High-load marine spirulina tablet and preparation method thereof

Abstract

The invention relates to the technical field of marine food manufacturing, in particular to a high-load marine spirulina tablet which is prepared from the following components in parts by mass: 80-95 parts of marine spirulina powder, 4-18 parts of composite auxiliary materials and 0.5-2 parts of a lubricant, the composite auxiliary material is prepared by mixing porous starch, chitosan, maltodextrin, cyclodextrin and a plant extract according to a mass ratio of (2-5): (1-3): (1-2): (0.5-1.5): (0.3-1), wherein the cyclodextrin and the plant extract are used for targeted embedding flavor modification; the plant extract is a honeysuckle flower extract. According to the spirulina tablets, the loading capacity of the spirulina active ingredients is larger than or equal to 80% and is far higher than that of existing conventional spirulina tablets, the tablets in unit dose can provide more spirulina active ingredients, the expected health-care effect can be achieved by taking fewer tablets by consumers, and the spirulina tablets are more convenient to use; meanwhile, the marine spirulina powder is selected from high-activity raw materials, the phycocyanin content is larger than or equal to 25%, and the protein content is larger than or equal to 70% (dry basis).

Description

Technical Field

[0001] This invention relates to the field of marine food manufacturing technology, specifically to a high-load marine spirulina tablet and its preparation method. Background Technology

[0002] Spirulina is an ancient marine cyanobacteria rich in protein, phycocyanin, chlorophyll, beta-carotene, various vitamins (B vitamins, vitamin E, etc.), minerals (iron, zinc, selenium, etc.), as well as polysaccharides, unsaturated fatty acids, and other bioactive components. It possesses numerous health benefits, including boosting immunity, anti-oxidation, regulating blood lipids, and supplementing nutrition, and is widely used in the food, health product, and pharmaceutical industries. With increasing health awareness, the demand for high-quality and effective spirulina products is constantly rising, making high-capacity, high-activity, easily absorbed, palatable, and highly safe spirulina preparations the mainstream in the market.

[0003] Currently, most spirulina tablets on the market are prepared using conventional pulverizing, mixing, and tableting processes, which presents the following technical problems:

[0004] 1. Low loading capacity: The content of spirulina active ingredients in regular spirulina tablets on the market is usually between 60% and 70%, with the remainder being fillers, binders and other excipients. This results in limited efficacy per unit dose of spirulina tablets, requiring consumers to take more tablets to achieve the desired effect, which is inconvenient.

[0005] 2. Low retention rate of active ingredients: Active ingredients such as phycocyanin and chlorophyll in spirulina are sensitive to conditions such as temperature, humidity and light. High-temperature drying and violent pulverization steps in conventional preparation processes can easily lead to their degradation and reduce product efficacy.

[0006] 3. Inappropriate selection of excipients: Most products use single excipients such as starch and lactose, which not only limit the loading capacity, but may also affect the disintegration rate and bioavailability of tablets. Some excipients may also cause lactose intolerance and other problems. In addition, flavor modification is not considered, resulting in a strong fishy smell and poor palatability.

[0007] 4. Non-optimized process parameters: Improper control of parameters such as particle size, mixing uniformity, and tableting pressure can easily lead to uneven tablet hardness, slow disintegration, and easy tablet cracking, affecting product stability and user experience. In addition, the lack of targeted contaminant removal processes results in a high risk of pesticide residues, heavy metals, and other potential contaminants remaining.

[0008] Furthermore, existing technologies, such as the spirulina tablet preparation methods disclosed in Chinese patents CN103655639A and CN104116093A, mainly focus on improving tablet formability and taste, without addressing core issues such as particle size, targeted deodorization, and contaminant removal. Additionally, attempts to increase the spirulina content in these methods result in poor tablet formability and brittleness, making it difficult to achieve a balance between high tablet loading and good formability. Summary of the Invention

[0009] The purpose of this invention is to solve the technical problems existing in the background art and to develop a marine spirulina tablet with high loading capacity, good retention of active ingredients, excellent formability, high bioavailability, good palatability, low pollutant residue, and simple preparation process suitable for industrial production, as well as the preparation method thereof.

[0010] A high-load marine spirulina tablet, by weight, is composed of the following components: 80-95 parts marine spirulina powder, 4-18 parts composite excipients, and 0.5-2 parts lubricant;

[0011] The composite excipient is prepared by mixing porous starch, chitosan, maltodextrin, cyclodextrin and plant extract in a mass ratio of 2-5:1-3:1-2:0.5-1.5:0.3-1, wherein the cyclodextrin and plant extract are used for targeted encapsulation of flavor modification; the plant extract is honeysuckle extract.

[0012] As a preferred embodiment of the above technical solution, a high-load marine spirulina tablet is composed of the following components by mass: 85 parts marine spirulina powder, 13.5 parts compound excipients, and 1.5 parts magnesium stearate.

[0013] As a preferred embodiment of the above technical solution, the composite excipient is prepared by mixing porous starch, chitosan, maltodextrin, cyclodextrin, and plant extract in a mass ratio of 3:2:1:1:0.5.

[0014] As a preferred embodiment of the above technical solution, the marine spirulina powder has a particle size of 10-50 micrometers, a phycocyanin content of ≥25%, and a protein content of ≥70%. The particle size range of 10-50 micrometers is most conducive to increasing the contact area with the digestive tract, accelerating the dissolution and absorption of active ingredients, and can improve the bioavailability of key active ingredients (such as phycocyanin and carotenoids) by approximately 30%-50%.

[0015] As a preferred embodiment of the above technical solution, the porous starch has a particle size of 80-120 mesh, a porosity of 30%-50%, and a specific surface area of ​​5-10 m². 2 / g, which has good adsorption properties, can effectively adsorb the active ingredients in spirulina, reduce loss during the preparation process, and improve the disintegration rate of tablets.

[0016] As a preferred embodiment of the above technical solution, the chitosan has a degree of deacetylation ≥85% and a molecular weight of 50,000-100,000 Da, exhibiting good adhesion and biocompatibility. It can improve the formability of tablets, prevent tablets from becoming brittle under high loading conditions, and protect the active ingredients from degradation.

[0017] As a preferred embodiment of the above technical solution, the maltodextrin has a DE value of 10-20, which has good solubility and stability, and can help improve the solubility and stability of tablets.

[0018] The cyclodextrin and the plant extract are targeted encapsulation flavor modifiers that can specifically adsorb volatile sulfur compounds and aldehydes and other fishy-smelling substances in spirulina, thereby achieving flavor modification.

[0019] The synergistic effect of porous starch, chitosan, maltodextrin, cyclodextrin and plant extracts can achieve high loading capacity while taking into account the tablet's formability, disintegration, active ingredient stability and palatability.

[0020] As a preferred embodiment of the above technical solution, the lubricant is one or more of magnesium stearate, calcium stearate and talc, which can reduce friction during the tableting process, prevent tablets from sticking and cracking, and does not affect the disintegration and dissolution of the tablets.

[0021] A method for preparing high-load marine spirulina tablets, the specific steps of which are as follows:

[0022] S1. Place the marine spirulina powder and compound excipients into a three-dimensional mixer, adjust the mixing speed to 200-300 r / min, and the mixing time to 15-25 min; ensure that all components are mixed evenly, especially that the cyclodextrin, plant extracts and spirulina powder are fully in contact, laying the foundation for subsequent targeted encapsulation and deodorization; control the ambient temperature at 20-25℃ and the relative humidity ≤60% during the mixing process to avoid moisture absorption of materials and degradation of active ingredients, and obtain the mixture.

[0023] S2. Add 5%-8% of its mass of a wetting agent to the mixture, wherein the wetting agent is a 5wt%-10wt% aqueous solution of ethanol, stir evenly to form a soft material, and achieve targeted adsorption and encapsulation of odorous substances by cyclodextrin and plant extracts through a special granulation process using ethanol and binder; place the soft material into a swing granulator and granulate it with an 18-20 mesh sieve to obtain wet granules; subject the wet granules to molecular sieve filtration to remove potential contaminants such as pesticide residues, heavy metals, and microorganisms, and then place them in a low-temperature drying oven and dry them at 45-55℃ until the moisture content of the wet granules is 3%-5%; finally, granulate them with a 16-18 mesh sieve to obtain qualified granules with high flowability, low odor, and low pollution.

[0024] In practice, an ethanol solution is used as a wetting agent with a concentration of 5wt%-10wt%. This reduces the impact of moisture on the active ingredients, accelerates the drying speed of wet granules, prevents degradation of active ingredients during the drying process, and ethanol can also synergistically achieve preliminary impurity removal. The dried granules are then dried using a vacuum dryer, which further improves drying efficiency and reduces the loss of active ingredients. The molecular sieve filtration step can be integrated into the granulation process to achieve deep removal of contaminants and ensure that the product meets high safety standards.

[0025] S3. The qualified granules are uniformly mixed with the lubricant. Pre-granulation pretreatment technology is used to physically reconstruct the powder structure, significantly enhancing the granule flowability and compressibility. Then, the mixture is placed in a rotary tablet press, with the tableting pressure set to 5-10 MPa (reduced to 50%-70% of the traditional direct tableting process to avoid thermal denaturation and mechanical shearing damage of the active ingredients caused by high pressure). The tableting speed is 30-50 tablets / min, and the tablet weight is 0.5-1.0 g / tablet, to obtain the initial tablets. During the tableting process, the ambient temperature is controlled at 20-25℃, and the relative humidity is ≤60%.

[0026] In practice, tableting pressure and tableting speed must be strictly controlled. Excessive tableting pressure will result in tablets that are too hard, prolonging the disintegration time, affecting bioavailability, and damaging the active ingredients. Insufficient tableting pressure will result in tablets that are not hard enough, making them brittle and prone to cracking. Excessive tableting speed will result in uneven filling of the mixture or granules, leading to excessive differences in tablet weight. Therefore, it is necessary to optimize the tableting parameters according to the material characteristics and combine them with pre-granulation pretreatment technology to ensure stable tablet quality and good retention of active ingredients.

[0027] S4. Place the pre-processed tablets into a granulator to remove burrs and fragments from the tablet edges. Then, use a screening machine to select tablets that are regular in shape, uniform in weight, free from cracks and sticking, have a hardness ≥50N, and a friability <0.5%. Remove unqualified tablets (those with a weight difference exceeding ±5%, or whose hardness and friability do not meet the requirements). The qualified high-load marine spirulina tablets are then obtained.

[0028] This invention provides a high-load marine spirulina tablet and its preparation method, which has the following beneficial effects:

[0029] 1. The spirulina tablets of this invention have an effective spirulina ingredient loading of ≥80%, which is much higher than that of existing conventional spirulina tablets. Each unit dose of tablet can provide more spirulina active ingredients, and consumers can achieve the expected health benefits by taking fewer tablets, making it more convenient to use. At the same time, the marine spirulina powder uses highly active raw materials, with a phycocyanin content of ≥25% and a protein content of ≥70% (dry basis), resulting in a high content of effective ingredients and further enhancing the product efficacy.

[0030] 2. This invention reduces the tableting pressure to 5-10 MPa, avoiding thermal denaturation and mechanical shearing damage of the active ingredients caused by high pressure, and ensuring that the retention rate of the core active ingredients is ≥95%. At the same time, the chitosan in the composite excipients has a good protective effect, which can prevent the active ingredients from being oxidized, and the addition of antioxidants can further improve the stability of the active ingredients.

[0031] 3. This invention uses a composite excipient composed of porous starch, chitosan, maltodextrin, cyclodextrin, and plant extracts. The five components work synergistically: porous starch enhances adsorption and disintegration, chitosan improves adhesion and formability, maltodextrin enhances solubility and stability, and cyclodextrin and plant extracts achieve flavor modification. By optimizing tableting parameters and pre-granulation pretreatment technology, the flowability and compressibility of the granules are significantly enhanced.

[0032] 4. This invention uses ethanol solution as a wetting agent, combined with cyclodextrin, plant extracts and other targeted encapsulation flavor modifiers, which can specifically adsorb volatile sulfur compounds and aldehydes and other fishy-smelling substances in spirulina, effectively reducing the perceived intensity of fishy smell by more than 70% and significantly improving the palatability of the product. This invention can deeply remove potential pollutants such as pesticide residues, heavy metals and microorganisms. All raw materials used meet food and health product standards. Marine spirulina powder is free of heavy metal pollution, and the compound excipients and lubricants are all food-grade raw materials with no harmful components and high safety. Attached Figure Description

[0033] Figure 1 This is a process flow diagram of the present invention. Detailed Implementation

[0034] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention.

[0035] Example 1

[0036] A high-load marine spirulina tablet, by mass parts, is composed of the following components: 85 parts marine spirulina powder, 13.5 parts compound excipients, and 1.5 parts magnesium stearate; the compound excipients are prepared by mixing porous starch, chitosan, maltodextrin, cyclodextrin, and plant extracts in a mass ratio of 3:2:1:1:0.5.

[0037] The marine spirulina powder has a particle size of 30 micrometers, a phycocyanin content of ≥25%, and a protein content of ≥70%.

[0038] The porous starch has a particle size of 100 mesh, a porosity of 40%, and a specific surface area of ​​8 m². 2 / g.

[0039] The chitosan has a degree of deacetylation ≥85% and a molecular weight of 80 kDa.

[0040] The DE value of the maltodextrin is 15.

[0041] The plant extract is honeysuckle extract produced by Shanxi Hengtian Biotechnology Co., Ltd.

[0042] The preparation method of the high-load marine spirulina tablets includes the following specific steps:

[0043] S1. Place the marine spirulina powder and compound excipients into a three-dimensional mixer, adjust the mixing speed to 250 r / min, and the mixing time to 20 min; ensure that all components are mixed evenly, especially that the cyclodextrin, plant extracts and spirulina powder are fully in contact, laying the foundation for subsequent targeted encapsulation and deodorization; control the ambient temperature at 22℃ and the relative humidity ≤60% during the mixing process to avoid moisture absorption of materials and degradation of active ingredients, and obtain a mixed material.

[0044] S2. Add 6% by weight of a wetting agent, wherein the wetting agent is a 7wt% ethanol aqueous solution, stir evenly to form a soft material, and achieve targeted adsorption and encapsulation of odorous substances by cyclodextrin and plant extracts through a special granulation process using ethanol and binder; place the soft material into a swing granulator and granulate it with an 18-20 mesh sieve to obtain wet granules; subject the wet granules to molecular sieve filtration to remove potential contaminants such as pesticide residues, heavy metals, and microorganisms, and then place them in a low-temperature drying oven and dry them at 50°C until the moisture content of the wet granules is 4%; finally, granulate them with a 16-18 mesh sieve to obtain qualified granules with high flowability, low odor, and low pollution.

[0045] In practice, an ethanol solution with a concentration of 7 wt% is used as a wetting agent to reduce the impact of moisture on the active ingredients, while accelerating the drying speed of wet granules and preventing the degradation of active ingredients during the drying process. Ethanol can also help achieve preliminary impurity removal. The dried granules are then dried using a vacuum dryer to further improve drying efficiency and reduce the loss of active ingredients. The molecular sieve filtration step can be integrated into the granulation process to achieve deep removal of contaminants and ensure that the product meets high safety standards.

[0046] S3. The qualified granules are uniformly mixed with the lubricant. Pre-granulation pretreatment technology is used to physically reconstruct the powder structure, which significantly enhances the flowability and compressibility of the granules. Then, the mixture is placed in a rotary tablet press, and the tableting pressure is set to 8 MPa (reduced to 50%-70% of the traditional direct tableting process to avoid thermal denaturation and mechanical shearing damage of the active ingredients caused by high pressure). The tableting speed is 40 tablets / min, and the tablet weight is 0.8 g / tablet to obtain the initial tablets. During the tableting process, the ambient temperature is controlled at 22℃ and the relative humidity is ≤60%.

[0047] In practice, tableting pressure and tableting speed must be strictly controlled. Excessive tableting pressure will result in tablets that are too hard, prolonging the disintegration time, affecting bioavailability, and damaging the active ingredients. Insufficient tableting pressure will result in tablets that are not hard enough, making them brittle and prone to cracking. Excessive tableting speed will result in uneven filling of the mixture or granules, leading to excessive differences in tablet weight. Therefore, it is necessary to optimize the tableting parameters according to the material characteristics and combine them with pre-granulation pretreatment technology to ensure stable tablet quality and good retention of active ingredients.

[0048] S4. Place the pre-processed tablets into a granulator to remove burrs and fragments from the tablet edges. Then, use a screening machine to select tablets that are regular in shape, uniform in weight, free from cracks and sticking, have a hardness ≥50N, and a friability <0.5%. Remove unqualified tablets (those with a weight difference exceeding ±5%, or whose hardness and friability do not meet the requirements). The qualified high-load marine spirulina tablets are then obtained.

[0049] Example 2

[0050] A high-load marine spirulina tablet, by mass parts, is composed of the following components: 80 parts marine spirulina powder, 4 parts compound excipients, and 0.5 parts talc powder; the compound excipients are prepared by mixing porous starch, chitosan, maltodextrin, cyclodextrin, and plant extracts in a mass ratio of 2:1:1:0.5:0.3.

[0051] The marine spirulina powder has a particle size of 50 micrometers, a phycocyanin content of ≥25%, and a protein content of ≥70%.

[0052] The porous starch has a particle size of 80 mesh, a porosity of 30%, and a specific surface area of ​​5 m². 2 / g.

[0053] The chitosan has a degree of deacetylation ≥85% and a molecular weight of 50 kDa.

[0054] The DE value of the maltodextrin is 10.

[0055] The plant extract is honeysuckle extract produced by Shanxi Hengtian Biotechnology Co., Ltd.

[0056] The preparation method of the high-load marine spirulina tablets includes the following specific steps:

[0057] S1. Place marine spirulina powder and compound excipients into a three-dimensional mixer, adjust the mixing speed to 200 r / min, and the mixing time to 15 min; during the mixing process, control the ambient temperature to 20℃ and the relative humidity to ≤60% to obtain the mixture.

[0058] S2. Add 5% by weight of a wetting agent, wherein the wetting agent is a 5wt% aqueous ethanol solution, and stir evenly to form a soft material; place the soft material into a gyratory pellet mill and granulate it using an 18-20 mesh sieve to obtain wet granules; filter the wet granules using a molecular sieve, and then place them in a low-temperature drying oven and dry them at 45°C until the moisture content of the wet granules is 3%; finally, granulate them using a 16-mesh sieve to obtain qualified granules.

[0059] S3. After uniformly mixing the qualified granules with the lubricant, place them into a rotary tablet press, set the tableting pressure to 5MPa, the tableting speed to 30 tablets / min, and the tablet weight to 0.5g / tablet to obtain preliminary tablets; during the tableting process, control the ambient temperature to 20℃ and the relative humidity to ≤60%.

[0060] S4. Place the pre-processed tablets into a granulator to remove unqualified tablets, thereby obtaining qualified high-load marine spirulina tablets.

[0061] Example 3

[0062] A high-load marine spirulina tablet, by mass parts, is composed of the following components: 95 parts marine spirulina powder, 18 parts compound excipients, and 1.5 parts calcium stearate; the compound excipients are prepared by mixing porous starch, chitosan, maltodextrin, cyclodextrin, and plant extracts in a mass ratio of 5:3:2:1.5:1.

[0063] The marine spirulina powder has a particle size of 50 micrometers, a phycocyanin content of ≥25%, and a protein content of ≥70%.

[0064] The porous starch has a particle size of 120 mesh, a porosity of 50%, and a specific surface area of ​​10 m². 2 / g.

[0065] The degree of deacetylation of the chitosan is ≥85%, and the molecular weight is 100kDa.

[0066] The DE value of the maltodextrin is 20.

[0067] The plant extract is honeysuckle extract produced by Shanxi Hengtian Biotechnology Co., Ltd.

[0068] The preparation method of the high-load marine spirulina tablets includes the following specific steps:

[0069] S1. Place marine spirulina powder and compound excipients into a three-dimensional mixer, adjust the mixing speed to 300 r / min, and the mixing time to 25 min; during the mixing process, control the ambient temperature to 25℃ and the relative humidity to ≤60% to obtain the mixture.

[0070] S2. Add 8% by weight of a wetting agent, wherein the wetting agent is a 10wt% aqueous ethanol solution, to the mixture and stir evenly to form a soft material; place the soft material into a gyratory pellet mill and granulate it using an 18-20 mesh sieve to obtain wet granules; filter the wet granules using a molecular sieve, then place them in a low-temperature drying oven and dry them at 55°C until the moisture content of the wet granules is 5%; finally, granulate them using a 16-18 mesh sieve to obtain qualified granules.

[0071] S3. After uniformly mixing the qualified granules with the lubricant, place them into a rotary tablet press, set the tableting pressure to 10MPa, the tableting speed to 50 tablets / min, and the tablet weight to 1.0g / tablet to obtain preliminary tablets; during the tableting process, control the ambient temperature to 25℃ and the relative humidity to ≤60%.

[0072] S4. Place the pre-processed tablets into a granulator to remove unqualified tablets, thereby obtaining qualified high-load marine spirulina tablets.

[0073] Comparative Example 1

[0074] This comparative example provides a spirulina tablet, which, by mass parts, consists of the following components: 85 parts marine spirulina powder, 13.5 parts monoporous starch, and 1.5 parts magnesium stearate. Compared with Example 1, this comparative example replaces the compound excipients with an equal amount of monoporous starch, and does not contain cyclodextrin, plant extracts, targeted encapsulation flavor modification, or molecular sieve filtration steps. The rest is the same as Example 1.

[0075] Comparative Example 2

[0076] This comparative example provides a spirulina tablet, which, by mass parts, consists of the following components: 85 parts marine spirulina powder, 13.5 parts single chitosan, and 1.5 parts magnesium stearate. Compared with Example 1, this comparative example replaces the compound excipients with an equal amount of single chitosan, and does not contain cyclodextrin, plant extracts, targeted encapsulation flavor modification, or molecular sieve filtration steps. The rest is the same as Example 1.

[0077] Comparative Example 3

[0078] This comparative example provides a spirulina tablet, which, by mass parts, consists of the following components: 85 parts marine spirulina powder, 13.5 parts compound excipients, and 1.5 parts magnesium stearate; the compound excipients are prepared by mixing porous starch, chitosan, maltodextrin, cyclodextrin, and honeysuckle extract in a mass ratio of 1:4:3:0.2:0.1. Compared with Example 1, the compound excipient ratio in this comparative example deviates from the scope of this invention, but the rest is completely consistent with Example 1.

[0079] Comparative Example 4 (the tableting pressure in the preparation process deviates from the range of this invention, but the rest is the same as Example 1)

[0080] This comparative example provides a spirulina tablet with the same composition as Example 1; the difference is that the tableting pressure in S3 is adjusted to 13 MPa, which is higher than that in Example 1 of this invention, while the other process parameters remain unchanged.

[0081] Blank control group

[0082] Commercially available spirulina tablets are prepared using conventional processes.

[0083] The eight types of Spirulina tablets provided in Examples 1-3, Comparative Examples 1-4, and the blank control group were tested for various indicators. The testing methods are as follows:

[0084] In the following examples and comparative examples, the test methods are as follows:

[0085] 1. Determination of Spirulina active ingredient loading: The protein content was determined by the Kjeldahl method (GB5009.5-2016), and the phycocyanin content was determined by spectrophotometry (ISO10260:1992). Spirulina active ingredient loading = (protein content + phycocyanin content) / total tablet mass × 100%;

[0086] 2. Determination of active ingredient retention rate: The phycocyanin and protein content of the tablets after preparation and after 12 months of storage were determined respectively. Active ingredient retention rate = active ingredient content after 12 months of storage / active ingredient content after preparation × 100%;

[0087] 3. Tablet hardness test: Using a tablet hardness tester, 10 tablets were randomly selected, and 3 points were measured on each tablet. The average value was taken and the unit was converted to N (1kg≈9.8N).

[0088] 4. Friability determination: The friability of tablets was determined according to the method for determining friability of tablets in Part IV of the Pharmacopoeia of the People's Republic of China (2020 edition). Ten tablets were randomly selected, and the friability was calculated after the determination.

[0089] 5. Disintegration time test: The disintegration time test was performed using a disintegration time tester according to the method for determining the disintegration time of tablets in Part IV of the Pharmacopoeia of the People's Republic of China (2020 Edition). Six tablets were taken and the average value was recorded.

[0090] 6. Dissolution test: A dissolution tester was used with purified water as the dissolution medium at a temperature of 37℃ and a rotation speed of 50 r / min. Samples were taken after 30 minutes to determine the total content of phycocyanin and protein in the dissolution solution. Dissolution rate = (total amount of active ingredients dissolved at 30 minutes / total amount of active ingredients in the tablet) × 100%.

[0091] 7. Bioavailability determination: Animal experiments were conducted to determine the in vivo absorption of the key active ingredient (phycocyanin) and calculate the bioavailability enhancement rate.

[0092] 8. Odor Evaluation: Ten evaluators were selected to use the sensory evaluation method to score the intensity of the odor of the tablets (0-10 points, 0 points for no odor and 10 points for extremely strong odor). The average score was calculated and compared with the original product to calculate the reduction rate of odor.

[0093] 9. Determination of pollutant residues: Gas chromatography was used to determine pesticide residues, atomic absorption spectrophotometry was used to determine heavy metal content, and microbial counting was used to determine total bacterial count to verify compliance with GB / T16919-2022 standard and relevant EU directives.

[0094] 10. Weight Variation Measurement: Randomly select 20 tablets, measure the weight of each tablet, and calculate the weight variation. Weight Variation = (Weight of a Single Tablet - Average Tablet Weight) / Average Tablet Weight × 100%;

[0095] 11. Stability test: Store the tablets in an environment with a temperature of 25°C and a relative humidity of 60% for 12 months. Observe the appearance, hardness, and friability of the tablets regularly, determine the content of active ingredients, and record the loss.

[0096] 12. Formability evaluation: Randomly select 100 tablets and observe whether there are cracks, sticking, burrs, etc. Calculate the proportion of qualified tablets (qualified tablets: regular shape, no cracks, no sticking, no burrs, hardness ≥50N, friability <0.5%, weight difference ≤±5%).

[0097] The test results are shown in Table 1 below:

[0098] Table 1

[0099] Active ingredient loading (%) Activity retention rate (%) Hardness (N) Friability (%) Disintegration timeout (min) Dissolution rate (%) Percentage reduction in fishy odor (%) Increased bioavailability (%) Pollutant residue Percentage of qualified tablets (%) Example 1 88 96 55 0.3 22 92 75 38 Meets standards 98 Example 2 92 97 58 0.2 20 94 78 42 Meets standards 99 Example 3 85 95 53 0.4 23 91 72 35 Meets standards 97 Comparative Example 1 86 88 42 1.2 35 82 25 15 Some exceeded the standard 75 Comparative Example 2 85 89 65 0.3 42 78 28 12 Some exceeded the standard 78 Comparative Example 3 84 90 48 0.8 32 85 45 22 Meets standards 88 Comparative Example 4 86 82 70 0.2 45 75 74 16 Meets standards 85 Blank control group 68 75 45 1.5 38 78 15 0 Meets standards 70

[0100] It can be seen from Table 1 above:

[0101] 1. The loadings of spirulina active ingredients in Examples 1-3 were 88%, 92%, and 85%, respectively, all ≥85%, significantly better than Comparative Examples 1-4 (84%-86%) and the blank control group (68%). The blank control group, representing conventional spirulina tablets, had a loading of only 68%, less than 80% of the minimum loading in the embodiments of this invention. This fully demonstrates that the present invention, through optimized compound excipient ratios and a high-loading pressing process, can achieve a high loading of spirulina active ingredients, overcoming the shortcomings of low loading and limited efficacy per unit dose in existing technologies.

[0102] 2. The retention rate of the core active ingredients in Examples 1-3 is ≥95%, while the retention rate of the active ingredients in Comparative Examples 1-4 and the blank control group is significantly lower than that in the Examples, especially the blank control group, which is only 75%. This indicates that the protective effect of chitosan in the composite excipients of the present invention can effectively prevent the degradation of active ingredients and greatly improve product stability.

[0103] 3. The tablets from Examples 1-3 all had a hardness between 53-58 N (≥50 N standard), a friability of <0.5% (0.2%-0.4%), and a qualified tablet ratio of ≥97% (97%-99%), with no tablet cracking or sticking issues. However, Comparative Examples 1-4 all exhibited poor formability and unstable quality. Comparative Example 4, due to its compression pressure exceeding the limits of this invention (13 MPa > 10 MPa), resulted in excessively high hardness and slow disintegration. Comparative Examples 1 and 2, by using a single excipient instead of a composite excipient, could not achieve the synergistic effect of adhesion and disintegration, resulting in extremely poor formability. This fully verifies the rationality of the optimized composite excipient ratio and process parameters of this invention.

[0104] 4. The disintegration time of Examples 1-3 was ≤23 min, the dissolution rate was ≥91%, and the bioavailability was improved by 35%-42%. However, Comparative Example 1 (disintegration 35 min, dissolution 82%, bioavailability improved by 15%), Comparative Example 4 (disintegration 45 min, dissolution 75%, bioavailability improved by 16%) and the blank control group (disintegration 38 min, dissolution 78%, no improvement in bioavailability) all performed poorly. This indicates that the present invention can accelerate tablet disintegration and dissolution of active ingredients and significantly improve bioavailability through micron-level particle size control, pre-granulation pretreatment and the synergistic effect of compound excipients.

[0105] 5. The reduction rate of fishy smell in Examples 1-3 is ≥72% (72%-78%), which can effectively improve the palatability of the product; Comparative Examples 1-2 and the blank control group have extremely poor fishy smell removal effect due to the lack of targeted encapsulation flavor modification by cyclodextrin and honeysuckle extract, which confirms the beneficial effect of "good palatability" of the present invention.

[0106] 6. Regarding safety, Comparative Examples 1 and 2, due to the absence of a molecular sieve filtration step for impurity removal, resulted in some contaminants exceeding the standard. This demonstrates that the present invention can effectively control contaminant residues, improve product safety, and meet high safety standards.

[0107] 7. Significant synergistic effect: The core indicators of Comparative Examples 1-4 and the blank control group were significantly inferior to those of Examples 1-3. Moreover, no comparative example could simultaneously achieve the comprehensive effects of high loading, high activity, excellent formability, high bioavailability and good palatability of the examples. This proves that the compound excipient ratio and process parameter optimization of the present invention are not simply superimposed, but form a synergistic technical solution that can simultaneously achieve multiple technical objectives.

[0108] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A high loading marine spirulina tablet, characterized in that, The marine spirulina powder, the composite excipient and the lubricant are mixed in a mass ratio of 80-95:4-18:0.5-2. The composite excipient is prepared by mixing porous starch, chitosan, malt dextrin, cyclodextrin and plant extract in a mass ratio of 2-5:1-3:1-2:0.5-1.5:0.3-1.

2. The high loading marine spirulina tablet according to claim 1, wherein: The marine spirulina powder, the composite excipient and the lubricant are mixed in a mass ratio of 80-95:4-18:0.5-2.

3. The high loading marine spirulina tablet according to claim 1, wherein: The composite excipient is prepared by mixing porous starch, chitosan, malt dextrin, cyclodextrin and plant extract in a mass ratio of 3:2:1:1:0.

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4. The high loading marine spirulina tablet according to claim 1, wherein: The marine spirulina powder has a particle size of 10-50 microns, an algal blue protein content of ≥25% and a protein content of ≥70%.

5. The high loading marine spirulina tablet according to claim 3, wherein: The porous starch has a particle size of 80-120 mesh, a porosity of 30-50%, and a specific surface area of 5-10 m 2 / g.

6. The high loading marine spirulina tablet according to claim 3, wherein: The chitosan has a deacetylation degree of ≥85% and a molecular weight of 50,000-100,000 Da.

7. The high loading marine spirulina tablet according to claim 3, wherein: The malt dextrin has a DE value of 10-20.

8. The high loading marine spirulina tablet according to claim 1, wherein: The lubricant is a combination of one or more of magnesium stearate, calcium stearate and talc.

9. The high loading marine spirulina tablet according to any one of claims 1-8, wherein, The preparation method comprises the following steps: S1, the marine spirulina powder and the composite excipient are placed in a three-dimensional mixer, the mixing speed is adjusted to 200-300 r / min, and the mixing time is 15-25 min; during the mixing process, the environmental temperature is controlled to be 20-25°C and the relative humidity is ≤60%, and a mixture is prepared; S2, 5%-8% of a wetting agent by mass of the mixture is added, the wetting agent is a 5wt%-10wt% ethanol aqueous solution, the mixture is stirred uniformly to form a soft material, the soft material is placed in a swinging granulator, 18-20 mesh sieve is used for granulation, wet granules are prepared, the wet granules are subjected to molecular sieve filtration treatment, then are placed in a low-temperature drying oven, and are dried at 45-55°C until the moisture content of the wet granules is 3%-5%, finally, the wet granules are sieved with 16-18 mesh sieve to obtain qualified granules; S3, the qualified granules and the lubricant are uniformly mixed, then are placed in a rotary tablet press, the tabletting pressure is set to 5-10 MPa, the tabletting speed is 30-50 tablets / min, the tablet weight is 0.5-1.0 g / tablet, and initial tablets are prepared; during the tabletting process, the environmental temperature is controlled to be 20-25°C and the relative humidity is ≤60%; S4, the initial tablets are placed in a sieving machine, and unqualified tablets are removed, and the qualified high-load marine spirulina tablets are obtained.

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