CN112067506B - Viscosity measurement method of bismuth potassium citrate-containing preparation - Google Patents
Viscosity measurement method 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 133
- 238000002360 preparation method Methods 0.000 title claims abstract description 77
- 238000000691 measurement method Methods 0.000 title abstract description 20
- 239000000084 colloidal system Substances 0.000 claims abstract description 96
- 238000000034 method Methods 0.000 claims abstract description 30
- 210000004051 gastric juice Anatomy 0.000 claims abstract description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000005303 weighing Methods 0.000 claims abstract description 24
- 238000005259 measurement Methods 0.000 claims abstract description 21
- 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 2
- 239000002245 particle Substances 0.000 abstract description 42
- 239000003814 drug Substances 0.000 abstract description 19
- 229940079593 drug Drugs 0.000 abstract description 10
- 238000013441 quality evaluation Methods 0.000 abstract description 8
- 238000011156 evaluation Methods 0.000 abstract description 5
- 230000009471 action Effects 0.000 abstract description 4
- 230000007246 mechanism Effects 0.000 abstract description 4
- 238000011160 research Methods 0.000 abstract description 4
- 238000000338 in vitro Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 187
- 239000012490 blank solution Substances 0.000 description 18
- 230000001681 protective effect Effects 0.000 description 18
- 208000025865 Ulcer Diseases 0.000 description 12
- 231100000397 ulcer Toxicity 0.000 description 12
- 210000001156 gastric mucosa Anatomy 0.000 description 10
- 239000008187 granular material Substances 0.000 description 10
- 230000003628 erosive effect Effects 0.000 description 9
- 239000010410 layer Substances 0.000 description 8
- 230000035945 sensitivity Effects 0.000 description 8
- 238000012360 testing method Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000010998 test method Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 244000201986 Cassia tora Species 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 210000004877 mucosa Anatomy 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
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 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
- 229940037467 helicobacter pylori Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 229910015902 Bi 2 O 3 Inorganic materials 0.000 description 1
- 206010061459 Gastrointestinal ulcer Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect 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
- 238000009509 drug development Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000004535 effect on gastrointestinal diseases Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
Classifications
-
- 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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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention belongs to the field of medicines, and particularly relates to a viscosity measurement method of a bismuth potassium citrate-containing preparation, which comprises the following steps: sample preparation: weighing a bismuth potassium citrate-containing 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 for the first standing is 1-5h; transferring the second solution to a separating funnel, standing for 10-30min for layering, and separating out colloid solution at the lower layer; viscosity measurement: and weighing the colloid solution, and measuring the viscosity of the colloid solution according to a third method rotational viscometer method of the four general rules 0633 of the Chinese pharmacopoeia of 2020 edition. According to the action mechanism of the bismuth potassium citrate-containing preparation, particularly the characteristics of bismuth potassium citrate particles, the viscosity of the preparation in artificial gastric juice is measured to conduct in-vitro evaluation and research, and a good means is provided for quality evaluation of the bismuth potassium citrate-containing preparation.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a viscosity measurement method of a bismuth potassium citrate-containing preparation.
Background
Among the diseases of the digestive tract system, the highest incidence is especially in the stomach and duodenum, and the number of diseases is more than 10% of the world population. Meanwhile, gastrointestinal ulcers are one of the main diseases affecting human health at present, so that searching for antiulcer drugs with good curative effect and low price is a hotspot in the field of drug development in China.
Bismuth potassium citrate is a bismuth-containing compound with indefinite composition, is white powder, salty in taste, very slightly soluble in ethanol, very easily soluble in water and forms a solution after dissolution. The bismuth potassium citrate is dissolved in warm water quantitatively and then taken orally, and the bismuth trioxide colloid precipitate can be generated after gastric juice hydrolysis, and the colloid precipitate forms a diffuse protective layer which covers the ulcer surface to isolate the erosion effect of gastric acid, pepsin and food on the ulcer mucosa. Bismuth potassium citrate also stimulates endogenous prostaglandin release, promoting ulcer mucosa regeneration and ulcer healing.
At present, the colloid characteristics of bismuth potassium citrate preparations such as bismuth potassium citrate particles, 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 characteristics of the bismuth potassium citrate preparations are, the stronger the protection effect of the bismuth potassium citrate preparations on gastrointestinal mucous membranes is, and the stronger the capability of the bismuth potassium citrate preparations to kill helicobacter pylori is. The viscosity of the bismuth potassium citrate-containing preparation can reflect the colloid characteristics of the medicine, the larger the viscosity of the medicine is, the better the colloid characteristics of the colloid solution are, the more firm 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 smaller the viscosity, the worse 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 erosion surface and the ulcer focus. So the viscosity of the bismuth potassium citrate-containing preparation is different, and the treatment effect on gastrointestinal diseases is also different. The viscosities of different bismuth potassium citrate-containing preparations are different, and the viscosities of bismuth potassium citrate-containing preparations produced by the same manufacturer and the same preparation method in different batches are 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, in the prior art, only the viscosity measurement method of colloidal bismuth pectin is used, and the research on the viscosity measurement method of the bismuth potassium citrate-containing preparation is still in a blank stage. The colloidal bismuth pectin is yellow powder, is insoluble in organic solvents such as ethanol, is easy to agglomerate in water, and can be uniformly dispersed in water after shaking to form a stable colloidal dispersion system. The colloidal bismuth pectin forms gel suspension in gastric juice, which is equivalent to forming a firm protective film on gastric mucosa, so as to enhance the barrier protection effect of the gastric mucosa. Whereas bismuth potassium citrate forms bismuth trioxide precipitates in gastric juice, so that their mechanism of action is different when used as a medicament. Therefore, in order to ensure the effectiveness of clinical medication, it is necessary to establish a viscosity detection method in the bismuth potassium citrate-containing preparation and control the limit of the viscosity.
Disclosure of Invention
The invention aims to provide a viscosity measurement method of a bismuth potassium citrate-containing preparation, which provides a good means for quality evaluation of the bismuth potassium citrate-containing preparation.
In order to achieve the above purpose, the invention adopts the following technical scheme:
the invention provides a viscosity measurement method of a bismuth potassium citrate-containing preparation, which comprises the following steps:
sample preparation: weighing a bismuth potassium citrate-containing 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 standing for the first time is 1-5h;
transferring the second solution to a separating funnel, standing for the second time, and separating out the colloid solution at the lower layer after layering, wherein the time of the second standing is 10-30min;
viscosity measurement: and weighing the colloid solution, and measuring the viscosity of the colloid solution according to a third method rotational viscometer method of the four general rules 0633 of the Chinese pharmacopoeia of 2020 edition.
In one embodiment, the mass-to-volume ratio of the total bismuth content of the weighed bismuth potassium citrate-containing preparation to the artificial gastric juice is 0.35-1.5mg/mL during the sample preparation process.
In one embodiment, the method for preparing artificial gastric juice comprises:
measuring a first volume of hydrochloric acid, adding water to dilute the first volume of hydrochloric acid to a second volume of hydrochloric acid, and obtaining dilute hydrochloric acid;
weighing the third volume of dilute hydrochloric acid, the fourth volume of water and the pepsin with preset mass, uniformly mixing, and adding water to a fifth volume to obtain the artificial gastric juice.
In one embodiment, in the step of measuring the viscosity, the volume of the colloidal solution is weighed to be 20-60mL.
In one embodiment, in the step of measuring the viscosity, the viscosity is measured using a viscometer number 0 spindle.
In one embodiment, the speed of rotation of the viscometer number 0 spindle is 50-70rpm/min.
According to the viscosity measurement method of the bismuth potassium citrate-containing preparation, according to the action mechanism of the bismuth potassium citrate-containing preparation, particularly the characteristics of bismuth potassium citrate particles, the viscosity of the preparation in artificial gastric juice is measured to conduct in-vitro evaluation research, so that a good means is provided for quality evaluation of the bismuth potassium citrate-containing preparation. Meanwhile, the method has the advantages of stable measurement data, sensitivity, reliability and good reproducibility.
Detailed Description
In order to make the technical problems, technical schemes and beneficial effects to be solved more clear, the invention is further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The embodiment of the invention provides a viscosity measurement method of a bismuth preparation, which comprises the following steps:
step S11, sample preparation: weighing a bismuth potassium citrate-containing 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 standing for the first time is 1-5h; transferring the second solution to a separating funnel, standing for the second time, and separating out the colloid solution at the lower layer after layering, wherein the time of the second standing is 10-30min;
step S12, viscosity measurement: and weighing the colloid solution, and measuring the viscosity of the colloid solution according to a third method rotational viscometer method of the four general rules 0633 of the Chinese pharmacopoeia of 2020 edition.
Further, the first temperature is 30 to 40℃and may be, for example, 30℃31℃32℃33℃34℃35℃36℃37℃38℃39℃40℃and the like, preferably 37 ℃.
The first standing time is 1 to 5 hours, for example, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, etc., preferably 1 hour.
In the above, the first temperature is 30-40deg.C, and the first standing time is 1-5h for normal gastric emptying time, so that the preparation process of the sample is more suitable for the action mechanism of bismuth potassium citrate preparation in human stomach.
The second standing time is 10-30min, for example, 10min, 11min, 12min, 13min, 14min, 15min, 20min, 25min, 30min, etc., preferably 10min.
Further, the mass volume ratio of the total content of bismuth in the weighed bismuth potassium citrate-containing preparation to the artificial gastric juice is 0.35-1.5mg/mL. For example, the viscosity 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., and within this ratio range, stable measurement of viscosity may be ensured.
The preparation method of the artificial gastric juice comprises the following steps:
weighing 234mL of hydrochloric acid, and adding water to dilute to 1000mL to obtain dilute hydrochloric acid with the HCl of 9.5-10.5%;
16.4mL of the diluted hydrochloric acid, 800mL of water and 10g of pepsin are weighed, uniformly mixed in a beaker, and then water is added to fix the volume to 1000mL, so that the artificial gastric juice is obtained.
Further, in step S12, the better the colloidal characteristics of the colloidal solution (the colloidal solution is a preparation containing bismuth potassium citrate), the stronger the protective effect on gastrointestinal mucosa, and the stronger the capability of killing helicobacter pylori. The viscosity of the colloid solution can reflect the colloid characteristics of the medicine, the larger the viscosity of the medicine is, the better the colloid characteristics of the colloid solution are, the more firm 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 smaller the viscosity, the worse 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 erosion surface and the ulcer focus. Therefore, a colloid solution viscosity measurement method is adopted to provide a good means for evaluating the quality of the bismuth potassium citrate-containing preparation.
The volume of the colloidal solution is 20 to 60mL, for example, 20mL, 21mL, 22mL, 23mL, 24mL, 25mL, 30mL, 40mL, 50mL, 60mL, etc., preferably 25mL.
The viscosity is measured by a viscometer No. 0 rotor at a rotation speed of 50-70rpm/min, for example, 50rpm/min, 51rpm/min, 52rpm/min, 53rpm/min, 54rpm/min, 55rpm/min, 60rpm/min, 65rpm/min, 70rpm/min, etc., preferably 60rpm/min.
According to the viscosity measurement method of the bismuth potassium citrate-containing preparation, provided by the embodiment of the invention, according to the action mechanism of the bismuth potassium citrate-containing preparation, especially the characteristics of bismuth potassium citrate particles, in-vitro evaluation research is carried out by adopting the viscosity of the measurement preparation in artificial gastric juice, so that a good means is provided for quality evaluation of the bismuth potassium citrate-containing preparation. Meanwhile, the method has the advantages of stable measurement data, sensitivity, reliability and good reproducibility.
The invention has been tested several times in succession, and the invention will be described in further detail with reference to a few test results, and will be described in detail with reference to specific examples.
Example 1
Step S1, sample preparation: weighing 3 bismuth potassium citrate tablets (each bismuth content is 0.11g, and the total bismuth content in the 3 bismuth potassium citrate tablets is 0.33 g), placing in a beaker, adding 300mL of artificial gastric juice, stirring to dissolve all the bismuth potassium citrate tablets, standing in a water bath at 37 ℃ for 1h until the bismuth potassium citrate tablets are layered, transferring to a separating funnel, standing for 10min, and separating out a colloid solution at the lower layer after the bismuth potassium citrate tablets are layered to obtain a colloid solution 1;
and S2, weighing 25mL of the colloidal solution 1, and measuring the viscosity of the colloidal solution 1 by adopting a rotor of a viscometer No. 0 according to a third method rotational viscometer method of the four general rules 0633 of Chinese pharmacopoeia of 2020 edition under the condition of rotating at 60rpm/min.
In the step S1, the model of the bismuth potassium citrate tablet is as follows: spanish marketed citric acidBismuth potassium acid tablet, the manufacturer is: tora Laboratories S.L., under the trade name Gastrorenol, specification: 120mg (in Bi) 2 O 3 Meter).
And (3) the same principle: according to 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 the analysis experiment, because of factors such as the operating environment (air pressure, temperature, humidity), the performance of the instrument, and the inconsistent processing of each sample by the analyst, errors exist in the measurement result, so in order to reduce the experimental error, a repeated method can be adopted for avoiding.
In this embodiment, the same batch of bismuth potassium citrate tablets is selected, and steps S1 and S2 are repeated 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 the viscosities of the colloidal solution 2, the colloidal solution 3, the colloidal solution 4, the colloidal solution 5 and the colloidal solution 6 are respectively measured.
In step S1, the volumes of the obtained colloidal solutions are inconsistent due to the experimental error, for example, the volume of the obtained colloidal solution 1 is 54mL, the volume of the colloidal solution 2 is 57mL, the volume of the colloidal solution 3 is 59mL, the volume of the colloidal solution 4 is 60mL, the volume of the colloidal solution 5 is 56mL, and the volume of the colloidal solution 6 is 57mL.
In this example, all bismuth potassium citrate tablets were from the same batch of medicine.
The preparation method of the artificial gastric juice comprises the following steps:
weighing 234mL of hydrochloric acid, and adding water to dilute to 1000mL to obtain dilute hydrochloric acid with the HCl of 9.5-10.5%;
16.4mL of the diluted hydrochloric acid, 800mL of water and 10g of pepsin are weighed, uniformly mixed in a beaker, and then water is added to fix the volume to 1000mL, so that the artificial gastric juice is obtained. In the following examples, the preparation method of the artificial gastric juice is the same as that of the example, and will not be described again.
The measurement results of step S2 are shown in the following table:
wherein the viscosity number of the blank solution was 1.14 mPas.
Conclusion: the viscosity test RSD values of the colloid solution 1, the colloid solution 2, the colloid solution 3, the colloid solution 4, the colloid solution 5 and the colloid solution 6 are smaller 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 a viscosity measurement method of the bismuth potassium citrate-containing preparation.
Example 2
Step S1, sample preparation: weighing 3 bismuth potassium citrate tablets (each bismuth content is 0.11g, and the total bismuth content in the 3 bismuth potassium citrate tablets is 0.33 g), placing in a beaker, adding 300mL of artificial gastric juice, stirring to dissolve all the bismuth potassium citrate tablets, standing in a water bath at 37 ℃ for 1h until the bismuth potassium citrate tablets are layered, transferring to a separating funnel, standing for 10min, and separating out a colloid solution at the lower layer after the bismuth potassium citrate tablets are layered to obtain a colloid solution 1;
and S2, weighing 20mL of the colloidal solution 1, and measuring the viscosity of the colloidal solution 1 by adopting a rotor of a viscometer No. 0 according to a third method rotational viscometer method of the four general rules 0633 of Chinese pharmacopoeia of 2020 edition under the condition of rotating at 60rpm/min.
In the step S1, the model of the bismuth potassium citrate tablet is as follows: bismuth potassium citrate tablets marketed by spanish, the manufacturer is: tora Laboratories S.L., under the trade name Gastrorenol, specification: 120mg (in Bi) 2 O 3 Meter).
And (3) the same principle: according to 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 bismuth potassium citrate tablets in the same batch, repeating the steps S1 and S2 for five times to prepare a colloid solution 2, a colloid solution 3, a colloid solution 4, a colloid solution 5 and a colloid solution 6, and measuring the viscosity of the colloid solution 2, the colloid solution 3, the colloid solution 4, the colloid solution 5 and the colloid solution 6 respectively.
In step S1, the volumes of the obtained colloidal solutions are inconsistent due to the experimental error, for example, the volume of the obtained colloidal solution 1 is 22.5mL, the volume of the obtained colloidal solution 2 is 20.5mL, the volume of the obtained colloidal solution 3 is 20.5mL, the volume of the obtained colloidal solution 4 is 21mL, the volume of the obtained colloidal solution 5 is 21mL, and the volume of the obtained colloidal solution 6 is 20mL.
In this example, all bismuth potassium citrate tablets were from the same batch of drugs, and were different from the batch in example 1, and from the batch in example 1.
The measurement results of step S2 are shown in the following table:
wherein the viscosity number of the blank solution was 1.19 mPas.
Conclusion: the viscosity test RSD values of the colloid solution 1, the colloid solution 2, the colloid solution 3, the colloid solution 4, the colloid solution 5 and the colloid solution 6 are smaller 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 a viscosity measurement method of the bismuth potassium citrate-containing preparation.
The comparison of the average viscosities of the two batches in the examples 1 and 2 shows that the viscosities of the same medicines produced in different batches are different, but 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 colloid characteristics of the medicines, the higher the viscosity of the medicines is, the more firm the protective film is formed on the gastric mucosa, the stronger the protective effect on the erosion surface and the ulcer focus is, and on the contrary, the lower the viscosity is, the weaker the protective film is formed on the gastric mucosa, the weaker the protective effect on the erosion surface 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 in different batches and in the same preparation method.
Example 3
Step S1, sample preparation: weighing 3 bags of bismuth potassium citrate particles (each bag of bismuth has the content of 0.11g, and the total content of bismuth in the 3 bags of bismuth potassium citrate particles is 0.33 g), placing in a beaker, adding 300mL of artificial gastric juice, stirring to dissolve all the bismuth potassium citrate particles, standing in a water bath at 37 ℃ for 1h until the bismuth potassium citrate particles are layered, transferring to a separating funnel, standing for 10min, and separating a colloidal solution at the lower layer after the bismuth potassium citrate particles are layered to obtain a colloidal solution 1;
and S2, weighing 25mL of the colloidal solution 1, and measuring the viscosity of the colloidal solution 1 by adopting a rotor of a viscometer No. 0 according to a third method rotational viscometer method of the four general rules 0633 of Chinese pharmacopoeia of 2020 edition under the condition of rotating at 60rpm/min.
In the embodiment, the sample is bismuth potassium citrate granules prepared by a laboratory, the bismuth content of each bag is 0.11g, and the total mass of each bag of bismuth potassium citrate granules is 1.2g.
And (3) the same principle: 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 bismuth potassium citrate particles in the same batch, repeating the steps S1 and S2 for five times, and preparing a colloid solution 2, a colloid solution 3, a colloid solution 4, a colloid solution 5 and a colloid solution 6, and respectively measuring the viscosity of the colloid solution 2, the colloid solution 3, the colloid solution 4, the colloid solution 5 and the colloid solution 6.
In step S1, the volumes of the obtained colloidal solutions are inconsistent due to the experimental error, for example, the volume of the obtained colloidal solution 1 is 51mL, the volume of the colloidal solution 2 is 42mL, the volume of the colloidal solution 3 is 44mL, the volume of the colloidal solution 4 is 46mL, the volume of the colloidal solution 5 is 47mL, and the volume of the colloidal solution 6 is 40mL.
In this example, all bismuth potassium citrate particles were produced from the same batch of bismuth potassium citrate particles.
The measurement results of step S2 are shown in the following table:
wherein the viscosity value of the blank solution is 1.10 mPas.
Conclusion: the viscosity test RSD values of the colloid solution 1, the colloid solution 2, the colloid solution 3, the colloid solution 4, the colloid solution 5 and the colloid solution 6 are smaller 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 a viscosity measurement method of the bismuth potassium citrate-containing preparation.
Example 4
Step S1, sample preparation: weighing 3 bags of bismuth potassium citrate particles (each bag of bismuth has the content of 0.11g, and the total content of bismuth in the 3 bags of bismuth potassium citrate particles is 0.33 g), placing in a beaker, adding 300mL of artificial gastric juice, stirring to dissolve all the bismuth potassium citrate particles, standing in a water bath at 37 ℃ for 1h until the bismuth potassium citrate particles are layered, transferring to a separating funnel, standing for 10min, and separating a colloidal solution at the lower layer after the bismuth potassium citrate particles are layered to obtain a colloidal solution 1;
and S2, weighing 25mL of the colloidal solution 1, and measuring the viscosity of the colloidal solution 1 by adopting a rotor of a viscometer No. 0 according to a third method rotational viscometer method of the four general rules 0633 of Chinese pharmacopoeia of 2020 edition under the condition of rotating at 60rpm/min.
In the embodiment, the sample is bismuth potassium citrate granules prepared by a laboratory, the bismuth content of each bag is 0.11g, and the total mass of each bag of bismuth potassium citrate granules is 1.2g.
And (3) the same principle: 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 bismuth potassium citrate particles in the same batch, repeating the steps S1 and S2 for five times, and preparing a colloid solution 2, a colloid solution 3, a colloid solution 4, a colloid solution 5 and a colloid solution 6, and respectively measuring the viscosity of the colloid solution 2, the colloid solution 3, the colloid solution 4, the colloid solution 5 and the colloid solution 6.
In step S1, the volumes of the obtained colloidal solutions are inconsistent due to the experimental error, for example, the volume of the obtained colloidal solution 1 is 38mL, the volume of the colloidal solution 2 is 35mL, the volume of the colloidal solution 3 is 38mL, the volume of the colloidal solution 4 is 40mL, the volume of the colloidal solution 5 is 30mL, and the volume of the colloidal solution 6 is 36mL.
In this example, all bismuth potassium citrate particles were produced from the same batch of bismuth potassium citrate particles, and were different from the batch in 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.
Conclusion: the viscosity test RSD values of the colloid solution 1, the colloid solution 2, the colloid solution 3, the colloid solution 4, the colloid solution 5 and the colloid solution 6 are smaller 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 a viscosity measurement method of the bismuth potassium citrate-containing preparation.
Example 5
Step S1, sample preparation: weighing 3 bags of bismuth potassium citrate particles (each bag of bismuth has the content of 0.11g, and the total content of bismuth in the 3 bags of bismuth potassium citrate particles is 0.33 g), placing in a beaker, adding 300mL of artificial gastric juice, stirring to dissolve all the bismuth potassium citrate particles, standing in a water bath at 37 ℃ for 1h until the bismuth potassium citrate particles are layered, transferring to a separating funnel, standing for 10min, and separating a colloidal solution at the lower layer after the bismuth potassium citrate particles are layered to obtain a colloidal solution 1;
and S2, weighing 25mL of the colloidal solution 1, and measuring the viscosity of the colloidal solution 1 by adopting a rotor of a viscometer No. 0 according to a third method rotational viscometer method of the four general rules 0633 of Chinese pharmacopoeia of 2020 edition under the condition of rotating at 60rpm/min. The sample is bismuth potassium citrate granules prepared by a laboratory, the bismuth content of each bag is 0.11g, and the total mass of each bag of bismuth potassium citrate granules is 1.2g.
And (3) the same principle: 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 a colloidal solution 2, a colloidal solution 3, a colloidal solution 4, a colloidal solution 5 and a colloidal solution 6, and the viscosities of the colloidal solution 2, the colloidal solution 3, the colloidal solution 4, the colloidal solution 5 and the colloidal solution 6 are respectively measured.
In step S1, the volumes of the obtained colloidal solutions are inconsistent due to the experimental error, for example, the volume of the obtained colloidal solution 1 is 50mL, the volume of the obtained colloidal solution 2 is 46mL, the volume of the obtained colloidal solution 3 is 44mL, the volume of the obtained colloidal solution 4 is 45mL, the volume of the obtained colloidal solution 5 is 48mL, and the volume of the obtained colloidal solution 6 is 43mL.
In this example, all bismuth potassium citrate particles were from bismuth potassium citrate particles produced in the same batch, and were different from the batches in examples 3 and 4.
The measurement results of step S2 are shown in the following table:
wherein the viscosity number of the blank solution was 1.14 mPas.
Conclusion: the viscosity test RSD values of the colloid solution 1, the colloid solution 2, the colloid solution 3, the colloid solution 4, the colloid solution 5 and the colloid solution 6 are smaller 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 a viscosity measurement method of the bismuth potassium citrate-containing preparation.
Example 6
Step S1, sample preparation: weighing 3 bags of bismuth potassium citrate particles (each bag of bismuth has the content of 0.11g, and the total content of bismuth in the 3 bags of bismuth potassium citrate particles is 0.33 g), placing in a beaker, adding 300mL of artificial gastric juice, stirring to dissolve all the bismuth potassium citrate particles, standing in a water bath at 37 ℃ for 1h until the bismuth potassium citrate particles are layered, transferring to a separating funnel, standing for 10min, and separating a colloidal solution at the lower layer after the bismuth potassium citrate particles are layered to obtain a colloidal solution 1;
and S2, weighing 25mL of the colloidal solution 1, and measuring the viscosity of the colloidal solution 1 by adopting a rotor of a viscometer No. 0 according to a third method rotational viscometer method of the four general rules 0633 of Chinese pharmacopoeia of 2020 edition under the condition of rotating at 60rpm/min. The sample is bismuth potassium citrate granules prepared by a laboratory, the bismuth content of each bag is 0.11g, and the total mass of each bag of bismuth potassium citrate granules is 1.2g.
And (3) the same principle: 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 a colloidal solution 2, a colloidal solution 3, a colloidal solution 4, a colloidal solution 5 and a colloidal solution 6, and the viscosities of the colloidal solution 2, the colloidal solution 3, the colloidal solution 4, the colloidal solution 5 and the colloidal solution 6 are respectively measured.
In step S1, the volumes of the obtained colloidal solutions are inconsistent due to the experimental error, for example, the volume of the obtained colloidal solution 1 is 38mL, the volume of the colloidal solution 2 is 35mL, the volume of the colloidal solution 3 is 38mL, the volume of the colloidal solution 4 is 40mL, the volume of the colloidal solution 5 is 30mL, and the volume of the colloidal solution 6 is 36mL.
In this example, all bismuth potassium citrate particles were from bismuth potassium citrate particles produced in the same batch, and were different from the batches in 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.
Conclusion: the viscosity test RSD values of the colloid solution 1, the colloid solution 2, the colloid solution 3, the colloid solution 4, the colloid solution 5 and the colloid solution 6 are smaller 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 a viscosity measurement method of the bismuth potassium citrate-containing preparation.
The comparison of the average viscosities of the four batches in examples 3, 4, 5 and 6 shows that the viscosities of the same medicine produced in different batches are different, and the viscosities are a quality evaluation means of the bismuth potassium citrate-containing preparation (the viscosity of the bismuth potassium citrate-containing preparation can reflect the colloid characteristics of the medicine, the higher the viscosity of the medicine is, the more firm the protective film is formed on the gastric mucosa, the stronger the protective effect on the erosion surface and the ulcer focus is, and conversely, the weaker the protective film is formed on the gastric mucosa, the weaker the protective effect on the erosion surface 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 in different batches and the same preparation method.
Bismuth Potassium citrate tablets of examples 1 and 2 were marketed as Spanish under the manufacturer Tora Laboratories S.L. under the trade name Gastrorenol with a specification of 120mg (Bi 2 O 3 Calculated) as a control drug for evaluation of the quality and efficacy consistency of bismuth potassium citrate imitation, the bismuth potassium citrate granules in examples 3, 4, 5 and 6 were imitation drugs of four batches of bismuth potassium citrate granules prepared by the skilled person in the laboratory. The viscosity averages measured in examples 1 and 2 were 2.08 mPas and 3.58 mPas, respectively, and the viscosity averages measured in examples 3, 4, 5 and 6 were 3.71 mPas, 3.48 mPas, 3.77 mPas and 4.54 mPas, respectively, as compared to the viscosity values of four laboratory-self-prepared bismuth potassium citrate particles all being higher than 2.08 mPas in example 1 and higher than or approximately 3.58 mPas in example 2, indicating that the quality of the four laboratory-self-prepared bismuth potassium citrate particles meets the requirements for consistency evaluation of the simulated drug quality as compared to the reference formulation.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the invention.
Claims (5)
1. A method for measuring the viscosity of a bismuth potassium citrate-containing preparation, comprising the steps of:
sample preparation: weighing a bismuth potassium citrate-containing 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 standing for the first time is 1-5h;
transferring the second solution to a separating funnel, standing for the second time, and separating out the colloid solution at the lower layer after layering, wherein the time of the second standing is 10-30min;
viscosity measurement: weighing the colloid solution, and measuring the viscosity of the colloid solution according to a third method rotational viscometer method of the four general rules 0633 of the Chinese pharmacopoeia of 2020 edition;
in the preparation process of the sample, the mass volume ratio of the total content of bismuth in the weighed bismuth potassium citrate-containing preparation to the artificial gastric juice is 0.35-1.5mg/mL.
2. The method for measuring the viscosity of a bismuth potassium citrate containing preparation according to claim 1, wherein the method for preparing artificial gastric juice comprises the following steps:
measuring a first volume of hydrochloric acid, adding water to dilute the first volume of hydrochloric acid to a second volume of hydrochloric acid, and obtaining dilute hydrochloric acid;
weighing the third volume of dilute hydrochloric acid, the fourth volume of water and the pepsin with preset mass, uniformly mixing, and adding water to a fifth volume to obtain the artificial gastric juice.
3. 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 volume of the colloidal solution is measured to be 20-60mL.
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 viscosity is measured by a viscometer No. 0 rotator.
5. The method for measuring the viscosity of a bismuth potassium citrate containing preparation according to claim 4, wherein the rotation speed of the No. 0 rotor of the viscometer is 50-70rpm/min.
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