limit is qualified, no blackening is seen, and the evaluation of the influence on die wear is also small.

[0085] B. When the number of parts of stearic acid is less than 1 part, or even completely not added, there are more coarse particles in granulation, the granulation yield is relatively low, the compressibility of the product is poor, and under relatively large pressure, the hardness achieved by the product is relatively low, the friability is relatively increased or even unqualified, the stability of the tablet pressing operation process is poor (RSD > 5%), the disintegration is qualified, but blackening occurs in magnesium oxide tablets, and the evaluation shows an impact on die wear.

[0086] C. When the number of parts of stearic acid > 2.5 parts, there are more fine powders in the granulation particles, the granulation yield is relatively high, the compressibility of the product becomes poor, and under relatively large pressure, the hardness achieved by the product is relatively low, the friability is qualified, the tablet pressing operation process is stable (RSD < 5%), the disintegration time limit is critical, no blackening is seen, and the evaluation of the influence on die wear is relatively small.

[0087] In summary, stearic acid has lubricating and partial binding effects. When the proportion is appropriate, it can improve the friction between particles, and because of its hydrophobicity, it is more conducive to the uniform dispersion of the binder during granulation. Therefore, tablets that meet the requirements can be obtained; when it is excessive, due to excessive lubrication and the problem that stearic acid has a low melting point and becomes soft, the compressibility of the product is poor, and because of its hydrophobicity, it also leads to the problem of a long disintegration time of the product. If it is added too little or not added at all, it will lead to problems such as coarser granulation particles and poor compressibility of the product. Therefore, the appropriate range of stearic acid in the present invention is 1 - 2.5 parts.

[0088] Example 4

[0089] This example explores the influence of the content of the composite binder. A total of 6 treatment groups are set, including implementation treatment groups 11 - 12 and comparative treatment groups 9 - 12. The formulations, related parameters, and performance results of each treatment group are shown in Table 4.

[0090] In each treatment group of this example, the preparation method of the tablets is as follows: S1. Mix the formulated amounts of magnesium oxide and stearic acid evenly to obtain a mixture. Add solid powders of HPMC and PVP-K30 with a weight ratio of 1:10 to ethanol to prepare a composite binder solution with a concentration of 20-25%. Use the composite binder solution to granulate the mixture, then dry and screen and size the granules to obtain microcapsules; S2. Mix the microcapsules with the formulated amounts of filler, disintegrant, glidant, and mold release agent to obtain a mixed material, and then use a tableting machine to tablet the mixed material to obtain tablets.

[0091] Table 4. Formulations, related parameters, and performance results of each treatment group in Example 4

[0092]

[0093]

[0094] As can be seen from Table 4:

[0095] A. When the amount of the composite binder (PVP-K30 and HPMC) is between 3.5 and 5.5 parts, the granulation particle uniformity is good, the granulation yield is relatively high, the compressibility of the product is good, and under a relatively small pressure, a better hardness can be achieved, the friability is also qualified, the tableting operation process is stable (RSD < 5%), the disintegration time limit is qualified, no blackening is seen, and the impact on die wear is also small.

[0096] B. When the amount of the composite binder (PVP-K30 and HPMC) is less than 3.5 parts, there are more fine powders in the granulation particles, the granulation yield is relatively high, the compressibility of the product is poor, and under a relatively large pressure, the achievable hardness is relatively low, and the friability is also on the high side or even exceeds the standard. The tableting operation process is relatively stable (RSD is close to 5%), the disintegration time limit is qualified, blackening occurs, and the impact on die wear is evaluated.

[0097] C. When the amount of the composite binder (PVP-K30 and HPMC) is more than 5.5 parts, there are more coarse particles in the granulation particles, the granulation yield is relatively low, the compressibility of the product is poor, and under a relatively large pressure, the achievable hardness is relatively low, and the friability is also on the high side. The tableting operation process is relatively stable (RSD is close to or even exceeds 5%), the disintegration time limit is qualified, blackening occurs, and the impact on die wear is evaluated.

[0098] In summary, within a certain addition range, the composite binder can significantly improve the uniformity of granulation particles and the compressibility of the product. Adding too little will lead to problems such as too many fine powders and poor compressibility; adding too much will result in more coarse particles and product blackening. Therefore, the suitable range of the composite binder (PVP-K30 and HPMC) in the present invention is 3.5 - 5.5 parts.

[0099] Example 5

[0100] In this example, the influence of the disintegrant content was explored. A total of 3 treatment groups, namely treatment groups 13 - 15, were set up. The formulations, related parameters, and performance results of each treatment group are shown in Table 5.

[0101] In each treatment group of this example, the preparation method of the tablets was as follows: S1. Mix the formulated amounts of magnesium oxide and stearic acid evenly to obtain a mixture. Add solid powders of HPMC and PVP-K30 with a weight ratio of 1:10 to ethanol to prepare a composite binder solution with a concentration of 20 - 25%. Use the composite binder solution to granulate the mixture, then dry and screen and size the granules to obtain microcapsules; S2. Mix the microcapsules with the formulated amounts of filler, disintegrant, glidant, and lubricant to obtain a mixed material, and then use a tableting machine to tablet the mixed material to obtain tablets.

[0102] Table 5. Formulations, related parameters, and performance results of each treatment group in Example 5

[0103]

[0104] As can be seen from Table 5:

[0105] When the number of parts of the disintegrant is 2 - 5 parts, the granulation particle uniformity is good, the granulation yield is relatively high, the compressibility of the product is good, under the condition of relatively small pressure, better hardness can be achieved, the friability is also qualified, the tableting operation process is stable (RSD < 5%), the disintegration time limit is qualified, no rubbing black situation is seen, and the influence on die wear is also small. Therefore, the appropriate range of the disintegrant in the present invention is 2 - 5 parts.

[0106] Example 6

[0107] In this example, the influence of the glidant and lubricant content was explored. A total of 4 treatment groups, namely treatment groups 16 - 19, were set up. The formulations, related parameters, and performance results of each treatment group are shown in Table 6.

[0108] In each treatment group of this example, the preparation method of the tablets was as follows: S1. Mix the formulated amounts of magnesium oxide and stearic acid evenly to obtain a mixture. Add solid powders of HPMC and PVP-K30 with a weight ratio of 1:10 to ethanol to prepare a composite binder solution with a concentration of 20 - 25%. Use the composite binder solution to granulate the mixture, then dry and screen and size the granules to obtain microcapsules; S2. Mix the microcapsules with the formulated amounts of filler, disintegrant, glidant, and lubricant to obtain a mixed material, and then use a tableting machine to tablet the mixed material to obtain tablets.

[0109] Table 6. Formulations, related parameters, and performance results of each treatment group in Example 6

[0110]

[0111] As can be seen from Table 6:

[0112] When the silica is 0.3 - 1.0 parts and the magnesium stearate is 1.2 - 2.0 parts, the granulation particle uniformity is good, the granulation yield is relatively high, the compressibility of the product is good, and under relatively low pressure, better hardness can be achieved, the friability is also qualified, the tableting operation process is stable (RSD < 5%), the disintegration time limit is qualified, no rubbing black situation is seen, and the impact on die wear is also small. Therefore, the suitable range of silica in the present invention is 0.3 - 1.0 parts, and the suitable range of magnesium stearate is 1.2 - 2.0 parts.

[0113] Example 7

[0114] This example explores the effects of adding functional components, fillers, and other disintegrants. A total of 7 treatment groups, namely treatment groups 20 - 26, are set up. The formulations, related parameters, and performance results of each treatment group are shown in Table 7.

[0115] In each treatment group of this example, the preparation method of the tablets is as follows: S1. Mix the formulated amounts of magnesium oxide and magnesium stearate evenly to obtain a mixture. Add solid powders of HPMC and PVP - K30 with a weight ratio of 1:10 to ethanol to prepare a composite binder solution with a concentration of 20 - 25%. Use the composite binder solution to granulate the mixture, then dry and screen and size the granules to obtain microcapsules; S2. Mix the microcapsules with the formulated amounts of fillers, disintegrants, glidants, lubricants, and functional components to obtain a mixed material, and then use a tableting machine to tablet the mixed material to obtain tablets.

[0116] Table 7. Formulations, related parameters, and performance results of each treatment group in Example 7

[0117]

[0118]

[0119] As can be seen from Table 7:

[0120] Other fillers, such as sorbitol, mannitol, lactose, etc. can also meet the requirements of the tablets. Other disintegrants, such as sodium carboxymethyl starch, cross - linked povidone, etc. can also meet the requirements of the tablets. Other functional components such as plant extracts and / or vitamins can also meet the requirements of the tablets.

[0121] The above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit the protection scope of the present invention. Although the present invention has been described in detail with reference to the above embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced, but such modifications or replacements are all within the protection scope of the present invention.

Claims

1. A microcapsule, characterized in that: The microcapsule comprises the following components in parts by weight: 70-83 parts of magnesium oxide, 1-2.5 parts of stearic acid, and 3.5-5.5 parts of a composite adhesive. The particle size D90 of the magnesium oxide is 15-150 μm. The composite adhesive is a composition of HPMC and PVP, and the PVP is PVP-K30.

2. The microcapsule according to claim 1, characterized in that: The weight ratio of PVP to HPMC in the composite adhesive is 7:1 to 11:

1.

3. The microcapsule according to claim 1 or 2, characterized in that: The weight ratio of PVP to HPMC in the composite adhesive is 7:1 to 10:

1.

4. A tablet, characterized in that include: The microcapsule according to any one of claims 1 to 3.

5. The tablet according to claim 4, characterized in that: The tablet further comprises at least one of a filler, a disintegrant, a glidant, a release agent, and a functional ingredient; Preferably, the filler comprises at least one of microcrystalline cellulose, sorbitol, mannitol, and lactose; Preferably, the disintegrant comprises at least one of cross-linked carboxymethyl cellulose sodium, sodium carboxymethyl starch, and cross-linked polyvinylpyrrolidone; Preferably, the glidant comprises silicon dioxide; Preferably, the release agent comprises magnesium stearate; Preferably, the functional ingredients include plant extracts and / or vitamins; more preferably, the plant extract includes at least one of fennel, citrus extract, and licorice extract, and the vitamins include at least one of vitamin A, vitamin C, vitamin D, vitamin E, and B vitamins.

6. The tablet according to claim 5, characterized in that The tablet comprises the following components in parts by weight: 74.5 to 91 parts of microcapsules, 5 to 20 parts of fillers, 1 to 6 parts of disintegrants, 0.1 to 1.5 parts of glidants, 1.0 to 2.0 parts of release agents, and 0 to 5 parts of functional ingredients.

7. The tablet according to any one of claims 4 to 6, characterized in that: The surface of the tablet is coated with a coating layer, the mass of the coating layer makes R 0-5%, wherein R = the mass of the coating layer / (the mass of the tablet - the mass of the coating layer); Preferably, the raw materials for preparing the coating layer include at least one of ethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol and polyethylene glycol.

8. A method for preparing microcapsules, characterized in that: The preparation method is used to prepare the microcapsule according to any one of claims 1 to 3, and the preparation method comprises the following steps: The magnesium oxide and stearic acid in the formula amount are uniformly mixed to obtain a mixture, the mixture is granulated with a composite binder solution, and then dried and sieved to obtain microcapsules; Preferably, the composite adhesive solution is prepared by adding a formula amount of HPMC and PVP solid powders into ethanol to prepare the composite adhesive solution with a concentration of 20 to 25%; Preferably, the granulation is wet granulation.

9. A method for preparing a tablet, characterized in that: The preparation method is used to prepare the tablet according to any one of claims 4 to 7, and the preparation method comprises the following steps: S1. The amount of magnesium oxide and stearic acid is uniformly mixed to obtain a mixture, the mixture is granulated using a composite binder solution, and then dried and sieved to obtain microcapsules; S2. Using a tablet press to compress the microcapsules to obtain the magnesium oxide tablets; Preferably, in S1, the HPMC and PVP solid powders in the formula amount are added to ethanol to prepare the composite adhesive solution with a concentration of 20-25%; Preferably, the granulation is wet granulation; Preferably, in S2, the microcapsules are mixed with a formula amount of a filler, a disintegrant, a glidant, a release agent and a functional component to obtain a mixed material, and then the mixed material is compressed using a tablet press to obtain the tablet; Preferably, the preparation method further comprises S3. coating the surface of the tablet with a coating layer to obtain the tablet with the coating layer.

10. Use of the microcapsule according to any one of claims 1 to 3 and / or the tablet according to any one of claims 4 to 7 in food and / or medicine.

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