CN116678794A - Particle size microscopic detection method of Lipropibicaine cream - Google Patents
Particle size microscopic detection method of Lipropibicaine cream Download PDFInfo
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- 239000006071 cream Substances 0.000 title claims abstract description 137
- 239000002245 particle Substances 0.000 title claims abstract description 73
- 238000001514 detection method Methods 0.000 title claims abstract description 34
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims abstract description 83
- 238000000034 method Methods 0.000 claims abstract description 26
- 239000011521 glass Substances 0.000 claims abstract description 24
- 239000006059 cover glass Substances 0.000 claims abstract description 18
- 239000011248 coating agent Substances 0.000 claims abstract description 11
- 238000000576 coating method Methods 0.000 claims abstract description 11
- 238000004898 kneading Methods 0.000 claims abstract description 7
- 230000003287 optical effect Effects 0.000 claims description 8
- 238000009826 distribution Methods 0.000 abstract description 18
- 230000000694 effects Effects 0.000 abstract description 7
- 239000006185 dispersion Substances 0.000 abstract description 3
- 238000005259 measurement Methods 0.000 abstract description 3
- 238000003384 imaging method Methods 0.000 abstract description 2
- 230000000052 comparative effect Effects 0.000 description 19
- 239000002270 dispersing agent Substances 0.000 description 17
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 9
- 230000000007 visual effect Effects 0.000 description 9
- 229920002125 Sokalan® Polymers 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229960001631 carbomer Drugs 0.000 description 6
- 238000011068 loading method Methods 0.000 description 6
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 6
- 229960001634 ritodrine Drugs 0.000 description 6
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000010627 cedar oil Substances 0.000 description 4
- 238000002296 dynamic light scattering Methods 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 238000000399 optical microscopy Methods 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
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- 238000007606 doctor blade method Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000001788 irregular Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000012798 spherical particle Substances 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 206010027146 Melanoderma Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 241000183024 Populus tremula Species 0.000 description 1
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- 238000004458 analytical method Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
- 229960001888 ipratropium Drugs 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000011192 particle characterization Methods 0.000 description 1
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- -1 polyoxyethylene Polymers 0.000 description 1
- 229960001807 prilocaine Drugs 0.000 description 1
- MVFGUOIZUNYYSO-UHFFFAOYSA-N prilocaine Chemical compound CCCNC(C)C(=O)NC1=CC=CC=C1C MVFGUOIZUNYYSO-UHFFFAOYSA-N 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000012764 semi-quantitative analysis Methods 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
The invention relates to a particle size microscopic detection method of a Lipobicaine cream, which comprises the following steps: (1) Directly coating a Li Bing bicaine cream sample on a glass slide; (2) Dripping n-decane on a Li Bing bicaine cream sample, covering with a cover glass, and lightly kneading to uniformly distribute the Li Bing bicaine cream sample; (3) observing and collecting images under a microscope. The method has the advantages of simple sample treatment, good dispersion effect, clear imaging, easy statistics and high repeatability, and ensures the accuracy of the particle size and particle size distribution data obtained by measurement.
Description
Technical Field
The invention belongs to the technical field of detection of pharmaceutical preparations, and particularly relates to a particle size microscopic detection method of a Lipobicaine cream.
Background
Cream is a uniform semisolid preparation formed by dissolving or dispersing common raw materials in emulsion type matrix, and can be divided into oil-in-water type cream and water-in-oil type cream according to the different matrixes.
The granularity is an important index for evaluating the cream, and according to the technical evaluation requirement (solicitation opinion manuscript) of the external skin imitation pharmacy of new registration classification issued by the drug evaluation center of the national drug administration, the indexes such as the droplet size and the rheological property of the preparation reflect the rationality of the prescription process and possibly influence the release effect and the clinical curative effect of the medicine, especially for the cream and the emulsion products with micrometer and nanometer scale, the droplet size and the distribution have important influence on the quality and the drug effect, and the comprehensive comparison research on the droplet size and the rheological property of imitation and reference preparation is recommended, and the variation trend of the droplet size is examined in the stability research.
In the characterization of the microstructure of semi-solid formulations and the determination of particle dimensions, the greatest challenge encountered is the need to develop a suitable sample preparation technique to meet the following requirements: (1) the particles or droplets can be strictly distinguished from other components in the formulation in order to obtain accurate particle counts; (2) dilution, evaporation, or other manipulation during sample preparation does not alter the original distribution of particles or droplets.
Many detection techniques are currently in practical use, including optical microscopy, morphology Directed Raman Spectroscopy (MDRS), dynamic Light Scattering (DLS), and Laser Diffraction (LD). Wherein, the measuring range of the optical microscopy and the MDRS method is 1-1000 mu m; the DLS and LD methods are applicable to the measurement of the size and distribution of microparticles of 10nm to 10 μm and 10nm to 1mm, respectively. The MDRS technology is suitable for semi-quantitative analysis; DLS and LD techniques are not suitable for viscous samples, require good flowability for the sample, and sufficiently dilute the viscous or microstructure-containing sample, which can easily cause distortion of particle size and particle size distribution data. The sample treatment methods of the three are complex, the equipment requirement is high, and the cost is high. The optical microscopy method has the advantages of small sample consumption, characterization of spherical particles and non-spherical particles, verification of calibration precision, simple and convenient sample preparation, quantification and the like, and is the most widely used tool in microstructure and morphological analysis of semisolid preparations.
The raw grinding product of Li Bing bicaine cream is O/W type cream produced by Aspen company, and the prescription comprises lidocaine (active ingredient), prilocaine (active ingredient), carbomer (thickener), polyoxyethylene hydrogenated castor oil (emulsifier) and sodium hydroxide (pH regulator), wherein the carbomer is acrylic acid crosslinked resin obtained by crosslinking acrylic acid with pentaerythritol and the like, and the carbomer is neutralized by sodium hydroxide to form salt to enable curled molecules to be thickened due to electric repulsive force opening. Both drug substances were present in the cream as co-melt droplets dispersed in a matrix of Yu Kabo m, but when Li Bing bicaine cream was observed by optical microscopy, the droplets were easily covered with carbomers, resulting in the droplets not appearing.
Therefore, it is necessary to find a suitable sample processing method, which can eliminate the influence of carbomer as much as possible when the particle size of Li Bing bicaine cream is measured by a microscope method, obtain a stable and clear image, facilitate the statistical analysis of the particle size, and ensure the accuracy of the particle size and the particle size distribution data.
Disclosure of Invention
The invention aims to solve the technical problems of overcoming the defects in the prior art and providing the particle size microscopic detection method of the Lipropibicaine emulsifiable paste.
In order to solve the technical problems, the invention adopts the following technical scheme:
a particle size microscopic detection method of a Lipobicaine cream comprises the following steps:
(1) Directly coating a Li Bing bicaine cream sample on a glass slide;
(2) Dripping n-decane on a Li Bing bicaine cream sample, covering with a cover glass, and lightly kneading to uniformly distribute the Li Bing bicaine cream sample;
(3) The images were observed and collected under a microscope.
Preferably, the Li Bing bicaine cream sample in step (1) is used in an amount of 1 to 5mg.
Further preferably, the Li Bing bicaine cream sample in step (1) is used in an amount of 1 to 3mg.
Preferably, the Li Bing bicaine cream sample in step (1) is not diluted.
Preferably, the n-decane in step (2) completely covers the Li Bing bicaine cream sample.
Preferably, the amount of n-decane used in step (2) is from 5 to 20. Mu.L.
Preferably, n-decane in the step (2) is added dropwise at one time.
Preferably, in the step (2), the Li Bing bicaine cream sample is evenly distributed until the cream sample is evenly semitransparent, and no bubbles exist in the cream sample.
Preferably, the microscope used in step (3) is an optical microscope of 180 times or more.
Further preferably, the microscope used in step (3) is a 200-fold optical microscope.
Preferably, the particle size microscopic detection method comprises the following steps:
(1) Spot-coating 1-3 mg Li Bing bicaine cream sample on a glass slide, wherein the Li Bing bicaine cream sample is not diluted;
(2) Dropwise adding 5-20 mu L of n-decane on a Li Bing bicaine cream sample, covering with a cover glass, and lightly rubbing to uniformly distribute the Li Bing bicaine cream sample until the cream sample is uniform and semitransparent, wherein no bubbles exist in the cream sample;
(3) The images were immediately observed and collected under a 200-fold light microscope.
Due to the adoption of the technical scheme, compared with the prior art, the invention has the following advantages:
1. according to the particle size microscopic detection method, the optimal scheme is determined through condition optimization such as dispersant screening, smear technique, cream sample loading and the like, and the sample treatment is simple and convenient;
2. the particle size microscopic detection method has the advantages of good dispersion effect, clear imaging and easy statistics, and can realize small-error image acquisition and counting;
3. the particle size microscopic detection method has high repeatability, ensures the accuracy of particle size and particle size distribution data, and provides data support for the quality improvement of cream;
4. according to the particle size microscopic detection method, the Li Bing bicaine cream sample in the step (1) is not diluted, so that the distortion of particle size and particle size distribution data caused by dilution of the sample in the prior art can be effectively avoided, and the authenticity of the data is ensured.
Drawings
FIG. 1 is a microscopic image of the Lipobicaine cream of example 1 with n-decane as dispersant;
FIG. 2 is a microscopic image of the Lipobicin cream of comparative example 1 with water as the dispersant;
FIG. 3 is a microscopic image of the bicaine cream of comparative example 2 Li Bing with cedar oil as the dispersant;
FIG. 4 is a microscopic image of the example 2 Li Bing bicaine cream as applied by the spot-on-tablet technique;
FIG. 5 is a microscopic image of the Lipobicaine cream of comparative example 3 as it was applied by the doctor blade technique;
FIG. 6 is a microscopic image of the example 3 ipratropium bicaine cream at a fixed loading of 1mg to 5 mg;
FIG. 7 is a microscopic image of the off-time dose of the Lipobicaine cream of comparative example 4;
FIG. 8 is a microscopic image of the Lipobicaine cream of comparative example 5 diluted with n-decane 1:1;
FIG. 9 is a microscopic image of the Lipobicaine cream of comparative example 6 diluted with n-decane 1:2.
Detailed Description
In order to make the technical scheme and the beneficial effects of the invention more obvious and understandable, the following detailed description is given by way of example. It is to be understood that these examples are provided only for illustrating the present invention and are not to be construed as limiting the scope of the present invention, and any product which is the same as or similar to the present invention obtained by any person who has the teaching of the present invention or who combines the present invention with other prior art features falls within the scope of protection of the present invention.
The following examples are not to be construed as particular techniques or conditions, but are generally carried out in accordance with conventional techniques or conditions described in the literature in this field or in accordance with the specifications of the product and the manufacturer's recommendations.
Unless otherwise indicated, the various starting materials and reagents were either commercially available or were synthesized according to known methods, and were used without further purification.
The invention discloses a particle size microscopic detection method of a Lipobicaine emulsifiable paste, which comprises the following steps:
(1) Directly coating a Li Bing bicaine cream sample on a glass slide;
(2) Dripping n-decane on a Li Bing bicaine cream sample, covering with a cover glass, and lightly kneading to uniformly distribute the Li Bing bicaine cream sample;
(3) The images were observed and collected under a microscope.
In certain specific embodiments, the Li Bing bicaine cream sample in step (1) is used in an amount of from 1 to 5mg.
In certain embodiments, the Li Bing bicaine cream sample of step (1) is used in an amount of 1 to 3mg, more specifically 1mg,2mg,3mg.
In certain specific embodiments, the Li Bing bicaine cream sample in step (1) is not diluted.
In certain specific embodiments, the n-decane in step (2) completely covers the Li Bing bicaine cream sample.
In certain specific embodiments, the specific operation of the gentle kneading in step (2) is: the cover glass is lightly placed and not pressed right above the sample, and the cover glass can be lightly pushed from the side edge of the cover glass in a small amplitude.
In certain embodiments, sufficient n-decane is used in step (2), preferably in an amount of from 5 to 20. Mu.L, and may preferably be from 5 to 18. Mu.L, from 5 to 16. Mu.L, from 5 to 14. Mu.L, from 5 to 12. Mu.L, and more particularly may be from 5. Mu.L, 6. Mu.L, 7. Mu.L, 8. Mu.L, 9. Mu.L, 10. Mu.L, 11. Mu.L, 12. Mu.L, 13. Mu.L, 14. Mu.L, 15. Mu.L, 18. Mu.L.
In certain specific embodiments, n-decane in step (2) is added dropwise at one time.
In certain embodiments, the gentle rubbing of step (2) results in a uniform distribution of Li Bing bicaine cream sample until the cream sample is uniformly translucent, with no air bubbles inside.
In certain embodiments, the microscope used in step (3) is an optical microscope at a magnification of 180, 190, 200, 210, 220, 230, 240.
In a specific embodiment, the microscope used in step (3) is a 200-fold optical microscope.
In a specific embodiment, the method for microscopic detection of the particle size of Li Bing bicaine cream comprises the following steps:
(1) Spot-coating 1-3 mg Li Bing bicaine cream sample on a glass slide, wherein the Li Bing bicaine cream sample is not diluted;
(2) Dropwise adding 5-20 mu L of n-decane on a Li Bing bicaine cream sample, covering with a cover glass, and lightly rubbing to uniformly distribute the Li Bing bicaine cream sample until the cream sample is uniform and semitransparent, wherein no bubbles exist in the cream sample;
(3) The images were immediately observed and collected under a 200-fold light microscope.
The invention lightly kneads the Li Bing bicaine cream sample to be distributed uniformly, does not apply downward acting force, avoids the emulsion drop from being pressed, characterizes abnormal shape and even demulsifies, and influences the particle size measurement.
Example 1
The particle size microscopic detection method of the lyprofen cream comprises the following steps:
(1) Spot-coating 3mg Li Bing of the bicaine cream sample onto a slide glass, the Li Bing bicaine cream sample not being diluted;
(2) Taking n-decane as a dispersing agent, dropwise adding 15 mu L of n-decane on a Li Bing bicaine cream sample at one time, covering with a cover glass, and lightly rubbing to ensure that the Li Bing bicaine cream sample is uniformly distributed until the cream sample is uniform and semitransparent, wherein no bubbles exist in the cream sample;
(3) The whole field of view of the coverslip was immediately examined under a 200-fold light microscope, the particle distribution was observed and an image was acquired, as shown in fig. 1.
The results show that: when n-decane is used as a dispersing agent, the liquid drops in the visual field are uniformly dispersed, and a particle photo with distinct contrast can be obtained by image acquisition, so that the effect of carbomer can be eliminated by n-decane, and a more ideal result can be obtained.
Comparative example 1
The particle size microscopic detection method of the ritodrine emulsifiable paste of the comparative example comprises the following steps:
(1) Spot-coating 3mg Li Bing of the bicaine cream sample onto a slide glass, the Li Bing bicaine cream sample not being diluted;
(2) Taking water as a dispersing agent, dripping 15 mu L of water on a Li Bing bicaine cream sample at one time, covering a cover glass, and lightly rubbing to ensure that the Li Bing bicaine cream sample is uniformly distributed until the cream sample is uniform and semitransparent, and no bubble exists in the cream sample;
(3) The whole field of view of the coverslip was immediately examined under a 200-fold light microscope, the particle distribution was observed and an image was acquired, as shown in fig. 2.
The results show that: when water is used as a dispersing agent, almost no obvious liquid drops exist in the visual field, emulsion drops are not dispersed, and the influence of carbomers cannot be eliminated when the water is used as the dispersing agent.
Comparative example 2
The particle size microscopic detection method of the ritodrine emulsifiable paste of the comparative example comprises the following steps:
(1) Spot-coating 3mg Li Bing of the bicaine cream sample onto a slide glass, the Li Bing bicaine cream sample not being diluted;
(2) Taking cedar oil as a dispersing agent, dripping 15 mu L cedar oil on a Li Bing bicaine cream sample at one time, covering a cover glass, and lightly rubbing to ensure that the Li Bing bicaine cream sample is uniformly distributed until the cream sample is uniform and semitransparent, wherein no bubbles exist in the cream sample;
(3) The whole field of view of the coverslip was immediately examined under a 200-fold light microscope, the particle distribution was observed and an image was acquired, as shown in fig. 3.
The results show that: when cedar oil is used as a dispersing agent, particle characterization with clear boundaries is observed in a visual field, but the background of the method is easy to generate a plurality of different contours to interfere sight and judgment, so the sample treatment method has no reference.
Example 2
The particle size microscopic detection method of the lyprofen cream comprises the following steps:
(1) A 5mg Li Bing bicaine cream sample was spot-coated onto a slide glass, and the Li Bing bicaine cream sample was not diluted;
(2) Taking n-decane as a dispersing agent, dropwise adding 15 mu L of n-decane on a Li Bing bicaine cream sample at one time, covering with a cover glass, and lightly rubbing to ensure that the Li Bing bicaine cream sample is uniformly distributed until the cream sample is uniform and semitransparent, wherein no bubbles exist in the cream sample;
(3) The whole field of view of the coverslip was immediately examined under a 200-fold light microscope, the particle distribution was observed and an image was acquired, as shown in fig. 4.
The results show that: in the figure, the liquid drops have good dispersion condition, no obvious carbomer layer shadow, good liquid drop shape and clear display.
Comparative example 3
The particle size microscopic detection method of the ritodrine emulsifiable paste of the comparative example comprises the following steps:
(1) 5mg Li Bing bicaine cream sample is loaded on a glass slide by a doctor blade method, and Li Bing bicaine cream sample is not diluted;
(2) Using n-decane as a dispersing agent, dropwise adding 15 mu L of n-decane on a Li Bing bicaine cream sample at one time, and covering with a cover glass to ensure that no bubble exists in the sample;
(3) The whole field of view of the coverslip was immediately examined under a 200-fold light microscope, the particle distribution was observed and an image was acquired, as shown in fig. 5.
The results show that: the particle background in the visual field has variegated shadows with different color depths, which may be caused by uneven scraping and uneven dispersing agent soaking; the large particle diameter and irregular shape particles in the visual field presumably are droplets of the n-decane dispersant which are not wetted, so that the sample treatment method is not effective.
Example 3
The particle size microscopic detection method of the lyprofen cream comprises the following steps:
(1) Spot-coating Li Bing bicaine cream samples on a glass slide, wherein the fixed loading amounts are 1mg,2mg,3mg,4mg and 5mg, and Li Bing bicaine cream samples are not diluted;
(2) Taking n-decane as a dispersing agent, dropwise adding 15 mu L of n-decane on a Li Bing bicaine cream sample at one time, covering with a cover glass, and lightly rubbing to ensure that the Li Bing bicaine cream sample is uniformly distributed until the cream sample is uniform and semitransparent, wherein no bubbles exist in the cream sample;
(3) The whole visual field of the cover glass was immediately examined under a 200-fold optical microscope, the particle distribution was observed and an image was collected, as shown in FIG. 6, in which the amounts of 1mg,2mg,3mg,4mg and 5mg were respectively shown in FIGS. 6-1, 6-2, 6-3, 6-4 and 6-5, and the resulting effect was plotted by dispersing n-decane in an amount sufficient to completely cover the immersed sample as the n-decane liquid droplets were, depending on the sample volume.
The results show that: the visual field diagrams with the dosage of 1mg,2mg and 3mg have the best effect, the liquid drops are almost completely dispersed and basically have no overlapping, the image acquisition software can directly count the liquid drops, the particles with the overlapping number of 4mg and more begin to appear, the more the sample loading amount is, the more the overlapping is, and the larger the counting error is.
Comparative example 4
The particle size microscopic detection method of the ritodrine emulsifiable paste of the comparative example comprises the following steps:
(1) A Li Bing bicaine cream sample is smeared on a glass slide, the loading amount is more than 5mg (such as 6mg,7mg and 8 mg), and the Li Bing bicaine cream sample is not diluted;
(2) N-decane is taken as a dispersing agent, 15 mu L of n-decane is added dropwise on a Li Bing bicaine cream sample at one time, the n-decane liquid drops can completely cover the soaked sample, a cover slip is covered, and the Li Bing bicaine cream sample is evenly distributed until the cream sample is in an even semitransparent state, and no bubble exists in the cream sample;
(3) The whole field of view of the coverslip was immediately examined under a 200-fold light microscope, the particle distribution was observed and an image was acquired, as shown in fig. 7.
The results show that: the sample particles in the visual field are uniformly distributed, but the particles are excessively overlapped due to too much sample loading, the black spot shadows in the figure are particles which are not shown in multiple particles, the particles at other layers are gradually shown by adjusting the focal length, and the particle size distribution collection, the particle size and the particle number statistics can be realized by a depth of field expansion technology in software. Errors in counting can be introduced in view of technical accessibility and overlap.
Comparative example 5
The particle size microscopic detection method of the ritodrine emulsifiable paste of the comparative example comprises the following steps:
(1) Diluting a Li Bing dicaine cream sample by using n-decane, wherein the mass ratio of the Li Bing dicaine cream sample to the n-decane is 1:1 (1 g Li Bing dicaine cream sample to 1g n-decane), and uniformly mixing;
(2) Taking 2mg of the mixed product, dispensing the mixed product on a glass slide, covering the glass slide, and lightly kneading the glass slide to ensure that the glass slide is uniformly distributed and has no bubbles in the glass slide;
(3) The whole field of view of the coverslip was immediately examined under a 200-fold light microscope, the particle distribution was observed and an image was acquired, as shown in fig. 8.
Comparative example 6
The particle size microscopic detection method of the ritodrine emulsifiable paste of the comparative example comprises the following steps:
(1) Diluting a Li Bing dicaine cream sample by using n-decane, wherein the mass ratio of the Li Bing dicaine cream sample to the n-decane is 1:2 (1 g Li Bing dicaine cream sample to 2g n-decane), and uniformly mixing;
(2) Taking 2mg of the mixed product, dispensing the mixed product on a glass slide, covering the glass slide, and lightly kneading the glass slide to ensure that the glass slide is uniformly distributed and has no bubbles in the glass slide;
(3) The whole field of view of the coverslip was immediately examined under a 200-fold light microscope, the particle distribution was observed and an image was acquired, as shown in fig. 9.
The results of comparative examples 5 and 6 show that: li Bing the bicaine cream is diluted by n-decane in different proportions, and the whole visual field of the cover glass is inspected under a 200-time optical microscope, so that the particles are rare, irregular in shape and size and huge in particle size, and the demulsification instability can be caused in the uniform dilution process.
It should be understood that the above examples are illustrative and are not intended to encompass all possible implementations encompassed by the claims. Various modifications and changes may be made in the above embodiments without departing from the scope of the disclosure. Likewise, the individual features of the above embodiments can also be combined arbitrarily to form further embodiments of the invention which may not be explicitly described. Therefore, the above examples merely represent several embodiments of the present invention and do not limit the scope of protection of the patent of the present invention.
Claims (10)
1. The method for microscopic detection of the particle size of the Lipobicaine cream is characterized by comprising the following steps:
(1) Directly coating a Li Bing bicaine cream sample on a glass slide;
(2) Dripping n-decane on a Li Bing bicaine cream sample, covering with a cover glass, and lightly kneading to uniformly distribute the Li Bing bicaine cream sample;
(3) The images were observed and collected under a microscope.
2. The method for microscopic detection of particle size of Li Bing bicaine cream according to claim 1, wherein the amount of Li Bing bicaine cream sample used in the step (1) is 1 to 5mg.
3. The method for microscopic detection of particle size of Li Bing bicaine cream according to claim 2, wherein the amount of Li Bing bicaine cream sample used in the step (1) is 1 to 3mg.
4. The method for microscopic detection of particle size of Li Bing bicaine cream according to claim 1, wherein n-decane in said step (2) completely covers Li Bing the bicaine cream sample.
5. The method for microscopic detection of particle size of Li Bing bicaine cream according to claim 1, wherein the amount of n-decane used in the step (2) is 5 to 20 μl.
6. The method for microscopic detection of particle size of Li Bing bicaine cream according to claim 1, wherein n-decane in the step (2) is added dropwise at one time.
7. The microscopic detection method of the particle size of Li Bing bicaine cream according to claim 1, wherein the step (2) is performed by gently rubbing the Li Bing bicaine cream until the cream is uniformly distributed and semitransparent, and no bubbles are generated in the cream.
8. The method for microscopic detection of particle size of Li Bing bicaine cream according to claim 1, wherein the microscope used in the step (3) is an optical microscope of 180 times or more.
9. The method for microscopic detection of particle size of Li Bing bicaine cream according to claim 8, wherein the microscope used in said step (3) is a 200-fold optical microscope.
10. The method for microscopic detection of the particle size of the Lipobicaine cream is characterized by comprising the following steps:
(1) Spot-coating 1-3 mg Li Bing of the bicaine cream sample on a glass slide, wherein the Li Bing bicaine cream sample is not diluted;
(2) Dropwise adding 5-20 mu L of n-decane on a Li Bing bicaine cream sample, covering with a cover glass, and lightly rubbing to uniformly distribute the Li Bing bicaine cream sample until the cream sample is uniform and semitransparent, wherein no bubbles exist in the cream sample;
(3) The images were immediately observed and collected under a 200-fold light microscope.
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