Magnesium oxide particle, preparation method thereof and magnesium oxide tablet

Abstract

The invention relates to the technical field of medicines, in particular to magnesium oxide particles, a preparation method thereof and magnesium oxide tablets. The magnesium oxide particles comprise the following components in percentage by mass: 50%-85% of magnesium oxide, 3%-10% of protein hydrophilic colloid, 3%-10% of a cross-linking agent and the balance of a filling agent, wherein the cross-linking agent comprises cellulose and / or cellulose derivatives. The preparation method comprises the following steps: S1, adding the protein hydrophilic colloid into water, stirring until the protein hydrophilic colloid is swelled, and heating or adjusting pH to induce hydrogel as slurry; s2, weighing magnesium oxide, a cross-linking agent and a filling agent according to a formula proportion, stirring and mixing, and then adding the slurry under stirring and shearing conditions for granulation and coating; and S3, granulating, drying and sieving the material to obtain the product. When the magnesium oxide particles are used for preparing tablets, the tablets can be effectively prevented from cracking, and meanwhile, the problem of black edges in the tabletting process can be solved.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to magnesium oxide particles and a preparation method thereof, and magnesium oxide tablets. Background Art

[0002] Magnesium oxide is widely used in food, health care products and pharmaceutical fields due to its non-toxic, tasteless and non-irritating properties. Magnesium oxide tablets are obtained by compressing the raw materials into tablets. We call the compression molding process the tableting process. In the tableting process, the compression operation is performed continuously and at high speed. Under such conditions, the pressure and density are dispersed inside the tablet, resulting in an uneven internal structure, easy cracking and stratification; and magnesium oxide tends to turn gray when it is pressed against metal, and black edges will appear over a long period of time. As the tableting progresses, the discoloration of magnesium oxide will become more and more serious, so that a batch of tablets will have a large color difference, which limits the application of magnesium oxide in tablet products.

[0003] At present, the prior art discloses the use of magnesium hydroxide as a raw material, which is calcined to generate magnesium oxide, and the magnesium oxide particles are prepared by adjusting the calcination temperature and time. This can improve tablet cracking and prevent stratification to a certain extent, but does not solve the problem of black edges of tablets. The tablets are usually required to be coated, which prolongs the process time and cost.

[0004] Therefore, it is necessary to adopt new technologies and new means to solve the problem of magnesium oxide turning gray and black during the tableting process, avoid direct contact between magnesium oxide and metal, and improve the production efficiency and quality of tablet products.

[0005] In view of this, the present invention is proposed. Summary of the invention

[0006] The first purpose of the present invention is to provide a magnesium oxide particle. The use of the magnesium oxide particle to prepare tablets can improve the black edge problem of magnesium oxide tablets, while avoiding tablet cracking and delamination, improving the compressibility of the product, and no additional coating treatment is required. The process time and cost can be shortened, the operation steps can be reduced, and energy consumption can be reduced.

[0007] The second object of the present invention is to provide a method for preparing the magnesium oxide particles as described above.

[0008] The third object of the present invention is to provide a magnesium oxide tablet, comprising the magnesium oxide particles as described above or the magnesium oxide particles prepared by the method for preparing the magnesium oxide particles as described above.

[0009] In order to achieve the above-mentioned purpose of the present invention, the following technical solutions are particularly adopted:

[0010] A magnesium oxide particle, comprising, by mass percentage, 50%-85% magnesium oxide, 3%-10% protein hydrophilic colloid, 3%-10% crosslinking agent and the remainder filler;

[0011] Wherein, the cross-linking agent includes cellulose and / or cellulose derivatives.

[0012] A method for preparing the magnesium oxide particles as described above comprises the following steps:

[0013] S1. Add the protein hydrophilic colloid into water, stir until swelling, heat or adjust the pH to induce the protein hydrophilic colloid solution to form a hydrogel, and use it as a slurry for later use;

[0014] S2. Using a wet granulation process, magnesium oxide, a crosslinking agent and a filler are weighed according to the formula ratio, stirred and mixed, and then the slurry is added under stirring and shearing conditions to granulate and achieve coating;

[0015] S3. The material in step S2 is granulated, dried and sieved to obtain the magnesium oxide particles.

[0016] A magnesium oxide tablet comprises the magnesium oxide particles as described above or the magnesium oxide particles prepared by the method for preparing the magnesium oxide particles as described above.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] (1) The protein hydrophilic colloid in the present invention serves as both an adhesive and a raw material for the wall material. The amino, hydroxyl and carboxyl functional groups in the protein hydrophilic colloid react chemically with the hydroxyl and amine functional groups on the surface of the cross-linking agent to form bonding forces such as covalent bonds or hydrogen bonds. The cross-linking and coating of the wall material are completed through the wet granulation process, which effectively resists the strong mechanical force in the tableting process, avoids direct contact between the metal and magnesium oxide, and avoids the generation of black edges in the tableting process. The filler can further increase the hardness and adhesion of the particles, avoid tablet stratification, and improve the compressibility of the product. The magnesium oxide particles in the present invention are used to prepare tablets, which can not only effectively prevent the cracking of the tablets, but also solve the problem of black edges in the tableting process, so that the tablets have better application in tablet products.

[0019] (2) The present invention completes coating at the same time as wet granulation, without the need for an additional coating step, and has a simple preparation process and fewer operating steps, thereby shortening the process time and cost and reducing energy consumption. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0021] Figure 1 The magnesium oxide tablets are obtained by pressing magnesium oxide particles available on the market;

[0022] Figure 2 The magnesium oxide tablets are obtained by tableting the magnesium oxide particles prepared in Example 5 of the present invention. DETAILED DESCRIPTION

[0023] The technical scheme of the present invention will be clearly and completely described below in conjunction with the accompanying drawings and specific embodiments, but it will be understood by those skilled in the art that the following described embodiments are part of embodiments of the present invention, rather than all embodiments, and are only used to illustrate the present invention, and should not be considered as limiting the scope of the present invention. Based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work are within the scope of protection of the present invention. If specific conditions are not specified in the embodiments, they are carried out according to normal conditions or conditions recommended by the manufacturer. If the manufacturer is not specified in the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0024] The first aspect of the present invention provides a magnesium oxide particle, which comprises, by mass percentage, 50%-85% magnesium oxide, 3%-10% protein hydrophilic colloid, 3%-10% cross-linking agent and the remainder filler;

[0025] The cross-linking agent includes cellulose and / or a cellulose derivative; at least a portion of the surface of the magnesium oxide is coated with a cross-linking product of a protein hydrophilic colloid and the cross-linking agent.

[0026] The present invention uses protein hydrophilic colloid as adhesive and wall material, and cellulose or its derivatives as cross-linking agent. After swelling, the protein has a certain adhesion force, can provide support between particles, and can be used as an adhesive. At the same time, the abundant hydroxyl, amino, imino and carboxyl groups in the protein structure form strong hydrogen bonds with the hydroxyl groups on the cross-linking agent skeleton or react with the functional groups on the surface of the cross-linking agent to form covalent bonds. The generated cross-linked product is coated on the surface of magnesium oxide, which can avoid direct contact between metal ions and magnesium oxide, so that no black edges are generated during the tableting process. Protein hydrophilic colloid is a natural nutritional food thickener with low antigenicity and biodegradability. Its molecular structure contains a large number of functional groups such as amino, hydroxyl and carboxyl groups, and the formed gel has good toughness. Cellulose is a macromolecular polysaccharide, rich in functional groups such as hydroxyl and amine groups, and its strong hydrogen bond network structure within and between molecules can provide greater physical support. After the two are cross-linked by covalent bonds, the strength of the composite film can be further improved, and the blackening of magnesium oxide in tablets can be effectively solved. The filler can further improve the hardness and adhesion of the particles, while avoiding tablet stratification and improving product compressibility, so that it has better application in tablet products. Compared with the prior art, the magnesium oxide particles provided by the present invention have better application effects, can not only effectively prevent tablet cracking, but also solve the black edge problem in the tableting process.

[0027] In some embodiments, typically but not limiting, for example, in the magnesium oxide particles, the mass percentage of magnesium oxide can be any value among 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or a range consisting of any two values; the mass percentage of the protein hydrophilic colloid can be any value among 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or a range consisting of any two values; the mass percentage of the cross-linking agent can be any value among 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or a range consisting of any two values.

[0028] In some specific embodiments of the present invention, the protein hydrocolloid includes at least one of gelatin, fish gelatin, whey protein, casein and its salt, soy protein isolate or alcohol-soluble protein.

[0029] In some embodiments of the present invention, the cross-linking agent includes at least one of microcrystalline cellulose, sodium carboxymethyl cellulose, methyl cellulose and hydroxypropyl methyl cellulose.

[0030] In some specific embodiments of the present invention, the filler includes at least one of maltodextrin, mannitol, and starch.

[0031] In some specific embodiments of the present invention, the particle size of the magnesium oxide particles is 20-100 mesh, for example, it can be any point value among 20 mesh, 40 mesh, 60 mesh, 80 mesh, 100 mesh, or a range value consisting of any two point values.

[0032] A second aspect of the present invention provides a method for preparing the magnesium oxide particles according to any one of the aforementioned embodiments, comprising the following steps:

[0033] S1. Add the protein hydrophilic colloid into water, stir until swelling, heat or adjust the pH to induce the protein hydrophilic colloid solution to form a hydrogel, and use it as a slurry for later use;

[0034] S2. A wet granulation process is adopted, magnesium oxide, a cross-linking agent and a filler are weighed according to the formula ratio, stirred and mixed, and then the slurry is added under stirring and shearing conditions to granulate and achieve coating; wherein the cross-linking agent includes cellulose and / or a cellulose derivative;

[0035] S3. The material in step S2 is granulated, dried and sieved to obtain the magnesium oxide particles.

[0036] The present invention adopts a wet granulation process, after the magnesium oxide, the crosslinking agent and the filler are stirred and mixed uniformly, a colloidal slurry is added under stirring and high-speed shearing action, and a protein hydrophilic colloid is coated around the magnesium oxide molecules. The cellulose or its derivatives have strong water absorption and can absorb the water in the colloidal slurry and swell into a network structure. The magnesium oxide is insoluble in water and can be adsorbed into the pore structure of the swelled cellulose or its derivatives during the mixing process. The amino, hydroxyl and carboxyl functional groups in the protein molecules react with the functional groups on the surface of the crosslinking agent, and the generated crosslinked products are coated on the surface of the magnesium oxide to obtain magnesium oxide particles coated with the protein hydrophilic colloid-cellulose crosslinked product. The prepared magnesium oxide particles can avoid direct contact between the magnesium oxide and the metal during tableting, thereby improving the black edge problem caused by tableting.

[0037] The magnesium oxide particles prepared by the method of the present invention are used to prepare magnesium oxide tablets, which can effectively prevent the tablets from cracking and stratification, and can solve the black edge problem in the tablet pressing process; and compared with conventional embedding technologies (such as spray drying, air suspension coating, condensation spray, etc.), this method has the advantages of high efficiency, time saving, greenness, and environmental protection. The prepared magnesium oxide particles can be directly used to prepare tablets without coating treatment, which can shorten the process time and cost, reduce the operation steps, and reduce energy consumption.

[0038] In some specific embodiments of the present invention, in step S1, the mass fraction of the protein hydrophilic colloid is 8%-10%, for example, it can be any point value among 8%, 8.5%, 9%, 9.5%, 10% or a range value composed of any two point values; when the concentration is too low, it cannot fully react with the cross-linking agent to cross-link, and the embedding effect is poor. When the concentration is too high, the viscosity will increase, the fluidity of the solution will deteriorate, and it cannot be evenly wrapped on the surface of magnesium oxide.

[0039] In some specific embodiments of the present invention, in step S1, the heating temperature is 60-80°C, for example, it can be any point value among 60°C, 65°C, 70°C, 75°C, 80°C or a range value consisting of any two point values.

[0040] In some specific embodiments of the present invention, in step S1, the pH value after adjusting the pH is 5-6.

[0041] In some specific embodiments of the present invention, in step S2, the stirring speed of mixing and the stirring speed of shear granulation are both 40-60 r / min, for example, can be any point value among 40 r / min, 45 r / min, 50 r / min, 55 r / min, 60 r / min or a range value consisting of any two point values.

[0042] In some specific embodiments of the present invention, in step S2, the shearing rotation speed is 1000-3000 r / min, for example, it can be any point value among 1000 r / min, 1500 r / min, 2000 r / min, 2500 r / min, 3000 r / min or a range value consisting of any two point values.

[0043] In some specific embodiments of the present invention, in step S2, the shearing granulation time is 40-60s, ensuring that the slurry fully wets the material and allows the protein hydrophilic colloid and the cross-linking agent to fully react. For example, the shearing granulation time can be any point value among 40s, 45s, 50s, 55s, 60s or a range value consisting of any two point values.

[0044] In some specific embodiments of the present invention, in step S3, the granulation is carried out in a swing granulator, and a 1.2 mm stainless steel punching mesh is used for granulation. Granulation after drying may damage the coating layer. The present invention first uses a wet granulation process for granulation and then dries, which has a better effect.

[0045] In some specific embodiments of the present invention, in step S3, the drying temperature is 40-60°C, for example, it can be any point value among 40°C, 45°C, 50°C, 55°C, and 60°C, or a range value consisting of any two point values; the drying time is 2-4h, for example, it can be any point value among 2h, 2.5h, 3h, 3.5h, and 4h, or a range value consisting of any two point values.

[0046] A third aspect of the present invention provides a magnesium oxide tablet, comprising the magnesium oxide particles described in any one of the aforementioned embodiments or the magnesium oxide particles prepared by the method for preparing the magnesium oxide particles described in any one of the aforementioned embodiments.

[0047] The following is a detailed description of some embodiments of the present invention in conjunction with specific examples. The raw materials used in the examples can be purchased from the market unless otherwise specified.

[0048] Example 1

[0049] The magnesium oxide particles comprise the following components by mass percentage: 60% magnesium oxide, 3% gelatin, 5% microcrystalline cellulose and 32% maltodextrin.

[0050] Preparation method:

[0051] S1. Using purified water as solvent, add gelatin with a mass fraction of 9%, heat to 80°C, stir until completely swollen, then cool to 45°C to induce the gelatin solution to form a hydrogel, which is used as a slurry for later use;

[0052] S2. Magnesium oxide, microcrystalline cellulose and maltodextrin were weighed according to the formula ratio and added to the wet granulator, and stirred at a high speed of 50 r / min until fully mixed, and then the slurry prepared in step S1 was slowly added under the conditions of high-speed stirring at 50 r / min and high-speed shearing at 2000 r / min, and shearing granulation was performed for 50 s to ensure that the slurry fully wetted the materials and the gelatin and microcrystalline cellulose were fully reacted;

[0053] S3. Use a swing granulator equipped with a 1.2 mm stainless steel screen to granulate the material obtained in step S2. Set the hot air circulation oven to 50°C, spread the material evenly on the tray, dry it for 3 hours after reaching the set temperature, and pass it through a 20-mesh standard sieve to obtain magnesium oxide particles.

[0054] Embodiment 2-8

[0055] The only difference between Examples 2-8 and Example 1 is that the amounts of magnesium oxide, gelatin, microcrystalline cellulose and maltodextrin are different, and the other conditions are the same as those of Example 1. The mass percentages of the components in Examples 1-8 are shown in Table 1.

[0056] Table 1

[0057]

[0058]

[0059] Comparative Examples 1-5

[0060] The difference between Comparative Examples 1-5 and Example 1 is that the amounts of magnesium oxide, gelatin, microcrystalline cellulose and maltodextrin are different, and the other conditions are the same as those of Example 1. The mass percentages of the components in Comparative Examples 1-5 are shown in Table 2.

[0061] Table 2

[0062] Composition ratio Magnesium oxide gelatin Microcrystalline Cellulose Maltodextrin Comparative Example 1 95％ 2.5％ 2.5％ / Comparative Example 2 60％ / 6％ 34％ Comparative Example 3 60％ 12％ 6％ 22％ Comparative Example 4 60％ 6％ / 34％ Comparative Example 5 60％ 6％ 12％ 22％

[0063] Test example

[0064] The magnesium oxide particles prepared in each embodiment and each comparative example were tableted, respectively, using a rotary automatic tablet press, according to the mass ratio of magnesium oxide particles: magnesium stearate of 99.5:0.5, after mixing evenly, added into the tablet press hopper, and the tablet press parameters were set: filling depth 75 mm, tablet thickness 3.5 mm, speed 5.0 r / min, and compressed. The appearance of the tablets was observed, the black edges were counted, and the average tablet weight, hardness and friability were tested. According to the provisions of the 2020 edition of the Chinese Pharmacopoeia, sampling was carried out for determination.

[0065] At the same time, another sample of magnesium oxide particles on the market was pressed according to the same proportion and parameters to compare the black edge generation situation. Figure 1 shown.

[0066] The test results are shown in Table 3.

[0067] Table 3

[0068]

[0069] It can be seen from the data in Table 3 that all indicators of the tablets prepared in Examples 1-8 meet the standard values, the tablets have a complete and smooth appearance, uniform color, appropriate hardness and wear resistance, and meet the relevant provisions of the 2020 edition of the Pharmacopoeia; the average hardness and friability rate of Comparative Example 1 are both unqualified. This is because the wall material accounts for a small proportion and cannot completely cover the magnesium oxide. Comparative Examples 2 and 4 are single wall materials with poor resistance to mechanical force. The tablets have black edges on the appearance. Although the hardness and friability of the tablets in Comparative Example 3 meet the standard values, due to the excessive proportion of gelatin, the particle yield is low, and it is not suitable for production, and the tablet appearance is uneven in color and has yellow spots. Comparative Example 5 is due to the excessive proportion of microcrystalline cellulose, the tablet friability rate is unqualified, and capping occurs. All comparative examples do not meet the relevant provisions of the 2020 edition of the Pharmacopoeia.

[0070] Depend on Figure 1 and Figure 2It can be seen that the magnesium oxide tablets obtained by tableting the existing magnesium oxide particles on the market have black edges, while the magnesium oxide tablets obtained by tableting the magnesium oxide particles prepared by the method of the present invention are complete, smooth, uniform in color, and have no black edges; this further illustrates that the use of the method of the present invention to prepare magnesium oxide particles can improve the black edge problem of magnesium oxide tablets, while avoiding cracking and delamination of tablets, thereby significantly improving the quality of magnesium oxide products.

[0071] Although the present invention has been illustrated and described with specific embodiments, it should be appreciated that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Those skilled in the art should understand that the technical solutions described in the above embodiments may be modified, or some or all of the technical features thereof may be replaced by equivalents without departing from the spirit and scope of the present invention. However, these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present invention. Therefore, this means that all such replacements and modifications within the scope of the present invention are included in the appended claims.

Claims

1. A magnesium oxide particle, characterized in that Calculated by mass percentage, it includes 50%-85% of magnesium oxide, 3%-10% of protein hydrophilic colloid, 3%-10% of cross-linking agent and the rest of filler; Wherein, the cross-linking agent includes cellulose and / or cellulose derivatives.

2. The magnesium oxide particles according to claim 1, characterized in that The protein hydrocolloid comprises at least one of gelatin, fish gelatin, whey protein, casein and its salt, soy protein isolate or alcohol-soluble protein.

3. The magnesium oxide particles according to claim 1, characterized in that The cross-linking agent includes at least one of microcrystalline cellulose, sodium carboxymethyl cellulose, methyl cellulose and hydroxypropyl methyl cellulose.

4. The magnesium oxide particles according to claim 1, characterized in that The filler includes at least one of maltodextrin, mannitol and starch.

5. The magnesium oxide particles according to claim 1, characterized in that The particle size of the magnesium oxide particles is 20-100 meshes.

6. The method for preparing magnesium oxide particles according to any one of claims 1 to 5, characterized in that: The following steps are involved: S1. Add the protein hydrophilic colloid into water, stir until swelling, heat or adjust the pH to induce the protein hydrophilic colloid solution to form a hydrogel, and use it as a slurry for later use; S2. Using a wet granulation process, magnesium oxide, a crosslinking agent and a filler are weighed according to the formula ratio, stirred and mixed, and then the slurry is added under stirring and shearing conditions to granulate and achieve coating; S3. The material obtained in step S2 is granulated, dried and sieved to obtain the magnesium oxide particles.

7. The method for preparing magnesium oxide particles according to claim 6, characterized in that: In step S1, at least one of the following features is included: (1) The mass fraction of the protein hydrophilic colloid is 8%-10%; (2) The heating temperature is 60-80° C.; (3) The pH value after the pH adjustment is 5-6.

8. The method for preparing magnesium oxide particles according to claim 6, characterized in that: In step S2, at least one of the following features is included: (1) The stirring speed is 40-60 r / min; (2) The shearing speed is 1000-3000 r / min; (3) The granulation time is 40-60s.

9. The method for preparing magnesium oxide particles according to claim 6, characterized in that: In step S3, the drying temperature is 40-60°C, and the drying time is 2-4 hours.

10. A magnesium oxide tablet, characterized in that: The invention comprises magnesium oxide particles as described in any one of claims 1 to 5 or magnesium oxide particles prepared by the method for preparing magnesium oxide particles as described in any one of claims 6 to 9.

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