CN113237802A - Method for measuring granularity and granularity distribution of progesterone medicament in progesterone vaginal sustained-release gel - Google Patents
Method for measuring granularity and granularity distribution of progesterone medicament in progesterone vaginal sustained-release gel Download PDFInfo
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- CN113237802A CN113237802A CN202110737832.1A CN202110737832A CN113237802A CN 113237802 A CN113237802 A CN 113237802A CN 202110737832 A CN202110737832 A CN 202110737832A CN 113237802 A CN113237802 A CN 113237802A
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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
- G01N15/0211—Investigating a scatter or diffraction pattern
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/38—Diluting, dispersing or mixing samples
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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
- G01N2015/025—Methods for single or grouped particles
Abstract
The invention relates to the technical field of drug analysis, in particular to a method for determining granularity and granularity distribution of a progesterone medicament in progesterone vaginal sustained-release gel. The method comprises the following steps: adding a sample into a dispersion medium according to a specified proportion, stirring for 15min, adding a proper amount of surfactant, stirring and ultrasonically treating to obtain a test solution, and detecting by using a laser particle size analyzer. The method is simple and convenient to operate, interference of other auxiliary materials in the progesterone vaginal sustained-release gel on progesterone drug granularity and granularity distribution measurement is removed through sample pretreatment, the progesterone is uniformly and stably dispersed in a dispersion medium, and the proved measurement result is accurate and reliable.
Description
Technical Field
The invention belongs to the field of drug analysis, and particularly relates to a method for determining granularity and granularity distribution of a progesterone drug in progesterone vaginal sustained-release gel.
Background
Progesterone (progestasterone) is a biologically active primary progestin secreted by the ovaries and acts in vivo on the estrogen-stimulated endometrium, essential for the maintenance of pregnancy. It is often used for the reactive diagnosis of the amenorrhea or amenorrhea cause caused by threatened abortion, habitual abortion, endometriosis, dysfunctional uterine bleeding, dysmenorrhea, and ovarian hypofunction.
Currently, progesterone preparations in various dosage forms are available on the market, including progesterone tablets, progesterone capsules, progesterone injection, progesterone vaginal sustained-release gel and the like. Progesterone is orally taken, about 90% is metabolized by the liver, and bioavailability is low. The progesterone injection is an oil solution, and has strong pain feeling during injection. The progesterone vaginal sustained-release gel can be continuously absorbed by vaginal epithelial cells and diffused to endometrium and muscular layer, and compared with injection and oral administration, the progesterone vaginal sustained-release gel has lower proportion of absorbed blood, so that higher drug concentration can be formed at local part of uterus, which is beneficial to improving the treatment effect and obviously reducing the adverse reaction.
Progesterone is a poorly soluble drug, and research shows that the solubility and the release of the drugs have a clear relationship with the particle size. The progesterone vaginal sustained-release gel is a preparation absorbed through skin, and the particle size of the progesterone in the gel has important influence on absorption, so the particle size and the particle size distribution of the progesterone medicament in the progesterone vaginal sustained-release gel are directly related to the quality of the medicament.
According to the guide principle of stability test of raw materials and preparations recorded in the current edition of Chinese pharmacopoeia, the granularity is an important investigation index for the stability research of the gel. However, there is no relevant literature or patent report at present, and a method for determining the particle size and the particle size distribution of the progesterone medicament in the progesterone vaginal sustained-release gel is provided.
The method for measuring the particle size and the particle size distribution recorded in the Chinese pharmacopoeia comprises the following steps: microscopy, sieving and light scattering. In the microscopic method, the particle size of a sample is observed under a microscope directly, and the ratio of the number of particles having a predetermined size to the total number of particles is calculated. The sieving method is to select a medicine sieve with specified mesh number, pass the sample through the medicine sieve, and calculate the proportion of powder or particles passing through the medicine sieve.
The light scattering method is a method in which a particle sample is scattered by a monochromatic light beam, and the energy distribution of the scattered light is related to the size of the particle, so that the particle size distribution of the particle is calculated by measuring the energy distribution of the scattered light. The light scattering method is classified into wet measurement suitable for a suspended sample or a sample insoluble in a dispersion medium and dry measurement suitable for a solid sample soluble or free of a suitable dispersion medium.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to provide a method for accurately measuring the granularity and the granularity distribution of progesterone in progesterone vaginal sustained-release gel without being interfered by other auxiliary materials in the progesterone vaginal sustained-release gel.
The purpose of the invention is realized by the following technical scheme:
a method for determining the granularity and the granularity distribution of a progesterone medicament in a progesterone vaginal sustained-release gel comprises the following steps:
adding a sample into a dispersion medium according to a specified proportion, stirring for 15min, adding a proper amount of surfactant, stirring and ultrasonically treating to obtain a test solution, and detecting by using a laser scattering particle size analyzer.
The sample is added into 10ml of dispersion medium according to the proportion of 0.5-1.5 g of sample.
The sample addition ratio is preferably 1.0g of sample to 10ml of dispersion medium.
The dispersion medium is first-grade ultrapure water.
The surfactant is anionic surfactant or nonionic surfactant, and the addition amount of the surfactant is 1.5-2.5%.
The anionic surfactant is preferably sodium dodecyl sulfate, and the nonionic surfactant is preferably tween-80.
The addition amount of the surfactant is preferably 2%.
The stirring time after the surfactant is added is 20-60 s, and the ultrasonic time is 2-20 min.
The stirring time after the surfactant is added is preferably 60s, and the ultrasonic time is preferably 10 min.
When the particle size analyzer is used for detection, the refractive index of the particles is 1.400-1.600, the absorption rate of the particles is 0-0.1, the light shielding degree is 12-20%, and the circulation speed is 2000 r.min-1。
The method can eliminate the interference of the auxiliary material particles in the sample on the measurement by designing a sample pretreatment method to obtain the results of the particle size and the particle size distribution of the progesterone drug particles.
Compared with the prior art, the invention has the following advantages and effects:
1. the invention selects water as a dispersion medium, almost all auxiliary materials in the progesterone vaginal sustained-release gel can be completely dissolved, and the progesterone drug is insoluble and dispersed in the dispersion medium.
2. According to the invention, the surface active dispersing auxiliary agent is added into the dispersing medium, so that the surface wettability of the progesterone medicament is increased, and meanwhile, the progesterone medicament can be fully dispersed, and the agglomeration phenomenon is avoided; in addition, the dispersion uniformity and stability of the progesterone medicament are enhanced by reasonable proportion of the medicament to the dispersion medium and assisted by stirring and ultrasonic treatment.
The method is simple and convenient to operate, the particle size and the particle size distribution of the progesterone medicament in the progesterone vaginal sustained-release gel can be measured by using a conventional wet light scattering method through sample pretreatment, and the measurement result is accurate and reliable through the verification of a special test, a precision test and a durability test.
Drawings
Figure 1 is a test report for determining the repeatability of the granularity and the granularity distribution of progesterone medicaments in progesterone vaginal sustained-release gel. Figure 2 is the intermediate precision test report for measuring the granularity and the granularity distribution of the progesterone medicament in the progesterone vaginal sustained-release gel.
Detailed Description
The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto.
Example 1
The test solution was prepared by the following steps:
and (3) taking the progesterone vaginal sustained-release gel of the brand A, extruding and weighing 1.0g of sample into a beaker, adding 10ml of first-level ultrapure water, stirring for 15min, adding 0.2g of sodium dodecyl sulfate, stirring for 60s, and carrying out ultrasound for 10 min.
When the particle size analyzer is used for detection, the refractive index of the particles is 1.520, the absorption rate of the particles is 0.1, and the circulation speed is 2000 r.min-1The shading degree is 12-20%. The results are shown in FIG. 1.
Example 2
The test solution was prepared by the following steps:
and (3) taking the progesterone vaginal sustained-release gel of the brand A, extruding and weighing 1.0g of sample into a beaker, adding 10ml of first-level ultrapure water, stirring for 15min, adding 0.2g of sodium dodecyl sulfate, stirring for 60s, and carrying out ultrasound for 10 min.
When the particle size analyzer is used for detection, the refractive index of the particles is 1.520, the absorption rate of the particles is 0.1, and the circulation speed is 2000 r.min-1The shading degree is 12-20%.
The results are shown in FIG. 2.
Claims (10)
1. A method for measuring the granularity and the granularity distribution of a progesterone medicament in a progesterone vaginal sustained-release gel is characterized by comprising the following steps: adding a sample into a dispersion medium according to a specified proportion, stirring for 15min, adding a proper amount of surfactant, stirring and ultrasonically treating to obtain a test solution, and detecting by using a laser scattering particle size analyzer.
2. The method according to claim 1, wherein the sample is added in a ratio of 0.5 to 1.5g to 10ml of the dispersion medium.
3. The method according to claim 2, wherein the sample is added in a ratio of 1.0g of sample to 10ml of dispersion medium.
4. The method of claim 1, wherein the dispersion medium is primary ultrapure water.
5. The method according to claim 1, wherein the surfactant is an anionic surfactant or a nonionic surfactant, and the surfactant is added in an amount of 1.5% to 2.5%.
6. The method of claim 5, wherein the anionic surfactant is sodium lauryl sulfate and the non-ionic surfactant is tween-80.
7. The method of claim 5, wherein the surfactant is added in an amount of 2%.
8. The method according to claim 1, wherein the stirring time after the surfactant is added is 20-60 s, and the ultrasonic time is 2-20 min.
9. The method of claim 8, wherein the time for stirring after adding the surfactant is 60s and the time for sonication is 10 min.
10. The method of claim 1, wherein the refractive index of the particles is 1.400-1.600, the absorption rate of the particles is 0-0.1, the light shielding degree is 12-20%, and the circulation speed is 2000 r-min when the particles are detected by a laser particle size analyzer-1。
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| Application Number | Priority Date | Filing Date | Title |
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| CN202110737832.1A CN113237802A (en) | 2021-06-30 | 2021-06-30 | Method for measuring granularity and granularity distribution of progesterone medicament in progesterone vaginal sustained-release gel |
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| CN202110737832.1A CN113237802A (en) | 2021-06-30 | 2021-06-30 | Method for measuring granularity and granularity distribution of progesterone medicament in progesterone vaginal sustained-release gel |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114527042A (en) * | 2021-12-24 | 2022-05-24 | 湖南醇健制药科技有限公司 | Method for detecting particle size distribution of progesterone in progesterone soft capsule contents |
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2021
- 2021-06-30 CN CN202110737832.1A patent/CN113237802A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114527042A (en) * | 2021-12-24 | 2022-05-24 | 湖南醇健制药科技有限公司 | Method for detecting particle size distribution of progesterone in progesterone soft capsule contents |
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