A method for preparing a vitamin C tablet

Abstract

The application discloses a preparation method of vitamin C tablets and belongs to the technical field of vitamin C tablets. The method comprises the following steps: dissolving vitamin C in sterile water, adding mesoporous silicon dioxide, stirring at room temperature, centrifuging, drying the precipitate, and obtaining mesoporous silicon dioxide microspheres loaded with vitamin C; placing the mesoporous silicon dioxide microspheres loaded with vitamin C in a rotating drum and preheating to 70-75 DEG C, spraying a chitosan film-forming solution on the surface of the mesoporous silicon dioxide microspheres loaded with vitamin C by using an airbrush, drying the obtained product at 90 DEG C to constant weight, and obtaining a core product; preparing the following weight parts of raw materials: 300-500 parts of the core product, 50-100 parts of mannitol, 10-15 parts of starch, and 3-12 parts of magnesium stearate; mixing and compressing the raw materials to obtain the vitamin C tablets. The preparation method of the vitamin C tablets is simple, and the obtained vitamin C tablets have high stability.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of vitamin C tablets, and particularly relates to a preparation method of a vitamin C tablet. BACKGROUND

[0002] Vitamin C, also known as ascorbic acid, is a water-soluble vitamin, and is commonly used for treating vitamin C deficiency in clinical practice. Vitamin C is also an auxiliary treatment drug for various diseases. Vitamin C tablets are convenient to take and have a wide audience, and thus are widely used in clinical practice. Unfortunately, vitamin C is susceptible to light, humidity and temperature, and problems such as discoloration and content reduction occur. Therefore, how to improve the stability of vitamin C tablets is a current research hotspot.

[0003] Chinese patent CN102614143A discloses a high-stability vitamin C tablet and a preparation process. The vitamin C tablet is composed of vitamin C, starch, dextrin, citric acid, disodium edetate, 6% starch paste, talc, compressible starch and magnesium stearate according to weight percentage. Although the vitamin C tablet obtained by the patent has certain stability, it still has problems such as poor heat resistance, high hydrophilicity and susceptibility to metal ions, and also has instability factors. SUMMARY

[0004] The application aims to provide a preparation method of a vitamin C tablet to solve the problem of poor stability of existing vitamin C tablets.

[0005] The object of the application can be achieved by the following technical scheme.

[0006] A preparation method of a vitamin C tablet comprises the following steps:

[0007] In the first step, vitamin C is dissolved in sterile water, and mesoporous silica is added. After stirring at room temperature for 2-3 min, centrifugation is performed at 8000-10000 r / min for 10 min. The precipitate is dried to obtain mesoporous silica microspheres loaded with vitamin C.

[0008] In the second step, the mesoporous silica microspheres loaded with vitamin C are placed in a rotating drum and preheated to 70-75 DEG C. The surface of the mesoporous silica microspheres loaded with vitamin C is sprayed with a chitosan film-forming solution at a rotating speed of 100-300 r / min by using a spray gun. The obtained product is dried at 90 DEG C to constant weight to obtain a core product.

[0009] In the third step, the following raw materials are prepared: 300-500 parts of the core product, 50-100 parts of mannitol, 10-15 parts of starch and 3-12 parts of magnesium stearate.

[0010] Fourth step, the starch is dried at 100-120℃ to moisture content ≤2%, the core product and mannitol are screened through 12-20 mesh sieve and mixed with the starch, magnesium stearate is added and mixed for 15-30min, and then the tablet is pressed.

[0011] As a further technical scheme of the present application, the dosage ratio of vitamin C, sterile water and mesoporous silica in the first step is 4-5g:10-20mL:1-2g.

[0012] As a further technical scheme of the present application, the mass ratio of the mesoporous silica microspheres loaded with vitamin C and the chitosan film-forming solution in the second step is 100:5-10.

[0013] As a further technical scheme of the present application, the chitosan film-forming solution is prepared by the following steps:

[0014] The modified chitosan is added into an acetic acid solution with a volume fraction of 0.5-2%, and is stirred by magnetic force for 20-30min, and then a glutaraldehyde aqueous solution is added, and is stirred at room temperature for 10-20min, wherein the dosage ratio of the modified chitosan, the acetic acid solution and the glutaraldehyde aqueous solution is 2-5g:80-100mL:0.06-0.15mL, and the mass fraction of the glutaraldehyde aqueous solution is 50%.

[0015] As a further technical scheme of the present application, the modified chitosan is prepared by the following steps:

[0016] S1, vanillin is dissolved in anhydrous ethanol, and is heated to 70℃ under stirring, and then an ethylenediamine anhydrous ethanol solution is added dropwise, and after the dropwise addition is completed, constant temperature stirring reaction is carried out for 2h, and then standing and cooling to room temperature are carried out, and then vacuum filtration is carried out, and then the filter cake is washed with anhydrous ethanol for 3-4 times, and then vacuum drying is carried out, to obtain an amino-terminated vanillin Schiff base;

[0017] S2, n-octyl succinic anhydride and benzene are added into a flask, and then the amino-terminated vanillin Schiff base is added, and then heating to 110℃ is carried out, and then stirring is carried out for 1h, and then cooling to 80℃ is carried out, and then triethylamine is added, and then heating to reflux is carried out for 36h, and then after the reaction is completed, benzene is removed by vacuum distillation, to obtain a carboxyl-terminated intermediate product;

[0018] S3, chitosan is added into an acetic acid solution with a volume fraction of 1%, and then stirring is carried out to obtain a chitosan dissolution solution, and then the carboxyl-terminated intermediate product and EDC are added into anhydrous ethanol, and then stirring is carried out for 3-5min, and then NHS is added, and then stirring is carried out in an ice bath for 1h to obtain a modification solution, and then the chitosan dissolution solution is added dropwise into the modification solution, and then after the dropwise addition is completed, stirring is carried out in an ice bath for 40min, and then stirring reaction is carried out at room temperature for 24h, and then after the reaction is completed, centrifugation is carried out at 10000r / min for 30min, and then the precipitate is freeze-dried, to obtain the modified chitosan.

[0019] Vanillin is an organic compound extracted from vanilla bean of Rutaceae, which is widely used in the industry of cakes, candies and baked foods, and has good antioxidant and sterilization effects, etc., the present application uses it as a base material, and uses the active aldehyde group of vanillin to react with the amino group of ethylenediamine to obtain an amino-terminated vanillin Schiff base containing an amino-terminated structure, a Schiff base structure and a vanillin structure, then the amino group of the amino-terminated vanillin Schiff base reacts with the anhydride group of n-octyl succinic anhydride to form an intermediate product containing an active carboxyl group, a hydrophobic alkyl long chain, a vanillin structure and a Schiff base structure, finally, under the action of EDC and NHS, the intermediate product reacts with chitosan to form an amide reaction, and the intermediate product is introduced into the molecular chain of chitosan, so that the chitosan has good hydrophobicity and antioxidant properties.

[0020] As a further technical solution of the present application, the molar ratio of vanillin to ethylenediamine in S1 is 1:1.

[0021] As a further technical solution of the present application, the amount ratio of n-octyl succinic anhydride, benzene, amino-terminated vanillin Schiff base and triethylamine in S2 is 0.01 mol: 50-60 mL: 2.1 g: 3-5 mL.

[0022] As a further technical solution of the present application, the amount ratio of chitosan, carboxyl-terminated intermediate product, EDC [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride] and NHS (N-hydroxysuccinimide) in S3 is 2-3 g: 0.3-0.5 g: 0.3-0.5 g: 0.2-0.3 g, the amount ratio of chitosan to acetic acid solution is 2 g: 100 mL, and the amount ratio of carboxyl-terminated intermediate product to anhydrous ethanol in the modification solution is 0.3 g: 10 mL.

[0023] As a further technical solution of the present application, mesoporous silica is obtained by technical means known to those skilled in the art.

[0024] The beneficial effects of the present application are:

[0025] The application provides a preparation method of vitamin C tablets. First, mesoporous silicon dioxide is used as a carrier to load vitamin C, so that the vitamin C is stored in the gap of the mesoporous silicon dioxide, and the light and heat stability of the vitamin C is improved by using the barrier effect (heat insulation and light insulation) of the silicon dioxide. However, the mesoporous silicon dioxide has high hygroscopicity. The application further uses a chitosan film-forming liquid to coat the mesoporous silicon dioxide microspheres loaded with the vitamin C, so as to further improve the stability. The modified chitosan in the chitosan film-forming liquid has good film-forming property and contains long-chain alkyl groups, so that the hydrophobicity is good, the influence of moisture on the vitamin C is reduced, and the modified chitosan also contains vanillin structures, so that the antioxidant and sterilization effects are good, and the stability of the vitamin C under the conditions of light and heat is further improved. In addition, the modified chitosan also contains Schiff base structures, the Schiff base structures have good complexation with metal ions, so that the influence of the metal ions on the vitamin C is further reduced. Finally, the core components, mannitol, starch and magnesium stearate coated by the chitosan film-forming liquid are used as raw materials, and a vitamin C tablet with high stability is obtained through a tablet pressing process. DETAILED DESCRIPTION

[0026] The technical solutions in the embodiments of the application will be clearly and completely described below in combination with the embodiments of the application. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments of the application. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the application.

[0027] Embodiment 1

[0028] Preparation of mesoporous silicon dioxide:

[0029] 1.28g of hexadecyl trimethyl ammonium bromide and 0.56g of sodium hydroxide are weighed into 500mL of deionized water, then 8mL of mesitylene is added, stirring and heating to 80℃, 6mL of tetraethyl orthosilicate is added dropwise, stirring at 500r / min for 2h, after the reaction is completed, a precipitate is generated in the lower layer, the obtained product is suction filtered, the filter cake is washed with anhydrous ethanol for 5 times, and vacuum drying is performed at 100℃ until the constant weight is obtained, to obtain a white powder. 0.5g of ammonium nitrate is weighed into 180mL of 95% ethanol, 1.2g of the white powder is added, stirring at 60℃ for 5h, suction filtering, and the filter cake is washed with anhydrous ethanol for 5 times, and vacuum drying is performed at 100℃ until the constant weight is obtained, to obtain mesoporous silicon dioxide.

[0030] Embodiment 2

[0031] The modified chitosan is prepared by the following steps:

[0032] S1, 30 mmol of vanillin was dissolved in 50 mL of anhydrous ethanol, and the solution was heated to 70°C while stirring, then a solution composed of 15 mmol of ethylenediamine and 30 mL of anhydrous ethanol was added dropwise, after the dropwise addition was completed, the reaction was stirred at constant temperature for 2 h, and then the solution was allowed to stand and cool to room temperature, the filter cake was washed with anhydrous ethanol 4 times under reduced pressure, and the filter cake was dried in a vacuum to obtain an amino-terminated vanillin Schiff base;

[0033] S2, 0.01 mol of n-octyl succinic anhydride and 50 mL of benzene were added to a flask, 2.1 g of the amino-terminated vanillin Schiff base was added, the solution was heated to 110°C and stirred for 1 h, then 3 mL of triethylamine was added while the temperature was lowered to 80°C, the solution was then heated to reflux and reacted for 36 h, after the reaction was completed, the benzene was removed by distillation under reduced pressure to obtain a carboxyl-terminated intermediate product;

[0034] S3, 2 g of chitosan was added to a 1% acetic acid solution to obtain a chitosan dissolution solution, 0.3 g of the carboxyl-terminated intermediate product and 0.3 g of EDC were added to anhydrous ethanol, the solution was stirred for 3 min, then 0.2 g of NHS was added, the solution was stirred in an ice bath for 1 h to obtain a modified solution, the chitosan dissolution solution was added dropwise to the modified solution, after the dropwise addition was completed, the solution was stirred in an ice bath for 40 min, then the solution was stirred at room temperature for 24 h, after the reaction was completed, the solution was centrifuged at 10,000 r / min for 30 min, the precipitate was freeze-dried to obtain modified chitosan, the amount of chitosan to acetic acid solution was 2 g: 100 mL, and the amount of carboxyl-terminated intermediate product to anhydrous ethanol in the modified solution was 0.3 g: 10 mL.

[0035] Example 3

[0036] The modified chitosan was prepared by the following steps:

[0037] S1, 30 mmol of vanillin was dissolved in 50 mL of anhydrous ethanol, and the solution was heated to 70°C while stirring, then a solution composed of 15 mmol of ethylenediamine and 30 mL of anhydrous ethanol was added dropwise, after the dropwise addition was completed, the reaction was stirred at constant temperature for 2 h, and then the solution was allowed to stand and cool to room temperature, the filter cake was washed with anhydrous ethanol 4 times under reduced pressure, and the filter cake was dried in a vacuum to obtain an amino-terminated vanillin Schiff base;

[0038] S2, 0.01 mol of n-octyl succinic anhydride and 60 mL of benzene were added to a flask, 2.1 g of the amino-terminated vanillin Schiff base was added, the solution was heated to 110°C and stirred for 1 h, then 5 mL of triethylamine was added while the temperature was lowered to 80°C, the solution was then heated to reflux and reacted for 36 h, after the reaction was completed, the benzene was removed by distillation under reduced pressure to obtain a carboxyl-terminated intermediate product;

[0039] S3, 3g of chitosan was added into 1% acetic acid solution to obtain a chitosan solution, 0.5g of the carboxyl-terminated intermediate and 0.5g of EDC were added into anhydrous ethanol, 0.3g of NHS was added after stirring for 5min, and the mixture was stirred in an ice bath for 1h to obtain a modified solution, the chitosan solution was added dropwise into the modified solution, after the dropwise addition was completed, the mixture was stirred in an ice bath for 40min, and the mixture was stirred at room temperature for 24h, after the reaction was completed, the mixture was centrifuged at 10000r / min for 30min, the precipitate was freeze-dried to obtain modified chitosan, and the amount ratio of chitosan to acetic acid solution was 2g:100mL, and the amount ratio of the carboxyl-terminated intermediate to anhydrous ethanol in the modified solution was 0.3g:10mL.

[0040] Example 4

[0041] A preparation method of a vitamin C tablet, comprising the following steps:

[0042] First step, 4g of vitamin C was dissolved in 10mL of sterile water, 1g of mesoporous silica of example 1 was added, and the mixture was stirred at room temperature for 2min, then centrifuged at 8000r / min for 10min, and the precipitate was dried to obtain mesoporous silica microspheres loaded with vitamin C;

[0043] Second step, 100g of mesoporous silica microspheres loaded with vitamin C were placed in a rotating drum and preheated to 70℃, and 5g of chitosan film-forming solution was sprayed onto the surface of the mesoporous silica microspheres loaded with vitamin C at a rotating speed of 100r / min, and the obtained product was dried at 90℃ until the weight was constant to obtain a core product;

[0044] Third step, the following raw materials were prepared: core product 300 parts, mannitol 50 parts, starch 10 parts, and magnesium stearate 3 parts;

[0045] Fourth step, the starch was dried at 100℃ until the water content was ≤2%, the core product and the mannitol were passed through a 12-mesh sieve and then mixed with the starch, and the magnesium stearate was added and mixed for 15min, and then the tablet was pressed.

[0046] The chitosan film-forming solution was prepared by the following steps:

[0047] 2g of modified chitosan of example 2 was added into 80mL of 0.5% acetic acid solution, and the mixture was magnetically stirred for 20min, then 0.06mL of glutaraldehyde aqueous solution was added, and the mixture was stirred at room temperature for 15min, and the mass fraction of the glutaraldehyde aqueous solution was 50%.

[0048] Example 5

[0049] A preparation method of a vitamin C tablet, comprising the following steps:

[0050] First step, 4.5g vitamin C was dissolved in 15mL sterile water, 1.5g mesoporous silica of example 1 was added, stirred at room temperature for 2min, then centrifuged at 9000r / min for 10min, the precipitate was dried, and mesoporous silica microspheres loaded with vitamin C were obtained;

[0051] Second step, 100g mesoporous silica microspheres loaded with vitamin C were placed in a rotating drum and preheated to 72℃, and 8g chitosan film-forming solution was sprayed onto the surface of the mesoporous silica microspheres loaded with vitamin C at a speed of 200r / min using a spray gun. The obtained product was dried at 90℃ until the weight was constant, and the core product was obtained;

[0052] Third step, the following weight parts of raw materials were prepared: core product 400 parts, mannitol 80 parts, starch 12 parts, magnesium stearate 6 parts;

[0053] Fourth step, the starch was dried at 110℃ until the water content was ≤2%, the core product and mannitol were passed through a 20 mesh sieve and mixed with the starch, magnesium stearate was added and mixed for 20min, and then the tablet was pressed.

[0054] The chitosan film-forming solution was prepared by the following steps:

[0055] 4g modified chitosan of example 3 was added to 90mL acetic acid solution with a volume fraction of 1%, magnetically stirred for 25min, then 0.15mL glutaraldehyde aqueous solution was added, stirred at room temperature for 15min, and the mass fraction of the glutaraldehyde aqueous solution was 50%.

[0056] Example 6

[0057] A preparation method of a vitamin C tablet, comprising the following steps:

[0058] First step, 5g vitamin C was dissolved in 20mL sterile water, 2g mesoporous silica of example 1 was added, stirred at room temperature for 3min, then centrifuged at 10000r / min for 10min, the precipitate was dried, and mesoporous silica microspheres loaded with vitamin C were obtained;

[0059] Second step, 100g mesoporous silica microspheres loaded with vitamin C were placed in a rotating drum and preheated to 75℃, and 10g chitosan film-forming solution was sprayed onto the surface of the mesoporous silica microspheres loaded with vitamin C at a speed of 300r / min using a spray gun. The obtained product was dried at 90℃ until the weight was constant, and the core product was obtained;

[0060] Third step, the following weight parts of raw materials were prepared: core product 500 parts, mannitol 100 parts, starch 15 parts, magnesium stearate 12 parts;

[0061] Fourthly, dry the starch at 120℃ until the water content is less than or equal to 2%, sieve the core product and mannitol through a 20 mesh sieve, mix with the starch, add magnesium stearate and mix for 30 minutes, and then press into tablets.

[0062] The chitosan film-forming solution is prepared by the following steps:

[0063] Add 5g of the modified chitosan of Example 3 to 100mL of a 2% acetic acid solution, magnetically stir for 30 minutes, then add 0.15mL of a 50% glutaraldehyde aqueous solution, stir at room temperature for 20 minutes, and then the product is obtained.

[0064] Comparative Example 1

[0065] Compared with Example 4, the modified chitosan of Example 4 is replaced by chitosan, and the remaining raw materials and preparation process are the same as those of Example 4.

[0066] Comparative Example 2

[0067] A preparation method of a vitamin C tablet, comprising the following steps:

[0068] Firstly, prepare the following raw materials by weight: 300 parts of mesoporous silica microspheres loaded with vitamin C, 50 parts of mannitol, 10 parts of starch, and 3 parts of magnesium stearate;

[0069] Secondly, dry the starch at 100℃ until the water content is less than or equal to 2%, sieve the core product and mannitol through a 12 mesh sieve, mix with the starch, add magnesium stearate and mix for 15 minutes, and then press into tablets.

[0070] The mesoporous silica microspheres loaded with vitamin C are the same as the product obtained in the first step of Example 4.

[0071] Test the vitamin C tablets obtained in Examples 4-6 and Comparative Examples 1-2, and the testing process is as follows:

[0072] Accelerated stability test: according to the conditions and methods specified in the quality standards for vitamin C in Chinese Pharmacopoeia 2010 edition volume II and the guidelines for stability test of pharmaceutical preparations in Chinese Pharmacopoeia 2010 edition volume II appendix XIX C, under the conditions of temperature 40℃±2℃ and relative humidity 75%±5%, according to the key inspection items of tablet stability, samples are taken at the end of the first month, third month and sixth month for testing, and the color, disintegration time and content determination of the solution are inspected, and the test results are shown in Table 1:

[0073] Table 1

[0074]

[0075] As can be seen from Table 1, the microorganism C tablets of Examples 4-6 have better stability than those of Comparative Examples 1 and 2.

[0076] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting; it is not intended to exclude myriad other embodiments of the present application that other present or future technologies can provide. It is further understood that the use of relational terms such as first and second, and the like, are used solely to distinguish one from another entity or action without necessarily implying any actual relationship or order between such entities or actions. Moreover, the terms "comprises", "comprising", or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but can also include other elements not expressly listed or inherent to such process, method, article, or apparatus.

[0077] While embodiments of the application have been shown and described, it is to be understood that the application is not limited to the details of the embodiments described, since numerous further modifications and changes can be apparent to one skilled in the art without departing from the spirit and scope of the application. The scope of the application is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a tablet of vitamin C, characterized by, The method comprises the following steps: The first step is to dissolve vitamin C in sterile water, add mesoporous silica, stir at room temperature, centrifuge, dry the precipitate, and obtain mesoporous silica microspheres loaded with vitamin C; The second step is to place the mesoporous silica microspheres loaded with vitamin C in a rotating drum and preheat to 70-75℃, spray a chitosan film-forming solution onto the surface of the mesoporous silica microspheres loaded with vitamin C using a spray gun, dry the obtained product at 90℃ until the weight is constant, and obtain the core product; The third step is to prepare the following weight parts of raw materials: core product 300-500 parts, mannitol 50-100 parts, starch 10-15 parts, and magnesium stearate 3-12 parts; The fourth step is to dry the starch, pass the core product and mannitol through a 12-20 mesh sieve, mix with the starch, add magnesium stearate, mix for 15-30 minutes, and press into tablets; The chitosan film-forming solution is prepared by the following steps: Add the modified chitosan to a 0.5-2% acetic acid solution, stir magnetically for 20-30 minutes, then add the glutaraldehyde aqueous solution, stir at room temperature for 10-20 minutes, and obtain the chitosan film-forming solution; The modified chitosan is prepared by the following steps: S1. Dissolve vanillin in anhydrous ethanol, stir and heat to 70℃, add an ethylenediamine anhydrous ethanol solution dropwise, after the dropwise addition is complete, constant temperature stirring reaction for 2h, to obtain an amino-terminated vanillin Schiff base; S2. Add n-octyl succinic anhydride and benzene to a flask, add the amino-terminated vanillin Schiff base, heat to 110℃ and stir for 1h, then cool to 80℃ and add triethylamine, continue to heat to reflux for 36h, to obtain a carboxyl-terminated intermediate product; S3. Add chitosan to a 1% acetic acid solution, stir to obtain a chitosan dissolution solution, add the carboxyl-terminated intermediate product and EDC to anhydrous ethanol, stir for 3-5 minutes, then add NHS, stir in an ice bath for 1h to obtain a modified solution, add the chitosan dissolution solution dropwise to the modified solution, after the dropwise addition is complete, stir in an ice bath for 40 minutes, stir at room temperature for 24h, and obtain the modified chitosan.

2. The method of claim 1, wherein the vitamin C tablet is prepared by the steps of: The amount ratio of vitamin C, sterile water and mesoporous silica in the first step is 4-5g:10-20mL:1-2g.

3. The method of claim 1, wherein the vitamin C tablet is prepared by the steps of: The mass ratio of mesoporous silica microspheres loaded with vitamin C and chitosan film-forming solution in the second step is 100:5-10.

4. The method of claim 1, wherein the vitamin C tablet is prepared by the steps of: The molar ratio of vanillin and ethylenediamine in S1 is 1:

1.

5. The method for preparing a vitamin C tablet according to claim 1, characterized in that, The amount ratio of n-octyl succinic anhydride, benzene, amino-terminated vanillin Schiff base and triethylamine in S2 is 0.01mol:50-60mL:2.1g:3-5mL.

6. The method of claim 1, wherein the vitamin C tablet is prepared by the steps of: The amount ratio of chitosan, carboxyl-terminated intermediate product, EDC and NHS in S3 is 2-3g:0.3-0.5g:0.3-0.5g:0.2-0.3g, the amount ratio of chitosan and acetic acid solution is 2g:100mL, and the amount ratio of carboxyl-terminated intermediate product and anhydrous ethanol in the modified solution is 0.3g:10mL.

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