A magnesium oxide double-layer sustained-release tablet and a preparation method and application thereof

Abstract

The application provides a magnesium oxide double-layer sustained-release tablet and a preparation method and application thereof, and the magnesium oxide double-layer sustained-release tablet comprises a quick-disintegration layer and a sustained-release layer which are stacked in sequence; the quick-disintegration layer comprises magnesium oxide and a first lubricant; the sustained-release layer comprises magnesium oxide and a second lubricant; wherein, according to the mass ratio, the mass of magnesium oxide in the quick-disintegration layer: the mass of magnesium oxide in the sustained-release layer = 0.2-1.3: 0.7-1.0; the tap density of magnesium oxide in the quick-disintegration layer and the sustained-release layer is 0.5-1.0 g / mL; and according to the mass ratio, the first lubricant: the second lubricant = 0.5-4: 2-6. The application controls the content of magnesium oxide in the quick-disintegration layer and the sustained-release layer, introduces the lubricant, improves the poor powder flowability difference of the quick-disintegration layer and the sustained-release layer, improves the interlayer bonding force, thereby improving the interlayer separation problem, realizes the preparation of the magnesium oxide double-layer sustained-release tablet and improves the bioavailability of the magnesium oxide.

Description

Technical Field

[0001] This invention belongs to the field of solid dosage form technology, and particularly relates to a magnesium oxide double-layer sustained-release tablet, its preparation method and application. Background Technology

[0002] Magnesium supplementation is crucial for maintaining human health, its importance stemming from its synergistic effects across multiple systems. Magnesium is a cofactor for over 300 enzymes, participating in energy metabolism (such as ATP synthesis), protein synthesis, and DNA repair. Magnesium deficiency can lead to fatigue, muscle cramps, and metabolic disorders. Simultaneously, magnesium stabilizes myocardial electrical activity by regulating calcium ion channels, reducing the risk of hypertension and arrhythmia, and synergistically enhances bone mineralization with vitamin D, preventing osteoporosis. Furthermore, magnesium has an inhibitory regulatory effect on the nervous system, relieving anxiety, improving sleep quality, and delaying cellular aging through antioxidant mechanisms.

[0003] Magnesium oxide boasts advantages such as high purity, low impurities, low cost, wide availability of raw materials, chemical stability, and long-term storage without deterioration, making it an ideal source of magnesium supplementation. For example, pharmaceutical-grade magnesium oxide utilizes a calcination process to control particle size and crystal morphology, ensuring that tablet hardness and disintegration meet standards. Magnesium oxide can be combined with other vitamins and minerals (such as calcium and vitamin D) to enhance bone health; its anti-acid and mild laxative properties can also improve gut health and enhance the overall efficacy of products. However, under current technologies, magnesium oxide as a source of magnesium supplementation also has significant drawbacks, primarily its extremely low bioavailability, low solubility in gastric acid (approximately 0.00062 g / 100 mL), and absorption rate of only 4%–12%. In contrast, chelated magnesium (such as magnesium glycinate and magnesium threonate) and magnesium citrate formulations offer advantages in absorption rate and safety.

[0004] In the field of pharmaceutical formulation, core strategies for improving bioavailability encompass multi-dimensional innovations, including chemical modification (such as prodrug design), modification of nanodelivery systems, synergistic application of compound absorption enhancers, and enteric coating sustained-release technology. In recent years, bilayer sustained-release tablets have emerged as a novel dosage form, achieving both rapid and long-lasting therapeutic effects through a physically layered structure design of the rapidly disintegrating layer and the sustained-release layer (which may contain the same or synergistic drugs). Bilayer sustained-release tablets combine the rapidly disintegrating layer and the sustained-release layer using a special process to form a composite tablet structure. The rapidly disintegrating layer rapidly disintegrates to relieve symptoms, while the sustained-release layer continuously releases the drug to maintain efficacy. Through synergistic effects (the drugs can be the same or two with synergistic effects), the frequency of dosing is reduced, the risk of dependence is avoided, and blood drug concentrations are stabilized. However, currently, there is no mature technology to prepare magnesium oxide bilayer sustained-release tablets, and breakthrough solutions are still needed to address the issue of technological compatibility. Summary of the Invention

[0005] To improve the bioavailability of magnesium oxide, this invention provides a magnesium oxide bilayer sustained-release tablet, its preparation method, and its application.

[0006] According to one aspect of the present invention, a magnesium oxide bilayer sustained-release tablet is provided, comprising a rapidly disintegrating layer and a sustained-release layer stacked sequentially; the rapidly disintegrating layer comprises magnesium oxide and a first lubricant; the sustained-release layer comprises magnesium oxide and a second lubricant; wherein, by mass ratio, the mass ratio of magnesium oxide in the rapidly disintegrating layer to the mass ratio of magnesium oxide in the sustained-release layer is 0.2~1.3 : 0.7~1.0; the tap density of magnesium oxide is 0.5~1.0 g / mL; and, by mass ratio, the first lubricant : the second lubricant is 0.5~4 : 2~6; the disintegration time of the rapidly disintegrating layer is T1, and the disintegration time of the sustained-release layer is T2; in the magnesium oxide bilayer sustained-release tablet, the following relationship is satisfied: T2-T1≥0.5 hours; T1<1 hour, and T2>1 hour.

[0007] The applicant discovered that, due to the hygroscopic nature of magnesium oxide, it inevitably absorbs moisture from the air during tablet preparation in ordinary workshops. Excessive moisture content can lead to particle agglomeration or reaction into magnesium hydroxide lumps, affecting its flowability and even causing sticking and tumbling during tableting. Therefore, when magnesium oxide is formulated into a bilayer sustained-release tablet with a composite structure of a rapid-disintegrating layer and a sustained-release layer, uneven compression pressure occurs, leading to problems such as tablet delamination, tablet cracking, and cross-contamination between layers. On the one hand, magnesium oxide itself is prone to hygroscopic agglomeration and poor flowability, resulting in delamination and gray-black edges during compression, making it unsuitable for tablet application. On the other hand, the differences in composition and properties between the rapid-disintegrating and sustained-release layers inevitably result in different compression responses. Uneven compression pressure distribution and insufficient interlayer bonding exacerbate the risk of separation, further leading to cross-contamination and structural failure. This invention improves the interlayer separation problem by controlling the content of magnesium oxide in the rapid-disintegration layer and the slow-release layer, and by introducing a lubricant to improve the difference in powder flowability between the rapid-disintegration layer and the slow-release layer, thereby improving the interlayer bonding force. This enables the preparation of a double-layer slow-release tablet of magnesium oxide and improves the bioavailability of magnesium oxide.

[0008] This invention achieves better sustained-release effects by controlling the disintegration time difference between the rapidly disintegrating layer and the sustained-release layer. The disintegration interval between the rapidly disintegrating layer and the sustained-release layer ensures a stepwise release of the drug in the gastrointestinal tract. The rapidly disintegrating layer creates a neutral microenvironment by neutralizing gastric acid, delaying the release of magnesium compounds in the sustained-release layer, causing them to dissociate primarily into magnesium ions in the intestine, avoiding absorption loss due to gastric emptying, thereby significantly improving the absorption efficiency of magnesium ions in the intestine. Furthermore, by simultaneously controlling the disintegration time of the rapidly disintegrating layer and the sustained-release layer, this invention achieves a sustained-release effect in the stomach and intestines, thereby continuously releasing magnesium oxide and increasing the concentration of magnesium in the human blood.

[0009] Preferably, T2 > 2 hours.

[0010] Preferably, the rapid-disintegration layer further includes a co-solvent; and in the rapid-disintegration layer, the mass ratio of magnesium oxide:co-solvent:first lubricant is 15~70:0.5~2:0.5~3. Furthermore, by introducing a co-solvent into the rapid-disintegration layer, the present invention effectively prevents magnesium oxide particles from forming physical aggregates (such as colloidal suspensions) in gastric acid through its dispersing effect, while significantly improving the dissolution rate and uniformity of magnesium oxide by reducing surface tension and enhancing wettability. Moreover, by controlling the mass ratio of magnesium oxide, co-solvent, and first lubricant in the rapid-disintegration layer, the rapid-disintegration effect of the rapid-disintegration layer can be further optimized.

[0011] Preferably, the mass percentage content of the cosolvent of the rapid disintegration layer in the magnesium oxide bilayer sustained-release tablet is 0.1~0.8%.

[0012] Preferably, the rapidly disintegrating layer further includes a first binder, and the sustained-release layer further includes a second binder; wherein, calculated by mass ratio, the first binder : second binder = 3.5~5 : 5~10. In the rapidly disintegrating layer, the first binder serves to provide adequate interparticle adhesion to ensure tablet formability, and its hydrophilicity promotes rapid hydration and disintegration in gastric juice; while in the sustained-release layer, the second binder serves to provide adequate interparticle adhesion to ensure tablet formability, and simultaneously forms a gel barrier to regulate the water penetration rate and drug diffusion rate, assisting in the slow release of magnesium oxide. Thus, the present invention, through the mass ratio between the first binder and the second binder, can further optimize the rapid disintegration effect of the magnesium oxide bilayer sustained-release tablet.

[0013] Preferably, the sustained-release layer further includes a second binder and a second filler; wherein, in the sustained-release layer, the mass percentage of magnesium oxide: second filler: second binder: second lubricant is 50~75%: 10~30%: 5~10%: 1~5%. Furthermore, by optimizing the formulation of the sustained-release layer, this invention can optimize the stepwise sustained-release effect of the magnesium oxide bilayer sustained-release tablet, achieving sustained release and structural stability of magnesium oxide in the gastrointestinal tract, meeting the application requirements of stable in vivo absorption of single-use magnesium supplementation and large-scale industrial production.

[0014] Preferably, the first lubricant and the second lubricant are selected from at least one of fatty acid lubricants, silicone compound lubricants, and polymer lubricants.

[0015] Preferably, the fatty acid lubricant includes at least one of magnesium stearate, stearic acid, and glyceryl behenate.

[0016] Preferably, the silicon-based compound lubricant includes at least one of silicon dioxide and its derivatives, silicates, and talc.

[0017] Preferably, the polymeric lubricant includes at least one of polyethylene glycol lubricant and polyvinyl alcohol lubricant.

[0018] Preferably, the co-solvent includes at least one of cyclodextrin-based co-solvents, surfactant-based co-solvents, organic acid-based co-solvents, organic base-based co-solvents, and polymer-based co-solvents.

[0019] Preferably, the cyclodextrin-based cosolvent includes at least one of α-cyclodextrin and its derivatives, and β-cyclodextrin and its derivatives.

[0020] Preferably, the surface-active cosolvent includes at least one of lecithin and polysorbate 80.

[0021] Preferably, the organic acid co-solvent includes citric acid.

[0022] Preferably, the organic base co-solvent includes meglumine.

[0023] Preferably, the polymeric cosolvent includes at least one of polyethylene glycol and polyvinyl alcohol.

[0024] Preferably, the first adhesive and the second adhesive are selected from at least one of natural polymer adhesives and synthetic polymer adhesives.

[0025] Preferably, the natural polymeric binder includes at least one of starch, gum arabic, konjac gum, sodium alginate, chitosan, xanthan gum, guar gum, locust bean gum, agar, pectin, pullulan, inulin, poria cocos polysaccharide, and gelatin.

[0026] Preferably, the synthetic polymeric adhesive includes at least one of hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, acrylic resin, hydroxypropyl starch, oxidized starch, hydroxypropyl cellulose derivatives, and polyvinyl ether derivatives.

[0027] Preferably, the rapid-disintegrating layer further includes a disintegrant, which includes at least one of starch-based disintegrants, cellulose-based disintegrants, polymer-based disintegrants, and effervescent disintegrants.

[0028] Preferably, the starch-based disintegrant includes at least one of dry starch, sodium carboxymethyl starch, pregelatinized starch, and cross-linked starch.

[0029] Preferably, the cellulose-based disintegrant includes at least one of microcrystalline cellulose, powdered cellulose, croscarmellose sodium, and low-substituted hydroxypropyl cellulose.

[0030] Preferably, the polymeric disintegrant includes at least one of cross-linked polyvinylpyrrolidone and cross-linked polyacrylic acid resin.

[0031] Preferably, the effervescent disintegrant includes at least one of sodium bicarbonate, potassium bicarbonate, sodium carbonate, and potassium carbonate. Furthermore, the above-mentioned components can also serve as antacids in the rapid-disintegrating layer. These materials can further neutralize local gastric acid, creating a synergistic microenvironment for the stable dispersion of magnesium oxide and the protective release of the sustained-release layer, thereby improving overall absorption efficiency.

[0032] Further preferred embodiments include at least one of the following: a combination of citric acid and sodium bicarbonate; a combination of tartaric acid and potassium carbonate; or a combination of fumaric acid and sodium bicarbonate.

[0033] Preferably, the rapid-blowout layer further includes a first filler.

[0034] Preferably, the first filler and the second filler are selected from at least one of sugar-based and derivative fillers, polyvinyl polymer fillers, inorganic salt fillers, and cellulose fillers.

[0035] Preferably, the sugar and derivative filler includes at least one of lactose, sucrose, mannitol, sorbitol, erythritol, and isomaltitol.

[0036] Preferably, the polyvinyl polymer filler includes at least one of polyvinyl ketones and copolyvinyl ketones.

[0037] Preferably, the inorganic salt filler includes at least one of calcium hydrogen phosphate, calcium dihydrogen phosphate, calcium phosphate, and calcium carbonate.

[0038] Preferably, the cellulose filler includes at least one of microcrystalline cellulose, powdered cellulose, hydroxypropyl cellulose, konjac gum, locust bean gum, and sodium alginate.

[0039] Preferably, the second filler is selected from at least two of the following: sugar and derivative fillers, polyvinyl polymer fillers, inorganic salt fillers, and cellulose fillers.

[0040] Preferably, the rapid-disintegration layer further includes a first flow aid, and / or the sustained-release layer further includes a second flow aid.

[0041] Preferably, the first and second flow aids are selected from inorganic salt flow aids, metal soap flow aids, silica gel flow aids, etc.

[0042] Preferably, the inorganic salt-based gliding agent includes at least one of talc, calcium hydrogen phosphate, and magnesium silicate.

[0043] Preferably, the metal soap-based flow aid includes at least one of magnesium stearate, sodium stearate fumarate, and glyceryl behenate.

[0044] Preferably, the silica-based flow aid includes at least one of silica and magnesium aluminum silicate.

[0045] Further preferred, the silica includes silica obtained by the gas phase method, silica obtained by the precipitation method, and silica obtained by the gel method.

[0046] Preferably, the rapid-disintegration layer further includes a first active ingredient, and / or the sustained-release layer further includes a second active ingredient.

[0047] Preferably, the first and second functional ingredients are selected from plant extracts, dietary fiber, probiotics, vitamins, and minerals.

[0048] Preferably, the plant extract active ingredients include at least one of citrus extract, okra extract, licorice extract, clove extract, fennel extract, and matcha powder.

[0049] Preferably, the dietary fiber functional components include at least one of resistant dextrin, β-glucan, inulin, white kidney bean fiber, flaxseed, citrus fiber, tremella fiber, fructooligosaccharide, polydextrose, and soybean fiber.

[0050] Preferably, the probiotic active ingredients include at least one of inactivated bacteria, postbiotics, and live bacteria.

[0051] Preferably, the inactivated bacteria include at least one of inactivated lactic acid bacteria and inactivated bifidobacteria.

[0052] Preferably, the metabiotic includes at least one of bacteriocins and extracellular polysaccharides.

[0053] Preferably, the live bacteria include at least one of conventional live bacteria and spore-type live bacteria.

[0054] Preferably, the vitamin-like active ingredients include at least one of fat-soluble vitamins and water-soluble vitamins.

[0055] Preferably, the fat-soluble vitamins include at least one of vitamin A, vitamin D, vitamin E, and vitamin K.

[0056] Preferably, the water-soluble vitamins include at least one of vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B12, and vitamin C.

[0057] Preferably, the mineral-based active ingredients include at least one of calcium, zinc, iron, selenium, manganese, and copper.

[0058] A second aspect of the present invention provides the application of the magnesium oxide bilayer sustained-release tablets described above in food, dietary supplements, pharmaceuticals, and pet food.

[0059] A third aspect of the present invention provides a method for preparing magnesium oxide bilayer sustained-release tablets as described above. The method includes the following steps: Step 1. Preparing a rapid-disintegrating layer premix and a sustained-release layer premix, respectively; Step 2. Pre-compressing the rapid-disintegrating layer premix or the sustained-release layer premix to form a base layer; Step 3. Laying the remaining premix that has not undergone pre-compressing treatment on top of the base layer, and then forming a magnesium oxide bilayer sustained-release tablet through tableting. In Step 3, the remaining premix refers to the sustained-release layer premix or the rapid-disintegrating layer premix that has not undergone pre-compressing treatment in Step 2.

[0060] Preferably, after tableting, the resulting tablets are coated.

[0061] Preferably, the coating used in the coating process is a film coating. Theoretically, the coating increases the tablet weight by 1-20%.

[0062] Preferably, the pre-compression pressure in the pre-compression treatment is 0.5~3KN.

[0063] Preferably, the overall hardness of the magnesium oxide double-layer sustained-release tablet after compression is >140N.

[0064] The preparation of the rapid disintegration layer premix includes the following steps: S11. The disintegrant and the first lubricant are divided into two parts, and then magnesium oxide, the first lubricant of the first part, the first filler, the disintegrant of the first part, and the active ingredient are weighed and mixed to obtain rapid disintegration layer granules; S12. The rapid disintegration layer granules are then mixed with the first binder, the co-solvent, and ethanol, and then stirred and shredded to obtain rapid disintegration layer wet granules; S13. The rapid disintegration layer wet granules are dried and sized and sieved to obtain rapid disintegration layer mixed granules; S14. The obtained rapid disintegration layer mixed granules are mixed with the first lubricant of the second part, the disintegrant of the second part, and the first flow aid to obtain the rapid disintegration layer premix.

[0065] The preparation of the sustained-release layer premix includes the following steps: S21. Divide the second lubricant and the second active ingredient into two parts, and the second binder into three parts. Then weigh and mix magnesium oxide, the second lubricant, the second gliding agent, the second filler, the second active ingredient, and the second binder to obtain a sustained-release layer granule; S22. Dissolve the second binder in ethanol, add it to the sustained-release layer granule, and stir and shred it to form sustained-release layer wet granules; S23. Dry the sustained-release layer wet granules, granulate and sieve them to obtain sustained-release layer mixed granules; S24. Mix the obtained sustained-release layer mixed granules with the second lubricant, the second binder, and the second active ingredient to obtain a sustained-release layer premix. The sustained-release layer premix prepared by the above method can further improve the adhesion between the sustained-release layer premixes, thereby improving the tablet forming effect and disintegration effect.

[0066] Preferably, the operating parameters in the drying process are to dry the wet particles to a moisture content of <5%.

[0067] Preferably, in the granulation and screening process of the rapid-collapse layer, the particle size distribution of coarse particles is D50 of 60 mesh and D95 ​​of 20 mesh.

[0068] Preferably, in the granulation and sieving process of the slow-release layer, the particle size distribution of the coarse particles is D50 of 40 mesh and D95 ​​of 20 mesh. Attached Figure Description

[0069] Figure 1 The sustained-release layer of the magnesium oxide double-layer sustained-release tablets exhibits a patchy, uneven appearance.

[0070] Figure 2 The rapid-disintegration layer of magnesium oxide bilayer sustained-release tablets exhibits a patchy, uneven appearance.

[0071] Figure 3 The magnesium oxide bilayer sustained-release tablets provided by this invention do not exhibit delamination or peeling at the interlayer interface. Detailed Implementation

[0072] To enable those skilled in the art to better understand the technical solutions of this invention, the technical solutions of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some embodiments of this invention, and not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of this invention.

[0073] Example 1

[0074] Processing group 1A

[0075] 1. Preparation of raw materials

[0076] In this embodiment, processing group 1A prepares the materials required for preparing magnesium oxide bilayer sustained-release tablets according to the formulation shown in Table 1.

[0077] Table 1. Materials required for preparing magnesium oxide bilayer sustained-release tablets in treatment group 1A

[0078]

[0079] 2. Preparation of magnesium oxide double-layer sustained-release tablets

[0080] This embodiment prepares magnesium oxide bilayer sustained-release tablets according to the following method: Step 1. Prepare a rapid-disintegrating layer and a sustained-release layer separately; Step 2. Compress the rapid-disintegrating layer and the sustained-release layer to form a tablet. Specifically, the tableting operation involves placing the rapid-disintegrating layer on top of the sustained-release layer and controlling the pre-compression pressure of the sustained-release layer to be 0.5~3KN, with an overall tablet hardness >140N; thus, a magnesium oxide bilayer sustained-release tablet is obtained. The tap density of magnesium oxide in the prepared magnesium oxide bilayer sustained-release tablet is 0.71g / mL.

[0081] The preparation of the rapid collapse layer includes the following steps:

[0082] S11. After the material is sieved, the raw materials are weighed according to the formula, and then magnesium oxide, stearic acid, matcha powder, microcrystalline cellulose, and cross-linked carboxymethyl cellulose sodium from the first part are mixed to obtain granulation material A;

[0083] S12 Take the formula amount of povidone K30, hydroxypropyl methylcellulose, polyethylene glycol and an appropriate amount of ethanol, stir and mix to dissolve, then add granulation material A, stir and chop to make wet granules A;

[0084] S13. Wet particles A are dried and sieved to obtain particles A; wherein, the drying process is to dry the wet particles to a moisture content of <5%; the particle size distribution is D50 of 60 mesh and D95 ​​of 20 mesh.

[0085] S14. The obtained particles A are compressed with the cross-linked sodium carboxymethyl cellulose, sodium bicarbonate, magnesium stearate, and silica from the second part to obtain a rapid disintegration layer.

[0086] The preparation of the sustained-release layer includes the following steps:

[0087] S21. After the material is sieved, the raw materials are weighed according to the formula, and then magnesium oxide, stearic acid, tremella composite fiber powder, konjac gum, silicon dioxide, microcrystalline cellulose and hydroxypropyl cellulose from the first part are mixed to obtain granulation material B.

[0088] S22. After dissolving the hydroxypropyl cellulose in ethanol, add the granulation material B, and then stir and crush it to make granules B;

[0089] S23. Wet particles B are dried and sieved to obtain particles B; wherein, the drying process is to dry the wet particles to a moisture content of <5%; the particle size range of particles is D50 of 40 mesh and D95 ​​of 20 mesh.

[0090] S24. The prepared granules B are mixed with the hydroxypropyl cellulose, inactivated bacteria and magnesium stearate of the third part, and then compressed into tablets to obtain a sustained-release layer.

[0091] Treatment groups 2A-8A and control groups 1A-4A

[0092] Magnesium oxide bilayer sustained-release tablets were prepared using the formulation and method provided in Treatment Group 1A of Example 1 for Treatment Groups 2A-8A and Control Groups 1A-4A. Specifically, the variables involved in Treatment Groups 2A-8A and Control Groups 1A-4A are shown in Table 2. In Treatment Groups 2A-8A and Control Groups 1A-4A, the mass fraction of magnesium oxide in the rapid-breakdown layer was maintained at 400 parts.

[0093] The mass fraction of the first lubricant was 15 parts. Apart from the differences mentioned above, the operating procedures for preparing magnesium oxide bilayer sustained-release tablets in treatment groups 2A-8A and control groups 1A-4A were strictly consistent with those in treatment group 1A of Example 1.

[0094] Table 2. Variables involved in treatment groups 2A-8A and control groups 1A-4A

[0095]

[0096] Comparison group 5A

[0097] This comparative group prepared magnesium oxide monolayer sustained-release tablets according to the formulation and method provided in treatment group 1A of Example 1. In preparing magnesium oxide monolayer sustained-release tablets, this comparative group mixed all materials together.

[0098] Test Example 1

[0099] 1. Test Object

[0100] Magnesium oxide bilayer sustained-release tablets prepared in each treatment group and control group of Example 1.

[0101] 2. Testing Methods

[0102] (1) Tablet Appearance: Under standard light, visual inspection is performed, and tablet colors are compared using a color comparison card. The tablet surface is also inspected by touch. For minor defects, a magnifying glass is required for observation. "O" indicates that both layers are smooth and without any uneven surfaces; and there should be no color overlap or interchange between the sustained-release layer and the rapid-disintegration layer, i.e., the sustained-release layer (white) should not contain any lumps (patches with a diameter > 5 μm) of the rapid-disintegration layer (grass green), and vice versa. "X" indicates that the tablet surface is uneven, or that other layer colors with a diameter > 5 μm appear in the rapid-disintegration layer and the sustained-release layer, such as... Figure 1 , Figure 2 As shown. The grass-green color in the rapid-disintegration layer is due to the presence of matcha powder in the sustained-release layer. This test example allows for a direct assessment of tablet quality by introducing a colored active ingredient into a single layer that has little impact on the tablet structure.

[0103] (2) Hardness: The hardness testing procedure and instrument requirements shall be in accordance with the following provisions:

[0104] Sample pretreatment: Take the test tablets (the standard for qualified test tablets: friability <1%, intact appearance, no unevenness or cracks on the surface), and clearly define the direction of the interlayer structure. Place the tablets on the stage of the hardness tester with the sustained-release layer facing down and the rapid-disintegration layer facing up, ensuring that the tablet axis is perpendicular to the direction of pressure. The instrument requirements are: the stage of the hardness tester should have a horizontal adjustment function, a flat and non-slip surface, and a size suitable for different tablet sizes to prevent tilting or sliding of the tablets during placement, which would affect the accuracy of the test.

[0105] Pressure application method: Apply pressure uniformly from both sides towards the center along the longest diameter direction of the tablet using a hardness tester probe until the tablet breaks into pieces. The instrument requirements are as follows: the hardness tester probe must be made of high-hardness, low-wear material, preferably hard alloy, with a smooth surface to ensure uniform contact with the tablet surface during pressure application. The pressure application device should have a high-precision servo motor drive system, with pressure control accuracy reaching ±0.1N, ensuring a stable and adjustable pressure application rate to meet the requirements of different testing standards.

[0106] Data Acquisition: The instrument automatically records the maximum pressure value at the moment the tablet breaks. This value is then converted into hardness data (in N) using a formula. The instrument requires the data acquisition system to have high-speed sampling capabilities to accurately capture the pressure peak at the moment of tablet breakage. The instrument should also have a built-in data processing module capable of automatically calculating tensile strength based on parameters such as tablet diameter and thickness.

[0107] In this test, hardness was expressed as bursting pressure. A higher hardness value indicates better core quality, which is beneficial for maintaining the core's shape during subsequent coating and packaging processes. In the absence of cracking, higher hardness indicates stronger adhesion between the two layers, making separation more difficult.

[0108] (3) Friability: The friability of tablets was tested according to the method specified in the pharmacopoeia, as follows: A transparent, wear-resistant plastic cylinder with an inner diameter of approximately 286 mm and a depth of 39 mm (the inner wall is polished and one side has an openable operating port) was used. An arc-shaped partition was placed inside the cylinder to promote tablet rolling. The cylinder was fixed by a coaxial horizontal rotating shaft, which was connected to a motor for driving. The rotation speed was set to 25 rpm ± 1 rpm. With each rotation, the tablets rolled or slid onto the cylinder wall or other tablets. During the test, samples were taken according to the tablet weight: several tablets with a total weight of approximately 6.5 g were taken for tablets ≤ 0.65 g, and 10 tablets with a total weight greater than 0.65 g were taken. After removing the surface powder with a blower / compressed air, the initial weight of the sample was accurately weighed and recorded as m1. Then, the sample was placed in the cylinder and the equipment was started and rotated 100 times. After the rotation, the surface powder was removed again with a blower / compressed air and the weight after the test was accurately weighed and recorded as m2. At the same time, it was necessary to ensure that no tablets were broken, cracked, or pulverized. In terms of friability, a lower friability value indicates stronger adhesion between particles, making it less prone to powder loss during subsequent coating processes. This ensures product quality, minimizes component deviation in individual tablets, and avoids content fluctuations. Friability is calculated using the following formula: Friability (%) = [(m1-m2) / m1]*100%.

[0109] (4) Disintegration time: Disintegration time refers to the time required for solid dosage forms such as tablets and capsules to completely disintegrate or break into fragments and pass through a sieve under specified conditions. This indicator is one of the core items of drug quality control, directly related to the release rate and bioavailability of the drug in the body. If disintegration is slow, the drug may remain in the body, affecting efficacy or causing safety issues. By checking the disintegration time, it can be ensured that the active ingredient is released within the specified time to meet clinical medication needs.

[0110] In this test case, the disintegration apparatus mainly consists of the following parts: Basket: Composed of 6 glass tubes, each 77.5mm ± 2.5mm long and 21.5mm in inner diameter, with a sieve (710μm inner diameter) attached to the lower end. Baffle: A smooth, transparent plastic block, 20.7mm ± 0.15mm in diameter and 9.5mm ± 0.15mm thick; the baffle surface has 7 through holes, each 2mm in diameter, with 1 hole in the center and 6 radially arranged around it, 6mm from the center. Support and lifting device: The basket is suspended from the support by a stainless steel shaft at the top and immersed in a 1000mL beaker containing water at 37℃ ± 0.5℃. The basket moves up and down 30–32 times per minute, with a lifting range of 55mm ± 2mm.

[0111] In this test example, the specific testing procedure for disintegration time is as follows: Take 6 tablets of the test sample (the requirements for the test sample are: intact appearance, friability <1%; hardness >50N), place them in the glass tube of the basket, and fix them with baffles. Immerse the basket in a beaker containing simulated gastric fluid at 37℃±0.5℃, start the instrument, and record the time. Observe the disintegration of the tablets. If the tablets are broken into granules and all pass through the sieve, or only a few granules remain (without a hard core), it is considered to be completely disintegrated. The water temperature in the beaker must be strictly controlled at 37℃±0.5℃ to simulate the human body temperature environment; before each test, check whether the basket sieve is clean to avoid residual drug affecting the results.

[0112] By simulating the acidic environment of the stomach using artificial gastric juice (pH 1.0–1.5), the stability and disintegration ability of drugs in gastric acid can be tested. Furthermore, the introduction of pepsin can break down protein excipients (such as starch and gelatin) in tablets, promoting the disintegration process and more realistically reflecting the drug's disintegration behavior in vivo. The artificial gastric juice is prepared according to the pharmacopoeia standard formula: 16.4 mL of dilute hydrochloric acid (containing approximately 10 g of HCl) is added to approximately 800 mL of water, along with 10 g of pepsin. After shaking well, the solution is diluted to 1000 mL with water, and the pH is adjusted to 1.0–1.5 using 0.1 mol / L hydrochloric acid solution or sodium hydroxide solution.

[0113] The criteria for judging the magnesium oxide double-layer sustained-release tablets provided by the present invention are as follows: the rapidly disintegrating layer should completely disintegrate within 60 minutes (covering 60 minutes), and there should be no remaining material of the rapidly disintegrating layer on the sustained-release layer; the sustained-release layer should completely disintegrate after more than 60 minutes (excluding 60 minutes).

[0114] (5) Mechanical pressure: This value refers to the pressure applied to the tablet core by the tableting mold during tableting. The pressure data displayed by the equipment parameters is recorded. In this experiment, the standard for tablet formation is: when the tablet core hardness is >50N, the tablet surface is smooth, the friability is <1%, and there are no cracks or fragments, it is considered formed; when the tablet core hardness is <50N, the tablet surface is uneven, the friability is >1%, or there are cracks or fragments, it is considered not formed.

[0115] (6) Interlayer interface situation:

[0116] The interlayer interface of the tablet is judged by combining the above-mentioned test methods for tablet appearance, hardness, and friability. The cross-sectional view of the tablet, indicated by "#", shows that each layer has a clear boundary, no interpenetration, no color mixing, meaning each layer retains its inherent color, and no color diffusion to other layers is observed. Furthermore, the two core layers are bonded together without cracking, and after the core breaks, no delamination or peeling occurs. Figure 3 As shown. Conversely, if any of the above conditions are not met, it is represented by "X".

[0117] 3. Test Results and Analysis

[0118] The test results for this test example are shown in Table 3. In comparison groups 1A and 3A-4A, the tablet hardness was 0, which did not meet the test conditions, making it impossible to test the disintegration time. This is because the mass ratio of the two magnesium oxide layers in comparison group 1A was too different, resulting in a large difference in the compressibility coefficients of the two layers. This prevented proper bonding at the joint, causing the tablet core to crack at the joint and fail to form a proper shape. Therefore, it was impossible to reasonably test the tablet's disintegration time and hardness. Similarly, in comparison groups 3-4A, the excessive amount of lubricant caused the tablets to become loose and fail to form a proper shape, making it impossible to test the tablet's disintegration time and hardness. When the mechanical pressure of tableting exceeds 30 kN, it will seriously affect the service life of the tableting mold and tableting equipment. Therefore, mechanical pressure exceeding 30 kN should be avoided as much as possible during tablet preparation. In addition, based on the data from the comparison group 5A, it can be seen that single-layer magnesium oxide tablets are brittle, resulting in problems such as tablet core chipping, surface powdering, and easy wear and tear on the mold. Furthermore, single-layer magnesium oxide tablets cannot achieve the effect of sustained release in the stomach and intestines sequentially; and they cannot achieve physical isolation of incompatible ingredients, thus affecting the shelf life.

[0119] Therefore, by combining the test data of treatment groups 1A~8A and control groups 1A~4A, it can be confirmed that in the prepared magnesium oxide bilayer sustained-release tablets, the mass ratio of magnesium oxide in the rapid disintegration layer and the sustained-release layer, as well as the mass ratio of the first lubricant and the second lubricant, will significantly affect the appearance, hardness, brittleness, and interlayer interface of the tablets.

[0120] Table 3. Test Results

[0121]

[0122] Example 2

[0123] In this embodiment, treatment group 1B prepares magnesium oxide bilayer sustained-release tablets according to the formulation and method provided in treatment group 1A of Example 1.

[0124] Treatments 2B-6B prepared magnesium oxide bilayer sustained-release tablets using the formulation and method provided in Treatment 1B of Example 2. Specifically, the variables involved in Treatments 2B-6B are shown in Table 4. In Treatments 2B-6B, the mass ratio of povidone K30 to hydroxypropyl methylcellulose in the rapidly disintegrating layer was maintained at 33.2:3.32. In Treatments 1B-6B, the mass fraction of the second binder in the sustained-release layer was maintained at 60 parts. Apart from the above differences, the operational steps for preparing the magnesium oxide bilayer sustained-release tablets in Treatments 2B-6B were strictly consistent with those in Treatment 1B of Example 2.

[0125] Table 4. Variables involved in treatment groups 1B-6B

[0126]

[0127] Test Example 2

[0128] 1. Test Object

[0129] Magnesium oxide bilayer sustained-release tablets prepared in each treatment group of Example 2.

[0130] 2. Testing Methods

[0131] This test case follows the test method provided in Test Case 1.

[0132] 3. Test Results and Analysis

[0133] The test results for this test case are shown in Table 5. The test data from treatment groups 1B to 6B show that the mass ratio of the first adhesive to the second adhesive affects the intralayer particle adhesion, interlayer adhesion, and disintegration time of the magnesium oxide bilayer sustained-release tablet.

[0134] Specifically, observation of the data in treatment groups 1B to 6B revealed that in treatment group 5B, due to the low amount of binder in the rapid-disintegrating layer, the particle adhesion effect was significantly reduced, resulting in tablets with higher mechanical pressure, slight powdering on the tablet surface, and slightly higher brittleness. In treatment group 6B, the amount of binder in the rapid-disintegrating layer was too high, resulting in a disintegration time of over 1 hour and a shortened time difference with the sustained-release layer, thus failing to achieve the desired distribution and release effect of the rapid-disintegrating and sustained-release layers in the gastrointestinal tract. Treatment groups 1B to 4B, however, showed better intralayer and interlayer particle adhesion in the magnesium oxide bilayer sustained-release tablets compared to treatment groups 5B to 6B. This is likely because both the first and second binders in the rapid-disintegrating and sustained-release layers provide adequate interlayer adhesion, ensuring tablet compressibility.

[0135] On the other hand, by controlling the mass ratio between the first and second adhesives, it is possible to further ensure that the disintegration time (T1) of the rapidly disintegrating layer and the disintegration time (T2) of the sustained-release layer satisfy the following conditions: T2 - T1 ≥ 0.5 hours, and T1 < 1 hour, and T2 > 1 hour. Specifically, the first adhesive in the rapidly disintegrating layer rapidly hydrates in gastric juice due to its hydrophilicity, promoting disintegration; while in the sustained-release layer, a gel barrier is simultaneously formed, regulating the water permeation rate and drug diffusion rate, assisting in the slow release of magnesium oxide. Thus, by controlling the mass ratio between the first and second adhesives and optimizing T1 and T2, this invention ensures the stepwise release of the drug in the gastrointestinal tract and also achieves the effect of sustained release in the stomach and intestines sequentially, thereby continuously releasing magnesium oxide and increasing the concentration of magnesium in the human blood.

[0136] Table 5. Test Results

[0137]

[0138] Example 3

[0139] In this embodiment, treatment group 1C prepares magnesium oxide bilayer sustained-release tablets according to the formulation and method provided in treatment group 1A of Example 1. Treatment groups 2C-5C prepare magnesium oxide bilayer sustained-release tablets with reference to the formulation and method provided in treatment group 1C of Example 3. In this embodiment, the mass percentage ratio of magnesium oxide, second filler, second binder, and second lubricant in the sustained-release layer is used as a variable. Specifically, the variables involved in treatment groups 2C-5C are shown in Table 6. Among them, in treatment groups 2C-5C, the mass ratio of magnesium oxide in the rapid-collapse layer to magnesium oxide in the sustained-release layer is maintained at 1.14:1, that is, the mass fraction of magnesium oxide in the sustained-release layer is maintained at 350 parts; the mass fraction of the first lubricant to the second lubricant is 1.5:1.8, that is, the mass fraction of the second lubricant is maintained at 18 parts. Except for the above differences, the operation steps for preparing magnesium oxide bilayer sustained-release tablets in treatment groups 2C-5C are strictly consistent with those in treatment group 1C of Example 3.

[0140] Table 6. Variables involved in treatment groups 1C-5C

[0141]

[0142] Processing group 6C

[0143] This treatment group prepared magnesium oxide bilayer sustained-release tablets according to the formulation and method provided in treatment group 1C of Example 3. In preparing the magnesium oxide bilayer sustained-release tablets, this treatment group replaced konjac gum with an equal mass fraction of microcrystalline cellulose when preparing the sustained-release layer. Apart from the above differences, the operating steps for preparing the magnesium oxide bilayer sustained-release tablets in this treatment group were strictly consistent with those in treatment group 1C of Example 3.

[0144] Processing group 7C

[0145] This treatment group prepared magnesium oxide bilayer sustained-release tablets according to the formulation and method provided in treatment group 1C of Example 3. In preparing the magnesium oxide bilayer sustained-release tablets, this treatment group substituted an equal mass fraction of locust bean gum for konjac gum when preparing the sustained-release layer. Apart from the above differences, the operating steps for preparing the magnesium oxide bilayer sustained-release tablets in this treatment group were strictly consistent with those in treatment group 1C of Example 3.

[0146] Processing group 8C

[0147] This treatment group prepared magnesium oxide bilayer sustained-release tablets according to the formulation and method provided in treatment group 1C of Example 3. In preparing the magnesium oxide bilayer sustained-release tablets, this treatment group replaced konjac gum with an equal mass fraction of sodium alginate when preparing the sustained-release layer. Apart from the above differences, the operating steps for preparing the magnesium oxide bilayer sustained-release tablets in this treatment group were strictly consistent with those in treatment group 1C of Example 3.

[0148] Test Example 3

[0149] 1. Test Object

[0150] Magnesium oxide bilayer sustained-release tablets prepared in each treatment group of Example 3.

[0151] 2. Testing Methods

[0152] This test case follows the test method provided in Test Case 1.

[0153] 3. Test Results and Analysis

[0154] The test results for this test case are shown in Table 7. Data from treatment groups 1C to 5C in this test case show that adjusting the mass ratio of magnesium oxide, the second filler, the second binder, and the second lubricant in the controlled-release layer affects the stepwise controlled-release effect of the layer. Specifically, it affects the disintegration time, hardness, and brittleness of the controlled-release layer.

[0155] Specifically, in treatment group 4C, the friability was lower, and the disintegration time of the sustained-release layer increased to 300 minutes. This was because the higher content of the second binder increased the disintegration time and improved the particle adhesion of the sustained-release layer. Although a sustained-release effect was achieved, the excessive addition of binder resulted in a high-concentration binder forming a continuous film, hindering moisture penetration and efficacy diffusion, leading to delayed disintegration. In other words, the rapid-disintegration layer had already finished disintegrating before the sustained-release layer even began to disintegrate, thus failing to guarantee a long-term and continuous release of magnesium oxide.

[0156] Similarly, in treatment group 5C, in addition to the prolonged disintegration time of the sustained-release layer, the high proportion of the second filler dilutes the active ingredient, potentially leading to uneven distribution of the active ingredient. This affects the reproducibility of subsequent active ingredient detection, increases the difficulty of quality control, and is detrimental to stable production in industrial-scale manufacturing. Furthermore, although the magnesium oxide double-layer sustained-release tablets provided by treatment group 5C can achieve sustained release, it cannot guarantee long-term stable and continuous uniform release of magnesium oxide. The situation also arises where the rapidly disintegrating layer has already disintegrated before the sustained-release layer has even begun to disintegrate.

[0157] Furthermore, based on the data from treatment groups 6C to 8C, it is known that replacing the material used in the second filler affects the hardness, friability, and disintegration time of the magnesium oxide bilayer sustained-release tablets. In treatment group 6C, because the microcrystalline cellulose in the formulation provided by this invention has relatively weak adhesive properties and a slightly weaker sustained-release effect compared to konjac gum, the disintegration time and the time difference between the sustained-release layers are shortened, failing to adequately meet the stepwise disintegration requirements of the gastrointestinal tract. Therefore, the data from treatment groups 6C to 8C demonstrate that the choice of the second filler material affects the adhesive effect of the sustained-release layer, thereby affecting the disintegration time of the sustained-release layer.

[0158] Table 7. Test Results

[0159]

[0160] Example 4

[0161] Processing Group 1D

[0162] This treatment group prepared magnesium oxide bilayer sustained-release tablets according to the formulation and method provided in treatment group 1A of Example 1. In preparing the magnesium oxide bilayer sustained-release tablets, this treatment group replaced polyethylene glycol (cosolvent) with an equal mass fraction of citric acid when preparing the rapid-disintegrating layer. Apart from the above differences, the operating steps for preparing the magnesium oxide bilayer sustained-release tablets in this treatment group were strictly consistent with those in treatment group 1A of Example 1.

[0163] Processing Group 2D

[0164] This treatment group prepared magnesium oxide bilayer sustained-release tablets according to the formulation and method provided in treatment group 1A of Example 1. In preparing the magnesium oxide bilayer sustained-release tablets, this treatment group replaced polyethylene glycol (a cosolvent) with an equal mass fraction of povidone K30 when preparing the rapid-disintegrating layer. Apart from the above differences, the operating steps for preparing the magnesium oxide bilayer sustained-release tablets in this treatment group were strictly consistent with those in treatment group 1A of Example 1.

[0165] Processing Group 3D

[0166] This treatment group prepared magnesium oxide bilayer sustained-release tablets according to the formulation and method provided in treatment group 1A of Example 1. In preparing the magnesium oxide bilayer sustained-release tablets, this treatment group replaced povidone with an equal mass fraction of sodium carboxymethyl cellulose in the preparation of the rapid-disintegrating layer. Apart from the above differences, the operating steps for preparing the magnesium oxide bilayer sustained-release tablets in this treatment group were strictly consistent with those in treatment group 1A of Example 1.

[0167] Processing Group 4D

[0168] This treatment group prepared magnesium oxide bilayer sustained-release tablets according to the formulation and method provided in treatment group 1A of Example 1. In preparing the magnesium oxide bilayer sustained-release tablets, this treatment group replaced povidone with an equal mass fraction of hydroxypropyl cellulose when preparing the rapidly disintegrating layer. Apart from the above differences, the operating steps for preparing the magnesium oxide bilayer sustained-release tablets in this treatment group were strictly consistent with those in treatment group 1A of Example 1.

[0169] Processing Group 5D

[0170] This treatment group prepared magnesium oxide bilayer sustained-release tablets with reference to the formulation and method provided in treatment group 1A of Example 1. In preparing the magnesium oxide bilayer sustained-release tablets, this treatment group replaced hydroxypropyl methylcellulose with an equal mass fraction of hydroxypropyl methylcellulose when preparing the sustained-release layer. Apart from the above differences, the operating steps for preparing the magnesium oxide bilayer sustained-release tablets in this treatment group were strictly consistent with those in treatment group 1A of Example 1.

[0171] Processing Group 6D

[0172] This treatment group prepared magnesium oxide bilayer sustained-release tablets with reference to the formulation and method provided in treatment group 1A of Example 1. In preparing the magnesium oxide bilayer sustained-release tablets, this treatment group replaced hydroxypropyl cellulose with an equal mass fraction of acrylic resin when preparing the sustained-release layer. Apart from the above differences, the operating steps for preparing the magnesium oxide bilayer sustained-release tablets in this treatment group were strictly consistent with those in treatment group 1A of Example 1.

[0173] Processing Group 7D

[0174] This treatment group prepared magnesium oxide bilayer sustained-release tablets according to the formulation and method provided in treatment group 1A of Example 1. In preparing the magnesium oxide bilayer sustained-release tablets, this treatment group substituted stearic acid and magnesium stearate with equal parts by mass of talc. Apart from the above differences, the operating steps for preparing the magnesium oxide bilayer sustained-release tablets in this treatment group were strictly consistent with those in treatment group 1A of Example 1.

[0175] Test Example 4

[0176] 1. Test Object

[0177] Magnesium oxide bilayer sustained-release tablets prepared in each treatment group of Example 4.

[0178] 2. Testing Methods

[0179] This test case follows the test method provided in Test Case 1.

[0180] 3. Test Results and Analysis

[0181] The test results for this test example are shown in Table 8. The experimental data from this test example confirm that the formulation provided by this invention is applicable to a variety of materials. Specifically, in treatment groups 1D-2D, replacing polyethylene glycol in the rapid-disintegrating layer with β-cyclodextrin and povidone K30 still maintained good solubilizing effects, thereby maintaining good interlayer interface conditions and tablet appearance. Similarly, in treatment groups 3D-4D, replacing the povidone in the rapid-disintegrating layer with sodium carboxymethyl cellulose and sodium alginate, respectively, still maintained good solubilizing effects.

[0182] Furthermore, in treatment groups 5D to 6D, by replacing the hydroxypropyl cellulose in the sustained-release layer with hydroxypropyl methyl cellulose and acrylic resin, the resulting magnesium oxide bilayer sustained-release tablets also exhibited good interlayer interface conditions and tablet appearance.

[0183] In the magnesium oxide bilayer sustained-release tablets provided by processing group 7D, the materials used for the first and second lubricants were replaced with talc. Although the hardness and brittleness decreased slightly, the interlayer interface and tablet appearance were still good.

[0184] Table 8. Test Results

[0185]

Claims

1. A magnesium oxide double-layer sustained-release tablet, characterized in that: The magnesium oxide double-layer sustained-release tablet comprises a rapidly disintegrating layer and a sustained-release layer stacked sequentially. The rapid-disintegration layer comprises magnesium oxide, a first lubricant, a first binder, a co-solvent, and a disintegrant; The slow-release layer comprises magnesium oxide, a second lubricant, a second binder, and a second filler; The first lubricant and the second lubricant are selected from at least one of fatty acid lubricants, silicone-based compound lubricants, and polymer lubricants; The disintegrant includes at least one of starch-based disintegrants, cellulose-based disintegrants, polymer-based disintegrants, and effervescent disintegrants; The mass ratio of magnesium oxide in the rapid-release layer to magnesium oxide in the slow-release layer is calculated as follows: 0.2~1.3 : 0.7~1.

0. The tap density of magnesium oxide is 0.5~1.0 g / mL; Furthermore, in the magnesium oxide bilayer sustained-release tablet, the mass ratio of the first lubricant to the second lubricant is 0.5~4:2~6; the mass ratio of the first adhesive to the second adhesive is 3.5~5:5~10. In the rapid collapse layer, the mass ratio of magnesium oxide to the co-solvent to the first lubricant is 15~70:0.5~2:0.5~3. In the sustained-release layer, the mass percentages of magnesium oxide : second filler : second binder : second lubricant are 50-75% : 10-30% : 5-10% : 1-5%; The disintegration time of the rapid-disintegration layer is T1, and the disintegration time of the slow-release layer is T2; In the magnesium oxide bilayer sustained-release tablets, the following relationship is satisfied: T2-T1 ≥ 0.5 hours; T1 < 1 hour, and T2 > 1 hour.

2. The application of the magnesium oxide double-layer sustained-release tablets as described in claim 1 in the preparation of food.

3. The application of the magnesium oxide bilayer sustained-release tablets as described in claim 1 in the preparation of pharmaceuticals.

4. The application of the magnesium oxide double-layer sustained-release tablets as described in claim 1 in the preparation of dietary supplements.

5. The application of the magnesium oxide bilayer sustained-release tablet as described in claim 1 in the preparation of pet food.

6. A method for preparing the magnesium oxide bilayer sustained-release tablet as described in claim 1, characterized in that, The method includes the following steps: Step 1. Prepare the rapid-disintegration layer premix and the slow-release layer premix separately; Step 2. Pre-compact the rapid-disintegration layer premix or the slow-release layer premix to form a base layer; Step 3. Lay the remaining premixed material that has not undergone pre-compression treatment on the base layer, and then form magnesium oxide double-layer slow-release tablets through tableting.

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