CN112121016A - Water-soluble florfenicol powder and preparation method thereof - Google Patents
Water-soluble florfenicol powder and preparation method thereof Download PDFInfo
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- CN112121016A CN112121016A CN202011072557.8A CN202011072557A CN112121016A CN 112121016 A CN112121016 A CN 112121016A CN 202011072557 A CN202011072557 A CN 202011072557A CN 112121016 A CN112121016 A CN 112121016A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
The invention relates to the technical field of veterinary medicines, and in particular relates to water-soluble florfenicol powder and a preparation method thereof. The water-soluble florfenicol powder comprises the following raw materials: florfenicol; at least one inclusion agent is selected from: beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin; at least one dispersant selected from: hypromellose, sodium alginate and sodium carboxymethylcellulose; at least one co-solvent is selected from: sodium citrate, sodium succinate and acetamide; and adopts a pressure type spray drying treatment mode. The solubility of the water-soluble florfenicol powder in water at 15 ℃ reaches 6mg/mL, which is far higher than 3mg/mL (25 ℃) of the prior art, and is more than 12 times of the solubility of the bulk drugs; the dissolution speed is high, and the dissolution time is less than 1 min; compared with similar products, the compound preparation has great advantages, improves the bioavailability of the medicine, solves the problem that the water line is easy to block when the concentrated drinking water administration of the livestock is carried out, and has good application prospect.
Description
Technical Field
The invention relates to the technical field of veterinary medicines, and in particular relates to water-soluble florfenicol powder and a preparation method thereof.
Background
FlorFenicol (FlorFenicol), also known as FlorFenicol, is an excellent broad-spectrum antibiotic special for animals, is mainly used for bacterial diseases of pigs, chickens and fish caused by sensitive bacteria, and has obvious curative effect on respiratory system infection and intestinal tract infection. Florfenicol belongs to class ii drugs in biopharmaceutical classification systems, i.e., low solubility/high permeability drugs. Because the solubility of the compound in water is extremely low and is less than 1mg/mL at normal temperature, the bioavailability is seriously influenced. When drinking water is concentrated for administration, the water line is easy to block. Therefore, improving the solubility of florfenicol in water becomes a hotspot and a difficulty of research.
At present, methods for improving the water solubility of florfenicol mainly comprise micronization, preparation of solid dispersions, inclusion compounds and the like. Patent application CN102697730A discloses a florfenicol soluble powder and a preparation method thereof, wherein the florfenicol soluble powder comprises: 65-75% of florfenicol, 600010-15% of polyethylene glycol, 5-10% of PVP and 5-10% of carbomer; and the florfenicol is prepared by a solid dispersion technology, but the method has limited effect of improving the florfenicol solubility. Patent applications CN101966340A and CN106798731A both disclose methods for preparing florfenicol powder by cyclodextrin inclusion technique, however, both of them use a large amount of DMF as a cosolvent, are flammable and explosive, are extremely unsafe to operate, and easily cause organic solvent residue. Patent application CN105055319A discloses florfenicol soluble powder and a preparation method thereof, wherein the florfenicol is prepared by an inclusion method, but a large amount of hydroxypropyl beta cyclodextrin is needed, so that the production cost is high. Patent application CN109602916A discloses a florfenicol inclusion compound and a preparation method thereof, wherein florfenicol powder is prepared by adopting normal-temperature inclusion, and the method has low yield due to the limitation of the solubility of cyclodextrin. Patent application CN108721220A discloses a high-efficiency water-soluble florfenicol powder and a preparation method thereof, wherein the florfenicol powder is prepared by a method of first inclusion and then centrifugal spray drying, and because the used dispersion carrier is poloxamer, the florfenicol has limited dispersion effect, the improvement of solubility is not significant, and the florfenicol powder can only be dissolved at most by 3mg/mL (25 ℃); in addition, because poloxamers have no crystallization inhibition effect, amorphous florfenicol is converted into crystals in the process of placing finished products, so that the solubility is reduced; because the centrifugal spray drying mode is adopted, the prepared particles are generally solid spheres, and water molecules are not easy to enter the spheres, so that the solubility is not high and the dissolving speed is low.
In short, the current methods for preparing florfenicol inclusion compounds using cyclodextrins and their derivatives have the following major drawbacks: (1) a large amount of DMF solvent is used in the preparation process, the operation is unsafe, and solvent residue is easy to cause; (2) a large amount of hydroxypropyl beta cyclodextrin is used, so the production cost is high; (3) the dispersant is not properly selected, the solubility is improved to a limited extent, and the product stability is problematic; (4) the solid particles are prepared by adopting a centrifugal spray granulation mode, and have low dissolubility and slow dissolution speed.
Disclosure of Invention
The present invention is directed to solving at least one of the problems of the prior art. Therefore, the invention provides the water-soluble florfenicol powder and the preparation method thereof, and the product has no organic solvent residue, high solubility in water, good stability, low production cost and high yield; the preparation method has simple process and easy operation, and is beneficial to large-scale production.
The technical scheme of the invention is shown as follows.
The invention provides a water-soluble florfenicol powder, which comprises the following raw materials:
florfenicol;
an inclusion agent selected from the group consisting of: at least one of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin;
a dispersant selected from the group consisting of: at least one of hypromellose, sodium alginate and sodium carboxymethylcellulose;
a co-solvent selected from: at least one of sodium citrate, sodium succinate and acetamide.
The water-soluble florfenicol powder adopts a molecular inclusion technology and a solid dispersion technology, the inclusion agent is added, so that most of medicines are included in high molecular beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin, and free medicines are highly dispersed in a solid dispersing agent, so that the solubility of the florfenicol powder is greatly improved. The dispersing agent selected by the invention has a strong dispersing effect on the florfenicol, the stability of the florfenicol powder during storage is obviously improved, and the water solubility is kept not to be reduced.
According to some embodiments of the invention, the encapsulating agent is a mixture of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin.
According to some embodiments of the invention, the mass ratio of β -cyclodextrin and hydroxypropyl- β -cyclodextrin in the inclusion agent (6.0 to 7.0): 1. beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin in a specific mass ratio are used as an inclusion agent, the water solubility of the hydroxypropyl-beta-cyclodextrin is superior to that of the beta-cyclodextrin, but the price is high, and the consumption of the hydroxypropyl-beta-cyclodextrin is reduced as much as possible on the premise of ensuring the performances such as the solubility of the florfenicol powder by combining the types of the dispersing agent and the cosolvent, so that the total cost is reduced.
According to some embodiments of the invention, the water-soluble florfenicol powder comprises the following raw materials in percentage by mass: 10-30% of florfenicol, 62-88% of inclusion agent, 1.0-4.0% of dispersing agent and 1.0-4.0% of cosolvent.
According to some embodiments of the invention, the water-soluble florfenicol powder comprises the following raw materials in percentage by mass: 15-25% of florfenicol, 72-83% of inclusion agent, 1.0-2.0% of dispersing agent and 1.0-2.0% of cosolvent.
The inventor greatly adjusts the dosage of each auxiliary agent according to the type of the auxiliary agent through a large amount of scientific experiments and creative labor, realizes the solubility far higher than that of the prior art, and has the advantages of good stability, low cost and no organic solvent residue.
According to some embodiments of the invention, the water-soluble florfenicol powder has a solubility in water at 15 ℃ of not less than 6 mg/mL.
According to some embodiments of the invention, the water-soluble florfenicol powder may also be formulated in other dosage forms.
The invention also provides a preparation method of the water-soluble florfenicol powder, which comprises the following steps:
1) adding florfenicol and a coating agent into water at the temperature of 80-90 ℃, and stirring until the florfenicol and the coating agent are completely dissolved;
2) continuously adding a dispersing agent and a cosolvent into the solution obtained in the step 1), and stirring for 1-3 hours under heat preservation;
3) carrying out pressure spray drying on the solution obtained in the step 2) to obtain the catalyst.
According to some embodiments of the invention, in step 1), the feed-liquid mass ratio of both florfenicol and the inclusion agent to water is 1: (2-4).
According to some embodiments of the invention, in step 3), the powder particle size is controlled to be 100 μm to 180 μm during pressure spray drying.
According to some embodiments of the invention, in the step 3), the inlet air temperature is 160-200 ℃ and the spraying pressure is 9-12 MPa during pressure spray drying.
The invention adopts a pressure type spray drying mode, can prepare the hollow ball and further improves the dissolving performance of the product.
The invention also provides the application of the water-soluble florfenicol powder or the preparation method of the water-soluble florfenicol powder in preparing antibacterial drugs for livestock.
The invention has the beneficial effects that:
the raw materials are strictly screened, the proportion of the raw materials is controlled, the solubility of the obtained product in water at 15 ℃ reaches 6mg/mL which is far higher than 3mg/mL (25 ℃) of the prior art, and the solubility of the product is more than 12 times of that of the raw material medicine; and the dissolution speed is high, and the dissolution time is less than 1 min.
The water-soluble florfenicol powder adopts a pressure type spray drying mode to obtain the small hollow spheres with specific particle sizes, and the solubility of the florfenicol powder can be further improved. In addition, an organic solvent is not needed in the preparation process, so that the safety is high, the production cost is low, and the yield is good; the prepared product has good stability, and the water solubility is basically unchanged after the acceleration for 3 months. Compared with similar products, the water-soluble florfenicol powder has great advantages, improves the bioavailability of the medicament, solves the problem that the water line is easy to block when the livestock and poultry intensively drink water for administration, and has good application prospect.
Detailed Description
The technical solutions and effects of the present invention will be further described and illustrated with reference to the following specific examples, but the present invention is not limited to these specific embodiments. The test methods used in the examples are all conventional methods unless otherwise specified; the materials, reagents and the like used are commercially available reagents and materials unless otherwise specified.
The dosage of the beta-cyclodextrin and the hydroxypropyl beta-cyclodextrin in the raw materials is calculated according to the effective components.
Example 1
Production of 20kg of water-soluble florfenicol powder
Raw materials: 2.0kg of florfenicol, 15.1kg of beta-cyclodextrin, 2.5kg of hydroxypropyl beta-cyclodextrin, 0.2kg of hydroxypropyl methylcellulose and 0.2kg of sodium citrate.
The preparation method comprises the following steps:
(1) the beta-cyclodextrin, the hydroxypropyl beta-cyclodextrin and the florfenicol are sequentially added into hot water at the temperature of 80 ℃ and continuously stirred until the beta-cyclodextrin, the hydroxypropyl beta-cyclodextrin and the florfenicol are completely dissolved, and the mass ratio of the material liquid to the liquid is 1: 3.5;
(2) adding sodium citrate and hydroxypropyl methylcellulose into the coating solution obtained in the step (1), and stirring for 2 hours under heat preservation after clarification;
(3) and then carrying out spray drying treatment on the powder by using a pressure type spray dryer, setting the air inlet temperature to be 180 ℃, adjusting the spray pressure to be 90ba, controlling the particle size of the prepared powder to be 100-180 mu m, and sieving the material by using a 80-mesh sieve to obtain a finished product.
Example 2
Production of 20kg of water-soluble florfenicol powder
Raw materials: 4.0kg of florfenicol, 13.2kg of beta-cyclodextrin, 2.0kg of hydroxypropyl-beta-cyclodextrin, 0.4kg of hydroxypropyl methylcellulose and 0.4kg of sodium citrate.
The preparation method comprises the following steps:
(1) the beta-cyclodextrin, the hydroxypropyl beta-cyclodextrin and the florfenicol are sequentially added into hot water at 85 ℃ and continuously stirred until the beta-cyclodextrin, the hydroxypropyl beta-cyclodextrin and the florfenicol are completely dissolved, wherein the mass ratio of the material liquid to the liquid is 1: 3.5;
(2) adding sodium citrate and hydroxypropyl methylcellulose into the coating solution obtained in the step (1), and stirring for 2 hours under heat preservation after clarification;
(3) and then carrying out spray drying treatment on the powder by using a pressure type spray dryer, setting the air inlet temperature to be 190 ℃, adjusting the spray pressure to be 9MPa, controlling the particle size of the prepared powder to be 100-180 mu m, and sieving the material by using a 80-mesh sieve to obtain a finished product.
Example 3
Production of 20kg of water-soluble florfenicol powder
Raw materials: 4.0kg of florfenicol, 12.6kg of beta-cyclodextrin, 1.8kg of hydroxypropyl-beta-cyclodextrin, 0.4kg of hydroxypropyl methylcellulose, 0.4kg of sodium alginate, 0.4kg of sodium citrate and 0.4kg of sodium succinate.
The preparation method comprises the following steps:
(1) the beta-cyclodextrin, the hydroxypropyl beta-cyclodextrin and the florfenicol are sequentially added into hot water at 85 ℃ and continuously stirred until the beta-cyclodextrin, the hydroxypropyl beta-cyclodextrin and the florfenicol are completely dissolved, wherein the mass ratio of the material liquid to the liquid is 1: 4.0;
(2) adding sodium citrate, sodium succinate, hydroxypropyl methylcellulose and sodium alginate into the coating solution obtained in the step (1), and stirring for 2 hours under heat preservation after clarification;
(3) and then carrying out spray drying treatment on the powder by using a pressure type spray dryer, setting the air inlet temperature to be 190 ℃, adjusting the spray pressure to be 11MPa, controlling the particle size of the prepared powder to be 100-180 mu m, and sieving the material by using a 80-mesh sieve to obtain a finished product.
Example 4
Production of 20kg of water-soluble florfenicol powder
Raw materials: 6.0kg of florfenicol, 10.9kg of beta-cyclodextrin, 1.5kg of hydroxypropyl-beta-cyclodextrin, 0.4kg of hydroxypropyl methylcellulose, 0.4kg of sodium carboxymethylcellulose, 0.4kg of sodium citrate and 0.4kg of acetamide.
The preparation method comprises the following steps:
(1) and (2) sequentially adding beta-cyclodextrin, hydroxypropyl beta-cyclodextrin and florfenicol into hot water at 90 ℃ and continuously stirring until the beta-cyclodextrin, the hydroxypropyl beta-cyclodextrin and the florfenicol are completely dissolved, wherein the material-liquid ratio is 1: 4.0;
(2) adding sodium citrate, acetamide, hydroxypropyl methylcellulose and sodium carboxymethylcellulose into the coating solution obtained in the step (1), and stirring for 2h under heat preservation after clarification;
(3) then a pressure type spray dryer is used for carrying out spray drying treatment on the powder, the air inlet temperature is set to be 200 ℃, the spray pressure is adjusted to be 12MPa, the particle size of the prepared powder is controlled to be 100-180 mu m, and the material is sieved by a 80-mesh sieve, so that a finished product is obtained.
Comparative example 1
The difference from the embodiment 2 is that the hydroxypropyl methylcellulose in the raw material is replaced by poloxamer, and the pressure spray drying is replaced by centrifugal spray drying treatment in the preparation method; the other steps and parameters were the same as in example 2.
Comparative example 2
The difference from example 2 is that the pressure spray drying was replaced by a centrifugal spray drying treatment in the preparation method; the other steps and parameters were the same as in example 2.
Comparative example 3
The difference from the example 3 is that the dosage of the hypromellose in the raw material is increased to 0.8 kg; the other steps and parameters were the same as in example 3.
Test example 1
In order to better show the performance of the florfenicol powder, the water-soluble florfenicol powder produced by the method is compared with a product prepared by a conventional method in the aspects of dissolution speed, dissolution effect and the like.
Experimental groups: water-soluble florfenicol powder prepared in example 2 and example 3 (specification: 20% based on florfenicol).
Control group: comparative example 1, comparative example 2 and comparative example 3 (specification: 20% in florfenicol).
The experimental method comprises the following steps:
(1) take 8 250mL beakers, number A1、A2、B1、B2、B3、C1、C2、D1、D2、D3Respectively containing 100mL of purified water (15 ℃) for standby;
(2) to A1、A2In the beaker, 1.5g of each of the water-soluble florfenicol powders of example 2 and example 3 (3 mg/mL in terms of florfenicol), B1、B2、B31.5g of each of the water-soluble florfenicol powders of comparative example 1, comparative example 2 and comparative example 3 (as florfenicol) was added to the beakerMetering 3mg/mL), stirring with a glass rod until the mixture is completely clarified, and recording the stirring time;
(3) to C1、C2In the beaker, 3.0g (6 mg/mL in terms of florfenicol) of each of the water-soluble florfenicol powders of example 2 and example 3, D1、D2、D3The water-soluble florfenicol powders of comparative example 1, comparative example 2 and comparative example 3 were each added to a beaker at 3.0g (6 mg/mL in florfenicol), stirred with a glass rod until completely clear and the stirring time was recorded.
The results of the experiment are shown in table 1.
Table 1 comparison of the results of the dissolution rate and dissolution effect between the test group and the control group
The experimental results in table 1 show that the solubility of the water-soluble florfenicol powder produced by the invention is obviously superior to that of a product (which is also a common method for products in the market) which independently applies an inclusion technology, and the water solubility of the florfenicol can be obviously improved by a solid dispersion technology and a pressure type spray drying technology. The invention combines the advantages of the florfenicol and the florfenicol, improves the water solubility of the florfenicol to 6mg/mL (6000ppm) at 15 ℃, and the highest water solubility of the market product (comparative example 1) is less than 3 mg/mL; the dissolution rate is within 1min, and the dissolution is very rapid.
Test example 2:
the water-soluble florfenicol powder produced by the method is compared with a product prepared by a conventional method in a test on stability.
Experimental groups: water-soluble florfenicol powder produced in example 2 and example 3 (specification: 20% in terms of florfenicol).
Control group: comparative example 1 and comparative example 2 (specification: 20% in florfenicol).
The experimental method comprises the following steps:
(1) packaging the samples of the experimental group and the control group by using aluminum plastic bags, placing the samples in a stability test box, and carrying out an accelerated test (40 ℃, 75% RH);
(2) samples were taken at 0, 1, 2, and 3 months and the florfenicol content and solubility (15 ℃) were determined.
The content detection method of florfenicol comprises the following steps: the content of the florfenicol powder in the first part of Chinese animal pharmacopoeia 2015 is detected by referring to a method under a content detection item, and the marked amount is obtained according to the mass percentage/specification of the florfenicol.
The solubility detection method comprises the following steps: taking 4 250mL beakers as in example 1, and respectively holding 100mL of purified water (15 ℃) for later use; then, 3.0g of each of the water-soluble florfenicol powders of example 2 and example 3 (6 mg/mL in terms of florfenicol) and 1.5g of each of the water-soluble florfenicol powders of comparative example 1 and comparative example 2 (3 mg/mL in terms of florfenicol) were added thereto, respectively, and stirred with a glass rod, and the dissolution rate and the dissolution effect were recorded.
The results of the experiment are shown in table 2.
TABLE 2 comparison of the stability of the experimental and control groups
The experimental results in table 2 show that the content and water solubility of the water-soluble florfenicol powder produced by the invention are basically unchanged, and the stability is good; and the water solubility of the comparative example 1 is obviously reduced, which shows that the hypromellose or sodium alginate has the effect of promoting the stability of the product.
While the invention has been disclosed with reference to specific embodiments, it will be apparent that other embodiments and variations of the invention may be devised by those skilled in the art without departing from the true spirit and scope of the invention, and it is intended that the following claims be interpreted to include all such embodiments and equivalent variations. In addition, the contents of all references cited herein are hereby incorporated by reference.
Claims (10)
1. The water-soluble florfenicol powder is characterized by comprising the following raw materials:
florfenicol;
an inclusion agent selected from the group consisting of: at least one of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin;
a dispersant selected from the group consisting of: at least one of hypromellose, sodium alginate and sodium carboxymethylcellulose;
a co-solvent selected from: at least one of sodium citrate, sodium succinate and acetamide.
2. The water-soluble florfenicol powder of claim 1 wherein the encapsulating agent is a mixture of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin.
3. The water-soluble florfenicol powder according to claim 2, wherein the mass ratio of the beta-cyclodextrin to the hydroxypropyl-beta-cyclodextrin in the inclusion agent is (6.0-7.0): 1.
4. the water-soluble florfenicol powder according to claim 1, wherein the raw materials comprise, in mass fraction: 10-30% of florfenicol, 62-88% of inclusion agent, 1.0-4.0% of dispersing agent and 1.0-4.0% of cosolvent.
5. The water-soluble florfenicol powder according to claim 1, wherein the raw materials comprise, in mass fraction: 15-25% of florfenicol, 72-83% of inclusion agent, 1.0-2.0% of dispersing agent and 1.0-2.0% of cosolvent.
6. The method for preparing water-soluble florfenicol powder according to any one of claims 1 to 5, comprising the steps of:
1) adding florfenicol and a coating agent into water at the temperature of 80-90 ℃, and stirring until the florfenicol and the coating agent are completely dissolved;
2) continuously adding a dispersing agent and a cosolvent into the solution obtained in the step 1), and stirring for 1-3 hours under heat preservation;
3) carrying out pressure spray drying on the solution obtained in the step 2) to obtain the product.
7. The preparation method according to claim 6, wherein in step 1), the mass ratio of both florfenicol and the inclusion agent to water is 1: (2-4).
8. The method according to claim 6, wherein in the step 3), the spray particle size is controlled to 100 to 180 μm in the pressure spray drying.
9. The preparation method according to claim 6, wherein in the step 3), the inlet air temperature is 160-200 ℃ and the spraying pressure is 9-12 MPa during pressure spray drying.
10. Use of the water-soluble florfenicol powder according to any one of claims 1 to 5 or the water-soluble florfenicol powder according to any one of claims 6 to 9 for the preparation of a veterinary antibacterial.
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| CN112716900A (en) * | 2021-01-12 | 2021-04-30 | 广州南方动物保健科技有限公司 | High-water-solubility florfenicol powder and preparation method thereof |
| CN113230233A (en) * | 2021-05-14 | 2021-08-10 | 中国农业科学院兰州畜牧与兽药研究所 | Florfenicol solid dispersion inclusion microcapsule and preparation method and application thereof |
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| CN116036020A (en) * | 2022-08-31 | 2023-05-02 | 瑞普（天津）生物药业有限公司 | Florfenicol powder with high bioavailability and preparation method thereof |
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| CN112641954A (en) * | 2020-12-30 | 2021-04-13 | 广东三水正大康畜牧发展有限公司 | Water-soluble florfenicol clathrate compound, simple molecular coating method thereof and prepared solid preparation |
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| CN113230233A (en) * | 2021-05-14 | 2021-08-10 | 中国农业科学院兰州畜牧与兽药研究所 | Florfenicol solid dispersion inclusion microcapsule and preparation method and application thereof |
| CN114272213A (en) * | 2021-12-28 | 2022-04-05 | 厦门惠盈动物药业有限公司 | Florfenicol powder and preparation method thereof |
| CN114272213B (en) * | 2021-12-28 | 2023-10-10 | 厦门惠盈动物药业有限公司 | Florfenicol powder and preparation method thereof |
| CN114209656A (en) * | 2021-12-31 | 2022-03-22 | 浙江金朗博药业有限公司 | Florfenicol soluble powder and preparation method thereof |
| CN116036020A (en) * | 2022-08-31 | 2023-05-02 | 瑞普（天津）生物药业有限公司 | Florfenicol powder with high bioavailability and preparation method thereof |
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