CN109580842B - Method for measuring dissolution rate of compound cholamine tablets - Google Patents
Method for measuring dissolution rate of compound cholamine tablets Download PDFInfo
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- CN109580842B CN109580842B CN201910043622.5A CN201910043622A CN109580842B CN 109580842 B CN109580842 B CN 109580842B CN 201910043622 A CN201910043622 A CN 201910043622A CN 109580842 B CN109580842 B CN 109580842B
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- G—PHYSICS
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Abstract
The invention relates to a method for measuring dissolution rate of a compound cholamine tablet, which comprises the following steps: preparing a solution of a reference substance; preparing a dissolving sample solution of the compound cholamine tablet by using a dissolving medium solution; measuring the control solution by liquid chromatography to obtain chromatogram peak-retention time chart of the control solution; and (3) determining the dissolved sample solution by liquid chromatography to obtain a liquid chromatogram of the dissolved sample solution, comparing the liquid chromatogram of the dissolved sample solution with the liquid chromatogram of the reference solution, and calculating to obtain the dissolution concentration of the compound choline chloride tablet. The determination method provided by the inventor is simple and easy to implement, requires short determination time, can accurately and quantitatively analyze the dissolution rate of the compound cholamine tablet, has very accurate result, accords with the development trend of a drug dissolution rate determination technology, and has strong popularization in the industry.
Description
Technical Field
The invention relates to a determination method, in particular to a determination method of dissolution rate of a compound cholamine tablet.
Background
The compound bile ammonia tablet is a nationwide exclusive variety independently developed by Wuhan biochemical pharmacy Co., Ltd, and is mainly designed aiming at the pathological characteristics of bronchitis, bronchial asthma, emphysema and pulmonary heart disease. The main components are as follows: ephedrine hydrochloride, aminophylline, sodium cholate, promethazine hydrochloride, and chlordiazepoxide
Wherein aminophylline has the functions of relaxing respiratory smooth muscle, dilating bronchus, and improving respiratory function; the sodium cholate has good effects of relieving cough and asthma, expanding bronchus and relieving the stimulation of aminophylline to intestinal tracts, and has scientific formula, reasonable compatibility, sufficient basis, unique curative effect and better effect of relieving cough and asthma.
Dissolution rate, also referred to as dissolution rate, refers to the rate and extent of dissolution of a drug from a solid dosage form such as a tablet, capsule, or granule, in a predetermined solvent and under predetermined conditions. Dissolution testing is an in vitro test method that simulates the disintegration and dissolution of an oral solid formulation in the gastrointestinal tract. The drug dissolution inspection is an effective means for evaluating the quality and the process level of the preparation, can reflect the differences of the crystal form, the granularity, the prescription composition, the variety and the property of auxiliary materials, the production process and the like of the main drug to a certain extent, and is also an effective standard for evaluating the bioavailability of active ingredients of the preparation and the uniformity of the preparation, thereby being one of the indispensable items for controlling the quality of the medicine. The existing compound cholamine tablet detection method has a quality standard, and no regulation is made on the drug dissolution rate inspection. Therefore, the new determination method has great significance in determining the dissolution rate of the compound cholamine tablets.
Disclosure of Invention
Aiming at the problems in the existing dissolution rate detection of the compound cholamine tablet, the method for determining the dissolution rate of the compound cholamine tablet is simple, convenient and feasible, accurate in result, short in determination time and strong in popularization.
The specific technical scheme is as follows:
a method for measuring dissolution rate of compound cholamine tablets is characterized by comprising the following steps:
step one, preparing a solution of a reference substance;
preparing a dissolving sample solution of the compound cholamine tablet by using a dissolving medium solution;
step three, measuring the reference substance solution prepared in the step one by liquid chromatography to obtain a chromatogram peak-retention time chart of the reference substance solution;
step four, measuring the dissolved sample solution prepared in the step two through a liquid chromatography to obtain a liquid chromatogram of the dissolved sample solution, and comparing the liquid chromatogram of the dissolved sample solution with the liquid chromatogram of the reference solution;
wherein, in the liquid chromatography, the mobile phase A is acetonitrile, the mobile phase B is phosphate buffer solution with pH value of 3.0, and the linear gradient elution conditions are as follows: 0-8min, 20% A, 80% B; 8-10min, 20-55% of A and 80-45% of B; 10-20min, 55% A, 45% B; 20-25min, 55-20% of A and 45-80% of B; 25-30min, 20% A and 80% B.
The above-mentioned determination method is also characterized in that the reference substances in the first step are aminophylline, ephedrine hydrochloride and chlordiazepoxide
And promethazine hydrochloride.
The above-mentioned measuring method is also characterized in that the preparation method of the solution of the reference substance in the first step is: respectively weighing reference substances, adding methanol to dissolve, adding methanol into a volumetric flask, and fixing the volume to prepare reference substance solutions with the concentrations of 50 mug/mL, 15 mug/mL, 5 mug/mL and 6 mug/mL respectively.
The above-mentioned measuring method is further characterized in that the dissolution medium solution in the second step is a phosphate buffer solution having a pH of 6.0.
The above-mentioned measuring method is also characterized in that the preparation method of the dissolution medium solution in the second step is: taking 27.22g of monopotassium phosphate, dissolving the monopotassium phosphate with water, and fixing the volume to 1000mL to obtain 0.2mol/L potassium dihydrogen phosphate solution; 8g of sodium hydroxide is taken, dissolved by water and added to 1000mL to obtain 0.2mol/L sodium hydroxide solution. Weighing 250mL of 0.2mol/L potassium dihydrogen phosphate solution, mixing with 28mL of 0.2mol/L sodium hydroxide solution, adding water to a constant volume of 1000mL, shaking up, and adding 0.03g of sodium dodecyl sulfate into each 100mL to obtain the sodium dodecyl sulfate.
The above-mentioned measuring method is also characterized in that the preparation method of the dissolution sample solution in the second step is: putting the compound cholamine tablet into 900mL of phosphate buffer solution, carrying out sample treatment by adopting a general rule-dissolution method (slurry method) of Chinese pharmacopoeia, and filtering 10mL of solution after the treatment to obtain filtrate, namely the dissolution sample solution.
Specifically, in the present invention, when the sample is processed by referring to the general rule of Chinese pharmacopoeia-dissolution testing method (slurry method), the stirring speed of the stirrer is 75 revolutions per minute, and the stirring processing time is 60 minutes.
The above-mentioned measuring method is also characterized in that the flow rate in the liquid chromatography of step three and step four is 1 mL/min.
The above-mentioned measuring method is also characterized in that the detection wavelength in the liquid chromatography of step three and step four is 254 nm.
The beneficial effect of above-mentioned scheme is:
the determination method provided by the inventor is simple and easy to implement, requires short determination time, can accurately and quantitatively analyze the dissolution rate of the compound cholamine tablet, has very accurate result, accords with the development trend of a drug dissolution rate determination technology, and has strong popularization in the industry.
Drawings
FIG. 1 is a chromatogram peak-retention time comparison of a solution of a control in accordance with the present invention.
FIG. 2 is a chromatogram of the compound bile-ammonia tablet in example 1 of the present invention;
fig. 3 is a chromatogram of the compound bile-ammonia tablet in example 2 of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It should be noted that the embodiments and features of the embodiments may be combined with each other without conflict.
The invention is further described with reference to the following drawings and specific examples, which are not intended to be limiting.
The determination method provided by the invention comprises the following steps:
step one, preparing a solution of a reference substance;
preparing a dissolving sample solution of the compound cholamine tablet by using a dissolving medium solution;
step three, measuring the reference substance solution prepared in the step one by liquid chromatography to obtain a chromatogram peak-retention time chart of the reference substance solution;
step four, determining the dissolved sample solution prepared in the step two through a liquid chromatography to obtain a liquid chromatogram of the dissolved sample solution, comparing the liquid chromatogram of the dissolved sample solution with a liquid chromatogram of a reference solution, and calculating to obtain the dissolved concentration of the compound cholamine tablet;
wherein, in the liquid chromatography, the liquid chromatograph is WATERS company e2695-2489, the chromatographic column is a Damma ODS ser #3149160 (filler is octadecylsilane chemically bonded silica, 250mm × 4.6mm, 5 μm), the mobile phase A is acetonitrile, the mobile phase B is phosphate buffer solution with pH 3.0, and the linear gradient elution conditions are as follows: 0-8min, 20% A, 80% B; 8-10min, 20-55% of A and 80-45% of B; 10-20min, 55% A, 45% B; 20-25min, 55-20% of A and 45-80% of B; 25-30min, 20% A, 80% B, detection wavelength of 254nm, sample injection volume of 20 μ L, and flow rate of 1 mL/min;
wherein, the preparation method of the solution of the reference substance in the step one comprises the following steps: respectively weighing aminophylline, ephedrine hydrochloride and chlorine nitrogen
Adding methanol (chromatographic purity) into a volumetric flask to prepare reference substance solutions with the concentrations of 50, 15, 5 and 6 mu g/mL respectively after adding the methanol (chromatographic purity) to dissolve the promethazine hydrochloride and the promethazine hydrochloride;
wherein, the dissolution medium solution in the second step is phosphate buffer solution with pH 6.0, and the preparation method comprises the following steps: taking 27.22g of monopotassium phosphate, dissolving the monopotassium phosphate with water, and fixing the volume to 1000mL to obtain 0.2mol/L potassium dihydrogen phosphate solution; 8g of sodium hydroxide is taken, dissolved by water and added to 1000mL to obtain 0.2mol/L sodium hydroxide solution. Weighing 250mL of 0.2mol/L potassium dihydrogen phosphate solution, mixing with 28mL of 0.2mol/L sodium hydroxide solution, adding water to a constant volume of 1000mL, shaking up, and adding 0.03g of sodium dodecyl sulfate into each 100mL to obtain the sodium dodecyl sulfate suspension;
wherein, the preparation method of the dissolution sample solution in the step two comprises the following steps: putting the compound cholamine tablet into 900mL of phosphate buffer solution, carrying out sample treatment by adopting a general rule-dissolution method (slurry method) of Chinese pharmacopoeia, and filtering 10mL of solution after the treatment to obtain filtrate, namely the dissolution sample solution.
In the invention, the reference substance solution is analyzed by liquid chromatography, and retention time and peak area of different chromatographic peaks are recorded to obtain chromatogram peak-retention time diagram of the reference substance, as shown in FIG. 1, wherein chromatographic peaks 1-4 are respectively the reference substances aminophylline, ephedrine hydrochloride, and chlorine nitrogen
Promethazine hydrochloride with a frontal area differentiation1317350, 18690, 703059, 799160 microvolts times second.
Example 1
Taking compound DAN' AN tablet sample (aminophylline, ephedrine hydrochloride, and chloranil)
Promethazine hydrochloride labeled 50mg, 15mg, 5mg, 6.25mg, respectively), measured according to the above measurement method, and the chromatogram obtained is shown in fig. 2.
In FIG. 2, aminophylline, ephedrine hydrochloride, and chlorine nitrogen are detected
The chromatographic peak areas of promethazine hydrochloride are 1296851, 14888, 532250, 659550 microvolts × seconds, respectively, and the product can be obtained by external standard method to obtain aminophylline, ephedrine hydrochloride, and chlorine nitrogen
Promethazine hydrochloride concentrations were 51.81, 16.77, 4.56, 6.76 μ g/mL, 93.3%, 100.6%, 82.0%, 97.4% of the indicated amounts, respectively.
Example 2
Taking compound DAN' AN tablet sample (aminophylline, ephedrine hydrochloride, and chloranil)
Promethazine hydrochloride labeled 50mg, 15mg, 5mg, 6.25mg, respectively), measured according to the above measurement method, and the chromatogram obtained is shown in fig. 3.
In figure 3, aminophylline, ephedrine hydrochloride, and chlorine nitrogen are detected
The chromatographic peak areas of promethazine hydrochloride are 1340000, 15035, 539144, 652390 microvolts times second, respectively, and the product can be calculated by external standard method to obtain aminophylline, ephedrine hydrochloride, and chlorine nitrogen
The promethazine hydrochloride concentrations are 53.59, 17.15, 4.63, 6.70 mu respectivelyg/mL, 96.5%, 102.9%, 83.3%, 96.5% of the indicated amounts, respectively.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.
Claims (4)
1. A method for measuring dissolution rate of a compound cholamine tablet is characterized by comprising the following steps:
step one, preparing a solution of a reference substance;
determining a dissolution medium solution, and preparing a dissolution sample solution of the compound cholamine tablet;
step three, measuring the reference substance solution prepared in the step one by liquid chromatography to obtain a chromatogram peak-retention time chart of the reference substance solution;
step four, determining the dissolved sample solution prepared in the step two through a liquid chromatography to obtain a liquid chromatogram of the dissolved sample solution, comparing the liquid chromatogram of the dissolved sample solution with a liquid chromatogram of a reference solution, and calculating to obtain the dissolved concentration of the compound cholamine tablet;
wherein the reference substances are aminophylline, ephedrine hydrochloride, chlorine nitrogen and promethazine hydrochloride; the dissolution medium solution is phosphate buffer with pH = 6.0; in the liquid chromatography, a chromatographic column takes octadecylsilane chemically bonded silica as a filler, the flow rate is 1mL/min, the detection wavelength is 254nm, a mobile phase A is acetonitrile, a mobile phase B is a phosphate buffer solution with the pH = 3.0, and the linear gradient elution conditions are as follows: 0-8min, 20% A, 80% B; 8-10min, 20-55% of A and 80-45% of B; 10-20min, 55% A, 45% B; 20-25min, 55-20% of A and 45-80% of B; 25-30min, 20% A and 80% B.
2. The assay method according to claim 1, wherein the solution of the control in the first step is prepared by: respectively weighing reference substances, adding methanol to dissolve, adding methanol into a volumetric flask, and fixing the volume to prepare reference substance solutions with the concentrations of 50 mug/mL, 15 mug/mL, 5 mug/mL and 6 mug/mL respectively.
3. The method according to claim 1, wherein the dissolution medium solution in the second step is prepared by: taking 27.22g of monopotassium phosphate, dissolving the monopotassium phosphate with water, and fixing the volume to 1000mL to obtain 0.2mol/L potassium dihydrogen phosphate solution; taking 8g of sodium hydroxide, dissolving with water and fixing the volume to 1000mL to obtain 0.2mol/L sodium hydroxide solution; weighing 250mL of 0.2mol/L potassium dihydrogen phosphate solution, mixing with 28mL of 0.2mol/L sodium hydroxide solution, adding water to a constant volume of 1000mL, shaking up, and adding 0.03g of sodium dodecyl sulfate into each 100mL to obtain the sodium dodecyl sulfate.
4. The method according to claim 1 or 3, wherein the preparation method of the dissolution sample solution in the second step is: putting the compound cholamine tablet into 900mL of phosphate buffer solution, carrying out sample treatment by adopting a general rule-dissolution determination slurry method of Chinese pharmacopoeia, and filtering 10mL of solution after the treatment, wherein the filtrate is the dissolution sample solution.
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