CN102860987A - Diclofenac sodium sustained-release capsule and preparation method thereof - Google Patents
Diclofenac sodium sustained-release capsule and preparation method thereof Download PDFInfo
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Abstract
The invention provides an anti-inflammation analgesia medicine, particularly provides a diclofenac sodium sustained-release capsule and a production method thereof. The preparation method of the diclofenac sodium sustained-release capsule includes that diclofenac sodium is prepared to be a sustained-release pellet, and the sustained-release pellet is filled in the capsule. The diclofenac sodium sustained-release pellets is composed of a blank pellet core serving as a parent nucleus, a main medicine layer and a sustained-release coating layer, the main medicine layer contains the diclofenac sodium and is coated outside the pellet core, and the sustained-release coating layer is coated outside the main medicine layer. The diclofenac sodium sustained-release capsule has the advantages that the preparation stability is good, the releasing effect is remarkably excellent, and compared with common capsules, the diclofenac sodium sustained-release capsule is safe and convenient for a patient to take in.
Description
Technical field
The present invention relates to a kind of slow releasing preparation, specifically, relate to a kind of diclofenac sodium extended release capsule and preparation method thereof, belong to medical technical field.
Background technology
Diclofenac sodium is nonsteroidal antiinflammatory drug, and its active ingredient is diclofenac, and is main by suppressing synthetic analgesia, antiinflammatory, the refrigeration function of producing of prostaglandin.Rheumatic arthritis, rheumatoid arthritis, degenerative osteoarthritis, gout, periarticular soft tissues inflammation, the caused arthralgia of damage had good therapeutical effect.Its curative effect is better than other steroid medicines such as indometacin, aspirin, ibuprofen, naproxen, and absorb fast, few side effects, the intestines and stomach reaction is lighter than most of nonsteroidal antiinflammatory drugs, better tolerance, dosage is little, and individual variation is little, therefore be widely used at present more than 120 countries and regions, countries in the world.
The dosage form of the present domestic listing of diclofenac sodium has Tablet and Capsula, its usage and dosage is: adult's rheumatoid arthritis 150-200mg/ days (3-4 grain/sky), every day repeatedly frequently medication brought very large inconvenience to the patient, and blood drug level is not steady, peak valley phenomenon occurs, the medication of high dose produces very large toxic and side effects.Slow releasing preparation then can make according to certain rules slow non-constant release of medicine, and medicine is the long period drug level of remaining valid in vivo, thereby reaches the minimizing drug dose, improves drug effect, prolong drug action time and reduce the purpose of adverse effect.The at present research of slow releasing preparation and production have caused extensive attention both domestic and external, become the focus of developmental research.
The pertinent literature of diclofenac salt slow releasing preparation seldom, the document that retrieves at present is Piclofenac potassium sustained release capsule and the production technology patent thereof of Hainan Baina Pharmaceutical Development Co., Ltd. application, its publication number is CN101322695A.But supplementary product kind and composition that the diclofenac potassium sustained-release pellet of above-mentioned patent uses are many, and its release and stability remain further to be improved.
Summary of the invention
The technical problem that this present invention will solve is to provide a kind of supplementary product kind of use and composition few, diclofenac sodium extended release capsule and production method thereof that release and stability further improve.
Technical scheme of the present invention comprises: a kind of study of diclofenac sodium sustained release micropellets, its by as the celphere of parent nucleus, be wrapped in the outer principal agent layer that contains diclofenac sodium of ball core and be wrapped in the outer sustained release coating layer of principal agent layer and form:
I. count by weight percentage, celphere 63%～70% is preferably 65-69%, principal agent layer 20%～35%,
Be preferably 20%～25%, surplus is the sustained release coating layer;
Ii. described principal agent layer is made by diclofenac sodium and binding agent, and counts by weight percentage, and contains diclofenac sodium 89%～99% in the principal agent layer, is preferably 95%～99%, surplus is binding agent;
Iii. described sustained release coating layer is made by slow releasing agent, antiplastering aid, porogen, plasticizer, count by weight percentage,
Contain in the sustained release coating layer that slow releasing agent 50%～60% is preferably 55%～58%, antiplastering aid.
Among the present invention, the binding agent that study of diclofenac sodium sustained release micropellets is used or porogen are selected from a kind of in polyvidone, the hypromellose or their various combinations, the technical scheme that preferred adhesive is identical with the porogen composition, more preferably binder dosage is 1/2nd of porogen; Used slow releasing agent is selected from a kind of in ethyl cellulose, the cellulose acetate or their various combinations; Used antiplastering aid is selected from a kind of in Pulvis Talci, magnesium stearate, the micropowder silica gel or their various combinations; Used plasticizer is selected from a kind of in triethyl citrate, dimethyl phthalate, the triacetin or their various combinations, the identical scheme of consumption of preferred porogen and plasticizer;
Among the present invention, celphere is comprised of sucrose, starch or microcrystalline Cellulose, and the size of celphere is 0.35～1.12mm, is preferably 0.6～0.9mm.
Study of diclofenac sodium sustained release micropellets of the present invention is loaded the capsule that forms, and contains diclofenac sodium 30～100mg in every capsules, is preferably 50mg.
The method of the study of diclofenac sodium sustained release micropellets of the present invention's preparation comprises the steps: that (1) joins celphere in the comminutor, behind the dissolve with ethanol of binding agent with 60%～95% percentage by weight, add principal agent, stirring and dissolving, celphere is joined in the comminutor, the coating solution that sprinkling prepares gets the pastille micropill in the celphere surface after the drying; (2) slow releasing agent of sustained release coating layer, porogen, plasticizer and antiplastering aid are made sustained release coating liquid with the dissolve with ethanol solution of 80%～95% percentage by weight; (3) the sustained release coating liquid for preparing is evenly sprayed on the pastille micropill surface for preparing, get study of diclofenac sodium sustained release micropellets after the drying.Wherein centrifugal coating granulator, fluidized bed coating granulator or the preparation of efficient film coating pan are adopted in step (1) and (3).
The determination of related substances method of diclofenac sodium extended release capsule of the present invention comprises following condition step: adopt high performance liquid chromatography, chromatographic condition: take octadecylsilane chemically bonded silica as filler, take methanol-4% glacial acetic acid solution by 65:35 as mobile phase, flow velocity 1.0ml/min detects wavelength 254nm; Theoretical cam curve should be not less than 5000 in the diclofenac sodium peak; Get diclofenac sodium extended release capsule an amount of (approximately being equivalent to diclofenac sodium 0.1g), accurately weighed, put in the 100ml measuring bottle, add methanol an amount of, supersound process 10min makes dissolving, lets cool, and is diluted to scale with methanol, shake up, centrifugal, get supernatant as need testing solution; Other gets dimethyl phthalate 5mg, puts in the 200ml measuring bottle, adds methanol and makes dissolving, and the accurate need testing solution 1ml that adds is diluted to scale with methanol, shakes up, in contrast solution.Get the diclofenac sodium reference substance an amount of, water is made the solution that approximately contains 1mg among every 1ml, get an amount of, put in the quartzy absorption cell, at the lower irradiation of ultra-violet lamp (254nm) 15min, get 20l, the injection liquid chromatography, the record chromatogram approximately impurity one peak occurring in the 0.8min place with diclofenac sodium peak relative retention time, and the separating degree between impurity peaks and the diclofenac sodium should be not less than 6.0; Get contrast solution 20l, the injection liquid chromatography is regulated detection sensitivity, makes the diclofenac sodium peak height be about 20% of full scale; Precision measures need testing solution again, each 20l of contrast solution, difference injection liquid chromatography, the record chromatogram is to 2 times of the main peak retention time, in the chromatogram of need testing solution if any impurity peaks, except the chromatographic peak before the diethyl phthalate peak meter, peak (impurity III) if any relative retention time 1.2～1.3, must not be greater than contrast solution main peak area (0.5%) after its peak area multiply by 0.5, other single impurity peak area must not be greater than contrast solution main peak area (0.5%), each impurity peak area and (the impurity III is by the peak area after proofreading and correct) must not be greater than 2 times (1.0%) of contrast solution main peak area.
The present invention is directed to the diclofenac sodium active pharmaceutical ingredient, by lot of experiments research, found that study of diclofenac sodium sustained release micropellets of the present invention forms and technique, and then made diclofenac sodium extended release capsule, have good preparation stability, outstanding good release profiles.The present invention can overcome and take conventional capsule and take the peak concentration of rear appearance, paddy phenomenon by the diclofenac sodium extended release capsule of preparation, can keep balance, lasting effective blood drug concentration in equal dosage and interval, thereby increase curative effect; Or reduce dosage when keeping equal drug effect, thereby reduce the side effect that drug administration brings to the patient.According to the diclofenac sodium usage and dosage, be grown up 150-200mg/ days (3-4 grain/sky), the present invention makes slow releasing capsule with diclofenac sodium, effectively reduce administration number of times, can keep for a long time drug effect concentration, reached long-acting purpose, and preparation technology is simple, production cost is low, takes and stores conveniently, has also reduced the toxic and side effects of medicine simultaneously.
Description of drawings
Fig. 1: embodiment 1 and cumulative release amount-time graph of 0 day 2,4,6,8,10,12 hours of comparative sample
The specific embodiment
The comparative example: the diclofenac sodium extended release capsule that obtains according to the formula preparation of the embodiment 3 among the documents CN101322695A, in this application referred to as comparative sample.
(1) the 300g celphere is joined in the comminutor, spray an amount of 80% alcoholic solution moistening, add the mixture of 200g diclofenac sodium and 45g lactose, 37g microcrystalline Cellulose, locate to make in 90 minutes ganoid pastille micropill;
(2) with 60%～95% dissolve with ethanol solution 153g cellulose acetate and 22g citron triethylenetetraminehexaacetic acid fat, 21g polyvidone, 34g Pulvis Talci, make sustained release coating liquid;
(3) the sustained release coating liquid for preparing is evenly sprayed on the pastille micropill surface for preparing, then the slow-release micro-pill of gained is placed 60 ℃ vacuum drying oven inner drying 4 hours, get slow-release micro-pill;
(4) content and the release of detection slow-release micro-pill, qualified rear calculating loading amount in the corresponding capsule shells of packing into, gets diclofenac sodium extended release capsule (comparative sample).
Embodiment 1 diclofenac sodium extended release capsule prescription forms and preparation method thereof
Preparation process is:
(1) 1g hypromellose K30 is joined in 95% ethanol of 4.5 times of weight stirring and dissolving; The diclofenac sodium of recipe quantity is added in the mentioned solution stirring and dissolving;
(2) the 150g celphere is joined in the comminutor, open temp and compressed air slowly are sprayed onto medicinal liquid (1) on the celphere, and preparation contains pill core;
(3) with 95% dissolve with ethanol solution 10g ethyl cellulose of 10 times of weight and 2g diethyl phthalate, 4.5g Pulvis Talci, 2g hypromellose, make sustained release coating liquid;
(4) the sustained release coating liquid (3) for preparing is evenly sprayed on the pastille micropill surface for preparing, then the slow-release micro-pill of gained is placed 65 ℃ vacuum drying oven inner drying 3 hours, get slow-release micro-pill;
(5) content and the release of detection slow-release micro-pill, qualified rear calculating loading amount is packed in the corresponding capsule shells, gets diclofenac sodium extended release capsule.
Embodiment 2 diclofenac sodium extended release capsules prescription and preparation method thereof
Preparation process is:
(1) 1.8g hypromellose K30 is joined in 95% ethanol of 4.5 times of weight stirring and dissolving; The diclofenac sodium of recipe quantity is added in the mentioned solution stirring and dissolving;
(2) the 150g celphere is joined in the comminutor, open temp and compressed air slowly are sprayed onto medicinal liquid (1) on the celphere, and preparation contains pill core;
(3) with 95% dissolve with ethanol solution 15g cellulose acetate of 11 times of weight and 3g triethyl citrate, 5g magnesium stearate, 3.6g hypromellose, make sustained release coating liquid;
(4) the sustained release coating liquid (3) for preparing is evenly sprayed on the pastille micropill surface for preparing, then the slow-release micro-pill of gained is placed 70 ℃ vacuum drying oven inner drying 2 hours, get slow-release micro-pill;
(5) content and the release of detection slow-release micro-pill, qualified rear calculating loading amount is packed in the corresponding capsule shells, gets diclofenac sodium extended release capsule.
Embodiment 3 diclofenac sodium extended release capsules prescription and preparation method thereof
Preparation process is:
(1) the 2g hypromellose is joined in 95% ethanol of 3.5 times of weight stirring and dissolving; The diclofenac sodium of recipe quantity is added in the mentioned solution stirring and dissolving;
(2) the 150g celphere is joined in the comminutor, open temp and compressed air slowly are sprayed onto medicinal liquid (1) on the celphere, and preparation contains pill core;
(3) with 95% dissolve with ethanol solution 15g cellulose acetate of 10 times of weight and 3g triacetin, 5g micropowder silica gel, 6g hypromellose, make sustained release coating liquid;
(4) the sustained release coating liquid (3) for preparing is evenly sprayed on the pastille micropill surface for preparing, then the slow-release micro-pill of gained is placed 70 ℃ vacuum drying oven inner drying 2 hours, get slow-release micro-pill;
(5) content and the release of detection slow-release micro-pill, qualified rear calculating loading amount is packed in the corresponding capsule shells, gets diclofenac sodium extended release capsule.
Embodiment 4 diclofenac sodium extended release capsules prescription and preparation method thereof
Preparation process is:
(1) the 0.8g PVP K30 is joined in 95% ethanol of 4 times of weight stirring and dissolving; The diclofenac sodium of recipe quantity is added in the mentioned solution stirring and dissolving;
(2) the 150g celphere is joined in the comminutor, open temp and compressed air slowly are sprayed onto medicinal liquid (1) on the celphere, and preparation contains pill core;
(3) with 95% dissolve with ethanol solution 10.5g ethyl cellulose of 10 times of weight and 1.8g diethyl phthalate, 4.5g Pulvis Talci, 1.6g PVP K30, make sustained release coating liquid;
(4) the sustained release coating liquid (3) for preparing is evenly sprayed on the pastille micropill surface for preparing, then the slow-release micro-pill of gained is placed 80 ℃ vacuum drying oven inner drying 2 hours, get slow-release micro-pill;
(5) content and the release of detection slow-release micro-pill, qualified rear calculating loading amount is packed in the corresponding capsule shells, gets diclofenac sodium extended release capsule.
Embodiment 5 diclofenac sodium extended release capsules prescription forms and preparation method thereof
Preparation process is:
(1) the 0.9g PVP K30 is joined in 95% ethanol of 4 times of weight stirring and dissolving; The diclofenac sodium of recipe quantity is added in the mentioned solution stirring and dissolving;
(2) the 150g celphere is joined in the comminutor, open temp and compressed air slowly are sprayed onto medicinal liquid (1) on the celphere, and preparation contains pill core;
(3) with 95% dissolve with ethanol solution 10.5g ethyl cellulose of 10 times of weight and 1.8g diethyl phthalate, 4.5g Pulvis Talci, 1.8g PVP K30, make sustained release coating liquid;
(4) the sustained release coating liquid (3) for preparing is evenly sprayed on the pastille micropill surface for preparing, then the slow-release micro-pill of gained is placed 70 ℃ vacuum drying oven inner drying 2 hours, get slow-release micro-pill;
(5) content and the release of detection slow-release micro-pill, qualified rear calculating loading amount is packed in the corresponding capsule shells, gets diclofenac sodium extended release capsule.
Embodiment 6 determination of related substances
Get embodiment 1,2,3,5 and prepare with diclofenac sodium extended release capsule and comparative sample (approximately being equivalent to diclofenac sodium 0.1g), carry out as follows the mensuration of related substance:
Adopt high performance liquid chromatography, chromatographic condition: take octadecylsilane chemically bonded silica as filler, take methanol-4% glacial acetic acid solution by 65:35 as mobile phase, flow velocity 1.0ml/min detects wavelength 254nm; Theoretical cam curve should be not less than 5000 in the diclofenac sodium peak; Get diclofenac sodium extended release capsule an amount of (approximately being equivalent to diclofenac sodium 0.1g), accurately weighed, put in the 100ml measuring bottle, add methanol an amount of, supersound process 10min makes dissolving, lets cool, and is diluted to scale with methanol, shake up, centrifugal, get supernatant as need testing solution; Other gets dimethyphthalate 5mg, puts in the 200ml measuring bottle, adds methanol and makes dissolving, and the accurate need testing solution 1ml that adds is diluted to scale with methanol, shakes up, in contrast solution.Get the diclofenac sodium reference substance an amount of, water is made the solution that approximately contains 1mg among every 1ml, get an amount of, put in the quartzy absorption cell, at the lower irradiation of ultra-violet lamp (254nm) 15min, get 20l, the injection liquid chromatography, the record chromatogram approximately impurity one peak occurring in the 0.8min place with diclofenac sodium peak relative retention time, and the separating degree between impurity peaks and the diclofenac sodium should be not less than 6.0; Get contrast solution 20l, the injection liquid chromatography is regulated detection sensitivity, makes the diclofenac sodium peak height be about 20% of full scale; Precision measures need testing solution again, each 20l of contrast solution, difference injection liquid chromatography, the record chromatogram is to 2 times of the main peak retention time, in the chromatogram of need testing solution if any impurity peaks, except the chromatographic peak before the diethyl phthalate peak meter, peak (impurity III) if any relative retention time 1.2～1.3, must not be greater than contrast solution main peak area (0.5%) after its peak area multiply by 0.5, other single impurity peak area must not be greater than contrast solution main peak area (0.5%), each impurity peak area and (the impurity III is by the peak area after proofreading and correct) must not be greater than 2 times (1.0%) of contrast solution main peak area.
The results are shown in Table 1.
Embodiment 7 assays
Get embodiment 1,2,3,5 and prepare with diclofenac sodium extended release capsule and comparative sample, the mensuration of content is arranged as follows:
The chromatographic condition octadecylsilane chemically bonded silica is filler, take methanol-4% glacial acetic acid solution (70:30) as mobile phase, detects wavelength 276nm.Get the diclofenac sodium reference substance an amount of, water is made the solution that approximately contains 1mg among every 1ml, get an amount of, put in the quartzy absorption cell, at the lower irradiation of uviol lamp (254nm) 15min, get 20l, the injection liquid chromatography, the record chromatogram approximately impurity one peak occurring in 0.8 place with diclofenac sodium peak relative retention time, and the separating degree between impurity peaks and the diclofenac sodium should be not less than 4.0.Measure according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia version in 2010), this product contains diclofenac sodium and should be 90.0%～110.0% of labelled amount.
The results are shown in Table 1.
Embodiment 8 drug release determinations
Get embodiment 1,2,3,5 and prepare with diclofenac sodium extended release capsule and comparative sample, carry out as follows drug release determination:
Get this product, according to drug release determination method (two appendix XD of Chinese Pharmacopoeia version in 2010 first method), adopt dissolution method (two appendix XC of Chinese Pharmacopoeia version in 2010) first method device, take phosphate buffer (pH6.8) 900ml as release medium, rotating speed is that per minute 100 turns, and solution 5ml was got respectively in operation at 2 hours, 6 hours, 12 hours in accordance with the law, filter, and immediately in process container, replenish synthermal release medium 5ml; It is an amount of that precision measures subsequent filtrate respectively, and each quantitatively dilutes with above-mentioned release medium and makes the solution that approximately contains 15g among every 1ml, as need testing solution; Get the diclofenac sodium reference substance an amount of, accurately weighed, add release medium dissolving and dilution and make the solution product solution in contrast that contains 15g among every 1ml.Get above-mentioned two solution, measure according to ultraviolet-spectrophotography (two appendix IVA of Chinese Pharmacopoeia version in 2010), measure respectively trap at the wavelength place of 276nm, calculate every in the burst size of different time.Every burst size at 2 hours, 6 hours, 12 hours of this product should be respectively labelled amount 25%～50%, 45%～80%, more than 75%, all should be up to specification.
The results are shown in Table 1.
With embodiment 1 and 0 day 2,4,6,8,10,12 hours release data instance of comparative sample, do cumulative release amount-time graph, the results are shown in accompanying drawing 1.
The mensuration of embodiment 9 stability
Get embodiment 1,2,3,5 and prepare with diclofenac sodium extended release capsule and comparative sample carried out under 40 ℃ of high temperature, relative humidity 75% ± 5% condition accelerated test 6 months and 25 ℃ of temperature, relative humidity 60% ± 10% condition under 18 months investigation of long term test, detect the variation of every quality index, the data obtained is shown in table 2 and table 3:
0 day quality testing result of table 1
Accelerated test is 6 months under 40 ℃ of table 2 high temperature, relative humidity 75% ± 5% condition
Long term test is 18 months under 25 ℃ of table 3 temperature, relative humidity 60% ± 10% condition
Can be found out by above data result, the diclofenac sodium extended release capsule that the present invention makes is compared with the capsule that documents CN101322695A prepares, and has better release and stability.
Claims (7)
1. study of diclofenac sodium sustained release micropellets, its by as the celphere of parent nucleus, be wrapped in the outer principal agent layer that contains diclofenac sodium of ball core and be wrapped in the outer sustained release coating layer of principal agent layer and form, it is characterized in that:
I. count by weight percentage, celphere 63%～70% is preferably 65～69%, and principal agent layer 20%～35% is preferably 20%～25%, and surplus is the sustained release coating layer;
The described principal agent layer of ii is made by diclofenac sodium and binding agent, and counts by weight percentage, and contains diclofenac sodium 89%～99% in the principal agent layer, is preferably 95%～99%, surplus is binding agent;
Iii. described sustained release coating layer is made by slow releasing agent, antiplastering aid, porogen, plasticizer, count by weight percentage, contain in the sustained release coating layer that slow releasing agent 50%～60% is preferably 55%～58%, antiplastering aid 18%～30% is preferably 23%～25%, porogen 5～15%, surplus are plasticizer.
2. study of diclofenac sodium sustained release micropellets according to claim 1, wherein said binding agent or porogen are selected from a kind of in polyvidone, the hypromellose or their various combinations, and preferred adhesive is identical with the porogen composition; Described slow releasing agent is selected from a kind of in ethyl cellulose, the cellulose acetate or their various combinations; Described antiplastering aid is selected from a kind of in Pulvis Talci, magnesium stearate, the micropowder silica gel or their various combinations; Described plasticizer is selected from a kind of in triethyl citrate, dimethyl phthalate, the triacetin or their various combinations.
3. each described study of diclofenac sodium sustained release micropellets according to claim 1-2, wherein said celphere is comprised of sucrose, starch or microcrystalline Cellulose, and the size of described celphere is 0.35～1.12mm, is preferably 0.6～0.9mm.
4. a diclofenac sodium extended release capsule is characterized in that loading the capsule that forms by each described study of diclofenac sodium sustained release micropellets of claim 1-3, contains diclofenac sodium 30～100mg in every capsules, is preferably 50mg.
5. a method for preparing each described study of diclofenac sodium sustained release micropellets of claim 1-3 is characterized in that comprising the steps:
(1) celphere is joined in the comminutor, behind the dissolve with ethanol of binding agent with 60%～95% percentage by weight, add principal agent, stirring and dissolving is made coating solution, and celphere is joined in the comminutor, the coating solution that sprinkling prepares gets the pastille micropill in the celphere surface after the drying;
(2) slow releasing agent of sustained release coating layer, porogen, plasticizer and antiplastering aid are made sustained release coating liquid with the dissolve with ethanol solution of 80%～95% percentage by weight;
(3) the sustained release coating liquid for preparing is evenly sprayed on the pastille micropill surface for preparing, get study of diclofenac sodium sustained release micropellets after the drying.
6. method according to claim 5 is characterized in that adopting in step (1) and (3) centrifugal coating granulator, fluidized bed coating granulator or the preparation of efficient film coating pan.
7. the determination of related substances method of diclofenac sodium extended release capsule claimed in claim 4, it is characterized in that adopting high performance liquid chromatography, chromatographic condition: take octadecylsilane chemically bonded silica as filler, take methanol-4% glacial acetic acid solution by 65:35 as mobile phase, flow velocity 1.0ml/min detects wavelength 254nm; Theoretical cam curve should be not less than 5000 in the diclofenac sodium peak; Get diclofenac sodium extended release capsule an amount of (approximately being equivalent to diclofenac sodium 0.1g), accurately weighed, put in the 100ml measuring bottle, add methanol an amount of, supersound process 10min makes dissolving, lets cool, and is diluted to scale with methanol, shake up, centrifugal, get supernatant as need testing solution; Other gets dimethyl phthalate 5mg, puts in the 200ml measuring bottle, adds methanol and makes dissolving, and the accurate need testing solution 1ml that adds is diluted to scale with methanol, shakes up, in contrast solution.Get the diclofenac sodium reference substance an amount of, water is made the solution that approximately contains 1mg among every 1ml, get an amount of, put in the quartzy absorption cell, at the lower irradiation of ultra-violet lamp (254nm) 15min, get 20 μ l, the injection liquid chromatography, the record chromatogram approximately impurity one peak occurring in 0.8 place with diclofenac sodium peak relative retention time, and the separating degree between impurity peaks and the diclofenac sodium should be not less than 6.0; Get contrast solution 20 μ l, the injection liquid chromatography is regulated detection sensitivity, makes the diclofenac sodium peak height be about 20% of full scale; Precision measures need testing solution again, each 20 μ l of contrast solution, difference injection liquid chromatography, the record chromatogram is to 2 times of the main peak retention time, in the chromatogram of need testing solution if any impurity peaks, except the chromatographic peak before the diethyl phthalate peak meter, peak (impurity III) if any relative retention time 1.2～1.3, must not be greater than contrast solution main peak area (0.5%) after its peak area multiply by 0.5, other single impurity peak area must not be greater than contrast solution main peak area (0.5%), each impurity peak area and (the impurity III is by the peak area after proofreading and correct) must not be greater than 2 times (1.0%) of contrast solution main peak area.
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| CN103156855A (en) * | 2013-03-21 | 2013-06-19 | 青岛正大海尔制药有限公司 | Paracetamol and caffeine slow-release capsule and preparation method thereof |
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| CN106680391B (en) * | 2016-12-23 | 2019-11-19 | 中国农业科学院兰州畜牧与兽药研究所 | The detection method of C14H10Cl2NNaO2 residual quantity in a kind of milk |
| CN106680391A (en) * | 2016-12-23 | 2017-05-17 | 中国农业科学院兰州畜牧与兽药研究所 | Detection method of diclofenac sodium residues in milk |
| CN108732261A (en) * | 2018-03-02 | 2018-11-02 | 中国农业科学院兰州畜牧与兽药研究所 | The detection method of C14H10Cl2NNaO2 is remained in ox edible tissue |
| CN108888599A (en) * | 2018-07-26 | 2018-11-27 | 国药集团致君（深圳）制药有限公司 | C14H10Cl2NNaO2 slow releasing composition and preparation method thereof |
| CN109330993A (en) * | 2018-11-26 | 2019-02-15 | 正大制药（青岛）有限公司 | A kind of cyclobenzaprine hydrochloride spansule and preparation method thereof |
| CN109602712A (en) * | 2019-01-23 | 2019-04-12 | 上海衡山药业有限公司 | A kind of slow-release material and preparation method thereof containing C14H10Cl2NNaO2 |
| CN110687229A (en) * | 2019-11-12 | 2020-01-14 | 山东省药学科学院 | Diclofenac sodium raw material and analysis method of related substances in preparation thereof |
| CN115317464A (en) * | 2022-09-01 | 2022-11-11 | 苏州弘森药业股份有限公司 | Diclofenac potassium microcapsule and preparation method thereof |
| CN115317464B (en) * | 2022-09-01 | 2023-08-08 | 苏州弘森药业股份有限公司 | Potassium diclofenac microcapsule and preparation method thereof |
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