CN106908553A - A kind of method for improving indapamide tablets stability in an acidic solution - Google Patents
A kind of method for improving indapamide tablets stability in an acidic solution Download PDFInfo
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- CN106908553A CN106908553A CN201710080270.1A CN201710080270A CN106908553A CN 106908553 A CN106908553 A CN 106908553A CN 201710080270 A CN201710080270 A CN 201710080270A CN 106908553 A CN106908553 A CN 106908553A
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- acid solution
- indapamide
- indopamide
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- G—PHYSICS
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- 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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Abstract
The invention discloses a kind of acid solution for improving indapamide tablet stability, it is characterised in that the acid solution is hydrochloric acid solution.Vitamin C can also be contained in the acid solution.After the present invention adds vitamin C in oxytropism solution, the unexpected stability for considerably improving indapamide tablets, and will not be also negatively affected to indapamide tablets dissolution rate in an acidic solution, for example it does not significantly increase indapamide tablets dissolution in an acidic solution, and this is beneficial to the measure of follow-up indapamide tablets dissolution rate.
Description
Technical field
The present invention relates to a kind of method for improving indapamide tablets stability in an acidic solution.
Background technology
Indapamide is sulfamido diuretics, and molecular weight is 365.83, is a kind of strong with diuresis and calcium antagonism
Effect, long-acting depressor.Clinically it is additionally operable to the treatment of water-sodium retention during congestive heart failure.
But, common indapamide tablets can degrade after dissolution sampling in strong acid medium, cause interval certain
Time after inject high performance liquid chromatograph after accumulative dissolution reduction, influence experimental data collect.
The content of the invention
Therefore, one of present invention is there is provided a kind of acid solution for improving indapamide tablet stability, the acid solution
It is hydrochloric acid solution.Indapamide tablets have certain stability in the hydrochloric acid solution.
Further, after the present invention adds vitamin C in oxytropism solution, indapamide is unexpectedly considerably improved
The stability of piece, and will not being also negatively affected to indapamide tablets dissolution in an acidic solution, for example it is simultaneously
Indapamide tablets dissolution in an acidic solution is not significantly increased, this is beneficial to follow-up indapamide tablets dissolution rate
Determine.
Inventor has found that the suitable ascorbic amount of addition, can obtain more excellent in oxytropism solution in research process
Effect, therefore, in a detailed embodiment, mass content of the vitamin C in the acid solution is
0.01% to 0.1%.
In a detailed embodiment, preferred mass content of the vitamin C in the acid solution is
0.01% to 0.05%.
In a detailed embodiment, the pH value of the acid solution is 1.0 to 2.2.
In a detailed embodiment, the preferable ph of the acid solution is 1.2 to 1.5.
In a detailed embodiment, salt is also contained in the acid solution.
In a detailed embodiment, mass content of the salt in the acid solution is 0.1% to 0.3%.
In a detailed embodiment, mass content of the salt in the acid solution be 0.15% to
0.25%.
In a detailed embodiment, the salt is sodium chloride.
The two of the present invention provide a kind of method for determining indapamide tablets dissolution rate, and methods described comprises the following steps：
1) acid solution as described in one of present invention containing the indapamide tablets is prepared；
2) using the dissolution rate of indapamide tablets described in high effective liquid chromatography for measuring.
In a detailed embodiment, in step 1) in, it is indapamide tablets leaching condition to use paddle method, wherein, turn
Speed is 50 revs/min to 75 revs/min.Rotating speed can be determined by those skilled in the art according to routine techniques.
In a detailed embodiment, the rotating speed is 50 revs/min to 60 revs/min.
In a detailed embodiment, 900ml dissolution mediums (hydrochloric acid solution) is prepared, dissolution medium temperature reaches 37
DEG C, to putting into indapamide tablets in medium, using 50 revs/min of paddle method, sampling time point is 5min, 10min, 15min,
30min, 45min, 60min, 90min.
The combination of the common knowledge of embodiments in accordance with the present invention and this area, it may be determined that high performance liquid chromatography
Column temperature, indopamide retention time and Detection wavelength.Therefore, in a detailed embodiment, step 2) in, the efficient liquid
The fixing phase used in phase chromatography is octadecylsilane chemically bonded silica；Mobile phase is 0.1% phosphoric acid solution-acetonitrile-methanol；
Chromatographic isolation test condition：Column temperature is 35 DEG C to 45 DEG C, and flow rate of mobile phase is controlled for that can make indopamide retention time
5min to 8min, ultraviolet detection wavelength is 240nm to 242nm；Number of theoretical plate is calculated according to the indopamide peak and is not less than
3500, tailing factor is not more than 1.5.
In a detailed embodiment, chromatographic isolation test condition：Column temperature is 38 DEG C to 42 DEG C, and flow rate of mobile phase is energy
Indopamide retention time is enough set to control in 6min to 7min；The number of theoretical plate exists according to indopamide peak computer capacity
3500-11000, tailing factor scope is in 0.9-1.1.
Those skilled in the art can determine the volume of 0.1% phosphoric acid solution-acetonitrile-methanol according to routine techniques
Than.Therefore, in a detailed embodiment, the volume ratio of 0.1% phosphoric acid solution-acetonitrile-methanol is (5.5-6.5)：
(2.5-3.5)：1, the volume ratio of such as 0.1% phosphoric acid solution-acetonitrile-methanol is 6:3:1.Those skilled in the art is according to normal
Rule technology determines the volume ratio of 0.1% phosphoric acid solution-acetonitrile-methanol.
In the present invention, just filtrate refers to the filtrate being first filtered, and filtrate degree of purity now not enough, is discarded,
First filtrate continues the filtrate for collecting after outwelling, then referred to as subsequent filtrate.
Brief description of the drawings
Fig. 1 is when m- accumulation dissolution rate figure of the indapamide tablets in sample 1-1#.
Fig. 2 is when m- accumulation dissolution rate figure of the indapamide tablets in sample 1-2#.
Fig. 3 is when m- accumulation dissolution rate figure of the indapamide tablets in sample 1-3#.
Fig. 4 is when m- accumulation dissolution rate figure of the indapamide tablets in sample 1-4#.
Fig. 5 is when m- accumulation dissolution rate figure of the indapamide tablets in sample 1-5#.
Fig. 6 is when m- accumulation dissolution rate figure of the indapamide tablets of sample D1# in strong acid medium.
Specific embodiment
With reference to embodiment in detail the present invention is described in detail, but the invention is not limited in these embodiments.
Unless otherwise instructed, the raw material in embodiments of the invention is bought by commercial sources.
Operating procedure：
(1) preparation of acid solution：Weigh a certain amount of salt and acid be diluted with water to 1000ml, determine its pH, mix,
Obtain final product.
(2) to adding appropriate additive, such as vitamin C in medium.
(3) indapamide tablets (2.5mg) are taken, is added in the medium of above-mentioned preparation, rotating speed is 50 turns per minute, through 5min,
Solution is taken after the dissolution of 10min, 15min, 30min, 45min, 60min, 90min respectively appropriate, discard 5ml just filtrates, taken continuous
Filtrate is need testing solution.Difference immediately, is spaced 5h in right amount to take need testing solution, is spaced 10h, and efficient liquid is injected after the 15h of interval
In chromatography, collection of illustrative plates is recorded.
(4) condition determination：The fixing phase of high performance liquid chromatograph is octadecylsilane chemically bonded silica, and mobile phase is volume
Than being 6:3:1 0.1% phosphoric acid solution-acetonitrile-methanol, Detection wavelength is 242nm, and sampling volume is 50 μ l, set column temperature as
40 DEG C, adjustment flow velocity is 1.2ml/min, and number of theoretical plate is calculated by indopamide peak and should be not less than 3500, tailing factor should be little
In 1.5.Computing formula=the A of the indapamide of dissolutionSample/CSample× f × 100%, f=CControl/AControl, the results are shown in Table 1.
Embodiment 1
Investigate dissolution of the ascorbic concentration to indapamide in the acid solution of the hydrochloric acid of pH 1.2
Vitamin C mass concentration is prepared to be respectively：0.01%th, 0.02%, 0.03%, 0.05%, 0.1% pH1.2
(wherein, sodium chloride mass content is for 0.2%) for hydrochloric acid solution.The sample for preparing respectively 1-1#, 1-2#, 1-3#, 1-4#,
1-5#.Other biconditional operation steps.
The measurement result of the indapamide of dissolution is shown in Table 1.
Embodiment 2
Investigate dissolution of the pH value of acid solution to indapamide in the acid solution of hydrochloric acid
Prepare pH and be respectively 1.0,1.2,1.5,2.2 hydrochloric acid solution, wherein containing the chlorination that mass content is 0.2%
Sodium, the sample for preparing respectively 2-1#, 2-2#, 2-3# and 2-4#.It is 0.02% to prepare mass content containing vitamin C again,
PH is respectively 1.0,1.2,1.5,2.2 hydrochloric acid solution, wherein containing the sodium chloride that mass content is 0.2%, preparing
Sample is respectively 2-5#, 2-6#, 2-7#, 2-8#.Other biconditional operation steps.
The measurement result of the indapamide of dissolution is shown in Table 1.
Embodiment 3
Investigate dissolution of the species of acid solution to indapamide in the acid solution of pH1.2
PH is prepared with phosphoric acid and be 1.2 acid solution, wherein containing the sodium chloride that mass content is 0.2%, preparing
Sample be 3-1#.Prepare again containing vitamin C 0.02%, pH is respectively 1.2 phosphoric acid solution, wherein containing mass content
It is 0.2% sodium chloride, the sample for preparing is 3-2#.Other biconditional operation steps.
The measurement result of the indapamide of dissolution is shown in Table 1.
Embodiment 4
Investigate dissolution of the species of antioxidant to indapamide in the acid solution of the hydrochloric acid of pH 1.2
Replace 0.02% vitamin c solution with 0.02% sodium pyrosulfite, 0.02% disodium ethylene diamine tetraacetate respectively, match somebody with somebody
PH processed is 1.2 hydrochloric acid solution, the sample for preparing respectively 4-1#, 4-2#,.Other are with embodiment 1.
The measurement result of the indapamide of dissolution is shown in Table 1.
Embodiment 5
Investigate dissolution of the presence or absence of the salt to indapamide in the acid solution of the hydrochloric acid of pH 1.2
Prepare not sodium chloride-containing and without the hydrochloric acid solution that ascorbic pH is 1.2, and sodium chloride-containing does not contain still
0.02% ascorbic pH is 1.2 hydrochloric acid solution, the sample for preparing respectively 5-1#, 5-2#.Other biconditional operations are walked
Suddenly.
The measurement result of the indapamide of dissolution is shown in Table 1.
Comparative example 1
Dissolution of the indapamide in the acid solution of the hydrochloric acid of the pH 1.2 without antioxidant
The pH that preparation is not added with antioxidant sodium chloride-containing 0.2% is 1.2 hydrochloric acid solution.The sample for preparing is D1#.Its
His biconditional operation step.
The measurement result of the indapamide of dissolution is shown in Table 1.
The indapamide tablets of table 1 are in acid medium
Accumulation dissolution rate after 0h, interval 5h, interval 10h, interval 15h
Conclusion：
1st, sodium pyrosulfite and disodium ethylene diamine tetraacetate can accelerate dissolution, therefore, although both materials can suppress
The degraded of indapamide, but because its dissolution for accelerating indapamide can cause to determine inaccurate, therefore be not suitable for adding
To in the acid solution for determining indapamide dissolution rate.
2nd, after changing hydrochloric acid into phosphoric acid, vitamin C does not have the effect of stabilization, and degraded is accelerated on the contrary, therefore, phosphoric acid solution
It is also unsuitable for determining indapamide dissolution rate.
The above, is only several embodiments of the present invention, any type of limitation is not done to the present invention, although this hair
It is bright to be disclosed as above with preferred embodiment, but and be not used to the limitation present invention, any those skilled in the art are not taking off
In the range of technical solution of the present invention, make a little variation using the technology contents of the disclosure above or modification is equal to
Effect case study on implementation, belongs in the range of technical scheme.
Claims (10)
1. it is a kind of improve indapamide tablet stability acid solution, it is characterised in that the acid solution be hydrochloric acid solution.
2. acid solution according to claim 1, it is characterised in that contain vitamin C in the acid solution.
3. acid solution according to claim 1 and 2, it is characterised in that the vitamin C is in the acid solution
Mass content is 0.01% to 0.1%；It is preferred that mass content of the vitamin C in the acid solution be 0.01% to
0.05%.
4. the acid solution according to any one in claim 1-3, it is characterised in that the pH value of the acid solution is
1.0 to 2.2；It is preferred that the pH value of the acid solution is 1.2 to 1.5.
5. the acid solution according to any one in claim 1-4, it is characterised in that also contain in the acid solution
Salt；
It is preferred that mass content of the salt in the acid solution is 0.1% to 0.3%；More preferably described salt is in the acidity
Mass content in solution is 0.15% to 0.25%；
More preferably described salt is sodium chloride.
6. it is a kind of determine indapamide tablets dissolution rate method, it is characterised in that methods described comprises the following steps：
1) acid solution as described in any one in claim 1-5 containing the indapamide tablets is prepared；
2) using the dissolution rate of indapamide tablets described in high effective liquid chromatography for measuring.
7. method according to claim 6, it is characterised in that in step 1) in, use paddle method molten for indapamide tablets
Go out condition, wherein, rotating speed is 50 revs/min to 75 revs/min.
8. the method according to claim 6 or 7, it is characterised in that step 2) in, make in the high performance liquid chromatography
Fixing phase is octadecylsilane chemically bonded silica；
Mobile phase is 0.1% phosphoric acid solution-acetonitrile-methanol；
Chromatographic isolation test condition：Column temperature is 35 DEG C to 45 DEG C, and flow rate of mobile phase is controlled for that can make indopamide retention time
In 5min to 8min, ultraviolet detection wavelength is 240nm to 242nm；Number of theoretical plate is calculated according to the indopamide peak and is not less than
3500, tailing factor is not more than 1.5.
9. method according to claim 8, it is characterised in that chromatographic isolation test condition：Column temperature is 38 DEG C to 42 DEG C, stream
Dynamic phase flow velocity is controlled in 6min to 7min for that can make indopamide retention time；The number of theoretical plate is according to the indopamide
, in 3500-11000, tailing factor scope is in 0.9-1.1 for peak computer capacity.
10. method according to claim 8 or claim 9, it is characterised in that the body of 0.1% phosphoric acid solution-acetonitrile-methanol
Product is than being (5.5-6.5)：(2.5-3.5)：1.
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| CN201710080270.1A CN106908553B (en) | 2017-02-15 | 2017-02-15 | Method for improving stability of indapamide tablets in acidic solution |
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| CN110849995A (en) * | 2019-11-27 | 2020-02-28 | 远大医药（中国）有限公司 | Detection method of DCU in indapamide bulk drug |
| CN111175388A (en) * | 2019-11-18 | 2020-05-19 | 远大医药（中国）有限公司 | Method for determining DCC content in indapamide bulk drug |
| CN111595954A (en) * | 2019-11-18 | 2020-08-28 | 远大医药（中国）有限公司 | Method for detecting content of DCC and DCU in indapamide bulk drug |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111595954A (en) * | 2019-11-18 | 2020-08-28 | 远大医药（中国）有限公司 | Method for detecting content of DCC and DCU in indapamide bulk drug |
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| CN110849995A (en) * | 2019-11-27 | 2020-02-28 | 远大医药（中国）有限公司 | Detection method of DCU in indapamide bulk drug |
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