Polaprezinc effervescent tablet and preparation method thereof

Abstract

The invention discloses a polaprezinc effervescent tablet and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The effervescent tablet is prepared from the following components in parts by weight: 30 to 40 parts of polaprezinc-HP-beta-CD inclusion compound microcapsules, 25 to 40 parts of an effervescing agent, 30 to 45 parts of spray-dried mannitol, 0.8 to 1.5 parts of a sweetening agent and 0.3 to 0.8 part of a lubricating agent, wherein the polaprezinc-HP-beta-CD clathrate compound microcapsule is prepared by the following steps: carrying out clathration on HP-beta-CD and polaprezinc, and then carrying out sugar-coating wrapping on the clathrate and the polaprezinc. The effervescent tablet disclosed by the invention is quick to disintegrate (the time limit is less than or equal to 16s), the dissolution rate in 5min is more than or equal to 97%, the taste is excellent (no metal flavor or gravel feeling), the effervescent tablet is uniformly dispersed and has no precipitate, the content change is less than or equal to 0.16% after the effervescent tablet is accelerated for 6 months, and the stability is excellent; the preparation problem of the insoluble polaprezinc effervescent tablet is effectively solved, the taking compliance of a patient and the bioavailability of the medicine are improved, and the polaprezinc effervescent tablet is suitable for treating gastric ulcer, duodenal ulcer and gastritis.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmaceutical preparations, in particular to a polaprezinc effervescent tablet and a preparation method thereof. BACKGROUND

[0002] Polaprezinc, with the chemical name L-carnosine zinc, is an effective gastric mucosa protective agent, which is widely used for treating gastric ulcer, duodenal ulcer and gastritis. It can form a protective film by combining with the protein at the ulcer site, and promote the expression of mucosa repair factors (such as EGF), thereby playing a role in local protection and healing promotion.

[0003] At present, the polaprezinc dosage forms on the market mainly include ordinary tablets, granules and capsules. However, polaprezinc itself is almost insoluble in water, and has a rough taste and a sand-like feeling after oral administration, especially for elderly patients, children or patients with severe illness who have difficulty in swallowing, the compliance is poor. The ordinary tablets need to be swallowed as a whole, which is inconvenient for patients who need to adjust the dosage or have swallowing disorders. Although the granules can be dispersed in water, they have poor solubility and are prone to sedimentation, resulting in uneven dosage and poor taste.

[0004] The effervescent tablet is a kind of solid preparation which can rapidly disintegrate and release carbon dioxide gas in a proper amount of water. Its advantages include convenient administration, rapid onset, easy adjustment of taste, high drug bioavailability, etc. However, there are significant challenges in preparing a poorly soluble drug into an effervescent tablet: 1) the drug particles may float or sink due to the bubbles generated by effervescence, resulting in uneven dispersion; 2) the acid-base reaction environment generated by effervescence may affect the stability of some drugs; 3) how to ensure that the poorly soluble drug particles can be effectively dispersed and smoothly swallowed without affecting the effervescence speed.

[0005] In the prior art, there is no report on successfully preparing a poorly soluble polaprezinc into an oral effervescent tablet with good taste, rapid disintegration and uniform dispersion. Therefore, it is of great clinical significance and market value to develop a new type of polaprezinc effervescent tablet to solve the problems of inconvenient administration and poor taste, and improve patient compliance. SUMMARY

[0006] In view of the defects of the polaprezinc oral effervescent tablet, such as slow dissolution, strong irritation, heavy odor and poor stability, the present application aims to provide a polaprezinc effervescent tablet and a preparation method thereof, which has the technical effects of rapid disintegration, easy dispersion, good taste and high stability.

[0007] The present application is achieved by the following technical scheme: a polaprezinc effervescent tablet is provided, which comprises the following components by weight: Polaprezinc-HP-β-CD inclusion complex microcapsules: 30-40 parts; Effervescent agent: 25-40 parts (molar ratio of acid effervescent agent: basic effervescent agent = 1: (1-1.1)); Filling agent: 30-45 parts. Sweetener: 0.8-1.5 parts (sucralose 1-1.5 parts); Lubricant: 0.3-0.8 parts (sodium stearyl fumarate, SSF). The preparation method of the polyprylline-HP-β-CD inclusion complex microcapsule is as follows: 1) Take HP-β-CD (hydroxypropyl-β-cyclodextrin) 5-8 parts, add purified water (solid-liquid ratio 1:10), stir at 40-45°C until completely dissolved, and obtain HP-β-CD aqueous solution; 2) Take polyprylline 5-15 parts, add ethanol (concentration 95%, solid-liquid ratio 1:5), and dissolve by ultrasonic (power 300W) to obtain polyprylline ethanol solution; 3) Slowly drop the polyprylline ethanol solution into the HP-β-CD aqueous solution (drop rate 1-2 mL / min), and stir at 40-45°C for 2-3 hours to form an inclusion reaction solution; 4) Place the inclusion reaction solution in a refrigerator at 4°C for 12-16 hours, and precipitate white crystals. Filter (0.45 μm filter membrane), and dry the filter cake at 40-45°C under vacuum (vacuum degree -0.08 to -0.09 MPa) to a moisture content of ≤1.5%. Crush and pass through a 120 mesh sieve to obtain polyprylline-HP-β-CD inclusion complex dry powder. 5) Spray the polyprylline-HP-β-CD inclusion complex dry powder on a fluidized bed, and spray a sugar coating. Dry, and increase the weight of the sugar coating by 4%-6% to obtain polyprylline-HP-β-CD inclusion complex microcapsules.

[0008] The acid effervescent agent is at least one selected from citric acid and tartaric acid.

[0009] The basic effervescent agent is at least one selected from sodium bicarbonate and potassium carbonate.

[0010] The filling agent is spray-dried mannitol. The second aspect of the present application also provides a preparation method of polyprylline effervescent tablets: S1: The preparation method of the polyprylline-HP-β-CD inclusion complex microcapsule is as follows: 1) Take HP-β-CD 5-8 parts, add purified water (solid-liquid ratio 1:10), and stir at 40-45°C until completely dissolved to obtain HP-β-CD aqueous solution; 2) Take polyprylline 5-15 parts, add ethanol (concentration 95%, solid-liquid ratio 1:5), and dissolve by ultrasonic (power 300W) to obtain polyprylline ethanol solution; 3) Slowly drop the poly- zinc-ethanol solution into the HP-β-CD aqueous solution (drop rate 1~2mL / min), constant temperature stirring at 40~45℃ for 2~3 hours to form an inclusion reaction solution; 4) Place the inclusion reaction solution in a refrigerator at 4℃ for 12~16 hours, precipitate white crystals, suction filtration (0.45μm filter membrane), filter cake at 40~45℃ vacuum drying (vacuum degree -0.08~-0.09MPa) to moisture ≤1.5%, crush and pass through a 120 mesh sieve to obtain poly- zinc-HP-β-CD inclusion compound dry powder. 5) Spray the poly- zinc-HP-β-CD inclusion compound dry powder on a fluidized bed and spray a sugar coating, dry, and the sugar coating weight gain is 4%-6% to obtain poly- zinc-HP-β-CD inclusion compound microcapsules.

[0011] S2: Preparation of oral effervescent tablets 1) Pretreatment: pass the inclusion compound microcapsules, effervescent agents (acidic / alkaline agents separately), fillers, sweeteners through a 100 mesh sieve, and pass the lubricant through a 120 mesh sieve; 2) Granule mixing: take the acidic effervescent agent, alkaline effervescent agent, filler, sweetener, inclusion compound microcapsule, and lubricant, and mix them evenly (resting angle ≤30°); 3) Tabletting: use a shallow concave punch, low pressure tabletting (pressure 1.5~2.0kN) at 20~22℃, RH≤40% environment, control the tablet hardness 1.5~2.0kg (avoid oral chewing difficulties), and obtain the effervescent tablets.

[0012] Beneficial effects

[0013] The present application provides poly- zinc effervescent tablets and a preparation method thereof, wherein the effervescent tablets have the technical effects of rapid disintegration, easy dispersion, good taste, and high stability.

[0014] Increase the dissolution rate and bioavailability potential.

[0015] Mechanism: The hydrophobic cavity of cyclodextrin (hydroxypropyl-β-cyclodextrin) can form an inclusion compound with poly- zinc molecules, converting them from a crystalline state to an amorphous or molecularly dispersed state. This greatly improves the apparent solubility of the drug.

[0016] In effervescent tablets: The effervescent agent is used in combination with spray-dried mannitol. Utilizing the porous nature of spray-dried mannitol, capillary action accelerates the simultaneous disintegration of the effervescent tablet from both the inside and outside of the tablet, significantly increasing the disintegration rate. After effervescence and disintegration, the drug is rapidly released into water in a "pre-dissolved" inclusion state, forming a molecular-level dispersion or colloidal solution, rather than the "suspension" produced by ordinary effervescent tablets. This avoids particle sedimentation, ensures absolutely uniform dosage, and may allow for faster and more uniform adsorption and distribution of the drug on the gastric mucosa, potentially improving local bioavailability.

[0017] It greatly improves the taste and masking effect.

[0018] Mechanism: The metallic taste and unpleasant mouthfeel of pipexazol primarily originate from the exposed zinc ions and the drug particles themselves. Cyclodextrin inclusion complexation essentially coats the drug molecules with a sugar coating, isolating them from the taste buds; combined with the effervescent tablet's own sweetener, the resulting solution has a clear, pure taste, free of off-flavors and gritty texture. This is crucial for patients requiring long-term medication (such as those with chronic gastritis) and children, significantly improving adherence.

[0019] Enhance drug stability.

[0020] Protection of the formulation process: During the preparation of effervescent tablets, the microcapsules, through sugar coating and synergistic effect with HP-β-CD, physically isolate polyprednisolone from the effervescent agent (acid and base), avoiding potential, slow solid-phase acid-base reactions before tableting or during storage. This is a key technical challenge in the preparation of effervescent tablets containing metal ion drugs. This improves formulation compatibility and product shelf life. Detailed Implementation

[0021] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. The described embodiments are only some preferred embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] Unless otherwise specified, all components and raw materials used in the embodiments and comparative examples of this invention are commercially available, and the same type of components and raw materials are used in each parallel experiment.

[0023] Example 1

[0024] A method for preparing polyprene zinc effervescent tablets, The preparation method of S1: Zinc-HP-β-CD inclusion complex microcapsules is as follows: 1) Take 15g of HP-β-CD, add purified water (solid-liquid ratio 1:10), stir at 40℃ until completely dissolved to obtain an HP-β-CD aqueous solution; 2) Take 24g of polypyrene zinc, add ethanol (concentration 95%, solid-liquid ratio 1:5), and dissolve by sonication (power 300W) to obtain polypyrene zinc ethanol solution; 3) Slowly add the polypyriphos zinc ethanol solution dropwise into the HP-β-CD aqueous solution (dropping rate 2 mL / min), and stir at a constant temperature of 40~45℃ for 2 hours to form an inclusion reaction solution; 4) Place the inclusion reaction solution at 4℃ for 12 hours to precipitate white crystals. Filter the solution (0.45μm filter membrane) and dry the filter cake at 40℃ under vacuum (vacuum degree -0.08~-0.09MPa) until the moisture content is ≤1.5%. After pulverizing, pass the solution through a 120-mesh sieve to obtain poly-P-P-Zn-HP-β-CD inclusion complex dry powder. 5) Spray the dry powder of polyprene zinc-HP-β-CD inclusion complex on a fluidized bed and coat it with sugar. After drying, the sugar coating increased in weight by 4%, thus obtaining polyprene zinc-HP-β-CD inclusion complex microcapsules.

[0025] The coating solution comprises 7 wt% gum arabic, 30 wt% sucrose, 3 wt% glycerol, and the remainder water.

[0026] S2: Preparation of oral effervescent tablets 1) Pretreatment: The inclusion complex microcapsules, effervescent agent (citric acid / sodium bicarbonate separated), spray-dried mannitol (filler), and sucralose (sweetener) were passed through a 100-mesh sieve, and sodium stearoyl fumarate (lubricant) was passed through a 120-mesh sieve. 2) Particle mixing: Mix 35g of inclusion microcapsules, 33g of effervescent agent (acidic effervescent agent, alkaline effervescent agent), 36g of spray-dried mannitol, 1g of sucralose, and 0.6g of sodium stearoyl fumarate evenly; 3) Tableting: Using a shallow concave die, low-pressure tableting (pressure 2.0kN) is performed at 20~22℃ and RH≤40% to obtain polyprene zinc effervescent tablets with a tablet weight of 0.5g / tablet.

[0027] Examples 2-4 Examples 2-4 are prepared using the same process as Example 1, with specific adjustments made to the amount of each component.

[0028] Comparative Example 1 Comparative Example 1 was prepared using the same method as Example 1, except that the preparation method of "S1: preparation method of polypyrene zinc-HP-β-CD inclusion complex microcapsules" was different. Step S1 was adjusted as follows: 1) Take 15g of HP-β-CD and 24g of polypyrene zinc and mix them evenly to obtain a polypyrene zinc-HP-β-CD mixture; 2) Spray the dry powder of polyprene zinc-HP-β-CD inclusion complex on a fluidized bed and coat it with sugar. After drying, the sugar coating increased in weight by 4%, thus obtaining polyprene zinc-HP-β-CD inclusion complex microcapsules.

[0029] The coating solution comprises 7 wt% gum arabic, 30 wt% sucrose, 3 wt% glycerol, and the remainder water.

[0030] Comparative Example 2 Comparative Example 2 was prepared using the same method as Example 1, except that "S1: Preparation method of polypyrene zinc-HP-β-CD inclusion complex microcapsules" was different (i.e., no sugar coating was used, and polypyrene zinc-HP-β-CD inclusion complex dry powder was used instead of inclusion complex microcapsules for preparing effervescent tablets). Step S1 was adjusted as follows: 1) Take 15g of HP-β-CD, add purified water (solid-liquid ratio 1:10), stir at 40℃ until completely dissolved to obtain an HP-β-CD aqueous solution; 2) Take 24g of polypyrene zinc, add ethanol (concentration 95%, solid-liquid ratio 1:5), and dissolve by sonication (power 300W) to obtain polypyrene zinc ethanol solution; 3) Slowly add the polypyriphos zinc ethanol solution dropwise into the HP-β-CD aqueous solution (dropping rate 2 mL / min), and stir at a constant temperature of 40~45℃ for 2 hours to form an inclusion reaction solution; 4) Place the inclusion reaction solution at 4℃ for 12 hours to precipitate white crystals. Filter the solution (0.45μm filter membrane) and dry the filter cake at 40℃ under vacuum (vacuum degree -0.08~-0.09MPa) until the moisture content is ≤1.5%. After pulverizing, pass the solution through a 120-mesh sieve to obtain poly-P-P-Zn-HP-β-CD inclusion complex dry powder.

[0031] Comparative Example 3 Comparative Example 3 was prepared using the same method as Example 1, except that an equal amount of sucrose (powder) was used instead of spray-dried mannitol as a filler.

[0032] Table 1. Ingredients (g) of Effervescent Tablets for Examples 1-4 and Comparative Examples 1-3

[0033] Performance verification test: The performance of the polyprene zinc effervescent tablets prepared in Examples 1-4 and Comparative Examples 1-3 was verified.

[0034] 1. Disintegration Time: According to the 2020 edition of the Chinese Pharmacopoeia, Part IV, General Chapter 0921, Disintegration Time Test Method for Effervescent Tablets, the test conditions were adjusted to simulate the oral environment. Test medium: 100 mL of purified water (simulating saliva, pH 6.8); medium temperature: 37℃±1℃ (oral temperature); procedure: Take 6 tablets of each sample and put them into the above medium. Record the time from the time of addition to complete disintegration (no visible solid particles) for each tablet, take the average value, and calculate the standard deviation.

[0035] 2. Dissolution: According to the Dissolution Test Method (Paddle Method) of General Chapter 0931, Part IV, Chinese Pharmacopoeia 2020 Edition. Dissolution medium: 900 mL of pH 1.2 hydrochloric acid solution (simulating gastric environment); Rotation speed: 50 rpm; Temperature: 37℃±0.5℃; Sampling time points: 2, 3, 4, 5, 6, 7, 8, 9, 10, and 15 minutes; Detection method: HPLC method, chromatographic column: C18 column (4.6 mm × 250 mm, 5 μm), mobile phase: methanol-water (60:40, v / v), detection wavelength: 220 nm, flow rate: 1.0 mL / min, column temperature: 30℃; Calculation: Calculate the cumulative dissolution rate (%) at each time point, take the average value of 6 tablets, and calculate the standard deviation.

[0036] 3. Taste Evaluation. Evaluation Panel: 10 professional sensory evaluators (5 males and 5 females, no oral diseases, and trained in taste); Evaluation Method: Blind evaluation. One tablet was taken from each sample, dissolved in 10mL of 37℃ warm water, and rinsed in the mouth for 30 seconds. The tablets were scored according to the following dimensions (total score 10 points): Scoring Dimensions: Odor Masking (0-3 points, no metallic taste 3 points, obvious metallic taste 0 points), Grainy Feel (0-3 points, no gritty feel 3 points, severe gritty feel 0 points), Appropriate Sweetness (0-2 points, moderate sweetness 2 points, too sweet / too bland 0 points), Overall Acceptability (0-2 points, willing to take long-term 2 points, refuse to take 0 points); Excellent: ≥8 points; Good: 6-7.9 points; Pass: 4-5.9 points; Unsatisfactory: <4 points.

[0037] 4. Dispersion uniformity: Take one tablet of each sample and add it to 100 mL of purified water at 37℃. After disintegration, stir magnetically for 1 minute (100 rpm) and take 5 mL of supernatant. Detection: Measure the turbidity (NTU) of the suspension using a turbidimeter (25℃). Perform three parallel measurements and take the average value. Let stand for 10 min and observe whether there is any precipitation (insoluble matter).

[0038] 5. Stability Test. Test conditions: accelerated test (40℃±2℃, relative humidity 75%±5%), stored for 6 months; test time points: 0, 1, 3, 6 months; test indicators: disintegration time, 5-minute dissolution rate, content (determined by HPLC for zinc content of polymethyl methacrylate, the actual content measured at 0 months is recorded as 100%); sample preparation: each sample is sealed in an aluminum-plastic blister pack and placed in a stability test chamber.

[0039] Table 2. Record of Disintegration Time, Dissolution Rate, Taste Score, and Dispersion Uniformity

[0040] As shown in Table 2, 1) the polyprene zinc effervescent tablets prepared in Examples 1-4 have the advantage of rapid disintegration, rapidly disintegrating within 15.3s-15.8s, increasing the convenience of oral disintegration for patients. Comparative Examples 1-2 used the same effervescent agent, spray-dried mannitol, and the same amount as Example 1. Effervescent agent and spray-dried mannitol are key components affecting the disintegration rate; therefore, the disintegration time of Comparative Examples 1-2 is comparable to that of Example 1. However, compared to Example 1, Comparative Example 3 replaced the spray-dried mannitol filler with sucrose powder. Since spray-dried mannitol has a porous structure while sucrose does not, the polypracene zinc effervescent tablets prepared in Comparative Example 3 disintegrated slowly from the tablet surface upon contact with water, continuously generating gas. However, Example 1 not only generated gas from the tablet surface but also utilized the capillary effect of the porous structure of spray-dried mannitol to continuously wet the interior of the tablet, synergistically generating gas from within and significantly accelerating the disintegration rate. 2) Examples 1-4 achieved a solubility of over 97.4% at 5 minutes. The difference between Comparative Example 1 and Example 1 is that polypracene zinc was physically blended with HP-β-CD, without encapsulating it within HP-β-CD. Because polypracene zinc encapsulated in HP-β-CD is in a molecularly dispersed state, it dissolves more easily. In contrast, the polypracene zinc in Comparative Example 1 is granular, resulting in a relatively slow dissolution rate, which may explain the lower solubility of Comparative Example 1 compared to Example 1. The longer disintegration time of Comparative Example 3 may be the reason for its lower dissolution rate. 3) The taste scores of Examples 1-4 are between 9.0 and 9.2, indicating excellent taste. Comparative Example 1 has a poor taste because the polypracene zinc is not encapsulated in HP-β-CD, making it difficult to form good microcapsules through sugar coating. The low taste score of Comparative Example 2 is because the polypracene zinc-HP-β-CD inclusion complex is a sugar coating. Comparing Example 1 with Comparative Examples 1-2 shows that encapsulating polypracene zinc with HP-β-CD and sugar coating can effectively improve the taste of polypracene zinc. 4) Examples 1-4 and Comparative Examples 2-3 have low turbidity, while Comparative Example 1 has high turbidity and precipitation. This is because the polypracene zinc in Comparative Example 1 is not encapsulated in HP-β-CD. HP-β-CD has the effect of increasing the solubility of polypracene zinc and can improve its dispersibility.

[0041] Table 3 Stability test data

[0042] Table 3 shows the stability test data. The disintegration time and dissolution rate of the polyprene zinc effervescent tablets prepared in Examples 1-4 and Comparative Examples 1-3 did not change significantly after 6 months at 40℃±2℃ and 75%±5% relative humidity. However, after 6 months, the polyprene zinc content in Examples 1-4 and Comparative Examples 1-3 decreased to varying degrees, indicating that high temperature and high humidity environments affect the stability of polyprene zinc effervescent tablets. However, the changes in polyprene zinc content in Examples 1-4 and Comparative Example 3 were minimal, all less than 0.16%; while the changes in polyprene zinc content in Comparative Examples 1 and 2 were significant, decreasing by 1.07% and 0.77%, respectively. The significant change in the content of polypyrene zinc in Comparative Example 1 may be due to the fact that polypyrene zinc was not encapsulated in HP-β-CD, and the sugar coating was unable to effectively encapsulate polypyrene zinc, resulting in direct contact between polypyrene zinc and the effervescent agent (citric acid / sodium bicarbonate). Effervescent agents (acids and alkalis) can easily reduce the stability of polypyrene zinc. Although polypyrene zinc formed an inclusion complex with HP-β-CD in Comparative Example 2, and HP-β-CD could reduce the direct contact between polypyrene zinc and the effervescent agent and play a role in stabilizing polypyrene zinc, the problem of poor stability of polypyrene zinc due to contact between polypyrene zinc and polypyrene zinc still exists.

[0043] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the invention to the specific implementations described. Clearly, many modifications and variations can be made based on the content of this specification. This specification selects and specifically describes these embodiments to better explain the principles and practical applications of the invention, thereby enabling those skilled in the art to better understand and utilize the invention. The invention is limited only by the claims and their full scope and equivalents.

Claims

1. A poly-ene zinc effervescent tablet, characterized in that, By weight parts, including the following components: Polyprawns zinc-HP-β-CD inclusion complex microcapsule: 30~40 parts; Effervescent agent: 25~40 parts; Filler: 30~45 parts; Sweetener: 0.8~1.5 parts; Lubricant: 0.3~0.8 parts; the filler is spray dried mannitol; The polyprawns zinc-HP-β-CD inclusion complex microcapsule is formed by 5~8 parts of hydroxypropyl-β-cyclodextrin HP-β-CD and 5~15 parts of polyprawns zinc to form polyprawns zinc-HP-β-CD inclusion complex, and then coated with 4%~6% of the weight of the inclusion complex.

2. The poly- zinc pyrithione effervescent tablet according to claim 1, wherein The sweetener is sucralose.

3. The poly- zinc pyrithione effervescent tablet according to claim 1, wherein The lubricant is sodium stearyl fumarate.

4. The poly- zinc pyrithione effervescent tablet according to claim 1, wherein The effervescent agent includes an acidic effervescent agent and an alkaline effervescent agent, and the molar ratio of the acidic effervescent agent to the alkaline effervescent agent is 1: (1~1.1).

5. The poly- zinc pyrithione effervescent tablet according to claim 4, wherein The acidic effervescent agent is selected from at least one of citric acid and tartaric acid.

6. The poly- zinc pyrithione effervescent tablet according to claim 4, wherein The alkaline effervescent agent is selected from at least one of sodium bicarbonate and potassium carbonate.

7. The poly- zinc sulfate effervescent tablet according to claim 4, wherein The preparation method of the polyprawns zinc-HP-β-CD inclusion complex microcapsule is as follows: 1) Take 5~8 parts of HP-β-CD, add purified water, and stir at 40~45℃ until completely dissolved to obtain an HP-β-CD aqueous solution; 2) Take 5~15 parts of polyprawns zinc, add 95% ethanol, and ultrasonically dissolve to obtain a polyprawns zinc ethanol solution; 3) Slowly drop the polyprawns zinc ethanol solution into the HP-β-CD aqueous solution, and stir at 40~45℃ for 2~3 hours to form an inclusion reaction solution; 4) Place the inclusion reaction solution in a 4℃ refrigerator for 12~16 hours, and precipitate white crystals. Vacuum dry the filter cake at 40~45℃, crush, and sieve to obtain polyprawns zinc-HP-β-CD inclusion complex dry powder; 5) Spray the polyprawns zinc-HP-β-CD inclusion complex dry powder on a fluidized bed, and spray a sugar coating. Dry, and increase the weight of the sugar coating by 4%-6% to obtain polyprawns zinc-HP-β-CD inclusion complex microcapsules.

8. The poly- zinc pyrithione effervescent tablet according to claim 1, wherein The coating liquid of the sugar coating includes 7wt% of gum arabic, 30wt% of sucrose, 3wt% of glycerol, and the balance of water.

9. The method of making poly- zinc sulfate effervescent tablets according to any one of claims 1-8, wherein, Including the following steps: S1: Preparation of polyprawns zinc-HP-β-CD inclusion complex microcapsules: 1) Take 5~8 parts of HP-β-CD, add purified water, and stir at 40~45℃ until completely dissolved to obtain an HP-β-CD aqueous solution; 2) Take 5~15 parts of polyprawns zinc, add 95% ethanol, and ultrasonically dissolve to obtain a polyprawns zinc ethanol solution; 3) Slowly drop the polyprawns zinc ethanol solution into the HP-β-CD aqueous solution, and stir at 40~45℃ for 2~3 hours to form an inclusion reaction solution; 4) Place the inclusion reaction solution in a 4℃ refrigerator for 12~16 hours, and precipitate white crystals. Vacuum dry the filter cake at 40~45℃, crush, and sieve to obtain polyprawns zinc-HP-β-CD inclusion complex dry powder; 5) Spray the polyprawns zinc-HP-β-CD inclusion complex dry powder on a fluidized bed, and spray a sugar coating. Dry, and increase the weight of the sugar coating by 4%-6% to obtain polyprawns zinc-HP-β-CD inclusion complex microcapsules; S2: Preparation of oral effervescent tablets: 1) Pretreatment: the inclusion microcapsule, effervescent agent, filler, sweetener are respectively passed through 100 mesh sieve, and the lubricant is passed through 120 mesh sieve; 2) Granule mixing: the effervescent agent, filler, sweetener, inclusion microcapsule and lubricant are uniformly mixed; 3) Tabletting: a shallow concave punch die is adopted, and tabletting is carried out under the condition of 20~22℃ and RH≤40%, and the tablet is obtained.

Images