A functional food piece for the elderly and a method for preparing the same

Abstract

This invention relates to the field of functional food preparation technology, and particularly to an age-appropriate fast-disintegrating functional food tablet and its preparation method. The preparation method of the age-appropriate fast-disintegrating functional food tablet includes steps such as preparing mucosal adhesion microparticles, preparing an inner phase rapid-release phase, preparing an outer phase fast-disintegrating framework phase, core-shell biphase tableting, inner enteric coating, and outer saliva-isolating coating. This invention solves the problems of enteric coating tablet breakage and premature gastric release caused by the mechanical mismatch between the microparticles and the matrix binary system, achieving the maintenance of the integrity of the inner enteric coating and the stability of tableting quality; the problems of traditional enteric coatings being directly exposed to oral saliva leading to surface pre-swelling, decreased integrity after entering the stomach, and premature dissolution in the elevated gastric pH environment of the elderly; and the inability of primary diffusion release to match the short intestinal absorption window, slow peristalsis, and uncontrollable retention time of active ingredients in the elderly.

Description

Technical Field

[0001] This invention relates to the field of functional food preparation technology, and in particular to an age-friendly, fast-disintegrating functional food tablet and its preparation method. Background Technology

[0002] With the accelerating aging of the population, the elderly population faces multiple physiological declines, including decreased swallowing function, prolonged gastric emptying time, reduced gastric acid secretion leading to increased gastric pH, slowed intestinal motility, and decreased absorption capacity. This presents a multifaceted demand for functional food tablets, requiring rapid oral disintegration, intact gastric protection, and efficient intestinal absorption. Enteric-coated rapid-disintegrating tablets, as a functional food dosage form that balances oral compliance and targeted intestinal release, have become a research hotspot in the field of geriatric nutritional intervention. Currently, the mainstream preparation route for this type of tablet involves physically mixing enteric-coated microspheres with an oral disintegration matrix and then pressing them into shape. While this technology has been applied in the general adult population, it has systemic shortcomings in terms of physiological compatibility with the elderly.

[0003] The existing technology has the following drawbacks: First, the mismatch in mechanical properties between the microspheres and the oral disintegration matrix leads to enteric coating failure: microspheres are rigid spheres, while the oral disintegration matrix is ​​a brittle porous body. The elastic modulus of the two differs significantly. During tableting, stress is concentrated on the surface of the microspheres, causing microcracks or even rupture in the enteric coating protective layer. The active ingredient leaks prematurely in the stomach, making it difficult to guarantee the integrity of the enteric coating. This problem is further aggravated when the tableting pressure fluctuates. Second, the intestinal release behavior of the active ingredient does not match the physiological rhythm of the elderly: after entering the intestine, the existing microspheres exhibit a dispersed first-order diffusion release, with the release rate decreasing exponentially over time. However, the elderly have prolonged gastric emptying time, slowed intestinal peristalsis, and a limited optimal absorption time window in the terminal ileum. The dispersed and slow release results in a large amount of active ingredient having already decreased in concentration before reaching the optimal absorption site. At the same time, the existing technology lacks active means to regulate the retention time of the active ingredient after intestinal release, and cannot form an integrated temporal-spatial control of release-retention, thus limiting bioavailability. Summary of the Invention

[0004] The purpose of this invention is to propose an age-appropriate, rapidly disintegrating functional food tablet and its preparation method, which solves the problems of enteric coating tablet rupture and premature gastric release caused by the mechanical mismatch between microparticles and matrix binary system; the problems of traditional enteric coatings being directly exposed to oral saliva leading to surface pre-swelling, decreased integrity after entering the stomach, and premature dissolution in the elevated gastric pH environment of the elderly; and the inability of primary diffusion release to match the short intestinal absorption window, slow peristalsis, and uncontrollable retention time of active ingredients in the elderly.

[0005] In a first aspect, embodiments of the present invention provide a method for preparing an age-appropriate, rapidly disintegrating functional food tablet, comprising the following steps: S1. Chitosan and carbomer are added to a 1% acetic acid aqueous solution at a mass ratio of 1:1 to 2:1, with a chitosan mass concentration of 2% to 4% and a carbomer mass concentration of 1% to 2%. After being stirred and dissolved at room temperature, the mixture is spray-dried and sieved to obtain mucosal adhesion microparticles with a particle size of 80μm to 150μm. S2. Based on the total mass of the internal phase rapid concentrated release phase, the functional active ingredients, lactose, low-substituted hydroxypropyl cellulose, dicalcium phosphate and the mucosal adhesion microparticles obtained in step S1 are mixed evenly, and wet granulation, drying and granulation are carried out using ethanol solution as the binding component to obtain internal phase rapid concentrated release phase particles. S3. Based on the total mass of the rapid-disintegration framework phase, mannitol, microcrystalline cellulose, cross-linked polyvinyl chloride, and flavoring agent are mixed evenly, and lubricating components are added and mixed further to obtain the rapid-disintegration framework phase powder. S4. Using a double-layer rotary tablet press, first fill the mold cavity with the inner phase rapid release phase particles obtained in step S2, with a filling amount of 30% to 40% of the total mass of the tablet core. Then fill the same mold cavity with the outer phase rapid disintegration skeleton phase powder obtained in step S3, with a filling amount of 60% to 70% of the total mass of the tablet core. Press to obtain a tablet core with a core-shell structure. S5. Dissolve cellulose acetate phthalate in a mixed solvent of ethanol and acetone in a volume ratio of 1:1 to prepare a coating solution with a mass concentration of 8% to 12%. Add triethyl citrate as a plasticizer to the coating solution. The amount of plasticizer is 20% to 30% of the mass of cellulose acetate phthalate. Coat the tablet core obtained in step S4 with fluidized bed side spray coating until the weight gain is 10% to 15% of the tablet core mass to obtain enteric coated tablet core. S6. Hydroxypropyl methylcellulose is dissolved in a mixed solvent of water and ethanol in a volume ratio of 3:7 to prepare a coating solution with a mass concentration of 3% to 5%. Polyethylene glycol 400 is added to the coating solution as a plasticizer, and the amount of plasticizer is 10% to 15% of the mass of hydroxypropyl methylcellulose. The enteric-coated tablet core obtained in step S5 is coated by fluidized bed side spray coating until the weight gain is 3% to 5% of the mass of the enteric-coated tablet core, thus obtaining an age-appropriate fast-disintegrating functional food tablet.

[0006] In one embodiment, in step S1, the stirring speed is 500 rpm and the stirring time is 3 hours; the spray drying inlet temperature is set to 120°C to 140°C, the outlet temperature is set to 60°C to 80°C, the atomization pressure is set to 0.2 MPa to 0.3 MPa, and an 80-mesh sieve is used for sieving.

[0007] In one embodiment, in step S2, the functional active ingredient accounts for 30% to 45% of the total mass of the internal phase rapid concentrated release phase, lactose accounts for 25% to 35% of the total mass of the internal phase rapid concentrated release phase, low-substituted hydroxypropyl cellulose accounts for 10% to 15% of the total mass of the internal phase rapid concentrated release phase, dicalcium phosphate accounts for 10% to 20% of the total mass of the internal phase rapid concentrated release phase, the mucosal adhesion microparticles obtained in step S1 account for 5% to 8% of the total mass of the internal phase rapid concentrated release phase, and the adhesive component is added at 3% to 5% of the total mass of the internal phase rapid concentrated release phase.

[0008] In one embodiment, in step S3, mannitol accounts for 40% to 50% of the total mass of the external phase rapid-disintegration framework, microcrystalline cellulose accounts for 30% to 40% of the total mass of the external phase rapid-disintegration framework, crospovidone accounts for 8% to 12% of the total mass of the external phase rapid-disintegration framework, flavoring agent accounts for 1% to 2% of the total mass of the external phase rapid-disintegration framework, and lubricating component accounts for 0.5% to 1% of the total mass of the external phase rapid-disintegration framework.

[0009] In one embodiment, in step S4, the pressing pressure is 5kN to 8kN, the total mass of the core is 150mg to 250mg, the core diameter is 7mm to 9mm, the core diameter is 3mm to 4mm, and the outer shell thickness is 1.5mm to 2mm.

[0010] In one embodiment, in step S5, the inlet air temperature of the fluidized bed side spray coating is set to 35°C to 45°C, the spray rate is set to 1.5 mL / min to 2.5 mL / min, and the atomization pressure is set to 0.15 MPa to 0.25 MPa.

[0011] In one embodiment, in step S6, the inlet air temperature of the fluidized bed side spray coating is set to 30°C to 40°C, the spray rate is set to 1.0 mL / min to 2.0 mL / min, and the atomization pressure is set to 0.1 MPa to 0.2 MPa.

[0012] In one embodiment, in step S2, the functional active ingredient is probiotic freeze-dried powder, compound digestive enzyme powder, or soybean peptide powder.

[0013] In one embodiment, in step S3, the lubricating component is magnesium stearate or talc.

[0014] Secondly, embodiments of the present invention provide an age-appropriate rapid-disintegration functional food tablet, which is prepared using a method for preparing age-appropriate rapid-disintegration functional food tablets.

[0015] The beneficial effects of this invention are: (1) This invention constructs a core-shell dual-phase integral tablet structure using a double-layer rotary tablet press. The functional active ingredients are concentrated in the core, and the outer shell is a pure rapid disintegration skeleton. During tableting, the stress is uniformly distributed by the continuous outer shell, and the core is not directly squeezed. This solves the problem of enteric coating tablet rupture and premature release in the stomach caused by the mechanical mismatch between the microspheres and the matrix binary system. It also achieves the maintenance of the integrity of the inner enteric coating and the stability of the tablet forming quality. (2) The present invention solves the problems of traditional enteric coatings being pre-swelled on the surface due to direct exposure to oral saliva, decreased integrity after entering the stomach, and premature dissolution in the elevated gastric pH environment of the elderly by combining a biphasic coating of cellulose acetate phthalate inner enteric coating and hydroxypropyl methylcellulose outer saliva isolation layer. It achieves the spatiotemporal separation of oral disintegration and gastric protection and the complete passage of the core into the gastric environment of the elderly. (3) This invention introduces lactose as an osmotic active substance and low-substituted hydroxypropyl cellulose as a swelling agent into the inner phase to construct a dual-driven rapid concentrated release mechanism driven by osmotic pressure and swelling. It also embeds chitosan and carbomer mucosal adhesion microparticles to achieve intestinal anchoring and prolonged retention. This solves the problems of the existing technology's primary diffusion release being unable to match the short intestinal absorption window, slow peristalsis, and uncontrollable retention time of active ingredients in the elderly. It achieves the synergistic control of rapid concentrated release and prolonged retention of active ingredients in the intestinal absorption window. Attached Figure Description

[0016] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used in conjunction with embodiments of the invention to explain the invention and do not constitute a limitation thereof. In the drawings: Figure 1 This is a flowchart of the preparation process of the present invention; Figure 2 This is a comparison chart of the cumulative release curves in simulated intestinal fluid according to the present invention; Figure 3 This is a schematic diagram of the intestinal anchoring mechanism of mucosal adhesion microparticles according to the present invention; Figure 4 This is a timing diagram of oral-gastric-intestinal release according to the present invention. Detailed Implementation

[0017] The present invention will now be described in further detail with reference to the accompanying drawings. These drawings are simplified schematic diagrams, illustrating only the basic structure of the invention, and therefore only show the components relevant to the invention.

[0018] A method for preparing an age-appropriate, rapidly disintegrating functional food tablet includes the following steps: S1: Preparation of mucosal adhesion microparticles.

[0019] Chitosan and carbomer were added to a 1% acetic acid aqueous solution at a mass ratio of 1:1 to 2:1, with a chitosan mass concentration of 2% to 4% and a carbomer mass concentration of 1% to 2%. The stirring speed was 500 rpm, and the stirring time was 3 hours. After dissolving at room temperature, the mixture was spray-dried using a spray dryer with an inlet temperature set at 120℃ to 140℃, an outlet temperature set at 60℃ to 80℃, and an atomization pressure set at 0.2MPa to 0.3MPa. The dried powder was collected and passed through an 80-mesh sieve to obtain mucosal adhesion microparticles with a particle size of 80μm to 150μm. This step aims to prepare microparticles with intestinal mucosal adhesion function. After the core enters the intestine and bursts, the mucosal adhesion microparticles disperse in the active ingredients. The active ingredients are anchored to the surface of intestinal villi through a dual mechanism: the positive charge of chitosan in a weakly alkaline environment generates electrostatic adsorption with the negatively charged glycoproteins on the intestinal mucosa surface, and the carbomer carboxyl groups form hydrogen bonds with the amino groups of intestinal mucosal glycoproteins. This prolongs the residence time in the absorption window.

[0020] S2: Preparation of the internal phase for rapid concentrated release.

[0021] Based on the total mass of the internal phase rapid concentrated release phase, the functional active ingredient, lactose, low-substituted hydroxypropyl cellulose, dicalcium phosphate, and the mucosal adhesion microparticles obtained in step S1 are mixed evenly. The mixture is then wet-granulated, dried, and sized using an ethanol solution as the binding component to obtain internal phase rapid concentrated release phase particles. Specifically, the functional active ingredient accounts for 30% to 45% of the total mass of the internal phase rapid concentrated release phase, lactose accounts for 25% to 35%, low-substituted hydroxypropyl cellulose accounts for 10% to 15%, dicalcium phosphate accounts for 10% to 20%, the mucosal adhesion microparticles obtained in step S1 account for 5% to 8%, and the binding component is added at 3% to 5% of the total mass of the internal phase rapid concentrated release phase. This step serves to prepare an internal phase containing osmolarly active substances and a swelling agent. Lactose, as an osmolarly active substance, dissolves in the intestine to generate a local high osmolarity of 3000 mOsm / kg to 5000 mOsm / kg. Low-substituted hydroxypropyl cellulose, as a swelling agent, expands by 200% to 300% after absorbing water. The two work together to generate a dual driving force of osmolarity and swelling, causing the core to burst within 15 to 30 minutes, resulting in rapid and concentrated release and avoiding concentration decay caused by primary diffusion release.

[0022] S3: Preparation of the external phase rapid collapse framework phase.

[0023] Based on the total mass of the rapidly disintegrating outer phase framework, mannitol, microcrystalline cellulose, crospovidone, and flavoring agent are mixed evenly, and a lubricating component is added and mixing continues to obtain the rapidly disintegrating outer phase framework powder. Specifically, mannitol accounts for 40% to 50% of the total mass of the rapidly disintegrating outer phase framework, microcrystalline cellulose accounts for 30% to 40%, crospovidone accounts for 8% to 12%, the flavoring agent accounts for 1% to 2%, and the lubricating component accounts for 0.5% to 1%. This step serves to prepare the oral rapidly disintegrating outer shell. Mannitol rapidly dissolves in saliva, creating dissolution channels, and crospovidone absorbs water and swells, generating disintegration stress that breaks the shell wall, causing the outer phase to disintegrate into fine powder within 20 to 30 seconds, releasing the core and avoiding the gritty feeling when swallowing caused by microparticle dispersion.

[0024] S4: Core-shell biphasic tablets.

[0025] Using a double-layer rotary tablet press, the inner phase rapid-release phase particles obtained in step S2 are first filled into the mold cavity, with a filling amount of 30% to 40% of the total tablet core mass. Then, the outer phase rapid-disintegration framework phase powder obtained in step S3 is filled into the same mold cavity, with a filling amount of 60% to 70% of the total tablet core mass. The tablets are then pressed at a pressure of 5 kN to 8 kN to obtain a tablet core with a core-shell structure. The total tablet core mass is 150 mg to 250 mg, the tablet diameter is 7 mm to 9 mm, the core diameter is 3 mm to 4 mm, and the outer shell thickness is 1.5 mm to 2 mm. This step aims to replace the physical mixing of microparticles and matrix with an integral core-shell structure. During tableting, stress is uniformly distributed by the continuous outer shell, the core is not directly compressed, and the integrity of the inner enteric coating is maintained, thus solving the problem of enteric coating failure caused by microparticle tablet rupture.

[0026] S5: Inner enteric coating.

[0027] Cellulose acetate phthalate (CAP) was dissolved in a mixed solvent of ethanol and acetone in a 1:1 volume ratio to prepare a coating solution with a mass concentration of 8% to 12%. Triethyl citrate was added to the coating solution as a plasticizer, with the amount of plasticizer being 20% ​​to 30% of the mass of cellulose acetate phthalate. The tablet cores obtained in step S4 were coated using a fluidized bed side-spray coating method until the weight gain was 10% to 15% of the tablet core mass, resulting in enteric-coated tablet cores. This step serves to construct a protective barrier in the stomach. Cellulose acetate phthalate is insoluble in environments with a pH not higher than 5. Even if the stomach pH of elderly individuals rises to 5.0, it can still ensure that the core remains intact in the stomach, with minimal leakage of the active ingredient, thus achieving minimal release of the active ingredient.

[0028] S6: Outer saliva barrier coating.

[0029] Hydroxypropyl methylcellulose (HMC) is dissolved in a mixed solvent of water and ethanol at a volume ratio of 3:7 to prepare a coating solution with a mass concentration of 3% to 5%. Polyethylene glycol 400 is added to the coating solution as a plasticizer, with the amount of plasticizer being 10% to 15% of the mass of HMC. The enteric-coated tablet core obtained in step S5 is coated using a fluidized bed side-spray coating method until the weight gain reaches 3% to 5% of the mass of the enteric-coated tablet core, resulting in an age-appropriate, rapidly disintegrating functional food tablet. This step serves to construct an oral barrier. HMC dissolves in saliva within 10 to 15 seconds, preventing saliva from contacting the inner cellulose acetate phthalate layer, thus preventing pre-swelling of the inner enteric coating in the mouth and ensuring that it remains intact after entering the stomach. This achieves spatiotemporal separation of oral disintegration and gastric protection.

[0030] The complete preparation process flow of S1 to S6 is as follows: Figure 1 As shown, the flow relationship between the input materials, process equipment and output intermediates in each step is clear. The microparticles obtained in step S1 are input into step S2. The internal phase particles obtained in step S2 and the external phase powder obtained in step S3 are input into step S4. The core-shell wafer obtained in step S4 is then coated with the inner layer in step S5 and the outer layer in step S6 to obtain the finished product.

[0031] In this invention, the chitosan has a degree of deacetylation of 85% to 95%, a molecular weight of 150,000 to 250,000, and a carbomer type of Carbomer 934P. This parameter range ensures that the mucosal adhesion particles carry a positive charge in the weakly alkaline environment of the intestine and electrostatically adsorb with the negatively charged glycoproteins on the surface of the intestinal mucosa. The functional active ingredients are probiotic freeze-dried powder, compound digestive enzyme powder, or soybean peptide powder, which can be flexibly replaced according to the nutritional needs of the elderly. Low-substituted hydroxypropyl cellulose is used as a swelling agent, and lactose is used as an osmotic pressure active substance, with a mass ratio of 2:1 to 3:1. This ratio can synergistically generate a dual-drive rapid concentration driven by osmotic pressure and swelling. Release; dicalcium phosphate, as a high-density filler, accounts for 10% to 20% of the total mass of the inner phase, which can increase the core density and control the burst strength; cross-linked polyvinyl ketone accounts for 8% to 12% of the total mass of the outer phase, which can ensure that the outer phase disintegrates within 20 to 30 seconds in the oral cavity; the cellulose acetate phthalate inner coating increases the weight by 10% to 15% of the tablet core mass, and can remain intact in an environment with a pH not higher than 5, which is suitable for the physiological environment of the elderly with a gastric pH that rises to 5.0; the hydroxypropyl methylcellulose outer coating increases the weight by 3% to 5% of the enteric coating tablet core mass, and can dissolve within 10 to 15 seconds in oral saliva and protect the inner enteric coating.

[0032] In some embodiments of the present invention, the molecular weight of chitosan in step S1 can be adjusted according to the adhesion requirements. When the molecular weight is large, the stirring and dissolving time can be extended to 4 hours to ensure complete dissolution. The inlet temperature of the spray dryer can be adjusted according to the ambient humidity. When the humidity is high, the upper limit of the inlet temperature of 140°C can be used to ensure drying efficiency.

[0033] In some embodiments of the present invention, the drying temperature after wet granulation in step S2 can be adjusted according to the ethanol concentration. When the ethanol concentration is high, the lower limit of the drying temperature of 50°C can be used to avoid the thermal inactivation of functional active ingredients. The mesh size of the granulation sieve can be adjusted according to the particle flowability. When the flowability is poor, a 35-mesh sieve can be used.

[0034] In some embodiments of the present invention, the pressing pressure in step S4 can be adjusted according to the hardness requirement of the tablet core. When the hardness requirement is high, the upper limit of the pressure can be 8kN, but the integrity of the core needs to be monitored simultaneously. The total mass of the tablet core can be adjusted according to the drug loading of the active ingredient. When the drug loading is low, the lower limit of the total mass of the tablet core can be 150mg.

[0035] In some embodiments of the present invention, the concentration of cellulose acetate phthalate coating solution in step S5 can be adjusted according to the coating efficiency. When the concentration is high, the spraying rate can be reduced to 1.5 mL / min to avoid coating solution sticking. The amount of plasticizer can be adjusted according to the coating flexibility requirements. When the coating is brittle, the upper limit of plasticizer amount of 30% can be used.

[0036] The preparation method of the age-friendly rapid disintegration functional food tablets of the present invention will be described in detail below with reference to specific embodiments. The raw materials in each embodiment are in accordance with the aforementioned ratio range, and the process steps are the same as the aforementioned complete process steps. Only some parameters are different. The total mass of raw materials in each embodiment is calculated based on a total core mass of 250mg.

[0037] Example 1 The preparation method of the age-appropriate rapid-disintegration functional food tablets provided in this embodiment includes the following specific steps: S1: Preparation of mucosal adhesion microparticles: 20.0 g of chitosan with a degree of deacetylation of 90% and a molecular weight of 200,000 and 15 g of carbomer 934P were weighed and added to 1000 mL of 1% acetic acid aqueous solution. The mixture was stirred at 500 rpm for 3 hours at room temperature to obtain a mixed solution with a chitosan mass concentration of 2% and a carbomer mass concentration of 1.5%. The mixed solution was spray-dried using a spray dryer with an inlet temperature of 130℃, an outlet temperature of 70℃, an atomization pressure of 0.25 MPa, and a nozzle orifice diameter of 1.0 mm. The dried powder was collected and passed through an 80-mesh sieve to obtain 32 g of mucosal adhesion microparticles with a particle size of 100 μm to 150 μm, with a yield of 91.4%.

[0038] S2: Preparation of the rapid concentrated release phase of the internal phase: Weigh the lyophilized powder of functional active ingredient probiotics, with a viable count of not less than 1×10⁻⁶. 11CFU / g, 40g, lactose, 30g (particle size 150μm), low-substituted hydroxypropyl cellulose (LH-11), 12g, dicalcium phosphate, 10g, high-density filler, and 6g of the mucosal adhesion microparticles obtained in step S1 were mixed in a three-dimensional mixer for 15 minutes. Povidone K30 was dissolved in anhydrous ethanol to prepare a 5% (w / w) adhesive solution. 4% of the total mass of the internal phase was added to the adhesive solution, and mixing continued for 5 minutes to obtain a soft material. The soft material was extruded through a 40-mesh sieve for granulation. The wet granules were placed in a fluidized bed dryer, with the inlet air temperature set at 55℃, and dried until the granule moisture content was 2.5%. The granules were then sieved through a 40-mesh sieve to obtain 92g of rapidly concentrated internal phase particles.

[0039] S3: Preparation of the external phase rapid-disintegrating framework: Weigh 45g of mannitol (direct compression grade), 35g of microcrystalline cellulose (PH102), 10g of crospovidone (disintegrant), and 1.5g of strawberry flavoring (flavoring agent). Mix in a three-dimensional mixer for 10 minutes. Then add 0.8g of magnesium stearate (lubricating component) and continue mixing for 3 minutes to obtain 92.3g of external phase rapid-disintegrating framework powder.

[0040] S4: Core-shell biphase tableting: A double-layer rotary tablet press with an 8mm die cavity diameter and a circular flat punch is used. First, the inner phase rapid-release phase particles obtained in step S2 are filled into the die cavity at a rate of 100mg / tablet. Then, the outer phase rapid-disintegration framework powder obtained in step S3 is filled into the same die cavity at a rate of 150mg / tablet. The tablets are pressed at a pressure of 6kN to obtain core-shell biphase tablets with a total core mass of 250mg and a tablet diameter of 8mm. Sampling measurements show that the core diameter is 3.5mm, the outer shell thickness is 1.75mm, and the core hardness is 40N to 50N.

[0041] S5: Inner Enteric Coating: Weigh 8.6g of cellulose acetate phthalate and dissolve it in a mixed solvent of 175mL ethanol and 175mL acetone to prepare a coating solution with a mass concentration of 9.9%. Add 9.6g of triethyl citrate as a plasticizer to the coating solution, with the amount of plasticizer being 24.9% of the mass of cellulose acetate phthalate. Place 2500 core-shell biphasic tablets obtained in step S4 into a fluidized bed side-spray coating machine, setting the inlet air temperature to 40℃, the spray rate to 2.0mL / min, and the atomization pressure to 0.2MPa, coating until the weight gain is 12% of the tablet core mass. Sampling tests showed that the coated tablet cores showed no cracks in simulated gastric fluid (pH 1.2) for 2 hours, and completely disintegrated in simulated intestinal fluid (pH 6.8) for 45 minutes.

[0042] S6: Outer Saliva-Induced Coating: Weigh 10g of hydroxypropyl methylcellulose (E5 grade) and dissolve it in a mixed solvent of 70mL water and 210mL ethanol to prepare a coating solution with a mass concentration of 3.6%. Add 1.2g of polyethylene glycol 400 as a plasticizer to the coating solution, with the amount of plasticizer being 12% of the mass of hydroxypropyl methylcellulose. Place the enteric-coated tablet core obtained in step S5 into a fluidized bed side-spray coating machine, set the inlet air temperature to 35℃, the spray rate to 1.5mL / min, and the atomization pressure to 0.15MPa, and coat until the weight gain is 4% of the enteric-coated tablet core mass. Obtain an age-appropriate, rapidly disintegrating functional food tablet with a total tablet weight of approximately 290mg.

[0043] Example 2 The difference between this embodiment and Embodiment 1 is that the mass ratio of chitosan to carbomer in step S1 is 1:1, while the other raw material ratios and process parameters are completely consistent with Embodiment 1.

[0044] S1: Preparation of mucosal adhesion microparticles: 20.0 g of chitosan with a degree of deacetylation of 90% and a molecular weight of 200,000 and 20.0 g of carbomer 934P were weighed and added to 1000 mL of 1% acetic acid aqueous solution. The mixture was stirred at 500 rpm for 3 hours at room temperature to obtain a mixed solution with a chitosan mass concentration of 2% and a carbomer mass concentration of 2%. The mixed solution was spray-dried using a spray dryer with an inlet temperature of 130℃, an outlet temperature of 70℃, an atomization pressure of 0.25 MPa, and a nozzle orifice diameter of 1.0 mm. The dried powder was collected and passed through an 80-mesh sieve to obtain 35.2 g of mucosal adhesion microparticles with a particle size of 100 μm to 150 μm, with a yield of 88.0%.

[0045] S2 to S6: Completely consistent with Example 1.

[0046] Example 3 The only difference between this embodiment and Embodiment 1 is that the mass ratio of chitosan to carbomer in step S1 is 2:1. The other raw material ratios and process parameters are completely consistent with those in Embodiment 1.

[0047] S1: Preparation of mucosal adhesion microparticles: 20.0 g of chitosan with a degree of deacetylation of 90% and a molecular weight of 200,000 and 10.0 g of carbomer 934P were weighed and added to 1000 mL of 1% acetic acid aqueous solution. The mixture was stirred at 500 rpm for 3 hours at room temperature to obtain a mixed solution with a chitosan mass concentration of 2% and a carbomer mass concentration of 1%. The mixed solution was spray-dried using a spray dryer with an inlet temperature of 130℃, an outlet temperature of 70℃, an atomization pressure of 0.25 MPa, and a nozzle orifice diameter of 1.0 mm. The dried powder was collected and passed through an 80-mesh sieve to obtain 28.5 g of mucosal adhesion microparticles with a particle size of 100 μm to 150 μm, with a yield of 95.0%.

[0048] S2 to S6: Completely consistent with Example 1.

[0049] Example 4 The only difference between this embodiment and Example 1 is that the mass concentration of the cellulose acetate phthalate coating solution in step S5 is 8.0%, while the other raw material ratios and process parameters are completely consistent with those in Example 1.

[0050] S5: Inner Enteric Coating: Weigh 30.4g of cellulose acetate phthalate and dissolve it in a mixed solvent of 175mL ethanol and 175mL acetone to prepare a coating solution with a mass concentration of 8.0%. Add 7.5g of triethyl citrate as a plasticizer to the coating solution, with the amount of plasticizer being 24.7% of the mass of cellulose acetate phthalate. Place 2500 core-shell biphasic tablets obtained in step S4 into a fluidized bed side-spray coating machine, setting the inlet air temperature to 40℃, the spray rate to 2.0mL / min, and the atomization pressure to 0.2MPa, coating until the weight gain is 12.0% of the tablet core mass. Sampling tests showed that the coated tablet cores showed no cracks in simulated gastric fluid (pH 1.2) for 2 hours, and completely disintegrated in simulated intestinal fluid (pH 6.8) for 45 minutes.

[0051] S1 to S4 and S6: completely consistent with Example 1.

[0052] Example 5 The only difference between this embodiment and Embodiment 1 is that the pressing pressure in step S4 is 5.0 kN, while the remaining raw material ratios and process parameters are completely consistent with Embodiment 1.

[0053] S4: Core-shell biphase tableting: A double-layer rotary tablet press with an 8mm die cavity diameter and a circular flat punch is used. First, the inner phase rapid-release phase particles obtained in step S2 are filled into the die cavity at a rate of 100mg / tablet. Then, the outer phase rapid-disintegration framework powder obtained in step S3 is filled into the same die cavity at a rate of 150mg / tablet. The tablets are pressed at a pressure of 5.0kN to obtain core-shell biphase tablets with a total core mass of 250mg and a diameter of 8mm. Sampling measurements show that the core diameter is 3.5mm, the outer shell thickness is 1.75mm, and the core hardness ranges from 32N to 42N.

[0054] S1 to S3, S5 to S6: completely consistent with Example 1.

[0055] Comparative Example 1 The difference between Comparative Example 1 and Example 1 is that no mucosal adhesion microparticles were added, while the other raw material ratios and process parameters are completely consistent with Example 1.

[0056] Comparative Example 2 The difference between Comparative Example 2 and Example 1 is that core-shell biphase tableting was not used. Instead, the rapid release phase particles of the inner phase obtained in step S2 and the rapid disintegration skeleton phase powder of the outer phase obtained in step S3 were directly mixed and then tableted in one batch. This is the traditional micro-pellet mixing and tableting scheme. The other raw material ratios and coating processes are completely consistent with Example 1.

[0057] Comparative Example 3 The difference between Comparative Example 3 and Example 1 is that it does not undergo double coating, but only single-layer cellulose acetate phthalate enteric coating, and there is no outer hydroxypropyl methylcellulose salivary barrier layer. The other raw material ratios and tableting process are completely the same as those in Example 1.

[0058] The performance of the age-friendly rapid disintegration functional food tablets prepared in Examples 1 to 5 and Comparative Examples 1 to 3 were tested. The test indicators included oral disintegration time, simulated gastric juice leakage rate, simulated intestinal juice cumulative release rate at 15 minutes, simulated intestinal juice cumulative release rate at 30 minutes, release concentration index T80 / T50, and adhesion force of isolated porcine small intestinal mucosa. Each example changed only one parameter. The specific differences are shown in Table 1, and the test results are shown in Table 2.

[0059] Table 1

[0060] Table 2

[0061] Note: Comparative Example 1 did not add mucosal adhesion microparticles; Comparative Example 2 did not use core-shell biphasic tableting, but was a traditional microgranule mixed tableting; Comparative Example 3 was only a single-layer enteric coating.

[0062] The simulated gastric fluid leakage rate in Examples 1 to 5 was no higher than 5.85%, the cumulative release rate of intestinal fluid over 15 minutes was no less than 77.12%, and the adhesion force of the isolated porcine small intestinal mucosa was no less than 0.68 N / cm. 2 In contrast, Comparative Example 2 showed a simulated gastric fluid leakage rate as high as 18.65%, Comparative Example 3 exhibited an oral disintegration time of 38.45 seconds, and Comparative Example 1 showed a mucosal adhesion force of only 0.15 N / cm. 2 .

[0063] Combining the data in Tables 1 and 2, the impact of each technical feature on performance can be derived, as detailed in the following analysis: 1. Effect of chitosan to carbomer mass ratio: Comparison of Examples 1 to 3 In Table 1, the mass ratio of chitosan to carbomer in Example 2 is 1:1, and in Example 3 it is 2:1. Other parameters are consistent with the 1.33:1 ratio in Example 1. Corresponding performance data in Table 2: The mucosal adhesion force in Example 2 is 0.68 N / cm. 2 It is lower than 0.72 N / cm in Example 1. 2The reason is that the increased carbomer ratio leads to a decrease in the relative content of chitosan, which reduces the positive charge density on the surface of the mucosal adhesion particles and weakens the electrostatic adsorption between them and the negatively charged glycoproteins of the intestinal mucosa; in Example 3, the mucosal adhesion force was 0.75 N / cm. 2 The leakage rates were higher than in Example 1 because the increased chitosan ratio led to a higher positive charge density, enhanced electrostatic adsorption, and increased entanglement between the chitosan chains and the intestinal mucosa. The leakage rates in Example 2 and Example 3 were 4.78%, similar to Example 1, indicating that the ratio change did not significantly affect enteric integrity. Considering both adhesion and process stability, a chitosan to carbomer mass ratio of 1.33:1 was the optimal ratio, and usability was maintained within the range of 1:1 to 2:1.

[0064] 2. Effect of CAP coating solution concentration: Comparison of Example 1 and Example 4 In Table 1, the CAP coating solution concentration in Example 4 is 8.0%, while other parameters are consistent with 9.9% in Example 1. Table 2 shows that the simulated gastric leakage rate in Example 4 is 5.85%, higher than 4.85% in Example 1. This is because the lower coating solution concentration leads to a slight decrease in coating layer density, resulting in a marginal weakening of gastric protection performance. However, the oral disintegration time, intestinal fluid release rate, and release concentration index in Example 4 are basically consistent with those in Example 1, indicating that an 8.0% concentration can still meet the core functional requirements. 9.9% is a relatively optimal concentration that balances coating density and process economy.

[0065] 3. The effect of compression pressure: a comparison between Example 1 and Example 5 In Table 1, the pressing pressure in Example 5 was 5.0 kN, while other parameters were consistent with 6.0 kN in Example 1. Table 2 shows that the simulated gastric fluid leakage rate in Example 5 was 5.12%, higher than 4.85% in Example 1. This is because the reduced pressure led to a decrease in core density, weakening the marginal tightness of the outer shell's encapsulation of the inner phase. The core hardness in Example 5 was 32 N to 42 N, lower than 40 N to 50 N in Example 1, but still met the strength requirements for subsequent coating and transportation. Within the range of 5.0 kN to 8.0 kN, 6.0 kN is the optimal pressure for balancing molding quality and leakage rate control.

[0066] 4. The necessity of comparative verification of key processes Key processes or components of this application are omitted in Comparative Examples 1, 2, and 3 of Table 1. Their necessity can be verified by referring to the performance data in Table 2. Comparative Example 1, without the addition of mucosal adhesion microparticles, showed oral disintegration time, simulated gastric juice leakage rate, intestinal juice release rate, and release concentration index that were essentially the same as in Example 1, indicating that the mucosal adhesion microparticles did not affect the preparation process or release behavior. However, the adhesion force of the isolated porcine small intestinal mucosa in Comparative Example 1 was 0.15 N / cm. 2This is far lower than the 0.72 N / cm in Example 1. 2 The reduction was as high as 79.2%, proving that mucosal adhesive microparticles are the key components for prolonging the retention time of active ingredients in the intestinal absorption window.

[0067] Comparative Example 2 did not use core-shell biphasic tableting, but instead used a traditional microgranule mixed tableting scheme. The simulated gastric fluid leakage rate was 18.65%, an improvement of 284.5% compared to Example 1. The cumulative release rate of intestinal fluid after 15 minutes was 62.35%, lower than 77.85% in Example 1. The T80 / T50 release concentration index was 3.42, higher than 1.82 in Example 1. The T80 / T50 release concentration index is defined as the ratio of the time required to reach 80% of the cumulative release rate to the time required to reach 50%. The smaller the index, the more concentrated and rapid the release of the active ingredient; the larger the index, the more dispersed and closer to a slow release mode of first-order diffusion. The 3.42 index of Comparative Example 2 proves that after the microgranules are dispersed, each unit releases independently and slowly, failing to form a release rate peak. In contrast, the 1.82 index of Example 1 proves that the core-shell biphasic structure causes the core to burst in the intestine, achieving rapid and concentrated release of the active ingredient. This comparison demonstrates that the core-shell biphasic integral tableting structure is a key process for ensuring enteric integrity and rapid and concentrated release from the intestine.

[0068] Comparative Example 3 was not coated with a double layer, but only with a single layer of cellulose acetate phthalate enteric coating. The oral disintegration time was 38.45s, which was much higher than 24.52s in Example 1. The simulated gastric juice leakage rate was 14.25%, which was higher than 4.85% in Example 1. This proves that the outer hydroxypropyl methylcellulose salivary barrier layer is the key structure for achieving rapid oral disintegration and intact gastric protection.

[0069] The intestinal anchoring mechanism of mucosal adherent microparticles, such as Figure 3 As shown, chitosan carries a positive charge in the weakly alkaline environment of the intestine and electrostatically adsorbs with negatively charged glycoproteins on the surface of the intestinal mucosa; carbomer forms hydrogen bonds with the amino groups of intestinal mucosal glycoproteins through carboxyl groups, and the dual adhesion mechanism anchors the complex formed by the active ingredients and the mucosal adhesion particles to the surface of the intestinal villi.

[0070] The release sequence in the oral cavity, gastrointestinal tract, and intestinal tract is as follows: Figure 4As shown. In the oral cavity stage, the outer salivary barrier dissolves within 10 to 15 seconds after contact with saliva, and the outer phase rapidly disintegrates into fine powder within 20 to 30 seconds, releasing a smooth core without a gritty feel. In the stomach stage, the core remains intact in an environment with a pH not higher than 5, and the active ingredients are basically not released, allowing it to pass through the stomach intact. In the intestinal stage, the inner enteric coating dissolves when the pH is greater than 6, allowing intestinal water to seep into the core. Lactose dissolution creates local high osmotic pressure, and low-substituted hydroxypropyl cellulose absorbs water and swells. These dual driving forces cause the core to burst within 15 to 30 minutes, resulting in the rapid and concentrated release of functional active ingredients. After bursting, mucosal adhering microparticles disperse in the active ingredients, anchoring to the surface of intestinal villi and prolonging the retention time by 30 to 60 minutes.

[0071] To further verify the rapid and concentrated release characteristics in the intestine, the cumulative release curves of Example 1 and Comparative Example 2 in simulated intestinal fluid were measured, and the results are as follows: Figure 2 As shown. The release curve of Example 1 exhibits rapid release characteristics, with a cumulative release rate of 45% from 0 to 10 minutes, reaching 77.85% at 15 minutes, forming a clear burst peak, and reaching 91.65% at 30 minutes; the release curve of Comparative Example 2 exhibits slow first-order diffusion characteristics, with a cumulative release rate of only 28.25% at 15 minutes and 58.45% at 30 minutes, without a clear burst peak, and a T80 / T50 release concentration index of 3.42, which is much higher than the 1.82 of Example 1.

[0072] To further verify the stability of the process, the parameters of Example 1 were repeated three times. The test results are shown in Table 3. The coefficient of variation was no higher than 3%, indicating that the parameter design in Table 1 has good repeatability and is suitable for industrial mass production.

[0073] Table 3

[0074] Summary: Based on the data and analysis in Tables 1 and 2, the core innovations of the preparation method of the age-appropriate rapid-disintegration functional food tablets in this application are as follows: The core-shell biphasic monolithic tableting and biphasic coating synergistic system: The core-shell biphasic structure is constructed using a double-layer rotary tableting machine. The functional active ingredients are concentrated in the core, while the outer shell is a pure rapid-disintegration skeleton. During tableting, the stress is uniformly distributed by the continuous outer shell, and the core is not directly squeezed, thus maintaining the integrity of the inner enteric coating. The outer hydroxypropyl methylcellulose salivary barrier layer prevents the inner cellulose acetate phthalate layer from being exposed in the oral cavity, achieving spatiotemporal separation between oral disintegration and gastric protection. This overcomes the dilemma of enteric coating failure in traditional microcapsule mixed compression and premature release due to increased gastric pH in the elderly.

[0075] A synergistic system of rapid concentrated release driven by osmotic pressure and expansion, and mucosal adhesion microparticle anchoring: By introducing lactose as an osmotic active substance and low-substituted hydroxypropyl cellulose as a swelling agent into the inner phase, osmotic pressure and expansion are synergistically generated in the high-moisture environment of the intestine, causing the core to burst within 15 to 30 minutes, resulting in rapid concentrated release; after bursting, chitosan-carbomer mucosal adhesion microparticles are dispersed in the active ingredients and anchored to the surface of intestinal villi through electrostatic adsorption and hydrogen bonding, prolonging the retention time by 30 to 60 minutes, matching the physiological characteristics of short intestinal absorption window and slow peristalsis in the elderly.

[0076] Multi-scenario parameter control and process stability: By optimizing key parameters such as the mass ratio of chitosan to carbomer, the concentration of CAP coating solution, and the pressing pressure, a standardized preparation system was established. The coefficient of variation in repeated experiments in Example 1 was no higher than 3.0%, ensuring stable product quality and avoiding performance fluctuations caused by experience-based operations in traditional processes, thus demonstrating the feasibility of industrial-scale mass production.

[0077] In summary, the specific embodiments of this invention, through a complete logical chain of parameter design, performance testing, pattern analysis, and application verification, demonstrate the innovation, stability, and practicality of the process. It not only solves the technical problems of micro-pellet rupture in traditional enteric-coated rapid-disintegrating tablets, poor gastric pH compatibility in the elderly, non-concentrated intestinal release, and a gritty feeling when swallowing, but also meets the comprehensive needs of functional foods for the elderly for oral compliance, gastric stability, and efficient intestinal absorption, thus possessing broad promotional value.

[0078] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing an age-appropriate, rapid-disintegration functional food tablet, characterized in that, Includes the following steps: S1. Chitosan and carbomer are added to a 1% acetic acid aqueous solution at a mass ratio of 1:1 to 2:1, with a chitosan mass concentration of 2% to 4% and a carbomer mass concentration of 1% to 2%. After being stirred and dissolved at room temperature, the mixture is spray-dried and sieved to obtain mucosal adhesion microparticles with a particle size of 80μm to 150μm. S2. Based on the total mass of the internal phase rapid concentrated release phase, the functional active ingredients, lactose, low-substituted hydroxypropyl cellulose, dicalcium phosphate and the mucosal adhesion microparticles obtained in step S1 are mixed evenly, and wet granulation, drying and granulation are carried out using ethanol solution as the binding component to obtain internal phase rapid concentrated release phase particles. S3. Based on the total mass of the rapid-disintegration framework phase, mannitol, microcrystalline cellulose, cross-linked polyvinyl chloride, and flavoring agent are mixed evenly, and lubricating components are added and mixed further to obtain the rapid-disintegration framework phase powder. S4. Using a double-layer rotary tablet press, first fill the mold cavity with the inner phase rapid release phase particles obtained in step S2, with a filling amount of 30% to 40% of the total mass of the tablet core. Then fill the same mold cavity with the outer phase rapid disintegration skeleton phase powder obtained in step S3, with a filling amount of 60% to 70% of the total mass of the tablet core. Press to obtain a tablet core with a core-shell structure. S5. Dissolve cellulose acetate phthalate in a mixed solvent of ethanol and acetone in a volume ratio of 1:1 to prepare a coating solution with a mass concentration of 8% to 12%. Add triethyl citrate as a plasticizer to the coating solution. The amount of plasticizer is 20% to 30% of the mass of cellulose acetate phthalate. Coat the tablet core obtained in step S4 with fluidized bed side spray coating until the weight gain is 10% to 15% of the tablet core mass to obtain enteric coated tablet core. S6. Hydroxypropyl methylcellulose is dissolved in a mixed solvent of water and ethanol in a volume ratio of 3:7 to prepare a coating solution with a mass concentration of 3% to 5%. Polyethylene glycol 400 is added to the coating solution as a plasticizer, and the amount of plasticizer is 10% to 15% of the mass of hydroxypropyl methylcellulose. The enteric-coated tablet core obtained in step S5 is coated by fluidized bed side spray coating until the weight gain is 3% to 5% of the mass of the enteric-coated tablet core, thus obtaining an age-appropriate fast-disintegrating functional food tablet.

2. The production method of the senility-preventing rapidly disintegrating functional food sheet according to claim 1, characterized by, In step S1, the stirring speed is 500 rpm and the stirring time is 3 hours; the spray drying inlet temperature is set to 120℃ to 140℃, the outlet temperature is set to 60℃ to 80℃, the atomization pressure is set to 0.2MPa to 0.3MPa, and an 80-mesh sieve is used for sieving.

3. The production method of the senility-adapted rapidly disintegrating functional food sheet according to claim 1, characterized by, In step S2, the functional active ingredient accounts for 30% to 45% of the total mass of the internal phase rapid concentrated release phase, lactose accounts for 25% to 35% of the total mass of the internal phase rapid concentrated release phase, low-substituted hydroxypropyl cellulose accounts for 10% to 15% of the total mass of the internal phase rapid concentrated release phase, dicalcium phosphate accounts for 10% to 20% of the total mass of the internal phase rapid concentrated release phase, the mucosal adhesion microparticles obtained in step S1 account for 5% to 8% of the total mass of the internal phase rapid concentrated release phase, and the adhesive component is added at 3% to 5% of the total mass of the internal phase rapid concentrated release phase.

4. The production method of the senility-adapted rapidly disintegrating functional food sheet according to claim 1, characterized by, In step S3, mannitol accounts for 40% to 50% of the total mass of the external phase rapid-disintegration framework, microcrystalline cellulose accounts for 30% to 40% of the total mass of the external phase rapid-disintegration framework, crospovidone accounts for 8% to 12% of the total mass of the external phase rapid-disintegration framework, flavoring agent accounts for 1% to 2% of the total mass of the external phase rapid-disintegration framework, and lubricating component accounts for 0.5% to 1% of the total mass of the external phase rapid-disintegration framework.

5. The production method of the senility-adapted rapidly disintegrating functional food sheet according to claim 1, characterized by, In step S4, the pressing pressure is 5kN to 8kN, the total mass of the tablet core is 150mg to 250mg, the tablet diameter is 7mm to 9mm, the core diameter is 3mm to 4mm, and the outer shell thickness is 1.5mm to 2mm.

6. The production method of the senility-adapted rapidly disintegrating functional food sheet according to claim 1, characterized by In step S5, the inlet air temperature for the fluidized bed side spray coating is set to 35°C to 45°C, the spray rate is set to 1.5 mL / min to 2.5 mL / min, and the atomization pressure is set to 0.15 MPa to 0.25 MPa.

7. The method for preparing the age-appropriate, rapid-disintegration functional food tablet according to claim 1, characterized in that, In step S6, the inlet air temperature of the fluidized bed side spray coating is set to 30°C to 40°C, the spray rate is set to 1.0 mL / min to 2.0 mL / min, and the atomization pressure is set to 0.1 MPa to 0.2 MPa.

8. The production method of the senility-preventing rapidly disintegrating functional food sheet according to Claim 1, characterized by, In step S2, the functional active ingredient is probiotic freeze-dried powder, compound digestive enzyme powder, or soybean peptide powder.

9. The production method of the senility-adapted rapidly disintegrating functional food sheet according to claim 1, characterized by, In step S3, the lubricating component is magnesium stearate or talc.

10. A fast-disintegrating functional food tablet suitable for the elderly, characterized in that, It is prepared using the preparation method of any one of claims 1 to 9 for age-appropriate rapid disintegration functional food tablets.

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