A water-soluble carrier and a method for preparing the same

Abstract

The application discloses a water-soluble carrier and a preparation method thereof, which is prepared from the following raw materials: magnesium sulfate, sodium sulfate, anhydrous glucose, potassium chloride, citric acid, tartaric acid, food pigment and nano-silicon dioxide. The water-soluble carrier prepared through reasonable control of the content of the components and through a spray drying process can effectively improve the unstable property, easy moisture absorption, easy caking or poor solubility of products such as medicines and feed additives, and is beneficial to prolonging the storage period.

Description

Technical Field

[0001] This invention relates to the field of veterinary drug carrier technology, and in particular to a water-soluble carrier and its preparation method. Background Technology

[0002] Currently, even when using water-soluble carriers, some feed additives, veterinary drugs, and their premixes still suffer from problems such as short shelf life, unstable properties, susceptibility to moisture absorption, clumping, and poor solubility. Some of these issues are even caused by the carrier itself. For example, the main carriers used in veterinary drugs in China are glucose or minerals, which have significant drawbacks. Anhydrous glucose is prone to moisture absorption, clumping, and poor flowability, potentially leading to insufficient drug dosage in animals and affecting treatment efficacy. Even with the addition of desiccants and anti-caking agents, some manufacturers cannot effectively solve the problems of unstable storage, susceptibility to moisture absorption, clumping, denaturation, or poor solubility. Therefore, it is necessary to improve existing technologies and develop a water-soluble carrier that can effectively address the instability, moisture absorption, clumping, and poor solubility issues in pharmaceuticals and feed additives. Summary of the Invention

[0003] Therefore, based on the above background, the present invention provides a water-soluble carrier and its preparation method. Using the carrier, veterinary drugs prepared by loading active ingredients have high stability, are not prone to moisture absorption or clumping, and have excellent solubility.

[0004] The technical solution provided by this invention is as follows: A water-soluble carrier, by weight, is made from the following components: Magnesium sulfate 30-50%, sodium sulfate 30-45%, anhydrous glucose 1-8%, potassium chloride 10-18%, citric acid 3-10%, tartaric acid 0.5-1.2%, food coloring 1-5%, nano silica 0.5-2%.

[0005] Furthermore, by weight, it is made from the following components as raw materials: Magnesium sulfate 40%, sodium sulfate 35%, anhydrous glucose 2%, potassium chloride 12%, citric acid 8%, tartaric acid 1%, food coloring 2%, nano silica 1%.

[0006] Furthermore, the food coloring is selected from carmine and tartrazine.

[0007] Furthermore, its preparation includes the following steps: ① Take magnesium sulfate, sodium sulfate, potassium chloride, and anhydrous glucose, dry them separately until the moisture content is <0.5%, then pulverize them and pass them through an 80-mesh sieve; ② Citric acid and tartaric acid are pulverized separately and then passed through a 100-mesh sieve; ③ Add magnesium sulfate, sodium sulfate, potassium chloride, and anhydrous glucose to water and dissolve them completely; then add citric acid and tartaric acid, stir, and obtain a mixture. ④ The mixture obtained in step ③ is spray-dried and granulated to obtain microspheres with a particle size of 50-100 μm; ⑤ Disperse food coloring and nano-silica in an ethanol solution to obtain a dispersion. Place the microspheres obtained in step ④ in a fluidized bed. After spraying the dispersion into the fluidized bed, dry the microspheres.

[0008] Furthermore, the tartaric acid is selected from DL-tartaric acid.

[0009] Based on the same inventive concept, the present invention provides the application of the above-mentioned water-soluble carrier for loading active ingredients in the preparation of veterinary drugs.

[0010] Furthermore, the active ingredient includes at least one of vitamin A, choline chloride, florfenicol, doxycycline hydrochloride, enrofloxacin, albendazole, sulfadiazine sodium, and ivermectin.

[0011] Based on the same inventive concept, the present invention also provides a method for preparing a veterinary drug mainly containing choline chloride, comprising the following steps: 1) Pass the above-mentioned water-soluble carrier through a 60-mesh sieve; 2) Pulverize choline chloride to a density of D90 ≤ 20 μm; the amount of choline chloride is 25-50% of the weight of the water-soluble carrier in step 1). 3) After mixing the water-soluble carrier and 50% choline chloride in step 1) for 5-10 minutes, add the remaining choline chloride and continue stirring for 25-45 minutes. Then, pass the mixture through a 40-mesh sieve.

[0012] Based on the same inventive concept, this invention provides a method for preparing a veterinary drug mainly containing florfenicol, comprising the following steps: (1) Dissolve florfenicol in a solvent to obtain a drug solution; (2) After passing the above water-soluble carrier through a 60-mesh sieve, add it to a fluidized bed, spray the drug solution into it, and then dry it.

[0013] Further, the solvent in step (1) is a mixture of acetone and ethanol in a volume ratio of 1:1.

[0014] The beneficial effects achieved by this invention are as follows: This invention, through the rational control of the content of magnesium sulfate, sodium sulfate, anhydrous glucose, potassium chloride, citric acid, tartaric acid, food coloring, and nano-silica, and the preparation of a water-soluble carrier via spray drying and other processes, effectively improves the problems of unstable properties, easy moisture absorption, easy clumping, or poor solubility in pharmaceuticals, feed additives, and other products, thus extending shelf life. Magnesium sulfate serves as the skeleton material, providing a rigid structure and inhibiting moisture absorption; sodium sulfate reduces the water activity in the carrier and veterinary drugs, improving the stability of the drugs; and the combination of anhydrous glucose and anhydrous sodium sulfate increases the hydrophilicity of the particles, further enhancing the low water content of the carrier and veterinary drugs. The dissolution rate is improved by micronization of potassium chloride, which increases the specific surface area, accelerates disintegration, and enhances the dissolution rate. Citric acid and tartaric acid are used to adjust the pH of the system, creating an acidic environment that inhibits microorganisms and their oxidation reactions. Citric acid can also chelate metal ions, inhibiting the oxidation of the active ingredients in the drug and improving stability. Combining citric acid with tartaric acid further enhances the high-temperature stability of veterinary drugs. Nano-silica not only fills pores to block capillary moisture absorption but also prevents the formation of hydrogen bonds between particles, reducing the likelihood of aggregation and improving stability. Furthermore, spray drying forms a porous microsphere structure, increasing the specific surface area and improving drug loading. Detailed Implementation

[0015] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention.

[0016] Example 1: A water-soluble carrier, by weight, is made from the following components as raw materials: Magnesium sulfate 40%, sodium sulfate 35%, anhydrous glucose 2%, potassium chloride 12%, citric acid 8%, tartaric acid 1%, food coloring 2%, nano silica 1%.

[0017] The particle size of nano-silica is 80-150nm.

[0018] The food coloring used in this embodiment is carmine.

[0019] The tartaric acid is selected from DL-tartaric acid, which has high water solubility.

[0020] The preparation of the water-soluble carrier in this embodiment includes the following steps: ① Take magnesium sulfate, sodium sulfate, potassium chloride, and anhydrous glucose, dry them separately until the moisture content is <0.5%, then pulverize them and pass them through an 80-mesh sieve; ② Citric acid and tartaric acid are pulverized separately and then passed through a 100-mesh sieve; ③ Add magnesium sulfate, sodium sulfate, potassium chloride, and anhydrous glucose to an appropriate amount of water and stir until completely dissolved; then add citric acid and tartaric acid, stir, and obtain a mixture. ④ The mixture obtained in step ③ is spray-dried and granulated to obtain microspheres with a particle size of 50-100 μm; Spray drying is performed using a centrifugal spray dryer. Inlet air temperature: 180±5℃; Air outlet temperature: 80±5℃; Atomizer disc rotation speed: 15000-20000 rpm; ⑤ Disperse food coloring and nano silica in an ethanol solution to obtain a dispersion. Place the microspheres obtained in step ④ in a fluidized bed. Spray the dispersion into the fluidized bed and dry the microspheres. Immediately seal them in an aluminum foil composite bag and store them in a cool, dry place for later use.

[0021] Comparative Example 1: A water-soluble carrier, by weight, is made from the following components as raw materials: Magnesium sulfate 40%, sodium sulfate 37%, potassium chloride 12%, citric acid 8%, tartaric acid 1%, food coloring 2%, nano silica 1%.

[0022] Compared to Example 1, this comparative example replaces anhydrous glucose with the same amount of sodium sulfate.

[0023] The food coloring used in this embodiment is carmine.

[0024] The tartaric acid is selected from DL-tartaric acid, which has high water solubility.

[0025] The preparation of the water-soluble carrier in this embodiment includes the following steps: ① Take magnesium sulfate, sodium sulfate and potassium chloride, dry them separately until the moisture content is <0.5%, then crush them and pass them through an 80-mesh sieve; ② Citric acid and tartaric acid are pulverized separately and then passed through a 100-mesh sieve; ③ Add magnesium sulfate, sodium sulfate, potassium chloride, and anhydrous glucose to an appropriate amount of water and stir until completely dissolved; then add citric acid and tartaric acid, stir, and obtain a mixture. ④ The mixture obtained in step ③ is spray-dried and granulated to obtain microspheres with a particle size of 50-100 μm; Spray drying is performed using a centrifugal spray dryer. Inlet air temperature: 180±5℃; Air outlet temperature: 80±5℃; Atomizer disc rotation speed: 15000-20000 rpm; ⑤ Disperse food coloring and nano silica in an ethanol solution to obtain a dispersion. Place the microspheres obtained in step ④ in a fluidized bed. Spray the dispersion into the fluidized bed and dry the microspheres. Immediately seal them in an aluminum foil composite bag and store them in a cool, dry place for later use.

[0026] Comparative Example 2: Example 1: A water-soluble carrier, by weight, is made from the following components as raw materials: Magnesium sulfate 40%, anhydrous glucose 37%, potassium chloride 12%, citric acid 8%, tartaric acid 1%, food coloring 2%, nano silica 1%.

[0027] Compared to Example 1, this comparative example replaces sodium sulfate with the same amount of anhydrous glucose.

[0028] The particle size of nano-silica is 80-150nm.

[0029] The food coloring used in this embodiment is carmine.

[0030] The tartaric acid is selected from DL-tartaric acid, which has high water solubility.

[0031] The preparation of the water-soluble carrier in this embodiment includes the following steps: ① Take magnesium sulfate, potassium chloride and anhydrous glucose, dry them to a moisture content of <0.5%, then pulverize them and pass them through an 80-mesh sieve; ② Citric acid and tartaric acid are pulverized separately and then passed through a 100-mesh sieve; ③ Add magnesium sulfate, sodium sulfate, potassium chloride, and anhydrous glucose to an appropriate amount of water and stir until completely dissolved; then add citric acid and tartaric acid, stir, and obtain a mixture. ④ The mixture obtained in step ③ is spray-dried and granulated to obtain microspheres with a particle size of 50-100 μm; Spray drying is performed using a centrifugal spray dryer. Inlet air temperature: 180±5℃; Air outlet temperature: 80±5℃; Atomizer disc rotation speed: 15000-20000 rpm; ⑤ Disperse food coloring and nano silica in an ethanol solution to obtain a dispersion. Place the microspheres obtained in step ④ in a fluidized bed. Spray the dispersion into the fluidized bed and dry the microspheres. Immediately seal them in an aluminum foil composite bag and store them in a cool, dry place for later use.

[0032] Comparative Example 3: A water-soluble carrier, by weight, is made from the following components as raw materials: Magnesium sulfate 40%, sodium sulfate 37%, potassium chloride 12%, citric acid 9%, food coloring 2%, nano silica 1%.

[0033] Replace tartaric acid with the same amount of citric acid.

[0034] The food coloring used in this embodiment is carmine.

[0035] The tartaric acid is selected from DL-tartaric acid, which has high water solubility.

[0036] The preparation of the water-soluble carrier in this embodiment includes the following steps: ① Take magnesium sulfate, sodium sulfate and potassium chloride, dry them separately until the moisture content is <0.5%, then crush them and pass them through an 80-mesh sieve; ② After pulverizing the citric acid separately, pass it through a 100-mesh sieve; ③ Add magnesium sulfate, sodium sulfate, potassium chloride, and anhydrous glucose to an appropriate amount of water and stir until completely dissolved; then add citric acid and tartaric acid, stir, and obtain a mixture. ④ The mixture obtained in step ③ is spray-dried and granulated to obtain microspheres with a particle size of 50-100 μm; Spray drying is performed using a centrifugal spray dryer. Inlet air temperature: 180±5℃; Air outlet temperature: 80±5℃; Atomizer disc rotation speed: 15000-20000 rpm; ⑤ Disperse food coloring and nano silica in an ethanol solution to obtain a dispersion. Place the microspheres obtained in step ④ in a fluidized bed. Spray the dispersion into the fluidized bed and dry the microspheres. Immediately seal them in an aluminum foil composite bag and store them in a cool, dry place for later use.

[0037] Comparative Example 4: A water-soluble carrier, by weight, is made from the following components: Magnesium sulfate 40%, sodium sulfate 37%, potassium chloride 12%, citric acid 9%, food coloring 2%, nano talc 1%.

[0038] The nano-silica was replaced with the same amount of nano-talc powder (particle size 60-120nm).

[0039] The food coloring used in this embodiment is carmine.

[0040] The tartaric acid is selected from DL-tartaric acid, which has high water solubility.

[0041] The preparation of the water-soluble carrier in this embodiment includes the following steps: ① Take magnesium sulfate, sodium sulfate and potassium chloride, dry them separately until the moisture content is <0.5%, then crush them and pass them through an 80-mesh sieve; ② After pulverizing the citric acid separately, pass it through a 100-mesh sieve; ③ Add magnesium sulfate, sodium sulfate, potassium chloride, and anhydrous glucose to an appropriate amount of water and stir until completely dissolved; then add citric acid and tartaric acid, stir, and obtain a mixture. ④ The mixture obtained in step ③ is spray-dried and granulated to obtain microspheres with a particle size of 50-100 μm; Spray drying is performed using a centrifugal spray dryer.

[0042] Inlet air temperature: 180±5℃; Air outlet temperature: 80±5℃; Atomizer disc rotation speed: 15000-20000 rpm; ⑤ Disperse food coloring and nano silica in an ethanol solution to obtain a dispersion. Place the microspheres obtained in step ④ in a fluidized bed. Spray the dispersion into the fluidized bed and dry the microspheres. Immediately seal them in an aluminum foil composite bag and store them in a cool, dry place for later use.

[0043] Veterinary drugs were prepared using the water-soluble carriers of Example 1 and Comparative Examples 1 to 4, respectively.

[0044] The preparation of veterinary drugs containing choline chloride includes the following steps: 1) Pass the water-soluble carriers prepared in Example 1, Comparative Examples 1 to 4 through a 60-mesh sieve; 2) Pulverize choline chloride to a density of D90 ≤ 20 μm; the amount of choline chloride is 45% of the weight of the water-soluble carrier in step 1). 3) After mixing the water-soluble carrier and 50% choline chloride in step 1) for 5-10 minutes, add the remaining choline chloride and continue stirring for 25-45 minutes. Then, pass the mixture through a 40-mesh sieve.

[0045] The drugs prepared in the different embodiments above are choline chloride veterinary drug group 1 (Example 1), choline chloride veterinary drug group 2 (Comparative Example 1), choline chloride veterinary drug group 3 (Comparative Example 2), choline chloride veterinary drug group 4 (Comparative Example 3), and choline chloride veterinary drug group 5 (Comparative Example 4). The stability, solubility, and anti-moisture and anti-caking properties of choline chloride veterinary drug group 1, choline chloride veterinary drug group 2, choline chloride veterinary drug group 3, choline chloride veterinary drug group 4 and choline chloride veterinary drug group 5 prepared above were tested (the results are shown in Table 1).

[0046] Table 1: Comparison of the performance of veterinary drugs containing choline chloride The preparation of the veterinary drug containing florfenicol includes the following steps: (1) Dissolve florfenicol in a solvent to obtain a drug solution; the solvent is a mixture of acetone and ethanol in a volume ratio of 1:1; (2) After passing the water-soluble carriers prepared in Example 1, Comparative Examples 1 to 4 through a 60-mesh sieve, add them to a fluidized bed, spray the drug solution into the fluidized bed, and then dry them. The amount of florfenicol is 15% of the amount of the water-soluble carrier.

[0047] The drugs prepared in the different embodiments above are respectively florfenicol veterinary drug group 1 (Example 1), florfenicol veterinary drug group 2 (Comparative Example 1), florfenicol veterinary drug group 3 (Comparative Example 2), florfenicol veterinary drug group 4 (Comparative Example 3) and florfenicol veterinary drug group 5 (Comparative Example 4). The stability, solubility and anti-moisture-reabsorption and anti-caking properties of florfenicol veterinary drug group 1, florfenicol veterinary drug group 2, florfenicol veterinary drug group 3, florfenicol veterinary drug group 4 and florfenicol veterinary drug group 5 prepared above were tested (the results are shown in Table 2).

[0048] Table 2: Comparison of the properties of veterinary drugs containing chlorflufenicol as the main ingredient The preparation of the additive, which mainly contains vitamin A, includes the following steps: (1) Dissolve vitamin A in a solvent to obtain a drug solution; the solvent is a mixture of acetone and ethanol in a volume ratio of 1:1; (2) After passing the water-soluble carriers prepared in Example 1, Comparative Examples 1 to 4 through a 60-mesh sieve, add them to a fluidized bed, spray the drug solution into the fluidized bed, and then dry them. The amount of vitamin A is 10% of the amount of the water-soluble carrier.

[0049] The drugs prepared in the different embodiments above are vitamin A additive group 1 (Example 1), vitamin A additive group 2 (Comparative Example 1), vitamin A additive group 3 (Comparative Example 2), vitamin A additive group 4 (Comparative Example 3), and vitamin A additive group 5 (Comparative Example 4). The stability, solubility, and anti-moisture and anti-caking properties of vitamin A additive group 1, vitamin A additive group 2, vitamin A additive group 3, vitamin A additive group 4, and vitamin A additive group 5 prepared above were tested (the results are shown in Table 3).

[0050] Table 3: Performance Comparison of Additives Mainly Containing Vitamin A The test results of the drug samples in each group show that the drug prepared with the carrier of Example 1 has the best stability, solubility, moisture resistance, and flowability. The drug sample prepared with the carrier of Comparative Example 2 has the worst performance compared to the others. This indicates that sodium sulfate plays a crucial role in improving the stability of the carrier and the drug. It is speculated that the absence of sodium sulfate in Comparative Example 2 reduces the ability to control water activity, leading to severe moisture absorption and clumping, resulting in the worst stability. Furthermore, comparing the performance of the drugs prepared with the carriers of Example 1 and Comparative Examples 1 and 2 shows that sodium sulfate and anhydrous glucose have a synergistic effect in improving drug stability. Comparing the carriers of Example 1 and Comparative Example 3 and the drugs prepared with them shows that the addition of tartaric acid is beneficial for improving drug stability. Comparing Example 1 and Comparative Example 4 shows that nano-silica is more beneficial for increasing the moisture barrier properties of the drug and enhancing its moisture resistance compared to nano-talc.

[0051] For detailed instructions on the above testing procedure, please refer to the following: 1) Stability testing (accelerated testing) Each group of samples was placed in a constant temperature and humidity chamber and stored for 30 days at a temperature of 40±2℃ and a relative humidity of 75±5%. Samples were taken on days 0, 10, 20, and 30 to determine the retention rate of the active ingredients.

[0052] Retention rate (%) = (content on day N / content on day 0) × 100%.

[0053] 2) Solubility test Take 1.0 g of sample and add it to 100 mL of distilled water at 25 °C. Stir magnetically (300 rpm) and time the process, recording the time (in seconds) required for complete dissolution. Simultaneously observe the clarity of the solution (whether there is any precipitate or suspended matter).

[0054] 3) Test of anti-moisture and anti-caking performance The sample was spread flat in a petri dish and placed in a constant humidity chamber at 30°C and 80% relative humidity. After 7 days, the clumping was observed and the moisture absorption weight gain rate was measured.

[0055] Moisture absorption weight gain rate = (W0-W7) / W0×100% (W0 is the initial weight, W7 is the weight after 7 days).

[0056] Clumping degree classification: Grade 0: No lumps (powder flows freely); Level 1: Slight clumping (breaks up easily with a light tap); Level 2: Obvious lumps (requires external force to break them apart); Level 3: Severe clumping (cannot be dispersed).

[0057] 4) Fluidity test (choline chloride veterinary drugs only) Using an angle of repose measuring instrument, the powder is allowed to flow naturally from a fixed height, and the angle of repose θ is measured. The smaller θ is, the better the flowability.

[0058] The present invention and its embodiments have been described above. This description is not restrictive, and the examples shown are merely illustrative. This is one embodiment of the present invention, and the actual structure is not limited thereto. In short, if those skilled in the art are inspired by this invention and design similar structures and embodiments without departing from the spirit of the invention, such designs should fall within the protection scope of the present invention.

Claims

1. A water-soluble carrier, characterized in that, By weight, it is made from the following components: Magnesium sulfate 30-50%, sodium sulfate 30-45%, anhydrous glucose 1-8%, potassium chloride 10-18%, citric acid 3-10%, tartaric acid 0.5-1.2%, food coloring 1-5%, nano silica 0.5-2%.

2. The water-soluble carrier according to claim 1, characterized in that, By weight, it is made from the following components: Magnesium sulfate 40%, sodium sulfate 35%, anhydrous glucose 2%, potassium chloride 12%, citric acid 8%, tartaric acid 1%, food coloring 2%, nano silica 1%.

3. A water-soluble carrier according to claim 1 or 2, characterized in that, The food coloring is selected from carmine and lemon yellow.

4. A water-soluble carrier according to any one of claims 1 to 3, characterized in that, Its preparation includes the following steps: ① Take magnesium sulfate, sodium sulfate, potassium chloride, and anhydrous glucose, dry them separately until the moisture content is <0.5%, then pulverize them and pass them through an 80-mesh sieve; ② Citric acid and tartaric acid are pulverized separately and then passed through a 100-mesh sieve; ③ Add magnesium sulfate, sodium sulfate, potassium chloride, and anhydrous glucose to water and dissolve them completely; then add citric acid and tartaric acid, stir, and obtain a mixture. ④ The mixture obtained in step ③ is spray-dried and granulated to obtain microspheres with a particle size of 50-100 μm; ⑤ Disperse food coloring and nano-silica in an ethanol solution to obtain a dispersion. Place the microspheres obtained in step ④ in a fluidized bed. After spraying the dispersion into the fluidized bed, dry the microspheres.

5. A water-soluble carrier according to claim 4, characterized in that, The tartaric acid used is DL-tartaric acid.

6. The application of the active ingredient loaded on a water-soluble carrier as described in any one of claims 1 to 5 in the preparation of veterinary drugs.

7. The application according to claim 6, characterized in that, The active ingredients include at least one of vitamin A, choline chloride, florfenicol, doxycycline hydrochloride, enrofloxacin, albendazole, sulfadiazine sodium, and ivermectin.

8. A method for preparing a veterinary drug mainly containing choline chloride, characterized in that, Includes the following steps: 1) Pass the water-soluble carrier according to any one of claims 1 to 5 through a 60-mesh sieve; 2) Pulverize choline chloride to a density of D90 ≤ 20 μm; the amount of choline chloride is 25-50% of the weight of the water-soluble carrier in step 1). 3) After mixing the water-soluble carrier and 50% choline chloride in step 1) for 5-10 minutes, add the remaining choline chloride and continue stirring for 25-45 minutes. Then, pass the mixture through a 40-mesh sieve.

9. A method for preparing a veterinary drug mainly containing florfenicol, characterized in that, Includes the following steps: (1) Dissolve florfenicol in a solvent to obtain a drug solution; (2) Take the water-soluble carrier described in any one of claims 1 to 5, pass it through a 60-mesh sieve, add it to a fluidized bed, spray the drug solution into it, and then dry it.

10. The method for preparing a veterinary drug containing florfenicol according to claim 9, characterized in that, The solvent in step (1) is a mixture of acetone and ethanol in a volume ratio of 1:1.

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