CN101283989A - Metronidazole vaginal tablet process and quality control method - Google Patents
Metronidazole vaginal tablet process and quality control method Download PDFInfo
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- CN101283989A CN101283989A CNA2008100492797A CN200810049279A CN101283989A CN 101283989 A CN101283989 A CN 101283989A CN A2008100492797 A CNA2008100492797 A CN A2008100492797A CN 200810049279 A CN200810049279 A CN 200810049279A CN 101283989 A CN101283989 A CN 101283989A
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- metronidazole
- clotrimazole
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Abstract
The invention relates to a preparation method and a quality control method of a new gynecologic drug, Metronidazole, Clotrimazole and Chlorhexidine Acetate Vaginal Tablets, with antibacterial and anti-inflammatory effects. The added lactic acid-calcium lactate buffer system results in a drug with pH of 3.5-4.0 t that is similar to the physiological pH in vagina, so as to effectively retain physiological environment in vagina, provide existing conditions suitable for vaginal beneficial bacteria, and promote rehabilitation. The main preparation method comprises the steps of compounding, granulating, grading, mixing, and tabletting. The quality control method comprises the steps of collecting one dosage unit of the product, grinding, adding 100mL water, shaking for 10min, and testing pH (should be 3.5-4.0); testing melting time limit (should be 30min); and measuring the nominal content of the three components by high performance liquid chromatography (should be both in the range of 90.0-110.0%).
Description
Technical field
The present invention relates to method for making and the method for quality control of a kind of gynecological with the new drug metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet of anti-inflammation.
Background technology
At present, infusorian, anaerobe, mycete and other bacterial infection gynaecopathia serious threat WomanHealths.Although the Amino-Cerv kind is a lot of, use and treat all to have certain problem; In addition, existing at present metronidazole, clotrimazole and chlorhexidime acetate vaginal effervescent tablet listing, there is storage moisture absorption aerogenesis in it, acid ingredient thorn Severe Pain; Influence the problem of vagina physiological PH value.
The objective of the invention is to overcome the deficiency of existing kind, the new formulation of a kind of spectrum, efficient, quick-acting, stable, good patient compliance is provided and method of quality control is provided.
Summary of the invention
The present invention is a kind of novel drugs that is mainly used in gynecological infection, vaginal tablet is easy-to-use, direct, rapid than suppository, washing liquid, vagina effervescence, after medicine contacts with focus is local, trace physiological secretions makes vaginal tablet moistening disintegrate, fill the air distribution, directly contact, immerse in its cell, give full play to the killing microorganisms effect with the focus pathogenic microorganism.The safe prescription element of two azoles has anaerobe resistant, anti-trichomonal, anti-ameba, antifungal, mycete, effects such as anti-aerobe can be used for anaerobe, aerobe, infusorian, the gynecological that the simple or mixed infection of mycete causes, anorectal, the skin commonly encountered diseases, as pelvic inflammatory disease, cervical erosion, vaginitis etc.Easy to use, clean, do not influence routine work study.
The invention has the advantages that tract local application, avoid or reduce the possible untoward reaction of systemic administration; diseased region medicine effective concentration height; help bringing into play therapeutical effect; the lactic acid of its adding, calcium lactate buffer system make the PH of medicine close with vagina physiology PH 3.5～4.0 between, effectively safeguard the vagina physiological environment; provide the vagina profitable strain suitable conditions of existence, promote rehabilitation.
The present invention is achieved in that
(1) (1000 preparation units): metronidazole 100～600g clotrimazole 80～480g chlorhexidine acetate 4～24g and pharmaceutically vaginal tablet acceptable auxiliary 200g～3500g make.
Adjuvant mainly is selected from but is not limited only to by filler starch in the prescription of this product, lactose, sucrose, glucose, dextrin, mannitol, Nulomoline, calcium hydrogen phosphate, kaolin, Montmorillonitum, PH buffer system lactic acid/calcium lactate that weak acid and its salt constitute, citric acid/citrate, fumaric acid/fumarate, phosphoric acid/phosphate, acetic acid/acetate, disintegrating agent carboxymethyl base Starch Sodium, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl starch sodium, carboxymethylcellulose calcium, cross-linked cellulose sodium, crospolyvinylpyrrolidone, alginic acid tungsten ammonium, fluidizer lubricant silicon dioxide, stearic acid and salt thereof, refining hydrogenated vegetable oil, liquid paraffin,light, Macrogol 4000 and 6000, Pulvis Talci, lauryl sulfate and the surfactant such as the tween 80 that add according to circumstances, Arlacel-60, the vaginal tablet that bromination cetyl potassium ammonium is made.
Metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet optimization prescription is: metronidazole 200g, clotrimazole 160g, chlorhexidine acetate 8g, lactose 40g, starch 20.0g, calcium lactate 60g, lactic acid 82g, hypromellose 6.0g, silicon dioxide 30.0g, microcrystalline Cellulose 182.0g, polyvinylpolypyrrolidone 120g (adding 40g), magnesium stearate 4.0g, make 1000.
The main preparation process of this product: A pretreatment: metronidazole, clotrimazole, chlorhexidine acetate and adjuvant are crossed sieve respectively No. 7.
B metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet preparation of granules: metronidazole, clotrimazole, chlorhexidine acetate and the filler, pH value buffer substance, the part disintegrating agent that take by weighing recipe quantity, select for use suitable adhesive (surfactant can be added wherein) to granulate, 16 orders are granulated, 60～70 ℃ of dryings, 16 mesh sieve granulate, the fluidizer lubricant and the residue disintegrating agent that add recipe quantity again, mixing.Survey the granule content of dispersion, basis of calculation sheet is heavy.
The C tabletting: select the fusiformis stamping of suitable size, tablet hardness is controlled at 5～6kg.
Those skilled in the art belong to category of the present invention to adjustment and the improvement without prejudice to the technology of the present invention essence that the present invention makes.
(2) quality standard of this product mainly comprises: 1. acidity is got this product an amount of (metronidazole that is equivalent to a preparation unit), and porphyrize adds water 100ml, and (two appendix VI of Chinese Pharmacopoeia version in 2005 H) measured in jolting in accordance with the law after 10 minutes, and pH value should be 3.5～4.0.
2. melt and become the time limit and get 3 of this product, check (two appendix X of Chinese Pharmacopoeia version in 2005 B) all should in 30 minutes, all melt, but open-porous metal disk residual fraction not to have the soft agglomerate of solid hard-core in accordance with the law.
3. [assay] is according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2005 D)
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica or amino bonded silica gel; (get potassium dihydrogen phosphate 4.35g with methanol-acetonitrile-phosphate solution, in the 1000ml measuring bottle, thin up is to scale, with phosphoric acid regulating ph value to 2.8) (55: 10: 35) or methanol-phosphate buffer (get phosphoric acid 5ml, add 50% methanol solution and be diluted to 1000ml, regulate pH value to 3.8 with triethylamine) (40: 60) or second eyeball: the 0.016mol/L potassium dihydrogen phosphate: dodecyl sodium sulfate (28: 31: 31, regulate pH value 8.0 with ammonia) is a mobile phase; The detection wavelength is 260nm.Number of theoretical plate calculates by the clotrimazole peak and is not less than 2000.
Algoscopy is got 10 of this product, and accurate the title decided porphyrize, precision takes by weighing in right amount (being equivalent to metronidazole 100mg approximately), puts in the 50ml measuring bottle, adds methanol and makes dissolving and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 5ml, puts in the 100ml measuring bottle, add mobile phase and be diluted to scale, shake up, get 20 μ l and inject chromatograph of liquid, the record chromatogram; It is an amount of that precision takes by weighing the chlorhexidine acetate reference substance in addition, adds methanol and make the solution that contains 80 μ g among every 1ml approximately; Precision takes by weighing metronidazole, clotrimazole in right amount in the 100ml measuring bottle again, add chlorhexidine acetate reference substance solution 5ml and make dissolving with an amount of methanol, add mobile phase and be diluted to scale, shake up, every 1ml contains the solution that metronidazole, clotrimazole, chlorhexidine acetate are respectively 100 μ g, 80 μ g, 4 μ g, measure with method.Press external standard method with C in the calculated by peak area test sample
6H
9N
3O
3, C
22H
17CIN
2With C
22H
30C
12N
102C
2H
4O
2Content, three kinds of compositions indicate content all should be in 90.0～110.0% limits.
The specific embodiment
Embodiment: (1) prescription metronidazole 200g, clotrimazole 160g, chlorhexidine acetate 8g, lactose 40g, starch 20.0g, calcium lactate 60g, lactic acid 82g, hypromellose 6.0g, silicon dioxide 30.0g, microcrystalline Cellulose 182.0g polyvinylpolypyrrolidone 120g (adding 40g), magnesium stearate 4.0g.
(2) method for making
The A pretreatment: except that lactic acid, with metronidazole, clotrimazole, chlorhexidine acetate, lactose, starch, calcium lactate, lactic acid, silicon dioxide, polyvinylpolypyrrolidone, microcrystalline Cellulose, magnesium stearate are crossed sieve respectively No. 7.
B metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet preparation of granules: metronidazole, clotrimazole, chlorhexidine acetate and the lactose, starch, calcium lactate, lactic acid, the polyvinylpolypyrrolidone 80g that take by weighing recipe quantity, with 2% hypromellose aqueous solution is adhesive, 16 orders are granulated, 60～70 ℃ of dryings, 16 mesh sieve granulate, add magnesium stearate, silicon dioxide, the microcrystalline Cellulose of recipe quantity and the polyvinylpolypyrrolidone 40g that adds, mixing.Survey the granule content of dispersion, basis of calculation sheet is heavy.
The C tabletting: select the fusiformis stamping of suitable size, tablet hardness is controlled at 5～6kg.
(3) effect of adjuvant in prescription:
1, lactose: filler.
2, starch: filler
3, magnesium stearate: be the lubricant of tablet, it can increase particulate flowability, prevents sticking.
4, calcium lactate: filler, PH buffer components.
5, lactic acid: acid constituents, PH buffer components.
6, silicon dioxide: filler, fluidizer.
7, polyvinylpolypyrrolidone: disintegrating agent.
8, microcrystalline Cellulose: adhesive, disintegrating agent
9, hypromellose: adhesive, disintegrating agent
Stability test
1, main test apparatus
High performance liquid chromatograph SPD-10ATVP island Tianjin LC-10ATVP
Tianjin, analytical balance AY120 island
Ultraviolet-uisible spectrophotometer FWZ800-D3B island Tianjin UV-2450
2, medicine
Supply test agent: metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet self-control lot number is: 061,001 061,002 061003
Reference substance: metronidazole: Metronidazole, lot number: 100191-200305
Reference substance: clotrimazole: Clotrimazole, lot number: 100037-200306
Reference substance: chlorhexidine acetate: Chlorhexidine Acetate, lot number: 100183-199902
3, accelerated stability test method
With the two aluminum packings of metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet (061,001 061,002 061003) (commercially available back on the plan), 40 ± 2 ℃ of temperature, placed 6 months under the condition of relative humidity 75% ± 5% (saturated aqueous common salt), respectively at 0 month, 1 the end of month, 2 the end of month, 3 the end of month, sampling in 6 months once, by stable high spot reviews project (character, melt become time limit, content) detection.
4, long-term stable experiment method
The two aluminum packings of metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet (061,001 061,002 061003) (plan commercially available back) 25 ± 2 ℃ of temperature, are placed under the condition of relative humidity 60% ± 10%.Respectively at 0 month, 3 the end of month, 6 the end of month, detect by stable high spot reviews project (character, melt become time limit, content).
5, stability test result
Metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet accelerated test (relative humidity 75% ± 5%, 40 ℃ ± 2 ℃ of temperature) test down, long term test (relative humidity 60% ± 10%, 25 ℃ ± 2 ℃ of temperature) observed 6 months continuously respectively, its to character, melt projects such as becoming time limit, content and detect, and 0 month, June the foot couple microbial limit investigate, have no significant change, the regulation that meets quality standard, the metronidazole, clotrimazole and chlorhexidime acetate vaginal tablet quality is stable, long-term stable experiment is still underway, and completed 12 menology phaneroplasm amounts are stable.Packaging material do not have influence to quality, tentative 24 months of effect duration.
6, influence factor's test
Stipulate according to Chinese Pharmacopoeia version appendix in 2005 XI XC " medicine stability test guideline ", adopt a batch sample (lot number: 061001) test of pilot product, experimental condition is respectively 60 ℃ of high temperature, high humidity 90% (25 ℃), high light (4500Lx ± 500Lx), measure respectively at sampling in 5,10 days, compare with 0 day measurement result.
(1) hot test
Get this product and place culture dish in right amount, put in 60 ℃ of calorstats and placed 10 days,, compare with 0 day measurement result respectively at the 5th, 10 day sampling and measuring.
(2) high wet test
Sample thief is put in the culture dish in right amount, and accurate the title decided weight, is placed in the container of constant humidity again, 25 ℃ of temperature, places under the condition of relative humidity 90%, in 5,10 days sampling and measuring, compares with 0 day measurement result.
(3) strong illumination
Get an amount of sample and spread out in culture dish, be placed on 4500 ± 500Lx illumination and place, and, compare with 0 day measurement result in 5,10 days sampling and measuring.
Result: stipulate according to pharmacopeia, with metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet exposed placement 10 days under high temperature, high humidity, strong illumination, and, content heavy to character, sheet at the 5th day, 10 days is investigated, compare with 0 day result, the sheet moisture absorption weightening finish under sheet weight and high humidity environment, content does not have significant change, meets the regulation of quality standard.The metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet is steady quality under high temperature, high humidity, strong illumination.
Safety testing
1, metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet mucomembranous pungency test
1.1 test objective:
After observation metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet is repeatedly inserted the rabbit vagina, to the irritant reaction situation that the rabbit vagina mucosa produces, untoward reaction such as the inflammation that mucosa may occur after the prompting clinical drug was used, tissue degeneratiaon.
1.2 test material
1.2.1 be subjected to the reagent thing
Metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet lot number: 061001, the negative control product: except that not containing the medicine, all the other are with the metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet.
1.2.2 laboratory animal
Animal varieties: Japan large ear rabbit, the unit of providing: science and technology exchange centre in Henan Province's provides credit number: scxk2005-0002, animal
Rank: regular grade, body weight, sex: 2.0～2.5kg, female, no pregnant.Number of animals: 12
Raising condition: regular grade Animal House, 1 in every cage, temperature: 20 ± 3 ℃; Humidity: 50%-70%; Light application time: 12 hours.Free diet.Laboratory observation 3 days, no abnormality seen.
1.3 test method
Animal is divided into 2 groups immediately, 6 every group, is respectively medication group and negative control group.With special instrument, slowly the metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet is inserted the rabbit vagina deep, negative control group same procedure administration.Administration every day 1 time, successive administration 7 days.The last administration was put to death the half animal respectively in 24 hours, 48 hours, cut vagina open, and warm water washes away residue, observed administration place mucosa situation of change and also drew materials, put in 10% the formaldehyde fixing after, carry out histopathologic examination.
1.4 result of the test
During the administration, it is good that each organizes the rabbit overall health of patients, animal activity freely, hair luster, the feed and defecation normal, the no abnormal secretions in vaginal orifice place shows no obvious abnormalities reaction; Each is organized the perusal of rabbit vagina mucous membrane tissue and is not seen phenomenons such as hyperemia, redness, breakage and erosion, the result of histopathologic examination, and each routine vaginal mucosa organizational structure of medication group and negative control group is complete, does not see hemorrhage, inflammation and necrosis, the results are shown in Table 1.
Behind the table 1 metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet topical rabbit vaginal mucosa is organized naked eyes and histological examination result
1.5 estimate and conclusion
Under this experimental condition, the metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet is to the effect of animal subject vaginal mucosa nonirritant.
2 metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet skin sensitivity tests
Summary is by test requirements document, carried out the skin allergy test of metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet with healthy guinea pig, and the result shows that under this experiment condition the metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet does not have sensitization to animal subject.
2.1 test objective
After repeating contact and tried thing by animal skin, observe body immune system and be reflected at performance on the skin.
2.2 test material
2.2.1 be subjected to the reagent thing: metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet lot number: 061001; Test medication:,, use preceding preparation with 0.9% sodium chloride injection furnishing pasty state (concentration about 40%) with metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet grind into fine powder; Reference substance: 0.9% sodium chloride injection, 05041634, Henan bamboo grove all living creatures pharmaceutical Co. Ltd provides.
2.2.2 laboratory animal
Animal varieties: healthy Hartley Cavia porcellus.The unit of providing: science and technology exchange centre in Henan Province's provides.Body weight, sex: 300～350g, male and female half and half.Number of animals: 40
Raising condition: regular grade Animal House, 5 in every cage, temperature: 20 ± 3 ℃; Humidity: 30%-70%; Light application time: 12 hours, free diet.Laboratory observation 5 days, no abnormality seen.
Positive sensitizer: 2,4-dinitro-chloro-benzene (DNCB), Tianjin recovery fine chemistry industry institute is produced lot number: 20030217.
Sensitization: be made into 1% solution for standby with 70% ethanol.
Excite: will go up liquid and be diluted to 0.1% standby.
2.3 test method
2.3.1 test grouping: Cavia porcellus is divided into three groups at random by the body weight sex, first group 20, tried thing metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet, second group 10, be blank (giving normal saline), the 3rd group 10, positive thing matched group (giving DNCB).
2.3.2 test key step:
2.3.2.1. tried preceding 24 hours of thing the guinea pig back diamond wool is removed about 4 * 6 square centimeters of the every side of unhairing scope with shaver in giving.
2.3.2.2. sensitization contact: get metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet pastel 0.2ml and be evenly coated in depilation district, animal left side.Cover with thin film, the external application gauze is then fixed with rubberized fabric adhere, continues 6 hours.The 7th day and the 14th day, in kind repeat once.The blank group is given normal saline 0.2ml; Positive controls is given 1% dinitro-chloro-benzene 0.2ml, and method is the same.
2.3.2.3 excite contact: in last give tried thing sensitization after 14 days, 0.2ml is applied to depilation district, guinea pig back right side with metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet pastel, with 0.1% dinitro-chloro-benzene 0.2ml, medication is the same with normal saline 0.2ml, positive controls for the blank group.Remove after 6 hours and tried thing, observe at once, observed the skin allergy situation once more in 24,48,72 hours then, press table 1 scoring.
Table 1 skin allergy standards of grading
Reaction meansigma methods=(erythema forms total points+edema and forms total points)/total number of animals
2.4, the result judges and estimate:
According to the difference of test group and the reaction of matched group guinea pig skin, press table 1 and judge that the metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet is to skin allergy character.The result: after the sensitization 6 hours first, to observe after removing covering, normal saline matched group, medication treated animal skin do not have significant change, and positive controls has 6 slight erythema to occur, disappears gradually after 72 hours; For the second time after the sensitization, normal saline matched group, medication treated animal skin do not have significant change, and positive controls has 53 of moderate erythema to occur and Mild edema occurs; After the sensitization, normal saline matched group, medication treated animal skin do not have significant change for the third time, and positive controls has 74 edema of moderate erythema to occur.Excite the back different time to observe, normal saline matched group, medication treated animal skin do not have erythema and edema, no skin allergy; Positive group different time observed result sees Table 2
Table 2 metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet skin hypersensitive test reaction evaluating
2.5 conclusion: after the administration, medication group, normal saline group all do not have erythema and edema to form to each treated animal as stated above, and the anaphylaxis of metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet skin is negative.
Claims (4)
1 metronidazole vaginal tablet process and method of quality control, it is characterized in that prescription (1000 preparation units) is: metronidazole 100～600g clotrimazole 80～480g chlorhexidine acetate 4～24g and pharmacy acceptable auxiliary 200g～3500g make.Adjuvant mainly is selected from but is not limited only to by filler starch in the prescription, lactose, sucrose, glucose, dextrin, mannitol, Nulomoline, calcium hydrogen phosphate, kaolin, Montmorillonitum, PH buffer system lactic acid/calcium lactate that weak acid and its salt constitute, citric acid/citrate, fumaric acid/fumarate, phosphoric acid/phosphate, acetic acid/acetate, tartaric acid/tartrate, disintegrating agent carboxymethyl base Starch Sodium, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl starch sodium, carboxymethylcellulose calcium, cross-linked cellulose sodium, crospolyvinylpyrrolidone, alginic acid tungsten ammonium, fluidizer lubricant silicon dioxide, stearic acid and salt thereof, refining hydrogenated vegetable oil, liquid paraffin,light, Macrogol 4000 and 6000, Pulvis Talci, lauryl sulfate and the surfactant tween 80 that adds according to circumstances, the vaginal tablet that bromination cetyl potassium ammonium is made.
2. described metronidazole vaginal tablet process of claim 1 and method of quality control, it is characterized in that optimizing prescription (1000 preparation units) is: metronidazole 200g, clotrimazole 160g, chlorhexidine acetate 8g, lactose 40g, starch 20.0g, calcium lactate 60g, lactic acid 82g, hypromellose 6.0g, silicon dioxide 30.0g, microcrystalline Cellulose 182.0g, polyvinylpolypyrrolidone 120g (adding 40g), magnesium stearate 4.0g, make 1000.
Described metronidazole vaginal tablet process of 3 claim 1 and method of quality control is characterized in that main preparation process is: the A pretreatment: except that lactic acid, metronidazole, clotrimazole, chlorhexidine acetate and adjuvant are crossed sieve respectively No. 7.
B metronidazole, clotrimazole and chlorhexidime acetate vaginal sheet preparation of granules: metronidazole, clotrimazole, chlorhexidine acetate and the filler, pH value buffer substance, the part disintegrating agent that take by weighing recipe quantity, select for use suitable adhesive (surfactant can be added wherein) to granulate, 16 orders are granulated, 60～70 ℃ of dryings, 16 mesh sieve granulate, the fluidizer lubricant and the residue disintegrating agent that add recipe quantity again, mixing.Survey the granule content of dispersion, basis of calculation sheet is heavy.
The C tabletting: select the fusiformis stamping of suitable size, tablet hardness is controlled at 5～6kg.
4. described metronidazole vaginal tablet process of claim 1 and method of quality control is characterized in that main quality control method is:
1. acidity is got this product an amount of (metronidazole that is equivalent to a preparation unit), and porphyrize adds water 100ml, and (two appendix VI of Chinese Pharmacopoeia version in 2005 H) measured in jolting in accordance with the law after 10 minutes, and pH value should be 3.5～4.0.
2. melt and become the time limit and get 3 of this product, check (two appendix X of Chinese Pharmacopoeia version in 2005 B) all should in 30 minutes, all melt, but open-porous metal disk residual fraction not to have the soft agglomerate of solid hard-core in accordance with the law.
3. [assay] is according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2005 D)
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica or amino bonded silica gel; (get potassium dihydrogen phosphate 4.35g with methanol-acetonitrile-phosphate solution, in the 1000ml measuring bottle, thin up is to scale, with phosphoric acid regulating ph value to 2.8) (55: 10: 35) or methanol-phosphate buffer (get phosphoric acid 5ml, add 50% methanol solution and be diluted to 1000ml, regulate pH value to 3.8 with triethylamine) (40: 60) or second eyeball: the 0.016mol/L potassium dihydrogen phosphate: dodecyl sodium sulfate (28: 31: 31, regulate pH value 8.0 with ammonia) is a mobile phase; The detection wavelength is 260nm.Number of theoretical plate calculates by the clotrimazole peak and is not less than 2000.
Algoscopy is got 10 of this product, and accurate the title decided porphyrize, precision takes by weighing in right amount (being equivalent to metronidazole 100mg approximately), puts in the 50ml measuring bottle, adds methanol and makes dissolving and be diluted to scale, shake up, filter, precision is measured subsequent filtrate 5ml, puts in the 100ml measuring bottle, add mobile phase and be diluted to scale, shake up, get 20 μ l and inject chromatograph of liquid, the record chromatogram; It is an amount of that precision takes by weighing the chlorhexidine acetate reference substance in addition, adds methanol and make the solution that contains 80 μ g among every 1ml approximately; Precision takes by weighing metronidazole, clotrimazole in right amount in the 100ml measuring bottle again, add chlorhexidine acetate reference substance solution 5ml and make dissolving with an amount of methanol, add mobile phase and be diluted to scale, shake up, every 1ml contains the solution that metronidazole, clotrimazole, chlorhexidine acetate are respectively 100 μ g, 80 μ g, 4 μ g, measure with method.Press external standard method with C in the calculated by peak area test sample
6H
9N
3O
3, C
22H
17CIN
2With C
22H
30C
12N
102C
2H
4O
2Content, three kinds of compositions indicate content all should be in 90.0 ~ 110.0% limits.
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| CNA2008100492797A CN101283989A (en) | 2008-02-28 | 2008-02-28 | Metronidazole vaginal tablet process and quality control method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014513124A (en) * | 2011-05-02 | 2014-05-29 | アプタリス ファーマテク，インコーポレイテッド | Fast dissolving tablet composition for vaginal administration |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014513124A (en) * | 2011-05-02 | 2014-05-29 | アプタリス ファーマテク，インコーポレイテッド | Fast dissolving tablet composition for vaginal administration |
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