阅读说明：本技术 一种氟苯尼考纳米晶及其制备方法 (Florfenicol nanocrystal and preparation method thereof ) 是由 李引乾 陈胡羚 辛怡霖 王虹雅 侯佳琪 于 2020-07-17 设计创作，主要内容包括：本发明属于药物制剂技术领域,涉及一种氟苯尼考纳米晶及其制备方法。其将氟苯尼考与纳米技术结合,以解决氟苯尼考溶解度低、生物利用度低及使用不便等问题,丰富氟苯尼考的使用剂型,为兽医临床使用氟苯尼考提供新方法。本发明采用的制备方法为1)氟苯尼考纳米乳的制备；2)旋转蒸发除去有机溶剂；3)冷冻干燥。(The invention belongs to the technical field of pharmaceutical preparations, and relates to florfenicol nanocrystal and a preparation method thereof. The florfenicol is combined with the nanotechnology so as to solve the problems of low solubility, low bioavailability, inconvenience in use and the like of the florfenicol, enrich the use dosage forms of the florfenicol and provide a new method for clinical use of the florfenicol by veterinarians. The preparation method adopted by the invention is 1) preparation of florfenicol nanoemulsion; 2) removing the organic solvent by rotary evaporation; 3) and (5) freeze drying.)

1. A preparation method of florfenicol nanocrystal is characterized by comprising the following steps: the preparation method comprises the following steps:

1) preparing florfenicol nanoemulsion;

2) removing the organic solvent by rotary evaporation;

3) and (5) freeze drying.

2. The preparation method of the florfenicol nanocrystal according to claim 1, comprising the steps of:

the specific method of the step 1) comprises the following steps:

1-1) dissolving 8-10g of florfenicol raw powder in 100ml of ethyl acetate, dripping a few drops of N, N-dimethylacetamide to assist dissolution to prepare a saturated solution, and removing impurities by using a 0.45 mu m microporous filter membrane for later use to prepare an organic phase for later use;

1-2) dissolving 1g of poloxamer 188 in 200ml of ethanol to prepare a mixed surfactant;

1-3) uniformly mixing the organic phase and the mixed surfactant according to the mass ratio of 1:2, and slowly dripping distilled water while stirring to prepare primary emulsion;

1-4) stirring the primary emulsion at a high speed by a high-speed homogenizer, and then homogenizing the primary emulsion at a high pressure to obtain a semitransparent uniform system which presents light white opalescence, namely the florfenicol nanoemulsion;

the specific method of the step 2) comprises the following steps:

removing the organic solvent by adopting a rotary evaporator to obtain florfenicol nanometer suspension, and freezing and storing the florfenicol nanometer suspension in a refrigerator at the temperature of-80 ℃;

the specific method of the step 3) comprises the following steps:

and drying the frozen florfenicol nanometer suspension by adopting a freeze dryer to obtain the florfenicol nanometer crystal.

3. The preparation method of the florfenicol nanocrystal according to claim 2, wherein the steps of: the volume ratio of the organic phase to the aqueous phase in the step 1-3) is 1:2.

4. The preparation method of the florfenicol nanocrystal according to claim 3, comprising the steps of: the stirring speed in the step 1-4) is 7000rpm, and the homogenizing time is 5 min; the homogenization pressure was 300bar and the homogenization was carried out 3 times.

5. The preparation method of the florfenicol nanocrystal, according to claim 1, is used for preparing the florfenicol nanocrystal.

6. The florfenicol nanocrystal of claim 5, wherein: the average grain size of the nano crystal is 215.6 +/-7.7 nm.

Technical Field

The invention belongs to the technical field of pharmaceutical preparations, and relates to florfenicol nanocrystal and a preparation method thereof.

Background

Florfenicol is taken as a special broad-spectrum antibiotic for animals, is continuously marketed in various countries in the 90 s of the 20 th century, is mainly applied to treating pig, cattle, sheep and chicken intestinal infections caused by sensitive bacteria and chronic respiratory diseases caused by mycoplasma, chicken colibacillosis, duck serositis, salmon-killing producing monads of fishes, eel vibrios and the like at present, and plays an important role in treating bacterial diseases of livestock and poultry.

Florfenicol belongs to a low-solubility/high-permeability drug, is minimally dissolved in water, and in order to improve the solubility of the florfenicol in water, the florfenicol is prepared into a water-soluble prodrug, is prepared into a phospholipid compound, is added with a cosolvent and a solubilizer, is prepared into an emulsion, is prepared into an inclusion compound, is prepared into a solid dispersion, is prepared into a liposome, and adopts a physical and chemical method such as an ultrafine grinding technology, a microcrystal technology and the like. However, the practical production often has the defects of high production cost, difficult feeding and the like, and limits the clinical application of the florfenicol.

The nano crystal has great advantages as a new drug form. The medicine is prepared into the nanocrystalline, so that the solubility of the insoluble medicine can be improved, the bioavailability of the medicine is increased, the curative effect of the medicine can be improved, the dosage is reduced, the adverse reaction is reduced, and the like. The nano crystal drug is a novel drug preparation with great development potential and value, and has wide medical prospect.

Disclosure of Invention

In view of the above, the invention provides a florfenicol nanocrystal and a preparation method thereof, which combines florfenicol with nanotechnology, solves the problems of low solubility, low bioavailability, inconvenient use and the like of the florfenicol, enriches the using dosage forms of the florfenicol, and provides a new method for clinical use of the florfenicol by veterinarians.

In order to solve the problems in the prior art, the technical scheme of the invention is as follows: a preparation method of florfenicol nanocrystal is characterized by comprising the following steps: the preparation method comprises the following steps:

1) preparing florfenicol nanoemulsion;

2) removing the organic solvent by rotary evaporation;

3) and (5) freeze drying.

Further, the specific method of the step 1) is as follows:

1-1) dissolving 8-10g of florfenicol raw powder in 100ml of ethyl acetate, dripping a few drops of N, N-dimethylacetamide to assist dissolution to prepare a saturated solution, and removing impurities by using a 0.45 mu m microporous filter membrane for later use to prepare an organic phase for later use;

1-2) dissolving 1g of poloxamer 188 in 200ml of ethanol to prepare a mixed surfactant;

1-3) uniformly mixing the organic phase and the mixed surfactant according to the mass ratio of 1:2, and slowly dripping distilled water while stirring to prepare primary emulsion;

1-4) stirring the primary emulsion at a high speed by a high-speed homogenizer, and then homogenizing the primary emulsion at a high pressure to obtain a semitransparent uniform system which presents light white opalescence, namely the florfenicol nanoemulsion;

the specific method of the step 2) comprises the following steps:

removing the organic solvent by adopting a rotary evaporator to obtain florfenicol nanometer suspension, and freezing and storing the florfenicol nanometer suspension in a refrigerator at the temperature of-80 ℃;

the specific method of the step 3) comprises the following steps:

and drying the frozen florfenicol nanometer suspension by adopting a freeze dryer to obtain the florfenicol nanometer crystal.

Further, the volume ratio of the organic phase to the aqueous phase in the step 1-3) is 1:2.

Further, the stirring speed in the step 1-4) is 7000rpm, and the homogenizing time is 5 min; the homogenization pressure was 300bar and the homogenization was carried out 3 times.

The average particle size of the florfenicol nanocrystal prepared by the preparation method of the florfenicol nanocrystal is 215.6 +/-7.7 nm.

Compared with the prior art, the invention has the following advantages:

1) at present, the florfenicol is mainly used in clinic by soluble powder and suspension, and florfenicol nanocrystalline preparations are not available in the market, so that the florfenicol exerts the drug effect in the form of nanocrystals, the solubility and other physical properties of the florfenicol in water are improved, the bioavailability of the florfenicol is improved, and better treatment effect is exerted in clinic;

2) the florfenicol nanocrystal prepared by the invention has good stability, the particle size reaches the standard of nano-drugs, the drug is placed in powder state for a long time, and the florfenicol nanocrystal is not easy to absorb moisture, agglomerate, store and use;

3) the preparation process is simple and feasible, has low production cost, is convenient for large-scale industrial production, and is favorable for market popularization;

4) the invention provides a new idea for the florfenicol solubilization research work, enriches the dosage forms of florfenicol, and provides a new method for veterinary clinical use of florfenicol.

Drawings

FIG. 1 influence of volume ratio of organic phase to aqueous phase on average particle size of florfenicol nanocrystals;

figure 2 effect of concentration of poloxamer 188 on the average particle size of florfenicol nanocrystals;

FIG. 3 influence of homogenization speed on the average particle size of florfenicol nanocrystals;

FIG. 4 influence of homogenization time on the average particle size of florfenicol nanocrystals;

FIG. 5 effect of homogenization pressure on the average particle size of florfenicol nanocrystals;

FIG. 6 effect of number of homogenizations on average particle size of florfenicol nanocrystals;

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are merely illustrative of the present invention and are not intended to limit the present invention.

The average grain diameter of the florfenicol nanocrystalline prepared by the invention is 215.6 +/-7.7 nm.