A kind of calcium gluconate zinc effervescent tablet with high calcium content and preparation method thereof

Abstract

The present invention discloses a calcium gluconate zinc effervescent tablet with a high calcium content and a preparation method thereof, belonging to the technical field of pharmaceutical preparations. The calcium content of a unit preparation of the calcium gluconate zinc effervescent tablet is not less than 100 mg, and the unit preparation weight is not more than 4.5 g. The prescription of the calcium gluconate zinc effervescent tablet comprises the following ingredients: calcium gluconate, zinc gluconate, an absorption enhancer, an acid source, an alkali source, a filler, an adhesive, a wetting agent, a lubricant, a sweetener, a colorant, and a flavor. The absorption enhancer comprises casein phosphopeptide. The calcium gluconate zinc effervescent tablet is prepared by wet granulation, drying, mixing, and tableting. The calcium gluconate zinc effervescent tablet of the present invention has a high calcium content, good stability, a good taste, and good calcium and zinc absorption, and is a calcium and zinc supplement that can be used long-term and safely.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparation preparation, and particularly relates to a calcium-zinc gluconate effervescent tablet with a high calcium content and a preparation method thereof. Background Art

[0002] Calcium deficiency can easily lead to symptoms such as rickets and osteoporosis, while zinc deficiency can cause growth and intellectual developmental delays in children. This product is a calcium and zinc supplement primarily used to treat and prevent diseases caused by calcium and zinc deficiency, including osteoporosis, tetany, bone dysplasia, rickets, growth retardation in children, anorexia, anorexia, recurrent oral ulcers, and acne. Casein phosphopeptides effectively promote the body's absorption and utilization of divalent mineral nutrients such as calcium and zinc and are commonly used as absorption enhancers in various nutritional and health foods. Casein phosphopeptides are bioactive peptides derived from bovine casein through biotechnology and have excellent safety. Maltitol is obtained by hydrolyzing starch into maltose syrup and reacting it with hydrogen in the presence of a catalyst. Maltitol has a sweet taste, a very low absorption rate, and a much smaller impact on blood sugar than sucrose. Therefore, the American Diabetes Association states that sugar alcohol foods are beneficial for blood sugar control. They are also not fermented by oral bacteria, which prevents tooth decay. Besides their low digestibility, the calories produced by the metabolism of absorbed sugar alcohols are much lower than the same amount or sweetness of sugar. Furthermore, animal studies have shown that maltitol promotes intestinal calcium absorption and increases bone mass and strength. Therefore, maltitol is a food that is very suitable for children and pregnant women, and is often used as a filler in medicines and health supplements.

[0003] Currently, calcium gluconate zinc products on the market are oral solutions, and their prescriptions mainly include calcium gluconate, zinc gluconate and lysine hydrochloride. This oral solution is a supersaturated solution, and white flocculent or granular precipitates often precipitate during freezing, low temperature and storage. It may also turn yellow or become turbid. The stability of the solution is not high, which reduces the quality of the drug. At the same time, the calcium content of the existing calcium gluconate zinc oral solution on the market is only 54mg. According to the Nutrient Supplements in the Health Food Ingredients Catalogue (2022 Edition) (Draft for Comment), the recommended daily calcium supplement is 120-500mg for children aged 1-3 years, 150-700mg for children aged 4-6 years, 200-800mg for children aged 7-10 years, 250-1000mg for children aged 11-13 years, 200-800mg for children aged 14-17 years, 200-1000mg for adults, 200-800mg for pregnant women, and 200-1000mg for nursing mothers. The calcium content of 54mg is far lower than the above recommended dosage, which is also due to its lower solubility. Therefore, how to prepare a calcium gluconate zinc oral preparation that is easy to use, stable during the circulation cycle, has a higher calcium content, and is convenient for children and the elderly to use is a difficult problem in the industry. Currently, no relevant literature, patents, or products have been retrieved that can meet the above requirements.

[0004] This product is a solid effervescent tablet that converts to a solution upon use, making it convenient and effectively addressing the stability issues of calcium gluconate zinc oral solution. Furthermore, this product utilizes casein phosphopeptides as calcium and zinc absorption enhancers, replacing the lysine hydrochloride in the original formulation. Casein phosphopeptides are food-derived, offering improved safety and effective calcium and zinc absorption. Calcium is readily absorbed only in its ionic form and readily forms insoluble salts with acid ions in neutral and weakly alkaline environments, leading to loss. The calcium absorption-enhancing effect of casein phosphopeptides is primarily manifested by their ability to bind to calcium in neutral and weakly alkaline environments, inhibiting the formation of insoluble precipitates and preventing calcium loss. Ultimately, this leads to passive absorption due to increased free calcium concentrations. Studies have shown that casein phosphopeptides can enhance calcium absorption in the small intestine, bones, and teeth. Casein phosphopeptides have been used in foods and health supplements such as children's curry rice, beverages, and chewing gum. Research and application in the treatment of calcium deficiency in children, osteoporosis in the elderly, infertility and dental care are also underway.

[0005] At present, there are no compound effervescent tablet products and public technologies for calcium gluconate zinc compositions for simultaneous supplementation of calcium and zinc, and containing calcium and zinc absorption promoters. The calcium source calcium gluconate contained in this product is organic calcium and is easily absorbed by the human body. The calcium content of a single tablet is much higher than the calcium content in one calcium gluconate zinc oral solution currently on the market (the maximum calcium content of the commercially available calcium gluconate zinc oral solution is 54 mg), overcoming the technical obstacle of long effervescent time under high calcium content. During the research process, we found that 54 mg of calcium cannot meet the needs of different groups of people for daily calcium supplementation. However, high-proportion calcium gluconate in the prescription and high content of calcium gluconate in a single tablet will significantly prolong the effervescent disintegration of the effervescent tablet in aqueous solution, making it impossible for the effervescent tablet to meet the standard requirement of the 2020 edition of the Chinese Pharmacopoeia that the disintegration time of the effervescent tablet is less than 5 minutes. Therefore, when the calcium gluconate added in the prescription is higher than 100 mg in terms of calcium content, the prescription ratio and preparation process of its ingredients are extremely challenging, which is why there are currently no such varieties on the market. Summary of the Invention

[0006] The present invention addresses the problems of the prior art and provides a calcium gluconate zinc effervescent tablet that has high calcium content, good stability, good taste, is easy to use, can promote calcium and zinc absorption, and contains no less than 100 mg of calcium per tablet. The present invention can effectively fill the market gap and has broad market prospects.

[0007] The present invention is achieved through the following technical solutions:

[0008] A calcium-zinc gluconate effervescent tablet with a high calcium content comprises an effective dose of calcium gluconate and zinc gluconate, casein phosphopeptide as an absorption enhancer, liquid PEG as a wetting agent, and one or more pharmaceutically acceptable excipients, such as an acid source, an alkali source, a filler, a binder, a sweetener, a lubricant, a colorant, and a flavor.

[0009] The invention is characterized in that the prescription composition comprises the following proportions: calcium gluconate: 28%-60%; zinc gluconate: 0.2%-3.9%;

[0010] Absorption enhancer: 0.2%-1.1%; wetting agent 0.1%-3.5%; acidic component (acid source) 8%-21%, alkaline component (alkaline source) 14%-35%; the remaining ingredients are one or more of fillers, adhesives, sweeteners, lubricants, colorants and flavors.

[0011] The wetting agent described herein is liquid polyethylene glycol, characterized in that the wetting agent is preferably a mixture of one or more of PEG 200, 300, 400, 500, and 600. According to the Chinese Pharmacopoeia (2020 edition), Section 0921 of the Disintegration Time Test, effervescent tablets should disintegrate within 5 minutes during the disintegration time test. Our research surprisingly discovered that liquid PEG can reduce granulation delamination after granulation and adjust the tablet's morphology in water during effervescence, enabling the tablet to maintain submerged effervescence even at relatively low tablet hardness, thereby meeting the standard requirement of an effervescence time of no more than 5 minutes. However, if liquid PEG is not added to the formulation, the prepared granules readily delaminate, resulting in unstable tablet weight and effervescence time with continuous tableting. Furthermore, when the tablet hardness is low, the tablet will float on the water surface during effervescence, resulting in less intense effervescence. When the tablet hardness is high, the tablet will sink to the bottom of the water at the beginning of effervescence, but the effervescence is also less intense, similarly failing to meet the 5-minute standard.

[0012] The acid source of the present invention is one or more of citric acid and its hydrates (also known as citric acid), lactic acid, tartaric acid and their hydrates, preferably citric acid and its hydrates and tartaric acid, or a combination thereof. The alkali source is one or more of sodium bicarbonate and sodium carbonate, or a mixture or combination thereof. After use of the effervescent tablet (one tablet is placed in approximately 250 ml of warm or cold water), the preferred acid source and alkali source of the present invention are used, and the pH value after dissolving in water is between 3.5 and 7.0.

[0013] Furthermore, after the effervescent tablet is used (one tablet is put into about 250 ml of warm or cold water), the preferred pH adjuster of the present invention is used, and the pH value after dissolving in water is between 4.0 and 7.0.

[0014] The effervescent tablet of the present invention further comprises at least one pharmaceutically acceptable sweetener, such as steviol glycoside, acesulfame potassium, aspartame, saccharin sodium, sucralose, and the like.

[0015] Beneficial effects

[0016] Beneficial effects of the present invention:

[0017] (1) The effervescent tablets of the present invention rapidly effervescently dissolve in water, ensuring product quality and effectiveness. The solid preparations are more convenient and more stable than existing commercially available oral solutions during production, transportation, and storage, effectively resolving the precipitation problem of oral solutions caused by oversaturation of calcium gluconate.

[0018] (2) Casein phosphopeptide is used in the prescription to promote the absorption of calcium and zinc.

[0019] (3) The combination of the acid source, alkali source and sweetener of the present invention can mask the astringency of calcium gluconate and zinc gluconate, improve the mouthfeel of the preparation, and enhance the compliance of administration.

[0020] (4) The present invention does not require the use of preservatives, which can better ensure the safety of the product.

[0021] (5) The calcium content in the single-tablet preparation of the present invention is not less than 100 mg, and the dosage is much higher than the commercially available calcium gluconate zinc oral solution, which can more efficiently meet the calcium supplementation needs of consumers.

[0022] (6) The present invention adopts effervescent preparation technology, which is very suitable for children, the elderly and patients who cannot swallow tablets. DETAILED DESCRIPTION

[0023] The present invention will be further described below with reference to specific embodiments. However, this should not be construed as limiting the scope of the present invention to the following embodiments. All technologies implemented based on the above contents of the present invention fall within the scope of the present invention.

[0024] The excipients in the following examples can be replaced with similar pharmaceutically acceptable excipients, or their amounts can be reduced or increased.

[0025] [Example 1] This example is used to demonstrate the effects of tablet weight range, dosage range of each ingredient, and calcium content on disintegration time.

[0026] Prescription List:

[0027]

[0028] *Note: This portion of Povidone K30 and PEG400 is prepared into a 95% ethanol solution and added during the granulation process. The ethanol solution is removed during drying.

[0029] [Example 2] Production process

[0030] The production process of the above prescription is as follows:

[0031] ① Grind citric acid, calcium gluconate, zinc gluconate and PEG6000 with a grinder, sieve and set aside.

[0032] ② According to the above formula ratios of F1-F7, weigh calcium gluconate, zinc gluconate, casein phosphopeptide, maltitol, and povidone K30 in order. After mixing evenly, add the binder solution and wet granulate. After the granules are dried (loss on drying not exceeding 3.0%), sieve the whole granules and set aside.

[0033] ③ Mix the above granules with an external amount of anhydrous citric acid, sodium bicarbonate, maltitol, stevia, flavor, sunset yellow, and PEG6000, and press into tablets to obtain the product.

[0034] [Example 3] Evaluation

[0035] Tablets with a calcium content exceeding 100 mg per unit dosage were compressed according to the formulation ratios in F1-F7. Taking formulation F1 as an example, tablets were compressed based on a calcium content of 125.132 mg per tablet. After conversion, the amount of calcium gluconate per tablet was 1400 mg. The moisture content, disintegration time, pH after effervescence, and mouthfeel of each formulation tablet were measured. The determination methods were as follows:

[0036] Moisture: A halogen moisture meter was used to determine the moisture content of the tablets.

[0037] Disintegration Time Test: According to the Chinese Pharmacopoeia General Chapter 0921 Disintegration Time Test Method: For effervescent tablets, place one tablet in a 250ml beaker (containing 200ml of water at 20°C ± 5°C). Bubbles should be released. When the gas around the tablet or fragments stops escaping, the tablet should dissolve or disperse in the water, with no aggregated particles remaining. Unless otherwise specified, test six tablets using the same method. Each tablet should disintegrate within 5 minutes. If one tablet fails to completely disintegrate, retest six more tablets, and all should meet the specified requirements.

[0038] pH: After the calcium zinc gluconate effervescent tablets effervescent solution is effervescent, the pH is measured. The pH of the effervescent tablets of the present invention is between 4.0 and 7.0.

[0039]

[0040] Formulas F1-F3 contain 125 mg of calcium per tablet, Formulas F4-F6 contain 160.8 mg of calcium per tablet, and Formula F7 contains 100 mg of calcium per tablet. The above experimental results show that as the calcium content per tablet increases, the disintegration time also increases.

[0041] [Example 4] This example is used to demonstrate the effects of the type and dosage range of the wetting agent PEG.

[0042] Prescription List

[0043]

[0044] *Note: This portion of Povidone K30 and PEG is prepared into a 95% ethanol solution and added during the granulation process. The ethanol solution is removed during drying.

[0045] [Example 5] Evaluation

[0046] The formulation in Example 4 was prepared according to the preparation process in Example 2. Tablets were compressed using the formulation ratios in F8-F14, with each tablet containing 1400 mg of calcium gluconate. The moisture content, disintegration time, pH after effervescence, and mouthfeel of each tablet were measured using the same testing methods as in Example 4.

[0047]

[0048] The dosage of PEG400 in formulations F8-F10 ranged from 0.1% to 3.5%. All test parameters of samples prepared from these three formulations met the requirements. However, when the dosage of PEG400 in formulation F10 was 0.1%, the disintegration time was significantly prolonged, at 281.5 seconds. Formulations F11-F14 used PEG600, PEG500, PEG300, and PEG200 at a dosage of 1%, and all test parameters of the samples prepared met the requirements.

[0049] [Comparative Example 1] This comparative example is used to demonstrate the effect of not adding the wetting agent PEG on the product.

[0050] Prescription List

[0051]

[0052] *Note 1: This portion of Povidone K30 was prepared as a 95% ethanol solution and added during the granulation process. The ethanol solution was removed during drying.

[0053] Note 2: The formulations of F15-F22 are basically the same as those of F1-F8. The only difference is that PEG is not added to the formulations of F15-F22, and the reduced amount of PEG is increased to the amount of the filler maltitol.

[0054] The formulation in Comparative Example 1 was prepared according to the preparation process in Example 2. The moisture content, disintegration time, pH after effervescence, and mouthfeel of each formulation tablet were measured using the same testing methods as in Example 4.

[0055]

[0056] From the above results, it can be seen that the disintegration time of the samples prepared from formulations F15-F22 without the addition of the wetting agent PEG all failed to meet the requirements and exceeded the limit by a large margin.

[0057] [Comparative Example 2] This comparative example is used to demonstrate the effect of calcium content in a single preparation on the product without the addition of PEG.

[0058] Prescription List

[0059]

[0060] *Note 1: This portion of Povidone K30 was prepared as a 95% ethanol solution and added during the granulation process. The ethanol solution was removed during drying.

[0061] Note 2: The material ratios in F23-F24 formulations are almost identical to those in F7, with the exception that they do not contain PEG and have lower calcium content per unit dosage form, at 95 mg / tablet and 85 mg / tablet, respectively. The calcium content per unit dosage form in F7 is 100 mg / tablet. The material ratios in F25-F30 formulations are almost identical to those in F1-F6, with the exception that they do not contain PEG and have lower calcium content per unit dosage form, at 85 mg / tablet, respectively. The calcium content per unit dosage form in F1-F6 formulations is greater than 100 mg / tablet.

[0062] The formulation in Comparative Example 2 was prepared according to the preparation process in Example 2. The moisture content, disintegration time, pH after effervescence, and mouthfeel of each formulation tablet were measured using the same testing methods as in Example 4.

[0063]

[0064] The above results show that the disintegration time of the sample prepared with F23 containing 95 mg of calcium per tablet failed the standard, the disintegration time of the samples prepared with F24-F27 containing 85 mg of calcium per tablet all passed the standard, and the disintegration time of the samples prepared with F28-F30 containing 85 mg of calcium per tablet also failed the standard. This result shows that, in the absence of the wetting agent PEG, the calcium content of a single preparation has a significant impact on the disintegration time, and a single preparation must contain less than 100 mg of calcium to achieve a satisfactory disintegration time.

[0065] [Comparative Example 3] This comparative example is used to demonstrate the effect of internal addition of acid and alkali on the product.

[0066] Prescription List

[0067]

[0068] *Note 1: This portion of povidone K30 and PEG is prepared into an anhydrous ethanol solution and added during the granulation process. The anhydrous ethanol solution is removed during drying.

[0069] Note 2: The proportions of ingredients in prescriptions F31-F37 are exactly the same as those in prescriptions F1-F7, and the total tablet weight and calcium content per unit preparation are also exactly the same. The only difference is the granulation method. For F1-F7, the main drug and some excipients are wet-granulated and dried together, and then acid, base, and other excipients are added and tableted; for F31-F37, acid, base, main drug and some excipients are wet-granulated and dried together, and then other excipients are added and tableted.

[0070] The formulation in Comparative Example 3 was prepared according to the preparation process in Example 2. The moisture content, disintegration time, pH after effervescence, and mouthfeel of each formulation tablet were measured using the same testing methods as in Example 4.

[0071]

[0072] From the above results, it can be seen that the disintegration of the samples prepared by F31-F37 is unqualified. During the experiment, it was found that after the addition of acid and alkali to granulate, the initial effervescence rate of the sample was significantly reduced, affecting the overall disintegration time.

[0073] [Comparative Example 4] This comparative example is used to demonstrate the effects of separate granulation of acid and alkali on the product.

[0074] Prescription List

[0075]

[0076] *Note 1: This portion of povidone K30 and PEG is prepared into a 95% ethanol solution and added during the granulation process. The ethanol solution is removed during drying.

[0077] Note 2: The proportions of ingredients in prescriptions F38-F44 and F1-F7 are exactly the same, and the total tablet weight and calcium content per unit preparation are also exactly the same. The only difference is the granulation method. For F1-F7, the main drug and some excipients are wet granulated and dried together, and then acid, alkali and other excipients are added and tableted; for F38-F44, the acid, main drug and some excipients are wet granulated and dried together, and the alkali is added to the binder for granulation and drying, and then the acid and alkali granules and the added excipients are mixed and tableted.

[0078] The formulation in Comparative Example 4 was prepared according to the preparation process in Example 2. The moisture content, disintegration time, pH after effervescence, and mouthfeel of each formulation tablet were measured using the same testing methods as in Example 4.

[0079]

[0080] From the above results, it can be seen that the disintegration of the samples prepared by F38-F44 is unqualified. During the experiment, it was found that after the addition of acid and alkali to granulate, the initial effervescence rate of the sample was significantly reduced, affecting the overall disintegration time.

[0081] [Comparative Example 5] This comparative example is used to demonstrate the effect of direct powder tableting on the product.

[0082] Prescription List

[0083]

[0084] *Note 1: The proportions of ingredients in prescriptions F45-F51 are exactly the same as those in prescriptions F1-F7, and the total tablet weight and calcium content per unit dosage form are also exactly the same. The only difference is the granulation method. For F1-F7, the main drug and some excipients are wet granulated and dried together, and then acid, base, and other excipients are added and tableted. For F45-F51, all materials are mixed and tableted.

[0085] The production process of the above prescription is as follows:

[0086] Crush citric acid, calcium gluconate, zinc gluconate and PEG6000 with a grinder, sieve and set aside.

[0087] According to the above prescription ratio of F45-F51, weigh the auxiliary materials in order, mix them evenly, and press them into tablets to obtain the product.

[0088] Experimental results: The fluidity of the mixed materials of prescriptions F45-F51 was poor and tableting could not be completed.

[0089] [Comparative Example 6] This comparative example is used to demonstrate the effect of the prescription of calcium gluconate effervescent tablets reported in the literature.

[0090] Prescription List

[0091]

[0092] Note 1: Prescription F52 is the one reported in the literature (Zhang Zidong. Calcium Gluconate Effervescent Tablets [J]. Chinese Journal of Pharmaceutical Sciences, 1966(05): 235.). The proportions of the components in prescription F53 are exactly the same as those in F52. The difference is that the calcium content in F53 is increased to 100 mg / tablet, and the total tablet weight is also increased accordingly.

[0093] Note 2: The preparation method of prescriptions F52 and F53 is consistent with the literature report (Zhang Zidong. Calcium Gluconate Effervescent Tablets [J]. Chinese Journal of Pharmaceutical Sciences, 1966(05): 235.). The literature report that the “No. 16 sieve” was used for granulation is inconsistent with common sense. Nowadays, the pharmacopoeia only includes No. 1-9 sieves. Based on general preparation experience, the “16-mesh sieve” was used for granulation.

[0094] The moisture content, disintegration time, pH after effervescence, and mouthfeel of each tablet were measured using the same testing methods as in Example 4. The data obtained at the optimal tableting hardness are as follows.

[0095]

[0096] The above results indicate that the disintegration time for prescription F52 met the prescribed time limit, but was very close to the 5-minute limit. When the calcium content in the prescription was increased to 100 mg / tablet (F53), the disintegration time significantly increased, resulting in a failure. Furthermore, after disintegration, a large amount of insoluble precipitate formed in prescriptions F52 and F53. This was confirmed to be the result of the reaction of tartaric acid and calcium gluconate in the solution, producing calcium tartrate, a substance with extremely low solubility, which hindered calcium absorption.

[0097] [Example 6] Batch scale-up test

[0098] Of the above prescriptions F1-F14, prescription F1 was selected for large-scale sample preparation, with a batch size of 10,000 tablets. After tableting, 6 tablets were selected for disintegration time testing, and 10 tablets were selected for tablet weight variation testing. The results are as follows:

[0099]

[0100]

[0101] The F1 samples were sealed and packaged in effervescent tablet bottles and placed at 37°C ± 2°C and 75% ± 5% relative humidity for 3 minutes. The quality of the products was examined. The results are as follows:

[0102]

[0103] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A calcium gluconate zinc effervescent tablet with high calcium content, characterized in that The invention comprises an effective dose of calcium gluconate, zinc gluconate, an absorption enhancer, a wetting agent, and one or more other pharmaceutically acceptable excipients; the absorption enhancer is casein phosphopeptide; the wetting agent is liquid polyethylene glycol, the amount of which accounts for 0.1%-3.5% of the total weight of the prescription; the weight of the unit preparation is not more than 4.5g, and the calcium content in the unit preparation is not less than 100mg; Its preparation method is: (1) Mix calcium gluconate, zinc gluconate, absorption enhancer, part of binder and part of filler uniformly; (2) adding 95% ethanol solution containing wetting agent and remaining binder for wet granulation; (3) After drying, granulation is performed, and an acid source, an alkali source, a colorant, a sweetener, a lubricant, and the remaining excipients are added; (4) Mix well and compress into tablets.

2. calcium gluconate zinc effervescent tablet as claimed in claim 1, is characterized in that The composition ratio of the prescription meets the following requirements: Calcium gluconate: 28%-60%; Zinc gluconate: 0.2%-3.9%; Absorption enhancer: 0.2%-1.1%; Acid source: 8%-21%; Alkali source: 14%-35%; Fillers: 4%-35%; Wetting agent: 0.1%-3.5%; The rest is one or more combinations of binders, sweeteners, lubricants, colorants and flavors; The total amount of each component is 100%.

3. The calcium gluconate zinc effervescent tablet according to claim 1 or 2, wherein: The wetting agent is selected from one or more mixtures of PEG200, PEG300, PEG400, PEG500 or PEG600.

4. The calcium gluconate zinc effervescent tablet according to claim 1 or 2, wherein: The acid source is selected from citric acid and its hydrates, tartaric acid and its hydrates, ascorbic acid or a combination of two or three of the above acids.

5. The calcium gluconate zinc effervescent tablet according to claim 1 or 2, wherein: The acid source is selected from citric acid and its hydrates, tartaric acid and its hydrates, or a combination thereof.

6. The calcium gluconate zinc effervescent tablet according to claim 1 or 2, wherein: The alkali source is selected from sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, calcium carbonate, and sodium glycine carbonate.

7. The calcium gluconate zinc effervescent tablet according to claim 1 or 2, wherein: The alkali source is selected from sodium bicarbonate, sodium carbonate, and a combination of sodium bicarbonate and sodium carbonate.

8. The calcium gluconate zinc effervescent tablet according to claim 1 or 2, wherein: The filler is selected from one or more of lactose, maltitol, mannitol, sucrose, starch or sodium chloride.

9. The calcium gluconate zinc effervescent tablet according to claim 1 or 2, wherein: The filler is maltitol.

10. The calcium gluconate zinc effervescent tablet according to claim 1 or 2, wherein: The adhesive is povidone K30.

11. The calcium gluconate zinc effervescent tablet according to claim 1 or 2, wherein: The sweetener is selected from one or more of steviol glycosides, sucralose, aspartame or sucrose; the lubricant is selected from one or more of PEG6000, magnesium stearate, sodium stearyl fumarate or glyceryl behenate.

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