Determination method for particle size of doxycycline

Abstract

The invention discloses a method for determining the particle size of doxycycline, and belongs to the technical field of drug analysis and detection. According to the determination method, a dry laser scattering method is adopted, and determination parameters comprise dispersion pressure and sample injection speed. According to the method, the particle size and the particle size distribution of the doxycycline are measured by utilizing a dry laser scattering method, the accuracy is high, the durability is good, the particle size distribution of the doxycycline can be effectively detected, and a basis is provided for improving the quality of a doxycycline product.

Description

Technical Field

[0001] The invention belongs to the technical field of drug analysis and detection, and particularly relates to a method for determining the particle size of doxycycline. Background Art

[0002] Doxycycline is a broad-spectrum semi-synthetic tetracycline antibiotic with an antibacterial activity 2 to 4 times stronger than tetracycline. It is currently the least toxic antibiotic in this class and has broad-spectrum and high-efficiency antibacterial characteristics. It is widely used in clinical practice and has a large market demand. It is mainly used for upper respiratory tract infections, tonsillitis, biliary tract infections, lymphadenitis, cellulitis, chronic bronchitis in the elderly, typhus, scrub typhus and mycoplasma pneumonia caused by sensitive Gram-positive cocci and Gram-negative bacilli.

[0003] The size of particles is called "particle size", also known as "particle size" or "diameter". The particle size of the particle to be measured is generally equated to the diameter of a homogeneous sphere with similar physical properties or physical behaviors. The diameter of the sphere is the equivalent particle size of the particle to be measured. Particle size distribution refers to the percentage of particles of different sizes in all particles. Particle size is one of the most important indicators of powder products. The size and distribution of the particle size of a substance directly affect the dispersion, stability, and optical properties of the substance. Therefore, accurate measurement of the particle size distribution of a substance is of great significance for the application of the substance in industrial processes, the control of product quality, and the safety of the production process. Currently, commonly used particle size distribution test methods include microscopy, screening, Coulter counting, sedimentation, specific surface area, laser diffraction, etc. The laser particle size analyzer based on the laser diffraction method is a new type of particle size distribution test equipment. Compared with traditional measuring equipment, laser particle size analyzer has the advantages of simple testing method, fast testing speed, wide application range and good data repeatability. This equipment is widely used in various fields of modern industry such as chemical industry, machinery, building materials, energy, and medicine.

[0004] Therefore, it is necessary to provide a method for determining the particle size distribution of doxycycline with high accuracy and good durability, so as to optimize the product production process and improve product quality and safety. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide a method for determining the particle size of doxycycline, which has good accuracy and durability, optimizes the product production process and improves the product quality and safety by controlling the particle size distribution in the quality standard of doxycycline.

[0006] In order to solve the above technical problems, the technical solution adopted by the present invention is as follows:

[0007] A method for determining the particle size of doxycycline, the method adopts a dry laser scattering method, and comprises the following steps:

[0008] 1) Instrument and sample selection;

[0009] 2) Set instrument parameter conditions;

[0010] 3) Prepare the test sample and keep it ready for use;

[0011] 4) Add the sample to the sample tray, start the method for determination, and after the background determination is completed, measure the sample and collect data.

[0012] Furthermore, the particle type is non-spherical.

[0013] Furthermore, the dispersion pressure is 0.5 bar to 2.0 bar.

[0014] Furthermore, the width of the injection nozzle is 4 mm.

[0015] Furthermore, the injection rate is 50% to 80%.

[0016] Furthermore, the sample measurement time is 20 s.

[0017] Furthermore, the background test time is 10 s, the signal integration time is 100 ms, and the cleaning time is 3 s.

[0018] Furthermore, during the sample testing process, D10, D50 and D90 are used as characteristic values ​​of particle size distribution.

[0019] Furthermore, the sample has a CoPt of ≥1% at the beginning and a CoPt of ≤1% after 3 seconds when it stops.

[0020] Furthermore, the preparation of the test sample: weigh about 0.2 g of doxycycline sample, and disperse the sample without agglomeration, as the test sample.

[0021] Compared with the prior art, the present invention has the following advantages:

[0022] (1) The present invention measures the particle size of doxycycline and controls the particle size distribution in the quality standard, thereby ensuring the uniformity of the doxycycline product and improving the product quality and safety.

[0023] (2) The method for determining the particle size of doxycycline of the present invention has high accuracy and good durability, and can effectively detect the particle size distribution of doxycycline, providing a basis for improving the quality of doxycycline products. DETAILED DESCRIPTION

[0024] The present invention is further illustrated below in conjunction with specific examples. The examples are implemented based on the technical solutions of the present invention. It should be understood that these examples are only used to illustrate the present invention and are not used to limit the scope of the present invention.

[0025] Example 1

[0026] A method for determining the particle size of doxycycline, using a dry laser scattering method, comprises the following steps:

[0027] 1) Instrument and sample selection:

[0028] Table 1 Instruments

[0029]

[0030] Table 2 Reagents

[0031]

[0032] 2) Instrument parameter settings:

[0033] Particle mode: non-spherical particle mode

[0034] Nozzle width: 4 mm

[0035] Dispersion pressure: 1.0~2.0 bar

[0036] Injection rate: 50%~80%

[0037] Funnel rotation: 0%

[0038] Cleaning duration: 3 s

[0039] Background test time: 10 s

[0040] Sample measurement time: 20 s

[0041] Signal integration time: 100 ms

[0042] Start: CoPt ≥ 1%

[0043] Stop at: 3 seconds after CoPt≤1%

[0044] 3) Preparation of test sample: Weigh about 0.2 g of doxycycline sample and make sure that the sample is dispersed without agglomeration as the test sample.

[0045] 4) Determination method: Use the Sympatec laser particle size analyzer, set the instrument parameters according to 2) above, add an appropriate amount of sample to the sample tray, select the appropriate lens, dispersion pressure and injection rate, and measure the sample after the background measurement is completed.

[0046] Example 2

[0047] The choice of pressure distribution

[0048] Take an appropriate amount of this product and adjust the pressure to 0.5 bar-2.0 bar according to the above particle size determination method, calculate the particle size distribution results respectively, collect data, and the results are shown in Table 3.

[0049] Table 3 Test results of different dispersion pressures

[0050]

[0051] It can be seen from Table 3 that the results of particle size measurement are slightly different when the dispersion pressure is 1.0 bar and 1.5 bar, so the dispersion pressure is selected as 1.0 bar and 1.5 bar.

[0052] Example 3

[0053] Selection of injection rate

[0054] Take an appropriate amount of this product and adjust the injection rate to 50%-80% according to the above-mentioned particle size determination method, calculate the particle size distribution results respectively, collect data, and the results are shown in Table 4.

[0055] Table 4 Experimental results of different injection rates

[0056]

[0057] As shown in Table 4, the injection rate has no significant effect on the particle size determination results. The RSD% of D10, D50, and D90 all meet the requirements and can be set at 50%-80%.

[0058] Example 4

[0059] Repeatability test

[0060] Set the dispersion pressure to 1.0 bar and the injection rate to 50%, take an appropriate amount of the product, and measure the sample 6 times in parallel according to the above particle size determination method. Calculate the RSD values ​​of the 6 measurements, and the results are shown in Table 5.

[0061] Table 5 Repeatability test results

[0062]

[0063] From the results in Table 5, it can be seen that the dispersion pressure is 1.0 bar, the injection rate is 50%, and the test sample is measured 6 times in parallel. （10） RSD<15%, D （50） RSD<10%, D （90） RSD<10%, which meets the requirements, indicating that the method has good repeatability.

[0064] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for determining the particle size of doxycycline, characterized in that: The method adopts a dry laser scattering method and comprises the following steps: 1) Instrument and sample selection; 2) Set instrument parameter conditions; 3) Prepare the test sample and keep it ready for use; 4) Add the sample to the sample tray, start the method for determination, and after the background determination is completed, measure the sample and collect data.

2. The method for determining the particle size of doxycycline according to claim 1, wherein: The particle type is non-spherical.

3. The method for determining the particle size of doxycycline according to claim 1, characterized in that: The dispersion pressure is 0.5 bar to 2.0 bar.

4. The method for determining the particle size of doxycycline according to claim 1, wherein: The width of the injection nozzle is 4 mm.

5. The method for determining the particle size of doxycycline according to claim 1, characterized in that: The injection rate is 50% to 80%.

6. The method for determining the particle size of doxycycline according to claim 1, characterized in that: The sample measurement time is 20 s.

7. The method for determining the particle size of doxycycline according to claim 1, characterized in that: The background test time is 10 s, the signal integration time is 100 ms, and the cleaning time is 3 s.

8. The method for determining the particle size of doxycycline according to claim 1, wherein: During the sample testing process, D10, D50 and D90 were used as characteristic values ​​of particle size distribution.

9. The method for determining the particle size of doxycycline according to claim 1, characterized in that: The sample started with CoPt ≥ 1% and stopped with CoPt ≤ 1% after 3 seconds.

10. The method for determining the particle size of doxycycline according to claim 1, characterized in that: Preparation of the test sample: Weigh about 0.2 g of doxycycline sample and make the sample dispersed without agglomeration as the test sample.

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