CN112986289A - Consistency evaluation and detection method of amoxicillin capsules - Google Patents
Consistency evaluation and detection method of amoxicillin capsules Download PDFInfo
- Publication number
- CN112986289A CN112986289A CN202110141988.3A CN202110141988A CN112986289A CN 112986289 A CN112986289 A CN 112986289A CN 202110141988 A CN202110141988 A CN 202110141988A CN 112986289 A CN112986289 A CN 112986289A
- Authority
- CN
- China
- Prior art keywords
- amoxicillin
- mobile phase
- solution
- consistency
- detected
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 title claims abstract description 105
- 229960003022 amoxicillin Drugs 0.000 title claims abstract description 105
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 title claims abstract description 105
- 239000002775 capsule Substances 0.000 title claims abstract description 92
- 238000001514 detection method Methods 0.000 title claims abstract description 23
- 238000011156 evaluation Methods 0.000 title description 4
- 238000002360 preparation method Methods 0.000 claims abstract description 51
- 239000013078 crystal Substances 0.000 claims abstract description 48
- 238000000034 method Methods 0.000 claims abstract description 44
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 39
- 239000012535 impurity Substances 0.000 claims abstract description 30
- 238000010828 elution Methods 0.000 claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 25
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229940079593 drug Drugs 0.000 claims abstract description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims abstract description 10
- 235000019796 monopotassium phosphate Nutrition 0.000 claims abstract description 10
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000000243 solution Substances 0.000 claims description 55
- 238000004090 dissolution Methods 0.000 claims description 18
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 15
- 238000005070 sampling Methods 0.000 claims description 13
- 239000012738 dissolution medium Substances 0.000 claims description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 238000002441 X-ray diffraction Methods 0.000 claims description 8
- 238000012360 testing method Methods 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 239000011259 mixed solution Substances 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 238000007865 diluting Methods 0.000 claims description 4
- 239000010439 graphite Substances 0.000 claims description 4
- 229910002804 graphite Inorganic materials 0.000 claims description 4
- 239000008351 acetate buffer Substances 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 3
- 239000008055 phosphate buffer solution Substances 0.000 claims description 3
- 230000001502 supplementing effect Effects 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000012085 test solution Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 11
- 230000035945 sensitivity Effects 0.000 abstract description 9
- 230000000052 comparative effect Effects 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000008187 granular material Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000011049 filling Methods 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 235000012239 silicon dioxide Nutrition 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 238000010586 diagram Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 241000194017 Streptococcus Species 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000011362 coarse particle Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- -1 Amixil Chemical compound 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 241000590002 Helicobacter pylori Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010087702 Penicillinase Proteins 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 241000588770 Proteus mirabilis Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007905 drug manufacturing Methods 0.000 description 1
- 229940032049 enterococcus faecalis Drugs 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 229940037467 helicobacter pylori Drugs 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229950009506 penicillinase Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N23/00—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00
- G01N23/20—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00 by using diffraction of the radiation by the materials, e.g. for investigating crystal structure; by using scattering of the radiation by the materials, e.g. for investigating non-crystalline materials; by using reflection of the radiation by the materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N30/14—Preparation by elimination of some components
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/86—Signal analysis
- G01N30/8624—Detection of slopes or peaks; baseline correction
- G01N30/8631—Peaks
- G01N30/8634—Peak quality criteria
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N2030/042—Standards
- G01N2030/047—Standards external
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N30/14—Preparation by elimination of some components
- G01N2030/146—Preparation by elimination of some components using membranes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
- G01N2030/8872—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample impurities
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2223/00—Investigating materials by wave or particle radiation
- G01N2223/05—Investigating materials by wave or particle radiation by diffraction, scatter or reflection
- G01N2223/056—Investigating materials by wave or particle radiation by diffraction, scatter or reflection diffraction
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2223/00—Investigating materials by wave or particle radiation
- G01N2223/10—Different kinds of radiation or particles
- G01N2223/101—Different kinds of radiation or particles electromagnetic radiation
- G01N2223/1016—X-ray
Landscapes
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Quality & Reliability (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for evaluating and detecting the consistency of an amoxicillin capsule, which systematically and comprehensively inspects and evaluates the consistency between the amoxicillin capsule to be tested for imitation drugs and a reference preparation of an original grinding drug by comparing crystal forms and impurities of the amoxicillin capsule to be tested and the reference preparation. Corresponding scanning speed and intensity are selected according to the crystal form characteristics of the amoxicillin capsule to be detected, the detection of the characteristic peaks of the crystal forms of the amoxicillin capsule to be detected and a reference preparation is sensitive, and the diffraction angles of the crystal forms of the two medicines are accurately detected. The mobile phase is a solution of potassium dihydrogen phosphate solution and one or more of acetonitrile solution, formamide solution or isopropanol solution for gradient elution, so that the elution effect is better, and the accuracy and the sensitivity of the detection result are improved. The invention is used for solving the technical problems of low accuracy and sensitivity and incomplete detection of the existing method for evaluating the consistency of the amoxicillin capsules.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a consistency evaluation detection method of an amoxicillin capsule.
Background
Amoxicillin (Amoxicillin, Amixil, Amoxicillin) is a penicillin antibiotic, and has good antibacterial activity against non-beta-lactamase-producing strains of streptococcus such as streptococcus pneumoniae and hemolytic streptococcus, non-penicillinase-producing staphylococcus, enterococcus faecalis and other aerobic gram-positive cocci, escherichia coli, proteus mirabilis, salmonella, haemophilus influenzae, neisseria gonorrhoeae and other aerobic gram-negative bacteria, and helicobacter pylori. Amoxicillin exerts a bactericidal effect by inhibiting the synthesis of bacterial cell walls, and can make bacteria quickly become spheroids to be dissolved and broken.
According to the national requirements, the quality consistency of the imitation drugs is evaluated by drug manufacturing enterprises according to the principle that the quality and the curative effect of the imitation drugs approved to be on the market are consistent with those of the original medicines, and the improvement of the production process which does not reach the standard is carried out, so that the quality and the curative effect of the medicines are improved, and the common people are benefited. Therefore, a production process needs to be researched so as to prepare the amoxicillin capsule which has consistent quality and curative effect with the original product. At present, the detection method for evaluating the consistency of the amoxicillin capsules is low in accuracy and sensitivity, incomplete in detection and deviated in consistency judgment of the amoxicillin capsules and the original ground medicines.
Disclosure of Invention
The invention provides a method for evaluating and detecting the consistency of an amoxicillin capsule, which is used for solving the technical problems of low accuracy and sensitivity and incomplete detection of the existing method for evaluating and detecting the consistency of the amoxicillin capsule.
In view of the above, the method for evaluating and detecting the consistency of the amoxicillin capsule provided by the invention comprises the following steps of carrying out crystal form comparison and impurity comparison on the amoxicillin capsule to be detected and a reference preparation;
the crystal form comparison comprises the steps of detecting the crystal forms of the amoxicillin capsules to be detected and the reference preparation by adopting an X-ray diffraction method, and the set parameters before the crystal form comparison and the test are as follows: the tube voltage of an X-ray tube is 37kV, the tube current is 22mA, the scanning speed is 0.3deg./min, and whether the characteristic peak and the diffraction angle of a crystal form spectrogram are consistent or not is compared;
the impurity comparison comprises detecting impurities in the amoxicillin capsules to be detected and the reference preparation by adopting a high performance liquid chromatography, wherein the high performance liquid chromatography comprises gradient elution by using a mobile phase A and a mobile phase B, and the mobile phase A is a potassium dihydrogen phosphate solution; the mobile phase B is one or a combination of more of acetonitrile solution, formamide solution or isopropanol solution, and the types and the contents of impurities in the two medicines are compared to determine whether the types and the contents of the impurities are consistent;
when the characteristic peaks and diffraction angles of the measured crystal form spectrograms of the amoxicillin capsule to be detected and the reference preparation are the same, and the types and contents of impurities in the two medicines are the same, the consistency of the structures and properties of the amoxicillin capsule to be detected and the reference preparation is judged.
Optionally, the reference formulation is AMOXICILLIN, and the dosage form is a capsule, with a specification of 500 mg.
Alternatively, the X-ray diffraction method employs a DX-2500 type X-ray diffractometer.
Alternatively, a DX-2500 model X-ray diffractometer is fitted with a DWS-3 model curved graphite crystal monochromator.
Alternatively, the mobile phase B is a mixed solution of a 90% acetonitrile solution and a 10% formamide solution.
Alternatively, the gradient elution order and the ratio of mobile phase a to mobile phase B are as follows:
carrying out first elution for 0-10 minutes by adopting the volume ratio of the mobile phase A to the mobile phase B to be 98: 2; carrying out secondary elution for 10-30 minutes when the volume ratio of the mobile phase A to the mobile phase B is 85: 15; carrying out third elution for 30-37 minutes at the volume ratio of the mobile phase A to the mobile phase B of 70: 30; and carrying out fourth elution for 37-45 minutes at the volume ratio of the mobile phase A to the mobile phase B of 98: 2.
Alternatively, the detection wavelength of high performance liquid chromatography is 254 nm; the flow rate is 1.5 mL/min; the column temperature was 35 ℃; the amount of sample was 10. mu.L.
Optionally, the method further comprises a dissolution curve comparison step, wherein the amoxicillin capsule to be tested and the reference preparation are taken, water, a pH4.5 acetate buffer solution, a pH6.8 phosphate buffer solution and a 0.1mol/L hydrochloric acid solution are respectively used as dissolution media, the set rotating speed is 100 revolutions per minute, different sampling times are selected for sampling, the dissolution rates of the amoxicillin capsule to be tested and the reference preparation in different dissolution media are respectively measured, and the dissolution rate is used as a vertical coordinate, and the sampling time is used as a horizontal coordinate for drawing to obtain the dissolution curve.
Optionally, the sampling time is 5min, 10min, 15min, 20min and 30 min.
Optionally, the sampling comprises filtering 10ml of the solution to be tested with 0.45 μm filter membrane, supplementing 10ml of dissolution medium in time, precisely transferring 5ml of filtrate into a 10ml measuring flask, diluting with 0.1mol/L sodium hydroxide solution to scale, shaking up, precisely measuring 20 μ L of the solution as a sample solution, and injecting into a high performance liquid chromatograph.
According to the technical scheme, the embodiment of the invention has the following advantages:
the invention provides a method for evaluating and detecting the consistency of an amoxicillin capsule, which systematically and comprehensively inspects and evaluates the consistency between the amoxicillin capsule to be tested for the imitation pharmacy and a reference preparation of the original medicine by comparing crystal forms and impurities of the amoxicillin capsule to be tested and the reference preparation. Corresponding scanning speed and intensity are selected according to the crystal form characteristics of the amoxicillin capsule to be detected, the detection of the characteristic peaks of the crystal forms of the amoxicillin capsule to be detected and a reference preparation is sensitive, and the diffraction angles of the crystal forms of the two medicines are accurately detected. The crystal form has great influence on the solubility and the bioavailability of the medicine, so when the characteristic peaks and diffraction angles of crystal form spectrograms of the amoxicillin capsule to be detected and a reference preparation are consistent, the effects of the solubility and the bioavailability are also consistent.
Gradient elution is carried out by adopting a mobile phase A and a mobile phase B, wherein the mobile phase A is a potassium dihydrogen phosphate solution, and the mobile phase B is one or a combination of more of an acetonitrile solution, a formamide solution or an isopropanol solution, so that the elution effect is better, and the accuracy and the sensitivity of a detection result are improved. When the types of the impurities in the reference preparation and the amoxicillin capsule to be detected are consistent, the process synthetic routes of the two medicines are the same; when the impurity contents are consistent, the process and process parameters of the two medicines are consistent, so that the product quality of the reference preparation and the amoxicillin capsule to be detected is consistent.
The invention provides a method for evaluating and detecting the consistency of amoxicillin capsules, which is used for solving the technical problems of low accuracy and sensitivity and incomplete detection of the existing method for evaluating and detecting the consistency of amoxicillin capsules.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments described in the present invention, and it is obvious for those skilled in the art to obtain other drawings according to these drawings.
FIG. 1 is a comparison spectrum of crystal forms of amoxicillin capsules to be tested and a reference preparation provided in the embodiment of the present invention;
FIG. 2 is a comparison chart of crystal forms of comparative example 1 and a reference formulation standard provided in examples of the present invention;
FIG. 3 is a schematic structural diagram of amoxicillin capsule impurities B, C and D to be detected provided in the embodiment of the present invention;
FIG. 4 is a schematic structural diagram of amoxicillin capsule impurities E, G, I and J to be detected in the embodiment of the present invention;
fig. 5 is a schematic diagram of dissolution curves of amoxicillin capsules to be tested in different dissolution media provided in the embodiment of the present invention.
Detailed Description
In order to make those skilled in the art better understand the technical solutions of the present invention, the following embodiments of the present invention are clearly and completely described, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. Unless otherwise specifically stated, various raw materials, reagents, instruments, equipment and the like used in the present invention are commercially available or can be prepared by existing methods.
Example 1
The invention provides an embodiment of a method for evaluating and detecting the consistency of an amoxicillin capsule, which comprises the following steps of carrying out crystal form comparison and impurity comparison on the amoxicillin capsule to be detected and a reference preparation;
the crystal form comparison comprises the steps of detecting the crystal forms of the amoxicillin capsules to be detected and the reference preparation by adopting an X-ray diffraction method, and the set parameters before the crystal form comparison and the test are as follows: the tube voltage of an X-ray tube is 37kV, the tube current is 22mA, the scanning speed is 0.3deg./min, and whether the characteristic peak and the diffraction angle of a crystal form spectrogram are consistent or not is compared;
the impurity comparison comprises detecting impurities in the amoxicillin capsules to be detected and the reference preparation by adopting a high performance liquid chromatography, wherein the high performance liquid chromatography comprises gradient elution by using a mobile phase A and a mobile phase B, and the mobile phase A is a potassium dihydrogen phosphate solution; the mobile phase B is one or a combination of more of acetonitrile solution, formamide solution or isopropanol solution, and the types and the contents of impurities in the two medicines are compared to determine whether the types and the contents of the impurities are consistent;
when the characteristic peaks and diffraction angles of the measured crystal form spectrograms of the amoxicillin capsule to be detected and the reference preparation are the same, and the types and contents of impurities in the two medicines are the same, the consistency of the structures and properties of the amoxicillin capsule to be detected and the reference preparation is judged.
It should be noted that the reference preparation adopted by the invention is AMOXICILLIN, the dosage form is capsule, and the specification is 500 mg.
The invention provides a method for evaluating and detecting the consistency of an amoxicillin capsule, which systematically and comprehensively inspects and evaluates the consistency between the amoxicillin capsule to be tested for the imitation pharmacy and a reference preparation of the original medicine by comparing crystal forms and impurities of the amoxicillin capsule to be tested and the reference preparation. Corresponding scanning speed and intensity are selected according to the crystal form characteristics of the amoxicillin capsule to be detected, the detection of the characteristic peaks of the crystal forms of the amoxicillin capsule to be detected and a reference preparation is sensitive, and the diffraction angles of the crystal forms of the two medicines are accurately detected. The crystal form has great influence on the solubility and the bioavailability of the medicine, so when the characteristic peaks and diffraction angles of crystal form spectrograms of the amoxicillin capsule to be detected and a reference preparation are consistent, the effects of the solubility and the bioavailability are also consistent.
Gradient elution is carried out by adopting a mobile phase A and a mobile phase B, wherein the mobile phase A is a potassium dihydrogen phosphate solution, and the mobile phase B is one or a combination of more of an acetonitrile solution, a formamide solution or an isopropanol solution, so that the elution effect is better, and the accuracy and the sensitivity of a detection result are improved. When the types of the impurities in the reference preparation and the amoxicillin capsule to be detected are consistent, the process synthetic routes of the two medicines are the same; when the impurity contents are consistent, the process and process parameters of the two medicines are consistent, so that the product quality of the reference preparation and the amoxicillin capsule to be detected is consistent.
The invention provides a method for evaluating and detecting the consistency of amoxicillin capsules, which is used for solving the technical problems of low accuracy and sensitivity and incomplete detection of the existing method for evaluating and detecting the consistency of amoxicillin capsules.
Example 2
According to one embodiment of the method for evaluating and detecting the consistency of the amoxicillin capsules, a DX-2500 type X-ray diffractometer is adopted in an X-ray diffraction method and is matched with a DWS-3 type bent graphite crystal monochromator, and the parameters are set before crystal form comparison test: the tube voltage of the X-ray tube is 37kV, the tube current is 22mA, and the scanning speed is 0.3 deg./min.
The corresponding scanning speed and intensity are selected according to the crystal form characteristics of the amoxicillin capsule to be detected. The crystal form comparison spectrogram of the amoxicillin capsule to be detected and the reference preparation is shown in figure 1, and the crystal form comparison result is as follows:
as can be seen from the figure 1 and the table above, the characteristic peak value and the diffraction angle in the X-ray diffraction patterns of the amoxicillin capsule to be tested and the reference preparation are consistent, and the crystal forms are consistent.
Comparative example 1
The invention provides a comparative example of a method for evaluating and detecting the consistency of amoxicillin capsules, wherein a DX-2500 type X-ray diffractometer is adopted in an X-ray diffraction method, a DWS-3 type bent graphite crystal monochromator is matched, and the set parameters before the crystal form comparison test are as follows: and measuring the characteristic peak spectrogram of the crystal form of the reference preparation by using an X-ray tube with the voltage of 45kV, the tube current of 35mA and the scanning speed of 0.8 deg./min.
As can be seen from fig. 2, compared with the existing known reference preparation spectrogram, the parameters set before the crystal form comparison test in the comparative example lead to the obvious shift of the spectrogram characteristic peak position and the distortion of the partial area line shape. Compared with the figure 1, the reference preparation spectrogram is basically the same as the characteristic peak position of the reference preparation standard, which indicates that the spectrogram detected in the example 2 is more accurate.
Example 3
In one embodiment of the consistency evaluation and detection method of the amoxicillin capsules, the detection wavelength of the high performance liquid chromatography is 254 nm; the flow rate is 1.5 mL/min; the column temperature was 35 ℃; the amount of sample was 10. mu.L. The high performance liquid chromatography comprises gradient elution with mobile phase A and mobile phase B, wherein the mobile phase A is potassium dihydrogen phosphate solution with optional concentration of 0.05mol/L and pH value of 5; the mobile phase B is one or the combination of acetonitrile solution, formamide solution or isopropanol solution, preferably the mixed solution of 90% acetonitrile solution and 10% formamide solution, so that the elution effect is better, and the accuracy and the sensitivity of the detection result are improved.
In order to accelerate the detection speed and enhance the elution effect, the gradient elution order and the ratio of the mobile phase A to the mobile phase B are selected as follows:
carrying out first elution for 0-10 minutes by adopting the volume ratio of the mobile phase A to the mobile phase B to be 98: 2; carrying out secondary elution for 10-30 minutes when the volume ratio of the mobile phase A to the mobile phase B is 85: 15; carrying out third elution for 30-37 minutes at the volume ratio of the mobile phase A to the mobile phase B of 70: 30; and carrying out fourth elution for 37-45 minutes at the volume ratio of the mobile phase A to the mobile phase B of 98: 2.
The impurity detection results of the amoxicillin capsule to be detected and the reference preparation are as follows:
the structures of the impurities B, C, D, E, G, I and J are shown in FIGS. 3 and 4, and the above table shows that the types and contents of the impurities of the amoxicillin capsules to be tested and the reference preparations are consistent.
Comparative example 2
The invention provides a comparative example of a method for evaluating and detecting the consistency of amoxicillin capsules, which adopts an examination method of related amoxicillin substances in the second part of the Chinese pharmacopoeia of 2015 edition to detect, selects a mixed solution with the volume ratio of 0.05mol/l potassium dihydrogen phosphate solution to acetonitrile of 99:1 as a mobile phase A, a mixed solution with the volume ratio of 0.05mol/l potassium dihydrogen phosphate solution to acetonitrile of 80:20 as a mobile phase B and 0.05mol/l potassium dihydrogen phosphate solution, adjusts the pH to 5.0 by using 2mol/l potassium hydroxide solution, the flow rate is 1.0ml/min, the wavelength is 254nm, the column temperature is 25 ℃, and the sample injection amount is 20 ul. Gradient elution was performed as follows:
| elution time (time) | Mobile phase A | |
| 0 | 92 | 8 |
| 25 | 0 | 100 |
| 40 | 0 | 100 |
| 41 | 92 | 8 |
| 55 | 92 | 8 |
To illustrate the advantages of the present invention, a recovery test was conducted for example 3 and comparative example 2, respectively.
The recovery was determined by HPLC according to the standard recovery test in the Chinese pharmacopoeia (2015 edition) as selected in example 3 using different mobile phases B and comparative example 2, and the results are shown below:
as can be seen from the above table, the average recovery rates of the HPLC methods of example 3 and comparative example 1 are both above 95%, indicating that the accuracy meets the production standard, and the RSD value also meets the requirement of precision in production. However, the high performance liquid chromatography of example 3 has higher accuracy and better precision than the high performance liquid chromatography of comparative example 1, and the working efficiency can be improved well in production. The high performance liquid chromatography in example 3 uses a mixed solution of a 90% acetonitrile solution and a 10% formamide solution as a mobile phase B, and thus the accuracy and precision of detection are optimal.
Example 4
The embodiment also provides a preparation method of the amoxicillin capsule to be detected, which comprises the following steps:
s1: preparing raw materials and auxiliary materials, wherein the raw materials comprise 250 parts by weight of amoxicillin, and the auxiliary materials comprise 1.25 parts by weight of silicon dioxide, 1 part by weight of magnesium stearate and 5 parts by weight of carboxymethyl starch sodium;
s2: sieving, namely respectively sieving silicon dioxide, sodium carboxymethyl starch and magnesium stearate by a 40-mesh sieve at the temperature of 18-26 ℃ and the humidity of 45-65%;
s3: weighing ingredients, namely weighing amoxicillin, silicon dioxide, sodium carboxymethyl starch and magnesium stearate according to the formula, and marking at the temperature of 18-26 ℃ and the humidity of 45-65%;
s4: granulating, namely adding the raw material amoxicillin into a dry granulating machine, and granulating through a 0.8mm screen to obtain amoxicillin granules, wherein the pressure of a compression roller of the dry granulating machine is 8-10 MPa, and the gap between the compression rollers is 0.6-0.9 mm; the rotating speed of the press roll is 15-20 r/min; sucking the finished amoxicillin particles into a ternary rotary vibration sieve by a vacuum feeding machine at the rotating speed of 100-120 r/min, removing coarse particles by using a 20-mesh screen, removing fine particles by using a 60-mesh screen, and finishing the coarse particles repeatedly to obtain heavy powder particles, wherein the temperature is 18-26 ℃, and the humidity is 45-65%;
s5: mixing, namely adding the raw and auxiliary materials into a mixing machine according to the sequence of amoxicillin granules, sodium carboxymethyl starch, silicon dioxide, magnesium stearate and amoxicillin granules, closing a feeding port, setting the mixing time to be 10 minutes, and mixing at a constant speed to obtain an intermediate product, wherein the temperature is 18-26 ℃, and the humidity is 45-65%; preferably, the amoxicillin granules added firstly are half of the prescription amount, and the amoxicillin granules added later are the other half of the prescription amount;
s6: filling, namely controlling a full-automatic capsule filling machine according to a filling production instruction to prepare the amoxicillin capsule to be detected, wherein the filling speed of the full-automatic capsule filling machine is 2000-2500 granules/minute, the temperature is 18-26 ℃, and the humidity is 45-65%, so as to prepare the amoxicillin capsule to be detected.
Example 5
As a further improvement to example 1, the method further comprises a dissolution curve comparison, taking an amoxicillin capsule to be tested and a reference preparation, taking water, a pH4.5 acetate buffer solution, a pH6.8 phosphate buffer solution and a 0.1mol/L hydrochloric acid solution as dissolution media respectively, rotating at 100 revolutions per minute, setting sampling time to be 5min, 10min, 15min, 20min and 30min for sampling, taking 10ml of the solution to be tested, filtering with a 0.45 μm filter membrane, supplementing 10ml dissolution media in time, precisely transferring 5ml of the filtrate into a 10ml measuring flask, diluting to a scale with 0.1mol/L sodium hydroxide solution, shaking up, precisely measuring 20 μ L as a test solution, injecting into a high performance liquid chromatograph to respectively measure dissolution rates of the amoxicillin capsule to be tested and the reference preparation in different dissolution media, taking another amoxicillin reference preparation 56mg, precisely weighing, placing into a 100ml measuring flask, dissolving with medium, diluting to scale, shaking, measuring with the same method, and calculating dissolution rate at each time point according to external standard method with peak area. The dissolution rate is taken as the ordinate, and the sampling time is taken as the abscissa to obtain the dissolution curve. The dissolution rate comparison result of the amoxicillin capsule to be tested and the reference preparation is as follows:
the dissolution rate comparison result is shown above, and the dissolution curves of the amoxicillin capsule to be tested and the reference preparation are consistent, which indicates that the drug release mechanism and the effect in human body are consistent. As can be seen from figure 5, the amoxicillin capsules to be tested have different dissolution rates in different dissolution media with different pH values, so that the amoxicillin capsules to be tested are dissolved in different parts of the human body to different degrees, and the requirements of the human body on the anti-inflammatory drug are met.
The above-mentioned embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the same; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (10)
1. A method for evaluating and detecting the consistency of an amoxicillin capsule is characterized by comprising the following steps of comparing the amoxicillin capsule to be detected with a reference preparation in a crystal form and impurity;
the crystal form comparison comprises the step of detecting the crystal forms of the amoxicillin capsule to be detected and the reference preparation by adopting an X-ray diffraction method, and the set parameters before the crystal form comparison test are as follows: the tube voltage of an X-ray tube is 37kV, the tube current is 22mA, the scanning speed is 0.3deg./min, and whether the characteristic peak and the diffraction angle of a crystal form spectrogram are consistent or not is compared;
the impurity comparison comprises detecting impurities in the amoxicillin capsule to be detected and the reference preparation by adopting a high performance liquid chromatography, wherein the high performance liquid chromatography comprises gradient elution by using a mobile phase A and a mobile phase B, and the mobile phase A is a potassium dihydrogen phosphate solution; the mobile phase B is one or a combination of more of acetonitrile solution, formamide solution or isopropanol solution, and the types and the contents of impurities in the two medicines are compared to determine whether the types and the contents of the impurities are consistent;
and when the characteristic peaks and diffraction angles of the crystal form spectrograms of the amoxicillin capsule to be detected and the reference preparation are the same, and the types and contents of impurities in the two medicines are the same, judging that the amoxicillin capsule to be detected and the reference preparation have consistency in structure and properties.
2. The method for evaluating and detecting the consistency of AMOXICILLIN capsules to be tested according to claim 1, characterized in that the reference preparation is AMOXICILLIN, the dosage form is a capsule, and the specification is 500 mg.
3. The method for evaluating and detecting the consistency of amoxicillin capsules to be tested according to claim 1, characterized in that a DX-2500 type X-ray diffractometer is adopted in the X-ray diffraction method.
4. The method for evaluating and detecting the consistency of the amoxicillin capsules to be tested according to claim 3, characterized in that the DX-2500 type X-ray diffractometer is matched with a DWS-3 type curved graphite crystal monochromator.
5. The method for evaluating and detecting the consistency of amoxicillin capsules to be tested according to claim 1, characterized in that the mobile phase B is a mixed solution of 90% acetonitrile solution and 10% formamide solution.
6. The method for evaluating and detecting the consistency of amoxicillin capsules to be tested according to claim 1, characterized in that the gradient elution order and the ratio of the mobile phase A to the mobile phase B are as follows:
carrying out first elution for 0-10 minutes by adopting the volume ratio of the mobile phase A to the mobile phase B to be 98: 2; performing second elution for 10-30 minutes at the volume ratio of the mobile phase A to the mobile phase B of 85: 15; carrying out third elution for 30-37 minutes at the volume ratio of the mobile phase A to the mobile phase B of 70: 30; and carrying out fourth elution for 37-45 minutes at the volume ratio of the mobile phase A to the mobile phase B of 98: 2.
7. The method for evaluating and detecting the consistency of amoxicillin capsules to be detected according to claim 1, characterized in that the detection wavelength of the high performance liquid chromatography is 254 nm; the flow rate is 1.5 mL/min; the column temperature was 35 ℃; the amount of sample was 10. mu.L.
8. The method for evaluating and detecting the consistency of the amoxicillin capsules to be detected according to claim 1, characterized by further comprising a dissolution curve comparison step, wherein the amoxicillin capsules to be detected and the reference preparation are taken, water, a pH4.5 acetate buffer solution, a pH6.8 phosphate buffer solution and a 0.1mol/L hydrochloric acid solution are respectively used as dissolution media, the set rotating speed is 100 revolutions per minute, different sampling times are selected for sampling, the dissolution rates of the amoxicillin capsules to be detected and the reference preparation in different dissolution media are respectively measured, and the dissolution rates are used as vertical coordinates and the sampling times are used as horizontal coordinates for drawing to obtain the dissolution curve.
9. The method for evaluating and detecting the consistency of amoxicillin capsules to be tested according to claim 8, characterized in that the sampling time is 5min, 10min, 15min, 20min and 30 min.
10. The method for evaluating and detecting the consistency of the amoxicillin capsules to be tested according to claim 8, characterized in that the sampling comprises filtering 10ml of a solution to be tested with a 0.45 μm filter membrane, supplementing 10ml of the dissolution medium in time, precisely transferring 5ml of the filtrate into a 10ml measuring flask, diluting to a scale with 0.1mol/L sodium hydroxide solution, shaking up, precisely measuring 20 μ L of the solution as a test solution, and injecting the solution into a high performance liquid chromatograph.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110141988.3A CN112986289A (en) | 2021-02-02 | 2021-02-02 | Consistency evaluation and detection method of amoxicillin capsules |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110141988.3A CN112986289A (en) | 2021-02-02 | 2021-02-02 | Consistency evaluation and detection method of amoxicillin capsules |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112986289A true CN112986289A (en) | 2021-06-18 |
Family
ID=76346118
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110141988.3A Pending CN112986289A (en) | 2021-02-02 | 2021-02-02 | Consistency evaluation and detection method of amoxicillin capsules |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112986289A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114767072A (en) * | 2022-06-24 | 2022-07-22 | 北京惠每云科技有限公司 | Method and device for determining consistency of curative effects of medicines, electronic equipment and storage medium |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2006310873A1 (en) * | 2005-10-31 | 2007-05-10 | Leo Pharma A/S | Preparation of an antibiotic crystalline fusidic acid |
| CN103183671A (en) * | 2011-12-29 | 2013-07-03 | 天津康鸿医药科技发展有限公司 | Novel moxifloxacin hydrochloride crystal, and preparation method and application thereof |
| US20170101660A1 (en) * | 2015-10-07 | 2017-04-13 | Gwangju Institute Of Science And Technology | Enzyme-immobilized porous membrane and preparation method of antibiotics using the same |
| CN108693292A (en) * | 2018-07-25 | 2018-10-23 | 广州白云山医药集团股份有限公司白云山制药总厂 | A kind of detection method of amoxil capsule impurity |
-
2021
- 2021-02-02 CN CN202110141988.3A patent/CN112986289A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2006310873A1 (en) * | 2005-10-31 | 2007-05-10 | Leo Pharma A/S | Preparation of an antibiotic crystalline fusidic acid |
| CN103183671A (en) * | 2011-12-29 | 2013-07-03 | 天津康鸿医药科技发展有限公司 | Novel moxifloxacin hydrochloride crystal, and preparation method and application thereof |
| US20170101660A1 (en) * | 2015-10-07 | 2017-04-13 | Gwangju Institute Of Science And Technology | Enzyme-immobilized porous membrane and preparation method of antibiotics using the same |
| CN108693292A (en) * | 2018-07-25 | 2018-10-23 | 广州白云山医药集团股份有限公司白云山制药总厂 | A kind of detection method of amoxil capsule impurity |
Non-Patent Citations (5)
| Title |
|---|
| ESEN BELLUR ATICI等: "阿莫西林克拉维酸钾制剂有关物质及含量分析的HPLC稳定性指示方法的建立与验证", 《JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS》, 27 December 2016 (2016-12-27) * |
| 周璟明等: "阿莫西林胶囊仿制药与原研药溶出行为研究及有区分力溶出方法的建立", 《中国抗生素杂志》, vol. 45, no. 07, 31 July 2020 (2020-07-31), pages 666 - 671 * |
| 屠颖, 屠洁: "β-内酰胺类抗生素分析方法进展", 国外医药.抗生素分册, no. 02, 25 February 2002 (2002-02-25) * |
| 梅梅: "他汀类仿制药质量一致性评价研究", 《工程科技Ⅰ辑》, no. 07, 15 July 2019 (2019-07-15), pages 4 - 7 * |
| 王婷婷;洪建文;: "阿莫西林胶囊国内外现状比较分析", 国外医药(抗生素分册), no. 02, 15 March 2019 (2019-03-15) * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114767072A (en) * | 2022-06-24 | 2022-07-22 | 北京惠每云科技有限公司 | Method and device for determining consistency of curative effects of medicines, electronic equipment and storage medium |
| CN114767072B (en) * | 2022-06-24 | 2022-09-06 | 北京惠每云科技有限公司 | Method and device for determining consistency of curative effects of medicines, electronic equipment and storage medium |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Viscomi et al. | Crystal forms of rifaximin and their effect on pharmaceutical properties | |
| CN104876947B (en) | Cefetamet Pivoxil Hydrochloride hydrate crystal and its dispersible tablet | |
| CN111721849A (en) | Analysis method for determining content of main drug in pramipexole dihydrochloride sustained-release tablets | |
| CN102949410A (en) | Compound omeprazole capsule and preparation method and detection method thereof | |
| CN112986289A (en) | Consistency evaluation and detection method of amoxicillin capsules | |
| CN103830192A (en) | Tenofovir disoproxil fumarate tablets allowing direct powder compression and preparation method thereof | |
| KR20190136037A (en) | Of (S)-[2-chloro-4-fluoro-5- (7-morpholin-4-ylquinazolin-4-yl) phenyl]-(6-methoxy-pyridazin-3-yl) methanol Solid form | |
| CN105085549B (en) | The pharmaceutical composition and its preparation of a kind of Cefaclor compound, the compound and bromhexine hydrochloride | |
| CN106966944B (en) | Vildagliptin crystal form compound and preparation method thereof | |
| CN104721158B (en) | A kind of everolimus tablet of stabilization | |
| CN102942577B (en) | Cefoxitin sodium compound-containing pharmaceutical composition | |
| CN109908104B (en) | Amoxicillin capsule and preparation method thereof | |
| CN112336693A (en) | Method for rapidly controlling and evaluating release of macitentan tablets | |
| CN112156082A (en) | Amoxicillin capsule preparation method and amoxicillin capsule | |
| CN103622916B (en) | Cefixime dry suspension and preparation method thereof | |
| CN106748996A (en) | A kind of Sorafenib Tosylate crystal-form compound and preparation method thereof | |
| CN104926835B (en) | A kind of cefotiam hydrochloride compound, its preparation method and its pharmaceutical composition | |
| CN110934833A (en) | Compound paracetamol and chlorphenamine maleate granules | |
| CN105949241B (en) | Crystal formation A of Yi Zhong oxazolidinone antibacterials sodium salts and its preparation method and application | |
| EP4268821A1 (en) | Pharmaceutical composition containing pyrroloquinoline quinone trilithium salt nonahydrate compound, capsule, and preparation method therefor | |
| CN103301081A (en) | Cefdinir dispersible tablet and preparation method thereof | |
| CN104844624B (en) | A kind of cefoperazone sodium sulbactam sodium eutectic and composition and method of making the same | |
| CN112691084B (en) | Pharmaceutical composition and preparation method thereof | |
| CN106310286B (en) | Tosufloxacin tosylate composition | |
| CN104072400B (en) | Oxiracetam compound and pharmaceutical composition thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |