Microcapsules, tablets, and methods of making and using the same

Abstract

The application provides a kind of microcapsule, tablet and its preparation method and application, microcapsule includes the following weight parts of component: magnesium oxide 70~83 parts, stearic acid 1~2.5 parts, composite binder 3.5~5.5 parts, the particle size D90 of magnesium oxide is 15~150 μm, composite binder is the combination of HPMC and PVP, and PVP is PVP-K30.The tablet includes magnesium oxide microcapsule.The preparation method of tablet includes the following steps: S1.mixed uniformly after formula amount of magnesium oxide and stearic acid to obtain mixture, the mixture is granulated using composite binder solution, then dried and sieved whole grain, to obtain microcapsule;S2.tablet is pressed to microcapsule using tablet press, to obtain tablet.The application reaches the effect of granulating particle uniform, product compressibility improves, improves product blackening problem, improves product yield and production stability, and improves equipment service life to a certain extent through specific material composition, specific magnesium oxide particle size range.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of dietary supplements, in particular to a microcapsule, a tablet and a preparation method and application thereof. BACKGROUND

[0002] Magnesium oxide is a white or off-white powder, odorless, tasteless, non-toxic, and is a typical alkaline earth metal oxide. The melting point of magnesium oxide is 2852℃, the boiling point is 3600℃, and the density at room temperature is 3.58g / cm 3 . Magnesium oxide dissolves in acid and ammonium salt solution, is difficult to dissolve in water, and is insoluble in alcohol. Its solubility in water is 0.00062g / 100mL (0℃), 0.0086g / 100mL (30℃), magnesium oxide exposed to air can easily absorb moisture and carbon dioxide in the air to form basic magnesium carbonate, and can combine with water under certain conditions to form magnesium hydroxide, showing a weak alkaline reaction, and the pH of the saturated aqueous solution is 10.3.

[0003] The magnesium oxide tablet is mainly composed of magnesium oxide, a filler, a binder and a disintegrant. Because the hardness of magnesium oxide is relatively high, its Mohs hardness is 5.5-6.6, in the production of existing magnesium oxide tablets, when the content of magnesium oxide is greater than 40%, it is easy to appear blackening after the mutual friction of the material and the metal parts of the tablet press, and the metal parts cannot be avoided in the current production process of magnesium oxide tablets. Therefore, many high-magnesium oxide content magnesium oxide tablets are prone to appear blackening patches on the surface, and a non-transparent coating powder can be used to cover the magnesium oxide tablets to cover the blackening. When the content of magnesium oxide is greater than 70%, the compressibility of the product is poor, and cracking or insufficient hardness may occur during the tabletting process, which seriously affects the production of the product. Although the addition of a binder can improve the situation, the addition of a binder can easily lead to coarse and hard granules after granulation, resulting in the waste of coarse granules and affecting the yield, and the high hardness can further aggravate the blackening and affect the service life of the tablet press.

[0004] In summary, in the current production process of high-content magnesium oxide tablets, it is easy to appear problems such as poor uniformity of granules after granulation, poor compressibility of products, low yield of products after granulation, difficult normal and stable operation of production, blackening on the surface of magnesium oxide tablets, and damage to the tablet press. SUMMARY

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

[0006] The first aspect of the present application provides a microcapsule, which 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 binder; the particle size D90 of the magnesium oxide is 15-150 μm; the composite binder is a combination of HPMC and PVP, and the PVP is PVP-K30.

[0007] The present application is dedicated to preparing a microcapsule with high content of magnesium oxide and uniform granulation. The specific means are as follows: first, selecting magnesium oxide with a specific particle size range, i.e., 100-800 mesh, as the main material; second, adding a suitable binder, i.e., a combination of HPMC and PVP (preferably PVP-K30), to coat the magnesium oxide; third, adding stearic acid to reduce the friction between the granulation particles and between the particles and metal parts, and to reduce the proportion of coarse particles generated during the granulation process; and fourth, limiting the specific ratio of magnesium oxide, stearic acid, and composite binder, i.e., (70-83):(1-2.5):(3.5-5.5). In this way, the present application uses stearic acid and magnesium oxide with a specific particle size range for granulation, and adds a combination of two binders (a combination of HPMC and PVP-K30) to coat the magnesium oxide with the composite binder and to lubricate with stearic acid, thereby reducing the friction between the granulation particles and between the particles and metal parts, and reducing the proportion of coarse particles generated during the granulation process, thereby improving the yield of the product and simultaneously improving the blackening problem of the microcapsule with high content of magnesium oxide.

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

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

[0010] The second aspect of the present application provides a tablet, which comprises the above-mentioned microcapsule.

[0011] The weight fraction of magnesium oxide in the microcapsule of the tablet is 70-83 parts, so as to prepare a tablet with high magnesium oxide content and uniform granulation. The specific means are as follows: first, selecting magnesium oxide with a specific particle size range, wherein the present application selects magnesium oxide with a particle size D90 of 15-150 μm, i.e. 100-800 mesh, as the main material; second, adding a suitable binder, wherein the present application selects a combination of HPMC and PVP-K30 as the composite binder to coat the magnesium oxide; third, adding stearic acid to achieve the purpose of lubrication, so as to reduce the friction between the granulation particles and between the particles and metal parts, and to reduce the proportion of coarse particles generated in the granulation process; and fourth, limiting the specific ratio of magnesium oxide, stearic acid and composite binder, i.e. (70-83):(1-2.5):(3.5-5.5). In this way, the present application adds stearic acid and magnesium oxide with a specific particle size range for granulation, and adds a combination of two binders (a combination of HPMC and PVP-K30) to coat the magnesium oxide with the composite binder, and uses stearic acid for lubrication, so as to reduce the friction between the granulation particles and between the particles and metal parts, and to reduce the proportion of coarse particles generated in the granulation process, thereby improving the yield of the product and simultaneously improving the problem of blackening of the high-content magnesium oxide tablet.

[0012] In summary, the present application achieves uniform granulation of the magnesium oxide by using the ratio of stearic acid+HPMC+PVP-K30 to magnesium oxide with a specific particle size range, improves the compressibility of the product, improves the problem of blackening of the product, improves the yield and production stability of the product, and to some extent, improves the service life of the equipment.

[0013] Preferably, the microcapsule is 74.5-91 parts.

[0014] Preferably, the tablet further comprises at least one of a filler, a disintegrant, a glidant, a release agent, and a functional ingredient. The addition of the filler, the disintegrant, the glidant and the release agent is more conducive to improving the uniformity of the granulation particles, the granulation yield and the problem of blackening of the magnesium oxide tablet, and can improve the compressibility of the product and the service life of the equipment. The addition of plant extracts and vitamins can impart corresponding effects to the magnesium oxide microcapsule.

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

[0016] Preferably, the disintegrant is 1-6 parts, 2-5 parts or 2-4 parts, and the disintegrant comprises at least one of croscarmellose sodium, sodium carboxymethyl starch and cross-linked povidone.

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

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

[0019] Preferably, the functional ingredient is 0-5 parts, and the functional ingredient comprises a plant extract and / or a vitamin.

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

[0021] Preferably, the tablet is coated with a coating layer, the mass of the coating layer is such that R is 0-5%, R = mass of the coating layer / (mass of the tablet - mass of the coating layer), and the preparation raw material of the coating layer comprises at least one of ethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, and polyethylene glycol. The coating layer is beneficial to covering up the defects such as mottling on the surface of the tablet, so as to ensure the good appearance of the tablet. The mass of the coating layer affects the disintegration time of the tablet and the covering effect, when the value of R satisfies the range of 0-5%, the coating layer can have a good covering effect and ensure the disintegration of the tablet within a specified time. When R is greater than 5%, the disintegration time of the tablet is prolonged, which affects the drug efficacy of the tablet. In theory, the tablet prepared by the present application has no defects such as mottling on the surface, and therefore the coating layer can not be coated.

[0022] The third aspect of the present application provides a preparation method of a microcapsule, which is used for preparing the microcapsule provided in the first aspect of the present application, and the preparation method comprises the following steps:

[0023] The formula amount of magnesium oxide and stearic acid are mixed uniformly to obtain a mixture, the mixture is granulated using a composite binder solution, and then dried and sieved to obtain the microcapsule.

[0024] Preferably, the configuration method of the composite binder solution is to add the formula amount of HPMC and PVP solid powders into ethanol to prepare a composite binder solution with a concentration of 20-25%.

[0025] Preferably, the granulation is wet granulation.

[0026] The fourth aspect of the present application provides a preparation method of a tablet, which is used for preparing the tablet provided in the second aspect of the present application, and the preparation method comprises the following steps:

[0027] S1. The formula amount of magnesium oxide and stearic acid are mixed uniformly to obtain a mixture, the mixture is granulated using a composite binder solution, and then dried and sieved to obtain the microcapsule;

[0028] S2. The microcapsule is tableted using a tablet press to obtain the tablet.

[0029] The preparation method of the present application is mainly used for producing tablet products, including but not limited to health foods, dietary supplements, the daily dosage of which is limited according to the efficacy material. The tablet of the present application is prepared by adding stearic acid and magnesium oxide with a specific particle size range for granulation, and adding a combination of two binders (a combination of HPMC and PVP-K30) to coat the magnesium oxide, and using stearic acid for lubrication, so as to reduce the friction between the granulated particles and between the particles and the metal parts, and reduce the proportion of coarse particles generated in the granulation process, thereby improving the yield of the product and simultaneously improving the problem of blackening of high-content magnesium oxide tablets.

[0030] Preferably, in S1, the formula amount of HPMC and PVP solid powder is 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 formula amount of fillers, disintegrants, glidants, release agents and functional ingredients to obtain a mixture, and then the mixture is tabletted using a tablet press to obtain tablets.

[0033] Preferably, the preparation method further comprises S3. Coating a coating layer on the surface of the tablet to obtain a tablet with a coating layer. In theory, the tablet prepared by the present application has no defects such as blackening on the surface, and no coating layer is needed. If defects such as blackening are generated due to improper operation of some steps during production, 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 tablet.

[0034] The fifth aspect of the present application provides a microcapsule and / or tablet for use in food and / or medicine. DETAILED DESCRIPTION

[0035] The technical features of the technical solutions provided by the present application will be further described clearly and completely in combination with the specific embodiments. Obviously, the described embodiments are only a part of the embodiments of the present application, not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0036] The materials used in the examples and comparative examples of the present application are all commercially available, wherein HPMC is carboxypropyl methyl cellulose, and PVP-K30 is a kind of polyvinylpyrrolidone.

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

[0038] The instruments used are electronic balance, friability tester and disintegration tester.

[0039] Test items:

[0040] (1) Granule uniformity: After granulation, the granules are sieved, and the proportion of particles in the 20-80 mesh interval is calculated, denoted as q; the proportion of particles in the <20 mesh interval is calculated, denoted as w. Wherein, q≥75% and w<12%, it means that the granules meet the requirements, the uniformity is high, and the proportion of coarse particles is low; w≥12%, it means that the proportion of coarse particles is high.

[0041] (2) Granulation yield a: The percentage value of the mass M1 of granules dried through a 20 mesh sieve to the mass M2 of the material before granulation: a = M1*100% / M2.

[0042] (3) Quality evaluation of tablets

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

[0044] Hardness: Place the tablet after tabletting on the friability hardness tester, click start test, measure the hardness value of the corresponding tablet, and read and record, unit N.

[0045] Pressure & hardness: The lower the pressure, the higher the hardness, indicating that the compressibility of the product is better, and vice versa, indicating that the compressibility of the product is worse.

[0046] Friability: According to the requirements of the Inspection Method for Tablet Friability in the Third Part of the Pharmacopoeia of the People's Republic of China (2020 Edition), the friability is measured, unit %. Friability can reflect the friability and strength of the product to some extent, and is used to evaluate the risk of subsequent coating, packaging and transportation. Under normal circumstances, the friability is required to be <1%.

[0047] (4) Disintegration time: The tablets prepared are measured according to the Disintegration Time Inspection Method in the Third Part of the Pharmacopoeia of the People's Republic of China (2020 Edition), unit min, the requirement is ≤60 min, and the conventional internal control requirement is ≤45 min.

[0048] (5) Degree of tablet rubbing black: Use GODA standard stain card to judge the degree of rubbing black of the pressed tablets, judgment criteria: A. No rubbing black: no rubbing black visible to the naked eye; B. Slight rubbing black: black spot length or diameter <1.0 mm; C. Partial rubbing black: black spot length or diameter between 1.0-1.5 mm; D. Obvious rubbing black: black spot length or diameter ≥1.5 mm.

[0049] (6) Evaluation of tabletting running stability (relative standard deviation RSD of tablet weight)

[0050] After the tabletting machine is running normally, 40 tablets are continuously taken out from the tablet outlet, the weight of each tablet is measured, the RSD value of the tablet weight under the operation of the equipment of this formula is recorded and calculated, and the RSD value is generally required to be ≤5%, which represents stable operation. The larger the RSD value, the poorer the stability of the operation. Relative standard deviation (RSD) = standard deviation (SD) / arithmetic mean of the calculation result (X).

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

[0052] (8) Test of magnesium oxide mesh number: The average 2-time particle size of magnesium oxide is measured by a laser scattering particle size distribution instrument.

[0053] Example 1

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

[0055] The preparation method of the tablets in each treatment group of this example is as follows: S1. Mix the formula amount of magnesium oxide and stearic acid uniformly to obtain a mixture. Add HPMC and PVP-K30 solid powders in 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 sieve the granules to obtain microcapsules; S2. Mix the microcapsules with the formula amount of filler, disintegrant, glidant and release agent to obtain a mixture, then use a tablet press to tablet the mixture to obtain tablets.

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

[0057]

[0058] Note: The parts of the composite binder are calculated according to the solute, and the calculation method is consistent in the subsequent examples.

[0059] From Table 1, it can be seen that:

[0060] A. When the parts of magnesium oxide are 70-83 parts, the granulation particle uniformity is good, the granulation yield is high, the compressibility of the product is good, and better hardness can be achieved under smaller pressure, the friability is also qualified, the tabletting operation process is stable (RSD < 5%), the disintegration time limit is qualified, no blackening is observed, and the influence on the mold wear is also small.

[0061] B. When the content of magnesium oxide is less than 70 parts, the product has a larger auxiliary material space, better product formability, etc.

[0062] C. When the content of magnesium oxide is more than 83 parts, the granulation particles have poor uniformity, more coarse particles, a low granulation yield, poor compressibility of the product, a large pressure required for product molding, a relatively low hardness, a relatively high friability, poor stability during tabletting (RSD>5%), a long disintegration time, partial blackening, and an impact on mold wear.

[0063] D. When the particle size of magnesium oxide is relatively coarse (320 um), the granulation particles have poor uniformity, a high proportion of coarse particles, poor compressibility of the product, high friability, a long disintegration time, and obvious blackening, which has a large impact on mold wear. When the particle size of magnesium oxide is relatively fine (11 um), the disintegration time is relatively long, because the material is too fine, the specific surface area is larger, and more water can be adsorbed. Moreover, the whole production process is more complicated, the screening time is longer, and the material is more difficult to disperse. Therefore, in order to improve the production efficiency, the material is not used.

[0064] In summary, because the hardness of magnesium oxide is relatively high, a high content of magnesium oxide will affect the molding, disintegration, and appearance of the product. Therefore, the suitable range of the high content of magnesium oxide in the present application is 70-83 parts, and the D90 particle size is 150 um-15 um.

[0065] Example 2

[0066] This example investigates the influence of the ratio of HPMC and PVP-K30 in the composite binder. There are 6-8 experimental treatment groups, 4-5 comparative treatment groups, a total of 5 treatment groups, and the formulations of the treatment groups and related parameters and performance results are shown in Table 2.

[0067] The preparation method of the tablets in each treatment group of this example is as follows: S1. Mix the formulation amount of magnesium oxide and stearic acid uniformly to obtain a mixture. Add a total of 4.5 parts of HPMC and PVP-K30 solid powder into 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 the whole to obtain microcapsules; S2. Mix the microcapsules with the formulation amount of fillers, disintegrants, glidants, and release agents to obtain a mixture, then use a tablet press to tablet the mixture to obtain tablets.

[0068] Table 2. Formulations of each treatment group in Example 2 and related parameters and performance results

[0069]

[0070] From Table 2, it can be seen that:

[0071] A. When the ratio of PVP-K30 to HPMC in the compound adhesive is between 7:1 and 10:1, the granulation particles are uniform, the granulation yield is high, the product has good compressibility, better hardness can be achieved under smaller pressure, the friability is qualified, the tabletting process is stable (RSD < 5%), the disintegration time is qualified, there is no blackening, and the impact on mold wear is small.

[0072] B. When the ratio of PVP-K30 to HPMC in the compound adhesive is 6:1 < 7:1, the granulation particles are not uniform, there are many coarse particles, the granulation yield is too low, the product has poor compressibility, a larger pressure is needed to form the product, the hardness is relatively low, the friability is relatively high, the tabletting process is not stable (RSD > 5%), the disintegration time is longer, there is a problem of blackening, and the impact on mold wear is significant.

[0073] C. When the ratio of PVP-K30 to HPMC in the compound adhesive is 11:1 > 10:1, there are more fine particles in the granulation, the product has poor compressibility, a larger pressure is needed to form the product, the hardness is relatively low, the friability is relatively high, and the tabletting process is not stable (RSD > 5%), the disintegration time is longer.

[0074] In summary, the viscosity of HPMC is higher than that of PVP-K30, so a higher proportion of HPMC will result in more coarse particles during granulation, which will affect the relevant indicators. However, if the proportion of HPMC is too low, the granulation particles will be powdery, which will affect the relevant indicators. Therefore, the suitable ratio of PVP-K30 to HPMC in the compound adhesive in the present application is 7:1 to 10:1.

[0075] Example 3

[0076] This example investigates the impact of stearic acid content. A total of 5 treatment groups are set up, including 9-10 treatment groups and 6-8 comparison treatment groups. The formulations and related parameters and performance results of each treatment group are shown in Table 3.

[0077] The preparation method of tablets in each treatment group of this example is as follows: S1. Mix the formula amount of magnesium oxide and stearic acid uniformly to obtain a mixture. Add HPMC and PVP-K30 solid powder in a weight ratio of 1:10 to ethanol to prepare a compound adhesive solution with a concentration of 20-25%. Granulate the mixture using the compound adhesive solution, then dry and sieve the granules to obtain microcapsules; S2. Mix the microcapsules with the formula amount of filler, disintegrant, glidant and release agent to obtain a mixture, then use a tablet press to tablet the mixture to obtain tablets.

[0078] Table 3. Formulations and related parameters and performance results of each treatment group in Example 3

[0079]

[0080] From Table 3, it can be seen that:

[0081] A. When the proportion of stearic acid is 1-2.5 parts, the granulation uniformity is good, the granulation yield is relatively high, the compressibility of the product is relatively good, the hardness can be better reached under the condition of smaller pressure, the friability is also qualified, the tabletting running process is stable (RSD < 5%), the disintegration time limit is qualified, there is no blackening situation, and the influence on the mold wear is also small.

[0082] B. When the proportion of stearic acid is less than 1 part, or even not added, there are more coarse particles in the granulation, the granulation yield is relatively low, the compressibility of the product is relatively poor, the hardness of the product is relatively low under the condition of larger pressure, the friability is also relatively increased or even unqualified, the tabletting running process stability is poor (RSD > 5%), the disintegration is qualified, but the magnesium oxide tablets appear blackening, and the influence on the mold wear is evaluated.

[0083] C. When the proportion of stearic acid is greater than 2.5 parts, the granulation has more fine powder, the granulation yield is relatively high, the compressibility of the product is poor, the hardness of the product is relatively low under the condition of larger pressure, the friability is qualified, the tabletting running process is stable (RSD < 5%), the disintegration time limit is critical, there is no blackening situation, and the influence on the mold wear is relatively small.

[0084] In summary, stearic acid has lubricating and partial adhesive effect, when the proportion is appropriate, it can improve the friction between the particles, and because of its hydrophobicity, it is more beneficial to the uniform dispersion of the adhesive during granulation, so that the quality of the tablets meeting the requirements can be obtained; when it is too much, because of excessive lubrication and the problem of softening caused by the low melting point of stearic acid, the compressibility of the product is poor, and because of its hydrophobicity, the disintegration time of the product is also long. If it is added too little or even not added, it will lead to problems such as coarse granulation and poor compressibility of the product. Therefore, the suitable range of stearic acid in the present application is 1-2.5 parts.

[0085] Example 4

[0086] This example explores the influence of the content of the composite adhesive, a total of 11-12 implementation treatment groups, 9-12 comparative treatment groups, a total of 6 treatment groups, the formula and related parameters and performance results of each treatment group are shown in Table 4.

[0087] The preparation method of the tablets in each processing group of the embodiment is as follows: S1. The formula amount of magnesium oxide and stearic acid is uniformly mixed to obtain a mixture, solid powders of HPMC and PVP-K30 in a weight ratio of 1:10 are added to ethanol to prepare a composite binder solution with a concentration of 20-25%, the composite binder solution is used for granulation of the mixture, then the mixture is dried and sieved to obtain microcapsules; S2. The microcapsules are mixed with the formula amount of fillers, disintegrating agents, glidants and release agents to obtain a mixture, and then the mixture is pressed by a tablet press to obtain tablets.

[0088] Table 4. Formulas and related parameters and performance results of each processing group in Example 4

[0089]

[0090] From Table 4, it can be seen that:

[0091] A. When the amount of composite binder (PVP-K30 and HPMC) is 3.5-5.5 parts, the granulation particles are uniform, the granulation yield is high, the compressibility of the product is good, the hardness can be better under smaller pressure, the friability is qualified, the tabletting process is stable (RSD<5%), the disintegration time limit is qualified, there is no blackening, and the influence on mold wear is small.

[0092] B. When the amount of composite binder (PVP-K30 and HPMC) is <3.5 parts, the granulation particles have more fine powder, the granulation yield is high, the compressibility of the product is poor, the hardness that can be achieved is low under larger pressure, the friability is also high or even exceeds the standard, the tabletting process is relatively stable (RSD close to 5%), the disintegration time limit is qualified, blackening occurs, and the influence on mold wear is evaluated.

[0093] C. When the amount of composite binder (PVP-K30 and HPMC) is >5.5 parts, the granulation particles have more coarse particles, the granulation yield is low, the compressibility of the product is poor, the hardness that can be achieved is low under larger pressure, the friability is also high, the tabletting process is relatively stable (RSD close to or even exceeds 5%), the disintegration time limit is qualified, blackening occurs, and the influence on mold wear is evaluated.

[0094] In summary, within a certain addition range, the composite binder can significantly improve the uniformity of the granulation particles and the compressibility of the product, and too little addition will result in more fine powder and poor compressibility, and too much addition will result in more coarse particles and product blackening. Therefore, the suitable range of the composite binder (PVP-K30 and HPMC) of the present application is 3.5-5.5 parts.

[0095] Example 5

[0096] The present embodiment explores the influence of disintegrant content, and a total of 13-15 implementation treatment groups are set, a total of 3 treatment groups, the formula and related parameters, performance results of each treatment group are shown in Table 5.

[0097] The preparation method of tablets in each treatment group of the present embodiment is as follows: S1. The formula amount of magnesium oxide and stearic acid is mixed uniformly to obtain a mixture, and the solid powder of HPMC and PVP-K30 in a weight ratio of 1:10 is added to ethanol to prepare a composite binder solution with a concentration of 20-25%, and the mixture is granulated using the composite binder solution, then dried and sieved to obtain microcapsules; S2. The microcapsules are mixed with the formula amount of filler, disintegrant, glidant and release agent to obtain a mixture, and then the mixture is tableted using a tablet press to obtain tablets.

[0098] Table 5. Formula and related parameters, performance results of each treatment group in Example 5

[0099]

[0100] From Table 5, it can be seen that:

[0101] When the disintegrant portion is 2-5 parts, the granulation particle uniformity is good, the granulation yield is higher, the product has better compressibility, better hardness can be achieved under smaller pressure, the friability is also qualified, the tabletting process is stable (RSD<5%), the disintegration time limit is qualified, there is no blackening, and the influence on mold wear is also small. Therefore, the suitable range of the disintegrant of the present application is 2-5 parts.

[0102] Example 6

[0103] The present embodiment explores the influence of disintegrant content, and a total of 13-15 implementation treatment groups are set, a total of 3 treatment groups, the formula and related parameters, performance results of each treatment group are shown in Table 5.

[0104] The preparation method of tablets in each treatment group of the present embodiment is as follows: S1. The formula amount of magnesium oxide and stearic acid is mixed uniformly to obtain a mixture, and the solid powder of HPMC and PVP-K30 in a weight ratio of 1:10 is added to ethanol to prepare a composite binder solution with a concentration of 20-25%, and the mixture is granulated using the composite binder solution, then dried and sieved to obtain microcapsules; S2. The microcapsules are mixed with the formula amount of filler, disintegrant, glidant and release agent to obtain a mixture, and then the mixture is tableted using a tablet press to obtain tablets.

[0105] Table 6. Formula and related parameters, performance results of each treatment group in Example 6

[0106]

[0107] From Table 6, it can be seen that:

[0108] When the silica is 0.3-1.0 parts and the magnesium stearate is 1.2-2.0 parts, the granulation uniformity is good, the granulation yield is higher, the compressibility of the product is better, the hardness can be better under the condition of smaller pressure, the friability is also qualified, the tabletting process is stable (RSD < 5%), the disintegration time is qualified, there is no blackening, and the influence on the mold wear is also small. Therefore, the suitable range of the silica is 0.3-1.0 parts, and the suitable range of the magnesium stearate is 1.2-2.0 parts.

[0109] Example 7

[0110] In this example, the influence of adding functional ingredients, fillers, and other disintegrants is explored. A total of 20-26 treatment groups are set, and a total of 7 treatment groups are set. The formulations of each treatment group and the related parameters and performance results are shown in Table 7.

[0111] In each treatment group of this example, the preparation method of the tablets is as follows: S1. The magnesium oxide and the stearic acid are mixed uniformly to obtain a mixture. The HPMC and PVP-K30 solid powders in a weight ratio of 1:10 are added to ethanol to prepare a composite binder solution with a concentration of 20-25%. The mixture is granulated using the composite binder solution, then dried and sieved to obtain microcapsules; S2. The microcapsules are mixed with the formula amount of fillers, disintegrants, glidants, release agents, and functional ingredients to obtain a mixture, and then the mixture is compressed using a tablet press to obtain tablets.

[0112] Table 7. Formulations of each treatment group in Example 7 and related parameters and performance results

[0113]

[0114] From Table 7, it can be seen that:

[0115] 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 ingredients, such as extracts and / or vitamins, can also meet the requirements of the tablets.

[0116] The above examples are only used to illustrate the technical solutions of the present application, and are not intended to limit the scope of protection of the present application. Although the present application has been described in detail with reference to the above examples, it should be understood by those skilled in the art that the technical solutions of the present application can be modified or replaced by equivalents, but these modifications or replacements are within the scope of protection of the present application.

Claims

1. A microcapsule, characterized in that, The microcapsules are made of the following components in parts by weight: 70-83 parts magnesium oxide, 1-2.5 parts stearic acid, and 3.5-5.5 parts composite binder. The particle size D90 of the magnesium oxide is 15-150 μm. The composite binder is a composition of HPMC and PVP. The weight ratio of PVP to HPMC in the composite binder is 7:1-11:

1. The PVP is PVP-K30. After mixing magnesium oxide and stearic acid in the prescribed amounts to obtain a mixture, the mixture is granulated using a composite binder solution, then dried and sieved to obtain the microcapsules.

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 10:

1.

3. A tablet, characterized in that, include: The microcapsule according to claim 1 or 2.

4. The tablet according to claim 3, characterized in that: The tablets also include at least one of the following: fillers, disintegrants, flow aids, release agents, and functional ingredients.

5. The tablet according to claim 4, characterized in that: The filler includes at least one of microcrystalline cellulose, sorbitol, mannitol, and lactose; And / or, the disintegrant includes at least one of croscarmellose sodium, carboxymethyl starch sodium, and croscarmellose. And / or, the flow aid comprises silica; And / or, the release agent comprises magnesium stearate; And / or, the functional ingredients include plant extracts and / or vitamins.

6. The tablet according to claim 5, characterized in that: The plant extract includes at least one of fennel extract, citrus extract, and licorice extract, and the vitamins include at least one of vitamin A, vitamin C, vitamin D, vitamin E, and B vitamins.

7. The tablet according to claim 4, characterized in that, The tablet comprises the following components in parts by weight: 74.5-91 parts microcapsules, 5-20 parts filler, 1-6 parts disintegrant, 0.1-1.5 parts glidant, 1.0-2.0 parts release agent, and 0-5 parts functional ingredient.

8. The tablet according to any one of claims 3-7, characterized in that: The tablet is coated with a coating layer, the mass of which is R = 0-5%, and R = mass of the coating layer / (mass of the tablet - mass of the coating layer).

9. The tablet according to claim 8, characterized in that: The raw materials for preparing the coating layer include at least one of ethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, and polyethylene glycol.

10. A method for preparing microcapsules, characterized in that, The preparation method is used to prepare the microcapsules according to claim 1 or 2, and the preparation method includes the following steps: After mixing magnesium oxide and stearic acid in the prescribed amounts to obtain a mixture, the mixture is granulated using a composite binder solution, then dried and sieved to obtain microcapsules.

11. The method for preparing microcapsules according to claim 10, characterized in that: The method for preparing the composite adhesive solution is to add the prescribed amounts of HPMC and PVP solid powders to ethanol to prepare the composite adhesive solution with a concentration of 20-25%. And / or, the granulation is wet granulation.

12. A method for preparing a tablet, characterized in that, The preparation method is used to prepare the tablet according to any one of claims 3-9, and the preparation method includes the following steps: S1. After mixing magnesium oxide and stearic acid in the prescribed amounts evenly, a mixture is obtained. The mixture is then granulated using a composite binder solution, dried, and sieved to obtain microcapsules. S2. The microcapsules are compressed using a tablet press to obtain the tablets.

13. The method for preparing tablets according to claim 12, characterized in that: In step S1, the formulated amounts of HPMC and PVP solid powders are added to ethanol to prepare a composite adhesive solution with a concentration of 20-25%. And / or, the granulation is wet granulation; And / or, in S2, the microcapsules are mixed with the formulated amounts of filler, disintegrant, glidant, release agent and functional ingredient to obtain a mixture, and then the mixture is compressed into tablets using a tableting machine to obtain the tablets; And / or, the preparation method further includes S3. coating the surface of the tablet with a coating layer to obtain the tablet having a coating layer.

14. The use of a microcapsule according to claim 1 or 2 and / or a tablet according to any one of claims 3-9 in food.

15. The use of a microcapsule according to claim 1 or 2 and / or a tablet according to any one of claims 3-9 in the preparation of a pharmaceutical product.

Images