CN116148207B - Method for quantitatively detecting microcrystalline cellulose in preparation by infrared spectrophotometry - Google Patents
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- 229920000168 Microcrystalline cellulose Polymers 0.000 title claims abstract description 72
- 235000019813 microcrystalline cellulose Nutrition 0.000 title claims abstract description 70
- 239000008108 microcrystalline cellulose Substances 0.000 title claims abstract description 62
- 229940016286 microcrystalline cellulose Drugs 0.000 title claims abstract description 62
- 238000000034 method Methods 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 238000004566 IR spectroscopy Methods 0.000 title claims abstract description 10
- 238000001514 detection method Methods 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 51
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 40
- 239000000523 sample Substances 0.000 claims description 39
- 239000002244 precipitate Substances 0.000 claims description 24
- 238000002329 infrared spectrum Methods 0.000 claims description 23
- 238000005303 weighing Methods 0.000 claims description 19
- 238000002156 mixing Methods 0.000 claims description 15
- 238000000227 grinding Methods 0.000 claims description 12
- 238000012360 testing method Methods 0.000 claims description 11
- 238000002835 absorbance Methods 0.000 claims description 10
- 239000006228 supernatant Substances 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 238000005119 centrifugation Methods 0.000 claims description 8
- 239000013074 reference sample Substances 0.000 claims description 7
- 239000013558 reference substance Substances 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 6
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- 230000010355 oscillation Effects 0.000 claims description 4
- 238000005070 sampling Methods 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 10
- 230000035945 sensitivity Effects 0.000 abstract description 3
- 229920000642 polymer Polymers 0.000 abstract description 2
- 239000007787 solid Substances 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 9
- 238000010521 absorption reaction Methods 0.000 description 7
- 239000012496 blank sample Substances 0.000 description 7
- 238000011084 recovery Methods 0.000 description 7
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 235000010980 cellulose Nutrition 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 239000007791 liquid phase Substances 0.000 description 4
- 238000002203 pretreatment Methods 0.000 description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 238000005903 acid hydrolysis reaction Methods 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000002452 interceptive effect Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 238000001069 Raman spectroscopy Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 241000209128 Bambusa Species 0.000 description 1
- 235000017166 Bambusa arundinacea Nutrition 0.000 description 1
- 235000017491 Bambusa tulda Nutrition 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 1
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 1
- 235000011777 Corchorus aestuans Nutrition 0.000 description 1
- 240000000491 Corchorus aestuans Species 0.000 description 1
- 235000010862 Corchorus capsularis Nutrition 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 235000015334 Phyllostachys viridis Nutrition 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920003081 Povidone K 30 Polymers 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
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- 239000011230 binding agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 235000009120 camo Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- 235000005607 chanvre indien Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 239000011487 hemp Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
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- 238000012986 modification Methods 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011165 process development Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/3563—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing solids; Preparation of samples therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/286—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/34—Purifying; Cleaning
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/38—Diluting, dispersing or mixing samples
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/286—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising
- G01N2001/2866—Grinding or homogeneising
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/3563—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing solids; Preparation of samples therefor
- G01N2021/3572—Preparation of samples, e.g. salt matrices
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- Physics & Mathematics (AREA)
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- Health & Medical Sciences (AREA)
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- General Health & Medical Sciences (AREA)
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- Immunology (AREA)
- Pathology (AREA)
- Spectroscopy & Molecular Physics (AREA)
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Abstract
The invention belongs to the field of polymer detection, and particularly relates to a method for quantitatively detecting microcrystalline cellulose in a preparation by using infrared spectrophotometry. The detection method has the advantages of high sensitivity, strong specificity, high precision, strong accuracy, simple and quick operation, wide applicability, low detection cost and high detection speed, and realizes the quantitative detection of microcrystalline cellulose which is a common auxiliary material in the oral solid preparation, thereby effectively guiding the self-made preparation to achieve the consistency with the prescription of the reference preparation.
Description
Technical Field
The invention relates to a method for detecting microcrystalline cellulose content in a preparation by an infrared spectrophotometry, belonging to the field of polymer detection.
Background
Microcrystalline cellulose (MCC, microcrystalline cellulose) is a white, odorless and tasteless crystalline powder composed of linear polysaccharide substance bonded by beta-1, 4-glucosidic bond and free-flowing superfine short rod-like or powdery porous particles of natural cellulose with limited degree of polymerization (LODP) by dilute acid hydrolysis. Is insoluble in water, dilute acid, organic solvent and grease, is partially dissolved in dilute alkali solution, is moist and swelled, and has higher reactivity in the processes of carboxymethylation, acetylation and esterification. The structural formula is as follows:
at present, the production of microcrystalline cellulose at home and abroad takes natural cellulose as raw materials, mainly including cotton linters, rice hulls, pine needles, hemp stems, indian bamboos, orange peels, jute and the like. The microcrystalline cellulose is prepared mainly by an acid hydrolysis method, and the main preparation principle and the method are consistent although the raw materials are different and the product properties are different, namely, cellulose purification treatment, acid hydrolysis, washing, drying, crushing and the like are adopted. The particle size and distribution of microcrystalline cellulose is determined by the structure of the feedstock, the acid concentration, temperature, time, hydrolysis process and degree of mechanical treatment.
In addition, microcrystalline cellulose is produced by microbial fermentation, i.e., enzymatic hydrolysis.
Microcrystalline cellulose is commonly used as an adsorbent, suspending agent, diluent, disintegrant. Microcrystalline cellulose is widely used in pharmaceutical formulations, mainly in oral tablets and capsules, as a diluent and binder, not only for wet granulation but also for dry direct compression.
Since the microcrystalline cellulose molecules have hydrogen bonds, and are associated with each other when pressed, the microcrystalline cellulose has high compressibility and is often used as an adhesive; when the pressed tablet encounters liquid, water rapidly enters the tablet containing microcrystalline cellulose, and hydrogen bonds are broken immediately, so that the tablet can be used as a disintegrating agent.
The microcrystalline cellulose powder can form stable dispersion system in water, and can be mixed with medicine to make into cream or suspension liquid medicine, and can also be used for making capsule. Microcrystalline cellulose is stirred vigorously in water to form a gel, which can also be used to make paste and suspension type pharmaceutical preparations.
Because of its wide application and important role in pharmaceutical formulations, pharmaceutical research and development institutions often need to determine the dosage of the pharmaceutical formulation during imitation, which is convenient for formulation prescription process development.
In the existing method for quantitatively detecting microcrystalline cellulose in the preparation, a common method is to use a Raman spectrometer and redox titration, but the Raman spectrometer is a common instrument, and has high value and high detection cost; the redox titration method has poor specificity, is only suitable for single-component quantitative detection, has complex preparation components, has interference on quantitative detection, and cannot realize the purpose of quantitative detection.
Based on the above, the invention provides a method for quantitatively detecting microcrystalline cellulose serving as an auxiliary material in a preparation by an infrared spectrophotometry.
Disclosure of Invention
In order to overcome the problem of high cost for quantifying microcrystalline cellulose in mixed components in the prior art, the invention provides a method for quantitatively detecting auxiliary microcrystalline cellulose in a preparation by a conventional infrared spectrophotometry, wherein the infrared spectrogram of microcrystalline cellulose is about 3330cm -1 Shows a strong band at about 1640cm -1 Showing a band of stretching and bending modes corresponding to surface hydroxyl groups at about 2902cm -1 The peak at the position belongs to the asymmetric stretching vibration of C-H in the pyran ring, and the wide absorption peak is about 1059cm -1 Corresponds to the C-O bond of cellulose.
The method utilizes the dissolution characteristic of microcrystalline cellulose and the characteristic absorption peak in an infrared spectrogram thereof, and removes other components which possibly interfere with quantitative detection of the characteristic peak through a certain sample pretreatment method, such as: lactose, soluble starch, dextrin, methyl cellulose and other saccharides and cellulose auxiliary materials. Among these adjuvants, the adjuvants commonly used in oral solid preparations such as tablets and capsules are lactose, soluble starch, dextrin, sodium carboxymethyl cellulose, polyethylene glycol, povidone K30, hydroxypropyl cellulose, hypromellose, polyvinylpyrrolidone, magnesium stearate, talcum powder and the like. For the common auxiliary materials, the infrared spectrogram and the dissolution characteristics of the auxiliary materials are researched, and the specific steps are as follows:
as can be seen from the comparison of the infrared spectrum characteristic peaks and the dissolution characteristics of the auxiliary materials in the table, when the microcrystalline cellulose is quantitatively detected by adopting an infrared spectrophotometry, the interference components can be removed by a method of carrying out hot water washing on a sample, so that good specificity of the method for quantitatively detecting the microcrystalline cellulose is obtained.
The invention uses the absorbance of characteristic peaks in the infrared spectrum of microcrystalline cellulose to present a certain linear relationship in a certain concentration range, and establishes an infrared spectrophotometry for measuring the content of microcrystalline cellulose by taking the absorbance as a quantitative basis of microcrystalline cellulose. In the infrared spectrogram, groups with stronger polarity (such as C=O, C-X and the like) vibrate, the absorption intensity is higher, and the absorption band is usually the strongest absorption band in the infrared spectrum; the absorption intensity is high, and the sensitivity is high. The method is detected after a specific pretreatment method of the sample, has the advantages of high specificity, high sensitivity, high accuracy, simple and convenient operation and the like, and is suitable for popularization and application in actual application.
A method for detecting microcrystalline cellulose content in a preparation by infrared spectrophotometry, comprising the following steps:
1. blank background: tabletting with blank potassium bromide, detecting infrared spectrum, and deducting as blank background system.
2. Drawing a standard curve of microcrystalline cellulose concentration and characteristic peak absorbance: precisely weighing microcrystalline cellulose reference substances with different masses, respectively mixing with potassium bromide, grinding with agate grinding bowl, mixing, weighing 200+ -10 mg tablet sample, detecting infrared spectrum, and recording characteristic peak (1640+ -5 cm) -1 ) Is a solid phase, and is a liquid phase. And drawing a standard curve by taking the concentration as an abscissa and the absorbance of the characteristic peak as an ordinate. Wherein, the concentration=microcrystalline cellulose reference sample (mg)/(microcrystalline cellulose reference sample+potassium bromide reference sample) (mg) is in the range of 0.0074-0.0176.
3. Sample detection: taking outAnd (3) accurately weighing a proper amount of a test sample, adding hot water, oscillating at a speed of 200rpm in a water bath at 80 ℃, centrifuging while the solution is hot, removing supernatant, adding hot water into the precipitate, shaking vigorously to uniformly disperse the precipitate in the hot water, oscillating at a speed of 200rpm in a water bath at 80 ℃, centrifuging while the solution is hot, and removing supernatant. Repeatedly washing the precipitate for 2-4 times (preferably 3 times) in the same way, taking the precipitate obtained after centrifugation, drying under a red light lamp, mixing with potassium bromide, grinding with agate bowl, mixing uniformly, weighing 200+ -10 mg of tablets, preparing samples, detecting infrared spectrum, and recording characteristic peaks (1640+ -5 cm -1 ) (the characteristic peak of step 2 is an absorption peak at the same wavenumber). Substituting the microcrystalline cellulose into the standard curve equation of the step 2 to obtain the concentration of microcrystalline cellulose, and then according to the formula: microcrystalline cellulose content = concentration x potassium bromide addition/[ (1-concentration) ×sample weight]And (5) calculating the content of microcrystalline cellulose in the test sample by using the method of X100%.
Preferably, the hot water in the step 3 is water at 60-100 ℃, and the optimal temperature is 80 ℃; the amount of hot water is such as to ensure that all water-soluble interfering components are dissolved.
Preferably, in the step 3, the time of the water bath oscillation at 80 ℃ is 15-30 min, and optimally 20min.
Preferably, the centrifugation in step 3 is performed at a rotational speed of 5000-10000 rpm, and most preferably 10000rpm.
Drawings
FIG. 1 is an infrared spectrum of hollow white potassium bromide of example 1;
FIG. 2 is an infrared spectrum of a hollow white sample of example 1;
FIGS. 3-7 are infrared spectrograms of standard curve samples in example 3;
FIG. 8 is an infrared spectrum of the recovered sample 1 of example 4;
FIG. 9 is an infrared spectrum of the recovered sample 2 of example 4;
FIG. 10 is an infrared spectrum of sample 3 recovered by applying a sample in example 4;
FIG. 11 is an infrared spectrum of sample 4 recovered by applying a sample in example 4;
FIG. 12 is an infrared spectrum of sample 5 recovered by loading in example 4;
FIG. 13 is an infrared spectrum of sample 6 recovered by loading in example 4;
FIG. 14 is a standard graph of example 3;
note that: the characteristic peaks for quantification in FIGS. 8, 10 and 13 are different in both the base line height and the characteristic peak height, FIG. 13 is a graph of 434.9cm -1 A non-characteristic peak at a wave number of 800-400 cm -1 In the wave number range, the base line heights of the three graphs are different, and the wave number values of the non-characteristic peaks are inconsistent;
the characteristic peaks for quantification in FIGS. 11 and 12 are different in both the base line height and the characteristic peak height, and FIG. 11 is 500 to 400cm -1 There are a number of non-characteristic peaks at wavenumbers, which are absent in fig. 12.
Detailed Description
The present invention is further described below by applicant in conjunction with examples and the accompanying drawings so that those skilled in the art can clearly understand the present invention, but the scope of the present invention is not limited to these examples.
The experimental methods used in the following examples are all conventional methods unless otherwise specified; the water used is ultrapure water; materials, reagents and the like used, unless otherwise indicated, are all commercially available.
The microcrystalline cellulose and microcrystalline cellulose controls used in the examples below were all available from Huzhou pharmaceutical company, inc., lot 20211004, model 101.
The infrared spectrometer used in the following examples was a Sieimer-Feis-5 infrared spectrometer.
Example 1: analytical method establishment (solvent selection)
Under the experimental conditions, room temperature water, 60 ℃ water, 80 ℃ water and 100 ℃ boiling water are respectively selected, common auxiliary materials such as lactose, soluble starch, sodium carboxymethyl cellulose and the like are selected for carrying out solubility test, and the auxiliary materials are stirred in water at different temperatures for 30min, and the dissolution situation is observed, and the result is as follows:
TABLE 1
From the above observations, the solubility of lactose and soluble starch in water increases with increasing water temperature; sodium carboxymethyl cellulose can be dissolved in cold water and hot water, but the sodium carboxymethyl cellulose can be dissolved only after being dispersed in advance when being dissolved singly. Because the test sample is a uniformly mixed multi-component mixture, the test sample can not be agglomerated during dissolution, and the test sample does not need to be dispersed in advance.
In conclusion, most of auxiliary materials interfering with characteristic peaks of microcrystalline cellulose can be completely dissolved after being dissolved and washed by water at 80 ℃.
Example 2: specificity experiments
1. Blank background: 200.17mg of blank potassium bromide was tabletted and tested for infrared spectra (FIG. 1) and subtracted as a blank background system.
2. Blank sample detection: 65.78mg of blank sample is precisely weighed and subjected to first cleaning: adding 10ml of 80 ℃ hot water, oscillating for 30min at 200rpm in 80 ℃ water bath, centrifuging for 5min at 10000rpm while hot, discarding supernatant, adding 10ml of 80 ℃ hot water into the precipitate, shaking vigorously to uniformly disperse the precipitate in hot water, oscillating for 15min at 200rpm in 80 ℃ water bath, centrifuging for 5min at 10000rpm while hot, discarding supernatant to obtain precipitate, and cleaning for the first time; the precipitate was washed 3 more times in the same manner. The precipitate after centrifugation was dried under a red light, then mixed with 2.03129g of potassium bromide, milled with an agate bowl, and mixed uniformly, 200.32mg of the pellet was weighed and sampled, and the infrared spectrum was measured (FIG. 2).
The prescription amounts of the hollow white sample in this example are as follows:
as can be seen from FIG. 2, after the sample is treated by the sample pretreatment method of the present invention, the characteristic peaks (1640 cm) of the non-interfering microcrystalline cellulose quantitative determination in the obtained infrared spectrogram -1 ) The method has good specificity.
Example 3: standard curve drawing of microcrystalline cellulose reference substance
FIG. 3-7 shows the IR spectrum of standard curve sample, precisely weighing about 15mg, 20mg, 25mg, 30mg, 35mg of microcrystalline cellulose reference substance, respectively, mixing with about 2.0g of potassium bromide (precisely weighing), grinding with agate grinding bowl, mixing, precisely weighing about 200mg of tablet, making sample, detecting IR spectrum, recording characteristic peak 1640cm -1 Is a solid phase, and is a liquid phase. The concentration is microcrystalline cellulose reference sample weighing amount/(microcrystalline cellulose reference sample weighing amount+potassium bromide sample weighing amount), and the concentration is taken as an abscissa, and the characteristic peak is 1640cm -1 The absorbance of (a) is plotted on the ordinate, and a standard curve (fig. 14) is plotted, specifically as shown in table 2 below:
TABLE 2
From the data, the absorbance and the concentration show good linear relation in the range of 0.0074mg/mg to 0.0176 mg/mg.
Example 4: accuracy test
Precisely weighing about 105mg of blank sample and about 45mg of microcrystalline cellulose reference substance respectively, adding the blank sample and about 45mg of microcrystalline cellulose reference substance into the same 10ml of hot water at 80 ℃, centrifuging at a speed of 200rpm in a water bath at 80 ℃ for 5min while the blank sample is still hot, removing supernatant, adding 10ml of hot water at 80 ℃ into the precipitate, shaking vigorously to uniformly disperse the precipitate in the hot water, centrifuging at a speed of 10000rpm for 5min while the blank sample and the microcrystalline cellulose reference substance are hot in a water bath at 80 ℃ to obtain precipitate, and completing the first cleaning; washing the precipitate for 3 times by the same method, taking the precipitate after centrifugation, drying under a red light lamp, mixing with 3.0g of potassium bromide, grinding with an agate bowl, mixing uniformly, precisely weighing about 200mg of tablets, preparing samples, detecting infrared spectra (figure 8-13), recording characteristic peaks of 1640cm -1 Is a solid phase, and is a liquid phase. Substituting the standard curve equation of example 3 to obtain the concentration of microcrystalline cellulose, and then according to the formula: recovery = measured MCC/added MCC x 100%, recovery was calculated, where measured MCC = concentration measured MCC x added potassium bromide/(1-MCC measured concentration). Parallel to each other6 parts were prepared.
The blank sample is prepared by mixing lactose, soluble starch, calcium stearate and celecoxib serving as raw materials according to the following proportion:
TABLE 3 Table 3
The accuracy results are as follows:
TABLE 4 Table 4
From the data, the samples are treated according to the pretreatment method, the recovery rates are 90-110%, the recovery rate RSD is 1.4%, and the accuracy and repeatability are good.
Example 5: sample detection
(1) Blank background: accurately weighing 203.12mg of potassium bromide, tabletting, detecting infrared spectrum, and subtracting as a blank background system.
(2) Sample preparation of a test sample: taking a proper amount of a test sample (about 18-27mg of microcrystalline cellulose), precisely weighing, adding 10ml of hot water at 80 ℃, oscillating for 30min at 200rpm in a water bath at 80 ℃, centrifuging for 5min at 10000rpm while hot, removing supernatant, adding 10ml of hot water at 80 ℃ into the precipitate, shaking vigorously to uniformly disperse the precipitate in hot water at 80 ℃, oscillating for 30min at 200rpm in a water bath at 80 ℃, centrifuging for 5min at 10000rpm while hot, discarding supernatant to obtain precipitate, and completing the first cleaning; washing the precipitate for 3 times by the same method, taking the precipitate after centrifugation, drying under a red light lamp, mixing with 2.0g (precisely weighed) of potassium bromide, grinding and uniformly mixing by an agate grinding bowl, precisely weighing about 200mg of tablets for sample preparation, detecting infrared spectrum, and recording characteristic peak 1640cm -1 Is a solid phase, and is a liquid phase. Substituting the standard curve equation of example 3 to obtain the concentration of microcrystalline cellulose, and then according to the formula: MCC measured = MCC measured concentration x potassium bromide added/(1-MCC measured concentration), recovery = MCC measured/MCCTheoretical amount x 100%, and recovery rate was calculated.
The amount of microcrystalline cellulose in the preparation samples was measured as follows:
TABLE 5 details of the proportions of the formulation components
TABLE 6 recovery calculation Table
The specific embodiments described herein are offered by way of example only to illustrate the spirit of the invention. It will be understood by those skilled in the art that equivalent substitutions and corresponding modifications to the technical features of the present invention are included within the scope of the present invention.
Claims (10)
1. A method for detecting microcrystalline cellulose content in a preparation by infrared spectrophotometry, comprising the following steps:
1) Blank background: tabletting with blank potassium bromide, drawing infrared spectrogram, and deducting as blank background system;
2) Drawing a standard curve of microcrystalline cellulose concentration and characteristic peak absorbance: precisely weighing microcrystalline cellulose reference substances with different masses, respectively mixing with potassium bromide, grinding with agate grinding bowl, mixing uniformly, weighing the mixture, tabletting, sampling, detecting infrared spectrum, and recording the absorbance of characteristic peak;
drawing a standard curve by taking the concentration as an abscissa and the absorbance of the characteristic peak as an ordinate; wherein, the concentration=microcrystalline cellulose reference sample amount/(microcrystalline cellulose reference sample amount+potassium bromide sample amount), the concentration is in the range of 0.0074-0.0176;
3) Sample detection: precisely weighing a sample, adding hot water, oscillating in a water bath at 80 ℃, centrifuging while the sample is hot, removing supernatant, adding hot water into the precipitate, shaking vigorously to uniformly disperse the precipitate in the hot water, oscillating in a water bath at 80 ℃, centrifuging while the sample is hot, and removing supernatant;
repeatedly cleaning the precipitate for 2-4 times by the same method, taking the precipitate obtained after centrifugation, drying under a red light lamp, mixing with potassium bromide, grinding and uniformly mixing with an agate grinding bowl, weighing the mixture, tabletting and preparing a sample, detecting an infrared spectrum, and recording the absorbance of a characteristic peak;
substituting the microcrystalline cellulose into the standard curve equation of the step 2 to obtain the concentration of microcrystalline cellulose, and then according to the formula: microcrystalline cellulose content = concentration x potassium bromide addition/[ (1-concentration) x sample weight of the test piece ] ×100%, the microcrystalline cellulose content in the test piece was calculated.
2. The method according to claim 1, wherein the characteristic peak is a wave number of 1640.+ -.5 cm -1 Is a peak of (2).
3. The method according to claim 1, wherein the hot water in step 3) is water at 60 ℃ to 100 ℃.
4. A method according to claim 3, wherein in step 3) the hot water is water at 80 ℃.
5. The method according to claim 1, wherein the rate of oscillation of the 80 ℃ water bath in step 3) is 200rpm, and the oscillation time is 15-30 min.
6. The method according to claim 5, wherein the time of the 80 ℃ water bath oscillation in step 3) is 20min.
7. The method of claim 1, wherein the centrifugation in step 3) is performed at a rotational speed of 5000 to 10000rpm.
8. The method according to claim 7, wherein the centrifugation in step 3) is performed at 10000rpm.
9. The method according to claim 1, wherein the sample is weighed 200±10mg when compressed.
10. The method according to claim 1, wherein the step 3) is repeated 3 times for the same washing of the precipitate.
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| CN101366849A (en) * | 2007-08-15 | 2009-02-18 | 未名天人中药有限公司 | Quality control method for traditional Chinese medicine citrus aurantium |
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| CN103852441A (en) * | 2014-02-21 | 2014-06-11 | 广东中烟工业有限责任公司 | Method for quantitative detection of tobacco lignin by adopting mid-infrared spectroscopy |
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| CN1932480A (en) * | 2005-09-12 | 2007-03-21 | 武汉科技学院 | Method for measuring raw hemp gum level utilizing infrared spectrum |
| CN101366849A (en) * | 2007-08-15 | 2009-02-18 | 未名天人中药有限公司 | Quality control method for traditional Chinese medicine citrus aurantium |
| CN102048778A (en) * | 2009-11-05 | 2011-05-11 | 天津天士力现代中药资源有限公司 | Method for detecting ginseng extract |
| CN103852441A (en) * | 2014-02-21 | 2014-06-11 | 广东中烟工业有限责任公司 | Method for quantitative detection of tobacco lignin by adopting mid-infrared spectroscopy |
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