CN114527042A - Method for detecting particle size distribution of progesterone in progesterone soft capsule contents - Google Patents
Method for detecting particle size distribution of progesterone in progesterone soft capsule contents Download PDFInfo
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- CN114527042A CN114527042A CN202111599233.4A CN202111599233A CN114527042A CN 114527042 A CN114527042 A CN 114527042A CN 202111599233 A CN202111599233 A CN 202111599233A CN 114527042 A CN114527042 A CN 114527042A
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- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 title claims abstract description 212
- 229960003387 progesterone Drugs 0.000 title claims abstract description 106
- 239000000186 progesterone Substances 0.000 title claims abstract description 106
- 239000002245 particle Substances 0.000 title claims abstract description 95
- 239000007901 soft capsule Substances 0.000 title claims abstract description 59
- 238000000034 method Methods 0.000 title claims abstract description 29
- 238000012360 testing method Methods 0.000 claims abstract description 61
- 229940057995 liquid paraffin Drugs 0.000 claims abstract description 58
- 238000001514 detection method Methods 0.000 claims abstract description 42
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 42
- 239000000523 sample Substances 0.000 claims description 35
- 239000012488 sample solution Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 5
- 239000012528 membrane Substances 0.000 claims description 5
- 238000001132 ultrasonic dispersion Methods 0.000 claims description 5
- 238000001471 micro-filtration Methods 0.000 claims description 3
- 239000002131 composite material Substances 0.000 claims description 2
- 239000011148 porous material Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000005259 measurement Methods 0.000 abstract description 5
- 238000004458 analytical method Methods 0.000 abstract description 2
- 230000000007 visual effect Effects 0.000 abstract description 2
- 238000001000 micrograph Methods 0.000 abstract 1
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
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- 238000004140 cleaning Methods 0.000 description 6
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- 238000010586 diagram Methods 0.000 description 6
- 238000007561 laser diffraction method Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000007865 diluting Methods 0.000 description 5
- 235000020238 sunflower seed Nutrition 0.000 description 5
- 235000015112 vegetable and seed oil Nutrition 0.000 description 5
- 239000008158 vegetable oil Substances 0.000 description 5
- 230000008859 change Effects 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- 230000007547 defect Effects 0.000 description 2
- 238000010191 image analysis Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000003703 image analysis method Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
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- 239000002600 sunflower oil Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
- G01N15/02—Investigating particle size or size distribution
- G01N15/0205—Investigating particle size or size distribution by optical means, e.g. by light scattering, diffraction, holography or imaging
Abstract
The invention discloses a method for detecting the particle size distribution of progesterone in a progesterone soft capsule content, which comprises the following steps: and adding the contents of the progesterone soft capsules into a saturated light liquid paraffin solution, uniformly dispersing by using ultrasonic, and carrying out particle size test by using a laser particle size detector to obtain the particle size distribution of the contents of the progesterone soft capsules. Compared with the existing microscope image analysis method, the invention has the advantages of more detection samples, relatively cheap detection equipment, better precision and applicability; the measuring instrument is widely used, the experimental result is visual and efficient, the relative standard deviation of the multiple measurement results of the D10 and D90 particle diameters is not more than 5 percent, the relative standard deviation of the multiple measurement results of the D50 particle diameters is not more than 3 percent, and the requirement of the Chinese pharmacopoeia on the repeatability of the detection result of the laser particle sizer is met.
Description
Technical Field
The application relates to the technical field of analysis and detection, in particular to a method for detecting the particle size distribution of progesterone in progesterone soft capsule contents.
Background
The progesterone soft capsule is a high-efficiency medicament for treating dysfunction and assisting pregnancy caused by progesterone deficiency, and has large market demand. The content of the progesterone soft capsule is an oil suspension, and the particle size distribution of the progesterone in the oil are important quality control indexes of the progesterone soft capsule.
The only test methods for the particle size and particle size distribution of the contents of progesterone soft capsules are currently microscopic image analysis. Because of the inherent defects of the microscopy, the method has the defects of low number of observed particles (only 1000-. In addition, in the related legal quality standard of the original developer, a Leica microscope and an image analysis system are required to be used, and the system is sold at a price of 60-80 ten thousand yuan, is expensive and has problems in popularization.
At present, the most widely applied particle size testing method is a laser diffraction method, which is divided into a dry laser diffraction method and a wet laser diffraction method, wherein the dry laser diffraction method is simpler than the wet test method, the testing efficiency is higher, and the cost is lower. However, since the progesterone is suspended in the soft capsule contents oil and it is very difficult to separate the oil from the progesterone particles, the dry laser diffraction method is not suitable for the measurement of the particle size distribution of the progesterone in the contents (suspension) of the progesterone soft capsule. The oil in the contents (suspension) of the progesterone soft capsules influences the detection result in the test by a wet laser diffraction method, and the granularity of the progesterone in the dispersion process is difficult to ensure not to change, so that the selection of a proper dispersing agent is very difficult, and the method cannot be used for testing the distribution of the progesterone in the contents (suspension) of the progesterone soft capsules.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a method for detecting the particle size distribution of progesterone in a progesterone soft capsule content, wherein saturated light liquid paraffin is used as a dispersing agent to dissolve the progesterone until the progesterone is saturated so as to obtain a saturated light liquid paraffin solution, the saturated light liquid paraffin solution is added into the progesterone soft capsule content, and the saturated light liquid paraffin solution is a saturated progesterone-light liquid paraffin solution, so that the saturated light liquid paraffin solution can dissolve oil in the progesterone soft capsule content (suspension), but hardly dissolves the progesterone in a detection time, so that the influence of the oil in the progesterone soft capsule content (suspension) on a detection result is avoided on one hand, and the change of the particle size caused by the dissolution of the progesterone in the progesterone soft capsule content (suspension) is avoided on the other hand, further, the detection method of the invention is more accurate, simple and efficient.
The invention provides a method for detecting the particle size distribution of progesterone in a progesterone soft capsule content, which comprises the following steps: adding the content of the progesterone soft capsule into a saturated light liquid paraffin solution, uniformly dispersing by ultrasonic, and carrying out particle size test by a laser particle size detector to obtain the particle size distribution of the progesterone in the content of the progesterone soft capsule;
wherein the saturated light liquid paraffin solution is a saturated progesterone-light liquid paraffin solution, and the solution is saturated in the dissolved progesterone.
In an embodiment of the present invention, the light liquid paraffin has a general meaning in the art, and is referred to as light wax, wherein the number of carbon atoms in the paraffin is C9 to C13.
In an embodiment of the present invention, the laser particle size detection instrument is a wet laser particle size tester.
In an embodiment of the present invention, the saturated light liquid paraffin solution is prepared by the following method: adding progesterone into light liquid paraffin, wherein the weight ratio of the progesterone to the light liquid paraffin is more than or equal to 1:400, stirring and dissolving for 10-24 hours at room temperature, and filtering to prepare the progesterone-containing composite.
In the present invention, "room temperature" includes a temperature in the range of 15 to 35 ℃.
In an embodiment of the invention, the filtration is effected by an oily microfiltration membrane.
In an embodiment of the present invention, the pore size of the oily microfiltration membrane is 0.25 μm or less, preferably 0.22 μm or less.
The method for detecting the particle size distribution of the progesterone in the progesterone soft capsule content specifically comprises the following steps:
s1, filling a detection pool of a laser particle size detection instrument with a pre-prepared saturated light liquid paraffin solution, and testing the background of the instrument;
s2, adding the content of the progesterone soft capsule into a prepared saturated light liquid paraffin solution, and performing ultrasonic dispersion uniformly to obtain a sample solution;
and S3, after the instrument background test is finished, deducting the background value, and dropwise adding the sample solution into a sample pool of the laser particle size detection instrument for particle size test.
In the embodiment of the invention, the mass-to-volume ratio of the content of the progesterone soft capsule to the saturated light liquid paraffin solution in the step S2 is 0.03-0.05 g/mL.
In an embodiment of the present invention, the ultrasonic dispersion in step S2 has a frequency of 30 to 40kHz and a time of 2 to 5 min.
In the embodiment of the present invention, in step S3, the sample solution is added dropwise to the sample cell of the laser particle size detection instrument until the refractive index reaches 8% to 15%, and then the particle size test is performed.
In an embodiment of the present invention, a suitable refractive index in step S3 is 8% to 15%. Detection is performed when the refractive index reaches and stabilizes within this numerical range. As mentioned above, the present invention uses the pre-prepared saturated light liquid paraffin solution, so the dissolution of the progesterone in the solution reaches saturation, and the progesterone in the progesterone soft capsule content does not continue to dissolve, so the reduction of the refractive index and the influence on the detection result are avoided.
The method for detecting the particle size distribution of the progesterone in the progesterone soft capsule content specifically comprises the following steps:
s1, opening a laser particle analyzer and preheating; running granularity testing software, cleaning instrument pipelines by using light liquid paraffin, filling a detection pool with a pre-configured saturated light liquid paraffin solution after exhausting, and adjusting an instrument and testing an instrument background;
s2, placing the content of the progesterone soft capsule into a container, adding a prepared saturated light liquid paraffin solution, and performing ultrasonic dispersion uniformly;
s3, after the instrument background test is finished, deducting a background value, and dropwise adding a sample solution into a sample pool until a proper refractive index is achieved;
and S4, carrying out sample test by using a test function button in the particle size test software to obtain a particle size distribution result.
The invention mainly encounters the following difficulties in the research and development process: the particles and the liquid (vegetable oil) in the contents (suspension) of the progesterone soft capsule cannot be separated, the vegetable oil interferes with detection in a water dispersion medium, and the progesterone is dissolved in a common dispersion medium capable of dissolving the vegetable oil, so that the refractive index is sharply reduced, and the accuracy of a detection result is further influenced. Through experimental screening, saturated light liquid paraffin is selected as a dispersion medium, the medium can dissolve vegetable oil, interference of the vegetable oil is eliminated, and the saturated light liquid paraffin hardly dissolves progesterone within detection time (has stable refractive index), so that the difficulty is solved.
In the invention, saturated light liquid paraffin is used as a dispersing agent to dissolve progesterone until the progesterone is saturated to obtain a saturated light liquid paraffin solution, and the saturated light liquid paraffin solution can be used for dissolving oil coated in the progesterone soft capsule content (suspension) without dissolving the progesterone in the progesterone soft capsule content, so that the influence of oil in the progesterone soft capsule content (suspension) on a detection result is avoided, and the change of the particle size caused by the dissolution of the progesterone in the progesterone soft capsule content (suspension) is avoided, thereby enabling the detection method to be more accurate, simple and efficient. In addition, compared with the existing microscopic image analysis method, the method has the advantages of more detected samples, relatively cheap detection equipment, and better precision and applicability. Furthermore, the measuring instrument is widely used, the experimental result is visual and efficient, the relative standard deviation of the multiple measurement results of the D10 and D90 particle sizes is not more than 5 percent, the relative standard deviation of the multiple measurement results of the D50 particle sizes is not more than 3 percent, and the requirement of the Chinese pharmacopoeia on the repeatability of the detection result of the laser particle sizer is met.
Drawings
In order to illustrate the invention more clearly, the drawings that are necessary for the embodiments to be used will be described below, which only show some embodiments of the invention, from which other drawings can be derived by a person skilled in the art without inventive faculty, which are within the scope of the invention.
FIG. 1 shows a particle size distribution diagram according to example 1 of the present invention.
Fig. 2 shows the values of RSD according to embodiment 1 of the present invention.
FIG. 3 shows a particle size distribution diagram according to example 2 of the present invention.
Fig. 4 shows the values of RSD according to embodiment 2 of the present invention.
FIG. 5 shows a particle size distribution diagram according to example 3 of the present invention.
Fig. 6 shows the value of RSD according to embodiment 3 of the present invention.
Fig. 7 shows a particle size distribution diagram of comparative example 1 according to the present invention.
Fig. 8 shows the values of RSD of comparative example 1 according to the present invention.
Fig. 9 shows a particle size distribution diagram of comparative example 2 according to the present invention.
Detailed Description
The embodiments of the present invention will now be described in detail, with reference to the accompanying drawings, wherein like reference numerals refer to like elements throughout. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The preparation method of the saturated light liquid paraffin comprises the following steps: 5g of progesterone is added into 2000g of light liquid paraffin (purchased from Hunanerkang pharmaceutical products Co., Ltd., executing the standard of Chinese pharmacopoeia 2020 edition No. 4), mixed, stirred and dissolved for 10-24 hours, and filtered by an oily microporous filter membrane of 0.22 μm to prepare the progesterone.
Example 1
A sample of the progesterone soft capsule contents, lot No. 21081501, was tested for particle size distribution as follows: the instrument was turned on and preheated for half an hour using a Bettersize2600 Intelligent laser particle sizer, Dandong Baite instruments. And (3) running granularity testing software, cleaning instrument pipelines by using light liquid paraffin, pouring saturated light liquid paraffin into the detector after the light liquid paraffin is completely discharged, and setting the circulating rotating speed to be 2000 rpm. Instrument centering was adjusted in the software window, and the instrument background was tested. Taking 0.5g of the content of the progesterone soft capsule, putting the content into a 50ml beaker, diluting the content to 10ml by using saturated light liquid paraffin, stirring the mixture to disperse the mixture, and preparing a test sample by using ultrasonic frequency of 36kHz and ultrasonic time of 3 mm. And (3) adding the sample to be tested into the sample pool until the refractive index is about 12%, clicking a test button in the software to test the sample, detecting for 5 times, automatically giving a test result by a computer after the test is finished, and calculating the RSD value of the five-time detection result. The particle size distribution is shown in FIG. 1, and the RSD value of the detection result is shown in FIG. 2.
As can be seen from FIG. 2, the RSD values of the five detection results of D10, D50 and D90 are 0.13%, 0.10% and 0.26% respectively, which meet the requirement of the third method in the particle size and particle size distribution determination method of ChP2020 rule (Chinese Pharmacopeia 2020, Chinese Pharmacopoeia 2020)0982 on the standard particle test repeatability (the RSD values of D10 and D90 are less than or equal to 5.0%, and the RSD value of D50 is less than or equal to 3.0%), and the repeatability of the parallel test sample in the detection method in the embodiment is proved to meet the industrial requirement.
Example 2
A sample of the progesterone soft capsule contents, lot No. 21081501, was tested for particle size distribution as follows: the instrument was turned on and preheated for half an hour using a Bettersize2600 Intelligent laser particle sizer, Dandong Baite instruments. And (3) running granularity testing software, cleaning instrument pipelines by using light liquid paraffin, pouring saturated light liquid paraffin into the detector after the light liquid paraffin is completely discharged, and setting the circulating rotating speed to be 2000 rpm. Instrument centering was adjusted in the software window, and the instrument background was tested. Taking 0.3g of the content of the progesterone soft capsule, putting the content into a 50ml beaker, diluting the content to 10ml by using saturated light liquid paraffin, stirring the mixture to disperse the content, and preparing a test sample by using ultrasonic frequency of 36kHz and ultrasonic time of 3 mm. And (3) adding the sample to be tested into the sample pool until the refractive index is about 12%, clicking a test button in the software to test the sample, detecting for 5 times, automatically giving a test result by a computer after the test is finished, and calculating the RSD value of the five-time detection result. The particle size distribution is shown in FIG. 3, and the RSD value of the detection result is shown in FIG. 4.
As can be seen from FIG. 4, the RSD values of the five detection results of D10, D50 and D90 are respectively 0.03%, 0.11% and 0.24%, and the requirement of the third method of the ChP2020 particle size and particle size distribution determination method on the repeatability of the parallel inspection of the standard particle inspection (the RSD values of D10 and D90 are less than or equal to 5.0%, and the RSD value of D50 is less than or equal to 3.0%) is met, so that the repeatability of the parallel inspection sample of the detection method in the embodiment meets the industrial requirement.
Example 3
A sample of the progesterone soft capsule contents, lot No. 21081501, was tested for particle size distribution as follows: the instrument was turned on and preheated for half an hour using a Bettersize2600 Intelligent laser particle sizer, Dandong Baite instruments. And (3) running granularity testing software, cleaning instrument pipelines by using light liquid paraffin, pouring saturated light liquid paraffin into the detector after the light liquid paraffin is completely discharged, and setting the circulating rotating speed to be 2000 rpm. Instrument centering was adjusted in the software window, and the instrument background was tested. Taking 0.5g of the content of the progesterone soft capsule, putting the content into a 50ml beaker, diluting the content to 10ml by using saturated light liquid paraffin, stirring the mixture to disperse the mixture, and preparing a test sample by using ultrasonic frequency of 36kHz and ultrasonic time of 3 mm. And (3) adding the sample to be tested into the sample pool until the refractive index is about 15%, clicking a test button in the software to test the sample, and automatically giving a test result by the computer after the test is finished. And (5) detecting for 5 times, automatically giving a test result by a computer after the test is finished, and calculating the RSD value of the five detection results. The particle size distribution is shown in FIG. 5, and the RSD value of the detection result is shown in FIG. 6.
As can be seen from FIG. 6, the RSD values of the five detection results of D10, D50 and D90 are 4.12%, 1.86% and 0.84%, respectively, and meet the requirement of the third method of the ChP2020 particle size and particle size distribution measurement method on the repeatability of the parallel test of the standard particle test (the RSD values of D10 and D90 are less than or equal to 5.0%, and the RSD value of D50 is less than or equal to 3.0%), which proves that the repeatability of the parallel test sample of the detection method in the embodiment meets the industrial requirement.
Comparative example 1
In contrast to example 3, the saturated light liquid paraffin was replaced by sunflower oil.
A sample of the progesterone soft capsule contents, lot No. 21081501, was tested for particle size distribution as follows: the instrument was turned on and preheated for half an hour using a Bettersize2600 Intelligent laser particle sizer, Dandong Baite instruments. And (3) running a granularity testing software, cleaning an instrument pipeline by using the sunflower seed oil, filling the sunflower seed oil into the detector after the sunflower seed oil is discharged, and setting the circulating rotating speed to 2000 rpm. Instrument centering was adjusted in the software window, and the instrument background was tested. Taking 0.5g of the content of the progesterone soft capsule, putting the progesterone soft capsule in a 50ml beaker, diluting the progesterone soft capsule to 10ml by using sunflower seed oil, stirring the sunflower seed oil to disperse the progesterone soft capsule, and preparing a test sample by using ultrasonic frequency of 36kHz and ultrasonic time of 3 mm. And (3) adding the sample to be tested into the sample pool until the refractive index is about 12%, clicking a test button in the software to test the sample, and automatically giving a test result by the computer after the test is finished. And (3) detecting for 5 times, automatically giving a test result by a computer after the test is finished, calculating the RSD value of the test result for five times, wherein the granularity distribution diagram is shown in figure 7, and the RSD value of the test result is shown in figure 8.
As can be seen from FIG. 8, the RSD values of the five test results of D10, D50 and D90 are 2.35%, 5.54% and 4.34%, respectively, which do not satisfy the requirement of the third method of the 0982 particle size and particle size distribution test method of the general rule of ChP2020 on the repeatability of the parallel test of the standard particle test (the RSD values of D10 and D90 are less than or equal to 5.0%, and the RSD value of D50 is less than or equal to 3.0%). This demonstrates that the reproducibility of the parallel test samples of the detection method in this comparative example does not meet the industry requirements. Further, from the results of fig. 7, it is estimated that the particle diameter is too large and the particle aggregates are not completely dispersed, and the reproducibility of the detection results is poor.
Comparative example 2
In comparison with example 3, the saturated light liquid paraffin was replaced with light liquid paraffin.
A sample of the progesterone soft capsule contents, lot No. 21081501, was tested for particle size distribution as follows: the instrument was turned on and preheated for half an hour using a Bettersize2600 Intelligent laser particle sizer, Dandong Baite instruments. And (3) running granularity testing software, cleaning instrument pipelines by using light liquid paraffin, pouring the light liquid paraffin into the detector after the light liquid paraffin is drained, and setting the circulating rotating speed to be 2000 rpm. Instrument centering was adjusted in the software window, and the instrument background was tested. Taking 0.5g of the content of the progesterone soft capsule, putting the content into a 50ml beaker, diluting the content to 10ml by using light liquid paraffin, stirring the mixture to disperse the content, and preparing a test sample by using ultrasonic frequency of 36kHz and ultrasonic time of 3 mm. And (3) adding the sample to be tested into the sample pool until the refractive index is about 12%, clicking a test button in the software to test the sample, and automatically giving a test result by the computer after the test is finished. And (5) detecting for 5 times, automatically giving a test result by a computer after the test is finished, and calculating the RSD value of the five detection results. The particle size distribution is shown in FIG. 9. The detected particle size distribution is obviously smaller than that of the saturated liquid paraffin, and the particle size detection value becomes smaller because the particles are dissolved in the liquid paraffin of the sample.
It will be understood that the above embodiments are merely exemplary embodiments taken to illustrate the principles of the present invention, which is not limited thereto. It will be apparent to those skilled in the art that various changes and modifications may be made therein without departing from the spirit and scope of the invention, and these are considered to fall within the scope of the invention.
Claims (9)
1. A method for detecting the particle size distribution of progesterone in progesterone soft capsule contents is characterized in that the progesterone soft capsule contents are added into a saturated light liquid paraffin solution, dispersed uniformly by ultrasonic, and subjected to particle size test by a laser particle size detector to obtain the particle size distribution of the progesterone in the progesterone soft capsule contents;
wherein the saturated light liquid paraffin solution is a saturated progesterone-light liquid paraffin solution, and the solution is saturated in the dissolved progesterone.
2. The method for detecting the particle size distribution of progesterone in the content of a progesterone soft capsule according to claim 1, wherein the laser particle size detector is a wet laser particle size tester.
3. The method for detecting the particle size distribution of progesterone in the content of the progesterone soft capsule according to claim 1, wherein the preparation method of the saturated light liquid paraffin solution comprises the following steps: adding progesterone into light liquid paraffin, wherein the weight ratio of the progesterone to the light liquid paraffin is more than or equal to 1:400, stirring and dissolving for 10-24 hours at room temperature, and filtering to prepare the progesterone-containing composite.
4. The method for detecting the particle size distribution of progesterone in the content of a progesterone soft capsule according to claim 1, wherein the filtration is performed by an oily microporous filtration membrane.
5. The method for detecting the particle size distribution of progesterone in the content of a progesterone soft capsule according to claim 4, wherein the pore size of the oily microfiltration membrane is 0.25 μm or less.
6. The method for detecting the particle size distribution of progesterone in the content of the progesterone soft capsule according to claim 1, comprising the following steps:
s1, filling a detection pool of a laser particle size detection instrument with a pre-prepared saturated light liquid paraffin solution, and testing the background of the instrument;
s2, adding the content of the progesterone soft capsule into a prepared saturated light liquid paraffin solution, and performing ultrasonic dispersion uniformly to obtain a sample solution;
and S3, after the instrument background test is finished, deducting the background value, and dropwise adding the sample solution into a sample pool of the laser particle size detection instrument for particle size test.
7. The method for detecting the particle size distribution of progesterone in the progesterone soft capsule content of claim 6, wherein the mass-to-volume ratio of the progesterone soft capsule content to the saturated light liquid paraffin solution in step S2 is 0.03-0.05 g/mL.
8. The method for detecting the particle size distribution of progesterone in the content of the progesterone soft capsule according to claim 6, wherein the ultrasonic dispersion is performed at a frequency of 30 to 40kHz for a time of 2 to 5min in step S2.
9. The method for detecting the particle size distribution of progesterone in the progesterone soft capsule content of claim 6, wherein in step S3, the sample solution is added dropwise to a sample cell of a laser particle size detector until a refractive index reaches 8% to 15%, and then a particle size test is performed.
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