CN114209656B - Florfenicol soluble powder and preparation method thereof - Google Patents
Florfenicol soluble powder and preparation method thereof Download PDFInfo
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- 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
- 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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- 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
- A61K9/143—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 inorganic compounds
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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
- A61K9/145—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 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
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- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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 comprises 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 and quick release effects, is very little influenced by water temperature, is convenient to use, and has good stability.
Description
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, fluprofen, is a white or off-white crystalline powder that is odorless and bitter. Molecular formula C 12 H 14 Cl 2 FNO 4 S, the chemical structural formula is as follows:
the florfenicol is a new generation of special broad-spectrum antibiotics for chloramphenicol veterinarian developed by the company of Mirabaoya in the United states in the 80 th century, has the characteristics of wide antibacterial spectrum, good absorption, wide in-vivo distribution, high efficiency, safety and the like, has remarkable treatment effect on poultry bacterial diseases caused by sensitive bacteria, has effects on gram positive bacteria and gram negative bacteria, and is a preferred medicament for various infections caused by typhoid bacillus, paratyphoid bacillus and Salmonella.
Florfenicol belongs to a time-dependent drug, the sterilization effect of the florfenicol mainly depends on the duration that the blood concentration exceeds the Minimum Inhibitory Concentration (MIC) of the bacteria, the relationship with the blood peak concentration is not great, and the longer the effective blood concentration maintenance time is after administration, 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 absorbed and utilized quickly through oral administration or intramuscular injection, but the solubility of the medicine in water is extremely low, and the medicine is slowly dissolved in the gastrointestinal tract, so that the absorption of the medicine is limited. The defect of low in-vivo solubility of the drug can be perfectly avoided by dissolving the florfenicol in water and then administering the drug, but the solubility of the florfenicol in water is extremely low, so how to improve the solubility of the florfenicol in water becomes one of research hotspots and one of difficulties of florfenicol preparations.
At present, methods for improving the water solubility of florfenicol can be mainly divided into two types: one physical method comprises the steps of adding a cosolvent, micronizing, clathrating with beta-cyclodextrin, preparing a solid dispersing agent and the like; the other is a chemical method, namely, florfenicol is prepared into a water-soluble prodrug, and the florfenicol is metabolized to play a role after entering an animal body. The chemical method has harsh preparation conditions, the required reagent is expensive, the biological activity of the florfenicol original drug can be influenced, 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 florfenicol soluble powder contains florfenicol polydopamine compound, so that not only can the solubility of florfenicol be effectively improved, but also the dissolution rate can be improved. 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, wherein florfenicol powder is added into a matrix diluent, and stirred and mixed uniformly at normal temperature to obtain a premix; adding urea, povidone k30 and polyethylene glycol 6000 to the premix, wherein the mass ratio of florfenicol, urea, povidone k30 and polyethylene glycol 6000 is 1:4:4:1, adding the rest 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 powdery florfenicol soluble powder. The soluble powder contains the florfenicol urea compound, so that the solubility of florfenicol can be effectively improved, and the dissolution rate can be increased.
Although the solubility of florfenicol is improved to some extent by adding a cosolvent, making florfenicol into ultrafine powder or adopting a beta-cyclodextrin inclusion technology, the florfenicol is not truly water-soluble (clear and transparent), thereby causing another problem of influencing the solubility, or when powders are mixed with a fluid (such as water), the powders tend to coagulate and disperse unevenly in the fluid, and a large amount of membranous and agglomerated, flocculent florfenicol adheres to the wall and the surface of the container after stirring. Thus, a large part of florfenicol is digested (adhered, attached and the like) by the drug delivery system in the drug delivery process, even if the florfenicol is difficult to be ingested 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 body when the florfenicol is dissolved out of the food, and the florfenicol is difficult to be absorbed by the digestive tract when the florfenicol is dissolved out of the body when the florfenicol is dissolved out of the food especially for livestock and poultry with very short digestive tract or livestock and poultry with digestive tract diseases.
In view of this, the present invention has been made.
Disclosure of Invention
The invention aims to provide the florfenicol soluble powder and the preparation method thereof, and 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 very little influenced by water temperature, is convenient to use and has good stability.
In order to achieve the purpose of the invention, the invention adopts the following technical scheme:
the florfenicol soluble powder comprises the following components:
further, the surfactant is sodium starch octenyl succinate, disodium ethylenediamine 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 stabilizer 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, and emulsifying and homogenizing to obtain emulsion;
4) And (3) performing 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 performed at the temperature of 35-65 ℃.
In the step 3), the rotation 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 step 4), the spray drying temperature 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 and quick release effects, is very little influenced by water temperature, is convenient to use, and has good stability.
Drawings
FIG. 1 is a schematic diagram of sampling points in the detection of the dissolution amount of an aqueous solution according to the present invention;
FIG. 2 is a graph showing the dissolution of the florfenicol soluble powder of example 1 of the present invention in water at different water temperatures;
FIG. 3 is a graph of the dissolution of the florfenicol soluble powder of comparative example 1 in water at different water temperatures;
fig. 4 is a graph showing the dissolution of florfenicol drug substance in water at different water temperatures.
Detailed Description
The following are specific embodiments of the present invention, which are described in order to further illustrate the invention, not to limit the invention.
Example 1
The raw materials comprise:
the preparation method comprises the following steps:
(1) Taking 300g of florfenicol and 500g of 95% ethanol, stirring at 50 ℃ and dissolving to obtain a solution 1;
(2) Adding 150g of sodium starch octenyl succinate, 250g of beta-cyclodextrin, 200g of sodium citrate and 100g of sodium alginate into 1000g of purified water, stirring at 50 ℃ and dissolving to obtain a solution 2;
(3) After the solution 1 and the solution 2 are mixed, a high-speed shearing emulsifying machine is started, and the rotating speed is set to 3000rpm for emulsification; starting a high-pressure homogenizer, setting a homogenizing pressure of 50MPa, and homogenizing the emulsified liquid at high pressure to obtain emulsion;
(4) Starting a spray dryer, setting the temperature to 180 ℃, and carrying out spray drying on the emulsion obtained in the step (3) at the rotating speed of 600rpm to obtain the florfenicol soluble powder.
Example 2
The raw materials comprise:
the preparation method comprises the following steps:
(1) 200g of florfenicol and 450g of 95% ethanol are taken and stirred at the temperature of 35 ℃ to be dissolved to obtain 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 35 ℃ and dissolving to obtain solution 2;
(3) After the solution 1 and the solution 2 are mixed, a high-speed shearing emulsifying machine is started, and the rotation speed is set to 5000rpm for emulsification; starting a high-pressure homogenizer, setting a homogenizing pressure of 30MPa, and homogenizing the emulsified liquid at high pressure to obtain emulsion;
(4) Starting a spray dryer, setting the temperature to 160 ℃, and carrying out spray drying on the emulsion obtained in the step (3) at the rotating speed of 600rpm to obtain the florfenicol soluble powder.
Example 3
The raw materials comprise:
the preparation method comprises the following steps:
(1) Taking 250g of florfenicol and 400g of 95% ethanol, stirring at 65 ℃ and dissolving to obtain a solution 1;
(2) 120g of sodium dodecyl benzene sulfonate, 220g of beta-cyclodextrin, 300g of sodium citrate and 80g of sodium alginate are taken and added into 1000g of purified water, and stirred at the temperature of 65 ℃ to be dissolved to obtain solution 2;
(3) After the solution 1 and the solution 2 are mixed, a high-speed shearing emulsifying machine is started, and the rotating speed is set to 4000rpm for emulsification; starting a high-pressure homogenizer, setting a homogenizing pressure of 70MPa, and homogenizing the emulsified liquid at high pressure to obtain emulsion;
(4) Starting a spray dryer, setting the temperature to 200 ℃, and carrying out spray drying on the emulsion obtained in the step (3) at the rotating speed of 600rpm to obtain the florfenicol soluble powder.
Example 4
The raw materials comprise:
the preparation method comprises the following steps:
(1) Taking 280g of florfenicol and 480g of 95% ethanol, stirring at 45 ℃ and dissolving to obtain a solution 1;
(2) 130g of disodium ethylenediamine tetraacetate, 230g of beta-cyclodextrin, 280g of sodium citrate and 60g of sodium alginate are taken, added into 1000g of purified water, stirred at the temperature of 45 ℃ and dissolved to obtain solution 2;
(3) After the solution 1 and the solution 2 are mixed, a high-speed shearing emulsifying machine is started, and the rotating speed is set to 3500rpm for emulsification; starting a high-pressure homogenizer, setting a homogenizing pressure of 60MPa, and homogenizing the emulsified liquid at high pressure to obtain emulsion;
(4) Starting a spray dryer, setting the temperature to 185 ℃, and carrying out spray drying on the emulsion obtained in the step (3) at the rotating speed of 600rpm to obtain the florfenicol soluble powder.
Example 5
The raw materials comprise:
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) 130g of disodium ethylenediamine tetraacetate, 240g of beta-cyclodextrin, 180g of sodium bicarbonate and 70g of sodium alginate are added into 1000g of purified water, and stirred at the temperature of 62 ℃ to be dissolved to obtain a solution 2;
(3) After the solution 1 and the solution 2 are mixed, a high-speed shearing emulsifying machine is started, and the rotation speed is set to 4800rpm for emulsification; starting a high-pressure homogenizer, setting a homogenizing pressure of 68MPa, and homogenizing the emulsified liquid at high pressure to obtain emulsion;
(4) Starting a spray dryer, setting the temperature to 172 ℃, and carrying out spray drying on the emulsion obtained in the step (3) at the rotating speed of 600rpm to obtain the florfenicol soluble powder.
Example 6
The raw materials comprise:
the preparation method comprises the following steps:
(1) Taking 230g of florfenicol and 440g of 95% ethanol, stirring at 48 ℃ and dissolving to obtain a solution 1;
(2) 110g of sodium dodecyl sulfate, 230g of beta-cyclodextrin, 250g of sodium carbonate and 90g of sodium alginate are taken and added into 1000g of purified water, and stirred at 48 ℃ to be dissolved to obtain solution 2;
(3) After the solution 1 and the solution 2 are mixed, a high-speed shearing emulsifying machine is started, and the rotation speed is set to 3200rpm for emulsification; starting a high-pressure homogenizer, setting a homogenizing pressure of 42MPa, and homogenizing the emulsified liquid at high pressure to obtain emulsion;
(4) Starting a spray dryer, setting the temperature to 163 ℃ and the rotating speed to 600rpm, and performing spray drying on the emulsion obtained in the step (3) to obtain the florfenicol soluble powder.
Example 7
The raw materials comprise:
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 sodium dodecyl 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, a high-speed shearing emulsifying machine is started, and the rotating speed is set to 4600rpm for emulsification; starting a high-pressure homogenizer, setting a homogenizing pressure of 55MPa, and homogenizing the emulsified liquid at high pressure to obtain emulsion;
(4) Starting a spray dryer, setting the temperature to 190 ℃, and carrying out spray drying on the emulsion obtained in the step (3) at the rotating speed of 600rpm to obtain the florfenicol soluble powder.
Example 8
The raw materials comprise:
the preparation method comprises the following steps:
(1) Taking 300g of florfenicol and 500g of 95% ethanol, stirring at 50 ℃ and dissolving to obtain a solution 1;
(2) Adding 150g of sodium dodecyl sulfate, 250g of beta-cyclodextrin, 200g of sodium citrate and 100g of acacia in 1000g of purified water, stirring at 50 ℃ and dissolving to obtain solution 2;
(3) After the solution 1 and the solution 2 are mixed, a high-speed shearing emulsifying machine is started, and the rotating speed is set to 3000rpm for emulsification; starting a high-pressure homogenizer, setting a homogenizing pressure of 50MPa, and homogenizing the emulsified liquid at high pressure to obtain emulsion;
(4) Starting a spray dryer, setting the temperature to 180 ℃, and carrying out spray drying on the emulsion obtained in the step (3) at the rotating speed of 600rpm to obtain the florfenicol soluble powder.
Comparative example 1
The raw materials comprise:
as in example 1.
The preparation method comprises the following steps:
(1) Taking 300g of florfenicol and 500g of 95% ethanol, and stirring at 50 ℃ to obtain a solution 1;
(2) 150g of sodium starch octenyl succinate, 250g of beta-cyclodextrin, 200g of sodium citrate and 100g of sodium alginate are taken, added into 1000g of purified water, and stirred at 50 ℃ to obtain solution 2;
(3) And (3) mixing the solution 1 and the solution 2 to obtain a mixed solution, starting a spray dryer, setting the temperature to 180 ℃, and carrying out spray drying on the obtained mixed solution at the rotating speed of 600rpm to obtain the florfenicol soluble powder.
Test example 1
The experimental example examines 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 the preparation method of example 8, except that the rotational speed of the emulsifying machine in step (3) was changed, and the influence of the rotational speed of the emulsifying machine on the solubility of the florfenicol soluble powder prepared 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 obtained florfenicol soluble powder
| Emulsifying machine rotation speed (rpm) | Solubility (g/L) |
| 2000 | 3.3 |
| 3000 | 5.6 |
| 4000 | 5.4 |
| 5000 | 5.1 |
| 6000 | 3.4 |
From the above test results, it can be seen that under the same conditions, the solubility of the obtained florfenicol soluble powder is higher when the rotational speed of the emulsifying machine is 3000-5000 rpm. Therefore, in the emulsification process, the rotating speed of the emulsifying machine is selected to be 3000-5000 rpm.
2. Homogenizing pressure
Florfenicol soluble powder was prepared according to the raw material composition and the 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 obtained florfenicol soluble powder was examined.
The results are shown in Table 2:
TABLE 2 influence of homogenization pressure on solubility of the obtained florfenicol soluble powder
| Homogenizing 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 |
As can be seen from the test results, under the same conditions, the solubility of the prepared florfenicol soluble powder is higher when the homogenizing pressure is 30-70 MPa. Therefore, in the homogenizing process, the homogenizing pressure is selected to be 30-70 MPa.
Test example 2
This test example examined the phenomenon of the wall and the surface of the container after the florfenicol soluble powder prepared in the above examples and comparative examples was dissolved in water.
The test method comprises the following steps: at room temperature, 1g of the florfenicol powder prepared in each of the examples and comparative examples was added to a beaker containing 100ml of purified water, and stirred uniformly to form a uniform solution, and the wall of the vessel and the phenomenon on the liquid surface were observed.
The test results are shown in Table 3:
TABLE 3 Table 3
From the test results, when the florfenicol soluble powder prepared by the method is mixed with water, the florfenicol soluble powder is uniformly dispersed in fluid water, and the wall and the liquid surface of the stirred container are not adhered, and film-shaped and flocculent florfenicol floats.
Test example 3
The present test example examined the dissolution rate of florfenicol powder in an aqueous solution after the florfenicol soluble powder prepared in the above examples and comparative examples was dissolved in water.
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, 1g of the florfenicol powder prepared in the examples and comparative examples was added to a beaker containing 100ml of purified water, the magnetic stirrer was turned on (rotation speed 100 rpm) to stir for 10 minutes, 1ml of the aqueous solution was precisely measured (sampling point is shown in FIG. 1), diluted to 100ml with mobile phase, injected into a liquid chromatograph, and a chromatogram was recorded;
control solution treatment method: taking a proper amount of florfenicol reference substance (purchased from a middle inspection station), diluting to 100ml by using a mobile phase, precisely measuring 10 mu L, injecting into a liquid chromatograph, and recording a chromatogram.
The aqueous solution content was calculated as peak area by 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:
the rest proportion=100% -the dissolution rate of the aqueous solution, and the rest is florfenicol powder adhered on the container wall or floating on the liquid surface.
The test results are shown in Table 4:
TABLE 4 results of aqueous solution dissolution rate measurements
| Florfenicol powder | Dissolution rate of aqueous solution (based on 100% of the amount of the material fed) | 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％ |
As can be seen from the above test results, the florfenicol soluble powder prepared by the method of the present invention was uniformly dispersed in fluid water when mixed with water, and was well dissolved in water, whereas the florfenicol soluble powder prepared in comparative example 1 was not completely dissolved in water, but had a part adhered to the wall of the container or suspended on the water surface, although it was also dissolved in water.
Test example 4, solubility test
The solubility of the florfenicol soluble powder prepared in each example and comparative example at different water temperatures was examined in this test example.
Solubility test method: and respectively dissolving a certain amount of powder sample in 100ml of room temperature purified water, 5 ℃ purified water and 15 ℃ purified water, placing in a laboratory stirrer, starting stirring at 50rpm, and stirring for 10min, wherein if the solution is completely clear and transparent, the amount of the powder is the solubility of the product.
The test results are shown in Table 5:
TABLE 5 solubility test results
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 little influenced by water temperature and is convenient to use.
Test example 5 stability test
The stability of the florfenicol soluble powder prepared by the invention is examined in the test example.
The test method comprises the following steps: according to the prescription and process of example 8, the invention selects an aluminum foil bag for packaging, futures the packaging specification, and uses three packaging specifications of 100 g/bag, 1000 g/bag and 25 kg/bag for stability investigation under the investigation condition of 40 ℃ and 75 percent RH.
The test results are shown in Table 6:
TABLE 6 stability test results
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The test results show that when the aluminum foil bags are used for packaging, three different packaging specifications of 100 g/bag, 1000 g/bag and 25 kg/bag are adopted, and the quality of the invention is stable.
Test example 6 dissolution test
The test example examines the dissolution of different florfenicol powders at different water temperatures.
Florfenicol is generally added to animal drinks for use, so water is selected as a dissolution medium to examine the dissolution condition of the florfenicol. The dissolution situation of florfenicol is tested according to the general rule 0931 of the 2015 edition of the beast pharmacopoeia of the people's republic of China. 200mg of florfenicol is weighed and placed in a dissolution cup, water is taken as dissolution medium, the volume is 900mL, and the rotating speed is 100 r.min -1 The temperature was 37.+ -. 0.5 ℃. 5mL are sampled at 5, 10, 20, 30, 45 and 60min respectively, the same volume of dissolution medium with the same temperature is supplemented, after the dissolution medium passes through a 0.22 mu m water system microporous filter membrane, the subsequent filtrate is taken, the absorption degree is measured at the wavelength of 266nm, the standard curve is substituted, the cumulative dissolution percentage is calculated, and the dissolution curve is drawn.
The solubility of the florfenicol soluble powder prepared in example 1 of the present invention in water at 15.+ -. 0.5 ℃ and 5.+ -. 0.5 ℃ was further examined according to the above-mentioned method, and the test results are shown in FIG. 2.
Meanwhile, the dissolution rates of the florfenicol soluble powder prepared in the comparative example 1 and the florfenicol bulk drug in water at 37+/-0.5 ℃, 15+/-0.5 ℃ and 5+/-0.5 ℃ are respectively examined according to the method, the dissolution test results of the florfenicol soluble powder in the comparative example 1 are shown in a graph 3, and the dissolution test results of the florfenicol bulk drug are shown in a graph 4. The florfenicol bulk drug is produced by Shandong Guobang pharmaceutical industry Co., ltd, and has the purity of 99.5%.
As can be seen from figures 2, 3 and 4, the florfenicol soluble powder prepared by the method has good dissolution and obvious quick release effect, is very little influenced by water temperature, and is convenient to use. The dissolution of the florfenicol soluble powder and the florfenicol bulk drug prepared in comparative example 1 is greatly affected by water temperature.
The florfenicol soluble powder prepared in other examples of the present invention was also subjected to dissolution investigation according to the above method, which is similar to the results of example 1.
Claims (8)
1. The florfenicol soluble powder is characterized by comprising the following components:
the inclusion agent is beta-cyclodextrin;
the preparation method of the florfenicol soluble powder 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, and emulsifying and homogenizing to obtain emulsion;
4) Spray drying the emulsion obtained in the step 3) to obtain the florfenicol soluble powder;
in the step 3), the rotation speed of the emulsifying machine is 3000-5000 rpm during emulsification, and the pressure of the homogenizing machine is 30-70 Mpa during homogenization.
2. The florfenicol soluble powder of claim 1, wherein the surfactant is sodium starch octenyl succinate, disodium edetate, sodium dodecyl benzene sulfonate or sodium dodecyl sulfate.
3. The florfenicol soluble powder of claim 1, wherein the co-solvent is sodium bicarbonate, sodium citrate, sodium carbonate or disodium citrate.
4. The florfenicol soluble powder according to claim 1, wherein the stabilizer is acacia or sodium alginate.
5. The florfenicol soluble powder according to claim 1, wherein the organic solvent is 95% ethanol.
6. A process for the preparation of a soluble powder of florfenicol as claimed in any one of claims 1 to 5, 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, and emulsifying and homogenizing to obtain emulsion;
4) Spray drying the emulsion obtained in the step 3) to obtain the florfenicol soluble powder;
in the step 3), the rotation speed of the emulsifying machine is 3000-5000 rpm during emulsification, and the pressure of the homogenizing machine is 30-70 Mpa during homogenization.
7. The method according to claim 6, wherein in step 1) and step 2), the stirring is performed at a temperature of 35 to 65 ℃.
8. The process according to claim 6, wherein in step 4), the spray-drying temperature is 160 to 200 ℃.
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| FORMULATION AND CHARACTERIZATION OF INCLUSION COMPLEXES USING HYDROXYPROPYL-beta-CYCLODEXTRIN AND FLORFENICOL WITH CHITOSAN MICROPARTICLES;CRISTIAN ROGEL et al.;《JOURNAL OF THE CHILEAN CHEMICAL SOCIETY》;第56卷(第1期);第574-579页 * |
| 氟苯尼考固体形态增溶技术研究进展;刘连超等;《动物医学进展》;第42卷(第4期);第104-108页 * |
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