CN110824122B - In-vitro release model and in-vitro release method of propofol fat emulsion injection - Google Patents
In-vitro release model and in-vitro release method of propofol fat emulsion injection Download PDFInfo
- Publication number
- CN110824122B CN110824122B CN201911036970.6A CN201911036970A CN110824122B CN 110824122 B CN110824122 B CN 110824122B CN 201911036970 A CN201911036970 A CN 201911036970A CN 110824122 B CN110824122 B CN 110824122B
- Authority
- CN
- China
- Prior art keywords
- vitro release
- release
- aqueous solution
- test vessel
- medium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Physics & Mathematics (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- External Artificial Organs (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses an in-vitro release model and an in-vitro release method of propofol fat emulsion injection, belonging to the field of in-vitro release models. The in vitro release method is characterized in that a reverse osmosis dialysis method is adopted to select a release medium, and a constant temperature control and shaking are carried out in a closed test vessel through a constant temperature oscillation incubator. The invention obviously improves the release rate to more than 90%.
Description
Technical Field
The invention relates to the field of in-vitro release models, in particular to an in-vitro release model and an in-vitro release method of propofol fat emulsion injection.
Background
The drug research and development process needs to provide in vitro release study data of the drug. Most in vitro release models aim at solid preparations, Chinese pharmacopoeia general rules have relevant guidance suggestions, but no guidance suggestion is given on the research method of the fat emulsion injection. Referring to the related art, studies are performed using simulated human physiological conditions, and a general method is: the dialysis method is used for in vitro release, the release medium is selected from buffer solution with physiological pH, and a certain proportion of Sodium Dodecyl Sulfate (SDS) or Tween 80 is added as the release medium for research.
The existing in vitro release model usually takes a Phosphate Buffered Saline (PBS) aqueous solution as a release medium, and the saturated solubility of propofol in PBS is 0.1395mg/ml through experimental determination, so that the condition of a dissolving leakage groove is not reached. The release rate is very slow in the implementation stage of the related embodiment, and in order to improve the solubility of the propofol, a solubilizer SDS is added into the solution, the addition amount is 1.0 percent, and the saturated solubility of the propofol reaches 4.4 mg/ml. By using PBS buffer containing 1% SDS and optimizing the test scheme, the release amount can reach 40% in 48h, but the release amount is still lower.
Disclosure of Invention
The technical problem to be solved by the invention is to provide an in vitro release model and an in vitro release method of propofol fat emulsion injection, and the release rate is remarkably improved to more than 90%.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
an in vitro release model of propofol fat emulsion injection comprises a closed test vessel, wherein a release medium is filled in the closed test vessel, and the closed test vessel is placed in a full-temperature oscillation incubator.
The technical scheme of the invention is further improved as follows: the release medium is any one of a 20-70% ethanol aqueous solution, an acetonitrile aqueous solution, a methanol aqueous solution, an isopropanol aqueous solution and an acetone aqueous solution.
An in vitro release method of propofol fat emulsion injection comprises selecting release medium, performing constant temperature control and shaking in a closed test vessel by a constant temperature shaking incubator by reverse osmosis dialysis method.
The technical scheme of the in vitro release method is further improved as follows: the release medium is any one of a 20-70% ethanol aqueous solution, an acetonitrile aqueous solution, a methanol aqueous solution, an isopropanol aqueous solution and an acetone aqueous solution.
The technical scheme of the in vitro release method is further improved as follows: the temperature was controlled at 37. + -. 0.5 ℃.
The technical scheme of the in vitro release method is further improved as follows: the oscillation frequency is 50-100 r/min.
Due to the adoption of the technical scheme, the invention has the technical progress that:
the in vitro release model and the in vitro release method of the invention obviously improve the release rate which can reach more than 90 percent, compared with the prior art, the release rate is obviously improved, and the invention has very important significance for research and development of medicines. Selecting any one of 20-70% ethanol aqueous solution, acetonitrile aqueous solution, methanol aqueous solution, isopropanol aqueous solution and acetone aqueous solution as a release medium, so as to achieve the sink conditions for dissolving out propofol; meanwhile, the in-vitro release is carried out in a closed test vessel, so that the stability of a system of the volatile release medium is ensured, and the deviation of the in-vitro release research data result is avoided; the incubator can provide a constant temperature for in vitro release and ensure shaking up effect.
Drawings
FIG. 1 is a graph of propofol control concentrations of the present invention;
FIG. 2 is a PBS release profile of 1% SDS;
figure 3 is a 50% ethanol release profile.
Detailed Description
The present invention will be described in further detail with reference to the following examples:
an in vitro release model of propofol fat emulsion injection comprises a closed test vessel, wherein a release medium is filled in the closed test vessel, and the closed test vessel is placed in a full-temperature oscillation incubator. Wherein the release medium is any one of 20-70% ethanol water solution, acetonitrile water solution, methanol water solution, isopropanol water solution and acetone water solution.
An in vitro release method of propofol fat emulsion injection is characterized in that 20-70% ethanol water solution is used as a release medium, and a reverse osmosis dialysis method is adopted to perform constant temperature control and shaking in a closed test vessel through a constant temperature shaking incubator. The temperature is controlled to be 37 +/-0.5 ℃, and the oscillation frequency is 50-100 r/min.
Wherein the release medium can be any one of 20-70% acetonitrile water solution, methanol water solution, isopropanol water solution and acetone water solution.
The release rate is described in detail below by taking an embodiment as an example:
1. the specific embodiment is as follows: taking 50% ethanol solution as release medium, performing reverse dialysis in a constant temperature shaking incubator at 37 deg.C and shaking speed of 100 rpm, placing 3.6 mL of the product in a 900mL threaded reagent bottle, suspending a dialysis bag containing 10mL of release medium at the bottle mouth, and sealing the bottle mouth. Taking 1ml of solution in the dialysis bag as a test solution after 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 24 and 48 hours respectively, and simultaneously supplementing 1ml of blank release medium.
2. Comparative experiment 1: (1% SDS-containing PBS buffer (pH7.4) as release medium): according to a dissolution and release determination method (second method of 9031 in the general rule of the four parts of the 2015 edition of Chinese pharmacopoeia), 3.6 mL of the product is taken and placed in a dissolution cup with 900mL of release medium by taking PBS buffer containing 1% SDS as the release medium and adopting a reverse dialysis method at 37 ℃ and 100 revolutions per minute, and a dialysis bag filled with 10mL of release medium is put into the dissolution cup. After 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 54 hours respectively, 1ml of the solution in the dialysis bag was taken as a test solution, and 1ml of a blank release medium was added.
3. Chromatographic conditions and system applicability test: the measurement is carried out according to high performance liquid chromatography (China pharmacopoeia 2015 edition of the general rules 0512 in four parts). ODS Hypersil (4.6X 100mm,5 μm) was used as a column, column temperature: the detection wavelength was 275 nm at 30 ℃. The mobile phase is tetrahydrofuran: water (40: 60), flow rate 1.8 ml/min, isocratic run for 10 min. And taking a proper amount of propofol reference substance and impurity II reference substance, adding isopropanol solution (containing 6.8% of water) for dissolving and diluting to prepare solution containing about 0.008 mg/ml of propofol and 0.8 mu g/ml of impurity II, and taking the solution as system applicability solution. Injecting 20 μ l into chromatograph, recording chromatogram, and determining separation degree between propofol peak and impurity II peak as shown in FIG. 1.
4. The determination method comprises the following steps: and taking another appropriate amount of propofol reference substance, adding an isopropanol solution (containing 6.8% of water) for dissolving, and diluting with a release medium to obtain a solution containing about 0.04mg of propofol in each 1ml (the addition amount of the isopropanol is not more than 2% of the total volume), wherein the solution is used as the reference substance solution. And respectively injecting 20 mu L of each sample solution and 20 mu L of each reference solution at each time point into a chromatograph, recording the chromatogram, calculating the release degree of propofol at each time point by peak area according to an external standard method, and drawing a release curve.
5. According to the in vitro release curve chart of 1% SDS in PBS solution in FIG. 2 and the in vitro release curve chart of 50% ethanol in water solution in FIG. 3, the PBS release curve of 1% SDS only reaches 40% and the 50% ethanol release curve, and the release rate reaches more than 90%.
Claims (1)
1. An in vitro release method of propofol fat emulsion injection is characterized in that: the in-vitro release model comprises a closed test vessel, wherein a release medium is filled in the closed test vessel, and the closed test vessel is placed in a full-temperature oscillation incubator; the closed test vessel is a threaded reagent bottle, the propofol fat emulsion injection is placed in the threaded reagent bottle releasing the medium, a dialysis bag filled with the releasing medium is hung at the bottle mouth, the bottle mouth is sealed, and constant-temperature control and shaking are carried out in the closed test vessel through a constant-temperature oscillation incubator by adopting a reverse osmosis dialysis method; the release medium is any one of a 20-70% ethanol aqueous solution, an acetonitrile aqueous solution, a methanol aqueous solution, an isopropanol aqueous solution and an acetone aqueous solution; controlling the temperature to be 37 +/-0.5 ℃; the oscillation frequency is 50-100 rpm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911036970.6A CN110824122B (en) | 2019-10-29 | 2019-10-29 | In-vitro release model and in-vitro release method of propofol fat emulsion injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911036970.6A CN110824122B (en) | 2019-10-29 | 2019-10-29 | In-vitro release model and in-vitro release method of propofol fat emulsion injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110824122A CN110824122A (en) | 2020-02-21 |
| CN110824122B true CN110824122B (en) | 2021-05-25 |
Family
ID=69550994
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911036970.6A Active CN110824122B (en) | 2019-10-29 | 2019-10-29 | In-vitro release model and in-vitro release method of propofol fat emulsion injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110824122B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114113077A (en) * | 2021-10-08 | 2022-03-01 | 华南理工大学 | Method for detecting in-vitro release of injection emulsion |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579338B (en) * | 2012-03-02 | 2013-06-19 | 首都医科大学 | Preparation method and application of paclitaxel intravenous fat emulsion |
| CN102805728B (en) * | 2012-08-22 | 2013-12-04 | 南京正大天晴制药有限公司 | Propofol fat emulsion injection and preparation method thereof |
| CN107884529B (en) * | 2016-09-29 | 2020-12-08 | 辽宁远大诺康生物制药有限公司 | Method for measuring drug encapsulation efficiency of fat emulsion preparation and application thereof |
| CN108007826B (en) * | 2016-11-02 | 2020-11-27 | 广东嘉博制药有限公司 | Method for measuring in-vitro accumulated release rate of long-acting liquid preparation |
| CN108254450A (en) * | 2016-12-29 | 2018-07-06 | 上海医药集团股份有限公司 | In Propofol/detection method of long chain fat emulsion injection envelop rate |
-
2019
- 2019-10-29 CN CN201911036970.6A patent/CN110824122B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN110824122A (en) | 2020-02-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Keire et al. | Analysis of crude heparin by 1H NMR, capillary electrophoresis, and strong-anion-exchange-HPLC for contamination by over sulfated chondroitin sulfate | |
| CN104965041B (en) | A kind of high-efficiency liquid chromatography method for detecting of Parecoxib Sodium isomer | |
| CN110824122B (en) | In-vitro release model and in-vitro release method of propofol fat emulsion injection | |
| CN104749269A (en) | Method for determining enantiomer impurity in alogliptin crude drug and preparation by virtue of HPLC | |
| Zhou et al. | Application of hollow fiber liquid phase microextraction coupled with high-performance liquid chromatography for the study of the osthole pharmacokinetics in cerebral ischemia hypoperfusion rat plasma | |
| CN106770855A (en) | A kind of method for separating and detecting of Sha Kubi song intermediates and its optical isomer based on high performance liquid chromatography | |
| Mellström et al. | Ion-pair liquid chromatography of amitriptyline and metabolites in plasma | |
| CN103251565A (en) | Voriconazole freeze-dried powder injection for injection and preparation method thereof | |
| CN113791148A (en) | Gas chromatography for determining residual quantity of organic solvent in parecoxib sodium raw material medicine | |
| CN110221003A (en) | The remaining detection method of ethyl alcohol in a kind of hemostatic material | |
| CN107957467B (en) | Method for separating and measuring lysophosphatidylcholine in pharmaceutical preparation | |
| CN204214826U (en) | A kind of aflatoxin B1 immune affinity column | |
| CN110286162B (en) | Method for determining dissolution rate of medicinal preparation containing acetaminophen, dextromethorphan hydrobromide and doxylamine succinate | |
| Naish et al. | Rapid assay for theophylline in clinical samples by reversed-phase high-performance liquid chromatography | |
| Derechin et al. | Yeast hexokinase. II. Molecular weight and dissociation behavior | |
| CN104569255A (en) | Method for determining Suvorexant intermediate employing HPLC | |
| KWIATKOWSKA-PUCHNIARZ et al. | HPLC METHOD FOR SEPARATING ENANTIOMERS OF IMIDAZOLE DERIVATIVES ñ ANTIFUNGAL COMPOUNDS | |
| CN106093233A (en) | The assay method of content of isomer in esomeprazole sodium freeze-dried powder injection | |
| Wiese et al. | Determination of benzylpenicillin in milk at the pg ml− 1 level by reversed-phase liquid chromatography in combination with digital subtraction chromatography technique | |
| CN112763623B (en) | Method for detecting peramivir trihydrate by reversed-phase high-performance liquid chromatography | |
| CN104374840A (en) | Method for measuring content of chlorpheniramine maleate in chlorpheniramine maleate cream by high-performance liquid chromatography | |
| CN103040845B (en) | Fat emulsion injection for supplementing fat-soluble vitamins | |
| CN109283279A (en) | Pass through high efficiency liquid chromatography for separating and determining Raltitrexed and its method of enantiomter | |
| CN110108810B (en) | Method for determining dissolution rate of pharmaceutical preparation containing acetaminophen, dextromethorphan hydrobromide and phenylephrine hydrochloride | |
| CN102928525A (en) | Method for detecting related substance II of cefpirome in cefpirome sulfate/sodium chloride injection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |