Melatonin rapidly disintegrating tablet and preparation method thereof

Abstract

The invention discloses a melatonin rapidly disintegrating oral tablet and a preparation method thereof, and the melatonin rapidly disintegrating oral tablet is prepared from the following raw materials in parts by weight: 40 to 55 parts of mannitol, 3 to 6 parts of cross-linked povidone, 0.5 to 2.0 parts of povidone, 2 to 6 parts of melatonin, 30 to 45 parts of filler and 0.3 to 1.5 parts of lubricant. Wherein the mannitol is beta-crystal form mannitol. According to the invention, mannitol of a limited type is matched with raw materials such as polyvinylpolypyrrolidone, and meanwhile, a specific mixing and tabletting process is adopted, so that the tablet can be rapidly disintegrated in an oral cavity while the hardness of the tablet is maintained, the bioavailability is high, and the requirements of the health food field on taking convenience, effectiveness and industrial production can be met.

Description

Technical Field

[0001] This application relates to a melatonin fast-disintegrating tablet and its preparation method, belonging to the field of health food technology. Background Technology

[0002] Melatonin is an endogenous hormone secreted by the pineal gland in the human body. It plays a physiological role in regulating the sleep-wake cycle and improving sleep quality, and has been widely used in the health food industry to alleviate sleep disorders such as insomnia and jet lag. Currently, commercially available melatonin preparations mainly include ordinary tablets, capsules, and oral liquids. Oral tablets and capsules need to be taken with water, which is inconvenient for people with swallowing difficulties (such as the elderly and children). Although oral liquids are convenient to take, they have drawbacks such as inconvenience in carrying, easy deterioration, and low dosage control precision.

[0003] To address the aforementioned issues, the industry has developed orally disintegrating tablets of melatonin. Their core advantage lies in the fact that they do not require water to take; they rapidly disintegrate in the mouth and are absorbed through the mucous membranes, resulting in faster onset of action and higher patient compliance. Currently, the preparation of orally disintegrating tablets primarily employs the following methods: 1. Effervescent foaming system: It accelerates disintegration by generating gas through effervescence reaction, but it has problems such as taste irritation (acid-base reaction produces off-flavors) and poor tablet stability (easy to absorb moisture and produce gas); 2. Using freeze-drying process: Rapid collapse is achieved by forming a porous structure through freeze-drying, but the production cycle is long and the cost is high, making it difficult to mass-produce industrially.

[0004] In addition, Chinese patent application CN114246834A – a melatonin orally disintegrating formulation for improving sleep and its manufacturing process – uses D-mannitol and other ingredients as a base material, combined with disintegrants such as crospovidone, which mainly solves the problem of tablet taste. However, current formulations generally have the following technical problems: (1) It is difficult to balance rapid disintegration and mechanical properties: In order to pursue rapid disintegration, the amount of binder is often reduced or the proportion of disintegrant is increased, resulting in problems such as insufficient tablet hardness and excessive brittleness, which cannot meet the requirements for transportation and storage; if the tablet hardness and other properties are improved, the tablet will disintegrate in the mouth for a long time, affecting the user experience.

[0005] (2) Insufficient bioavailability: Melatonin is a fat-soluble compound with poor water solubility. Although existing fast-disintegrating tablets can disintegrate quickly, the drug dissolution rate is low, and the bioavailability needs to be improved.

[0006] Therefore, there is an urgent need to develop a melatonin rapid-disintegrating tablet that does not rely on effervescent agents, has a simple manufacturing process, and can simultaneously achieve rapid oral disintegration, suitable mechanical properties, and high bioavailability. Summary of the Invention

[0007] To address the aforementioned issues, a melatonin orally disintegrating tablet and its preparation method are provided. By using a limited type of mannitol combined with crospovidone and other raw materials, and employing a specific mixing and tableting process, rapid disintegration in the oral cavity is achieved while maintaining tablet hardness. This results in high bioavailability and meets the needs of the health food industry for convenient administration, effectiveness, and industrialized production.

[0008] According to one aspect of this application, a melatonin fast-disintegrating tablet is provided, which is prepared by comprising the following raw materials in parts by weight: 40-55 parts mannitol, 3-6 parts crospovidone, 0.5-2.0 parts povidone, 2-6 parts melatonin, 30-45 parts filler, and 0.3-1.5 parts lubricant. The mannitol in question is β-crystalline mannitol.

[0009] Optionally, it is prepared from the following raw materials in parts by weight: 45-55 parts mannitol, 4-6 parts crospovidone, 0.8-2.0 parts povidone, 2-5 parts melatonin, 35-45 parts filler, and 1-1.5 parts lubricant.

[0010] Optionally, the mannitol is obtained by spray drying and has a particle size of 80-100 μm; the cross-linked polyvinylpyrrolidone has a particle size of 50-80 μm and the polyvinylpyrrolidone is K30. Preferably, the mannitol is obtained by spray drying and has a D50 particle size of 80-100 μm, and the cross-linked polyvinylpyrrolidone has a D50 particle size of 50-80 μm.

[0011] Specifically, the raw materials used are D-mannitol (purity ≥99%, food grade) and purified water; the equipment is a centrifugal spray dryer.

[0012] The method for preparing β-crystalline mannitol by spray drying is as follows: (1) Heat purified water to 65°C, add mannitol powder while stirring, and prepare a mannitol aqueous solution with a mass concentration of 35%; continue stirring for 15 minutes until the mannitol is completely dissolved and a clear and transparent solution is formed (without undissolved particles) to avoid affecting the subsequent atomization effect.

[0013] (2) Setting and operating spray drying parameters Inlet air temperature: 170℃. This temperature allows the surface of the droplets to evaporate quickly and form a hard shell, while the internal moisture escapes through diffusion, forming a porous structure. Avoid excessively high temperatures (>190℃) as this will cause local carbonization of mannitol, and excessively low temperatures (<150℃) as the particles are prone to sticking together and cannot form β-crystals.

[0014] Outlet air temperature: 80℃. The outlet air temperature should be matched with the inlet air temperature to ensure that the moisture content of the particles is ≤0.5% (excessive moisture content will cause the particles to clump together and affect their flowability).

[0015] Atomization speed: 20,000 rpm (centrifugal nebulizer). The solution is atomized into droplets with a diameter of 50-100 μm by high-speed rotation.

[0016] Feed rate: 80 mL / min. Adjustable according to equipment specifications to ensure a residence time of 10 s for droplets within the drying tower.

[0017] Air intake volume: 40 m³ 3 / h. Ensure sufficient contact between hot air and mist droplets to improve drying efficiency.

[0018] (3) Collection and screening The dried mannitol particles were collected by a cyclone separator and sieved using an 80-200 mesh standard sieve. The intermediate fraction of 50-100 μm was taken, and particles that were too large or too small were discarded.

[0019] First, a specific β-crystalline form of mannitol is prepared using spray drying with a defined particle size range. These particles contain numerous interconnected micropores (5-20 μm in diameter), providing a uniform "three-dimensional framework" for cross-linked povidone adhesion. Cross-linked povidone also possesses a highly cross-linked network structure, allowing for rapid water absorption and swelling upon contact with water. This swelling force is transmitted throughout the tablet via the microporous structure of mannitol, creating a multi-point simultaneous expansion effect, accelerating tablet breakage and effectively speeding up tablet disintegration. Furthermore, the amount of povidone (K30) is controlled at 0.5-2.0 parts, ensuring it only plays a dispersing role for melatonin without increasing the overall tablet viscosity and hindering water penetration. Therefore, compared to existing technologies that rely on effervescent agents (gas production from acid-base reactions) for disintegration, this method achieves rapid disintegration through physical water absorption and swelling, resulting in odorless, non-irritating particles and avoiding stability issues caused by effervescent agents' moisture absorption.

[0020] Secondly, β-crystalline mannitol also has good mechanical strength, forming a "rigid-elastic" composite skeleton with microcrystalline cellulose: mannitol provides structural support, while microcrystalline cellulose enhances particle binding force through intermolecular hydrogen bonds. The two work together to enable the tablet to maintain stable hardness.

[0021] Melatonin is a fat-soluble compound with poor water solubility. Povidone (K30), on the other hand, is a water-soluble polymer that can bind with melatonin molecules to form a stable complex, increasing molecular dispersion. At the same time, the hydrophilic surface of β-crystalline mannitol provides a dissolution platform for the complex, accelerating the release of melatonin and effectively improving bioavailability.

[0022] Optionally, the weight ratio of mannitol to crospovidone is (8-10):1.

[0023] Specifically, by limiting the ratio of specific β-crystalline mannitol to crospovidone prepared by spray drying, a balance is achieved between the disintegration and mechanical strength (hardness, friability) of the tablets. Specifically, this balances the "crospovidone swelling force" and the "mannitol-microcrystalline cellulose skeleton binding force," ultimately achieving effective regulation of the disintegration rate and the mechanical strength of the tablets.

[0024] When the weight ratio of mannitol to cross-linked polyvinyl alcohol (CPV) is controlled within the above range, the continuous hydrophilic / porous network constructed by mannitol can efficiently guide water into the tablet, quickly triggering capillary water absorption and swelling of CPV. This results in a significantly shortened disintegration time and a low brittleness rate while maintaining tablet hardness and mechanical strength. Specifically, mannitol dominates the matrix phase, forming interconnected pathways. CPV is embedded in the matrix in the form of dispersed particles. When water rapidly penetrates along the channels formed by mannitol, CPV is quickly wetted and swells, forming local ruptures and amplifying the channels, resulting in a chain reaction of fragmentation, ultimately leading to the rapid disintegration of the entire tablet.

[0025] Optionally, the tablet hardness is 60-80 N.

[0026] Optionally, the filler is microcrystalline cellulose; the lubricant is magnesium stearate.

[0027] According to another aspect of this application, a method for preparing the above-mentioned melatonin rapid-disintegrating tablets is provided, comprising the following steps: (1) Mannitol, filler, povidone and some cross-linked povidone are premixed and mixed at low speed to obtain a premix; (2) Mix the premix with the melatonin until homogeneous; (3) After mixing the mixture from step (2) with the remaining crosslinked polyvinyl ketone evenly, add the lubricant and mix evenly; (4) Compress the mixture into tablets to obtain the melatonin rapid disintegration tablets.

[0028] Optionally, in step (1), the amount of cross-linked polyvinyl ketone added is 60-80%, the mixing speed is 10-15 rpm, and the mixing time is 4-10 min.

[0029] Optionally, the rotation speed in step (2) is 30-40 rpm, and the mixing time in step (2) is 3-6 min; In step (3), the mixing time of the mixture with the remaining crosslinked polyvinyl ketone is 0.5-2 min and the rotation speed is 20-30 rpm. After adding the lubricant, the mixing time is 1-2 min and the rotation speed is 12-25 rpm.

[0030] Optionally, in step (4), the tableting pressure is 10-15 kN and the rotation speed is 16-20 rpm.

[0031] The beneficial effects of this application include, but are not limited to: 1. The melatonin orally disintegrating tablets of this application utilize β-crystalline mannitol spray-dried with a specific particle size. By leveraging its porous structure and the synergistic effect of a limited ratio of cross-linked povidone, the tablets disintegrate rapidly in saliva in the oral cavity. The micropores of β-crystalline mannitol rapidly absorb liquid through capillary effect, while cross-linked povidone expands synchronously to generate thrust, forming a highly efficient disintegration chain of "water absorption-swelling-breakdown". This avoids the taste irritation and moisture stability problems caused by traditional effervescent tablets. At the same time, the natural sweetness of β-crystalline mannitol can mask the slight bitterness of melatonin, eliminating the need for additional flavorings or sweeteners. There is no gritty feeling in the mouth, significantly improving the taste and compliance.

[0032] 2. The method for preparing melatonin orally disintegrating tablets of this application, on the one hand, involves the stepwise addition of crospovidone (CPV), i.e., adding 60-80% premix first, followed by 20-40% short-mix. This allows the later-added CPV to accumulate on the tablet surface, forming a "surface-active disintegrating layer" that preferentially contacts the oral cavity and immediately exerts its water-absorbing and swelling effect, significantly shortening the initial disintegration time. The premixed CPV is distributed inside the tablet, ensuring the continuity and integrity of overall disintegration and preventing the remaining collapse after only the surface layer breaks down. In addition, the premixing stage ensures that most of the CPV is thoroughly mixed with other excipients, which is beneficial for maintaining batch-to-batch consistency during production. On the other hand, by controlling parameters such as compression pressure, the final tablet hardness is maintained at 60-80N. This pressure range allows for the formation of appropriate mechanical bonding forces between particles, which not only meets the requirements for transportation and storage but also effectively shortens the disintegration time during later use. The two components work synergistically to form a multi-stage disintegration structure where the tablet surface initiates the disintegration, followed by continuous disintegration driven by the internal bulk phase. Appropriate compression parameters ensure that the tablet is sufficiently dense to withstand external forces while retaining the effective microchannel network composed of mannitol and CPV. This achieves shorter initial disintegration at a target hardness of 60-80 N, resulting in a shorter overall disintegration time and rapid release of the active ingredient. Detailed Implementation

[0033] The present application is described in detail below with reference to the embodiments, but the present application is not limited to these embodiments.

[0034] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of skill in the art. The reagents and raw materials used in this invention are readily available through conventional means, and unless otherwise specified, they shall be used in accordance with conventional methods in the art or as per the product instructions. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to the methods of this invention. The preferred embodiments and materials described in this patent are for illustrative purposes only.

[0035] The following raw materials or manufacturers are listed in this application: Melatonin - Hebei Weidakang Biotechnology Co., Ltd.; Mannitol - Hebei Huaxu Pharmaceutical Co., Ltd.; Crospovidone, Povidone - Kollidon; Microcrystalline Cellulose - PH-101, Jiangxi Alpha High-Tech Pharmaceutical Co., Ltd.; Magnesium Stearate - Tianli Pharmaceutical Excipients Co., Ltd.

[0036] Example 1: Melatonin Fast-Disintegrating Tablet 1# According to the weight parts, Melatonin Rapid Disintegration Tablet 1# is prepared from the following raw materials: 50 parts mannitol, 5 parts crospovidone, 1 part povidone, 3 parts melatonin, 40 parts filler, and 1 part lubricant. Mannitol is β-crystalline mannitol. Mannitol is obtained by spray drying, with a D50 particle size of 80-100 μm; crospovidone has a D50 particle size of 50-80 μm. The weight ratio of mannitol to crospovidone is 10:1; the tablet hardness is 70 N. The filler is microcrystalline cellulose; the lubricant is magnesium stearate.

[0037] The preparation method of melatonin rapid-disintegrating tablets #1 includes the following steps: (1) Mannitol, filler, povidone and some cross-linked povidone are premixed and mixed at low speed to obtain a premix; (2) Mix the premix with the melatonin until homogeneous; (3) After mixing the mixture from step (2) with the remaining crosslinked polyvinyl ketone evenly, add the lubricant and mix evenly; (4) Compress the mixture into tablets to obtain melatonin rapid disintegration tablet 1#.

[0038] In step (1), the amount of cross-linked polyvinyl acetate added is 60%, the mixing speed is 12 rpm, and the mixing time is 8 min. In step (2), the speed is 35 rpm, and the mixing time is 5 min. In step (3), the mixing time of the mixture with the remaining cross-linked polyvinyl acetate is 1 min, the speed is 25 rpm, and after adding the lubricant, the mixing time is 1 min, and the speed is 18 rpm. In step (4), the tableting pressure is 12 kN, and the speed is 18 rpm.

[0039] Example 2: Melatonin Fast-Disintegrating Tablets #2 According to the weight parts, Melatonin Rapid Disintegration Tablet 2# is prepared from the following raw materials: 45 parts mannitol, 5 parts crospovidone, 0.5 parts povidone, 2 parts melatonin, 35 parts filler, and 0.4 parts lubricant. Mannitol is β-crystalline mannitol. Mannitol is obtained by spray drying, with a D50 particle size of 80-100 μm; crospovidone has a D50 particle size of 50-80 μm. The weight ratio of mannitol to crospovidone is 9:1; the tablet hardness is 60 N. The filler is microcrystalline cellulose; the lubricant is magnesium stearate.

[0040] The preparation method of melatonin rapid-disintegrating tablets #2 includes the following steps: (1) Mannitol, filler, povidone and some cross-linked povidone are premixed and mixed at low speed to obtain a premix; (2) Mix the premix with the melatonin until homogeneous; (3) After mixing the mixture from step (2) with the remaining crosslinked polyvinyl ketone evenly, add the lubricant and mix evenly; (4) Compress the mixture into tablets to obtain melatonin rapid disintegration tablet 2#.

[0041] In step (1), the amount of cross-linked polyvinyl acetate added is 70%, the mixing speed is 10 rpm, and the mixing time is 10 min. In step (2), the speed is 30 rpm, and the mixing time is 6 min. In step (3), the mixing time of the mixture with the remaining cross-linked polyvinyl acetate is 0.5 min, the speed is 30 rpm, and after adding the lubricant, the mixing time is 1 min, and the speed is 25 rpm. In step (4), the tableting pressure is 10 kN, and the speed is 16 rpm.

[0042] Example 3: Melatonin Fast-Disintegrating Tablets #3 According to the weight parts, Melatonin Rapid Disintegration Tablet 3# is prepared from the following raw materials: 54 parts mannitol, 6 parts crospovidone, 2.0 parts povidone, 6 parts melatonin, 45 parts filler, and 1.5 parts lubricant. Mannitol is β-crystalline mannitol. Mannitol is obtained by spray drying, with a particle size of 80-100 μm; crospovidone has a particle size of 50-80 μm. The weight ratio of mannitol to crospovidone is 9:1; the tablet hardness is 80 N. The filler is microcrystalline cellulose; the lubricant is magnesium stearate.

[0043] The preparation method of melatonin rapid-disintegrating tablets #3 includes the following steps: (1) Mannitol, filler, povidone and some cross-linked povidone are premixed and mixed at low speed to obtain a premix; (2) Mix the premix with the melatonin until homogeneous; (3) After mixing the mixture from step (2) with the remaining crosslinked polyvinyl ketone evenly, add the lubricant and mix evenly; (4) Compress the mixture into tablets to obtain melatonin rapid disintegration tablet 3#.

[0044] In step (1), the amount of cross-linked polyvinyl acetate added is 80%, the mixing speed is 15 rpm, and the mixing time is 4 min. In step (2), the speed is 40 rpm, and the mixing time is 3 min. In step (3), the mixing time of the mixture with the remaining cross-linked polyvinyl acetate is 2 min, the speed is 20 rpm, and after adding the lubricant, the mixing time is 2 min, and the speed is 12 rpm. In step (4), the tableting pressure is 15 kN, and the speed is 20 rpm.

[0045] Example 4: Melatonin Fast-Disintegrating Tablet #4 The difference between Example 4 and Example 1 is that the average particle size of mannitol in Example 4 is 200 μm.

[0046] Example 5: Melatonin Fast-Disintegrating Tablet #5 The difference between Example 5 and Example 1 is that the weight ratio of mannitol to crospovidone in Example 5 is 4:1.

[0047] Comparative Example 1 vs. Melatonin Rapid-Disintegrating Tablet #1 The difference between Comparative Example 1 and Example 1 is that α-crystalline mannitol is used in Comparative Example 1.

[0048] Comparative Example 2 vs. Melatonin Rapid-Disintegrating Tablet 2# The difference between Comparative Example 2 and Example 1 is that the preparation method of Comparative Example 2 does not use the stepwise addition of cross-linked polyvinyl ketone, but adds all the cross-linked polyvinyl ketone in step (1).

[0049] Comparative Example 3 vs. Melatonin Rapid-Disintegrating Tablet 3# The difference between Comparative Example 3 and Example 1 is that the tablets prepared in Comparative Example 3 have a hardness of 100N.

[0050] Experimental Example I. Testing of Disintegration Time and Mechanical Performance Indicators of Melatonin Rapid-Disintegrating Tablets The disintegration time and mechanical properties of the melatonin rapid-disintegrating tablets prepared in Examples 1-5 and Comparative Examples 1-3 were tested, and the results are shown in Table 1.

[0051] 1. Hardness test Instrument: Tablet hardness tester (Schleuniger 8M model) Test method: Take 10 tablets of each example and each comparative example, place each tablet between the two indenters of the hardness tester, apply pressure at a uniform speed until the tablet breaks, record the maximum pressure value (N), and calculate the average value.

[0052] Judgment criteria: General Chapter 0923, Part IV, Chinese Pharmacopoeia 2025 Edition.

[0053] 2. Friability test Instrument: Tablet Friability Tester (Erweka TA model) Test method: Take 10 tablets of each example and comparative example, dried to constant weight, accurately weigh the total weight (W1), place them in the drum of a friability tester (rotation speed 25 rpm), rotate 100 times, remove them, sieve away the powder, accurately weigh the total weight of the remaining tablets (W2), and calculate the friability: Friability (%) = (W1-W2) / W1×100% Judgment criteria: It should meet the requirements of General Chapter 0923 of Part IV of the 2025 edition of the Chinese Pharmacopoeia, with a friability of ≤0.25% and no obvious fragments or cracks.

[0054] 3. Linear reciprocating friction test (wear resistance) Instrument: Tablet friction tester (PharmaTest PTG model, equipped with a reciprocating friction platform) Test method: Take 10 tablets of each example and each comparative example, place each tablet on a friction platform, apply 200g pressure (simulating compression during transportation), and rub back and forth at a frequency of 30 times / min (stroke 50mm) for 10 minutes. Then observe whether the tablet surface shows any flaking or cracking.

[0055] Judgment criteria: No obvious damage to the surface, ensuring stability during transportation.

[0056] 4. Disintegration time limit detection Instrument: Intelligent disintegration device (ZBS-6G model, equipped with a special basket for oral disintegration tablets) Test conditions: Simulate oral environment, medium is artificial saliva at 37℃±0.5℃ (formula: potassium dihydrogen phosphate 0.34g, disodium hydrogen phosphate 1.36g, sodium chloride 0.45g, water added to 1000mL, pH6.8), no baffle required.

[0057] Test method: Take 5 tablets of each sample from each embodiment and each comparative example, place them in the glass tube of the basket, start the instrument, record the time for each tablet to completely disintegrate (without solid particle residue), and take the average value.

[0058] Judgment criteria: Requirements for orally disintegrating tablets in General Chapter 0921 of Part IV of the 2025 edition of the Chinese Pharmacopoeia.

[0059] Table 1. Test results of disintegration time and mechanical properties of melatonin rapid-disintegrating tablets.

[0060] II. Melatonin Bioavailability Test 1. In vitro release rate test Instrument: Intelligent dissolution tester (USP701 model, paddle method) Test conditions: The medium was 900 mL of artificial intestinal fluid (pH 6.8 phosphate buffer), the temperature was 37℃±0.5℃, and the paddle speed was 50 rpm.

[0061] Test method: Five tablets of each example and each comparative example were placed into dissolution cups. 5 mL samples were taken at 5, 10, 15, 30 and 60 min (with an equal amount of medium added at the same temperature). The samples were filtered through a 0.45 μm filter membrane. The melatonin concentration in the filtrate was determined by high performance liquid chromatography (HPLC). The average value was taken, and the cumulative release rate was calculated: Cumulative release rate (%) = (dissolved amount at a certain time point / labeled amount) × 100%.

[0062] HPLC conditions: C18 column (250 mm × 4.6 mm, 5 μm), mobile phase methanol-water (60:40), flow rate 1.0 mL / min, detection wavelength 222 nm, column temperature 30 °C.

[0063] Judgment criteria: cumulative release ≥90% at 3 min, ≥95% at 60 min, and RSD ≤10% between 5 tablets. The experimental results are shown in Table 2.

[0064] Table 2. Results of in vitro release rate test of melatonin rapid-disintegrating tablets (cumulative release rate, %)

[0065] Based on the above experimental data, it can be seen that the melatonin oral rapid-disintegrating tablets prepared using the raw materials and preparation method specified in this application have a hardness in the range of 60-80N, a friability of ≤0.25%, a short disintegration time, good disintegration effect, and good performance in linear reciprocating friction tests, with disintegration time ≤30s. The overall mechanical properties are excellent, meeting the performance requirements of high-quality rapid-disintegrating tablets. In Example 4, the disintegration time was prolonged and slight surface flaking occurred due to the excessively large mannitol particle size (200μm). In Example 5, the final friability exceeded the specified range due to the ratio of mannitol to cross-linked polyvinylpyrrolidone, resulting in a longer disintegration time.

[0066] Furthermore, in terms of bioavailability, Examples 1-3 of this application exhibited a 3-minute release rate ≥90% and a 60-minute release rate ≥99%, with good uniformity (RSD ≤ 3.5%). Comparative Examples 1-3 and Examples 4-5 showed significantly lower release rates, failing to meet the requirements for high-efficiency release. Comparative Example 1, due to the use of α-crystalline mannitol, suffered from overall deterioration in disintegration and release performance; Comparative Example 2, due to the one-step addition of cross-linked povidone, had insufficient disintegration kinetics, resulting in a longer disintegration time and generally lower release rate; Comparative Example 3, due to its excessively high hardness (100N), hindered drug release, also had a longer disintegration time.

[0067] The above description is merely an embodiment of this application and is not intended to limit the scope of this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the scope of the claims of this application.

Claims

1. A melatonin fast-disintegrating tablet, characterized in that, Based on parts by weight, it is prepared from the following raw materials: 40-55 parts mannitol, 3-6 parts crospovidone, 0.5-2.0 parts povidone, 2-6 parts melatonin, 30-45 parts filler, and 0.3-1.5 parts lubricant; The mannitol in question is β-crystalline mannitol.

2. The melatonin rapid-disintegration tablet according to claim 1, characterized in that, It is prepared from the following raw materials in parts by weight: 45-55 parts mannitol, 4-6 parts crospovidone, 0.8-2.0 parts povidone, 2-5 parts melatonin, 35-45 parts filler, and 1-1.5 parts lubricant.

3. The melatonin rapid-disintegration tablet according to claim 1, characterized in that, The mannitol was obtained by spray drying and had a particle size of 80-100 μm; the cross-linked polyvinylpyrrolidone had a particle size of 50-80 μm.

4. The melatonin rapid-disintegration tablet according to claim 1, characterized in that, The weight ratio of mannitol to crospovidone is (8-10):

1.

5. The melatonin rapid-disintegration tablet according to claim 1, characterized in that, The tablets have a hardness of 60-80 N.

6. The melatonin rapid-disintegration tablet according to claim 1, characterized in that, The filler is microcrystalline cellulose; the lubricant is magnesium stearate.

7. A method for preparing melatonin rapid-disintegrating tablets as described in any one of claims 1-6, characterized in that, Includes the following steps: (1) Mannitol, filler, povidone and some cross-linked povidone are premixed and mixed at low speed to obtain a premix; (2) Mix the premix with the melatonin until homogeneous; (3) After mixing the mixture from step (2) with the remaining crosslinked polyvinyl ketone evenly, add the lubricant and mix evenly; (4) Compress the mixture into tablets to obtain the melatonin rapid disintegration tablets.

8. The preparation method according to claim 7, characterized in that, In step (1), the amount of cross-linked polyvinyl ketone added is 60-80%, the mixing speed is 10-15 rpm, and the mixing time is 4-10 min.

9. The preparation method according to claim 7, characterized in that, The rotation speed in step (2) is 30-40 rpm, and the mixing time in step (2) is 3-6 min; In step (3), the mixing time of the mixture with the remaining crosslinked polyvinyl ketone is 0.5-2 min and the rotation speed is 20-30 rpm. After adding the lubricant, the mixing time is 1-2 min and the rotation speed is 12-25 rpm.

10. The preparation method according to claim 7, characterized in that, In step (4), the tablet pressing pressure is 10-15 kN and the rotation speed is 16-20 rpm.

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