Vitamin C effervescent tablet and preparation method thereof

Abstract

The invention relates to the technical field of solid preparation production, and particularly discloses a preparation method of vitamin C effervescent tablets and the vitamin C effervescent tablets prepared by the preparation method. The preparation method of the vitamin C effervescent tablet comprises the following steps: pretreating the raw materials, pre-mixing and granulating, drying and granulating, totally mixing and tabletting. The vitamin C effervescent tablet provided by the invention can be used for preventing or improving vitamin C deficiency and enhancing resistance, and has the advantages of rapid disintegration and improved stability; in addition, the preparation method disclosed by the invention has the advantages of reducing sticking and improving the production efficiency.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of solid preparation production, and more particularly to a preparation method of vitamin C effervescent tablets and the vitamin C effervescent tablets prepared by the method. BACKGROUND

[0002] The vitamin C effervescent tablet is a dietary supplement for brewing and drinking, mainly used for supplementing vitamin C in daily diet, helping to enhance immunity and promote collagen synthesis. The vitamin C effervescent tablet has the characteristics of fast dissolution and good taste, but attention should be paid to reasonable dosage to avoid side effects caused by excessive dosage.

[0003] Common vitamin C effervescent tablets are usually prepared from vitamin C (ascorbic acid), effervescent agents (such as sodium bicarbonate and organic acids), sweeteners, flavors, fillers and possibly added pigments or minerals. In preparation, the vitamin C and the organic acid are mixed according to the prescription, an appropriate amount of organic solvent is added to prepare a soft material, the acid granules are prepared after drying and granulating; the sweeteners, fillers and the like are mixed according to the prescription, and then mixed with sodium bicarbonate solution to prepare a soft material, the base granules are prepared after drying and granulating; the acid granules and the base granules are mixed, and the prescribed amount of essence, micronized silica gel and the like are added, mixed and pressed into tablets to prepare the vitamin C effervescent tablets.

[0004] Therefore, in the preparation process of the vitamin C effervescent tablets, the acid granules and the base granules need to be granulated respectively, and then other raw materials are mixed, so as to reduce the possibility of early contact and reaction of the acid and the base, and finally the vitamin C effervescent tablets are prepared. However, a large amount of time is consumed, and the production efficiency is adversely affected. SUMMARY

[0005] In order to improve the production efficiency, the application provides a vitamin C effervescent tablet and a preparation method thereof.

[0006] In a first aspect, the application provides a preparation method of a vitamin C effervescent tablet, which adopts the following technical scheme: A preparation method of a vitamin C effervescent tablet, comprising the following steps: S1, raw material pretreatment: 30±1 parts by weight of vitamin C granules, 20±1 parts by weight of tartaric acid granules 80 mesh, 50±1 parts by weight of sucrose granules 40 mesh, 4±1 parts by weight of sodium chloride granules, 2±1 parts by weight of saccharin sodium granules 60 mesh, 30±1 parts by weight of sodium bicarbonate powder 40 mesh are crushed; 1-2 parts by weight of crushed sucrose granules are used to prepare a 40±1% sucrose solution with purified water; S2, premix granulation: 20-23 parts by weight of the vitamin C powder prepared in S1, 15-20 parts by weight of the tartaric acid granules prepared in S1 are mixed at a stirring speed of 300±1 rpm and a cutter speed of 60±1 rpm for 5±1 min, 3±0.1 parts by weight of the sucrose solution prepared in S1 is added, and granulation is performed at a stirring speed of 300±1 rpm and a cutter speed of 1250±1 rpm for 5±1 min to prepare 16-mesh premix granules; S3, drying and sizing: the premix granules prepared in S2 are dried at an inlet air temperature of 65±1℃ until the moisture content of the premix granules is less than 0.5%, and the dried granules are sized to prepare dry granules; S4, total mixing: 0-0.5 parts by weight of the flavor, 0.4-0.6 parts by weight of the pigment, 1-3 parts by weight of the sodium chloride granules, and 0.2-0.6 parts by weight of the sodium saccharin granules are mixed for 3±1 min, and then 30-40 parts by weight of the sucrose granules prepared in S1, 20-24 parts by weight of the sodium bicarbonate powder, and the dry granules prepared in S3 are mixed at 8±1 rpm for 15±1 min to prepare a total mixture; S5, tabletting: the total mixture prepared in S4 is tabletted using a φ25 mm steel flat punch according to a specification of (4.6±0.1) g / tablet to prepare vitamin C effervescent tablets.

[0007] By using the above technical solution, the vitamin C powder, the tartaric acid powder, and the sucrose solution are first mixed and dried to prepare dry granules of the acid, and then the flavor, the pigment, the sodium chloride, the sodium saccharin, the sucrose granules, the sodium bicarbonate powder, and the dry granules of the acid are mixed to prepare vitamin C effervescent tablets, thereby reducing the step of preparing dry granules of the base, improving the production efficiency, and first pre-milling the raw materials before preparing the vitamin C effervescent tablets, so that the particle sizes of the raw material granules are similar, thereby improving the flowability of the raw material granules, facilitating the mixing and tabletting of the raw materials, and further improving the production efficiency.

[0008] Preferably, in S1, the weight ratio of the sucrose granules having a particle size of 40 mesh-80 mesh to the sucrose granules having a particle size of <80 mesh in the sieved sucrose granules is (30-40):(60-70).

[0009] By adopting the technical scheme, when the particle size of the sucrose particles is controlled to be in the above range during the crushing, the sucrose particles have a similar particle size to the other raw material particles, so that the mixing with the other raw materials is facilitated, the mixing efficiency is improved, and when the tablet is pressed, the sucrose particles with a particle size of less than 80 microns fill the pores between the raw material particles, the compressibility is improved, and the possibility of loosening of the prepared vitamin C effervescent tablets during packaging and transportation is reduced; when the particle size of the sucrose particles with a particle size of 40-80 microns exceeds the above range, the sucrose particles filling the pores between the raw material particles are reduced, and the prepared vitamin C effervescent tablets are prone to be loosened during packaging and transportation, affecting the quality of the prepared vitamin C effervescent tablets; when the particle size of the sucrose particles with a particle size of less than 80 microns exceeds the above range, the large-particle-size sucrose particles are reduced, and the small-particle-size sucrose particles are increased, so that the small-particle-size sucrose particles are prone to agglomerate during the mixing of the raw materials, further affecting the production efficiency.

[0010] Preferably, in S5, the magnesium stearate is sprayed onto the steel flat punch at an atomization pressure of 0.13±0.01 MPa when the tablet is pressed, and the content of magnesium stearate in the prepared vitamin C effervescent tablets is negligible.

[0011] By adopting the technical scheme, the lubricant magnesium stearate is sprayed onto the steel flat punch, so that the tablet pressing adhesion is reduced, the additional magnesium stearate makes the content of magnesium stearate in the prepared vitamin C effervescent tablets extremely small and negligible, the possibility of affecting the disintegration of the prepared vitamin C effervescent tablets by adding magnesium stearate to the raw materials is reduced, the disintegration time limit of the prepared vitamin C effervescent tablets is improved, and since magnesium stearate is insoluble in water, the possibility of generating a large amount of floating substances in the prepared vitamin C effervescent tablets during brewing is also reduced, and the compliance of the prepared vitamin C effervescent tablets is improved.

[0012] Preferably, the method for preparing vitamin C effervescent tablets comprises the following steps: S1, raw material pretreatment: 30±1 parts by weight of vitamin C particles, 20±1 parts by weight of tartaric acid particles 80 mesh, 50±1 parts by weight of sucrose particles 40 mesh, 4±1 parts by weight of sodium chloride particles, 2±1 parts by weight of saccharin sodium particles 60 mesh, 30±1 parts by weight of sodium bicarbonate powder 40 mesh; 1-2 parts by weight of the crushed sucrose particles are used to prepare a 40±1% sucrose solution with purified water; S2, pre-mixed granulation: 20-23 parts by weight of the vitamin C powder prepared in S1, 15-20 parts by weight of the tartaric acid particles prepared in S1 are weighed and mixed at a stirring speed of 300±1 rpm and a cutter speed of 60±1 rpm for 5±1 min, 3±0.1 parts by weight of the sucrose solution prepared in S1 is added, and mixed at a stirring speed of 300±1 rpm and a cutter speed of 1250±1 rpm for 5±1 min to prepare 16 mesh pre-mixed particles; S3, drying and granulating: drying the premixed granules prepared in S2 at an air inlet temperature of 65±1℃ until the moisture content of the premixed granules is less than 0.5%, and then granulating to obtain dry granules; S4, coating and compounding disintegrants: uniformly mixing 0.4-0.6 parts by weight of compounded disintegrants with the dry granules prepared in S3 to obtain mixed granules, wherein the compounded disintegrants are prepared by mixing modified sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose at a weight ratio of (1-3):1; S5, total mixing: mixing 0-0.5 parts by weight of essence, 0.4-0.6 parts by weight of pigment, 1-3 parts by weight of sodium chloride granules and 0.2-0.6 parts by weight of sodium saccharin granules for 3±1 min, and then adding 30-40 parts by weight of sucrose granules prepared in S1, 20-24 parts by weight of sodium bicarbonate powder and the mixed granules prepared in S4 to a mixer and mixing at 8±1 rpm for 15±1 min to obtain a total mixture; S6, tabletting: tabletting the total mixture prepared in S5 according to a specification of (4.6±0.1) g / tablet using a φ25 mm steel flat punch to obtain Vitamin C effervescent tablets.

[0013] By using the above technical scheme, in the process of preparing the Vitamin C effervescent tablets, the acid granules are first prepared by mixing, drying and granulating the Vitamin C powder, the tartaric acid granules and the sucrose solution, the compounded disintegrants are coated on the outside of the prepared acid granules, and then the essence, the pigment, the sodium chloride, the sodium saccharin, the sucrose granules, the sodium bicarbonate powder and the acid granules coated with the compounded disintegrants are mixed to obtain the Vitamin C effervescent tablets. At this time, the compounded disintegrants are located between the acid granules and other raw material granules, which reduces the possibility of contact between the acid granules and the sodium bicarbonate, and the compounded disintegrants swell by absorbing water during the brewing process, thereby facilitating the rapid disintegration of the prepared Vitamin C effervescent tablets, and further facilitating the rapid mixing and disintegration of the acid granules and the sodium bicarbonate granules, and further improving the disintegration rate. Since the modified sodium carboxymethyl cellulose mainly destroys the structure of the prepared Vitamin C effervescent tablets by swelling through water absorption, and the low-substituted hydroxypropyl cellulose mainly assists the water penetration through capillary action, when the amount of the modified sodium carboxymethyl cellulose exceeds the above range, it is easy to cause the disintegration dominated by swelling to be hindered by the possibility of too thick gel layer to hinder water diffusion, and the possibility of mechanical interlocking between particles to be enhanced due to the cross-linked structure of the modified sodium carboxymethyl cellulose during tabletting, which may cause the prepared Vitamin C effervescent tablets to have too high hardness, and further delay the dissolution of Vitamin C and prolong the disintegration time. When the low-substituted hydroxypropyl cellulose exceeds the above range, it is easy to cause the possibility of prolonged disintegration time due to the lack of sufficient swelling force dominated by the modified sodium carboxymethyl cellulose, and the possibility of reduced hardness of the prepared Vitamin C effervescent tablets due to the weak adhesion of the low-substituted hydroxypropyl cellulose, which further affects the stability of transportation.

[0014] Preferably, in the S4, the modified sodium carboxymethyl cellulose is prepared by cross-linking carboxymethyl chitosan and sodium carboxymethyl cellulose in a weight ratio of 1: (1-3).

[0015] By adopting the above technical solution, the carboxymethyl chitosan and the sodium carboxymethyl cellulose are cross-linked to form the modified sodium carboxymethyl cellulose with a three-dimensional cross-linked network by the above-mentioned ratio, so as to facilitate rapid swelling during brewing of the vitamin C effervescent tablet, accelerate the disintegration of the vitamin C effervescent tablet through capillary action, and further shorten the disintegration time. The cross-linked structure can maintain the physical stability of the prepared vitamin C effervescent tablet during storage, and reduce the possibility of premature disintegration caused by moisture absorption or pressure change. When the addition amount of carboxymethyl chitosan exceeds the above-mentioned range, it is easy to increase the cross-linking density, so that the grid structure is too tight, which delays the swelling and disintegration speed of the prepared vitamin C effervescent tablet after water, and at the same time limits the diffusion of carbon dioxide gas generated by disintegration, which affects the foaming effect of the prepared vitamin C effervescent tablet. Carboxymethyl chitosan itself has a slight astringent taste and strong hydrophilicity, and excessive amount can affect the taste of the prepared vitamin C effervescent tablet, and can easily cause the prepared vitamin C effervescent tablet to absorb moisture during storage, reducing the stability. Since the sodium carboxymethyl cellulose has high water absorption, when the sodium carboxymethyl cellulose exceeds the above-mentioned range, it is easy to accelerate the disintegration of the prepared vitamin C effervescent tablet, but it is easy to cause the possibility of uneven disintegration, and excessive sodium carboxymethyl cellulose can weaken the mechanical strength of the cross-linked network, and further cause the possibility of fragmentation of the prepared vitamin C effervescent tablet during storage or transportation.

[0016] Preferably, the preparation method of the modified sodium carboxymethyl cellulose is as follows: A1, adding carboxymethyl cellulose powder into a mixed solvent of isopropyl alcohol and water in a volume ratio of 3±0.1:1, dissolving, adding 30±1% sodium hydroxide solution at 30-50℃ to adjust pH to 10-11, and preparing a mixed solution; A2, adding carboxymethyl chitosan to the mixed solution prepared in A1, slowly adding chloroacetic acid, the molar ratio of chloroacetic acid to carboxymethyl chitosan being (1.5±0.1):1, and reacting at 50±1℃ for 3-5h, adjusting pH to 6.5-7.0 with glacial acetic acid, and preparing a cross-linked product; A3, washing the cross-linked product prepared in A2 with 70±1% ethanol solution, vacuum drying at 60±1℃, and preparing the modified sodium carboxymethyl cellulose after crushing.

[0017] By adopting the technical scheme, the chloroacetic acid is selected as a grafting agent to cross-link the carboxymethyl chitosan and sodium carboxymethyl cellulose, and impurities are removed through washing and drying, so that the modified sodium carboxymethyl cellulose with a three-dimensional cross-linked network is prepared, which is convenient for swelling rapidly when the vitamin C effervescent tablet is brewed, accelerates the disintegration of the vitamin C effervescent tablet through capillary action, and further shortens the disintegration time, while maintaining the physical stability of the prepared vitamin C effervescent tablet during storage, and reducing the possibility of premature disintegration caused by moisture absorption or pressure change.

[0018] Preferably, the modified sodium carboxymethyl cellulose is 70±10 mesh.

[0019] By adopting the technical scheme, the modified sodium carboxymethyl cellulose in the above particle size range is selected, which is parallel to the specific surface area and the swelling speed, is convenient for swelling rapidly after meeting water, and promotes the penetration of moisture through capillary action, accelerates the disintegration of the prepared vitamin C effervescent tablet, and the modified sodium carboxymethyl cellulose in this range is similar to other raw material particles, has moderate flowability and specific surface area, reduces the risk of moisture absorption, prolongs the storage stability, is convenient for cooperation with sodium bicarbonate powder and tartaric acid particles, and improves the disintegration speed. When the modified sodium carboxymethyl cellulose is greater than the above particle size range, it is easy to cause the possibility of reducing the water absorption and swelling speed due to the reduction of the specific surface area, and further prolong the disintegration time of the prepared vitamin C effervescent tablet, and the pore structure on the surface of the modified sodium carboxymethyl cellulose is more sparse, the moisture penetration efficiency is reduced, and further affects the synergistic effect with sodium bicarbonate powder and tartaric acid particles, the flowability is reduced, the tablet weight difference or the possibility of tablet cracking is easy to occur during tabletting, and the prepared vitamin C effervescent tablet is easy to cause the possibility of premature disintegration failure during storage. When the modified sodium carboxymethyl cellulose is less than the above particle size range, the specific surface area is increased, which is easy to cause the possibility of increasing the moisture absorption, and further causes the prepared vitamin C effervescent tablet to be invalid due to premature reaction, and the modified sodium carboxymethyl cellulose is too fine, which may cause the flowability to be reduced due to electrostatic adsorption, affects the uniformity of tabletting, and further affects the production efficiency.

[0020] In the second aspect, the application provides a vitamin C effervescent tablet, which adopts the following technical scheme: A vitamin C effervescent tablet is prepared by the preparation method of the vitamin C effervescent tablet.

[0021] By adopting the technical scheme, the vitamin C effervescent tablet prepared by the preparation method of the application improves the disintegration time limit and the stability during storage, improves the situation that a large amount of floating substances are generated during brewing, and further improves the compliance, shortens the production time during preparation, and improves the production efficiency.

[0022] In summary, the application has the following beneficial effects: 1. First, vitamin C powder, tartaric acid powder, and sucrose solution are mixed and dried to obtain dried acid granules. Then, flavoring, pigment, sodium chloride, sodium saccharin, sucrose granules, sodium bicarbonate powder, and the obtained dried acid granules are mixed to obtain vitamin C effervescent tablets. This reduces the steps of preparing dried alkali granules, improves production efficiency, and pre-crushes the raw materials before preparing vitamin C effervescent tablets to make the particle size of the raw materials similar, thereby improving the flowability of the raw material particles, facilitating the mixing and tableting of the raw materials, and further improving production efficiency.

[0023] 2. Spraying magnesium stearate as a lubricant onto the steel flat punch reduces tablet sticking. The external addition of magnesium stearate results in a negligible amount of magnesium stearate in the prepared vitamin C effervescent tablets, reducing the possibility of magnesium stearate affecting the disintegration of the prepared vitamin C effervescent tablets and thus improving the disintegration time of the prepared vitamin C effervescent tablets. Furthermore, since magnesium stearate is insoluble in water, it also reduces the possibility of a large amount of floating matter being generated during the preparation of the prepared vitamin C effervescent tablets, improving the compliance of the prepared vitamin C effervescent tablets.

[0024] 3. Acid granules are prepared by mixing, drying, and granulating vitamin C powder, tartaric acid granules, and sucrose solution. A compound disintegrant is then coated on the outside of the acid granules. Flavoring, coloring, sodium chloride, sodium saccharin, sucrose granules, sodium bicarbonate powder, and the acid granules coated with the compound disintegrant are then mixed with the acid granules to prepare vitamin C effervescent tablets. At this point, the compound disintegrant is located between the acid granules and other raw material granules, reducing the possibility of contact between the acid granules and sodium bicarbonate. During the brewing process, the compound disintegrant absorbs water and expands, thereby facilitating the rapid disintegration of the prepared vitamin C effervescent tablets. This, in turn, facilitates the rapid mixing and disintegration of the acid granules and sodium bicarbonate granules, further improving the disintegration rate. Detailed Implementation

[0025] The present application will be further described in detail below with reference to the embodiments.

[0026] The methods for testing the production time, disintegration time, and hardness of the vitamin C effervescent tablets prepared in all embodiments and comparative examples are as follows: 1. Production time Vitamin C effervescent tablets of the same total mass were prepared according to the same preparation method. Five batches were prepared using the same preparation method. The production time of each batch of vitamin C effervescent tablets was recorded and the average value was calculated.

[0027] 2. Disintegration time limit The method for testing the disintegration time of vitamin C effervescent tablets using a disintegration analyzer is as follows: 1) Testing Standards and Instruments According to the 2020 edition of the Chinese Pharmacopoeia, the disintegration time of effervescent tablets should be ≤5 minutes.

[0028] Use the lifting disintegrator (including basket, screen and baffle), the medium is purified water at 15±1℃, the volume is 100ml.

[0029] 2) Operating steps Sample preparation: 6 tablets of each example and control sample were taken and equilibrated at 20±2℃ and 65±5% humidity for 24 hours.

[0030] Instrument settings: Adjust the basket so that the screen is 25mm from the bottom of the beaker, and when raised to the highest point, the screen is ≥15mm from the liquid surface.

[0031] The water temperature is constant at 15±1℃, the lifting frequency is 30-32 times / min, and the stroke is 55±2mm.

[0032] Detection process: Place the effervescent tablets in the 6 baskets respectively, start the disintegrator and time.

[0033] Observe whether the tablets disintegrate rapidly (release bubbles) and disperse completely, and observe whether there are floating objects, record the disintegration time of each tablet and calculate the average value.

[0034] 3) Results All 6 tablets must disintegrate completely within 5 minutes, if 1 tablet is unqualified, it is directly judged as unqualified (no retest).

[0035] If adhesion to the baffle occurs, take another 6 tablets without the baffle for retesting.

[0036] 3. Hardness The specific method for detecting the hardness of vitamin C effervescent tablets by tablet hardness tester is as follows: 1) Detection standards and instruments According to the detection standards of Chinese Pharmacopoeia 0941 and GB / T 20104-2022 Tablets Hardness Tester, use the tablet hardness tester, the range is usually 10-500N, and the resolution is up to ±0.1N.

[0037] 2) Operating steps Sample preparation: 10 tablets of each example and control sample were taken and equilibrated at 20±2℃ and 65±5% humidity for 24 hours.

[0038] Calibration of the instrument: after turning on the machine, use the standard weight to calibrate the sensor to ensure that the zero error is ≤0.2%.

[0039] Test process: Place the effervescent tablets vertically between the two pressure plates and press radially to break them.

[0040] The peak pressure value (i.e. hardness) was recorded, and 10 tablets were tested repeatedly to obtain an average value. Raw materials

[0041] The raw materials in the examples and comparative examples of the present application can be commercially available. Among them, the carboxymethyl chitosan is food-grade carboxymethyl chitosan, and the carboxymethyl cellulose is a food-grade raw material with a degree of substitution ≥0.8 and a purity ≥99%.

[0042] The present application is based on a theoretical tablet weight of 4.6 g / tablet, and 100,000 tablets are counted. Preparation Example

[0043] Preparation Example 1 Modified sodium carboxymethyl cellulose Preparation Example 1.1 A modified sodium carboxymethyl cellulose is prepared by the following steps: A1, 1.5 kg of carboxymethyl cellulose sodium powder is dissolved in 8.93 L of isopropanol-water mixed solvent with a volume ratio of 3:1, 30% sodium hydroxide solution is added at 30°C to adjust the pH to 10, and a mixed solution is prepared; A2, 1.5 kg of carboxymethyl chitosan is added to the mixed solution prepared in A1, 4.2 kg of chloroacetic acid is slowly added, and the reaction is carried out at 50°C for 3h, and the pH is adjusted to 6.5 with glacial acetic acid to prepare a cross-linked product; A3, the cross-linked product prepared in A2 is washed with 70% ethanol solution, vacuum dried at 60°C, and after crushing, a modified sodium carboxymethyl cellulose with a mesh of 70 is prepared.

[0044] Preparation Example 1.2 Different from Preparation Example 1.1, the addition amount of carboxymethyl chitosan in Preparation Example 1.2 is 1 kg, and the addition amount of carboxymethyl cellulose sodium powder is 2 kg.

[0045] Preparation Example 1.3 Different from Preparation Example 1.1, the addition amount of carboxymethyl chitosan in Preparation Example 1.3 is 0.75 kg, and the addition amount of carboxymethyl cellulose sodium powder is 2.25 kg.

[0046] Preparation Example 1.4 Different from Preparation Example 1.1, the addition temperature of 30% sodium hydroxide solution in Preparation Example 1.4 is 40°C, and the reaction time of adding chloroacetic acid in A2 is 4h.

[0047] Preparation Example 1.5 Different from Preparation Example 1.1, the addition temperature of 30% sodium hydroxide solution in Preparation Example 1.5 is 50°C, and the reaction time of adding chloroacetic acid in A2 is 5h.

[0048] Preparation Example 2 Compound disintegrant Preparation Example 2.1 A compound disintegrant was prepared by mixing 1.5 kg of the modified sodium carboxymethyl cellulose prepared in Preparation Example 1.1 with 1.5 kg of low-substituted hydroxypropyl cellulose.

[0049] Preparation Example 2.2 Preparation Example 2.2 was different from Preparation Example 2.1 in that the amount of the modified sodium carboxymethyl cellulose prepared in Preparation Example 1.1 added was 2 kg and the amount of low-substituted hydroxypropyl cellulose added was 1 kg.

[0050] Preparation Example 2.3 Preparation Example 2.3 was different from Preparation Example 2.1 in that the amount of the modified sodium carboxymethyl cellulose prepared in Preparation Example 1.1 added was 2.25 kg and the amount of low-substituted hydroxypropyl cellulose added was 0.75 kg.

[0051] Preparation Example 2.4 Preparation Example 2.4 was different from Preparation Example 2.1 in that the modified sodium carboxymethyl cellulose prepared in Preparation Example 1.1 was replaced with an equal amount of sodium carboxymethyl cellulose.

[0052] Preparation Examples 2.5-2.8 Preparation Examples 2.5-2.8 were different from Preparation Example 2.2 in that the modified sodium carboxymethyl cellulose was replaced with an equal amount of the modified sodium carboxymethyl cellulose prepared in Preparation Examples 1.2-1.5, respectively.

[0053] Example Example 1 without compound disintegrant Example 1.1 A vitamin C effervescent tablet was prepared by the following steps: S1, raw material pretreatment: 138 kg of vitamin C granules, 92 kg of tartaric acid granules 80 mesh, 230 kg of sucrose granules 40 mesh, the prepared sucrose granules were prepared by mixing sucrose granules with a particle size of 40-80 μm and sucrose granules with a particle size of <80 μm at a weight ratio of 3:7, 23 kg of sodium chloride granules, 13.8 kg of saccharin sodium granules 60 mesh, 138 kg of sodium bicarbonate powder 40 mesh; 4.6 kg of the crushed sucrose granules were mixed with purified water to prepare a 40% sucrose solution; S2, pre-mixing granulation: 92 kg of vitamin C powder prepared in S1, 92 kg of tartaric acid granules prepared in S1 were weighed and mixed at a stirring speed of 300 rpm and a cutter speed of 60 rpm for 5 min, 11.5 kg of the prepared sucrose solution was added, and mixed at a stirring speed of 300 rpm and a cutter speed of 1250 rpm for 5 min, then granulated to prepare 16 mesh pre-mixed granules; S3, drying and granulating: the pre-mixed granules prepared in S2 were dried at an inlet air temperature of 65°C until the moisture content of the pre-mixed granules was <0.5%, and then granulated to prepare dried granules; S4, total mixing: 2.3 kg of essence, 1.84 kg of pigment, 13.8 kg of sodium chloride particles and 0.92 kg of sodium saccharin particles were mixed for 3 min, then 184 kg of sucrose particles prepared in S1, 92 kg of sodium bicarbonate powder and dry particles prepared in S3 were added and mixed for 15 min at 8 rpm to prepare a total mixed material; S5, tabletting: the total mixed material prepared in S4 was tabletted using a φ25 mm steel flat punch according to a specification of 4.6 g / tablet, magnesium stearate was sprayed to the steel flat punch at an atomization pressure of 0.13 MPa, and the content of magnesium stearate in the prepared vitamin C effervescent tablet was negligible, thereby preparing a vitamin C effervescent tablet.

[0054] Examples 1.2-1.3 Different from Example 1.1, the ratio of raw materials in Examples 1.2-1.3 was different, as shown in Table 1.

[0055] Table 1. Raw material ratio of Examples 1.1-1.3

[0056] Example 1.4 Different from Example 1.1, the sucrose particles prepared in S1 in Example 1.4 were all prepared by mixing sucrose particles with a particle size of 40-80 mesh and sucrose particles with a particle size of <80 mesh at a weight ratio of 7:13.

[0057] Example 1.5 Different from Example 1.1, the sucrose particles prepared in S1 in Example 1.5 were all prepared by mixing sucrose particles with a particle size of 40-80 mesh and sucrose particles with a particle size of <80 mesh at a weight ratio of 2:3.

[0058] Comparative Example 1 A vitamin C effervescent tablet was prepared by the following steps: 1) Preparation of acid particles: 189.4 kg of 80 mesh vitamin C and 37.9 kg of 80 mesh citric acid were weighed according to the prescription, mixed uniformly, added with 47.35 ml of 5% PVP-k30 anhydrous ethanol solution to prepare a soft material, granulated with a 16 mesh nylon screen, dried at 50°C, and sized with a 14 mesh nylon screen.

[0059] 2) Preparation of base particles: 71.9 kg of 60 mesh lactose, 22.7 kg of 60 mesh sorbitol and 5.68 kg of 60 mesh sodium saccharin were mixed uniformly, 71.9 kg of 40 mesh sodium bicarbonate was first added with 20.5 ml of 5% PVP-k30 anhydrous ethanol solution, then mixed with the mixture of lactose, sorbitol and sodium saccharin to prepare a soft material, granulated with a 16 mesh nylon screen, dried at 45°C, and sized with a 14 mesh nylon screen.

[0060] 3) mixing and tabletting: the prepared acid granules and base granules were combined, 1.9 kg of powder essence, 5.68 kg of fine silica gel and 5.68 kg of PEG6000 were added, and the mixture was mixed uniformly. The total mixture prepared in S4 was tabletted using a φ25 mm steel punch according to a specification of 4.6 g / tablet to prepare the Vitamin C effervescent tablets.

[0061] Comparative Example 2 A kind of Vitamin C effervescent tablets, prepared by the following steps: S1, raw material pretreatment: 138 kg of Vitamin C granules, 92 kg of tartaric acid granules 80 mesh were crushed, 230 kg of sucrose granules 40 mesh were crushed, the prepared sucrose granules were prepared by mixing sucrose granules with a particle size of 40-80 mesh and sucrose granules with a particle size of <80 mesh in a weight ratio of 3:7, 23 kg of sodium chloride granules, 13.8 kg of sodium saccharin granules 60 mesh were crushed, 138 kg of sodium bicarbonate powder 40 mesh was crushed; 4.6 kg of crushed sucrose granules were prepared into 40% sucrose solution with purified water; S2, pre-mixed granulation: 92 kg of Vitamin C powder prepared in S1 and 92 kg of tartaric acid granules prepared in S1 were mixed at a stirring speed of 300 rpm and a cutter speed of 60 rpm for 5 min, 11.5 kg of prepared sucrose solution was added, and the mixture was granulated at a stirring speed of 300 rpm and a cutter speed of 1250 rpm for 5 min to prepare 16 mesh pre-mixed granules; S3, drying and granulating: the pre-mixed granules prepared in S2 were dried at an inlet air temperature of 65°C until the moisture content of the pre-mixed granules was <0.5%, and then the dried granules were prepared by granulating; S4, total mixing: 2.3 kg of essence, 1.84 kg of pigment, 13.8 kg of sodium chloride granules and 0.92 kg of sodium saccharin granules were mixed for 3 min, then 184 kg of sucrose granules prepared in S1, 92 kg of sodium bicarbonate powder and the dried granules prepared in S3 were added and mixed at 8 rpm for 15 min to prepare the total mixture; S5, tabletting: 0.75 kg of magnesium stearate was added to the total mixture prepared in S4 and mixed uniformly, and then the total mixture prepared in S4 was tabletted using a φ25 mm steel punch according to a specification of 4.6 g / tablet to prepare the Vitamin C effervescent tablets.

[0062] In the production of Vitamin C in Example 1 and Comparative Examples 1-2, whether there were residual drug powder on the surface of the steel punch or whether the edges of the tablets were rough were observed and recorded. The production time, disintegration time and hardness of the Vitamin C effervescent tablets prepared in Example 1 and Comparative Examples 1-2 were detected, as shown in Table 2.

[0063] Table 2 Performance detection data table of Example 1 and Comparative Examples 1-2

[0064] In combination with Table 2, it can be seen that the Vc effervescent tablets prepared in Examples 1.1-1.5 are superior to the Vc effervescent tablets prepared in Comparative Example 1 in terms of production time, presence of residual powder, roughness of the edges of the tablets, disintegration time and hardness, which can be attributed to the fact that the preparation of the base granules is omitted in Examples 1.1-1.5, thereby improving the production efficiency, and the raw materials are first pre-milled before the preparation of the Vc effervescent tablets, and the particle size distribution of the sucrose granules is controlled, so that the particle size of the sucrose granules is similar to that of the other raw materials, thereby facilitating the mixing of the raw materials and improving the mixing efficiency, and the sucrose granules with a particle size of less than 80 μm fill the pores between the raw material particles, thereby improving the compressibility and reducing the possibility of loosening of the prepared Vc effervescent tablets during packaging and transportation.

[0065] In addition, the Vc effervescent tablets prepared in Examples 1.1-1.5 are superior to the Vc effervescent tablets prepared in Comparative Example 1 in terms of production time, presence of residual powder, roughness of the edges of the tablets, disintegration time and hardness, which can be attributed to the fact that the magnesium stearate is added in the form of magnesium stearate in Examples 1.1-1.5, so that the content of magnesium stearate in the prepared Vc effervescent tablets is extremely small and can be ignored, thereby reducing the possibility of affecting the disintegration of the prepared Vc effervescent tablets due to the addition of magnesium stearate to the raw materials, and further improving the disintegration time of the prepared Vc effervescent tablets, and since magnesium stearate is insoluble in water, the possibility of generating a large amount of floating substances during the brewing process of the prepared Vc effervescent tablets is also reduced, thereby improving the compliance of the prepared Vc effervescent tablets.

[0066] Examples 1.1-1.3 investigate the influence of the raw material ratio, and it is found that the Vc effervescent tablets prepared in Example 1.2 are superior in terms of production time, presence of residual powder, roughness of the edges of the tablets, disintegration time and hardness, which indicates that the raw material ratio selected in Example 1.2 is beneficial to improve the performance of the Vc effervescent tablets in terms of production time, presence of residual powder, roughness of the edges of the tablets, disintegration time and hardness.

[0067] Examples 1.4-1.5 investigate the influence of the particle size distribution of the sucrose granules, with Example 1.2 as a control, and it is found that the Vc effervescent tablets prepared in Example 1.4 are superior in terms of production time, presence of residual powder, roughness of the edges of the tablets, disintegration time and hardness, which indicates that the particle size distribution of the sucrose granules selected in Example 1.4 is beneficial to improve the performance of the Vc effervescent tablets in terms of production time, presence of residual powder, roughness of the edges of the tablets, disintegration time and hardness.

[0068] Example 2 Adding a compounded disintegrant Example 2.1 A Vc effervescent tablet is prepared by the following steps: S1, raw material pretreatment: 138 kg of vitamin C granules, 92 kg of tartaric acid granules 80 mesh, 230 kg of sucrose granules 40 mesh, the prepared sucrose granules were prepared by mixing sucrose granules with a particle size of 40-80 mesh and sucrose granules with a particle size of <80 mesh at a weight ratio of 7:13, 23 kg of sodium chloride granules, 13.8 kg of saccharin sodium granules 60 mesh, 138 kg of sodium bicarbonate powder 40 mesh; 4.6 kg of crushed sucrose granules were prepared into a 40% sucrose solution with purified water; S2, pre-mixed granulation: 100 kg of vitamin C powder prepared in S1, 78.16 kg of tartaric acid granules prepared in S1 were weighed and mixed at a stirring speed of 300 rpm and a cutter speed of 60 rpm for 5 min, 14 kg of prepared sucrose solution was added, and mixed at a stirring speed of 300 rpm and a cutter speed of 1250 rpm for 5 min to prepare granules, and 16 mesh pre-mixed granules were prepared. S3, drying and granulating: the pre-mixed granules prepared in S2 were dried at an inlet air temperature of 65°C until the moisture content of the pre-mixed granules was <0.5%, and the dried granules were prepared by granulating. S4, coating and compounding disintegrating agent: 1.84 kg of the compounded disintegrating agent from Preparation Example 2.1 was uniformly mixed with the dried granules prepared in S3 to prepare mixed granules.

[0069] S5, total mixing: 1.6 kg of flavor, 2.5 kg of pigment, 9 kg of sodium chloride granules and 1.8 kg of saccharin sodium granules were mixed for 3 min, then 159.48 kg of sucrose granules prepared in S1, 100 kg of sodium bicarbonate powder and mixed granules prepared in S4 were added and mixed at 8 rpm for 15 min to prepare the total mixed material; S6, tabletting: the total mixed material prepared in S5 was tabletted using a φ25mm steel flat punch according to a specification of 4.6g / tablet, and magnesium stearate was sprayed onto the steel flat punch at a atomizing pressure of 0.13MPa, and the content of magnesium stearate in the prepared vitamin C effervescent tablets was negligible, and the vitamin C effervescent tablets were prepared.

[0070] Example 2.2 Different from Example 2.1, the addition amount of the compounded disintegrating agent from Preparation Example 2.1 in Example 2.2 was 2.3 kg, and the addition amount of tartaric acid granules in S2 was 77.7 kg.

[0071] Example 2.3 Different from Example 2.1, the addition amount of the compounded disintegrating agent from Preparation Example 2.1 in Example 2.3 was 2.76 kg, and the addition amount of tartaric acid granules in S2 was 77.24 kg.

[0072] Examples 2.4-2.10 Different from example 2.2, the compound disintegrant in examples 2.4-2.10 is equimolar from preparation examples 2.2-2.8, respectively.

[0073] The production time, disintegration time limit and hardness of the vitamin C effervescent tablets prepared in example 2 were detected, and the details are shown in table 3.

[0074] Table 3 Performance detection data table of example 2

[0075] As can be seen from table 2 and table 3, the performances of the vitamin C effervescent tablets prepared in examples 2.1-2.10 in production time, whether there is residual drug powder or whether the edges of the tablets are rough, disintegration time limit and hardness are all better than those of the vitamin C effervescent tablets prepared in example 1.4, which may be due to the fact that the compound disintegrant is added in examples 2.1-2.10, and the compound disintegrant is located between the acid granules and other raw material granules, which reduces the possibility of contact between the acid granules and sodium bicarbonate, and the compound disintegrant swells by absorbing water during the brewing process, thereby facilitating the rapid disintegration of the prepared vitamin C effervescent tablets, and further facilitating the rapid mixing and disintegration of the acid granules and sodium bicarbonate granules.

[0076] Examples 2.1-2.3 investigated the influence of raw material ratio, and the results showed that the performances of the vitamin C effervescent tablets prepared in example 2.2 in production time, whether there is residual drug powder or whether the edges of the tablets are rough, disintegration time limit and hardness are better, which indicates that the raw material ratio selected in example 2.2 is beneficial to improve the performances of the vitamin C effervescent tablets in production time, whether there is residual drug powder or whether the edges of the tablets are rough, disintegration time limit and hardness.

[0077] Examples 2.4-2.5 investigated the influence of compound disintegrant ratio, with example 2.2 as a control, and the results showed that the performances of the vitamin C effervescent tablets prepared in example 2.4 in production time, whether there is residual drug powder or whether the edges of the tablets are rough, disintegration time limit and hardness are better, which indicates that the particle grading of sucrose granules selected in example 2.2 is beneficial to improve the performances of the vitamin C effervescent tablets in production time, whether there is residual drug powder or whether the edges of the tablets are rough, disintegration time limit and hardness.

[0078] Example 2.6 investigated the influence of sodium carboxymethyl cellulose replacing modified sodium carboxymethyl cellulose, with example 2.1 as a control, and the results showed that the performances of the vitamin C effervescent tablets prepared in example 2.1 in production time, whether there is residual drug powder or whether the edges of the tablets are rough, disintegration time limit and hardness are better, which indicates that the compound disintegrant prepared by replacing modified sodium carboxymethyl cellulose with sodium carboxymethyl cellulose in example 2.6 is not good at improving the performances of the vitamin C effervescent tablets in production time, whether there is residual drug powder or whether the edges of the tablets are rough, disintegration time limit and hardness.

[0079] In comparison with Example 2.4, Examples 2.7-2.8 investigated the influence of the raw material ratio of modified sodium carboxymethyl cellulose, and it was found that the Vitamin C effervescent tablets prepared in Example 2.7 had better performance in production time, whether there was residual drug powder or whether the tablet edge was rough, disintegration time limit and hardness, which indicated that the raw material ratio of modified sodium carboxymethyl cellulose selected in Example 2.7 was beneficial to improve the performance of Vitamin C effervescent tablets in production time, whether there was residual drug powder or whether the tablet edge was rough, disintegration time limit and hardness.

[0080] In comparison with Example 2.7, Examples 2.9-2.10 investigated the influence of the process parameters for preparing modified sodium carboxymethyl cellulose, and it was found that the Vitamin C effervescent tablets prepared in Example 2.9 had better performance in production time, whether there was residual drug powder or whether the tablet edge was rough, disintegration time limit and hardness, which indicated that the process parameters for preparing modified sodium carboxymethyl cellulose selected in Example 2.9 were beneficial to improve the performance of Vitamin C effervescent tablets in production time, whether there was residual drug powder or whether the tablet edge was rough, disintegration time limit and hardness.

[0081] The specific embodiments are only an explanation of the present application, which is not a limitation of the present application, and those skilled in the art can make modifications to the embodiments without creative contribution after reading the specification, but as long as it is within the scope of the claims of the present application, it is protected by the patent law.

Claims

1. A process for the preparation of ascorbic acid effervescent tablets, characterized in that, Comprising the following steps: S1, raw material pretreatment: 30±1 parts by weight of vitamin C particles, 20±1 parts by weight of tartaric acid particles 80 mesh, 50±1 parts by weight of sucrose particles 40 mesh, 4±1 parts by weight of sodium chloride particles, 2±1 parts by weight of sodium saccharin particles 60 mesh, 30±1 parts by weight of sodium bicarbonate powder 40 mesh; 1-2 parts by weight of crushed sucrose particles and purified water to prepare 40±1% sucrose solution; S2, pre-mixed granulation: 20-23 parts by weight of S1 prepared vitamin C powder, 15-20 parts by weight of S1 prepared tartaric acid particles were mixed at a stirring speed of 300±1 rpm and a cutter speed of 60±1 rpm for 5±1 min, 3±0.1 parts by weight of S1 prepared sucrose solution was added, and mixed at a stirring speed of 300±1 rpm and a cutter speed of 1250±1 rpm for 5±1 min to granulate, and 16 mesh pre-mixed particles were prepared; S3, drying and granulating: the pre-mixed particles prepared in S2 were dried at an inlet air temperature of 65±1℃ until the moisture content of the pre-mixed particles was less than 0.5%, and then granulated to obtain dry granules; S4, total mixing: 0-0.5 parts by weight of essence, 0.4-0.6 parts by weight of pigment, 1-3 parts by weight of sodium chloride particles and 0.2-0.6 parts by weight of sodium saccharin particles were mixed for 3±1 min, then 30-40 parts by weight of S1 prepared sucrose particles, 20-24 parts by weight of sodium bicarbonate powder and S3 prepared dry granules were mixed at 8±1 rpm for 15±1 min to prepare a total mixed material; S5, tabletting: using φ25mm steel flat punch, the total mixed material prepared in S4 was tabletted according to the specification of (4.6±0.1) g / tablet to prepare vitamin C effervescent tablets.

2. The method of claim 1, wherein the method comprises: In S1, the weight ratio of sucrose particles with a particle size of 40-80 mesh to sucrose particles with a particle size of <80 mesh in the crushed and sieved sucrose particles is (30-40):(60-70).

3. The method for preparing vitamin C effervescent tablets according to claim 2, characterized in that: In S5, magnesium stearate was sprayed onto the steel flat punch at an atomization pressure of 0.13±0.01 MPa during tabletting, and the content of magnesium stearate in the prepared vitamin C effervescent tablets was negligible.

4. The method of claim 3, wherein the Vitamin C effervescent tablet is prepared by the steps of: Comprising the following steps: S1, raw material pretreatment: 30±1 parts by weight of vitamin C particles, 20±1 parts by weight of tartaric acid particles 80 mesh, 50±1 parts by weight of sucrose particles 40 mesh, 4±1 parts by weight of sodium chloride particles, 2±1 parts by weight of sodium saccharin particles 60 mesh, 30±1 parts by weight of sodium bicarbonate powder 40 mesh; 1-2 parts by weight of crushed sucrose particles and purified water to prepare 40±1% sucrose solution; S2, pre-mixed granulation: 20-23 parts by weight of S1 prepared vitamin C powder, 15-20 parts by weight of S1 prepared tartaric acid particles were mixed at a stirring speed of 300±1 rpm and a cutter speed of 60±1 rpm for 5±1 min, 3±0.1 parts by weight of S1 prepared sucrose solution was added, and mixed at a stirring speed of 300±1 rpm and a cutter speed of 1250±1 rpm for 5±1 min to granulate, and 16 mesh pre-mixed particles were prepared; S3, drying and granulating: drying the premixed granules prepared in S2 at an inlet air temperature of 65±1℃ until the moisture content of the premixed granules is less than 0.5%, and then granulating to obtain dried granules; S4, coating and mixing disintegrating agents: uniformly mixing 0.4-0.6 parts by weight of mixed disintegrating agents with the dried granules prepared in S3 to obtain mixed granules, wherein the mixed disintegrating agents are prepared by mixing modified sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose at a weight ratio of (1-3):1; S5, total mixing: mixing 0-0.5 parts by weight of essence, 0.4-0.6 parts by weight of pigment, 1-3 parts by weight of sodium chloride granules and 0.2-0.6 parts by weight of sodium saccharin granules for 3±1min, then adding 30-40 parts by weight of sucrose granules prepared in S1, 20-24 parts by weight of sodium bicarbonate powder and the mixed granules prepared in S4, and mixing at 8±1rpm for 15±1min to obtain a total mixture; S6, tabletting: tabletting the total mixture prepared in S5 using a φ25mm steel flat punch according to a specification of (4.6±0.1)g / tablet to obtain the Vitamin C effervescent tablets.

5. The method of claim 4, wherein the method further comprises: In S4, the modified sodium carboxymethyl cellulose is prepared by cross-linking carboxymethyl chitosan and sodium carboxymethyl cellulose at a weight ratio of 1:(1-3). ​ 6. The method of claim 5, wherein the method further comprises: The preparation method of the modified sodium carboxymethyl cellulose is as follows: ​ A1, adding sodium carboxymethyl cellulose powder into a mixed solvent of isopropyl alcohol and water at a volume ratio of 3±0.1:1, dissolving, adding 30±1% sodium hydroxide solution at 30-50℃ to adjust the pH to 10-11 to obtain a mixed solution; A2, adding carboxymethyl chitosan into the mixed solution prepared in A1, slowly adding chloroacetic acid at a molar ratio of (1.5±0.1):1, and reacting at 50±1℃ for 3-5h, and adjusting the pH to 6.5-7.0 with glacial acetic acid to obtain a cross-linked product; A3, washing the cross-linked product prepared in A2 with 70±1% ethanol solution, vacuum drying at 60±1℃, and then crushing to obtain the modified sodium carboxymethyl cellulose.

7. The method of claim 6, wherein the method further comprises: The modified sodium carboxymethyl cellulose is 70±10 mesh. ​ 8. A C-vitamin effervescent tablet, characterized in that: The Vitamin C effervescent tablets are prepared by the preparation method of any one of claims 1-7.

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