CN112067506A - Method for measuring viscosity of bismuth potassium citrate-containing preparation - Google Patents
Method for measuring viscosity of bismuth potassium citrate-containing preparation Download PDFInfo
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- KZFDVWZZYOPBQZ-UHFFFAOYSA-K bismuth;potassium;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [K+].[Bi+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KZFDVWZZYOPBQZ-UHFFFAOYSA-K 0.000 title claims abstract description 122
- 238000002360 preparation method Methods 0.000 title claims abstract description 75
- 238000000034 method Methods 0.000 title claims abstract description 43
- 210000004051 gastric juice Anatomy 0.000 claims abstract description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000005259 measurement Methods 0.000 claims abstract description 22
- 238000005303 weighing Methods 0.000 claims abstract description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
- 229910052797 bismuth Inorganic materials 0.000 claims description 24
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims description 24
- 102000057297 Pepsin A Human genes 0.000 claims description 5
- 108090000284 Pepsin A Proteins 0.000 claims description 5
- 229940111202 pepsin Drugs 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 19
- 239000008187 granular material Substances 0.000 abstract description 18
- 230000009471 action Effects 0.000 abstract description 6
- 230000007246 mechanism Effects 0.000 abstract description 5
- 238000011160 research Methods 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 188
- 239000002245 particle Substances 0.000 description 26
- 239000012490 blank solution Substances 0.000 description 18
- 230000001681 protective effect Effects 0.000 description 18
- 208000025865 Ulcer Diseases 0.000 description 12
- 238000010998 test method Methods 0.000 description 12
- 231100000397 ulcer Toxicity 0.000 description 12
- 210000001156 gastric mucosa Anatomy 0.000 description 10
- 230000003628 erosive effect Effects 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- 230000035945 sensitivity Effects 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 238000013441 quality evaluation Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000000084 colloidal system Substances 0.000 description 4
- 210000004877 mucosa Anatomy 0.000 description 4
- 244000201986 Cassia tora Species 0.000 description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000001814 pectin Substances 0.000 description 3
- 235000010987 pectin Nutrition 0.000 description 3
- 229920001277 pectin Polymers 0.000 description 3
- NCAIGTHBQTXTLR-UHFFFAOYSA-N phentermine hydrochloride Chemical compound [Cl-].CC(C)([NH3+])CC1=CC=CC=C1 NCAIGTHBQTXTLR-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 241000590002 Helicobacter pylori Species 0.000 description 2
- WMWLMWRWZQELOS-UHFFFAOYSA-N bismuth(III) oxide Inorganic materials O=[Bi]O[Bi]=O WMWLMWRWZQELOS-UHFFFAOYSA-N 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 229940037467 helicobacter pylori Drugs 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 206010061459 Gastrointestinal ulcer Diseases 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N11/00—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties
- G01N11/10—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties by moving a body within the material
- G01N11/14—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties by moving a body within the material by using rotary bodies, e.g. vane
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- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention belongs to the field of medicaments, and particularly relates to a method for measuring the viscosity of a bismuth potassium citrate-containing preparation, which comprises the following steps: sample preparation: weighing a bismuth potassium citrate preparation, adding artificial gastric juice, and dissolving to obtain a solution I; carrying out water bath on the first solution at a first temperature, and then standing for the first time to obtain a second solution, wherein the first temperature is 30-40 ℃, and the time of the first standing is 1-5 hours; transferring the solution II to a separating funnel, standing for the second time, and separating out the colloidal solution at the lower layer after layering, wherein the standing time for the second time is 10-30 min; and (3) viscosity measurement: the colloidal solution is weighed, and the viscosity of the colloidal solution is measured according to a rotational viscometer method of a third method of general rules 0633 of the four parts of China pharmacopoeia, 2020 edition. The invention adopts the measurement of the viscosity of the preparation in the artificial gastric juice to evaluate and research the preparation in vitro according to the action mechanism of the preparation containing the bismuth potassium citrate, in particular to the characteristics of the bismuth potassium citrate granules, and provides a good means for evaluating the quality of the preparation containing the bismuth potassium citrate.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a method for measuring viscosity of a bismuth potassium citrate-containing preparation.
Background
Digestive tract diseases are common diseases and frequently encountered diseases, the incidence rate of the diseases of the stomach and the duodenum is the highest among the diseases of the digestive tract, and the number of the diseases accounts for more than 10 percent of the world population. Meanwhile, gastrointestinal ulcer is one of the main diseases affecting human health at present, so that finding an anti-ulcer medicament with good curative effect and low price is a hot spot in the research and development field of Chinese medicaments.
Bismuth potassium citrate is a bismuth-containing compound of indefinite composition, is a white powder, is salty in taste, dissolves very slightly in ethanol, is very soluble in water, and forms a solution after dissolution. The bismuth potassium citrate is dissolved in warm water in a certain amount and taken orally, and after being hydrolyzed by gastric juice, firm bismuth trioxide colloid precipitate can be generated, and the colloid precipitate forms a diffuse protective layer to cover the ulcer surface so as to isolate the erosion action of gastric acid, pepsin and food on ulcer mucosa. The bismuth potassium citrate can also stimulate the release of endogenous prostaglandin and promote the regeneration of ulcer mucosa and the healing of ulcer.
At present, the colloid characteristics of bismuth potassium citrate preparations such as bismuth potassium citrate granules, bismuth potassium citrate capsules, bismuth potassium citrate tablets and the like in China are related to the treatment effect of gastrointestinal diseases, and the better the colloid characteristic of the bismuth potassium citrate preparation is, the stronger the protection effect on gastrointestinal mucosa is, and the stronger the helicobacter pylori killing capability is. The viscosity of the bismuth potassium citrate-containing preparation can reflect the colloidal characteristics of the medicament, the higher the viscosity of the medicament is, the better the colloidal characteristics of the colloidal solution are, the firmer the protective film formed on the gastric mucosa is, and the stronger the protective effect on the erosion face and the ulcer focus is; conversely, the lower the viscosity, the poorer the colloidal properties of the colloidal solution, the weaker the protective film formed on the gastric mucosa and the weaker the protective effect on the erosive surface and the ulcer focus. Therefore, preparations containing bismuth potassium citrate have different viscosities and thus have different therapeutic effects on gastrointestinal diseases. The viscosity of different bismuth potassium citrate-containing preparations is different, and the viscosity of the bismuth potassium citrate-containing preparation produced by the same manufacturer in different batches and the same preparation method is also different, so that the treatment effect of the bismuth potassium citrate-containing preparation on gastrointestinal diseases can be evaluated by measuring the viscosity of the bismuth potassium citrate-containing preparation.
However, only the method for measuring the viscosity of colloidal bismuth pectin in the prior art is still blank, and the research on the method for measuring the viscosity of bismuth potassium citrate-containing preparations is still blank. The colloidal bismuth pectin is yellow powder, is insoluble in organic solvents such as ethanol and the like, is easy to agglomerate in water, and can be uniformly dispersed in the water after shaking to form a stable colloidal dispersion system. The colloidal bismuth pectin forms a gel suspension in gastric juice, which is equivalent to a layer of firm protective film formed on gastric mucosa, so that the barrier protection effect of the gastric mucosa is enhanced. Bismuth potassium citrate forms bismuth trioxide precipitates in gastric juice, so that the action mechanism of bismuth potassium citrate as a medicament is different. Therefore, in order to ensure the effectiveness of clinical medication, it is necessary to establish a viscosity detection method for bismuth potassium citrate-containing preparations and control the viscosity limit thereof.
Disclosure of Invention
The invention aims to provide a method for measuring the viscosity of a bismuth potassium citrate-containing preparation, which provides a good means for evaluating the quality of the bismuth potassium citrate-containing preparation.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a method for measuring the viscosity of a bismuth potassium citrate-containing preparation, which comprises the following steps:
sample preparation: weighing a bismuth potassium citrate preparation, adding artificial gastric juice, and dissolving to obtain a solution I;
carrying out water bath on the first solution at a first temperature, and then standing for the first time to obtain a second solution, wherein the first temperature is 30-40 ℃, and the first standing time is 1-5 hours;
transferring the solution II to a separating funnel, standing for the second time, and separating out the colloidal solution at the lower layer after layering, wherein the standing time for the second time is 10-30 min;
and (3) viscosity measurement: the colloidal solution is weighed, and the viscosity of the colloidal solution is measured according to a rotational viscometer method of a third method of general rules 0633 of the four parts of China pharmacopoeia, 2020 edition.
In one embodiment, in the sample preparation process, the ratio of the total bismuth content in the bismuth potassium citrate-containing preparation to the mass volume of the artificial gastric juice is 0.35-1.5 mg/mL.
In one embodiment, the method for preparing the artificial gastric juice comprises:
measuring hydrochloric acid with a first volume, and adding water to dilute the hydrochloric acid to a second volume to obtain dilute hydrochloric acid;
weighing the dilute hydrochloric acid with the third volume, the water with the fourth volume and the pepsin with the preset mass, uniformly mixing, and adding water to a constant volume to a fifth volume to obtain the artificial gastric juice.
In one embodiment, in the viscosity measuring step, the colloidal solution is weighed to a volume of 20-60 mL.
In one embodiment, in the viscosity measuring step, the viscosity is measured with a viscometer No. 0 spindle.
In one embodiment, the viscometer spindle # 0 has a speed of 50-70 rpm/min.
The method for measuring the viscosity of the bismuth potassium citrate-containing preparation provided by the invention adopts the measurement of the viscosity of the preparation in artificial gastric juice to evaluate and research the preparation in vitro according to the action mechanism of the bismuth potassium citrate-containing preparation, particularly the characteristics of bismuth potassium citrate granules, and provides a good means for evaluating the quality of the bismuth potassium citrate-containing preparation. Meanwhile, the method also has the advantages of stable measured data, sensitivity, reliability and good reproducibility.
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects to be solved by the present invention more clearly apparent, the present invention is further described in detail below with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The embodiment of the invention provides a method for measuring the viscosity of a bismuth preparation, which comprises the following steps:
step S11, sample preparation: weighing a bismuth potassium citrate preparation, adding artificial gastric juice, and dissolving to obtain a solution I; carrying out water bath on the first solution at a first temperature, and then standing for the first time to obtain a second solution, wherein the first temperature is 30-40 ℃, and the first standing time is 1-5 hours; transferring the solution II to a separating funnel, standing for the second time, and separating out the colloidal solution at the lower layer after layering, wherein the standing time for the second time is 10-30 min;
step S12, viscosity measurement: the colloidal solution is weighed, and the viscosity of the colloidal solution is measured according to a rotational viscometer method of a third method of general rules 0633 of the four parts of China pharmacopoeia, 2020 edition.
Further, the first temperature is 30 to 40 ℃, for example, 30 ℃, 31 ℃, 32 ℃, 33 ℃, 34 ℃, 35 ℃, 36 ℃, 37 ℃, 38 ℃, 39 ℃, 40 ℃ and the like, preferably 37 ℃.
The time for the first standing is 1 to 5 hours, and for example, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours and the like, preferably 1 hour.
The first temperature is 30-40 ℃ which is the temperature of gastric juice of a human body, and the first standing time is 1-5h which is the normal gastric emptying time, so that the sample preparation process is more consistent with the action mechanism of the bismuth potassium citrate-containing preparation in the stomach of the human body.
The time for the second standing is 10-30min, for example, 10min, 11min, 12min, 13min, 14min, 15min, 20min, 25min, 30min, etc., preferably 10 min.
Further, the mass volume ratio of the total bismuth content in the preparation containing bismuth potassium citrate to the artificial gastric juice is 0.35-1.5 mg/mL. For example, it may be 0.35mg/mL, 0.45mg/mL, 0.55mg/mL, 0.65mg/mL, 0.75mg/mL, 1mg/mL, 1.25mg/mL, 1.5mg/mL, etc., within which ratio a stable measurement of viscosity can be ensured.
Wherein, the preparation method of the artificial gastric juice comprises the following steps:
measuring 234mL of hydrochloric acid, and adding water to dilute the hydrochloric acid to 1000mL to obtain dilute hydrochloric acid containing 9.5-10.5% of HCl;
weighing 16.4mL of the dilute hydrochloric acid, 800mL of water and 10g of pepsin, uniformly mixing in a beaker, adding water to a constant volume of 1000mL, and obtaining the artificial gastric juice.
Further, in step S12, the better the colloidal property of the colloidal solution (the colloidal solution is a bismuth potassium citrate-containing preparation), the stronger the protective effect on the gastrointestinal mucosa, and the stronger the ability to kill helicobacter pylori. The viscosity of the colloidal solution can reflect the colloidal characteristics of the medicine, the higher the viscosity of the medicine is, the better the colloidal characteristics of the colloidal solution are, the firmer the protective film formed on the gastric mucosa is, and the stronger the protective effect on the erosion surface and the ulcer focus is; conversely, the lower the viscosity, the poorer the colloidal properties of the colloidal solution, the weaker the protective film formed on the gastric mucosa and the weaker the protective effect on the erosive surface and the ulcer focus. Therefore, a good means is provided for the quality evaluation of the bismuth potassium citrate-containing preparation by adopting a method for measuring the viscosity of the colloidal solution.
The volume of the colloidal solution is 20 to 60mL, and may be, for example, 20mL, 21mL, 22mL, 23mL, 24mL, 25mL, 30mL, 40mL, 50mL, 60mL, or the like, and preferably 25 mL.
The viscosity is measured with a viscometer spindle No. 0 during the measurement, and the rotational speed is 50 to 70rpm/min, for example, 50rpm/min, 51rpm/min, 52rpm/min, 53rpm/min, 54rpm/min, 55rpm/min, 60rpm/min, 65rpm/min, 70rpm/min, etc., preferably 60 rpm/min.
The method for measuring the viscosity of the bismuth potassium citrate-containing preparation provided by the embodiment of the invention adopts the measurement of the viscosity of the preparation in artificial gastric juice to carry out in-vitro evaluation research according to the action mechanism of the bismuth potassium citrate-containing preparation, particularly the characteristics of bismuth potassium citrate granules, and provides a good means for the quality evaluation of the bismuth potassium citrate-containing preparation. Meanwhile, the method also has the advantages of stable measured data, sensitivity, reliability and good reproducibility.
The invention is described in further detail with reference to a number of tests performed in sequence, and a part of the test results are used as reference, and the following detailed description is given with reference to specific examples.
Example 1
Step S1, sample preparation: weighing 3 bismuth potassium citrate tablets (the bismuth content of each tablet is 0.11g, and the total bismuth content of the 3 bismuth potassium citrate tablets is 0.33g), placing the 3 bismuth potassium citrate tablets in a beaker, adding 300mL of artificial gastric juice, stirring to completely dissolve the bismuth potassium citrate tablets, standing in a water bath at 37 ℃ for 1h for layering, then transferring to a separating funnel for standing for 10min, and separating out a colloidal solution positioned at the lower layer after layering to obtain a colloidal solution 1;
step S2, weighing 25mL of colloidal solution 1, and measuring the viscosity of the colloidal solution 1 by adopting a viscometer No. 0 rotor under the condition of a rotating speed of 60rpm/min according to a rotational viscometer method of a third method of general rules 0633 of the fourth division of China pharmacopoeia of 2020 edition.
In step S1, the bismuth potassium citrate tablet has the model number: the bismuth potassium citrate tablet marketed by Spain is produced by the following steps: tora Laboratories s.l., trade name gastrodienol, specification: 120mg (in Bi)2O3Meter).
The same principle is that: according to the steps S1 and S2, a blank solution was prepared without adding bismuth potassium citrate tablets, and the viscosity of the blank solution was measured.
In addition, in an analysis experiment, measurement results have errors due to factors such as operating environments (air pressure, temperature and humidity), performance of instruments, inconsistent processing of samples by analysts and the like, so that a repeated method can be adopted to avoid the reduction of experimental errors.
In this embodiment, the same batch of bismuth potassium citrate tablets is selected, and steps S1 and S2 are repeated five times to prepare colloidal solution 2, colloidal solution 3, colloidal solution 4, colloidal solution 5, and colloidal solution 6, and the viscosities of colloidal solution 2, colloidal solution 3, colloidal solution 4, colloidal solution 5, and colloidal solution 6 are measured, respectively.
In step S1, due to the existence of experimental error, the volumes of the obtained colloidal solutions are inconsistent, such as 54mL of the obtained volume of the colloidal solution 1, 57mL of the obtained volume of the colloidal solution 2, 59mL of the obtained volume of the colloidal solution 3, 60mL of the obtained volume of the colloidal solution 4, 56mL of the obtained volume of the colloidal solution 5, and 57mL of the obtained volume of the colloidal solution 6.
In this embodiment, all bismuth potassium citrate tablets are in the same batch.
The preparation method of the artificial gastric juice comprises the following steps:
measuring 234mL of hydrochloric acid, and adding water to dilute the hydrochloric acid to 1000mL to obtain dilute hydrochloric acid containing 9.5-10.5% of HCl;
weighing 16.4mL of the dilute hydrochloric acid, 800mL of water and 10g of pepsin, uniformly mixing in a beaker, adding water to a constant volume of 1000mL, and obtaining the artificial gastric juice. In the following examples, the preparation method of the artificial gastric juice is the same as that of the examples, and thus, the description thereof is omitted.
The measurement results of step S2 are shown in the following table:
wherein the viscosity value of the blank solution was 1.14 mPas.
And (4) conclusion: the RSD value of the viscosity test of the colloidal solution 1, the colloidal solution 2, the colloidal solution 3, the colloidal solution 4, the colloidal solution 5 and the colloidal solution 6 is less than 10, which shows that the viscosity test method has the advantages of stable measurement data, sensitivity, reliability and good reproducibility, and can be used as the viscosity test method of the bismuth potassium citrate-containing preparation.
Example 2
Step S1, sample preparation: weighing 3 bismuth potassium citrate tablets (the bismuth content of each tablet is 0.11g, and the total bismuth content of the 3 bismuth potassium citrate tablets is 0.33g), placing the 3 bismuth potassium citrate tablets in a beaker, adding 300mL of artificial gastric juice, stirring to completely dissolve the bismuth potassium citrate tablets, standing in a water bath at 37 ℃ for 1h for layering, then transferring to a separating funnel for standing for 10min, and separating out a colloidal solution positioned at the lower layer after layering to obtain a colloidal solution 1;
step S2, weighing 20mL of colloidal solution 1, and measuring the viscosity of the colloidal solution 1 by adopting a viscometer No. 0 rotor under the condition of a rotating speed of 60rpm/min according to a rotational viscometer method of a third method of general rules 0633 of the fourth division of China pharmacopoeia of 2020 edition.
In step S1, the bismuth potassium citrate tablet has the model number: the bismuth potassium citrate tablet marketed by Spain is produced by the following steps: tora Laboratories s.l., trade name gastrodienol, specification: 120mg (in Bi)2O3Meter).
The same principle is that: according to the steps S1 and S2, a blank solution was prepared without adding bismuth potassium citrate tablets, and the viscosity of the blank solution was measured. Selecting the same batch of bismuth potassium citrate tablets, repeating the steps S1 and S2 five times to prepare a colloidal solution 2, a colloidal solution 3, a colloidal solution 4, a colloidal solution 5 and a colloidal solution 6, and respectively measuring the viscosity of the colloidal solution 2, the colloidal solution 3, the colloidal solution 4, the colloidal solution 5 and the colloidal solution 6.
In step S1, due to the existence of experimental errors, the volumes of the obtained colloidal solutions are inconsistent, such as 22.5mL of the obtained colloidal solution 1, 20.5mL of the obtained colloidal solution 2, 20.5mL of the obtained colloidal solution 3, 21mL of the obtained colloidal solution 4, 21mL of the obtained colloidal solution 5, and 20mL of the obtained colloidal solution 6.
In this example, all bismuth potassium citrate tablets were from the same batch of drug, and were different from the batch in example 1, and different from the batch in example 1.
The measurement results of step S2 are shown in the following table:
wherein the viscosity value of the blank solution was 1.19 mPas.
And (4) conclusion: the RSD value of the viscosity test of the colloidal solution 1, the colloidal solution 2, the colloidal solution 3, the colloidal solution 4, the colloidal solution 5 and the colloidal solution 6 is less than 10, which shows that the viscosity test method has the advantages of stable measurement data, sensitivity, reliability and good reproducibility, and can be used as the viscosity test method of the bismuth potassium citrate-containing preparation.
The comparison of the viscosity averages of the two batches in example 1 and example 2 shows that the viscosity of the same drug produced in different batches is different, and the viscosity is a quality evaluation means of the bismuth potassium citrate-containing preparation (the viscosity of the bismuth potassium citrate-containing preparation can reflect the colloidal property of the drug, the higher the viscosity of the drug is, the firmer the protective film formed on the gastric mucosa is, the stronger the protective effect on the erosion face and the ulcer focus is, and conversely, the lower the viscosity is, the weaker the protective film formed on the gastric mucosa is, the weaker the protective effect on the erosion face and the ulcer focus is, so the viscosity measurement method provides a good means for the quality evaluation of the bismuth potassium citrate-containing preparation of different batches with the same preparation method.
Example 3
Step S1, sample preparation: weighing 3 bags of bismuth potassium citrate particles (the content of bismuth in each bag is 0.11g, and the total content of bismuth in the 3 bags of bismuth potassium citrate particles is 0.33g), placing the 3 bags in a beaker, adding 300mL of artificial gastric juice, stirring to completely dissolve the bismuth potassium citrate particles, standing in a water bath at 37 ℃ for 1h for layering, then transferring to a separating funnel for standing for 10min, and separating out a colloidal solution positioned at the lower layer after layering to obtain a colloidal solution 1;
step S2, weighing 25mL of colloidal solution 1, and measuring the viscosity of the colloidal solution 1 by adopting a viscometer No. 0 rotor under the condition of a rotating speed of 60rpm/min according to a rotational viscometer method of a third method of general rules 0633 of the fourth division of China pharmacopoeia of 2020 edition.
In this example, the sample was bismuth potassium citrate granules self-made by laboratory, the bismuth content per bag was 0.11g, and the total mass of bismuth potassium citrate granules per bag was 1.2 g.
The same principle is that: according to steps S1 and S2, a blank solution was prepared without adding bismuth potassium citrate particles, and the viscosity of the blank solution was measured. Selecting the same batch of bismuth potassium citrate particles, repeating the steps S1 and S2 five times to prepare a colloidal solution 2, a colloidal solution 3, a colloidal solution 4, a colloidal solution 5 and a colloidal solution 6, and respectively measuring the viscosities of the colloidal solution 2, the colloidal solution 3, the colloidal solution 4, the colloidal solution 5 and the colloidal solution 6.
In step S1, due to the existence of experimental errors, the volumes of the obtained colloidal solutions are inconsistent, such as 51mL of the obtained colloidal solution 1, 42mL of the obtained colloidal solution 2, 44mL of the obtained colloidal solution 3, 46mL of the obtained colloidal solution 4, 47mL of the obtained colloidal solution 5, and 40mL of the obtained colloidal solution 6.
In this example, all of the bismuth potassium citrate granules are from the same batch of bismuth potassium citrate granules produced.
The measurement results of step S2 are shown in the following table:
wherein the viscosity value of the blank solution was 1.10 mPas.
And (4) conclusion: the RSD value of the viscosity test of the colloidal solution 1, the colloidal solution 2, the colloidal solution 3, the colloidal solution 4, the colloidal solution 5 and the colloidal solution 6 is less than 10, which shows that the viscosity test method has the advantages of stable measurement data, sensitivity, reliability and good reproducibility, and can be used as the viscosity test method of the bismuth potassium citrate-containing preparation.
Example 4
Step S1, sample preparation: weighing 3 bags of bismuth potassium citrate particles (the content of bismuth in each bag is 0.11g, and the total content of bismuth in the 3 bags of bismuth potassium citrate particles is 0.33g), placing the 3 bags in a beaker, adding 300mL of artificial gastric juice, stirring to completely dissolve the bismuth potassium citrate particles, standing in a water bath at 37 ℃ for 1h for layering, then transferring to a separating funnel for standing for 10min, and separating out a colloidal solution positioned at the lower layer after layering to obtain a colloidal solution 1;
step S2, weighing 25mL of colloidal solution 1, and measuring the viscosity of the colloidal solution 1 by adopting a viscometer No. 0 rotor under the condition of a rotating speed of 60rpm/min according to a rotational viscometer method of a third method of general rules 0633 of the fourth division of China pharmacopoeia of 2020 edition.
In this example, the sample was bismuth potassium citrate granules self-made by laboratory, the bismuth content per bag was 0.11g, and the total mass of bismuth potassium citrate granules per bag was 1.2 g.
The same principle is that: according to steps S1 and S2, a blank solution was prepared without adding bismuth potassium citrate particles, and the viscosity of the blank solution was measured. Selecting the same batch of bismuth potassium citrate particles, repeating the steps S1 and S2 five times to prepare a colloidal solution 2, a colloidal solution 3, a colloidal solution 4, a colloidal solution 5 and a colloidal solution 6, and respectively measuring the viscosities of the colloidal solution 2, the colloidal solution 3, the colloidal solution 4, the colloidal solution 5 and the colloidal solution 6.
In step S1, due to the existence of experimental errors, the volumes of the obtained colloidal solutions are inconsistent, such as 38mL of the obtained colloidal solution 1, 35mL of the obtained colloidal solution 2, 38mL of the obtained colloidal solution 3, 40mL of the obtained colloidal solution 4, 30mL of the obtained colloidal solution 5, and 36mL of the obtained colloidal solution 6.
In this example, all bismuth potassium citrate granules were from the same batch of bismuth potassium citrate granules produced, and were different from the batch of example 3.
The measurement results of step S2 are shown in the following table:
wherein the viscosity value of the blank solution was 1.08 mPas.
And (4) conclusion: the RSD value of the viscosity test of the colloidal solution 1, the colloidal solution 2, the colloidal solution 3, the colloidal solution 4, the colloidal solution 5 and the colloidal solution 6 is less than 10, which shows that the viscosity test method has the advantages of stable measurement data, sensitivity, reliability and good reproducibility, and can be used as the viscosity test method of the bismuth potassium citrate-containing preparation.
Example 5
Step S1, sample preparation: weighing 3 bags of bismuth potassium citrate particles (the content of bismuth in each bag is 0.11g, and the total content of bismuth in the 3 bags of bismuth potassium citrate particles is 0.33g), placing the 3 bags in a beaker, adding 300mL of artificial gastric juice, stirring to completely dissolve the bismuth potassium citrate particles, standing in a water bath at 37 ℃ for 1h for layering, then transferring to a separating funnel for standing for 10min, and separating out a colloidal solution positioned at the lower layer after layering to obtain a colloidal solution 1;
step S2, weighing 25mL of colloidal solution 1, and measuring the viscosity of the colloidal solution 1 by adopting a viscometer No. 0 rotor under the condition of a rotating speed of 60rpm/min according to a rotational viscometer method of a third method of general rules 0633 of the fourth division of China pharmacopoeia of 2020 edition. The sample is bismuth potassium citrate particles self-made by a laboratory, the content of bismuth in each bag is 0.11g, and the total mass of bismuth potassium citrate particles in each bag is 1.2 g.
The same principle is that: according to steps S1 and S2, a blank solution was prepared without adding bismuth potassium citrate particles, and the viscosity of the blank solution was measured.
In this embodiment, the same batch of bismuth potassium citrate particles is selected, and steps S1 and S2 are repeated five times to prepare colloidal solution 2, colloidal solution 3, colloidal solution 4, colloidal solution 5, and colloidal solution 6, and the viscosities of colloidal solution 2, colloidal solution 3, colloidal solution 4, colloidal solution 5, and colloidal solution 6 are measured, respectively.
In step S1, due to the existence of experimental error, the volumes of the obtained colloidal solutions are inconsistent, such as 50mL of the obtained volume of the colloidal solution 1, 46mL of the obtained volume of the colloidal solution 2, 44mL of the obtained volume of the colloidal solution 3, 45mL of the obtained volume of the colloidal solution 4, 48mL of the obtained volume of the colloidal solution 5, and 43mL of the obtained volume of the colloidal solution 6.
In this example, all of the bismuth potassium citrate granules were from the same batch of bismuth potassium citrate granules produced, and were different from the batches of examples 3 and 4.
The measurement results of step S2 are shown in the following table:
wherein the viscosity value of the blank solution was 1.14 mPas.
And (4) conclusion: the RSD value of the viscosity test of the colloidal solution 1, the colloidal solution 2, the colloidal solution 3, the colloidal solution 4, the colloidal solution 5 and the colloidal solution 6 is less than 10, which shows that the viscosity test method has the advantages of stable measurement data, sensitivity, reliability and good reproducibility, and can be used as the viscosity test method of the bismuth potassium citrate-containing preparation.
Example 6
Step S1, sample preparation: weighing 3 bags of bismuth potassium citrate particles (the content of bismuth in each bag is 0.11g, and the total content of bismuth in the 3 bags of bismuth potassium citrate particles is 0.33g), placing the 3 bags in a beaker, adding 300mL of artificial gastric juice, stirring to completely dissolve the bismuth potassium citrate particles, standing in a water bath at 37 ℃ for 1h for layering, then transferring to a separating funnel for standing for 10min, and separating out a colloidal solution positioned at the lower layer after layering to obtain a colloidal solution 1;
step S2, weighing 25mL of colloidal solution 1, and measuring the viscosity of the colloidal solution 1 by adopting a viscometer No. 0 rotor under the condition of a rotating speed of 60rpm/min according to a rotational viscometer method of a third method of general rules 0633 of the fourth division of China pharmacopoeia of 2020 edition. The sample is bismuth potassium citrate particles self-made by a laboratory, the content of bismuth in each bag is 0.11g, and the total mass of bismuth potassium citrate particles in each bag is 1.2 g.
The same principle is that: according to steps S1 and S2, a blank solution was prepared without adding bismuth potassium citrate particles, and the viscosity of the blank solution was measured.
In this embodiment, the same batch of bismuth potassium citrate particles is selected, and steps S1 and S2 are repeated five times to prepare colloidal solution 2, colloidal solution 3, colloidal solution 4, colloidal solution 5, and colloidal solution 6, and the viscosities of colloidal solution 2, colloidal solution 3, colloidal solution 4, colloidal solution 5, and colloidal solution 6 are measured, respectively.
In step S1, due to the existence of experimental errors, the volumes of the obtained colloidal solutions are inconsistent, such as 38mL of the obtained colloidal solution 1, 35mL of the obtained colloidal solution 2, 38mL of the obtained colloidal solution 3, 40mL of the obtained colloidal solution 4, 30mL of the obtained colloidal solution 5, and 36mL of the obtained colloidal solution 6.
In this example, all bismuth potassium citrate granules were from the same batch of bismuth potassium citrate granules produced, and were different from the batches of examples 3, 4 and 5.
The measurement results of step S2 are shown in the following table:
wherein the viscosity value of the blank solution was 1.08 mPas.
And (4) conclusion: the RSD value of the viscosity test of the colloidal solution 1, the colloidal solution 2, the colloidal solution 3, the colloidal solution 4, the colloidal solution 5 and the colloidal solution 6 is less than 10, which shows that the viscosity test method has the advantages of stable measurement data, sensitivity, reliability and good reproducibility, and can be used as the viscosity test method of the bismuth potassium citrate-containing preparation.
The comparison of the viscosity averages of four batches in examples 3, 4, 5 and 6 shows that the viscosity of the same medicament produced by different batches is different, and the viscosity is a quality evaluation means of the bismuth potassium citrate-containing preparation (the viscosity of the bismuth potassium citrate-containing preparation can reflect the colloidal property of the medicament, the higher the viscosity of the medicament is, the firmer the protective film formed on the gastric mucosa is, the stronger the protective effect on the erosion face and the ulcer focus is, and conversely, the weaker the protective film formed on the gastric mucosa is, the weaker the protective effect on the erosion face and the ulcer focus is, so that the viscosity measurement method provides a good means for the quality evaluation of the bismuth potassium citrate-containing preparations of different batches and the same preparation method.
The bismuth potassium citrate tablets in examples 1 and 2 were 120mg (in Bi) in a specification of the manufacturer marketed by Spain under the name of Tora Laboratories S.L. under the name of Gastrodenol2O3Calculated) of two batches of reference formulation, as a control drug for the evaluation of the quality and efficacy consistency of bismuth potassium citrate imitation drugs, the bismuth potassium citrate granules in examples 3, 4, 5 and 6 are four batches of bismuth potassium citrate granules self-made by the laboratory of the skilled person. The viscosity averages measured in examples 1 and 2 were 2.08mPa · s and 3.58mPa · s, respectively, and the viscosity averages measured in examples 3, 4, 5, and 6 were 3.71mPa · s, 3.48mPa · s, 3.77mPa · s, and 4.54mPa · s, respectively, comparing that the viscosity values of the four batches of bismuth potassium citrate particles self-made by the laboratory were all higher than 2.08mPa · s in example 1 and higher than or similar to 3.58mPa · s in example 2, demonstrating that the mass of the four batches of bismuth potassium citrate particles self-made by the skilled artisan, as compared to the reference formulation, satisfied the requirement for the evaluation of the consistency of the pharmaceutical quality.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (6)
1. A method for measuring the viscosity of a bismuth potassium citrate-containing preparation, which is characterized by comprising the following steps:
sample preparation: weighing a bismuth potassium citrate preparation, adding artificial gastric juice, and dissolving to obtain a solution I;
carrying out water bath on the first solution at a first temperature, and then standing for the first time to obtain a second solution, wherein the first temperature is 30-40 ℃, and the first standing time is 1-5 hours;
transferring the solution II to a separating funnel, standing for the second time, and separating out the colloidal solution at the lower layer after layering, wherein the standing time for the second time is 10-30 min;
and (3) viscosity measurement: the colloidal solution is weighed, and the viscosity of the colloidal solution is measured according to a rotational viscometer method of a third method of general rules 0633 of the four parts of China pharmacopoeia, 2020 edition.
2. The method of claim 1, wherein the ratio of the total bismuth content in the bismuth potassium citrate-containing preparation to the volume by mass of the artificial gastric juice in the sample preparation process is 0.35-1.5 mg/mL.
3. The method for measuring viscosity of bismuth potassium citrate-containing formulation according to claim 1, wherein the artificial gastric juice is prepared by a method comprising:
measuring hydrochloric acid with a first volume, and adding water to dilute the hydrochloric acid to a second volume to obtain dilute hydrochloric acid;
weighing the dilute hydrochloric acid with the third volume, the water with the fourth volume and the pepsin with the preset mass, uniformly mixing, and adding water to a constant volume to a fifth volume to obtain the artificial gastric juice.
4. The method for measuring the viscosity of a bismuth potassium citrate-containing preparation according to claim 1, wherein in the step of measuring the viscosity, the colloidal solution is weighed so as to have a volume of 20 to 60 mL.
5. The method of claim 1, wherein the viscosity of the bismuth potassium citrate-containing preparation is measured using a viscometer with spindle No. 0.
6. The method of claim 5, wherein the spindle of the viscometer No. 0 is at 50-70 rpm/min.
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