CN106018604A - Method for measuring dissolution rates of esomeprazole magnesium enteric-coated preparation in different media - Google Patents

Method for measuring dissolution rates of esomeprazole magnesium enteric-coated preparation in different media Download PDF

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CN106018604A
CN106018604A CN201610357133.3A CN201610357133A CN106018604A CN 106018604 A CN106018604 A CN 106018604A CN 201610357133 A CN201610357133 A CN 201610357133A CN 106018604 A CN106018604 A CN 106018604A
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solution
esomeprazole magnesium
dissolution
enteric coated
coated preparation
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CN106018604B (en
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谭银合
余思琴
钟露露
颜楚红
赵明馨
杨新明
蒋林波
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Guangdong Pd Pharmaceutical Co Ltd
Sun Yat Sen University
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Guangdong Pd Pharmaceutical Co Ltd
Sun Yat Sen University
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/04Preparation or injection of sample to be analysed
    • G01N30/06Preparation
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N2030/022Column chromatography characterised by the kind of separation mechanism
    • G01N2030/027Liquid chromatography

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Abstract

The invention discloses a method for measuring the dissolution rates of an esomeprazole magnesium enteric-coated preparation in different media. The method is characterized in that a step of establishing a linear regression equation is added, that is, a sodium hydroxide solution and ethyl alcohol are added into the content of an esomeprazole magnesium enteric-coated tablet or capsule to perform ultrasonic dissolution, then filtration is conducted, the filtrate is taken out, subjected to constant-volume treatment and then placed in a water bath of 37+/-0.5 DEG C, a sample is taken at each dissolution time and is injected into a high performance liquid chromatograph, chromatograms are recorded, and the linear relationship between a main peak and a relative retention time 2.7 impurity peak is found out from the area change relationship between the main peak and the relative retention time 2.7 impurity peak to obtain the linear regression equation which is applied to calculation of the dissolution quantity of esomeprazole magnesium. The method solves the problem that the dissolution rate of the esomeprazole magnesium enteric-coated preparation cannot be accurately measured in the prior art, and has the advantages of being convenient, quick, accurate, excellent in repeatability, high in sensitivity and strong in practicability during operation.

Description

Esomeprazole magnesium enteric coated preparation assay method of dissolution in different medium
Technical field
The present invention relates to System In Pharmaceutical Preparation Analysis detection field, particularly relate to a kind of esomeprazole magnesium enteric coated preparation and exist The assay method of dissolution in different medium.
Background technology
Esomeprazole magnesium (Esomeprazole Magnesium, double-S-5-methoxyl group-2-{ [(4-methoxyl group-3, 5-dimethyl-2-pyridine radicals) methyl] sulfenyl-1H-benzimidazole magnesium trihydrate) a kind of new proton pump inhibitor, its Molecular formula is C34H36MgN6O6S2·3H2O, molecular weight 767.17, chemical structural formula is as follows:
Esomeprazole magnesium, also referred to as esomeprazole magnesium, be the S-configuration optical isomer of omeprazole, and it is weak Alkalescence, concentration be converted into active matter sulfenic acids amide in parietal cell secretes the high acid environment of sour micro-pipe is then thin with coat of the stomach H on born of the same parents+-K+Sulfydryl on-ATP enzyme subunit cysteine residues passes through disulfide-bonded, makes the oxidized inactivation of enzyme, thus Make the H of parietal cell+Gastral cavity can not be transported to, and then play gastric acid secretion inhibiting, and then play the therapeutical effect of gastric acid inhibitory.
There is sulfoxide group in esomeprazole magnesium structure so that it is extremely sensitive to acid medium, easily degrade, this also leads Cause its process in leaching in the media such as pH6.0 phosphate buffer, pH6.8 phosphate buffer, water is degraded, unfavorable Accurate calculating in dissolution result.But, retrieve the documents and materials about esomeprazole magnesium preparation dissolution control method And patent, and find no the research report of related fields.This is the most just difficult to evaluate esomeprazole magnesium enteric system accurately The process in leaching of agent.
Summary of the invention
Based on this, it is an object of the invention to provide the assay method of a kind of esomeprazole magnesium enteric coated preparation dissolution.
The concrete technical scheme realizing foregoing invention purpose is as follows:
The assay method of a kind of esomeprazole magnesium enteric coated preparation dissolution, comprises the following steps:
(1) preparation of need testing solution a
Take esomeprazole magnesium enteric coated preparation add dissolution instrument dissolution medium in, speed of agitator be 50rpm~ 100rpm, temperature is 37 DEG C ± 0.5 DEG C, takes dissolution fluid in different time points and filters, and takes filtrate and adds sodium hydroxide solution, described The concentration of sodium hydroxide solution is 0.1mol/L~0.5mol/L, and taken filtrate is 1:0.1-with the volume ratio of sodium hydroxide solution 0.14, shake up, be the need testing solution a of each time point;
(2) preparation of esomeprazole magnesium solution b
Take esomeprazole magnesium enteric coated preparation, finely ground, weigh finely ground powder and add sodium hydroxide solution, ultrasonic, add second Alcohol, continues ultrasonic, quantitatively dilutes with sodium hydroxide solution, obtains solution I, filters, obtains filtrate I, take filtrate I quantitative with described acid medium Dilution, obtains solution II;Solution II is placed in 37 DEG C ± 0.5 DEG C water-bath, respectively at different time points sampling filtering, obtains each time point Filtrate II, takes filtrate II and adds sodium hydroxide solution, and taken filtrate II is 1:0.1-0.14 with the volume ratio of sodium hydroxide solution, shakes up, It is the esomeprazole magnesium solution b of described each time point;The concentration of described sodium hydroxide solution is 0.01mol/L~1.0mol/L;
(3) preparation of reference substance solution
Take omeprazole reference substance, dissolve with ethanol, more quantitatively dilute with dissolution medium, pipette the solution after dilution, add Enter sodium hydroxide solution, shake up, be reference substance solution;The concentration of described sodium hydroxide solution is 0.1mol/L~0.5mol/ L, the solution after described dilution is 1:0.1-0.14 with the volume ratio of sodium hydroxide solution;
(4) high performance liquid chromatography detection
Step I: carry out need testing solution a and reference substance solution by high performance liquid chromatography, records need testing solution a Main peak peak area AA masterPeak area A with the impurity peaks that relative retention time is 2.7A is miscellaneous;And the peak area of reference substance solution;
Step II: detect the esomeprazole magnesium solution b of each time point by high performance liquid chromatography, record is each Time point main peak peak area AB masterPeak area A with the impurity peaks that relative retention time is 2.7B is miscellaneous;Set up each time point relatively to retain Time is the impurity peaks peak area A of 2.7B is miscellaneousValue added and main peak peak area AB masterReduced value between equation of linear regression y= Kx+m and its correlation coefficient r, wherein y is the reduced value of main peak peak area, and x is the value added of impurity peaks peak area;
According to the peak area A of the impurity peaks that relative retention time is 2.7 of record in step IA is miscellaneousAnd step II is linear Regression equation y=kx+m, is calculated the reduced value of the main peak peak area of need testing solution a, adds the master of record in step I Peak-to-peak area AA master, it is calculated the stripping quantity that esomeprazole magnesium is actual, and then obtains dissolution.
Wherein in some embodiments, described esomeprazole magnesium enteric coated preparation is esomeprazole magnesium enteric coated micropill Capsule or esomeprazole magnesium enteric coated tablet.
Wherein in some embodiments, described dissolution medium is phosphate buffered solution or the water of pH5.5-7.0.
Wherein in some embodiments, the chromatograph of the high performance liquid chromatography detection described in step (3) and step (4.2) Condition is:
Chromatographic column: C18 chromatographic column, specification is 5 μm, 4.6*150mm;Flowing phase: acetonitrile-phosphate buffered solution-water, institute Stating acetonitrile, phosphate buffered solution is 33-37:48-52:13-17 with the volume ratio of water, and the pH of described phosphate buffered solution is 7.2-7.4;Flow velocity: 0.7~0.9mL/min;Sample size: 20 μ L;Column temperature: 25 DEG C~35 DEG C;Detection wavelength: 302nm.
Wherein in some embodiments, described acetonitrile, phosphate buffered solution are 35:50:15 with the volume ratio of water, described The pH of phosphate buffered solution is 7.3, and its compound method is for taking 1mol/L sodium dihydrogen phosphate 10.5ml and 0.5mol/L phosphorus Acid disodium hydrogen solution 60ml, is diluted with water to 1000ml, shakes up and get final product;Flow velocity: 0.8mL/min;Column temperature: 30 DEG C.
Wherein in some embodiments, the esomeprazole magnesium in esomeprazole magnesium enteric coated preparation in step (1) It is 20mg:900-1000mL with the proportioning of dissolution medium;The concentration of described sodium hydroxide solution is 0.25mol/L~0.5mol/ L, taken filtrate is 1:0.12 with the volume ratio of sodium hydroxide solution.
Wherein in some embodiments, the rotating speed of step (1) described stirring is 50rpm~75rpm.
Wherein in some embodiments, ethanol described in step (2) is joined with esomeprazole magnesium enteric coated preparation powder Ratio is 7~8ml:100mg, the magnesium enteric coated preparation powder 5mg/mL Han esomeprazole in described solution I;Taken filtrate I and institute The volume ratio obtaining solution II is 1:50.
Wherein in some embodiments, the concentration of sodium hydroxide solution described in step (2) be 0.25mol/L~ 0.5mol/L, taken filtrate II is 1:0.12 with the volume ratio of sodium hydroxide solution.
Wherein in some embodiments, in step (3) described reference substance solution, the content of omeprazole is 20 μ g/ml.
Wherein in some embodiments, in step (4) described equation of linear regression y=kx+m, 1.0≤k≤5.0,20000 ≤ m≤100000, correlation coefficient r is more than 0.995.
The assay method of the esomeprazole magnesium enteric coated preparation dissolution of the present invention has the following advantages and beneficial effect:
Esomeprazole magnesium enteric coated preparation is degradable in the process in leaching in acid medium, with existing method measure its During stripping quantity in acid medium, main peak area elapses in time and is gradually reduced, and all peaks of chromatogram on each time point Peak area summation inconsistent, this causes the stripping quantity that cannot accurately calculate esomeprazole magnesium.The present inventor passes through Lot of experiments finds, is dissolved in acid medium by esomeprazole magnesium, along with the change of standing time, main peak peak area The increase of peak area of the impurity peaks that minimizing and relative retention time are 2.7 there is certain linear relationship, therefore inventor's wound The property made in the test process of its dissolution, add step and the concrete grammar thereof setting up equation of linear regression, i.e. set up main peak Equation of linear regression between the increase of the peak area of the minimizing of peak area and impurity peaks that relative retention time is 2.7, utilizing should Regression equation can accurately calculate the time dependent minimizing of main peak area in process in leaching of esomeprazole magnesium enteric coated preparation, Main peak area further according to practical measurement can accurately calculate esomeprazole magnesium enteric coated preparation difference in acid medium The dissolution of time point, and then set up stripping curve, this stripping curve can be used to accurate evaluation esomeprazole magnesium enteric The process in leaching in different medium of preparation, the especially process in leaching in the phosphate buffered solution that pH is 6.0 or water.
Therefore, the assay method of the esomeprazole magnesium enteric coated preparation dissolution of the present invention solve prior art can not Accurate Determining esomeprazole magnesium enteric coated preparation problem of dissolution in acid medium, the method for the present invention has conveniently, Fast, accurately, favorable reproducibility, highly sensitive, the advantage such as the most practical.
Accompanying drawing explanation
Fig. 1 is the height that in embodiment 1, esomeprazole magnesium enteric coatel tablets are degraded in the phosphate-buffered liquid medium of pH6.0 Effect liquid phase chromatogram figure;
Fig. 2 is the high-efficient liquid phase chromatogram degraded in esomeprazole magnesium enteric coatel tablets aqueous medium in embodiment 2;
Fig. 3 is esomeprazole magnesium enteric coated preparation dissolution in the phosphate-buffered liquid medium of pH6.0 in embodiment 4 Curve chart;
Fig. 4 is esomeprazole magnesium enteric coated preparation stripping curve figure in aqueous medium in embodiment 5.
Detailed description of the invention
Below in conjunction with specific embodiment, the assay method of the esomeprazole magnesium enteric coated preparation dissolution of the present invention is made Further describe, but protection scope of the present invention is not limited to these implements row.Every change without departing substantially from present inventive concept Or within equivalent replacement is included in protection scope of the present invention.
Unless otherwise indicated, raw material or reagent used in following example are commercially available.
In following example, the chromatographic condition of high performance liquid chromatography detection is:
Chromatographic column: C18 post, specification is 5 μm, 4.6*150mm;Flowing phase: acetonitrile-phosphate buffered solution-water, acetonitrile, The volume ratio of phosphate buffered solution and water is 35:50:15, and the pH of phosphate buffered solution is 7.3 (to join by the following method System: take 1mol/L sodium dihydrogen phosphate 10.5ml and 0.5mol/L disodium phosphate soln 60ml, be diluted with water to 1000ml, Shake up);Flow velocity: 0.8ml/min;Sample size: 20 μ L;Column temperature: 30 DEG C;Detection wavelength: 302nm.
Embodiment 1 esomeprazole magnesium enteric coatel tablets or enteric-coated pellet capsule degradation rule in pH6.0 phosphate buffer
Take specification 20mgEsomeprazole magnesium enteric coatel tablets or enteric-coated pellet capsule (remove capsule shells, in taking Tolerant, lower with) put in mortar, finely ground, weigh 100mg in 20ml volumetric flask, add 0.0125mol/L sodium hydroxide solution 12mL, ultrasonic 5min, add 7.5ml ethanol and continue ultrasonic 3min, with 0.0125mol/L sodium hydroxide solution constant volume.Filter, take filter In liquid 2ml to 100ml volumetric flask, with pH6.0 phosphate buffer constant volume, put in 37 DEG C ± 0.5 DEG C water-bath, respectively at 0,15, 30,45,60,90,120,180,240min sampling, filter.Take subsequent filtrate 5ml in cillin bottle, be separately added into 0.5mol/L hydrogen Sodium oxide 600 μ l, mixing, the accurate 20 μ l that draw inject chromatograph of liquid, record chromatogram.Owing to sample is at pH6.0 phosphate Buffer is degraded, adds up with the degradation impurity peak of main peak and one of them relative retention time 2.7, the results are shown in Table 1, table 2;And respectively with main peak peak area AMainReduced value as y value, the value added of the impurity peaks peak area of relative retention time 2.7 is made For x value;AMainMain peak peak area A when reduced value computational methods are main peak 0minMainThis main peak peak being individually subtracted each time point Area, correspondingly, AMiscellaneousValue added computational methods are the impurity peaks peak area (A at each time point of relative retention time 2.7Miscellaneous) Deduct this impurity peak area during 0min, carry out regression equation calculation, the results are shown in Table 3 and table 4.
Table 1. esomeprazole magnesium enteric coatel tablets degradation data in the phosphate-buffered liquid medium of pH6.0
Table 2. esomeprazole magnesium enteric-coated pellet capsule degradation data in the phosphate buffer of pH6.0
Table 3. esomeprazole magnesium enteric coatel tablets equation of linear regression in the phosphate buffer of pH6.0
Sheet number Regression equation Correlation coefficient r
1 Y=3.5587x+42043 0.9995
2 Y=3.5285x+38124 0.9995
3 Y=3.5688x+47602 0.9995
Averagely Y=3.5527x+42534 0.9997
Table 4. esomeprazole magnesium enteric-coated pellet capsule equation of linear regression in the phosphate buffer of pH6.0
Capsule number Regression equation Correlation coefficient r
1 Y=3.9230x+48002 0.9965
2 Y=3.4722x+57510 0.9950
3 Y=3.5605x+59336 0.9952
Averagely Y=3.6563x+54476 0.9970
Embodiment 2. esomeprazole magnesium enteric coatel tablets or enteric-coated pellet capsule degradation rule in water
Take specification 20mgEsomeprazole magnesium enteric coatel tablets or enteric-coated pellet capsule (remove capsule shells, in taking Tolerant) put in mortar, finely ground, weigh 100mg in 20ml volumetric flask, with 0.0125mol/L sodium hydroxide solution 12mL, ultrasonic 5min, adds 7.5ml ethanol and continues ultrasonic 3min, 0.0125mol/L sodium hydroxide solution constant volume, filter, take subsequent filtrate 2ml and arrive In 100ml volumetric flask, adjust pH to 7.0 ± 0.05 with the hydrochloric acid of 0.1mol/L, then use water constant volume, be placed in 37 DEG C ± 0.5 DEG C water-bath In, respectively at 0,30,60,90,120,180,240,300,360min sampling filtering, take subsequent filtrate 5ml, add 0.25mol/ respectively L sodium hydroxide 600 μ l, mixing, the accurate 20 μ l that draw inject chromatograph of liquid, record chromatogram.Owing to sample is in aqueous medium Degraded, adds up with the degradation impurity peak of main peak and a relative retention time 2.7, the results are shown in Table 5 and table 6;With reference to implementing The data processing method of example 1 is respectively using the reduced value of main peak peak area as y value, the value added conduct of corresponding impurity peaks peak area X value, carries out regression equation calculation, the results are shown in Table 7 and table 8.
Table 5. esomeprazole magnesium enteric coatel tablets degradation data in aqueous medium
Table 6. esomeprazole magnesium enteric-coated pellet capsule degradation data in aqueous medium
Table 7. esomeprazole magnesium enteric coatel tablets equation of linear regression in aqueous medium
Sheet number Regression equation Correlation coefficient r
1 Y=4.2901x+66207 0.9992
2 Y=4.3704x+65325 0.9982
3 Y=4.848x+83248 0.9959
Averagely Y=4.481x+70939 0.9984
Table 8. esomeprazole magnesium enteric-coated pellet capsule equation of linear regression in aqueous medium
Capsule number Regression equation Correlation coefficient r
1 Y=4.4894x+47670 0.9984
2 Y=4.4383x+46822 0.9986
3 Y=4.2855x+59080 0.9978
Averagely Y=4.4111x+52818 0.9993
Embodiment 3. esomeprazole magnesium enteric coatel tablets stripping quantity measures the accuracy (average recovery) of analysis method and tests Card
(1) average recovery in the phosphate-buffered liquid medium of pH6.0
Prepared by reference substance solution: weigh omeprazole about 20mg, puts in 100ml measuring bottle, dissolves with ethanol and is diluted to carve Degree, as reference substance solution.
The preparation of need testing solution: take the blank auxiliary in the esomeprazole magnesium enteric coatel tablets prescription of specification 20mg, grind Carefully, weigh 100mg powder in 100ml volumetric flask, add 0.0125mol/L sodium hydroxide solution, ultrasonic 5min, add ethanol 37.5ml, ultrasonic 3min, it is settled to scale with 0.0125mol/L sodium hydroxide solution.Filter, take subsequent filtrate 5ml and put 100ml appearance In measuring bottle, take 9 parts altogether, be separately added into reference substance solution 1ml, 3ml, 5ml each three parts in respective volume bottle, use pH6.0 respectively Phosphate buffer be diluted to scale, shake up, filter, take subsequent filtrate 5ml, add 0.5mol/L sodium hydroxide solution 600ul, As need testing solution.
The accurate each 20ul of above-mentioned solution of absorption injects chromatograph of liquid, records chromatogram.Relatively protect according to chromatogram record Stay the peak area of time 2.7 impurity peaks.This impurity peaks peak area of integral and calculating (peak area initial value is 0), substitutes into linear regression In equation y=3.5527x+42534, calculate the reduced value of main peak peak area, and combine the corresponding main peak of this chromatogram record Peak area, draws the main peak peak area of reality, calculates the amount of actual esomeprazole magnesium with one point external standard method, utilizes and reclaims Rate (%)=principal agent measured amount/principal agent addition is multiplied by 100%, calculates the response rate, the results are shown in Table 9.
Table 9. esomeprazole magnesium enteric coatel tablets average recovery in the phosphate-buffered liquid medium of pH6.0
Draw from table 9: the value added of the impurity peaks peak area of relative retention time 2.7 is substituted into this linear regression y= Trying to achieve the peak area of principal agent degraded, and then the method obtaining total main peak area in 3.5527x+42534, its response rate is good. Illustrate that the method is accurately and reliably.
(2) average recovery in aqueous medium
Prepared by reference substance solution: weigh omeprazole about 20mg, puts in 50ml measuring bottle, dissolves with ethanol and is diluted to carve Degree, as reference substance solution.
The preparation of need testing solution: take the blank auxiliary in specification 20mg esomeprazole magnesium enteric coatel tablets prescription and be placed in and grind In alms bowl, finely ground, weigh 100mg powder in 100ml volumetric flask, add 0.0125mol/L sodium hydroxide solution, ultrasonic 5min, Add ethanol 37.5ml, ultrasonic 3min, be settled to scale with 0.0125mol/L sodium hydroxide solution.3500rpm is centrifuged 20min, Take supernatant liquid filtering, take subsequent filtrate 1ml and put in 100ml measuring bottle, take 9 parts altogether, be separately added into reference substance solution 1ml, 3ml, 5ml each Put in corresponding measuring bottle, be diluted to scale with aqueous medium, shake up for three parts, filter, take subsequent filtrate 5ml, add 0.25mol/L hydroxide Sodium solution 600ul, as need testing solution.
The accurate each 20ul of above-mentioned solution of absorption injects chromatograph of liquid, records chromatogram.Relatively protect according to chromatogram record Stay the peak area of time 2.7 impurity peaks.Calculate the value added of this impurity peaks peak area, substitute into equation of linear regression y=4.481x+ In 70939, use the data processing method of embodiment 3. (1), calculate the reduced value of main peak peak area, and plus this chromatograph seal The corresponding main peak peak area of record, draws the main peak peak area of reality, thus calculates the amount of the esomeprazole magnesium of reality, meter Calculate the response rate, the results are shown in Table 10.
Table 10. esomeprazole magnesium enteric coatel tablets average recovery in aqueous medium
Draw from table 10, the value added of the impurity peak area of relative retention time 2.7 is substituted into this linear regression y= 4.4111x+52818 asks the peak area obtaining degraded principal agent degraded, and then the method obtaining total main peak area, its response rate Well.Illustrate that the method is accurately and reliably.
Embodiment 4. esomeprazole magnesium enteric coatel tablets and pellet capsule dissolution in the phosphate-buffered liquid medium of pH6.0 The mensuration of curve
(1) preparation of need testing solution
Take specification 20mg esomeprazole magnesium enteric coatel tablets 6 or esomeprazole magnesium enteric coated micropill enteric coated capsule 6, Use paddle method dissolution instrument, with reference to Chinese Pharmacopoeia version dissolutions in 2015 and drug release determination method (general rule 0,931 second method method 1), every or every with 1000ml pH 6.0 phosphate buffer as dissolution medium, rotating speed 50rpm, respectively at 15,30,45, 60,90,120, the time of 180min take solution, filter, take subsequent filtrate 5ml and add 0.25mol/L sodium hydroxide solution 600 μ l, Shake up, as need testing solution.
(2) preparation of reference substance solution
Take omeprazole reference substance 20mg, accurately weighed, put in 100ml measuring bottle, add ethanol 10ml and make dissolving, be situated between with dissolution Matter is diluted to scale, shakes up, and precision measures in right amount, quantitatively dilutes make in every 1ml containing about 0.02mg molten with this dissolution medium Liquid, then precision measures 5ml, precision adds 0.25mol/L sodium hydroxide solution 600 μ l, shakes up, as reference substance solution.
(3) high performance liquid chromatography detection
By high performance liquid chromatography, need testing solution and the reference substance solution of the dissolution of each time point are detected, Chromatogram, record main peak peak area and relative retention time are the peak area of the impurity peaks of 2.7.
The peak area of the impurity peaks of each time point relative retention time 2.7 according to liquid chromatogram record, when calculating each Between put the value added of this impurity peaks peak area, this value added is substituted into gained equation of linear regression y=3.5527x+42534 (sheet) Or in y=3.6563x+54476 (pellet capsule), calculate the reduced value of each time point main peak peak area, and plus this chromatograph Main peak peak area corresponding in figure, draws the main peak peak area that each time point is actual, when calculating each dissolution with one point external standard method Between put the stripping quantity of reality, calculate dissolution (representing with meansigma methods ± SD), and draw stripping curve, esomeprazole magnesium intestinal Molten and capsule stripping curve figure in the phosphate-buffered liquid medium of pH6.0 are shown in that Fig. 3, dissolution results are shown in Table 11.Dissolution Degree computing formula is as follows.
Dissolution computing formula:
Note: ASupply: esomeprazole peak area and degradation peak's area sum thereof in need testing solution
ARight: omeprazole peak area in reference substance solution
CRight: reference substance solution concentration (mg/ml)
PSupply: need testing solution extension rate
Accumulation dissolution computing formula:
Note: An: record dissolution for each time point
V1: each time point fixes sample volume (10ml)
V2: dissolution medium volume, 1000ml
Table 11. esomeprazole magnesium enteric coated preparation dissolution (n=6) in pH6.0 phosphate buffer
Embodiment 5. esomeprazole magnesium enteric coatel tablets and pellet capsule mensuration of stripping curve in aqueous medium
(1) preparation of need testing solution
Take esomeprazole magnesium enteric coatel tablets 6 or the esomeprazole magnesium enteric-coated pellet capsule 6 of specification 20mg, adopt With paddle method dissolution instrument, with reference to Chinese Pharmacopoeia version dissolutions in 2015 and drug release determination method (general rule 0,931 second method method 1), Every or every with 1000ml water as dissolution medium, rotating speed is 50rpm, respectively at 30,60,90,120,180,240,300, The dissolution time point of 360min takes solution, filters, and takes subsequent filtrate 5ml and adds 0.25mol/L sodium hydroxide solution 600 μ l, shakes up, As need testing solution.
(2) preparation of reference substance solution
Take omeprazole reference substance 20mg, accurately weighed, put in 100ml measuring bottle, add ethanol 10ml and make dissolving, be situated between with dissolution Matter is diluted to scale, shakes up, and precision measures in right amount, quantitatively dilutes make in every 1ml containing about 0.02mg molten with this dissolution medium Liquid, then precision measures 5ml, precision adds 0.25mol/L sodium hydroxide solution 600 μ l, shakes up, as reference substance solution.
(3) high performance liquid chromatography detection
By high performance liquid chromatography, need testing solution and the reference substance solution of the dissolution of each time point are detected, Chromatogram, record main peak peak area and relative retention time are the peak area of the impurity peaks of 2.7.
The peak area of the impurity peaks of each time point relative retention time 2.7 according to liquid chromatogram record, when calculating each Between put the value added of this impurity peaks peak area, this value added is substituted into gained equation of linear regression y=4.481x+70939 (sheet) Or in y=4.4111x+52818 (pellet capsule), calculate the reduced value of each time point main peak peak area, and plus this chromatograph Main peak peak area corresponding in figure, draws the main peak peak area that each time point is total, calculates each dissolution time with one point external standard method The stripping quantity that point is actual, calculates dissolution (representing with meansigma methods ± SD), and draws stripping curve (with reference to embodiment 4).Ai Si Magnesium omeprazole enteric coatel tablets and the capsule stripping curve figure in aqueous medium is shown in that Fig. 4, dissolution results are shown in Table 12.
Table 12. esomeprazole magnesium enteric coated preparation dissolution (n=6) in aqueous medium
Each technical characteristic of embodiment described above can combine arbitrarily, for making description succinct, not to above-mentioned reality The all possible combination of each technical characteristic executed in example is all described, but, as long as the combination of these technical characteristics is not deposited In contradiction, all it is considered to be the scope that this specification is recorded.
Embodiment described above only have expressed the several embodiments of the present invention, and it describes more concrete and detailed, but also Can not therefore be construed as limiting the scope of the patent.It should be pointed out that, come for those of ordinary skill in the art Saying, without departing from the inventive concept of the premise, it is also possible to make some deformation and improvement, these broadly fall into the protection of the present invention Scope.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.

Claims (10)

1. the assay method of an esomeprazole magnesium enteric coated preparation dissolution, it is characterised in that comprise the following steps:
(1) preparation of need testing solution a
Taking in the dissolution medium that esomeprazole magnesium enteric coated preparation adds dissolution instrument, speed of agitator is 50rpm~100rpm, Temperature is 37 DEG C ± 0.5 DEG C, takes dissolution fluid in different time points respectively and filters, and takes filtrate and adds sodium hydroxide solution, described hydrogen The concentration of sodium hydroxide solution is 0.1mol/L~0.5mol/L, and taken filtrate is 1:0.1-with the volume ratio of sodium hydroxide solution 0.14, shake up, be the need testing solution a of each time point;
(2) preparation of esomeprazole magnesium solution b
Take esomeprazole magnesium enteric coated preparation, finely ground, weigh finely ground esomeprazole magnesium enteric coated preparation powder and add hydrogen Sodium hydroxide solution, ultrasonic, add ethanol, continue ultrasonic, quantitatively dilute with sodium hydroxide solution, obtain solution I, filter, obtain filtrate I, take filtrate I and quantitatively dilute with described dissolution medium, obtain solution II;Solution II is placed in 37 DEG C ± 0.5 DEG C water-bath, respectively at Different time points sampling filtering, obtains the filtrate II of each time point, takes filtrate II and adds sodium hydroxide solution, taken filtrate II and hydrogen The volume ratio of sodium hydroxide solution is 1:0.1-0.14, shakes up, and is the esomeprazole magnesium solution b of described each time point;Institute The concentration stating sodium hydroxide solution is 0.01mol/L~1.0mol/L;
(3) preparation of reference substance solution
Take omeprazole reference substance, dissolve with ethanol, more quantitatively dilute with dissolution medium, pipette the solution after dilution, add hydrogen Sodium hydroxide solution, shakes up, and is reference substance solution;The concentration of described sodium hydroxide solution is 0.1mol/L~0.5mol/L, institute The volume ratio stating the solution after dilution and sodium hydroxide solution is 1:0.1-0.14;
(4) high performance liquid chromatography detection
Step I: detect need testing solution a and reference substance solution by high performance liquid chromatography, records need testing solution a Main peak peak area AA masterPeak area A with the impurity peaks that relative retention time is 2.7A is miscellaneous;And the peak area of reference substance solution;
Step II: by high performance liquid chromatography, the esomeprazole magnesium solution b of each time point is detected, record each time Point main peak peak area AB masterPeak area A with the impurity peaks that relative retention time is 2.7B is miscellaneous;Set up each time point relative retention time It is the impurity peaks peak area A of 2.7B is miscellaneousValue added and main peak peak area AB masterReduced value between equation of linear regression y=kx+m And its correlation coefficient r, wherein y is the reduced value of main peak peak area, and x is the value added of impurity peaks peak area;
According to the peak area A of the impurity peaks that relative retention time is 2.7 of record in step IA is miscellaneousAnd the linear regression of step II Equation y=kx+m, is calculated the reduced value of the main peak peak area of need testing solution a, adds the main peak peak of record in step I Area AA master, it is calculated the stripping quantity that esomeprazole magnesium is actual, and then obtains dissolution.
The assay method of esomeprazole magnesium enteric coated preparation dissolution the most according to claim 1, it is characterised in that institute Stating esomeprazole magnesium enteric coated preparation is esomeprazole magnesium enteric-coated pellet capsule or esomeprazole magnesium enteric coated tablet.
The assay method of esomeprazole magnesium enteric coated preparation dissolution the most according to claim 1, it is characterised in that institute State phosphate buffered solution or water that dissolution medium is pH5.5-7.0.
4., according to the assay method of the esomeprazole magnesium enteric coated preparation dissolution described in any one of claim 1-3, it is special Levying and be, the chromatographic condition of the high performance liquid chromatography detection described in step (4) is:
Chromatographic column: C18 chromatographic column, specification is 5 μm, 4.6*150mm;Flowing phase: acetonitrile-phosphate buffered solution-water, described second Nitrile, phosphate buffered solution are 33-37:48-52:13-17 with the volume ratio of water, and the pH of described phosphate buffered solution is 7.2- 7.4;Flow velocity: 0.7~0.9mL/min;Sample size: 20 μ L;Column temperature: 25 DEG C~35 DEG C;Detection wavelength: 302nm.
The assay method of esomeprazole magnesium enteric coated preparation dissolution the most according to claim 4, it is characterised in that institute Stating acetonitrile, phosphate buffered solution is 35:50:15 with the volume ratio of water;The pH of described phosphate buffered solution is 7.3, and it is joined Method processed, for taking 1mol/L sodium dihydrogen phosphate 10.5ml and 0.5mol/L disodium phosphate soln 60ml, is diluted with water to 1000ml, shakes up and get final product;Flow velocity: 0.8mL/min;Column temperature: 30 DEG C.
6., according to the assay method of the esomeprazole magnesium enteric coated preparation dissolution described in any one of claim 1-3, it is special Levying and be, in step (1), the esomeprazole magnesium in esomeprazole magnesium enteric coated preparation with the proportioning of dissolution medium is 20mg:900-1000mL;The concentration of described sodium hydroxide solution is 0.25mol/L~0.5mol/L, taken filtrate and hydroxide The volume ratio of sodium solution is 1:0.12.
7., according to the assay method of the esomeprazole magnesium enteric coated preparation dissolution described in any one of claim 1-3, it is special Levying and be, ethanol described in step (2) is 7-8ml:100mg with the proportioning of esomeprazole magnesium enteric coated preparation powder, described The magnesium enteric coated preparation powder 5mg/mL Han esomeprazole in solution I;Taken filtrate I is 1 with the volume ratio of gained solution II: 50。
8., according to the assay method of the esomeprazole magnesium enteric coated preparation dissolution described in any one of claim 1-3, it is special Levying and be, described in step (2), the concentration of sodium hydroxide solution is 0.25mol/L~0.5mol/L, taken filtrate II and hydrogen-oxygen The volume ratio changing sodium solution is 1:0.12.
9., according to the assay method of the esomeprazole magnesium enteric coated preparation dissolution described in any one of claim 1-3, it is special Levying and be, in step (3) described reference substance solution, the content of omeprazole is 20 μ g/ml.
10., according to the assay method of the esomeprazole magnesium enteric coated preparation dissolution described in any one of claim 1-3, it is special Levy and be, in step (4) described equation of linear regression y=kx+m, 1.0≤k≤5.0,20000≤m≤100000, correlation coefficient R is more than 0.995.
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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107561195A (en) * 2017-07-26 2018-01-09 郑州泰丰制药有限公司 The preparation method of reference substance and need testing solution used in a kind of Omeprazole dissolution measure
CN107843668A (en) * 2017-12-05 2018-03-27 上海信谊万象药业股份有限公司 The assay method of drug content in a kind of omeprazole solid preparation
CN107957381A (en) * 2017-12-13 2018-04-24 南京双科医药开发有限公司 A kind of assay method of spirolactone Dissolution of Tablet
CN108469398A (en) * 2018-04-27 2018-08-31 丽珠医药集团股份有限公司 A kind of dissolution determination method of Iprazole pharmaceutical composition
CN111103368A (en) * 2019-12-23 2020-05-05 河北科技大学 Method for predicting validity period of esomeprazole enteric-coated tablet
CN111665337A (en) * 2020-06-30 2020-09-15 北京诺康达医药科技股份有限公司 Rapid detection method for acid resistance of enteric-coated tablets
CN113092614A (en) * 2021-04-01 2021-07-09 海南海力制药有限公司 Omeprazole enteric capsule impurity detection method and consistency evaluation method
CN118311216A (en) * 2024-06-07 2024-07-09 湖南明瑞制药股份有限公司 Rapid determination method for dissolution rate of sodium rabeprazole enteric-coated tablets

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080220441A1 (en) * 2001-05-16 2008-09-11 Birnbaum Eva R Advanced drug development and manufacturing
CN103776933A (en) * 2014-02-11 2014-05-07 润泽制药(苏州)有限公司 Method for determining dissolution rate of rosuvastatin calcium preparation
CN105125517A (en) * 2015-07-16 2015-12-09 广东彼迪药业有限公司 Esomeprazole magnesium enteric pellet capsule and preparation method thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080220441A1 (en) * 2001-05-16 2008-09-11 Birnbaum Eva R Advanced drug development and manufacturing
CN103776933A (en) * 2014-02-11 2014-05-07 润泽制药(苏州)有限公司 Method for determining dissolution rate of rosuvastatin calcium preparation
CN105125517A (en) * 2015-07-16 2015-12-09 广东彼迪药业有限公司 Esomeprazole magnesium enteric pellet capsule and preparation method thereof

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
SYED NAEEM RAZZAQ等: "DEVELOPMENT AND VALIDATION OF LIQUID CHROMATOGRAPHIC METHOD FOR NAPROXEN AND ESOMEPRAZOLE IN BINARY COMBINATION", 《J. CHIL. CHEM. SOC.》 *
张闪闪等: "埃索美拉唑镁肠溶微丸片的制备及质量控制", 《中国新药杂志》 *
李婷婷等: "RP-HPLC法测定埃索美拉唑钠的有关物质", 《药物分析杂志》 *
蔡垠等: "阿托伐他汀钙片溶出度研究", 《中国药物警戒》 *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107561195A (en) * 2017-07-26 2018-01-09 郑州泰丰制药有限公司 The preparation method of reference substance and need testing solution used in a kind of Omeprazole dissolution measure
CN107843668A (en) * 2017-12-05 2018-03-27 上海信谊万象药业股份有限公司 The assay method of drug content in a kind of omeprazole solid preparation
CN107957381A (en) * 2017-12-13 2018-04-24 南京双科医药开发有限公司 A kind of assay method of spirolactone Dissolution of Tablet
CN108469398A (en) * 2018-04-27 2018-08-31 丽珠医药集团股份有限公司 A kind of dissolution determination method of Iprazole pharmaceutical composition
CN111103368A (en) * 2019-12-23 2020-05-05 河北科技大学 Method for predicting validity period of esomeprazole enteric-coated tablet
CN111665337A (en) * 2020-06-30 2020-09-15 北京诺康达医药科技股份有限公司 Rapid detection method for acid resistance of enteric-coated tablets
CN111665337B (en) * 2020-06-30 2021-08-03 北京诺康达医药科技股份有限公司 Rapid detection method for acid resistance of enteric-coated tablets
CN113092614A (en) * 2021-04-01 2021-07-09 海南海力制药有限公司 Omeprazole enteric capsule impurity detection method and consistency evaluation method
CN113092614B (en) * 2021-04-01 2022-12-13 海南海力制药有限公司 Omeprazole enteric capsule impurity detection method and consistency evaluation method
CN118311216A (en) * 2024-06-07 2024-07-09 湖南明瑞制药股份有限公司 Rapid determination method for dissolution rate of sodium rabeprazole enteric-coated tablets

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