CN110286162A - A kind of measuring method of the pharmaceutical preparation dissolution rate containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate - Google Patents
A kind of measuring method of the pharmaceutical preparation dissolution rate containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate Download PDFInfo
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- CN110286162A CN110286162A CN201910353138.2A CN201910353138A CN110286162A CN 110286162 A CN110286162 A CN 110286162A CN 201910353138 A CN201910353138 A CN 201910353138A CN 110286162 A CN110286162 A CN 110286162A
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- dissolution
- pharmaceutical preparation
- paracetamol
- dextromethorphan hydrobromide
- doxylamine succinate
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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
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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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/027—Liquid chromatography
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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
- G01N2030/062—Preparation extracting sample from raw material
Abstract
The invention discloses a kind of measuring methods of pharmaceutical preparation dissolution rate containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate, steps are as follows: (1) will be added in dissolution medium containing the pharmaceutical preparation of paracetamol, dextromethorphan hydrobromide and doxylamine succinate and carry out dissolution processing, sampling filtering obtains dissolution fluid；(2) content of paracetamol, dextromethorphan hydrobromide and doxylamine succinate in the dissolution fluid is detected；(3) dissolution rate of the pharmaceutical preparation is determined according to the testing result of step (2).The present invention can effectively simulate intracorporal dissolved corrosion in vitro, determine the dissolution rate of the soft capsule containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate, provide technical support for the research and development and quality control of drug.The present invention can measure simultaneously the dissolution of three kinds of substances as a result, detection time and testing cost is greatly saved under identical conditions, accuracy and favorable reproducibility.
Description
Technical field
The present invention relates to pharmaceutical technology fields, more particularly to one kind to contain paracetamol, dextromethorphan hydrobromide and amber
The measuring method of the pharmaceutical preparation dissolution rate of amber acid doxylamine.
Background technique
For flu as a kind of common respiratory disease, the symptom showed is main are as follows: headache, fever, cough, nasal obstruction,
Rhinorrhea, allergy etc..It include: analgesic-antipyretic (paracetamol), antitussive commonly used in treating the drug of these symptoms
(dextromethorphan hydrobromide), antihistamine (doxylamine succinate).
Soft capsule containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate is a kind of using gelatin system
At compound oral solid pharmaceutical preparation, preparation method is as described in Chinese patent 201310359375.2, at present for the product
Research still has much room for improvement.In the prior art there are no can dissolved corrosion effectively in analogue body, determine and contain paracetamol, hydrogen
The method of the soft capsule dissolution rate of bromic acid dextromethorphan and doxylamine succinate.
Summary of the invention
To solve above-mentioned shortcoming and defect existing in the prior art, the purpose of the present invention is to provide one kind can be effective
The external of dissolved corrosion determines the flexible glue containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate in analogue body
The method of capsule dissolution rate.
To realize its purpose, the technical scheme adopted by the invention is as follows:
A kind of survey of the pharmaceutical preparation dissolution rate containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Determine method comprising following steps:
(1) it will be added and dissolve out containing the pharmaceutical preparation of paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Dissolution processing is carried out in medium, sampling filtering obtains dissolution fluid；
(2) content of paracetamol, dextromethorphan hydrobromide and doxylamine succinate in the dissolution fluid is detected；
(3) dissolution rate of the pharmaceutical preparation is determined according to the testing result of step (2).
Preferably, the dissolution medium is purified water.Inventor is found through experiments that, using purified water as dissolution medium,
Paracetamol, dextromethorphan hydrobromide and the doxylamine succinate in pharmaceutical preparation, Er Qiechun can not only effectively be dissolved out
Change water to be easy to get, use cost is low.
Preferably, the revolving speed of the process in leaching is 100rpm/min.Inventor is found through experiments that revolving speed is
Under conditions of 100rpm/min, the pharmaceutical preparation containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Result of extraction is preferable, and the precision of dissolution determination result can be improved.
Preferably, the time point of sampling is 45min.Each ingredient (paracetamol, dextromethorphan hydrobromide when 45min
And doxylamine succinate) dissolution reach balance.Therefore, using 45min as sampling time point, drug can more reasonably be reacted
Dissolved corrosion.
Preferably, in the step (2), using high performance liquid chromatography detect paracetamol in the dissolution fluid,
The content of dextromethorphan hydrobromide and doxylamine succinate.
Preferably, the chromatographic condition of the high performance liquid chromatography includes:
Chromatographic column: C18,4.6mm × 150mm, 5 μm；
Mobile phase A: the aqueous solution of potassium dihydrogen phosphate and the mixed solution of methanol；
Mobile phase B: acetonitrile；
Flow velocity: 1.0mL/min；
Sampling volume: 30 μ L；
Detection wavelength: 275nm；
Using gradient elution, elution program is as follows, and wherein mobile phase ratio is percent by volume:
| Time | Mobile phase A | Mobile phase B |
| 0min | 100% | 0% |
| 4min | 100% | 0% |
| 25min | 70% | 30% |
| 26min | 100% | 0% |
| 30min | 100% | 0% |
Preferably, in the mobile phase A, the concentration of the aqueous solution of potassium dihydrogen phosphate is 0.05M, and pH value is 3.5 ± 0.2；
Preferably, in the mobile phase A, the aqueous solution of potassium dihydrogen phosphate and the volume ratio of methanol are 88:12~92:8.
It will be appreciated by those skilled in the art that the composition of the type of the chromatographic condition of HPLC, especially chromatographic column, mobile phase
And flow velocity can all significantly affect HPLC method and determine that how western paracetamol in dissolution fluid, dextromethorphan hydrobromide and succinic acid be
The accuracy of stretching-sensitive content.Inventor is found through experiments that, using above-mentioned HPLC condition, can accurately be based on HPLC map
The peak area of middle paracetamol, dextromethorphan hydrobromide and doxylamine succinate determines containing for each ingredient in dissolution fluid
Amount, and there is preferable precision.Meanwhile inventor also found, it, may can not be effectively when using other HPLC conditions
The characteristic peak for acquiring paracetamol, dextromethorphan hydrobromide and doxylamine succinate simultaneously, thus can not accurate ground
The peak area of paracetamol, dextromethorphan hydrobromide and doxylamine succinate determines right in dissolution fluid in HPLC map
The content of Paracetamol, dextromethorphan hydrobromide and doxylamine succinate.In addition, inventor also found, by using upper
State the peak area of HPLC condition paracetamol obtained, dextromethorphan hydrobromide and doxylamine succinate and to acetyl
There are apparent lines in biggish content range between amino phenols, dextromethorphan hydrobromide and the content of doxylamine succinate
Sexual intercourse.
Preferably, the calculation formula of the dissolution rate of the pharmaceutical preparation is as follows:
AsplIndicate the peak area of some determinand in sample map；
AstdIndicate the peak area of some determinand in control map；
CstdIndicate the concentration of some determinand control；
VsplIndicate the extension rate of sample；
LC indicates the mark amount of some determinand.
Inventors discovered through research that each substance (paracetamol, dextromethorphan hydrobromide and the more hilas of succinic acid
It is quick) all there is apparent linear relationship in biggish content range, it can be calculated within the scope of a certain concentration using above-mentioned formula
All dissolution values.
Preferably, the pharmaceutical preparation is soft capsule.
Further, when the soft capsule shell of gelatin substrate crosslinks, and leads to not dissolution, need to add in dissolution medium
Add the enzyme of gelatin hydrolysate.Preferably, the enzyme is pancreatin.In this way, the interference of gelatin crosslinking can be eliminated, pharmaceutical preparation sheet is reacted
The dissolution situation of body, while simulating the intracorporal dissolved corrosion of human body.
The invention has the benefit that measuring method of the invention can effectively simulate the intracorporal dissolution row of human body in vitro
To determine the dissolution rate of the soft capsule containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate, being drug
Research and development and quality control provide technical support.The present invention can measure simultaneously three kinds of substance (i.e. acetparaminosalol under identical conditions
Phenol, dextromethorphan hydrobromide and doxylamine succinate) dissolution as a result, detection time and testing cost is greatly saved, it is quasi-
True property and favorable reproducibility.
Detailed description of the invention
Fig. 1 is soft capsule dissolution of the present invention containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate
The flow diagram of the measuring method of degree；
Fig. 2 is in experimental example 1 of the present invention containing the soft of paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Dissolution curve (doxylamine succinate) of the capsule in different dissolution mediums；
Fig. 3 is in experimental example 1 of the present invention containing the soft of paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Dissolution curve (paracetamol) of the capsule in different dissolution mediums；
Fig. 4 is in experimental example 1 of the present invention containing the soft of paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Dissolution curve (dextromethorphan hydrobromide) of the capsule in different dissolution mediums；
Fig. 5 is in experimental example 2 of the present invention containing the soft of paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Dissolution curve (doxylamine succinate) of the capsule under different rotating speeds；
Fig. 6 is in experimental example 2 of the present invention containing the soft of paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Dissolution curve (paracetamol) of the capsule under different rotating speeds；
Fig. 7 is in experimental example 2 of the present invention containing the soft of paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Dissolution curve (dextromethorphan hydrobromide) of the capsule under different rotating speeds；
Fig. 8 is the HPLC spectrogram of blank control in experimental example 4 of the present invention；
Fig. 9 is in experimental example 4 of the present invention containing the soft of paracetamol, dextromethorphan hydrobromide and doxylamine succinate
The HPLC spectrogram of capsule dissolution contrast solution；
Figure 10 is in experimental example 4 of the present invention containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate
The HPLC spectrogram of soft capsule dissolution sample solution.
Specific embodiment
To better illustrate the object, technical solutions and advantages of the present invention, the present invention passes through the following example furtherly
It is bright.It should be understood that the embodiment of the present invention is merely to illustrate technical effect of the invention, protection model and is not intended to limit the present invention
It encloses.In embodiment, method therefor is conventional method unless otherwise instructed.Meanwhile in embodiment, material used, reagent
Deng being commercially available unless otherwise specified.
The embodiment of the invention provides a kind of containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate
The measuring method of soft capsule dissolution rate.Below with reference to Fig. 1, measuring method of the invention is described in detail comprising as follows
Step:
One, dissolution is handled
Using dissolution medium to the flexible glue to be measured containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Capsule carries out dissolution processing, to obtain dissolution fluid.In the embodiment of the present invention, the dissolution medium is purified water.Inventor is by real
Verifying, purified water can effectively make three ingredients (paracetamol, dextromethorphan hydrobromide and ambers in soft capsule
Sour doxylamine) dissolution.
In the embodiment of the present invention, dissolution processing can be carried out using conventional medicament dissolution instrument.The present invention is sent out in experiment
Existing, capsule solution sticks stripping rotor bottom, occasionally there is floating, so the embodiment of the present invention selects basket method to carry out, thus, it is possible to further mention
The accuracy and reproducibility of height dissolution measurement.
Inventor passes through experimental verification, containing the soft of paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Result of extraction of capsule under the conditions of 100rpm/min is more preferably.Thus, the present invention selects 100 rpm/min as process in leaching
Revolving speed, to improve the precision of dissolution results.
Inventor has also carried out curve determination, and when 45min is arrived in discovery, the dissolution of each ingredient can be only achieved dissolution balance, institute
To select 45min as the sample point of dissolving-out method, more reasonably to react dissolved corrosion.
Two, each component content is detected
After obtaining the dissolution fluid containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate,
The content of paracetamol, dextromethorphan hydrobromide and doxylamine succinate in the solution is detected in the step.This field
Technical staff is, it is understood that term " paracetamol, dextromethorphan hydrobromide and succinic acid used in herein
The content of doxylamine " shall be understood in a broad sense, either the right U.S. of paracetamol, hydrobromic acid is husky in obtained dissolution fluid
Fragrant and doxylamine succinate Specific amounts, is also possible to that any there are the parameters of correlation, such as HPLC inspection with the Specific amounts
Corresponding characteristic peak or its area etc. in map obtained by surveying.
Preferably, the present invention detects paracetamol, hydrogen in the dissolution fluid using high performance liquid chromatography (HPLC)
The content of bromic acid dextromethorphan and doxylamine succinate.
Further, the chromatographic condition of the HPLC includes:
Chromatographic column: C18,4.6mm × 150mm, 5 μm；
Mobile phase A: the mixed solution of potassium dihydrogen phosphate aqueous solution and methanol；The concentration of potassium dihydrogen phosphate aqueous solution is
0.05M, pH value are 3.5 ± 0.2；The volume ratio of potassium dihydrogen phosphate aqueous solution and methanol is 88:12~92:8；
Mobile phase B: acetonitrile；
Flow velocity: 1.0mL/min；
Sampling volume: 30 μ L；
Detection wavelength: 275nm；
Using gradient elution, elution program is as follows, and wherein mobile phase ratio is percent by volume:
| Time | Mobile phase A | Mobile phase B |
| 0min | 100% | 0% |
| 4min | 100% | 0% |
| 25min | 70% | 30% |
| 26min | 100% | 0% |
| 30min | 100% | 0% |
Inventor is found through experiments that, using above-mentioned HPLC condition, can accurately be based in HPLC map to acetyl ammonia
The peak area of base phenol, dextromethorphan hydrobromide and doxylamine succinate determines the content of each ingredient in dissolution fluid, and has
Preferable precision.In addition, inventor also found, when using other HPLC conditions, may effectively can not acquire simultaneously
Paracetamol, dextromethorphan hydrobromide and doxylamine succinate characteristic peak, so that HPLC map can not be accurately based on
Middle paracetamol, dextromethorphan hydrobromide and doxylamine succinate peak area determine paracetamol in dissolution fluid,
The content of dextromethorphan hydrobromide and doxylamine succinate.By using above-mentioned HPLC condition acetparaminosalol obtained
Peak area and paracetamol, the dextromethorphan hydrobromide and amber of phenol, dextromethorphan hydrobromide and doxylamine succinate
There are apparent linear relationships in biggish content range between the content of sour doxylamine.
Three, dissolution rate is determined
The content of paracetamol, dextromethorphan hydrobromide and doxylamine succinate in the dissolution fluid obtained by determining
Afterwards, it is based further on obtained paracetamol, dextromethorphan hydrobromide and doxylamine succinate in this step
Content determines the dissolution rate of the soft capsule to be measured containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate.This
Field technical staff, it is understood that herein used in term " containing paracetamol, dextromethorphan hydrobromide and
The dissolution rate of the soft capsule of doxylamine succinate " refers to how western containing paracetamol, dextromethorphan hydrobromide and succinic acid
Active constituent, that is, paracetamol, dextromethorphan hydrobromide and doxylamine succinate in the soft capsule of stretching-sensitive, three's is molten
Out-degree.
The soft capsule to be measured containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate is determined by following formula
Dissolution rate:
AsplIndicate the peak area of some determinand in sample map；
AstdIndicate the peak area of some determinand in control map；
CstdIndicate the concentration of some determinand control；
VsplIndicate the extension rate of sample；
LC indicates the mark amount of some determinand.
Experimental example
Experimental method:
The dissolution determination side of soft capsule containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Method comprising following steps:
(a) dissolution medium is placed in water-bath, is preheating to 41 DEG C, vacuum filtration degassing 10min；
(b) the dissolution medium 900mL after degassing is added in stripping rotor, constant temperature is to 37 DEG C；
(c) soft capsule containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate is put into dissolution
In cup；
(d) digestion instrument is run, revolving speed is set as 100rpm/min, in 45min, takes dissolution fluid 10mL, filters, takes continuous filter
Liquid is as dissolution fluid；
(e) using paracetamol, dextromethorphan hydrobromide and doxylamine succinate in HPLC method measurement dissolution fluid
Content；Chromatographic condition includes:
Chromatographic column: C18,4.6mm × 150mm, 5 μm；
Mobile phase A: the mixed solution of potassium dihydrogen phosphate aqueous solution and methanol；The concentration of potassium dihydrogen phosphate aqueous solution is
0.05M, pH value 3.5；The volume ratio of potassium dihydrogen phosphate aqueous solution and methanol is 90:10；
Mobile phase B: acetonitrile；
Flow velocity: 1.0mL/min；
Sampling volume: 30 μ L；
Detection wavelength: 275nm；
Using gradient elution, elution program is as follows, and wherein mobile phase ratio is percent by volume:
| Time | Mobile phase A | Mobile phase B |
| 0min | 100% | 0% |
| 4min | 100% | 0% |
| 25min | 70% | 30% |
| 26min | 100% | 0% |
| 30min | 100% | 0% |
(f) soft capsule containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate is calculated according to the following formula
Dissolution rate:
AsplIndicate the peak area of some determinand in sample map；
AstdIndicate the peak area of some determinand in control map；
CstdIndicate the concentration of some determinand control；
VsplIndicate the extension rate of sample；
LC indicates the mark amount of some determinand.
Experimental example 1:
In this experimental example, a variety of dissolution mediums are compared, determine optimal dissolution medium.Specifically, respectively with pure
Change the phosphate buffer of water, 0.1N HCl solution, the acetate buffer of pH=4.5 and pH=6.8 as dissolution medium, according to
Above-mentioned experimental method operates with different dissolution medium measurements containing paracetamol, dextromethorphan hydrobromide and succinic acid
The dissolution rate of the soft capsule of doxylamine, as a result as shown in Fig. 2~4 and table 1~4.
1 dissolution medium of table is the dissolution rate of purified water
2 dissolution medium of table is the dissolution rate of 0.1N HCl solution
3 dissolution medium of table is the dissolution rate of pH=4.5 acetate buffer
4 dissolution medium of table is the dissolution rate of pH=6.8 phosphate buffer
It can be seen that from said determination result, containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Result of extraction of the soft capsule in purified water is best, and purified water most easily obtains, and use cost is low.Thus, the present invention selects pure
Change water as dissolution medium, to improve conventional efficient and save experimental cost.
Experimental example 2:
In this experimental example, different rotating speeds are compared, determine optimal revolving speed.According to the operation of above-mentioned experimental method
Contain paracetamol, dextromethorphan hydrobromide and amber using different revolving speed (50rpm/min and 100rpm/min) measurements
The dissolution rate of the soft capsule of sour doxylamine, as a result as shown in Fig. 5~7 and table 5~6.
5 revolving speed of table is the dissolution rate of 50rpm/min
6 revolving speed of table is the dissolution rate of 100rpm/min
It can be seen that from said determination result, containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Result of extraction of soft capsule under the conditions of 100rpm/min is more preferable.
Experimental example 3:
This experimental example determines the solubility of paracetamol and dextromethorphan hydrobromide, to select suitable dissolution to be situated between
Plastid product.
Measurement result: the solubility of paracetamol in water is about 16.4mg/mL, and dextromethorphan hydrobromide is in water
Solubility be about 21.7mg/mL.In conjunction with the dissolution side containing paracetamol and Suppress in table 7
Method, volume of the final choice 900mL of the present invention as dissolving-out method.
The related preparations dissolving-out method enumerated in 7 United States Pharmacopeia of table and Chinese Pharmacopoeia
Experimental example 4:
This experimental example demonstrates the feasibility of chromatographic condition used in the present invention.Specifically, this experimental example is in dissolution medium
Purified water, dissolution volume is 900mL, under conditions of revolving speed is 100rpm/min, using the chromatographic condition point of above-mentioned experimental method
Blank control, the reference substance of three ingredients and to be measured containing paracetamol, dextromethorphan hydrobromide and succinic acid are not determined
The HPLC separating effect of the soft capsule dissolution sample solution of doxylamine, as a result as shown in figs. 8-10.
It can be seen that from Fig. 8~10, the three principal component peaks collected using HPLC condition of the invention are not had nearby
Other Interference Peaks, separating degree are good.
Experimental example 5:
This experimental example determined three kinds of " paracetamol ", " dextromethorphan hydrobromide " and " doxylamine succinate " at
The range of linearity divided, the results are shown in Table 8.
Table 8
| Ingredient | The range of linearity | Standard curve | R2 |
| Doxylamine succinate | 3.44~11.01 μ g/mL | Y=204904.03x-58310.26 | 1.00 |
| Paracetamol | 178.87~572.39 μ g/mL | Y=422917.33x+1846342.95 | 1.00 |
| Dextromethorphan hydrobromide | 7.94~25.41 μ g/mL | Y=153113.77x-19493.34 | 1.00 |
Experimental example 6:
This experimental example is measured in parallel 6 containing paracetamol, the right U.S. sand of hydrobromic acid according to the description of above-mentioned experimental method
Dissolution rate of fragrant and doxylamine succinate the soft capsule in 45min, the results are shown in Table 9.
Table 9
Paracetamol, dextromethorphan hydrobromide are contained using HPLC condition measurement of the invention it can be seen from upper table 9
There is preferable precision with the dissolution results of the soft capsule of doxylamine succinate.
Experimental example 7:
This experimental example demonstrates the soft capsule containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate
The stability of dissolution fluid, dissolution rate when measuring 2 days respectively according to the description of above-mentioned experimental method, the results are shown in Table 10.
Table 10
What is obtained in the process of the present invention it can be seen from upper table 10 contains paracetamol, dextromethorphan hydrobromide and amber
The dissolution fluid of the soft capsule of amber acid doxylamine has preferable stability.
Experimental example 8:
This experimental example verifies the accuracy of HPLC method of the present invention by recovery experiment.Three levels are selected to be respectively
50%, 100%, 160% each ingredient solution and blank control measure each ingredient according to the description of above-mentioned experimental method respectively
The rate of recovery, as a result as shown in the following table 11~13.
The rate of recovery result of 11 doxylamine succinate of table
The rate of recovery result of 12 paracetamol of table
The rate of recovery result of 13 dextromethorphan hydrobromide of table
It can be seen that from above-mentioned table 11~13, it can be accurately based on right in HPLC map using HPLC condition of the invention
The peak area of Paracetamol, dextromethorphan hydrobromide and doxylamine succinate determines the content of each ingredient in dissolution fluid.
Experimental example 9:
This experimental example passes through the durability of experimental verification HPLC method of the present invention.Selection end value is studied, with determination side
The durable range of method, as a result as shown in the following table 14~21.
Table 14 adjusts the result of study when pH to 3.3 of potassium dihydrogen phosphate aqueous solution in mobile phase A
Table 15 adjusts the result of study when pH to 3.7 of potassium dihydrogen phosphate aqueous solution in mobile phase A
Table 16 adjusts the result of study when pH to 3.0 of potassium dihydrogen phosphate aqueous solution in mobile phase A
Table 17 adjusts the result of study when pH to 4.0 of potassium dihydrogen phosphate aqueous solution in mobile phase A
Table 18 adjusts the result of study when percent by volume of methanol in mobile phase A is 8%
Table 19 adjusts the result of study when percent by volume of methanol in mobile phase A is 12%
Table 20 adjusts the result of study when percent by volume of methanol in mobile phase A is 5%
Table 21 adjusts the result of study when percent by volume of methanol in mobile phase A is 15%
It can be seen that from above-mentioned table 14~21, using HPLC condition and range of the invention, can obtain more reliable to acetyl
The content of amino phenols, dextromethorphan hydrobromide and doxylamine succinate.
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than protects to the present invention
The limitation of range is protected, although the invention is described in detail with reference to the preferred embodiments, those skilled in the art should
Understand, it can be with modification or equivalent replacement of the technical solution of the present invention are made, without departing from the essence of technical solution of the present invention
And range.
Claims (10)
1. a kind of measurement of the pharmaceutical preparation dissolution rate containing paracetamol, dextromethorphan hydrobromide and doxylamine succinate
Method, which comprises the steps of:
(1) dissolution medium will be added containing the pharmaceutical preparation of paracetamol, dextromethorphan hydrobromide and doxylamine succinate
In carry out dissolution processing, sampling filtering obtains dissolution fluid；
(2) content of paracetamol, dextromethorphan hydrobromide and doxylamine succinate in the dissolution fluid is detected；
(3) dissolution rate of the pharmaceutical preparation is determined according to the testing result of step (2).
2. the measuring method of pharmaceutical preparation dissolution rate as described in claim 1, which is characterized in that the dissolution medium is purifying
Water.
3. the measuring method of pharmaceutical preparation dissolution rate as described in claim 1, which is characterized in that the revolving speed of the process in leaching
For 100rpm/min.
4. the measuring method of pharmaceutical preparation dissolution rate as claimed in claim 3, which is characterized in that the time point of the sampling is
45min。
5. the measuring method of pharmaceutical preparation dissolution rate as described in claim 1, which is characterized in that in the step (2), use
High performance liquid chromatography detects containing for paracetamol in the dissolution fluid, dextromethorphan hydrobromide and doxylamine succinate
Amount.
6. the measuring method of the pharmaceutical preparation dissolution rate as described in power hydrochloric acid benefit requires 5, which is characterized in that the high-efficient liquid phase color
The chromatographic condition of spectrometry includes:
Chromatographic column: C18,4.6mm × 150mm, 5 μm；
Mobile phase A: the aqueous solution of potassium dihydrogen phosphate and the mixed solution of methanol；
Mobile phase B: acetonitrile；
Flow velocity: 1.0mL/min；
Sampling volume: 30 μ L；
Detection wavelength: 275nm；
Using gradient elution, elution program is as follows, and wherein mobile phase ratio is percent by volume:
Preferably, in the mobile phase A, the concentration of the aqueous solution of potassium dihydrogen phosphate is 0.05M, and pH value is 3.5 ± 0.2；
Preferably, in the mobile phase A, the aqueous solution of potassium dihydrogen phosphate and the volume ratio of methanol are 88:12~92:8.
7. the measuring method of pharmaceutical preparation dissolution rate as described in claim 1, which is characterized in that the dissolution of the pharmaceutical preparation
The calculation formula of degree are as follows:
In formula,
AsplIndicate the peak area of some determinand in sample map；
AstdIndicate the peak area of some determinand in control map；
CstdIndicate the concentration of some determinand control；
VsplIndicate the extension rate of sample；
LC indicates the mark amount of some determinand.
8. the measuring method of pharmaceutical preparation dissolution rate as described in claim 1, which is characterized in that the pharmaceutical preparation is flexible glue
Wafer.
9. the measuring method of pharmaceutical preparation dissolution rate as claimed in claim 8, which is characterized in that when the soft capsule of gelatin substrate
Shell crosslinks, and when leading to not dissolution, the enzyme of gelatin hydrolysate need to be added in dissolution medium.
10. the measuring method of pharmaceutical preparation dissolution rate as claimed in claim 9, which is characterized in that the enzyme is pancreatin.
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