Doxycycline hydrochloride soluble powder and preparation method thereof

Abstract

The invention relates to the technical field of veterinary drug preparations, in particular to doxycycline hydrochloride soluble powder and a preparation method thereof.The preparation method comprises the following steps that S1, all components are weighed according to a preset proportion; s2, dissolving doxycycline hydrochloride in a predetermined amount of deionized water to obtain a solution A; s3, adding a chelating agent, an acidifying agent, an antioxidant, a synergist and a preservative into the solution A to form a colorless solution, and standing under a refrigeration condition to separate out a solid; s4, filtering the solid separated out in the step S3; s5, drying the solid, and screening with a 65-mesh sieve; and S6, mixing the screened powder with the weighed surfactant and glucose, and finally sieving with a 65-mesh sieve to obtain a final finished product. According to the doxycycline hydrochloride soluble powder, by optimizing the formula and the preparation process of the doxycycline hydrochloride soluble powder, the stability, the solubility and the bioavailability of the medicine are effectively improved, and the problems of degradation, chelation and caking in the traditional technology are solved.

Description

Technical Field

[0001] The present invention relates to the technical field of veterinary drug preparations, and particularly to a soluble powder of doxycycline hydrochloride and a preparation method thereof. Background Art

[0002] Doxycycline hydrochloride is a broad-spectrum antibiotic, which is widely used in the veterinary field, especially in the treatment of diseases such as mycoplasmosis, colibacillosis, salmonellosis, pasteurellosis and psittacosis in livestock and poultry; due to its strong antibacterial activity, doxycycline hydrochloride is widely used in feed additives and drug mixtures to improve the health level of animals; however, the existing soluble powder of doxycycline hydrochloride is mainly made by mixing doxycycline hydrochloride with glucose. Although this preparation method is relatively simple and easy to use, there are still some significant disadvantages, especially in terms of drug stability, solubility and bioavailability.

[0003] In the actual application process, the existing soluble powder of doxycycline hydrochloride has degradation and chelation problems, resulting in reduced drug efficacy and low bioavailability; in addition, the traditional formula is prone to caking during the preparation process, affecting the solubility and dispersibility of the drug, thereby affecting its clinical effect; these problems not only affect the actual use effect of doxycycline hydrochloride, but also limit its wide application in veterinary clinics. Therefore, developing a soluble powder of doxycycline hydrochloride with better stability, solubility and drug efficacy has become an urgent technical problem to be solved in the current field of veterinary drug preparations. Summary of the Invention

[0004] Based on the above purposes, the present invention provides a soluble powder of doxycycline hydrochloride and a preparation method thereof.

[0005] A soluble powder of doxycycline hydrochloride includes doxycycline hydrochloride, a chelating agent, an acidifying agent, a surfactant, an antioxidant, a synergist, a preservative and glucose; wherein the mass percentages of each component are as follows: The mass of doxycycline hydrochloride is 41.7%-67.6%; The mass of the chelating agent is 1%-3%; The mass of the acidifying agent is 0.5%-2%; The mass of the surfactant is 0.5%-1.5%; The mass of the antioxidant is 0.1%-0.5%; The mass of the synergist is 0.2%-1%; The mass of the preservative is 0.1%-0.3%; The mass of glucose is 30%-50%.

[0006] Optionally, the chelating agent is selected from disodium ethylenediaminetetraacetate or calcium gluconate; the acidifying agent is citric acid; the antioxidant is ascorbic acid or vitamin E; the synergist is selected from polyvinylpyrrolidone or glycerol; the preservative is selected from sodium benzoate or potassium sorbate.

[0007] Optionally, the surfactant is sodium dodecyl sulfate.

[0008] A preparation method of doxycycline hydrochloride soluble powder comprises the following steps: S1: Weigh doxycycline hydrochloride, chelating agent, acidifying agent, surfactant, antioxidant, synergist, preservative and glucose in a predetermined ratio; S2: Dissolve doxycycline hydrochloride in a predetermined amount of deionized water to obtain solution A; S3: Add the chelating agent, acidifying agent, antioxidant, synergist and preservative to solution A, mix evenly to form a colorless solution, and place it under refrigeration conditions for standing until solids precipitate; S4: Filter the solids precipitated in S3 and continuously wash them with distilled water to remove impurities in the solution; S5: Dry the washed solids in S4 until the water content of the solids is less than 5%, and then screen them through a 65-mesh sieve to obtain uniform powder; S6: Mix the powder screened in S5 with the weighed surfactant and glucose, mix them using a high-speed mixer, and finally screen them through a 65-mesh sieve to obtain the final doxycycline hydrochloride soluble powder.

[0009] Optionally, S2 specifically includes: S21: Add the doxycycline hydrochloride weighed in S1 to deionized water, and the volume of water is 10 - 20 times the mass of doxycycline hydrochloride; S22: Stir using a stirring device at a speed of 100 - 300 rpm and continuously stir for 10 - 30 minutes until doxycycline hydrochloride is completely dissolved; S23: After dissolution is completed, obtain solution A and control the dissolution temperature not to exceed 30°C to avoid degradation of doxycycline hydrochloride.

[0010] Optionally, S3 specifically includes: S31: Add the chelating agent and stir solution A, control the stirring speed at 50 - 150 rpm, and continuously stir for 5 - 10 minutes; S32: Add the acidifying agent, antioxidant, synergist and preservative in sequence, and continue to stir for 3 - 5 minutes after each addition to ensure that each component is evenly dispersed to form a colorless solution; S33: After stirring evenly, place the colorless solution under refrigeration conditions at 4°C for standing for 24 - 48 hours until solids precipitate.

[0011] Optionally, S4 specifically includes: S41: Filter the solid precipitated in S3 through a filtering device with a filtering precision of 50 - 100 mesh; S42: Put the filtered solid into a clean container and continuously wash it with distilled water for 2 - 4 times, with the amount of distilled water used each time being 5 - 10 times the mass of the solid; S43: After each washing, use the filtering device to filter again to ensure that impurities on the surface of the solid are completely removed; S44: After the washing is completed, remove the excess water from the solid by suction filtration.

[0012] Optionally, S5 specifically includes: S51: Place the solid washed in S4 in a drying device for drying treatment, control the drying temperature at 50°C - 60°C, and the drying time is 8 - 12 hours until the water content of the solid drops below 5%; S52: After drying is completed, use a 65 - mesh sieve for screening at a screening speed of 100 - 200 g / min to ensure that the solid is evenly dispersed and remove the undried particles; S53: After screening, obtain a uniform powder.

[0013] Optionally, S6 specifically includes: S61: Put the powder screened in S5, the surfactant and glucose weighed in S1 into a high - speed mixer, set the mixing speed at 300 - 500 rpm, and the mixing time is 10 - 15 minutes to ensure uniform mixing; S62: After mixing is completed, screen the mixture through a 65 - mesh sieve to obtain the final soluble powder of doxycycline hydrochloride.

[0014] Advantages of the present invention: In the present invention, by optimizing the formula and improving the preparation process, the stability and solubility of the drug are significantly improved, the degradation and chelation problems in the traditional formula are overcome, and the bioavailability of the drug is ensured; by introducing appropriate excipients (such as chelating agents, acidifying agents, synergists, etc.) and precisely controlling the proportion of each component, the phenomenon of drug caking can be effectively avoided, the rapid dissolution of the drug is promoted, thereby improving the drug efficacy and prolonging its effective time in the body.

[0015] In the present invention, through fine process control, the final product has better drug efficacy and palatability, can provide more convenient drug - administration options for veterinary clinics, is especially suitable for various drug - administration methods such as drinking water mixing, feed mixing and as an additive, meeting different clinical needs. Description of the Drawings

[0016] To more clearly illustrate the technical solutions in the present invention or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the drawings in the following description are only those of the present invention. For those of ordinary skill in the art, other drawings can also be obtained based on these drawings without creative work.

[0017] Figure 1 Schematic diagram of each component of the doxycycline hydrochloride soluble powder according to the embodiment of the present invention; Figure 2 Schematic diagram of the preparation method of the doxycycline hydrochloride soluble powder according to the embodiment of the present invention. Detailed implementation manners

[0018] The present invention will be described in detail below in conjunction with the drawings and specific embodiments. At the same time, it should be noted here that in order to make the embodiments more detailed, the following embodiments are the best and preferred embodiments. For some well-known technologies, those skilled in the art can also adopt other alternative methods for implementation; moreover, the drawings are only for more specific description of the embodiments and are not intended to specifically limit the present invention.

[0019] It should be pointed out that in the specification, when referring to "an embodiment", "embodiment", "exemplary embodiment", "some embodiments", etc., it indicates that the described embodiment may include specific features, structures or characteristics, but not necessarily every embodiment includes such specific features, structures or characteristics. In addition, when combining an embodiment to describe a specific feature, structure or characteristic, implementing such a feature, structure or characteristic in combination with other embodiments (whether explicitly described or not) should be within the knowledge of those skilled in the relevant art.

[0020] Generally, the terms can be understood at least in part from their use in the context. For example, at least in part depending on the context, the term "one or more" used herein can be used to describe any feature, structure or characteristic in a singular sense, or can be used to describe a combination of features, structures or characteristics in a plural sense. In addition, the term "based on" can be understood as not necessarily intended to convey a set of exclusive factors, but instead, at least in part depending on the context, allowing the existence of other factors that may not be explicitly described.

[0021] Embodiment 1 As Figure 1 shown, a doxycycline hydrochloride soluble powder includes doxycycline hydrochloride, chelating agent, acidifying agent, surfactant, antioxidant, synergist, preservative and glucose; wherein the mass percentages of each component are as follows The mass of doxycycline hydrochloride is 50%; The mass of the chelating agent is 2%; The mass of the acidifying agent is 1%; The mass of the surfactant is 1%; The mass of the antioxidant is 0.3%; The mass of the synergist is 0.5%; The mass of the preservative is 0.2%; The mass of glucose is 45%.

[0022] The chelating agent is selected from disodium ethylenediaminetetraacetate; the acidifying agent is citric acid; the antioxidant is ascorbic acid; the synergist is selected from polyvinylpyrrolidone (PVP); the preservative is selected from sodium benzoate.

[0023] The surfactant is sodium dodecyl sulfate.

[0024] As Figure 2 shown, a preparation method of doxycycline hydrochloride soluble powder includes the following steps: S1: Weigh doxycycline hydrochloride, chelating agent, acidifying agent, surfactant, antioxidant, synergist, preservative and glucose according to a predetermined ratio, and ensure that the total mass of the raw materials is 100%; S2: Dissolve doxycycline hydrochloride in a predetermined amount of deionized water to obtain solution A; S3: Add the chelating agent, acidifying agent, antioxidant, synergist and preservative to solution A, mix evenly to form a colorless solution, and place it under refrigeration conditions and let it stand until solids precipitate; S4: Filter the solids precipitated in S3, and continuously wash them with distilled water to remove impurities in the solution; S5: Dry the solids washed in S4 until the water content of the solids is less than 5%, and then screen them through a 65-mesh sieve to obtain uniform powder; S6: Mix the powder screened in S5 with the weighed surfactant and glucose, mix them using a high-speed mixer, and finally screen them through a 65-mesh sieve to obtain the final doxycycline hydrochloride soluble powder.

[0025] S2 specifically includes: S21: Add the doxycycline hydrochloride weighed in S1 to deionized water, and the volume of water is 15 times the mass of doxycycline hydrochloride; S22: Use a stirring device to stir at a speed of 250 rpm and continuously stir for 20 minutes until the doxycycline hydrochloride is completely dissolved; S23: After the dissolution is completed, obtain solution A, and control the dissolution temperature not to exceed 30 °C to avoid the degradation of doxycycline hydrochloride.

[0026] S3 specifically includes: S31: Add the chelating agent and stir solution A, control the stirring speed at 100 rpm, and continuously stir for 8 minutes to ensure its complete dissolution; S32: Sequentially add an acidifying agent, an antioxidant, a synergist, and a preservative, and continue stirring for 4 minutes after each addition to ensure that each component is evenly dispersed, forming a colorless solution; S33: After stirring evenly, place the colorless solution in a refrigerator at 4°C and let it stand for 36 hours until a solid precipitates; during the standing process, ensure that the solution is not affected by external light to avoid component degradation.

[0027] S4 specifically includes: S41: Filter the solid precipitated in S3 through a filtering device with a filtering accuracy of 75 mesh; S42: Put the filtered solid into a clean container and continuously wash it with distilled water 3 times, with the amount of distilled water used each time being 7 times the mass of the solid; S43: After each washing, use the filtering device to filter again to ensure that impurities on the surface of the solid are completely removed; S44: After the washing is completed, remove the excess moisture from the solid by suction filtration to prepare for the subsequent steps.

[0028] S5 specifically includes: S51: Place the solid washed in S4 in a drying device for drying, control the drying temperature at 55°C, and the drying time is 8 - 12 hours until the water content of the solid drops to 2%; S52: After drying is completed, use a 65 - mesh sieve for screening at a screening speed of 150 g / min to ensure that the solid is evenly dispersed and remove the undried particles; S53: After screening, obtain a uniform powder and prepare for the subsequent mixing step.

[0029] S6 specifically includes: S61: Put the powder screened in S5, the surfactant weighed in S1, and glucose into a high - speed mixer, set the mixing speed at 400 rpm, and the mixing time at 12 minutes to ensure uniform mixing; S62: After mixing is completed, screen the mixture through a 65 - mesh sieve to obtain the final doxycycline hydrochloride soluble powder.

[0030] Example 2 S1: Weigh 41.7% doxycycline hydrochloride, 3% chelating agent (calcium gluconate), 2% acidifying agent (citric acid), 1.5% surfactant (sodium dodecyl sulfate), 0.5% antioxidant (vitamin E), 1% synergist (glycerol), 0.3% preservative (potassium sorbate), and 50% glucose in accordance with a predetermined ratio; S2: Add doxycycline hydrochloride to the weighed deionized water. The volume of water is 10 times the mass of doxycycline hydrochloride. Use a stirring device to stir at 100 rpm for 10 minutes to ensure that doxycycline hydrochloride is completely dissolved. Control the dissolution temperature not to exceed 30 °C to obtain Solution A. S3: Add the weighed chelating agent to Solution A. Stir the solution at a stirring speed of 50 rpm for 5 minutes. Add citric acid, ascorbic acid, polyvinylpyrrolidone, and sodium benzoate in sequence. After each addition, continue to stir for 3 minutes until the solution is homogeneous. Then place the colorless solution in a refrigerator at 4 °C and let it stand for 24 hours until a solid precipitates. S4: Filter the precipitated solid through a 50-mesh filtering device. Wash the filtered solid continuously with distilled water 2 times. The amount of distilled water used for each wash is 5 times the mass of the solid. After each wash, use the filtering device to filter again to ensure that impurities on the surface of the solid are completely removed. Finally, remove the excess water by suction filtration. S5: Place the washed solid in a drying device at 50 °C and dry for 8 hours until the water content of the solid drops to 4%. After drying, sieve with a 65-mesh sieve at a sieving speed of 100 g / min to obtain a uniform powder. S6: Put the sieved powder, the weighed surfactant, and glucose into a high-speed mixer. Set the mixing speed to 300 rpm and the mixing time to 10 minutes to ensure uniform mixing. After mixing, sieve the mixture through a 65-mesh sieve to finally obtain soluble doxycycline hydrochloride powder.

[0031] Example 3 S1: Weigh 67.6% of doxycycline hydrochloride, 1% chelating agent (disodium ethylenediaminetetraacetate), 0.5% acidifying agent (citric acid), 0.5% surfactant (sodium dodecyl sulfate), 0.1% antioxidant (ascorbic acid), 0.2% synergist (polyvinylpyrrolidone), 0.1% preservative (sodium benzoate), and 30% glucose according to a predetermined ratio. S2: Add doxycycline hydrochloride to the weighed deionized water. The volume of water is 20 times the mass of doxycycline hydrochloride. Use a stirring device to stir at 300 rpm for 30 minutes to ensure that doxycycline hydrochloride is completely dissolved. Control the dissolution temperature not to exceed 30 °C to obtain Solution A. S3: Add the weighed chelating agent to Solution A. Stir the solution at a stirring speed of 150 rpm for 10 minutes. Add citric acid, ascorbic acid, polyvinylpyrrolidone, and sodium benzoate in sequence. After each addition, continue to stir for 5 minutes until the solution is homogeneous. Then place the colorless solution in a refrigerator at 4 °C and let it stand for 48 hours until a solid precipitates. S4: Filter the precipitated solid through a 100-mesh filtering device. Continuously wash the filtered solid 4 times with distilled water, with the amount of distilled water used for each wash being 10 times the mass of the solid. After each wash, use the filtering device to filter again to ensure that impurities on the surface of the solid are completely removed. Finally, remove the excess water by suction filtration. S5: Place the washed solid in a drying device at 60 °C and dry for 12 hours until the water content of the solid drops to 5%. After drying, sieve with a 65-mesh sieve at a sieving speed of 200 g / min to obtain uniform powder. S6: Put the sieved powder, the weighed surfactant, and glucose into a high-speed mixer, set the mixing speed at 500 rpm, and mix for 15 minutes to ensure uniform mixing. After mixing, sieve the mixture through a 65-mesh sieve to finally obtain the soluble powder of doxycycline hydrochloride.

[0032] Comparative Example 1 Step 1: Weigh 60% of doxycycline hydrochloride, 2% of citric acid, 1% of sodium dodecyl sulfate, and 37% of glucose. Ensure that the total mass of each component is 100%. Step 2: Dissolve doxycycline hydrochloride in an appropriate amount of deionized water (10 times the amount of water by the mass of doxycycline hydrochloride), and stir until completely dissolved. Then add citric acid, sodium dodecyl sulfate, and glucose, and continue to stir and mix for 10 - 15 minutes to ensure that all components are evenly distributed. Step 3: Subject the obtained solution to spray drying or freeze drying to obtain the soluble powder of doxycycline hydrochloride.

[0033] Table 1 Comparison of finished product performance parameters From the above Table 1, Solubility Example 1 performed the best with a dissolution time of 150 seconds. The dissolution rate of Example 3 was relatively fast (120 seconds), while that of Comparative Example 1 was the worst (210 seconds); for Particle Size, the particles of Example 1 were smaller (120 μm) and the powder dispersibility was better. Example 3 performed relatively well (110 μm), and Comparative Example 1 had the largest particles (150 μm), which might affect dissolution and application; for Powder Fluidity, Example 3 performed the best with a fluidity of 62 g / cm², Example 1 was slightly worse (60 g / cm²), and Comparative Example 1 had the lowest fluidity (55 g / cm²); for Moisture Content, Example 1 had the lowest moisture content (2%), while Comparative Example 1 and Example 2 had higher moisture contents (5%), which might affect the storage stability of the powder; for Color, the colors of Example 1 and Example 3 were white and the color was good, while Example 2 was light yellow, which might affect the appearance; for Stability, Example 3 had the best stability (15 months), while Comparative Example 1 had the worst stability (9 months), and Example 1 had better stability (12 months); for Solubility, Example 1 had the best solubility (98%), showing a relatively high bioavailability. Example 2 (95%) and Example 3 (96%) were slightly inferior, and Comparative Example 1 had the lowest solubility (92%); overall, Example 1 performed the best in multiple properties, especially in terms of solubility and moisture content; although Example 3 had a smaller particle size and a faster dissolution rate, its moisture content was relatively high; Comparative Example 1 performed poorly, especially in terms of solubility, powder fluidity, and stability.

[0034] Comparison of Other Performance Parameters in Table 2 As can be seen from Table 2 above, the dissolution rate of Example 1 is the highest (98%), and its dissolution rate after use is relatively fast; the dissolution rate of Comparative Example 1 is the lowest (92%); the average particle size of Example 3 is the smallest (110 μm), indicating that this formulation is superior to other examples in terms of particle size control; the particle size of Comparative Example 1 is the largest (150 μm); the bulk density of Example 1 is relatively low (0.4 g / cm³), indicating that its powder structure is relatively compact; while the bulk density of Comparative Example 1 is the highest (0.6 g / cm³), which may affect fluidity; the particle size distribution width of Example 1 is relatively narrow (50 μm), which is beneficial to improving the uniformity of the product; the distribution width of Comparative Example 1 is the widest (70 μm), which may affect the final dissolution and application effects; Example 3 is produced at a relatively low preparation temperature (23 °C), which helps to protect the stability of the components; the preparation temperature of Comparative Example 1 is relatively high (30 °C), which may affect the retention of the active ingredients; the packaging stability of Example 1 is the best (99%), indicating that it can maintain stability better during storage; the packaging stability of Comparative Example 1 is relatively poor (94%). Generally speaking, Example 1 performs best in terms of various properties, especially having obvious advantages in dissolution rate, packaging stability, particle size distribution and preparation temperature control The present invention covers any alternatives, modifications, equivalent methods and solutions made within the spirit and scope of the present invention. For the public to have a thorough understanding of the present invention, specific details are described in detail in the following preferred embodiments of the present invention, and those skilled in the art can fully understand the present invention without the description of these details. In addition, well-known methods, processes, procedures, components and circuits, etc. are not described in detail to avoid unnecessary confusion to the essence of the present invention

[0035] The above description is only a preferred embodiment of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention

Claims

1. A doxycycline hydrochloride soluble powder, characterized in that, It includes doxycycline hydrochloride, chelating agent, acidifying agent, surfactant, antioxidant, synergist, preservative and glucose; among which the components are in the following mass percentages: The mass of doxycycline hydrochloride is 41.7% - 67.6%; The mass of the chelating agent is 1% - 3%; The mass of the acidifying agent is 0.5% - 2%; The mass of the surfactant is 0.5% - 1.5%; The mass of the antioxidant is 0.1% - 0.5%; The mass of the synergist is 0.2% - 1%; The mass of the preservative is 0.1% - 0.3%; The mass of glucose is 30% - 50%.

2. The soluble powder of doxycycline hydrochloride according to claim 1, wherein The chelating agent is selected from disodium ethylenediaminetetraacetate or calcium gluconate; the acidifying agent is citric acid; the antioxidant is ascorbic acid or vitamin E; the synergist is selected from polyvinylpyrrolidone or glycerol; the preservative is selected from sodium benzoate or potassium sorbate.

3. The soluble powder of doxycycline hydrochloride according to claim 1, characterized in that The surfactant is sodium dodecyl sulfate.

4. A preparation method of doxycycline hydrochloride soluble powder, which is used to prepare the doxycycline hydrochloride soluble powder according to any one of claims 1-3, and is characterized in that, It includes the following steps: S1: Weigh doxycycline hydrochloride, chelating agent, acidifying agent, surfactant, antioxidant, synergist, preservative and glucose according to a predetermined ratio; S2: Dissolve doxycycline hydrochloride in a predetermined amount of deionized water to obtain solution A; S3: Add the chelating agent, acidifying agent, antioxidant, synergist and preservative to solution A, mix evenly to form a colorless solution, and place it under refrigeration conditions and let it stand until solids precipitate; S4: Filter the solids precipitated in S3, and continuously wash them with distilled water to remove impurities in the solution; S5: Dry the solids washed in S4 until the water content of the solids is less than 5%, and then screen them through a 65-mesh sieve to obtain uniform powder; S6: Mix the powder screened in S5 with the weighed surfactant and glucose, use a high-speed mixer to mix, and finally screen through a 65-mesh sieve to obtain the final soluble powder of doxycycline hydrochloride.

5. The preparation method of a soluble powder of doxycycline hydrochloride according to claim 4, characterized in that, The specific content of S2 includes: S21: Add the doxycycline hydrochloride weighed in S1 to deionized water, and the volume of water is 10 - 20 times the mass of doxycycline hydrochloride; S22: Use a stirring device to stir at a speed of 100 - 300 rpm, and continuously stir for 10 - 30 minutes until doxycycline hydrochloride is completely dissolved; S23: After dissolution is completed, obtain solution A, and control the dissolution temperature not to exceed 30°C to avoid the degradation of doxycycline hydrochloride.

6. The preparation method of a soluble powder of doxycycline hydrochloride according to claim 4, characterized in that, The specific content of S3 includes: S31: Add the chelating agent and stir solution A, control the stirring speed at 50 - 150 rpm, and continuously stir for 5 - 10 minutes; S32: Add the acidifying agent, antioxidant, synergist and preservative in sequence, and continue to stir for 3 - 5 minutes after each addition to ensure that each component is evenly dispersed to form a colorless solution; S33: After stirring evenly, place the colorless solution under refrigeration conditions at 4°C and let it stand for 24 - 48 hours until solids precipitate.

7. The preparation method of a soluble powder of doxycycline hydrochloride according to claim 4, characterized in that, The specific content of S4 includes: S41: Filter the solids precipitated in S3 through a filtering device, and the filtering accuracy is 50 - 100 meshes; S42: Put the filtered solids into a clean container, and continuously wash them with distilled water. The number of washing times is 2 - 4 times, and the amount of distilled water used each time is 5 - 10 times the mass of the solids; S43: After each washing, use a filtering device to filter again to ensure that impurities are completely removed from the solid surface; S44: After washing is completed, remove the excess moisture from the solid by draining and filtering.

8. The preparation method of a soluble powder of doxycycline hydrochloride according to claim 4, characterized in that, The specific steps of S5 include: S51: Place the washed solid in S4 in a drying device for drying. Control the drying temperature at 50°C - 60°C and the drying time at 8 - 12 hours until the water content of the solid drops below 5%; S52: After drying is completed, use a 65-mesh sieve for screening at a screening speed of 100 - 200 g / min to ensure that the solid is evenly dispersed and remove the particles that are not completely dry; S53: After screening, obtain uniform powder.

9. The preparation method of a soluble powder of doxycycline hydrochloride according to claim 4, characterized in that, The specific steps of S6 include: S61: Put the powder screened in S5, the surfactant weighed in S1, and glucose into a high-speed mixer. Set the mixing speed at 300 - 500 rpm and the mixing time at 10 - 15 minutes to ensure uniform mixing; S62: After mixing is completed, screen the mixture through a 65-mesh sieve to obtain the final doxycycline hydrochloride soluble powder.

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