CN114209656A - Florfenicol soluble powder and preparation method thereof - Google Patents

Florfenicol soluble powder and preparation method thereof Download PDF

Info

Publication number
CN114209656A
CN114209656A CN202111683239.XA CN202111683239A CN114209656A CN 114209656 A CN114209656 A CN 114209656A CN 202111683239 A CN202111683239 A CN 202111683239A CN 114209656 A CN114209656 A CN 114209656A
Authority
CN
China
Prior art keywords
florfenicol
soluble powder
solution
parts
sodium
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202111683239.XA
Other languages
Chinese (zh)
Other versions
CN114209656B (en
Inventor
舒毅成
陈玉龙
徐根
任永焕
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zhejiang Jinlongbo Pharmaceutical Co ltd
Original Assignee
Zhejiang Jinlongbo Pharmaceutical Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zhejiang Jinlongbo Pharmaceutical Co ltd filed Critical Zhejiang Jinlongbo Pharmaceutical Co ltd
Priority to CN202111683239.XA priority Critical patent/CN114209656B/en
Publication of CN114209656A publication Critical patent/CN114209656A/en
Application granted granted Critical
Publication of CN114209656B publication Critical patent/CN114209656B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141Intimate 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
    • A61K9/146Intimate 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/165Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141Intimate 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
    • A61K9/143Intimate 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 inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141Intimate 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
    • A61K9/145Intimate 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 compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Inorganic Chemistry (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention belongs to the field of veterinary medicines, and particularly relates to florfenicol soluble powder and a preparation method thereof. The florfenicol soluble powder is prepared from the following components: 200-300 parts of florfenicol, 100-150 parts of surfactant, 200-250 parts of inclusion agent, 150-300 parts of cosolvent, 50-100 parts of stabilizer, 400-500 parts of organic solvent and 1000 parts of pure water. The florfenicol soluble powder provided by the invention has good solubility, can be uniformly dispersed in fluid (such as water), has good dissolution, good quick-release effect, very small influence of water temperature, convenient use and good stability.

Description

Florfenicol soluble powder and preparation method thereof
Technical Field
The invention belongs to the field of veterinary medicines, and particularly relates to florfenicol soluble powder and a preparation method thereof.
Background
Florfenicol (FF), also known as florfenicol and flurbiprofen, is a white or off-white crystalline powder, odorless and bitter. Molecular formula C12H14Cl2FNO4S, the chemical structural formula is as follows:
Figure BDA0003451139180000011
florfenicol is a new-generation broad-spectrum antibiotic specially used for chloramphenicol veterinarians developed by the company of Mr. Ling & Bao in the end of the 20 th century and the 80 th century, has the characteristics of wide antibacterial spectrum, good absorption, wide in-vivo distribution, high efficiency, safety and the like, has obvious treatment effect on poultry bacterial diseases caused by sensitive bacteria, has effects on gram positive bacteria and gram negative bacteria, and is a first-choice medicine for various infections caused by typhoid bacillus, paratyphoid bacillus and salmonella.
Florfenicol belongs to time-dependent drugs, the sterilization effect of which mainly depends on the duration time that the blood concentration exceeds the Minimum Inhibitory Concentration (MIC) of the targeted bacteria, and the relationship with the blood peak concentration is not large, and after administration, the longer the effective blood concentration maintenance time is, the better the clinical effect is. Furthermore, florfenicol belongs to class II drugs, i.e., low solubility/high permeability drugs, in the Biopharmaceutical Classification System (BCS). The medicine can be quickly absorbed and utilized by oral administration or intramuscular injection, but has extremely low solubility in water and slow dissolution in gastrointestinal tracts, thereby limiting the absorption of the medicine. The disadvantage of low solubility of the florfenicol in vivo can be perfectly avoided by dissolving the florfenicol in water and then administering the florfenicol, but the solubility of the florfenicol in water is extremely low, so that how to improve the solubility of the florfenicol in water becomes one of the research hotspots of florfenicol preparations and is also one of the difficulties.
At present, methods for improving the water solubility of florfenicol can be mainly divided into two methods: one is a physical method, which comprises adding cosolvent, micronizing, clathrating with beta-cyclodextrin, and making into solid dispersant; the other method is a chemical method, namely, the florfenicol is prepared into a water-soluble prodrug, and the florfenicol is metabolized to play a role after entering the body of an animal. The chemical method has harsh preparation conditions, expensive required reagents and the possibility of influencing the biological activity of the florfenicol technical product, and the physical method is relatively simple, low in cost and easy to industrialize.
Chinese patent application 201510996047.2 discloses a florfenicol soluble powder and a preparation method thereof, wherein the soluble powder contains a florfenicol polydopamine compound, which not only can effectively improve the solubility of florfenicol, but also can improve the dissolution speed. The method is simple and easy to implement, the preparation time is short, and the production energy consumption is low.
Chinese patent application 202011180411.5 discloses a preparation method of florfenicol soluble powder, which comprises adding florfenicol powder into a matrix diluent, and uniformly stirring at normal temperature to obtain a premix; adding urea, povidone k30 and polyethylene glycol 6000 into the premix, wherein the mass ratio of the florfenicol to the urea to the povidone k30 to the polyethylene glycol 6000 is 1: 4: 4: 1, adding the rest of matrix diluent to 1000g, and continuously stirring for 0.5-2 hours to obtain a florfenicol mixture; and (3) carrying out spray drying on the florfenicol mixture to obtain powdered florfenicol soluble powder. The soluble powder contains the florfenicol urea compound, so that the solubility of the florfenicol can be effectively improved, and the dissolution speed can be improved.
Although florfenicol solubility is improved to some extent by the addition of co-solvents, micronization of florfenicol or inclusion of the product using beta-cyclodextrin, etc., it is not truly water soluble (clear and transparent), thereby creating another solubility-affecting problem in that when powders are mixed with fluids (e.g., water), they tend to clump and disperse unevenly in the fluid, and there is a large amount of membranous, lumpy, flocculent florfenicol adhered to and floating on the walls and surfaces of the container after agitation. Therefore, a large part of the florfenicol is digested (adhered, attached and the like) by a drug delivery system in the drug delivery process, even if the florfenicol is not easy to be taken into the digestive tract by livestock and poultry, the florfenicol is mixed with food, so that the florfenicol is difficult to dissolve out of the food, and especially for the livestock and poultry with short digestive tract or the livestock and poultry with digestive tract diseases, a large amount of florfenicol is discharged out of the body after being dissolved out of the food and is difficult to be absorbed by the digestive tract.
In view of the above, the present invention is particularly proposed.
Disclosure of Invention
The florfenicol soluble powder provided by the invention has good solubility, can be uniformly dispersed in fluid (such as water), has good quick-release effect, is slightly influenced by water temperature, is convenient to use and has good stability.
In order to realize the purpose of the invention, the invention adopts the following technical scheme:
the florfenicol soluble powder is prepared from the following components:
Figure BDA0003451139180000031
further, the surfactant is sodium starch octenyl succinate, disodium ethylene diamine tetraacetate, sodium dodecyl benzene sulfonate or sodium dodecyl sulfate.
Further, the inclusion agent is beta-cyclodextrin.
Further, the cosolvent is sodium bicarbonate, sodium citrate, sodium carbonate or disodium citrate.
Further, the stabilizing agent is acacia or sodium alginate.
Further, the organic solvent is 95% ethanol.
The invention also provides a preparation method of the florfenicol soluble powder, which comprises the following steps:
1) taking the florfenicol and the organic solvent in parts by weight, stirring and dissolving to obtain a solution 1;
2) adding the surfactant, the inclusion agent, the cosolvent and the stabilizer in parts by weight into the pure water in parts by weight, stirring and dissolving to obtain a solution 2;
3) mixing the solution 1 and the solution 2, emulsifying and homogenizing to obtain emulsion;
4) and (3) carrying out spray drying on the emulsion obtained in the step 3) to obtain the florfenicol soluble powder.
In the preparation method, in the step 1), the stirring is carried out at the temperature of 35-65 ℃.
In the step 3), the rotating speed of the emulsifying machine is 3000-5000 rpm during emulsification, and the pressure of the homogenizing machine is 30-70 Mpa during homogenization.
In the step 4), the temperature of spray drying is 160-200 ℃.
Compared with the prior art, the invention has the following advantages:
the florfenicol soluble powder provided by the invention has good solubility, can be uniformly dispersed in fluid (such as water), has good dissolution, good quick-release effect, very small influence of water temperature, convenient use and good stability.
Drawings
FIG. 1 is a schematic view of a sampling point in the measurement of the dissolved amount of an aqueous solution according to the present invention;
FIG. 2 is a graph of the dissolution profile of florfenicol soluble powder of example 1 of the present invention in water at different water temperatures;
FIG. 3 is a graph of the dissolution profile of the florfenicol soluble powder of comparative example 1 in water at different water temperatures;
figure 4 is a graph of the dissolution profile of florfenicol drug substance in water at different water temperatures.
Detailed Description
The following are specific embodiments of the present invention, which are intended to further illustrate the invention and not to limit it.
Example 1
The raw materials comprise:
Figure BDA0003451139180000041
the preparation method comprises the following steps:
(1) taking 300g of florfenicol and 500g of 95% ethanol, stirring at the temperature of 50 ℃, and dissolving to obtain a solution 1;
(2) adding 150g of sodium starch octenylsuccinate, 250g of beta-cyclodextrin, 200g of sodium citrate and 100g of sodium alginate into 1000g of purified water, stirring at the temperature of 50 ℃, and dissolving to obtain a solution 2;
(3) mixing the solution 1 and the solution 2, starting a high-speed shearing emulsifying machine, and emulsifying at a set rotating speed of 3000 rpm; starting a high-pressure homogenizer, setting the homogenizing pressure to be 50MPa, and carrying out high-pressure homogenization on the emulsified liquid to obtain emulsion;
(4) and (3) starting a spray dryer, setting the temperature at 180 ℃, rotating at 600rpm, and carrying out spray drying on the emulsion obtained in the step (3) to obtain the florfenicol soluble powder.
Example 2
The raw materials comprise:
Figure BDA0003451139180000051
the preparation method comprises the following steps:
(1) taking 200g of florfenicol and 450g of 95% ethanol, stirring at the temperature of 35 ℃, and dissolving to obtain a solution 1;
(2) adding 100g of sodium dodecyl sulfate, 200g of beta-cyclodextrin, 150g of sodium citrate and 50g of sodium alginate into 1000g of purified water, stirring at the temperature of 35 ℃, and dissolving to obtain a solution 2;
(3) mixing the solution 1 and the solution 2, starting a high-speed shearing emulsifying machine, and setting the rotating speed to be 5000rpm for emulsification; starting a high-pressure homogenizer, setting the homogenizing pressure to be 30MPa, and carrying out high-pressure homogenization on the emulsified liquid to obtain emulsion;
(4) and (3) starting a spray dryer, setting the temperature at 160 ℃, rotating at 600rpm, and carrying out spray drying on the emulsion obtained in the step (3) to obtain the florfenicol soluble powder.
Example 3
The raw materials comprise:
Figure BDA0003451139180000052
Figure BDA0003451139180000061
the preparation method comprises the following steps:
(1) taking 250g of florfenicol and 400g of 95% ethanol, stirring at the temperature of 65 ℃, and dissolving to obtain a solution 1;
(2) adding 120g of sodium dodecyl benzene sulfonate, 220g of beta-cyclodextrin, 300g of sodium citrate and 80g of sodium alginate into 1000g of purified water, stirring at the temperature of 65 ℃, and dissolving to obtain a solution 2;
(3) mixing the solution 1 and the solution 2, starting a high-speed shearing emulsifying machine, and setting the rotation speed to 4000rpm for emulsification; starting a high-pressure homogenizer, setting the homogenizing pressure to be 70MPa, and carrying out high-pressure homogenization on the emulsified liquid to obtain emulsion;
(4) and (3) starting a spray dryer, setting the temperature to be 200 ℃, rotating the speed to be 600rpm, and carrying out spray drying on the emulsion obtained in the step (3) to obtain the florfenicol soluble powder.
Example 4
The raw materials comprise:
Figure BDA0003451139180000062
the preparation method comprises the following steps:
(1) taking 280g of florfenicol and 480g of 95% ethanol, stirring at the temperature of 45 ℃, and dissolving to obtain a solution 1;
(2) adding 130g of disodium ethylene diamine tetraacetate, 230g of beta-cyclodextrin, 280g of sodium citrate and 60g of sodium alginate into 1000g of purified water, stirring at the temperature of 45 ℃, and dissolving to obtain a solution 2;
(3) mixing the solution 1 and the solution 2, starting a high-speed shearing emulsifying machine, and setting the rotating speed to be 3500rpm for emulsification; starting a high-pressure homogenizer, setting the homogenizing pressure to be 60MPa, and carrying out high-pressure homogenization on the emulsified liquid to obtain emulsion;
(4) and (3) starting a spray dryer, setting the temperature to be 185 ℃, rotating the speed to be 600rpm, and carrying out spray drying on the emulsion obtained in the step (3) to obtain the florfenicol soluble powder.
Example 5
The raw materials comprise:
Figure BDA0003451139180000071
the preparation method comprises the following steps:
(1) taking 260g of florfenicol and 460g of 95% ethanol, stirring at the temperature of 62 ℃, and dissolving to obtain a solution 1;
(2) adding 130g of disodium ethylene diamine tetraacetate, 240g of beta-cyclodextrin, 180g of sodium bicarbonate and 70g of sodium alginate into 1000g of purified water, stirring at the temperature of 62 ℃, and dissolving to obtain a solution 2;
(3) mixing the solution 1 and the solution 2, starting a high-speed shearing emulsifying machine, and emulsifying at a set rotating speed of 4800 rpm; starting a high-pressure homogenizer, setting the homogenizing pressure to be 68MPa, and carrying out high-pressure homogenization on the emulsified liquid to obtain emulsion;
(4) and (3) starting a spray dryer, setting the temperature to be 172 ℃, rotating the speed to be 600rpm, and carrying out spray drying on the emulsion obtained in the step (3) to obtain the florfenicol soluble powder.
Example 6
The raw materials comprise:
Figure BDA0003451139180000072
Figure BDA0003451139180000081
the preparation method comprises the following steps:
(1) taking 230g of florfenicol and 440g of 95% ethanol, stirring at the temperature of 48 ℃, and dissolving to obtain a solution 1;
(2) adding 110g of lauryl sodium sulfate, 230g of beta-cyclodextrin, 250g of sodium carbonate and 90g of sodium alginate into 1000g of purified water, stirring at the temperature of 48 ℃, and dissolving to obtain a solution 2;
(3) mixing the solution 1 and the solution 2, starting a high-speed shearing emulsifying machine, and emulsifying at a set rotating speed of 3200 rpm; starting a high-pressure homogenizer, setting the homogenizing pressure to be 42MPa, and carrying out high-pressure homogenization on the emulsified liquid to obtain emulsion;
(4) and (3) starting a spray dryer, setting the temperature to be 163 ℃, rotating the speed to be 600rpm, and carrying out spray drying on the emulsion obtained in the step (3) to obtain the florfenicol soluble powder.
Example 7
The raw materials comprise:
Figure BDA0003451139180000082
the preparation method comprises the following steps:
(1) taking 250g of florfenicol and 450g of 95% ethanol, stirring at the temperature of 43 ℃, and dissolving to obtain a solution 1;
(2) adding 150g of lauryl sodium sulfate, 220g of beta-cyclodextrin, 250g of disodium citrate and 100g of sodium alginate into 1000g of purified water, stirring at the temperature of 43 ℃, and dissolving to obtain a solution 2;
(3) after the solution 1 and the solution 2 are mixed, starting a high-speed shearing emulsifying machine, and setting the rotating speed of 4600rpm for emulsification; starting a high-pressure homogenizer, setting the homogenizing pressure to be 55MPa, and carrying out high-pressure homogenization on the emulsified liquid to obtain emulsion;
(4) and (3) starting a spray dryer, setting the temperature to be 190 ℃, rotating the speed to be 600rpm, and carrying out spray drying on the emulsion obtained in the step (3) to obtain the florfenicol soluble powder.
Example 8
The raw materials comprise:
Figure BDA0003451139180000091
the preparation method comprises the following steps:
(1) taking 300g of florfenicol and 500g of 95% ethanol, stirring at the temperature of 50 ℃, and dissolving to obtain a solution 1;
(2) adding 150g of lauryl sodium sulfate, 250g of beta-cyclodextrin, 200g of sodium citrate and 100g of Arabic gum into 1000g of purified water, stirring at the temperature of 50 ℃, and dissolving to obtain a solution 2;
(3) mixing the solution 1 and the solution 2, starting a high-speed shearing emulsifying machine, and emulsifying at a set rotating speed of 3000 rpm; starting a high-pressure homogenizer, setting the homogenizing pressure to be 50MPa, and carrying out high-pressure homogenization on the emulsified liquid to obtain emulsion;
(4) and (3) starting a spray dryer, setting the temperature at 180 ℃, rotating at 600rpm, and carrying out spray drying on the emulsion obtained in the step (3) to obtain the florfenicol soluble powder.
Comparative example 1
The raw materials comprise:
the same as in example 1.
The preparation method comprises the following steps:
(1) taking 300g of florfenicol and 500g of 95% ethanol, and stirring at the temperature of 50 ℃ to obtain a solution 1;
(2) adding 150g of sodium starch octenylsuccinate, 250g of beta-cyclodextrin, 200g of sodium citrate and 100g of sodium alginate into 1000g of purified water, and stirring at the temperature of 50 ℃ to obtain a solution 2;
(3) and mixing the solution 1 and the solution 2 to obtain a mixed solution, starting a spray dryer, setting the temperature at 180 ℃ and the rotation speed at 600rpm, and carrying out spray drying on the obtained mixed solution to obtain the florfenicol soluble powder.
Test example 1
The test example investigates the influence of the emulsification and homogenization process on the solubility of the prepared florfenicol soluble powder.
1. Rotational speed of emulsifying machine
Florfenicol soluble powder was prepared according to the raw material composition and preparation method of example 8, except that the rotation speed of the emulsifier in step (3) was changed, and the influence of the rotation speed of the emulsifier on the solubility of the prepared florfenicol soluble powder was examined.
The results are shown in Table 1:
TABLE 1 influence of the rotational speed of the emulsifying machine on the solubility of the florfenicol soluble powder produced
Mulser speed (rpm) Solubility (g/L)
2000 3.3
3000 5.6
4000 5.4
5000 5.1
6000 3.4
From the test results, under the same other conditions, when the rotation speed of the emulsifying machine is 3000-5000 rpm, the solubility of the prepared florfenicol soluble powder is high. Therefore, in the emulsifying process, the rotating speed of the emulsifying machine is 3000-5000 rpm.
2. Pressure of homogenization
Florfenicol soluble powder was prepared according to the raw material composition and preparation method of example 8, except that the homogenization pressure in step (3) was changed and the influence of the homogenization pressure on the solubility of the prepared florfenicol soluble powder was examined.
The results are shown in Table 2:
TABLE 2 Effect of homogenization pressure on the solubility of the florfenicol soluble powder produced
Homogeneous pressure (MPa) Solubility (g/L)
20 3.4
30 5.1
40 5.3
50 5.6
60 5.4
70 5.3
80 3.2
From the test results, under the same other conditions, when the homogenization pressure is 30-70 MPa, the solubility of the prepared florfenicol soluble powder is higher. Therefore, in the homogenizing process, the homogenizing pressure is selected to be 30-70 MPa.
Test example 2
The test example investigates the phenomena of the florfenicol soluble powder prepared in the above examples and comparative examples on the wall and the liquid surface of the container after the florfenicol soluble powder is dissolved in water.
The test method comprises the following steps: at room temperature, 1g of florfenicol powder prepared in the examples and the comparative examples is respectively added into a beaker filled with 100ml of purified water, the mixture is stirred uniformly to form a uniform solution, and the phenomena on the wall and the liquid surface of the container are observed.
The test results are shown in table 3:
TABLE 3
Figure BDA0003451139180000111
Figure BDA0003451139180000121
From the test results, the florfenicol soluble powder prepared by the method of the invention is uniformly dispersed in fluid water when being mixed with water, and membranous, cluster and flocculent florfenicol is not adhered, floated on the wall and the liquid surface of the container after stirring.
Test example 3
The test example examines the florfenicol soluble powder prepared in the above examples and comparative examples, and the florfenicol soluble powder is dissolved in water, and then the dissolution rate of the florfenicol powder in the water solution is examined.
The method for measuring the content of the aqueous solution comprises the following steps:
the aqueous solution treatment method comprises the following steps: at room temperature, respectively taking 1g of florfenicol powder prepared in the examples and the comparative examples, adding the florfenicol powder into a beaker filled with 100ml of purified water, starting a magnetic stirrer (rotating speed of 100rpm) to stir for 10 minutes, precisely measuring 1ml of aqueous solution (sampling points are shown in figure 1), diluting the aqueous solution to 100ml by using a mobile phase, injecting the aqueous solution into a liquid chromatograph, and recording a chromatogram;
control solution treatment method: taking a proper amount of florfenicol reference substance (purchased from China center), diluting to 100ml with a mobile phase, precisely measuring 10 mu L, injecting into a liquid chromatograph, and recording a chromatogram.
The content of the aqueous solution was calculated by the peak area according to the external standard method, and the examples and comparative examples were measured in the same manner.
The dissolution rate of florfenicol powder in the aqueous solution is calculated according to the following formula:
Figure BDA0003451139180000122
the rest is 100 percent to the dissolution rate of the aqueous solution, and the rest is florfenicol powder adhered to the container wall or floating on the liquid surface.
The test results are shown in table 4:
TABLE 4 results of measurement of dissolution rate in aqueous solution
Florfenicol powder Dissolution rate of aqueous solution (measured by 100% of material charge) The rest proportion
Example 1 100.00% 0%
Example 2 100.00% 0%
Example 3 100.00% 0%
Example 4 100.00% 0%
Example 5 100.00% 0%
Example 6 100.00% 0%
Example 7 100.00% 0%
Example 8 100.00% 0%
Comparative example 1 86.40% 13.60%
From the above test results, it can be seen that the florfenicol soluble powder prepared by the method of the present invention is uniformly dispersed in the fluid water and can be well dissolved in the water when being mixed with water, while the florfenicol soluble powder prepared by the comparative example 1 can be dissolved in the water, but cannot be completely dissolved in the water, and a part of the florfenicol soluble powder is adhered to the container wall or suspended on the water surface.
Test example 4 solubility test
The test example examines the solubility of the florfenicol soluble powder prepared in each example and comparative example at different water temperatures.
Solubility test method: dissolving a certain amount of powder samples in 100ml of room temperature purified water, 5 ℃ purified water and 15 ℃ purified water respectively, placing in a laboratory stirrer, starting stirring at 50rpm for 10min, and if the solution is completely clear and transparent, the dosage of the powder is the solubility of the product.
The test results are shown in table 5:
TABLE 5 solubility test results
Figure BDA0003451139180000131
Figure BDA0003451139180000141
The test results show that the solubility of the florfenicol soluble powder prepared by the invention is obviously improved, and the florfenicol soluble powder is very slightly influenced by water temperature and is convenient to use.
Test example 5 stability test
The test example examines the stability of the florfenicol soluble powder prepared by the invention.
The test method comprises the following steps: according to the prescription and the process of the embodiment 8, the aluminum foil bags are selected for packaging, the packaging specifications are searched, three packaging specifications of 100 g/bag, 1000 g/bag and 25 kg/bag are respectively used for stability test, and the test conditions are 40 ℃ and 75% RH.
The test results are shown in table 6:
TABLE 6 stability test results
Figure BDA0003451139180000142
The test results show that when the aluminum foil bags are used for packaging, the aluminum foil bags adopt three different packaging specifications of 100 g/bag, 1000 g/bag and 25 kg/bag, and the aluminum foil bags have stable quality.
Test example 6 dissolution test
The test example investigates the dissolution rates of different florfenicol powders at different water temperatures.
Florfenicol is generally added to animal drinking water for use, and therefore, water is selected as a dissolution medium to examine the dissolution. The florfenicol dissolution was tested according to 0931, the first guideline of the pharmacopoeia of the people's republic of China 2015. Weighing 200mg of florfenicol, placing the florfenicol into a dissolving cup, taking water as a dissolving medium, wherein the volume is 900mL, and the rotating speed is 100 r.min-1The temperature is 37 +/-0.5 ℃. Sampling 5mL at 5, 10, 20, 30, 45 and 60min respectively, simultaneously supplementing dissolution medium with the same volume and temperature, filtering with 0.22 μm water system microporous membrane, collecting filtrate, measuring absorbance at 266nm, substituting into standard curve, calculating cumulative dissolution percentage, and drawing dissolution curve.
The florfenicol soluble powder prepared in example 1 of the present invention was further examined for dissolution in water at 15 + -0.5 deg.C and 5 + -0.5 deg.C, respectively, according to the above-mentioned methods, and the test results are shown in FIG. 2.
Meanwhile, the florfenicol soluble powder prepared in the comparative example 1 and the dissolution rates of florfenicol raw material medicines in water with the temperature of 37 +/-0.5 ℃, 15 +/-0.5 ℃ and 5 +/-0.5 ℃ are respectively examined according to the method, the dissolution test result of the florfenicol soluble powder in the comparative example 1 is shown in figure 3, and the dissolution test result of the florfenicol raw material medicines is shown in figure 4. Wherein the florfenicol raw material medicine is produced by Shandong national Pont pharmaceutical industry GmbH, and the purity is 99.5%.
As can be seen from the figures 2, 3 and 4, the florfenicol soluble powder prepared by the method has good dissolution, obvious quick release effect, little influence of water temperature and convenient use. The florfenicol soluble powder and the florfenicol bulk drug prepared in the comparative example 1 are greatly influenced by the water temperature.
The florfenicol soluble powder prepared by other examples of the invention was also tested for dissolution according to the above method, which is similar to the results of example 1.

Claims (10)

1. The florfenicol soluble powder is characterized by comprising the following components:
Figure FDA0003451139170000011
2. the florfenicol soluble powder of claim 1 wherein the surfactant is sodium starch octenyl succinate, disodium ethylene diamine tetraacetate, sodium dodecyl benzene sulfonate, or sodium dodecyl sulfate.
3. The soluble florfenicol powder of claim 1 wherein the encapsulating agent is beta-cyclodextrin.
4. The florfenicol soluble powder of claim 1 wherein the co-solvent is sodium bicarbonate, sodium citrate, sodium carbonate, or disodium citrate.
5. The soluble powder of florfenicol as claimed in claim 1, wherein the stabilizing agent is acacia gum or sodium alginate.
6. The florfenicol soluble powder of claim 1 wherein the organic solvent is 95% ethanol.
7. A method for preparing florfenicol soluble powder according to any one of claims 1-6, comprising the steps of:
1) taking the florfenicol and the organic solvent in parts by weight, stirring and dissolving to obtain a solution 1;
2) adding the surfactant, the inclusion agent, the cosolvent and the stabilizer in parts by weight into the pure water in parts by weight, stirring and dissolving to obtain a solution 2;
3) mixing the solution 1 and the solution 2, emulsifying and homogenizing to obtain emulsion;
4) and (3) carrying out spray drying on the emulsion obtained in the step 3) to obtain the florfenicol soluble powder.
8. The preparation method according to claim 7, wherein in the step 1) and the step 2), the stirring is performed at a temperature of 35-65 ℃.
9. The method according to claim 7, wherein in the step 3), the rotation speed of the emulsifier is 3000-5000 rpm and the pressure of the homogenizer is 30-70 MPa.
10. The method according to claim 7, wherein the temperature of the spray drying in the step 4) is 160 to 200 ℃.
CN202111683239.XA 2021-12-31 2021-12-31 Florfenicol soluble powder and preparation method thereof Active CN114209656B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111683239.XA CN114209656B (en) 2021-12-31 2021-12-31 Florfenicol soluble powder and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111683239.XA CN114209656B (en) 2021-12-31 2021-12-31 Florfenicol soluble powder and preparation method thereof

Publications (2)

Publication Number Publication Date
CN114209656A true CN114209656A (en) 2022-03-22
CN114209656B CN114209656B (en) 2023-08-01

Family

ID=80707672

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111683239.XA Active CN114209656B (en) 2021-12-31 2021-12-31 Florfenicol soluble powder and preparation method thereof

Country Status (1)

Country Link
CN (1) CN114209656B (en)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090062397A1 (en) * 2007-04-27 2009-03-05 Schering-Plough Animal Health Corporation Compounds and methods for enhancing solubility of florfenicol and structurally-related antibiotics using cyclodextrins
CN105477642A (en) * 2015-12-15 2016-04-13 中牧南京动物药业有限公司 Florfenicol composition with high bioavailability and preparation method thereof
CN108969486A (en) * 2018-06-05 2018-12-11 王琴 A kind of florfenicol soluble powder and preparation method thereof
CN109432013A (en) * 2018-12-22 2019-03-08 山东国邦药业股份有限公司 A kind of florfenicol soluble powder and preparation method thereof
CN112121016A (en) * 2020-10-09 2020-12-25 清远海贝生物技术有限公司 Water-soluble florfenicol powder and preparation method thereof
CN113425738A (en) * 2021-06-25 2021-09-24 中牧南京动物药业有限公司 Tilmicosin gamma-cyclodextrin inclusion compound and preparation method and application thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090062397A1 (en) * 2007-04-27 2009-03-05 Schering-Plough Animal Health Corporation Compounds and methods for enhancing solubility of florfenicol and structurally-related antibiotics using cyclodextrins
CN105477642A (en) * 2015-12-15 2016-04-13 中牧南京动物药业有限公司 Florfenicol composition with high bioavailability and preparation method thereof
CN108969486A (en) * 2018-06-05 2018-12-11 王琴 A kind of florfenicol soluble powder and preparation method thereof
CN109432013A (en) * 2018-12-22 2019-03-08 山东国邦药业股份有限公司 A kind of florfenicol soluble powder and preparation method thereof
CN112121016A (en) * 2020-10-09 2020-12-25 清远海贝生物技术有限公司 Water-soluble florfenicol powder and preparation method thereof
CN113425738A (en) * 2021-06-25 2021-09-24 中牧南京动物药业有限公司 Tilmicosin gamma-cyclodextrin inclusion compound and preparation method and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CRISTIAN ROGEL ET AL.: "FORMULATION AND CHARACTERIZATION OF INCLUSION COMPLEXES USING HYDROXYPROPYL-beta-CYCLODEXTRIN AND FLORFENICOL WITH CHITOSAN MICROPARTICLES", 《JOURNAL OF THE CHILEAN CHEMICAL SOCIETY》, vol. 56, no. 1, pages 574 - 579 *
刘连超等: "氟苯尼考固体形态增溶技术研究进展", 《动物医学进展》, vol. 42, no. 4, pages 104 - 108 *

Also Published As

Publication number Publication date
CN114209656B (en) 2023-08-01

Similar Documents

Publication Publication Date Title
CN103610649A (en) Medicament microsphere and preparation method thereof
CN109394727A (en) A kind of Enrofloxacin taste masking sustained-release granular formulation for animals and preparation method thereof
CN105287607B (en) Animal compound Doxycycline Hyclate florfenicol slowly-releasing microballoon suspension injection
US20240082160A1 (en) Amlodipine dry suspension and preparation method therefor
CN109260177A (en) A kind of preparation method and applications of Berberine hydrochloride complex nanometer granule
CN104523606B (en) The method that self-assembly method prepares gossypol and its derivative pluronic nano-particle
BR112019016118A2 (en) dosage form of lamotrigine oral suspension
CN107595782A (en) A kind of Linezolid dry suspensoid agent and preparation method thereof
CN104434797B (en) A kind of Florfenicol solid self-emulsifying preparation
CN113425738A (en) Tilmicosin gamma-cyclodextrin inclusion compound and preparation method and application thereof
CN114209656B (en) Florfenicol soluble powder and preparation method thereof
CN110251487B (en) Preparation method and application of alcohol soluble protein nanoparticles for improving drug-loading rate and oral bioavailability of docetaxel
CN107837231A (en) A kind of Nimodipime nanometer method and its dry suspensoid agent
CN100562322C (en) Colon targeting preparation of a kind of 5-aminosalicylic acid and preparation method thereof
CN103263385B (en) A kind of celecoxib long-acing nano injection and preparation method thereof
CN102028655B (en) Zanamivir solid lipid nanosphere oral preparation and preparation method thereof
CN104415340A (en) Solid drug preparation and preparing method thereof
WO2016119114A1 (en) Puerarin nanocrystalline capsule and preparation method therefor
CN101890015B (en) Liposome injection of pharmaceutical composition comprising piperacillin sodium and tazobactam sodium
CN109316449A (en) A kind of pomalidomide nanocrystal lipid microcapsule and preparation method thereof
CN105832694A (en) Penicillins medicine capsule and preparation method of same
CN114796128B (en) Tiamulin fumarate premix and preparation method and application thereof
CN108578417A (en) A kind of compound sulfonamide chlorine pyridazine sodium dry suspensoid agent and preparation method thereof
CN102940609B (en) A kind of high encapsulation rate Octreotide sustained-release micro-spheres and preparation method thereof
BRPI0804639A2 (en) A process for preparing a veterinary suspension formulation for administering a water-insoluble medicament by means of water delivery systems and their veterinary suspension formulation for administering a water-insoluble medicament

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant