CN108226353A - A kind of assay method of calcium hydrophenyl sulfonate capsule stripping curve - Google Patents
A kind of assay method of calcium hydrophenyl sulfonate capsule stripping curve Download PDFInfo
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- CN108226353A CN108226353A CN201611181769.3A CN201611181769A CN108226353A CN 108226353 A CN108226353 A CN 108226353A CN 201611181769 A CN201611181769 A CN 201611181769A CN 108226353 A CN108226353 A CN 108226353A
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- stripping curve
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- 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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
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- 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
Abstract
The present invention relates to a kind of assay methods of the stripping curve similitude of drug, comprise the concrete steps that：Take this product paper clip or after thin wire fixes, using Rotating shaker, using citrate buffer (pH6.8) 1000ml of 0.05mol/L as dissolution medium, rotating speed is 75 turns per minute, is operated in accordance with the law, during through 15 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, solution 10ml is taken respectively, is filtered, as test solution, using high effective liquid chromatography for measuring, chromatogram is recorded.This law differentiation effect is strong, accuracy is high, it is often more important that homogeneity is good between batch, and available for the measure of calcium hydrophenyl sulfonate capsule stripping curve similitude, the quality control for this product provides reliable method.
Description
Technical field：The invention belongs to Pharmaceutical Analysis fields, are related to the stripping curve similitude of calcium hydrophenyl sulfonate capsule
Assay method.
Background technology：
For the quality of the domestic imitation medicine of General Promotion, reach in former triturate body, outer quality and the consistent level of curative effect,
State Food and Drug Administration has carried out the Conformance Assessment work of imitation medicine comprehensively, it is desirable that each pharmaceutical producing enterprise
This work must be completed before the end of the year 2018, the Conformance Assessment work of imitation medicine already becomes all relevant enterprises and faces
Urgent problems the most.Just synthesis domestic at present and technological level, Control of Impurities is masterly, but to accomplish body
Interior bioequivalence still acquires a certain degree of difficulty, and in order to make anticipation to vivo biodistribution equivalence trial, improves bioequivalence examination
The success rate tested, establishing a kind of strong In Vitro Dissolution detection method of distinction then becomes solid orally ingestible Conformance Assessment work
The key points and difficulties of work.
Calcium Dobesilate is a kind of diabetic microangiopathies and glomerulosclerosis clinical application, and the country is existing more at present
Family's imitation medicine listing, reference preparation are produced by Ebewe Pharma Ges M. B. H. Nfg KG.The drug can be used for microangiopathy
Treatment；The treatment of varication syndrome；Occur together the treatment of venous insufficiency with microcirculation disorder；Vein is removed and vein is hard
The auxiliary treatment of change method.
At present, in the calcium hydrophenyl sulfonate capsule quality standard recorded in pharmacopoeia of each country, the inspection of dissolution rate is not provided；State
The family drug standards (WS1(X-068) -2003Z) specified in dissolution test method operated using slurry processes, rotating speed is per minute
50 turns, using hydrochloric acid solution (9 → 1000) 900ml as dissolution medium, through 20 minutes when samples, and limit is the 80% of labelled amount.But
It is that capsule dissolution rate in hydrochloric acid solution is very fast, and batch interior homogeneity is poor, the coefficient of variation (RSD values) larger, Wu Faqu
Separate the difference of different sample rooms；The difference of its external dissolved corrosion between former triturate can not be evaluated, is that vivo biodistribution is equivalent
Property experiment make prediction；Reliable method can not be provided for the quality control of this product, specific measurement result is as follows.Stripping curve
See attached drawing 1.
Invention content：
Goal of the invention：It is an object of the invention to overcome the shortcomings of existing standard, it is molten to provide a kind of calcium hydrophenyl sulfonate capsule
Go out the assay method of similarity of curves.
Technical solution：
During the foundation of technical solution of the present invention, influence of the different dissolving-out methods to this product dissolved corrosion has been investigated.
At present, the phenomenon that existing standard is operated using slurry processes, and calcium hydrophenyl sulfonate capsule has floating in dissolution medium directly uses
Slurry processes operation is simultaneously improper, therefore slurry processes operation adjustment is Rotating shaker by this method.
During the foundation of technical solution of the present invention, influence of the different rotating speeds to this product dissolved corrosion has been investigated.When turn
When speed is improved to 100 turns per minute, 150 turns, 200 turns, the dissolution rate at each time point differs greatly between every capsule, does not apply to
In the comparison of dissolved corrosion similitude, therefore 75 turns per minute of rotating speed of this method final choice.
During the foundation of technical solution of the present invention, shadow of the different buffer salt types to this product dissolved corrosion has been investigated
It rings.It is investigated respectively using pH6.8 phosphate buffers and pH6.8 citrate buffers as dissolution medium, as a result in pH6.8
In phosphate buffer, calcium ion can be combined with phosphate anion, and the dissolubility of the calcium phosphate of generation in aqueous solution is poor, has
Precipitation, therefore the dissolution rate that conventional pH6.8 phosphate buffers is used to be not suitable for this product is investigated, and need to use pH6.8 lemons
Lemon phthalate buffer is as dissolution medium.
During the foundation of technical solution of the present invention, influence of the different dissolution mediums to this product dissolved corrosion has been investigated.
It is carried out respectively using water, 0.1mol/L hydrochloric acid solutions, pH4.5 acetate buffers, pH6.8 citrate buffers as dissolution medium
It investigates, as a result in pH6.8 citrate buffers, the distinction of method is most strong, therefore finally uses pH6.8 lemon acid bufferings
Liquid is as dissolution medium.
Finally determining dissolving-out method differentiation effect is strong, accuracy is high, available for calcium hydrophenyl sulfonate capsule stripping curve phase
Like the measure of property, the quality control for this product provides reliable method.
The stripping curve assay method of a kind of calcium hydrophenyl sulfonate capsule.It is characterized in that, this method the specific steps are：
This product paper clip is taken or after thin wire fixes, using Rotating shaker, with the citrate buffer (pH6.8) of 0.05mol/L
1000ml is dissolution medium, and rotating speed was 75 turns per minute, through 15 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 points
Clock, 150 minutes when, take solution 10ml respectively, filter, as test solution, and immediately supplement it is mutually synthermal, same volume
Dissolution medium；The solution at each time point is taken respectively, using high effective liquid chromatography for measuring, records chromatogram.
Assay method of the present invention, which is characterized in that after capsule paper clip or thin wire are first fixed by needs
It is measured, the variation of position generation immediately in process in leaching to prevent it.
Assay method of the present invention, which is characterized in that this method need to be operated using Rotating shaker, and rotating speed is set as
75 turns per minute, sampling time point is respectively 15 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes
When.
Assay method of the present invention, which is characterized in that the dissolution medium of this method is that the citric acid of 0.05mol/L delays
Fliud flushing (pH6.8) 1000ml.The specific preparation method of dissolution medium is：Trisodium citrate dihydrate 102.9g is taken (to be approximately equivalent to
0.35mol), water 7L is added to make dissolving, adjusts pH value to 6.8 with saturated lemon, mixing filters.
Assay method of the present invention, which is characterized in that this method is detected using high performance liquid chromatograph, color
Spectral condition is：
1. detector：UV detector；Detection wavelength：300nm
2. chromatographic column：Using Agela Promosil C18(4.6mm × 250mm, 5 μm) chromatographic column
3. mobile phase：Acetonitrile -0.05mol/L ammonium dihydrogen phosphates (2: 98)
4. flow velocity：1.0ml/min
5. sampling volume：10μl
Assay method of the present invention, which is characterized in that this method is used to measure calcium hydrophenyl sulfonate capsule.
Using this law four batches of different prescriptions are made by oneself with samples and original grinds sample and carries out stripping curve measure, different prescriptions it
Between dissolved corrosion difference it is apparent, illustrate that this law has stronger differentiation effect, suitable for the measure of the capsule stripping curve, tool
The measurement result of body is as follows, and stripping curve is shown in attached drawing 2.
| 0min | 15min | 30min | 45min | 60min | 90min | 120min | 150min | |
| Prescription 5 | 0.00 | 52.83 | 77.51 | 88.32 | 92.15 | 94.86 | 95.01 | 95.19 |
| Prescription 31 | 0.00 | 38.53 | 56.78 | 69.44 | 78.38 | 88.46 | 93.97 | 94.12 |
| Prescription 32 | 0.00 | 24.51 | 46.37 | 59.09 | 68.16 | 82.60 | 91.69 | 93.65 |
| Prescription 34 | 0.00 | 16.92 | 35.10 | 45.88 | 53.94 | 66.22 | 76.30 | 82.82 |
| Original is ground | 0.00 | 13.96 | 31.49 | 43.58 | 52.27 | 66.58 | 80.58 | 90.07 |
Sample to be ground to a collection of original using this law and carries out stripping curve measure, the coefficient of variation of 6 sample rooms meets the requirements,
Illustrate that the homogeneity of this law is good, suitable for the measure of the capsule stripping curve, specific measurement result is as follows, and stripping curve is shown in
Attached drawing 3.
| Original is ground | 0min | 15min | 30min | 45min | 60min | 90min | 120min | 150min |
| Piece 1 | 0.00 | 11.88 | 28.27 | 40.27 | 49.37 | 64.79 | 79.22 | 91.76 |
| Piece 2 | 0.00 | 11.93 | 29.37 | 41.69 | 50.44 | 65.43 | 79.32 | 88.69 |
| Piece 3 | 0.00 | 16.16 | 33.45 | 44.81 | 53.67 | 67.06 | 79.83 | 90.83 |
| Piece 4 | 0.00 | 13.14 | 32.05 | 44.74 | 53.52 | 66.45 | 83.09 | 90.79 |
| Piece 5 | 0.00 | 15.17 | 33.73 | 46.10 | 54.96 | 69.64 | 82.65 | 89.05 |
| Piece 6 | 0.00 | 15.45 | 32.09 | 43.86 | 51.65 | 66.10 | 79.39 | 89.29 |
| Mean value | 0.00 | 13.96 | 31.49 | 43.58 | 52.27 | 66.58 | 80.58 | 90.07 |
| RSD% | 13.47 | 7.01 | 5.00 | 4.09 | 2.55 | 2.22 | 1.36 |
Same a batch self-control sample is repeated three times using this law, measurement result no significant difference, illustrates this law three times
Repeatability it is good, suitable for the measure of the capsule stripping curve, measurement result is as follows, and stripping curve is shown in attached drawing 4.
| Prescription 34 | 0min | 15min | 30min | 45min | 60min | 90min | 120min | 150min |
| For the first time | 0.00 | 16.92 | 35.10 | 45.88 | 53.94 | 66.22 | 76.30 | 82.82 |
| Second | 0.00 | 16.88 | 35.10 | 45.76 | 53.99 | 66.12 | 75.18 | 82.05 |
| For the third time | 0.00 | 17.15 | 36.88 | 46.95 | 55.21 | 67.75 | 77.83 | 83.29 |
Based on the above results, this law has stronger separating capacity, can distinguish the difference between different prescriptions, and uniform
Property and repeatability meet the requirements, illustrate that this method is suitable for evaluating the difference between the capsule batch, while can also evaluate it
The difference of external dissolved corrosion between former triturate is made prediction for vivo biodistribution equivalence trial, improves bioequivalence examination
The success rate tested.
Description of the drawings
Fig. 1 national drug standards (WS1(X-068) -2003Z) specified in dissolution test method
The four batches of self-control samples and original that Fig. 2 assay methods of the present invention measure grind sample stripping curve
Fig. 3 assay methods of the present invention measure the stripping curve that 6 originals grind sample
Fig. 4 assay methods of the present invention are measured to be repeated three times with a batch self-control sample.
Claims (6)
1. a kind of stripping curve assay method of calcium hydrophenyl sulfonate capsule.It is characterized in that, this method the specific steps are：Take this
After product paper clip or thin wire are fixed, using Rotating shaker, using citrate buffer (pH6.8) 1000ml of 0.05mol/L as
Dissolution medium, rotating speed was 75 turns per minute, through 15 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 points
Zhong Shi takes solution 10ml respectively, filtration, as test solution, and supplements mutually synthermal, same volume dissolution immediately and is situated between
Matter；The solution at each time point is taken respectively, using high effective liquid chromatography for measuring, records chromatogram.
2. the assay method is required according to right 1, which is characterized in that need first by capsule paper clip or thin wire by its
It is measured after fixation, the variation of position generation immediately in process in leaching to prevent it.
3. the assay method is required according to right 1, which is characterized in that this method need to be operated using Rotating shaker, rotating speed
Be set as 75 turns per minute, sampling time point is respectively 15 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes,
At 150 minutes.
4. the assay method is required according to right 1, which is characterized in that the dissolution medium of this method is the Chinese holly of 0.05mol/L
Rafter acid buffer (pH6.8) 1000ml.The specific preparation method of dissolution medium is：Take Trisodium citrate dihydrate 102.9g (about
It is equivalent to 0.35mol), water 7L is added to make dissolving, adjusts pH value to 6.8 with saturated lemon, mixing filters.
5. the assay method is required according to right 1, which is characterized in that this method is examined using high performance liquid chromatograph
It surveys, chromatographic condition is：
1. detector：UV detector；Detection wavelength：300nm
2. chromatographic column：Using Agela Promosil C18(4.6mm × 250mm, 5 μm) chromatographic column
3. mobile phase：Acetonitrile -0.05mol/L ammonium dihydrogen phosphates (2: 98)
4. flow velocity：1.0ml/min
5. sampling volume：10μl .
6. the assay method is required according to right 1, which is characterized in that this method is used to measure calcium hydrophenyl sulfonate capsule.
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| CN201611181769.3A CN108226353A (en) | 2016-12-14 | 2016-12-14 | A kind of assay method of calcium hydrophenyl sulfonate capsule stripping curve |
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| CN201611181769.3A CN108226353A (en) | 2016-12-14 | 2016-12-14 | A kind of assay method of calcium hydrophenyl sulfonate capsule stripping curve |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112730680A (en) * | 2020-12-24 | 2021-04-30 | 瀚晖制药有限公司 | Dissolution curve determination method of mycophenolate mofetil |
Citations (4)
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|---|---|---|---|---|
| JP2000356632A (en) * | 1999-04-16 | 2000-12-26 | Nippon Zoki Pharmaceut Co Ltd | Testing method |
| CN1771927A (en) * | 2005-11-03 | 2006-05-17 | 上海复星朝晖药业有限公司 | Calcium hydrophenyl sulfonate capsule and its prepn process |
| CN103257192A (en) * | 2013-05-08 | 2013-08-21 | 北京满格医药科技有限公司 | Dissolution rate determination method of soft capsules |
| CN104330495A (en) * | 2014-11-04 | 2015-02-04 | 天津医药集团津康制药有限公司 | Method for determining similarity of dissolution curves of cefdinir dry suspension |
-
2016
- 2016-12-14 CN CN201611181769.3A patent/CN108226353A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000356632A (en) * | 1999-04-16 | 2000-12-26 | Nippon Zoki Pharmaceut Co Ltd | Testing method |
| CN1771927A (en) * | 2005-11-03 | 2006-05-17 | 上海复星朝晖药业有限公司 | Calcium hydrophenyl sulfonate capsule and its prepn process |
| CN103257192A (en) * | 2013-05-08 | 2013-08-21 | 北京满格医药科技有限公司 | Dissolution rate determination method of soft capsules |
| CN104330495A (en) * | 2014-11-04 | 2015-02-04 | 天津医药集团津康制药有限公司 | Method for determining similarity of dissolution curves of cefdinir dry suspension |
Non-Patent Citations (2)
| Title |
|---|
| DKSHTM: "仿制药质量一致性评价-普通口服固体制剂溶出曲线测定与比较指导原则(草案)http://www.doc88.com/p-9921475794069.html", 《道客巴巴》 * |
| 于梦等: "ＲP-HPLC测定羟苯磺酸钙含量及有关物质", 《中国实验方剂学杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112730680A (en) * | 2020-12-24 | 2021-04-30 | 瀚晖制药有限公司 | Dissolution curve determination method of mycophenolate mofetil |
| CN112730680B (en) * | 2020-12-24 | 2024-02-13 | 浙江长典药物技术开发有限公司 | Method for determining dissolution curve of mycophenolate mofetil |
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