CN101695503A - Quality control method of pediatric paracetamol, atificial cow-bezoar and chlorphenamine maleate effervescent tablets - Google Patents
Quality control method of pediatric paracetamol, atificial cow-bezoar and chlorphenamine maleate effervescent tablets Download PDFInfo
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Abstract
The invention discloses a quality control method of pediatric paracetamol, atificial cow-bezoar and chlorphenamine maleate effervescent tablets. The tablets are prepared from 125 grams of paracetamol, 5 grams of calculus bovis artifactus, 0.5 gram of chlorphenamine maleate, 200 grams of citric acid, 250 grams of sodium bicarbonate, 1,338 grams of lactose, 30.5 grams of aspartame, 40 grams of essence, 10 grams of magnesium stearate and 1 gram of pigment. The method has the advantages of effectively controlling the quality of medicaments, keeping the best medicament effect of medicaments, reducing production cost and saving raw material medicaments.
Description
Technical field
The present invention relates to a kind of method of quality control, relate in particular to a kind of method of quality control of effervescence tablet of Xiao ' er Anfen Huangnamin.
Background technology
Yellow that of child ammonia phenol is the specific drug of treatment children's common cold, be used for common cold or grippal heating, yellow that the existing preparation type of child ammonia phenol mainly is a granule, though granule is applicable to child, but its bitterness is big, child easily produces resisting psychology, to be accepted by child easily as changing granule into effervescent tablet, can well bring into play drug effect, meanwhile, it is necessary that yellow that effervescent tablet of child ammonia phenol is carried out quality control, by method of quality control medicament is made to be fit to the different dosage form that most of children use.
Summary of the invention
The object of the present invention is to provide a kind of method of quality control of effervescence tablet of Xiao ' er Anfen Huangnamin, choose suitable disintegration by effective quality control, process etc. satisfy the mass industrial production needs.
The present invention is achieved like this; acetaminophen 125g, artificial Calculus Bovis 5g, chlorphenamine maleate 0.5g, citric acid 200g, sodium bicarbonate 250g, the sweet 30.5g of lactose 1338g, A Siba, essence 40g, magnesium stearate 10g, pigment 1g; above-mentioned raw materials is made 1000 altogether, it is characterized in that method of quality control comprises the following steps:
(1) location is differentiated
The discriminating of a, acetaminophen: with the acetaminophen reference substance is contrast, and acetaminophen in the sample has been carried out the TLC discriminating, and clear spot is negative noiseless, can be used as the discriminating of acetaminophen in this preparation;
B, artificial Calculus Bovis's discriminating: with artificial Calculus Bovis's control medicinal material is contrast, and biliographic data has carried out the TLC discriminating to artificial Calculus Bovis in the sample, and clear spot is negative noiseless, can be used as the discriminating of artificial Calculus Bovis in this preparation;
The discriminating of c, chlorphenamine maleate: with the chlorphenamine maleate reference substance is contrast, and chlorphenamine maleate in the sample has been carried out the TLC discriminating, and clear spot is negative noiseless, can be used as the discriminating of chlorphenamine maleate in this preparation;
(2) assay
The assay of a, acetaminophen
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filler, with volume ratio methanol: water be 25: 75 be mobile phase, the detection wavelength is 257nm, and number of theoretical plate calculates by acetaminophen should be not less than 5000, and separating degree should be up to specification between main peak and adjacent peak;
Algoscopy: get 10 of this product, porphyrize, precision takes by weighing and is equivalent to acetaminophen 10mg, put in the 250ml measuring bottle, add the mutual-assistance dissolving of flowing, and be diluted to scale with mobile phase, shake up, filter membrane filters, and precision is measured subsequent filtrate 20ul, inject high performance liquid chromatograph, the record chromatogram, precision takes by weighing the acetaminophen reference substance in addition, with mobile phase dissolving and make the solution that every 1ml contains acetaminophen 40ug, measure with method, calculate respectively with peak area by external standard method, promptly;
B, content for Chlorphenamine Maleate are measured
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filler; With acetonitrile: 3% glacial acetic acid: triethylamine (20: 80: 0.08) is a mobile phase; The detection wavelength is 262nm, and theoretical cam curve is calculated by chlorphenamine maleate should be not less than 2500, and separating degree should be up to specification between main peak and adjacent peak;
Algoscopy: get 10 of this product, porphyrize, precision takes by weighing and is equivalent to chlorphenamine maleate 0.5mg, put in the 50ml measuring bottle, add the mutual-assistance dissolving of flowing, ultrasonic 10 minutes, and be diluted to scale with mobile phase, shake up, filter membrane filters, and precision is measured subsequent filtrate 20ul, injects high performance liquid chromatograph, the record chromatogram, in addition precision takes by weighing the chlorphenamine maleate reference substance, with the mobile phase dissolving and make the solution that every 1ml contains acetaminophen 20ug, measures with method, calculate respectively with peak area by external standard method, promptly;
(3) selection of preparation condition
A, citric acid baking temperature and the selection of time
Tabletting is granulated after adopting acid, the direct mixing of alkali, because of containing certain water of crystallization in the citric acid, easily discharge in the process of placing, so it is carried out drying and dehydrating, baking temperature and time are investigated, get the 100g citric acid, claim to decide weight, put 80 ℃ of dryings 3,4,5,6h respectively, claim to decide weight, other gets citric acid 100g, and dry 5h under 60 ℃, 70 ℃, 80 ℃, 90 ℃, 100 ℃ claims to decide weight;
The selection of b, granulation solvent
Medicine behind the equivalent incremental method mixing, needs to granulate routinely, because the strict control moisture of effervescent tablet so test use dehydrated alcohol and PVP are dissolved in the dehydrated alcohol as binding agent, is granulated with 5%PVP anhydrous alcohol solution 20 mesh sieves through repetition test;
The investigation of c, granulation ambient humidity
Because the hygroscopicity of effervescent tablet adjuvant is strong, response environment humidity in granule tabletting process, temperature is controlled to some extent, through the experiment, when ambient temperature at 20-26 ℃ of relative humidity in 45%, the tabletting effect is better, be difficult for taking place problems such as sticking, when relative humidity was higher than 50-55%, granule easily absorbed the water in air branch, and " sticking " phenomenon easily takes place;
D, particle drying temperature are selected and granulate
Because sodium bicarbonate is to responsive to temperature, high temperature easily decomposes, and therefore the particle drying temperature is needed to investigate, through repetition test, good to this product drying effect when selecting baking temperature to be 50 ℃, drying time is short, so selecting baking temperature is 50 ℃, dried granule is used for tabletting through 20 mesh sieve granulate;
E, mobility of particle are investigated
Granule needs certain fluidity could adapt to large-scale production, should add certain lubricant, commonly used have magnesium stearate, a PEG6000, because magnesium stearate is water insoluble, adopt to add water-soluble PEG6000,, add granule with 3% ratio through test, mobile suitable, tabletting sticking situation is had some improvement.
Optimal preparation effervescence tablet of Xiao ' er Anfen Huangnamin method of the present invention is: will get 80 ℃ of dryings of citric acid 5 hours; pulverize; it is standby to cross 80 mesh sieves; get chlorphenamine maleate, artificial Calculus Bovis, acetaminophen by equivalent incremental method mixing,, essence sweet with sodium bicarbonate, citric acid, A Siba, pigment and lactose mixing are granulated with the 5%PVP ethanol solution; 50 ℃ of dryings; 20 mesh sieve granulate, tabletting, promptly.
Advantage of the present invention is: effectively medicine is carried out quality control, can keep bringing into play the best drug effect of medicine, reduce production costs, medicine economizes in raw materials.
The specific embodiment
One, prescription
Acetaminophen 125g, artificial Calculus Bovis 5g, chlorphenamine maleate 0.5g, citric acid 200g, sodium bicarbonate 250g, the sweet 30.5g of lactose 1338g, A Siba, essence 40g, magnesium stearate 10g, pigment 1g, above-mentioned raw materials is made 1000 altogether,
Two, technology
To get 80 ℃ of dryings of citric acid 5 hours, and pulverize, it is standby to cross 80 mesh sieves.Get chlorphenamine maleate, artificial Calculus Bovis, acetaminophen by equivalent incremental method mixing;, essence sweet, pigment and lactose mixing with sodium bicarbonate, citric acid, A Siba; granulate with 5% polyvinylpyrrolidone (PVP) ethanol solution; 50 ℃ of dryings; 20 mesh sieve granulate; tabletting, promptly.
Three, the selection of dosage form
Effervescence tablet of Xiao ' er Anfen Huangnamin is to be changed by the agent of former Ministry of Public Health standard WS-10001-(HD-0214)-2002 pediatric paracetamol,atificial cowbezoar and chlorphenamine maleate granule to form.The oral administration effervescing sheet is specially adapted to child patient, and its acid-base reaction generates carbon dioxide and impels whole tablet to dissolve at short notice, and drug effect is rapid, and mouthfeel is good, and the child is happy to accept.Effervescence tablet of Xiao ' er Anfen Huangnamin is compared with former dosage form, dissolves sooner, and the stability and the uniformity are better and carry more convenient.Former dosage form standard is lower, and this project has increased the TLC chromatograph of acetaminophen, artificial Calculus Bovis, chlorphenamine maleate to be differentiated, and increased acetaminophen and content for Chlorphenamine Maleate is measured.
Five, Chu Fang screening
This product is a compound preparation; contain 3 kinds of active medicines in the prescription; its specification and dosage are made up of acetaminophen, artificial Calculus Bovis and chlorphenamine maleate according to the standard of the former national drug standards " WS-10001-(HD-0214)-2002 " pediatric paracetamol,atificial cowbezoar and chlorphenamine maleate granule.The composition of other adjuvant detects the effervescent tablet that this prescription prepares through behind the prescription screening and the better formula of determining is formed by quality standard (draft), meets every detection index.
This product is the effervescent tablet preparation, so be inspection item with its disintegration, gas release, compressibility and mouthfeel in this product quality standard.We have designed four kinds of prescriptions, adopt direct matching type that compressibility, disintegration, gas release and the mouthfeel that the design prescription carries out tablet compared behind the tabletting, finally determine preferable accessory formula composition.
1, prescription design
We are main in prescription to consider that the adjuvant of usefulness is divided into aspect three, and selecting effervescent tablet citric acid, tartaric acid commonly used is acid source; Selecting sodium bicarbonate and sodium carbonate is carbon dioxide source; Selecting sucrose, lactose is filler and correctives; Because of water insoluble lubricants influences clarity of solution, be lubricant so select PEG6000 for use; We press the equivalent reaction principle ratio of soda acid, and all the other sweeting agents, essence, pigment feed intake routinely, see Table 1 by supplementary product consumption in each prescription of 2g/ sheet calculating.Carry out tabletting by following conventional preparation method.
Table 1 respectively write out a prescription Chinese medicine and supplementary product consumption (g) (every prescription is 500 consumptions)
2, method for making
(1) various medicines and adjuvant are crossed 80 mesh sieves;
(2) take by weighing various adjuvants and medicine, mix homogeneously by prescription one, two, three, four;
(3) be binding agent with the 5%PVP ethanol solution, add in the mixture, stir into even soft material;
(4) granulate with 20 order nylon mesh, dry under 50-55 ℃ of temperature;
(5) dried granule adds magnesium stearate in 20 order granulate, and tabletting is made 500;
(6) get effervescent tablet and carry out disintegration, gas release, mouthfeel detection.
3, algoscopy
Disintegration: get 6 parts of this product, according to " two appendix XA of Chinese pharmacopoeia version in 2005 inspection technique disintegration is measured in accordance with the law, get 1 respectively, put in the 250ml beaker, fill 200ml water in the beaker, 15～25 ℃ of water temperatures, there is numerous air-bubble to emit, when the gas around tablet or the fragment stopped to overflow, tablet was answered disintegrate, dissolves or is dispersed in the water, and no aggregated particle is left.
Gas release: reference literature
[1]Make a kind of draining gas collecting apparatus, the gas of release can correctly be measured, the separatory funnel that water is filled in employing links to each other with base buret by a latex tubing, the horizontal plane of separatory funnel and the minimum scle height of base buret are consistent, add this product 1g, immediately that the separatory funnel lid is tight, observe the reading that liquid level raises in the base buret, i.e. the gas volume number.
Mouthfeel: get one of effervescent tablet, add in the 100ml water, how taste the liquid mouthfeel.
Compressibility: observe whether the sticking situation takes place when medicine is granulated back granule tabletting easily.
4, result
By above preparation method each prescription is pressed into effervescent tablet, and carries out every index and measure, its comparing result sees Table 2.
Each prescription preparation effervescent tablet comparing result of table 2
Show from effervescent tablet result of each prescription preparation: from disintegration and gas release, to write out a prescription one, two for well; From mouthfeel, to write out a prescription one, two for well; From the granule compressibility, all there is the different sticking phenomenon of degree in 4 prescriptions, and prescription one, three is better relatively, to sum up consider, to write out a prescription one as optimizing prescriptions, promptly acid source is selected citric acid, and alkali source is selected sodium bicarbonate, and filler selects lactose as adjuvant.
Six, the selection of adjuvant ratio
Above-mentioned prescription screening result has determined to adopt sodium bicarbonate, citric acid, lactose is basic adjuvant, but optimal proportion is not determined yet between the soda acid, because effervescent tablet has the clarity requirement, therefore use magnesium stearate improper in this preparation, the magnesium stearate that should adopt good water solubility is as lubricant, test in the ratio of adjuvant shown in the table 3 and " method for making ", and carry out pH, mouthfeel, disintegration and compressibility and detect.The results are shown in Table 4.
4, detection method
4.1pH pH-value determination pH: get 1 of this product, effervescent is scattered in the 100ml water, measure the pH value of solution.
4.2 check disintegration: get 1 of this product, put in the 250ml beaker, add hot water 200ml in the beaker, have numerous air-bubble to emit, when gas stopped to overflow, tablet should dissolve or be dispersed in the water, there is not accumulative granule residue, by inspection technique check disintegration, get 6 of this product, each sheet all should disintegrate in 5min.
Adopt the aggregate balancing method, with the pH value of tablet, disintegration etc. be that index is evaluated.The results are shown in Table 3,4.The result shows, prescription six, prescription seven adjuvant ratios are more suitable, form prescription A and prescription B, as optional with prescription.
Supplementary product consumption (g) in each prescription of table 3
Table 4 testing result
Prescription A acetaminophen 125g
Artificial Calculus Bovis 5g
Chlorphenamine maleate 0.5g
Citric acid 225g
Sodium bicarbonate 250g
Lactose 1313g
The sweet 30.5g of A Siba
Essence 40g
Magnesium stearate 10g
Pigment 1g
Be pressed into 1000
Prescription B
Acetaminophen 125g
Artificial Calculus Bovis 5g
Chlorphenamine maleate 0.5g
Citric acid 200g
Sodium bicarbonate 250g
Lactose 1338g
The sweet 30.5g of A Siba
Essence 40g
Magnesium stearate 10g
Pigment 1g
Be pressed into 1000
Seven, Selection of technological conditions
Neutralization reaction easily takes place produce water owing to effervescent tablet contains acid source and alkali source simultaneously, the water content height easily is easy to generate " disintegrating tablet ", instability, and the adjuvant sodium bicarbonate is to responsive to temperature simultaneously, easily produces and decomposes when temperature is higher than 60 ℃
[5], therefore reply moisture content and temperature should be controlled in art production process.
1. the investigation of citric acid baking temperature and time
Tabletting is granulated behind process using acid, the direct mixing of alkali, because of containing certain water of crystallization in the citric acid, easily discharges in the process of placing, so it is carried out drying and dehydrating, baking temperature and time is investigated.Get the 100g citric acid, claim to decide weight, put 80 ℃ of dryings 3,4,5,6h respectively, claim to decide weight, other gets citric acid 100g, and dry 5h under different temperatures claims to decide weight, the results are shown in Table 5.Definite preferable with dry 5 hours dehydrating effects under 80 ℃ of conditions, the results are shown in Table 6.
The investigation of table 5 citric acid baking temperature
The investigation of table 6 citric acid drying time
2. the selection of granulation solvent
Medicine is routinely behind the equivalent incremental method mixing, need to granulate, because the strict control moisture of effervescent tablet, so test uses dehydrated alcohol and PVP to be dissolved in the dehydrated alcohol as binding agent, granulate with 5%PVP anhydrous alcohol solution 20 mesh sieves through repetition test, effective.
The selection of table 7 granulation solvent
3. the investigation of granulation ambient humidity
Because the hygroscopicity of effervescent tablet adjuvant is strong, response environment humidity in granule tabletting process, temperature is controlled to some extent, through the experiment, when ambient temperature at 20-26 ℃ of relative humidity in 45%, the tabletting effect is better, be difficult for taking place problems such as sticking, when relative humidity was higher than 50-55%, granule easily absorbed the water in air branch, and " sticking " phenomenon easily takes place.
4. the particle drying temperature is selected and granulate
Because sodium bicarbonate is to responsive to temperature, high temperature easily decomposes, and therefore the particle drying temperature is needed to investigate.Through repetition test, good to this product drying effect when selecting baking temperature to be 50 ℃, drying time is short, is 50 ℃ so select baking temperature, and dried granule is used for tabletting through 20 mesh sieve granulate.
5. mobility of particle is investigated
Granule needs certain fluidity could adapt to large-scale production, should add certain lubricant, commonly used have magnesium stearate, a PEG6000, because magnesium stearate is water insoluble, adopt to add water-soluble PEG6000,, add granule with 3% ratio through test, mobile suitable, tabletting sticking situation is had some improvement.
Best process flow: will get 80 ℃ of dryings of citric acid 5 hours, and pulverize, it is standby to cross 80 mesh sieves.Get chlorphenamine maleate, artificial Calculus Bovis, acetaminophen by equivalent incremental method mixing,, essence sweet with sodium bicarbonate, citric acid, A Siba, pigment and lactose mixing are granulated with the 5%PVP ethanol solution; 50 ℃ of dryings; 20 mesh sieve granulate, tabletting, promptly.
Eight, preparation factors influencing
Rationally feasible for the technology of investigating prescription one, two, whether quality is stable, and whether sensitivity designs following test method and examination inspection item to light, heat, humidity.
1. exposure experiments to light method: with this product is irradiation 10 days under the 4500Lux in illuminance directly, and be 0,5,10 day detection time.
2. hot test method: this product was directly placed 10 days in 60 ± 1 ℃ of calorstats of temperature, and be 0,5,10 day detection time.
3. high humidity test method: this product directly is placed on (RH=75 ± 5%) in the exsiccator that contains saturated NaCl solution, and be 0,5,10 day detection time.
4. test item
4.1 character
4.2pH value: get 1 of this product, effervescent is scattered in the 100mL water, adopt pH meter to measure the pH value of solution.
4.3 disintegration: get 6 parts of this product, according to " two appendix XA of Chinese pharmacopoeia version in 2005 inspection technique disintegration is measured in accordance with the law, get 1 respectively, put in the 250ml beaker, fill 200ml water in the beaker, 15～25 ℃ of water temperatures, there is numerous air-bubble to emit, when the gas around tablet or the fragment stopped to overflow, tablet was answered disintegrate, dissolves or is dispersed in the water, and no aggregated particle is left.
4.4 assay:
4.4.1 acetaminophen assay
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica; With methanol-water (25: 75) is mobile phase; The detection wavelength is 257nm.Number of theoretical plate calculates by acetaminophen should be not less than 5000, and separating degree should be up to specification between main peak and adjacent peak.
Algoscopy is got 10 of this product, porphyrize, and precision takes by weighing in right amount (being equivalent to acetaminophen 10mg), puts in the 250ml measuring bottle, add the mutual-assistance dissolving of flowing, and be diluted to scale with mobile phase, shake up, filter membrane filters, precision is measured subsequent filtrate 20ul, injects high performance liquid chromatograph, the record chromatogram.It is an amount of that in addition precision takes by weighing the acetaminophen reference substance, with the mobile phase dissolving and make the solution that every 1ml contains acetaminophen 40ug, measures with method, calculates respectively with peak area by external standard method, promptly.
4.4.2 content for Chlorphenamine Maleate is measured
Chromatographic condition and system suitability test are filler with the octadecylsilane chemically bonded silica; With acetonitrile-3% glacial acetic acid-triethylamine (20: 80: 0.08) is mobile phase; The detection wavelength is 262nm.Theoretical cam curve is calculated by chlorphenamine maleate should be not less than 2500, and separating degree should be up to specification between main peak and adjacent peak.
Algoscopy is got 10 of this product, porphyrize, precision take by weighing in right amount (being equivalent to chlorphenamine maleate 0.5mg), put in the 50ml measuring bottle, add the mutual-assistance dissolving of flowing, ultrasonic 10 minutes, and be diluted to scale with mobile phase, shake up, filter membrane filters, precision is measured subsequent filtrate 20ul, injects high performance liquid chromatograph, the record chromatogram.It is an amount of that in addition precision takes by weighing the chlorphenamine maleate reference substance, with the mobile phase dissolving and make the solution that every 1ml contains acetaminophen 20ug, measures with method, calculates respectively with peak area by external standard method, promptly.
5, result
Characteristic according to this product is formulated test item, detects character, disintegration, pH value and content that the influence factor examines or check the back sample.Test and testing result see Table 8,9,10.
Table 8 exposure experiments to light result
Table 9 hot test result (60 ± 1 ℃)
Table 10 high humidity result of the test (RH=75 ± 5%)
From table 8,9,10 results as seen, this product prescription A, B are under high light, high humidity, hot conditions, observed its character all changed to some extent in the 5th day and the 10th day, but other index all there is not tangible influence, so when storage, should guard against damp, should adopt sealing to store, therefore, select drug packaging to add high density polyethylene bottle double casing as commercially available back with aluminium foil.Comprehensively relatively write out a prescription A and the prescription B, the influence factor there is no significant difference to both influences, is children's's oral formulations because of this product again, take all factors into consideration its influence to mouthfeel, the acid of prescription A mouthfeel may be uncomfortable to the child, think that the prescription B of this product is better, so the formal prescription of this product is defined as follows.
Acetaminophen 125g
Artificial Calculus Bovis 5g
Chlorphenamine maleate 0.5g
Citric acid 200g
Sodium bicarbonate 250g
Lactose 1338g
The sweet 30.5g of A Siba
Essence 40g
Magnesium stearate 10g
Pigment 1g
Be pressed into 1000
Nine, pilot scale is amplified
By above-mentioned preparation technology, by multiple batches of amplification production, investigated pilot scale technical data such as dosage, output, yield rate respectively, the result proves the product process stabilizing, the production technology data see Table 11.And, the results are shown in Table 12 to three batches of pilot product quality examinations.
Table 11 is optimized the checking and the pilot plant test technical data of technology
Three batches of pilot product quality examinations of table 12 are table as a result
The result: test agent is examined entirely by the quality standard of drafting in three batches, and the result is all up to specification.
Ten, primary raw material source and quality standard
Primary raw material title source standard
1. acetaminophen Liaoyuan City hundred health pharmaceutcal corporation, Ltd Chinese Pharmacopoeias version in 2000 is two ones
2. the auspicious nation of artificial Calculus Bovis's ShenFang,SiChuan plant company limited Chinese Pharmacopoeia version in 2000 is one one
3. chlorphenamine maleate Henan Province work of nature pharmaceutical factory Chinese Pharmacopoeia version in 2000 is two ones.
Claims (2)
1. the method for quality control of an effervescence tablet of Xiao ' er Anfen Huangnamin; acetaminophen 125g, artificial Calculus Bovis 5g, chlorphenamine maleate 0.5g, citric acid 200g, sodium bicarbonate 250g, the sweet 30.5g of lactose 1338g, A Siba, essence 40g, magnesium stearate 10g, pigment 1g; above-mentioned raw materials is made 1000 altogether, it is characterized in that method of quality control comprises the following steps:
(1) location is differentiated
The discriminating of a, acetaminophen: with the acetaminophen reference substance is contrast, and acetaminophen in the sample has been carried out the TLC discriminating, and clear spot is negative noiseless, can be used as the discriminating of acetaminophen in this preparation;
B, artificial Calculus Bovis's discriminating: with artificial Calculus Bovis's control medicinal material is contrast, and biliographic data has carried out the TLC discriminating to artificial Calculus Bovis in the sample, and clear spot is negative noiseless, can be used as the discriminating of artificial Calculus Bovis in this preparation;
The discriminating of c, chlorphenamine maleate: with the chlorphenamine maleate reference substance is contrast, and chlorphenamine maleate in the sample has been carried out the TLC discriminating, and clear spot is negative noiseless, can be used as the discriminating of chlorphenamine maleate in this preparation;
(2) assay
The assay of a, acetaminophen
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filler, with volume ratio methanol: water be 25: 75 be mobile phase, the detection wavelength is 257nm, and number of theoretical plate calculates by acetaminophen should be not less than 5000, and separating degree should be up to specification between main peak and adjacent peak;
Algoscopy: get 10 of this product, porphyrize, precision takes by weighing and is equivalent to acetaminophen 10mg, put in the 250ml measuring bottle, add the mutual-assistance dissolving of flowing, and be diluted to scale with mobile phase, shake up, filter membrane filters, and precision is measured subsequent filtrate 20ul, inject high performance liquid chromatograph, the record chromatogram, precision takes by weighing the acetaminophen reference substance in addition, with mobile phase dissolving and make the solution that every 1ml contains acetaminophen 40ug, measure with method, calculate respectively with peak area by external standard method, promptly;
B, content for Chlorphenamine Maleate are measured
Chromatographic condition and system suitability test: with the octadecylsilane chemically bonded silica is filler; With acetonitrile: 3% glacial acetic acid: triethylamine (20: 80: 0.08) is a mobile phase; The detection wavelength is 262nm, and theoretical cam curve is calculated by chlorphenamine maleate should be not less than 2500, and separating degree should be up to specification between main peak and adjacent peak;
Algoscopy: get 10 of this product, porphyrize, precision takes by weighing and is equivalent to chlorphenamine maleate 0.5mg, put in the 50ml measuring bottle, add the mutual-assistance dissolving of flowing, ultrasonic 10 minutes, and be diluted to scale with mobile phase, shake up, filter membrane filters, and precision is measured subsequent filtrate 20ul, injects high performance liquid chromatograph, the record chromatogram, in addition precision takes by weighing the chlorphenamine maleate reference substance, with the mobile phase dissolving and make the solution that every 1ml contains acetaminophen 20ug, measures with method, calculate respectively with peak area by external standard method, promptly;
(3) selection of preparation condition
A, citric acid baking temperature and the selection of time
Tabletting is granulated after adopting acid, the direct mixing of alkali, because of containing certain water of crystallization in the citric acid, easily discharge in the process of placing, so it is carried out drying and dehydrating, baking temperature and time are investigated, get the 100g citric acid, claim to decide weight, put 80 ℃ of dryings 3,4,5,6h respectively, claim to decide weight, other gets citric acid 100g, and dry 5h under 60 ℃, 70 ℃, 80 ℃, 90 ℃, 100 ℃ claims to decide weight;
The selection of b, granulation solvent
Medicine behind the equivalent incremental method mixing, needs to granulate routinely, because the strict control moisture of effervescent tablet so test use dehydrated alcohol and PVP are dissolved in the dehydrated alcohol as binding agent, is granulated with 5%PVP anhydrous alcohol solution 20 mesh sieves through repetition test;
The investigation of c, granulation ambient humidity
Because the hygroscopicity of effervescent tablet adjuvant is strong, response environment humidity in granule tabletting process, temperature is controlled to some extent, through the experiment, when ambient temperature at 20-26 ℃ of relative humidity in 45%, the tabletting effect is better, be difficult for taking place problems such as sticking, when relative humidity was higher than 50-55%, granule easily absorbed the water in air branch, and " sticking " phenomenon easily takes place;
D, particle drying temperature are selected and granulate
Because sodium bicarbonate is to responsive to temperature, high temperature easily decomposes, and therefore the particle drying temperature is needed to investigate, through repetition test, good to this product drying effect when selecting baking temperature to be 50 ℃, drying time is short, so selecting baking temperature is 50 ℃, dried granule is used for tabletting through 20 mesh sieve granulate;
E, mobility of particle are investigated
Granule needs certain fluidity could adapt to large-scale production, should add certain lubricant, commonly used have magnesium stearate, a PEG6000, because magnesium stearate is water insoluble, adopt to add water-soluble PEG6000,, add granule with 3% ratio through test, mobile suitable, tabletting sticking situation is had some improvement.
2. the method for quality control of effervescence tablet of Xiao ' er Anfen Huangnamin according to claim 1; it is characterized in that described optimal preparation effervescence tablet of Xiao ' er Anfen Huangnamin method is: will get 80 ℃ of dryings of citric acid 5 hours; pulverize; it is standby to cross 80 mesh sieves; get chlorphenamine maleate, artificial Calculus Bovis, acetaminophen by equivalent incremental method mixing;, essence sweet, pigment and lactose mixing with sodium bicarbonate, citric acid, A Siba; granulate with the 5%PVP ethanol solution; 50 ℃ of dryings; 20 mesh sieve granulate; tabletting, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910186300A CN101695503A (en) | 2009-10-23 | 2009-10-23 | Quality control method of pediatric paracetamol, atificial cow-bezoar and chlorphenamine maleate effervescent tablets |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910186300A CN101695503A (en) | 2009-10-23 | 2009-10-23 | Quality control method of pediatric paracetamol, atificial cow-bezoar and chlorphenamine maleate effervescent tablets |
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| CN101695503A true CN101695503A (en) | 2010-04-21 |
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| CN200910186300A Pending CN101695503A (en) | 2009-10-23 | 2009-10-23 | Quality control method of pediatric paracetamol, atificial cow-bezoar and chlorphenamine maleate effervescent tablets |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101982179A (en) * | 2010-11-04 | 2011-03-02 | 海南新中正制药有限公司 | Xiao er Anfen Huang Namin granule and preparation method thereof |
| CN106387597A (en) * | 2016-08-31 | 2017-02-15 | 重庆市秀山红星中药材开发有限公司 | Instant honeysuckle flower solid beverage and preparation method thereof |
-
2009
- 2009-10-23 CN CN200910186300A patent/CN101695503A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101982179A (en) * | 2010-11-04 | 2011-03-02 | 海南新中正制药有限公司 | Xiao er Anfen Huang Namin granule and preparation method thereof |
| CN101982179B (en) * | 2010-11-04 | 2012-07-25 | 海南新中正制药有限公司 | Xiao er Anfen Huang Namin granule |
| CN106387597A (en) * | 2016-08-31 | 2017-02-15 | 重庆市秀山红星中药材开发有限公司 | Instant honeysuckle flower solid beverage and preparation method thereof |
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