Pharmaceutical preparation for improving stability and preparation process thereof
By defining the purity and particle size of the active pharmaceutical ingredients in veterinary drug preparations, and adopting a composite stabilizer and strict preparation process, the problems of easy degradation of the active ingredients and insufficient stability of the preparation are solved, and the long-term stability and high-efficiency efficacy of the drug are achieved.
Patent Information
- Application Number
- CN202411807784.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-10
- Publication Date
- 2025-03-14
AI Technical Summary
The active ingredients in existing veterinary drug preparations are prone to degradation and the overall stability of the preparations is poor, resulting in a decrease in drug efficacy and a shortened shelf life.
By limiting the purity of veterinary active pharmaceutical ingredients not less than 95% and the particle size range is 10-50 μm, and a composite stabilizer of ascorbyl palmitate and disodium ethylenediaminetetraacetate is used, combined with strict raw material pretreatment and multi-step preparation process, a stable pharmaceutical dosage form structure is formed.
It significantly improves the stability of the active ingredients of the drug and the stability of the overall preparation, extends the shelf life of the drug, and ensures the full use of the drug effect.
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Figure BDA0005179740760000081 
Figure BDA0005179740760000091
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of veterinary medicines, in particular to a pharmaceutical preparation with improved stability and a preparation process thereof. Background Art
[0002] In many fields such as modern animal husbandry, pet healthcare, and aquatic animal farming, veterinary drug preparations play a vital role and are one of the key factors in ensuring animal health and promoting the sustainable development of the industry. With the continuous expansion of the scale of breeding and the increasing attention paid to animal health, higher requirements have been put forward for the quality, stability, and efficacy of veterinary drug preparations. However, the existing veterinary drug preparation technology still has many problems to be solved in practical applications, which limits its better service for animal disease prevention and health management. Therefore, it is urgent to develop new veterinary drug preparation technologies with better performance.
[0003] (1) Active ingredients are easily degraded: In most existing veterinary drug preparations, the particle size control of active drug ingredients is not precise enough, and the particle sizes are often uneven. For example, some antibiotic drugs have a wide range of particle sizes in preparations. Compared with small particles, large particles of active drug ingredients have a smaller specific surface area and a slower dissolution rate. During storage, they are prone to excessive local concentrations and accelerate their own degradation. At the same time, the lack of an effective synergistic stabilization system makes it difficult to resist the influence of external environmental factors (such as high temperature, high humidity, light, etc.), resulting in the chemical structure of the active ingredients being easily destroyed during storage, and the effective content gradually decreasing, affecting the efficacy and shelf life of the drug. For example, the common enrofloxacin preparation will show a significant decrease in its active ingredient content after being stored in a high temperature and high humidity environment for a period of time, and the expected therapeutic effect cannot be guaranteed.
[0004] (II) Poor overall stability of the preparation: In terms of the preparation process, the existing technology often does not pay enough attention to the pretreatment of raw materials, and does not strictly control key indicators such as the moisture content in the raw materials, which makes the drug prone to hydrolysis due to moisture during subsequent storage, especially some drug components containing easily hydrolyzed structures such as ester bonds and amide bonds. In addition, the parameter settings of the granulation and drying process are not reasonable, resulting in a loose and uneven structure of the drug particles. During transportation or long-term storage, the particles are easy to break and the drug components migrate, which ultimately greatly reduces the stability of the entire preparation and cannot maintain a good quality state for a long time. Summary of the invention
[0005] The object of the present invention is to provide a pharmaceutical preparation with improved stability and a preparation process thereof, so as to solve the problem of insufficient drug stability of existing veterinary pharmaceutical preparations in the above-mentioned background technology.
[0006] To achieve the above object, the present invention provides the following technical solutions:
[0007] A pharmaceutical preparation with improved stability comprises the following raw materials in parts by weight: 10-50 parts of veterinary active pharmaceutical ingredients, 3-15 parts of stabilizers, 5-20 parts of cosolvents, 15-40 parts of excipients and 1-5 parts of lubricants, wherein the veterinary active pharmaceutical ingredients comprise antibiotic drugs, anthelmintic drugs, nutritional supplement drugs or antipyretic, analgesic and anti-inflammatory drugs.
[0008] Preferably, the purity of the veterinary active pharmaceutical ingredient is not less than 95%, and its particle size range is 10-50 μm.
[0009] Preferably, the stabilizer is a composite stabilizer in which ascorbyl palmitate and disodium ethylenediaminetetraacetate are mixed in a ratio of 1:1.
[0010] Preferably, the co-solvent is selected from one or more of polyethylene glycol and propylene glycol, and the polyethylene glycol includes PEG400 or PEG600.
[0011] Preferably, the excipient is a mixture of microcrystalline cellulose and lactose in a weight ratio of 1:1-3:1.
[0012] Preferably, the lubricant is ultrafinely pulverized magnesium stearate, with a particle size of less than 10 μm.
[0013] Preferably, the antibiotic drug includes neomycin sulfate or enrofloxacin, the anthelmintic drug includes albendazole or ivermectin, the nutritional supplement drug includes vitamin C, and the antipyretic, analgesic and anti-inflammatory drug includes carbaspirin calcium.
[0014] On the other hand, the present invention also provides a process for preparing a pharmaceutical preparation with improved stability, which specifically comprises the following steps:
[0015] S10 Raw material pretreatment: micronize the veterinary active pharmaceutical ingredients to a particle size of 10-50 μm, and dry the stabilizer, cosolvent, excipient and lubricant to a moisture content of less than 3%;
[0016] S20 mixing: weighing the raw materials according to the above weight parts, first placing the veterinary active pharmaceutical ingredient, the stabilizer and the co-solvent in a mixer, and mixing for 15-30 minutes at a speed of 100-300 r / min to obtain a premix;
[0017] S30 secondary mixing: adding excipients to the premix in step S20, and continuing to mix at a speed of 200-400 r / min for 20-40 minutes;
[0018] S40 granulation: add an appropriate amount of adhesive to the secondary mixed material to make a soft material, and granulate it through a sieve with a mesh size of 10-20;
[0019] S50 drying: the obtained wet granules are placed in a drying device at a temperature of 40-60°C and dried until the moisture content is less than 5%;
[0020] S60 granulation and total mixing: the dried granules are granulated, and then a lubricant is added, and the mixture is mixed for 10-20 minutes at a rotation speed of 150-350 r / min to obtain the pharmaceutical preparation with improved stability.
[0021] Preferably, the adhesive is starch slurry or povidone, and the added amount is 1-5% of the veterinary active pharmaceutical ingredient.
[0022] Preferably, the micronization treatment is carried out by a jet mill with a pulverizing pressure of 0.4-0.8 MPa, and the drying equipment is a vacuum drying oven or a fluidized bed dryer.
[0023] Compared with the prior art, the present invention has the following beneficial effects:
[0024] (1) Good protection effect of active ingredients: By limiting the purity of veterinary active pharmaceutical ingredients to no less than 95% and a specific particle size range (10-50μm), the active ingredients can have better uniformity and dispersibility, and reduce the occurrence of instability such as agglomeration and degradation caused by factors such as uneven particle size. For example, for antibiotics such as neomycin sulfate and enrofloxacin, the appropriate particle size helps them to be evenly distributed in the preparation, avoiding excessive local concentration and causing excessive decomposition, thereby better maintaining their chemical structure integrity during storage and ensuring drug efficacy. A composite stabilizer is used in which ascorbyl palmitate and disodium ethylenediaminetetraacetate are mixed in a 1:1 ratio, and the two play a synergistic role. Ascorbyl palmitate can effectively resist oxidation and prevent the active pharmaceutical ingredients from deteriorating due to oxidation; disodium ethylenediaminetetraacetate can chelate metal ions and reduce the catalytic effect of metal ions on chemical reactions such as drug oxidation and hydrolysis. It ensures the stability of active pharmaceutical ingredients under different storage conditions (such as high temperature and high humidity environments) from multiple ways, and extends the shelf life of the drug.
[0025] (2) Enhanced overall formulation stability:
[0026] In the preparation process, strict pretreatment of raw materials, such as drying each raw material to make its moisture content less than 3%, can avoid drug hydrolysis, mildew and other stability problems caused by excessive moisture. Especially for some water-sensitive drug ingredients (such as some anthelmintics, antibiotics, etc.), such pretreatment is an important link to maintain the long-term stability of the preparation.
[0027] After multiple steps and reasonable mixing, granulation, drying, granulation and total mixing, the raw materials can be evenly distributed and tightly combined in the preparation to form a stable drug dosage form structure. For example, selecting a suitable binder (such as starch slurry or povidone) in the granulation process and controlling its addition amount and the number of meshes of the granulation screen can help to produce a preparation with uniform particles and a tight structure, and prevent the particles from breaking and drug component migration during storage and transportation, which may lead to a decrease in stability.
[0028] (3) The drug efficacy is fully exerted:
[0029] Since the preparation has good stability and dissolution properties, the active pharmaceutical ingredients can function stably and efficiently in animals. Whether it is treating infectious diseases (such as using antibiotic active ingredients such as neomycin sulfate and enrofloxacin to deal with various infections in livestock and poultry), expelling parasites (such as albendazole and ivermectin to play an anthelmintic role), or relieving symptoms such as fever, pain, and inflammation in animals (with the help of antipyretic, analgesic, and anti-inflammatory drugs such as carbaspirin calcium) and supplementing nutrition (through vitamin C, etc.), it can achieve better therapeutic or health care effects, improve the health level of animals, and have a positive promoting effect on industries such as animal husbandry.
[0030] (4) Wide range of applications:
[0031] It covers veterinary active pharmaceutical ingredients of various functional types (antibiotics, anthelmintics, nutritional supplements, antipyretic, analgesic and anti-inflammatory drugs). The active ingredients in the formula can be flexibly adjusted according to the needs of different animal species and different diseases to prepare targeted pharmaceutical preparations. It can be widely used in disease prevention and health management in multiple fields such as livestock, pets and aquatic animals, and has strong practicality and market application prospects. DETAILED DESCRIPTION
[0032] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.
[0033] Example 1
[0034] Raw materials preparation:
[0035] Veterinary active pharmaceutical ingredients: 30 parts of neomycin sulfate with a purity of 98% were selected and micronized by a jet mill at a crushing pressure of 0.6 MPa to a particle size of 30 μm.
[0036] Stabilizer: Weigh 10 parts of a composite stabilizer prepared by mixing ascorbyl palmitate and disodium ethylenediaminetetraacetate in a ratio of 1:1, and dry the composite stabilizer in a vacuum drying oven to a moisture content of less than 3%.
[0037] Cosolvent: Use 12 parts of PEG400 and also perform drying treatment to ensure that the moisture content meets the requirements.
[0038] Excipient: Mix microcrystalline cellulose and lactose in a weight ratio of 2:1 to obtain 25 parts of excipient, and dry them for later use.
[0039] Lubricant: Take 3 parts of magnesium stearate that has been ultrafinely crushed and has a particle size of less than 10 μm and set aside.
[0040] Preparation process steps:
[0041] S20 mixing: put the treated neomycin sulfate, composite stabilizer and PEG400 into a mixer, and mix them for 20 minutes at a rotation speed of 200 r / min to obtain a premix.
[0042] S30 Secondary mixing: Add excipients to the premix and continue mixing at a speed of 300 r / min for 30 minutes.
[0043] S40 granulation: Add starch slurry (the added amount is 3% of neomycin sulfate) to the secondary mixed material to make a soft material, and granulate through a 15-mesh screen.
[0044] S50 drying: The prepared wet granules are placed in a vacuum drying oven at a temperature of 50°C and dried until the moisture content is less than 5%.
[0045] S60 granulation and total mixing: The dried granules were granulated, and then magnesium stearate was added and total mixed for 15 minutes at a rotation speed of 250 r / min to obtain a pharmaceutical preparation with improved stability.
[0046] Example 2
[0047] Raw materials preparation:
[0048] Veterinary active pharmaceutical ingredient: 20 parts of enrofloxacin with a purity of 96% were selected and micronized to a particle size of 20 μm using a jet mill at a crushing pressure of 0.5 MPa.
[0049] Stabilizer: Prepare 8 parts of a composite stabilizer prepared by mixing ascorbyl palmitate and disodium ethylenediaminetetraacetate in a ratio of 1:1, and dry it to a moisture content of less than 3%.
[0050] Cosolvent: Take 10 parts of propylene glycol and 5 parts of PEG600, dry them and set aside.
[0051] Excipients: Mix microcrystalline cellulose and lactose in a weight ratio of 1.5:1 into 30 parts of excipients and complete drying.
[0052] Lubricant: Prepare 2 parts of ultrafinely ground magnesium stearate with a particle size of less than 10 μm.
[0053] Preparation process steps:
[0054] S20 mixing: put enrofloxacin, composite stabilizer, propylene glycol and PEG600 into a mixer and mix at a speed of 150 r / min for 25 minutes to obtain a premix.
[0055] S30 Secondary mixing: add excipients to the premix, followed by mixing at a rotation speed of 250 r / min for 35 minutes.
[0056] S40 granulation: Add povidone (the amount added is 2% of enrofloxacin) as a binder to make a soft material, and granulate through a 12-mesh sieve.
[0057] S50 Drying: The wet granules were dried in a fluidized bed dryer at 45°C until the moisture content was less than 5%.
[0058] S60 granulation and total mixing: After the dried granules are granulated, magnesium stearate is added and the mixture is mixed for 18 minutes at a rotation speed of 200 r / min to obtain a pharmaceutical preparation with improved stability.
[0059] Example 3
[0060] Raw materials preparation:
[0061] Veterinary active pharmaceutical ingredients: 15 parts of albendazole, 10 parts of vitamin C, and 5 parts of carbaspirin calcium are mixed (the purity of the three is not less than 95%), and micronized by a jet mill at a pressure of 0.7 MPa to make the particle size of each component in the range of 10-50 μm.
[0062] Stabilizer: Weigh 12 parts of a composite stabilizer prepared by mixing ascorbyl palmitate and disodium ethylenediaminetetraacetate in a ratio of 1:1, and dry the mixture until the moisture content is less than 3%.
[0063] Co-solvent: Use 8 parts of PEG400 and dry it for later use.
[0064] Excipient: 35 parts of excipient were obtained by mixing microcrystalline cellulose and lactose in a weight ratio of 3:1 and used after drying.
[0065] Lubricant: Prepare 4 parts of magnesium stearate with a particle size of less than 10 μm.
[0066] Preparation process steps:
[0067] S20 mixing: the mixed veterinary active pharmaceutical ingredients, the composite stabilizer and PEG400 are placed in a mixer, and mixed for 18 minutes at a rotation speed of 250 r / min to obtain a premix.
[0068] S30 Secondary mixing: Add excipients to the premix and continue mixing at a speed of 350 r / min for 25 minutes.
[0069] S40 granulation: Add starch slurry (the amount added is 4% of the total weight of albendazole, vitamin C and carbaspirin calcium) to make a soft material, and granulate through an 18-mesh screen.
[0070] S50 drying: The wet granules are placed in a vacuum drying oven at 55°C and dried until the moisture content is less than 5%.
[0071] S60 granulation and total mixing: The dried granules were granulated, and then magnesium stearate was added and total mixed for 12 minutes at a rotation speed of 300 r / min to obtain a pharmaceutical preparation with improved stability.
[0072] Comparative Example 1
[0073] Raw materials preparation:
[0074] Veterinary active pharmaceutical ingredient: 30 parts of neomycin sulfate (purity 98%, not micronized, particle size greater than 50 μm) were selected.
[0075] Stabilizer: Only 5 parts of ascorbyl palmitate was used (without composite stabilizer), and a simple drying process was performed to make its moisture content slightly lower than 3%.
[0076] Cosolvent: Take 12 parts of PEG400 and dry it for later use.
[0077] Excipient: 25 parts of an excipient mixed with microcrystalline cellulose and lactose at a ratio of 2:1, used after drying.
[0078] Lubricant: 3 parts of ordinary magnesium stearate (not subjected to ultrafine grinding treatment, particle size greater than 10 μm).
[0079] Preparation process steps:
[0080] S20 mixing: neomycin sulfate, ascorbyl palmitate and PEG400 are put into a mixer and mixed for 20 minutes at a rotation speed of 200 r / min to obtain a premix.
[0081] S30 Secondary mixing: Add excipients to the premix and continue mixing at a speed of 300 r / min for 30 minutes.
[0082] S40 granulation: Add starch slurry (the added amount is 3% of neomycin sulfate) to make a soft material, and granulate through a 15-mesh screen.
[0083] S50 drying: The wet granules are placed in a vacuum drying oven at 50°C and dried until the moisture content is less than 5%.
[0084] S60 granulation and mixing: The dried granules were granulated, and then magnesium stearate was added and mixed for 15 minutes at a rotation speed of 250 r / min to obtain a pharmaceutical preparation.
[0085] Comparative Example 2
[0086] Raw materials preparation:
[0087] Veterinary active pharmaceutical ingredient: 20 parts of enrofloxacin (purity 96%, micronized to a particle size of 20 μm as required) were selected.
[0088] Stabilizer: 8 parts of a composite stabilizer prepared by mixing ascorbyl palmitate and disodium ethylenediaminetetraacetate in a ratio of 1:1 was used, and dried to reduce the moisture content to less than 3%.
[0089] Cosolvent: Take 10 parts of propylene glycol and 5 parts of PEG600, dry them and set aside.
[0090] Excipients: Microcrystalline cellulose and lactose were mixed in a weight ratio of 1.5:1 to form 30 parts of excipients and dried.
[0091] Lubricant: Prepare 2 parts of ultrafinely ground magnesium stearate with a particle size of less than 10 μm.
[0092] Preparation process steps:
[0093] S20 mixing: put enrofloxacin, composite stabilizer, propylene glycol and PEG600 into a mixer and mix at a speed of 150 r / min for 25 minutes to obtain a premix.
[0094] S30 Secondary mixing: add excipients to the premix, followed by mixing at a rotation speed of 250 r / min for 35 minutes.
[0095] S40 granulation: No binder was added, and granulation was directly attempted through a 12-mesh screen (compared with Example 2, the granulation conditions were changed here to remove the binder).
[0096] S50 Drying: The wet granules were dried in a fluidized bed dryer at 45°C until the moisture content was less than 5%.
[0097] S60 granulation and total mixing: After the dried granules are granulated, magnesium stearate is added and the mixture is mixed for 18 minutes at a rotation speed of 200 r / min to obtain a pharmaceutical preparation.
[0098]
[0099]
[0100] The pharmaceutical preparation with improved stability and its preparation process of the present invention have the following characteristics:
[0101] (1) Good protection effect of active ingredients: By limiting the purity of veterinary active pharmaceutical ingredients to no less than 95% and a specific particle size range (10-50μm), the active ingredients can have better uniformity and dispersibility, and reduce the occurrence of instability such as agglomeration and degradation caused by factors such as uneven particle size. For example, for antibiotics such as neomycin sulfate and enrofloxacin, the appropriate particle size helps them to be evenly distributed in the preparation, avoiding excessive local concentration and causing excessive decomposition, thereby better maintaining their chemical structure integrity during storage and ensuring drug efficacy. A composite stabilizer is used in which ascorbyl palmitate and disodium ethylenediaminetetraacetate are mixed in a 1:1 ratio, and the two play a synergistic role. Ascorbyl palmitate can effectively resist oxidation and prevent the active pharmaceutical ingredients from deteriorating due to oxidation; disodium ethylenediaminetetraacetate can chelate metal ions and reduce the catalytic effect of metal ions on chemical reactions such as drug oxidation and hydrolysis. It ensures the stability of active pharmaceutical ingredients under different storage conditions (such as high temperature and high humidity environments) from multiple ways, and extends the shelf life of the drug.
[0102] (2) Enhanced overall formulation stability:
[0103] In the preparation process, strict pretreatment of raw materials, such as drying each raw material to make its moisture content less than 3%, can avoid drug hydrolysis, mildew and other stability problems caused by excessive moisture. Especially for some water-sensitive drug ingredients (such as some anthelmintics, antibiotics, etc.), such pretreatment is an important link to maintain the long-term stability of the preparation.
[0104] After multiple steps and reasonable mixing, granulation, drying, granulation and total mixing, the raw materials can be evenly distributed and tightly combined in the preparation to form a stable drug dosage form structure. For example, selecting a suitable binder (such as starch slurry or povidone) in the granulation process and controlling its addition amount and the number of meshes of the granulation screen can help to produce a preparation with uniform particles and a tight structure, and prevent the particles from breaking and drug component migration during storage and transportation, which may lead to a decrease in stability.
[0105] The pharmaceutical preparation with improved stability and the preparation process thereof of the present invention improve the quality and performance of the pharmaceutical preparation:
[0106] (1) The drug efficacy is fully exerted:
[0107] Since the preparation has good stability and dissolution properties, the active pharmaceutical ingredients can function stably and efficiently in animals. Whether it is treating infectious diseases (such as using antibiotic active ingredients such as neomycin sulfate and enrofloxacin to deal with various infections in livestock and poultry), expelling parasites (such as albendazole and ivermectin to play an anthelmintic role), or relieving symptoms such as fever, pain, and inflammation in animals (with the help of antipyretic, analgesic, and anti-inflammatory drugs such as carbaspirin calcium) and supplementing nutrition (through vitamin C, etc.), it can achieve better therapeutic or health care effects, improve the health level of animals, and have a positive promoting effect on industries such as animal husbandry.
[0108] (2) Wide range of applications:
[0109] It covers veterinary active pharmaceutical ingredients of various functional types (antibiotics, anthelmintics, nutritional supplements, antipyretic, analgesic and anti-inflammatory drugs). The active ingredients in the formula can be flexibly adjusted according to the needs of different animal species and different diseases to prepare targeted pharmaceutical preparations. It can be widely used in disease prevention and health management in multiple fields such as livestock, pets and aquatic animals, and has strong practicality and market application prospects.
[0110] In summary, the pharmaceutical preparation and preparation process of the present invention improve the comprehensive performance of the drug in many aspects, and are of great significance to the improvement of product quality in the field of veterinary medicine and the prevention and treatment of animal diseases.
[0111] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments. The above embodiments and descriptions are only preferred examples of the present invention and are not intended to limit the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, which fall within the scope of the present invention. The scope of protection of the present invention is defined by the attached claims and their equivalents.
Claims
1. A pharmaceutical preparation with improved stability, characterized in that: The raw materials include the following parts by weight: 10-50 parts of veterinary active drugs, 3-15 parts of stabilizers, 5-20 parts of cosolvents, 15-40 parts of excipients and 1-5 parts of lubricants. The veterinary active drugs include antibiotics, anthelmintics, nutritional supplements or antipyretic, analgesic and anti-inflammatory drugs.
2. The pharmaceutical preparation with improved stability according to claim 1, characterized in that: The purity of the veterinary active drug is not less than 95%, and its particle size range is 10-50 μm.
3. The pharmaceutical preparation with improved stability according to claim 1, characterized in that: The stabilizer is a composite stabilizer in which ascorbyl palmitate and disodium ethylenediaminetetraacetate are mixed in a ratio of 1:
1.
4. The pharmaceutical preparation with improved stability according to claim 1, characterized in that: The cosolvent is selected from one or more of polyethylene glycol and propylene glycol, and the polyethylene glycol includes PEG400 or PEG600.
5. The pharmaceutical preparation with improved stability according to claim 1, characterized in that: The excipient is a mixture of microcrystalline cellulose and lactose in a weight ratio of 1:1-3:
1.
6. The pharmaceutical preparation with improved stability according to claim 1, characterized in that: The lubricant is magnesium stearate that has been subjected to ultrafine grinding treatment, and its particle size is less than 10 μm.
7. The pharmaceutical preparation with improved stability according to claim 1, characterized in that: The antibiotic drugs include neomycin sulfate or enrofloxacin, the anthelmintic drugs include albendazole or ivermectin, the nutritional supplement drugs include vitamin C, and the antipyretic, analgesic and anti-inflammatory drugs include carbaspirin calcium.
8. A process for preparing a pharmaceutical preparation with improved stability, comprising the pharmaceutical preparation with improved stability according to any one of claims 1 to 7, characterized in that: The specific steps include: S10 Raw material pretreatment: micronize the veterinary active drug cost to make its particle size reach 10-50μm, and dry the stabilizer, co-solvent, excipient and lubricant respectively to make its moisture content less than 3%; S20 mixing: weighing the raw materials according to the above weight parts, first placing the veterinary active drug cost, stabilizer and co-solvent in a mixer, and mixing for 15-30 minutes at a speed of 100-300 r / min to obtain a premix; S30 secondary mixing: adding excipients to the premix in step S20, and continuing to mix at a speed of 200-400 r / min for 20-40 minutes; S40 granulation: add an appropriate amount of adhesive to the secondary mixed material to make a soft material, and granulate it through a sieve with a mesh size of 10-20; S50 drying: the obtained wet granules are placed in a drying device at a temperature of 40-60°C and dried until the moisture content is less than 5%; S60 granulation and total mixing: the dried granules are granulated, and then a lubricant is added, and the mixture is mixed for 10-20 minutes at a rotation speed of 150-350 r / min to obtain the pharmaceutical preparation with improved stability.
9. The process for preparing a pharmaceutical preparation with improved stability according to claim 8, characterized in that: The adhesive is selected from starch slurry or polyvidone, and the added amount is 1-5% of the cost of the veterinary active drug.
10. The process for preparing a pharmaceutical preparation with improved stability according to claim 8, characterized in that: The micronization treatment is carried out by using a jet mill with a crushing pressure of 0.4-0.8 MPa, and the drying equipment is a vacuum drying oven or a fluidized bed dryer.