CN114113077A - Method for detecting in-vitro release of injection emulsion - Google Patents
Method for detecting in-vitro release of injection emulsion Download PDFInfo
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Abstract
The invention provides a method for detecting in-vitro release of an injection emulsion, which utilizes the principle that the light scattering intensity is in direct proportion to the sextuple of the particle size of particles, and the tiny change of the particle size caused by drug release can be reflected by the scattered light intensity. The injection emulsion is added into a release medium containing serum albumin, the injection emulsion is rapidly diffused into the release medium, the whole process is recorded, the reverse phase processing and the gray value analysis are carried out on the shot image by using software, and the cumulative release rate is calculated. The method has the advantages that: the provided detection method can complete the release rate of the instantaneous sampling point of the 24-frame picture within 1s, draw a precise accumulated release curve reaching the equilibrium state, the accumulated release rate can reach the level of complete release, and the detection of the release rate is more accurate. The invention has the advantages of simple equipment, simple and convenient operation and little time and cost consumption.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a method for detecting in-vitro release of an injection emulsion.
Background
The injection emulsion contains a plurality of pharmaceutic adjuvants, belongs to lipid complex injection, and lacks an in-vitro evaluation method of the preparation in the current pharmacopoeia. The injection emulsion is applied in a large amount clinically, the demand increases year by year, but the evaluation of in vitro release is not well solved all the time, and particularly, the detection difficulty of in vitro release of the medicament with low solubility, high release rate and poor stability is higher. The consistency evaluation of lipid emulsion injections is a great challenge compared to oral solid preparations and common injections.
The in vitro release experiment is an essential link in the evaluation of the pharmaceutical imitation consistency, can predict the in vivo release process of the pharmaceutical preparation, and provides a basis for in vitro evaluation, in vivo and in vitro correlation evaluation and a drug release mechanism. In order to better simulate the in vivo environment, the PBS solution is difficult to truly simulate the in vivo environment, so the addition of serum albumin in the PBS buffer solution can more truly reflect the release of the drug in the human body.
Conventional methods of detection of injected emulsions involve sample handling and analytical determination. After administration of the fast acting injectable emulsion, release is achieved within tens of seconds, even seconds. Conventional in vitro release of injectable emulsions is commonly performed by dialysis, where the free drug reaches equilibrium transmembrane, typically within 60 min. For example, Diprivan (Deperpulan) specification notes that the emulsion is a quick-release preparation which is quickly distributed in the whole body after intravenous injection, can generate a sleep state within 40s and quickly enter an anesthesia state, so that the actual release process (40s) in the fat emulsion is much faster than the in-vitro transmembrane process (60min) of free medicaments, and the in-vitro release rate of the fat emulsion measured by a dialysis method has hysteresis due to the transmembrane process of the free medicaments. The increase in agitation rate does not change much the in vitro release rate, probably because the dialysis bag is slow in isolating free drug, typically requiring several hours, even tens of hours. However, the actual release rate of fat emulsion is very fast, so that the permeation of free drug through the dialysis membrane is the rate-limiting step in the dialysis determination process, which results in the hysteresis of the dialysis determination of the in vitro release rate, and it is difficult to measure the process that the injection emulsion actually completes the in vitro release in tens of seconds, and the in vivo release cannot be predicted. The conventional emulsion release detection process involves time consuming sampling, preparation and analytical testing. Therefore, it is highly desirable to develop an in vitro release assay suitable for emulsion injection.
Disclosure of Invention
The invention uses light scattering intensity to be in direct proportion to the sextuple of the particle size, the tiny change of the particle size can be reflected by the scattered light intensity, and the reduction of the light scattering intensity reflects the particle size reduction of emulsion particles and is related to the release and dissolution of the medicine in the emulsion. The invention aims to provide a method for detecting in-vitro release of an injection emulsion, which inspects the in-vitro release rate of the injection emulsion and provides a basis for in-vitro evaluation, in-vivo and in-vitro correlation evaluation and drug release mechanism analysis of the injection emulsion.
The purpose of the invention is realized by the following technical scheme:
a method for detecting in vitro release of an injection emulsion, comprising the steps of:
(1) preparing a release medium;
(2) measuring a proper amount of the release medium solution in the step (1), placing the release medium solution in a sample bottle, adding a stirrer, adding the injection emulsion in the stirring process, and recording the video of a high-definition video recorder in the whole process of adding and releasing the injection emulsion;
(3) and extracting each frame of image in the sample acquisition process in the video by using software, performing inverse processing on the image, selecting the maximum gray value and the minimum gray value after determining the gray values of all the images, and calculating the release rate according to the gray value of each frame of image.
In some examples, serum albumin or plasma is added to the buffer as a release medium. Preferably, the serum albumin is bovine serum albumin, or mouse serum albumin. Preferably, the buffer is PBS phosphate buffer.
In some examples, in step (1), the serum albumin is present in the release medium solution at a mass fraction of 0.1% to 20%. Preferably, the mass portion is 3% -8%.
In some examples, in step (1), the mass fraction of bovine serum albumin or mouse serum albumin in the release medium solution is 0.1% to 20%. Preferably, the mass portion is 3% -8%.
In some examples, step (1) is performed by shaking or stirring until the plasma or serum albumin is completely dissolved.
In some examples, in step (1), the pH of the PBS phosphate buffer solution is 7.4.
In some examples, in step (2), the emulsion is injected by dripping.
In some examples, the stirring speed in step (2) is 100-. Preferably, the stirring speed is 500-.
In some examples, in step (2), the volume of the release medium solution is 0.01-499 mL.
In some examples, in step (2), the injectable emulsion is added in an amount of 0.01-1 mL. Preferably, the injection emulsion is added in an amount of 0.1-0.8 mL.
In some examples, in step (2), the injection emulsion is added at a volume ratio of 1/1-1/500 in the release medium, i.e., at a volume dilution factor of 1-500. Preferably, the volume dilution factor is 10 to 200.
In some examples, in step (2), the high-definition video recorder is any video recording device capable of high-definition video recording. The high-definition video recorder can be a mobile phone with a high-definition video recording function. For example, the high-definition video recorder may be a Huacheng mobile phone.
In some examples, in step (3), each frame of image during the sample collection process in the video is extracted using software such as PotPlayer or Adobe Premiere Pro CS. The images were processed in reverse phase using Adobe Photoshop CS. And (4) carrying out gray value analysis on the Image by using Image J software, and calculating the release rate according to the gray value of each frame of Image.
In some examples, in step (3), a cumulative release profile is plotted as a function of release rate.
In some examples, in step (3), the image is extracted and processed by selecting the image from the area of 1cm below the stirrer, with the liquid level and the two sides of the sample bottle as boundaries2Within.
In some examples, in step (3), the maximum gray value is the gray value obtained by processing the picture with the software using the real solution at the time of 0 seconds. The minimum gray value is the minimum gray value obtained during the determination of the cumulative release rate.
In some examples, in step (3), the% release can be calculated by the following equation:
wherein A isMax: maximum gray value, AMin: minimum gray value, a: gray value at the instant of sampling.
In some examples, the injection emulsion is a fat emulsion injection.
In some examples, the injection emulsion is tetracaine fat emulsion injection, propofol fat emulsion injection, or flurbiprofen axetil fat emulsion injection. Preferably, the propofol fat emulsion injection is a medium/long-chain propofol fat emulsion injection.
In some examples, a method of detecting in vitro release of an injectable emulsion comprises the steps of:
(1) serum albumin was added to PBS phosphate buffered saline (pH 7.4) and shaken or stirred until serum albumin was completely dissolved, which served as a release medium. Wherein the mass fraction of the serum albumin in the PBS solution is 0.1-20%, and the preferable mass fraction is 3-8%.
(2) Measuring 0.01-499mL of the release medium solution in the step (1), placing the release medium solution in a sample bottle, and adding a stirrer, wherein the stirring speed is 100-.
(3) 0.01-1mL of injection emulsion is added during the stirring process in (2), and the preferable addition amount is 0.1-0.8 mL. The volume of the injection emulsion added in the release medium is 1/1-1/500, namely the volume dilution factor is 1-500 times, the preferred dilution factor is 20-200 times, and a high-definition video recorder is used for video recording in the whole process of adding and releasing the injection emulsion.
(4) Extracting each frame of Image in the sample collection process in the video by using PotPlayer or Adobe Premiere Pro CS software and the like, respectively carrying out reverse phase processing on the Image by using Adobe Photoshop CS and Image J software, selecting the Image to the position above the stirrer downwards by taking the liquid level and two sides of the sample bottle as boundaries, and selecting the Image with the area of 1cm at each time2Within. After all image gray values were determined, the maximum gray value was chosen (0 second instant true solution applied to the softThe gray value obtained by processing the picture) and the minimum gray value (the minimum gray value obtained in the process of measuring the accumulative release rate), and then the release rate is calculated according to the gray value of each frame of image, and an accumulative release curve is drawn. The release rate can be calculated by the following formula:
wherein A isMax: maximum gray value, AMin: minimum gray value, a: gray value at the instant of sampling.
The operation method related by the technology of the invention is simple and quick. The invention can be realized by only dropping, recording and processing pictures in the selection of an in vitro release method, and the inventor can obtain the release rate of the instantaneous sampling point of 24 frames of pictures in 1s by using software such as Adobe premix Pro CS, Adobe Photoshop CS, Image J and the like without the limitation of temperature, equipment and the like, and the detection result is extremely quick and sensitive.
The invention has the following beneficial effects:
the method is simple and quick. The invention can be realized by only dropping, recording and processing pictures in the selection of an in vitro release method, and the inventor can obtain the release rate of the instantaneous sampling point of 24 frames of pictures in 1s by using software such as Adobe premix Pro CS, Adobe Photoshop CS, Image J and the like without the limitation of temperature, equipment and the like, and the detection result is extremely quick and sensitive. The invention provides a basis for in vitro evaluation, in vivo and in vitro correlation evaluation and imitation drug consistency evaluation of the injection emulsion.
Drawings
FIG. 1 is a graph showing the cumulative release rate of tetracaine fat emulsion 5s used in examples 1-6 (enlarged view of a dotted line portion (within 1 s)).
FIG. 2 is a graph of the cumulative release rate over 1s for medium/long chain propofol fat emulsions used in examples 7-12.
Fig. 3 is a cumulative release curve within 1s of flurbiprofen axetil fat emulsion used in example 13.
Detailed Description
Embodiments of the present invention will be described in detail below with reference to examples, and it will be understood by those skilled in the art that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The invention provides a method for detecting in vitro release of an injection emulsion, which adds the injection emulsion in a dripping mode, wherein the injection emulsion is diffused in the process of releasing a medicament, so that the turbidity of a system can be changed.
Examples 1-6 use tetracaine fat emulsion injection, examples 7-12 use medium/long chain propofol fat emulsion injection, and example 13 use flurbiprofen axetil fat emulsion injection. The technical solution provided by the present invention is further described with reference to the following examples.
Example 1 in vitro Release assay for Tetracaine fat emulsion injection
Preparing a PBS solution with pH being 7.4: potassium dihydrogen phosphate (KH)2PO4): 0.12g of disodium hydrogen phosphate (Na)2HPO4.12H20): 1.82g, sodium chloride (NaCl): 4.0g, potassium chloride (KCl): 0.1g, adding deionized water about 400mL, fully stirring and dissolving, then adding concentrated hydrochloric acid to adjust the pH to 7.4, and finally making the volume to 500 mL.
Preparing a bovine serum albumin PBS solution: 1.819g of bovine serum albumin (emd millipore corporation, Lot: D00169946) was weighed into a conical flask, then 23.983g of PBS solution was weighed into the flask, and mixed with stirring to prepare 7.0% (W/W) bovine serum albumin PBS solution.
Adding 1.9ml of the bovine serum albumin PBS solution into a screw bottle, adding a stirrer, stirring at 600rpm, then dripping 0.1ml of tetracaine fat emulsion (10mg/ml, self-made), namely diluting by 20 times, and opening a high-definition video recorder (Hua mate 30 Pro mobile phone) to record videos. Extracting each frame of Image in the sample acquisition process in the required analysis time period in the video by using PotPlayer or Adobe Premiere Pro CS software and the like, performing reverse phase processing on the images by using Adobe Photoshop CS and Image J software respectively, measuring the gray values of three groups of parallel samples, calculating an average value, calculating the release rate according to the maximum gray value, the minimum gray value and the gray value of each frame of Image, and drawing an accumulated release curve. The mean gray value and release rate calculated in example 1 are shown in table 1.
Table 1 example 1 tetracaine fat emulsion average grey scale value and release rate (n ═ 3)
Example 2 in vitro Release assay for Tetracaine fat emulsion injection
This example differs from example 1 in that the amount of tetracaine fat emulsion added was 0.3ml, the amount of bovine serum albumin PBS solution added was changed to 5.7ml (20-fold dilution), the stirring speed was changed to 1200rpm, and the other involved test methods and other materials were the same as in example 1.
Example 3 in vitro Release assay for Tetracaine fat emulsion injection
The difference between this example and example 1 is that 0.910g of bovine serum albumin is weighed and added into a conical flask, then 24.993g of PBS solution is weighed and added, stirring and mixing are carried out to prepare 3.5% (W/W) bovine serum albumin PBS solution, the adding amount of tetracaine fat emulsion is 0.5ml, the adding amount of the bovine serum albumin PBS solution is changed to 9.5ml (20 times dilution), and other related test methods and other materials are the same as example 1.
Example 4 in vitro Release assay for Tetracaine fat emulsion injection
This example differs from example 1 in that the amount of tetracaine fat emulsion added was 0.1ml, the amount of bovine serum albumin PBS solution added was changed to 9.9ml (100-fold dilution), and the other involved test methods and other materials were the same as in example 1.
Example 5 in vitro Release assay for Tetracaine fat emulsion injection
This example differs from example 2 in that 29.7ml (100-fold dilution) of bovine serum albumin in PBS was added, and the other test methods and other materials involved were the same as in example 2.
Example 6 in vitro Release assay for Tetracaine fat emulsion injection
This example differs from example 3 in that 49.5ml (100-fold dilution) of bovine serum albumin in PBS was added, and the other test methods and other materials involved were the same as in example 3.
The in vitro release conditions of examples 1-6 are shown in Table 2, and their cumulative release profile over 5 seconds is shown in FIG. 1; the dotted line part of the figure is a partial (within 1 s) enlarged view.
TABLE 2 examples 1-6 in vitro Release conditions of Tetracaine fat emulsion injection
As can be seen from FIG. 1, the initial release rates of the added tetracaine fat emulsion and the dilution times are different from each other, the dilution times have the most obvious influence on the initial release rates of the tetracaine fat emulsion, and the cumulative release rates are different from each other under the condition of different rotation speeds. The detection method provided by the invention can be used for accurately completing the determination of the accumulative release rate in a time-saving manner, and the accumulative release rate can achieve the effect of complete release within 1 second, namely the determination of the accumulative release rate can be completed.
Example 7 in vitro Release assay for Medium/Long chain Propofol fat emulsion injection
This example differs from example 1 in that the added fat emulsion was changed to medium/long chain propofol fat emulsion (10mg/ml, Guangdong Jiabo pharmaceutical Co., Ltd.). The other test methods and materials involved are the same as in example 1.
Example 8 in vitro Release assay for Medium/Long chain Propofol fat emulsion injection
This example differs from example 7 in that the volume of bovine serum albumin PBS solution is 5.7ml, the amount of medium/long chain propofol fat milk added is 0.3ml (20 fold dilution), and other involved test methods and other materials are the same as in example 7.
Example 9 in vitro Release assay for Medium/Long chain Propofol fat emulsion injection
The difference between this example and example 7 is that 0.910g bovine serum albumin is weighed and added into a conical flask, then 24.993g PBS solution is weighed and added, stirring and mixing are carried out to prepare 3.5% (W/W) bovine serum albumin PBS solution, the stirring speed is changed to 1200rpm, the volume of the bovine serum albumin PBS solution is 9.5ml, the addition amount of the medium/long chain propofol fat milk is 0.5ml (diluted by 20 times), and other related test methods and other materials are the same as example 7.
Example 10 in vitro Release assay for Medium/Long chain Propofol fat emulsion injection
This example differs from example 7 in that the amount of bovine serum albumin PBS solution added was changed to 9.9ml (100-fold dilution), and the other involved test methods and other materials were the same as in example 7.
Example 11 in vitro Release assay for Medium/Long chain Propofol fat emulsion injection
This example differs from example 7 in that 0.3ml of medium/long chain propofol fat milk is added, 29.7ml (100 fold dilution) of bovine serum albumin in PBS is added, the stirring speed is changed to 1200rpm, and the other involved test methods and other materials are the same as in example 7.
Example 12 in vitro Release assay for Medium/Long chain Propofol fat emulsion injection
This example differs from example 9 in that 0.5ml of medium/long chain propofol fat milk is added, 49.5ml of bovine serum albumin (100 fold dilution) is added, and the other involved test methods and materials are the same as in example 9.
The in vitro release conditions for examples 7-12 are shown in Table 3, and their cumulative release profile over 1 second is shown in FIG. 2.
Table 3 examples 7-12 in vitro release conditions for medium/long chain propofol fat emulsion injection
As can be seen from FIG. 2, the initial release rate is relatively fast when the rotation speed is high or when a large volume of medium/long chain propofol fat milk is dripped. The initial release rate is faster at 100-fold dilution compared to 20-fold dilution. Although the rotation speed, dilution times and dropping volume have certain influence on the initial release rate of the medium/long-chain propofol fat emulsion before 0.5 second, the cumulative release rate after 0.5 second has no obvious influence. The detection method provided by the invention is time-saving and accurate, namely the detection of the release rate is more accurate, the cumulative release rate of 0.5 second can reach 90%, and the determination of the cumulative release rate can be completed within 1 second.
Example 13 in vitro Release assay for flurbiprofen axetil fat emulsion injection
The difference between this example and example 1 is that the fat emulsion used is flurbiprofen axetil fat emulsion (10mg/ml, self-made), two 0.910g portions of mouse serum albumin freeze-dried powder are accurately weighed and respectively added into two conical flasks, and appropriate amounts of PBS solution are weighed and respectively prepared into PBS solution with mouse serum albumin content of 3.5% and 7% (W/W). The cumulative release profiles over 1 second for both concentrations are shown in figure 3. The release of flurbiprofen axetil is also above 90% at around 0.5s, indicating that the method is also applicable to other fat emulsions and other similar release media.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical scheme and the determination object of the present invention, and the related detection method is not limited to the above fat emulsion injections, and is not limited to the in vitro release detection method of commercially available fat emulsion injections; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (9)
1. A method for detecting in vitro release of an injection emulsion, comprising the steps of:
(1) preparing a release medium;
(2) measuring a proper amount of the release medium solution in the step (1), placing the release medium solution in a sample bottle, adding a stirrer, adding the injection emulsion in the stirring process, and recording the video of a high-definition video recorder in the whole process of adding and releasing the injection emulsion;
(3) and extracting each frame of image in the sample acquisition process in the video by using software, performing inverse processing on the image, selecting the maximum gray value and the minimum gray value after determining the gray values of all the images, and calculating the release rate according to the gray value of each frame of image.
2. The method for detecting in vitro release of an injectable emulsion according to claim 1, wherein in step (1), serum albumin is added to the buffer as a release medium.
3. The method for detecting the in vitro release of an emulsion injection according to claim 2, wherein in the step (1), the mass fraction of the serum albumin in the release medium solution is 0.1% -20%, preferably 3% -8%.
4. The method for detecting in vitro release of an injectable emulsion according to claim 2, wherein in the step (1), a buffer containing bovine serum albumin is used as a release medium; the buffer was PBS phosphate buffer.
5. The method for detecting in vitro release of an injection emulsion according to claim 1, wherein in the step (2), the stirring speed is 1500rpm and preferably 500rpm 1300 rpm.
6. The method for detecting in vitro release of an injectable emulsion according to claim 1, wherein in step (2), the injectable emulsion is added in an amount of 0.01-1mL, preferably in an amount of 0.1-0.8 mL.
7. The method for detecting in vitro release of an emulsion injection according to claim 1, wherein in step (2), the volume of the emulsion injection added to the release medium is 1/1-1/500, i.e. the dilution factor by volume is 1-500 times, preferably 10-200 times.
8. The method for detecting in vitro release of an injection emulsion according to claim 1, wherein in the step (3), software such as PotPlayer or Adobe Premiere Pro CS is used for extracting each frame of Image in the process of collecting samples in a video, Adobe Photoshop CS and Image J software are used for respectively carrying out reversed phase processing and gray value analysis on the Image, and then the release rate is calculated according to the gray value of each frame of Image to draw an accumulated release curve.
9. The method for detecting in vitro release of an injectable emulsion according to claim 1, wherein in the step (3), the release rate% can be calculated by the following formula:
wherein A isMax: maximum gray value, AMin: minimum gray value, a: gray value at the instant of sampling.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110736813A (en) * | 2019-10-25 | 2020-01-31 | 广东嘉博制药有限公司 | Method for measuring in-vitro release rate of pharmaceutical preparations |
| CN110824122A (en) * | 2019-10-29 | 2020-02-21 | 江苏盈科生物制药有限公司 | In-vitro release model and in-vitro release method of propofol fat emulsion injection |
| CN110865160A (en) * | 2019-10-25 | 2020-03-06 | 广东嘉博制药有限公司 | Method for measuring in-vitro release degree of propofol fat emulsion |
| CN111122802A (en) * | 2019-12-30 | 2020-05-08 | 广东嘉博制药有限公司 | Method for measuring release curve of propofol fat emulsion injection |
-
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110736813A (en) * | 2019-10-25 | 2020-01-31 | 广东嘉博制药有限公司 | Method for measuring in-vitro release rate of pharmaceutical preparations |
| CN110865160A (en) * | 2019-10-25 | 2020-03-06 | 广东嘉博制药有限公司 | Method for measuring in-vitro release degree of propofol fat emulsion |
| CN110824122A (en) * | 2019-10-29 | 2020-02-21 | 江苏盈科生物制药有限公司 | In-vitro release model and in-vitro release method of propofol fat emulsion injection |
| CN111122802A (en) * | 2019-12-30 | 2020-05-08 | 广东嘉博制药有限公司 | Method for measuring release curve of propofol fat emulsion injection |
Non-Patent Citations (1)
| Title |
|---|
| 金沙: "脂质药物递送制剂体外释放方法开发及其机理研究" * |
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