CN103340855B - Compound amoxicillin and clavulanate potassium tablet and preparation method thereof - Google Patents
Compound amoxicillin and clavulanate potassium tablet and preparation method thereof Download PDFInfo
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- CN103340855B CN103340855B CN201310297361.2A CN201310297361A CN103340855B CN 103340855 B CN103340855 B CN 103340855B CN 201310297361 A CN201310297361 A CN 201310297361A CN 103340855 B CN103340855 B CN 103340855B
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Abstract
The invention relates to a compound amoxicillin and clavulanate potassium tablet and a preparation method thereof. The tablet consists of the following components in percentage by weight: 15 to 30 percent of amoxicillin, 5 to 15 percent of a clavulanate potassium mixture, 30 to 65 percent of a filler, 1.5 to 8 percent of crosslinked povidone, 0.6 to 3 percent of povidone K30, 1 to 3 percent of silica and 1 to 5 percent of glyceryl behenate. The preparation method comprises the following steps: adding the amoxicillin, the filler and the crosslinked povidone into a pelletizer, mixing and adding an adhesive in a mixing process; and adding the prepared amoxicillin granules and clavulanate potassium mixture, the silica and the glyceryl behenate into a mixing machine, mixing, discharging and tabletting. Although the compound amoxicillin and clavulanate potassium tablet adopts a half-wet method to pelletize, the clavulanate potassium is unlikely to degrade, so that the stability of a medicine is guaranteed effectively.
Description
Technical field
The present invention relates to the preparation technology of a kind of medicine and this medicine, especially a kind of tablet, belongs to technical field of medicine.
Background technology
The compound preparation that amoxicillin and clavulanate potassium tablets is made up of amoxicillin and clavulanate potassium, amoxicillin is wherein spectrum Penicillin antibiotics, clavulanate potassium itself only has faint antibacterial activity, but has the beta-lactam enzyme hydrolysis of powerful spectrum.In-vitro antibacterial research shows, clavulanic acid can improve inha enzyme is produced in amoxicillin antibacterial activity 4 ~ 32 times to minority intestinals such as Klebsiella proteus vulgaris, improve the antibacterial activity 32 times to Haemophilus influenzae, improve amoxicillin to the antibacterial activity 4 ~ 32 times of that Moraxella of card.Clinical practice also shows, amoxicillin and clavulanate potassium compound preparation expands the antibiotic property of amoxicillin, strengthen its antibacterial strength, there is the advantages such as good effect, incidence of side effects are lower, now become clinical treatment produce enzyme fastbacteria and responsive microbial in, the preferred antibiotics of severe infection.
Amoxicillin and clavulanate potassium compound preparation the most conventional clinically is at present oral tablet.On market, amoxicillin and clavulanate potassium oral tablet is first mixed with clavulanate potassium amoxicillin mostly, and then the technique mixed with other adjuvants.The preparation method of tablet is divided into wet granule compression tablet method and compressing dry granulation by preparation technology, wet granule compression tablet method be by the powder mix homogeneously of medicine and adjuvant after add the method that liquid adhesive prepares granule, because clavulanate potassium easily decomposes, so traditional wet granule compression tablet method is not suitable for the preparation of amoxicillin clavulanate potassium tablets.
Chinese patent literature CN200810212280.7 discloses a kind of amoxicillin/clavulanate potassium 8: 1 and preparation method thereof.This amoxicillin/clavulanate potassium 8: 1 tablet, be principal agent source with blended stock in the middle of quality controllability, amoxicillin/clavulanate potassium (8: 1) that mixing homogeneity is good, this preparation method technique is comparatively simple.
Chinese patent literature CN200910074500.9 discloses a kind of preparation method of amoxicillin and clavulanate potassium tablets, 120 ~ 135 parts, amoxicillin, clavulanate potassium 40 ~ 45 parts, microcrystalline Cellulose 27 ~ 32 parts, cross-linking sodium carboxymethyl cellulose 1 ~ 3 part, micropowder silica gel 1 ~ 3 part, magnesium stearate 2 ~ 4 parts; After being granulated in amoxicillin, according to the mass ratio of 4: 1, mix with clavulanate potassium, form major ingredient; Adjuvant micropowder silica gel, cross-linking sodium carboxymethyl cellulose (ADS) and microcrystalline Cellulose are mixed according to equivalent method of progressively increasing, then progressively increases to drop in mixer with major ingredient equivalent and mix 36 ~ 70 minutes; Mixed powder is carried out tabletting.After amoxicillin granules mixes with clavulanate potassium by this preparation method, then add all adjuvants by the equivalent method of progressively increasing and mix, incorporation time is longer, and reinforced requirement is comparatively strict, the stability of wayward technique.
Above two kinds is all typical compressing dry granulation, be widely used in the preparation of amoxicillin clavulanate potassium tablets, but the tablet produced of compressing dry granulation can cause crystal conversion due to high pressure and active to reduce, the stability of tablet is had an impact, in addition, also especially easily produce the phenomenons such as top is split, sticking, tablet appearance product are mutually undesirable.
Summary of the invention
The technical problem to be solved in the present invention is, a kind of employing wet granulation is proposed, clavulanate potassium still can be made not easily to degrade, effectively ensure the amoxicillin clavulanate potassium tablets of the stability of medicine, and a kind of technique is simple, easy and simple to handle, controllability is good, can ensure the preparation method of the amoxicillin clavulanate potassium tablets of tablet surface smooth and beautiful appearance.
The present invention is the technical scheme solving one of them technical problem above-mentioned proposition: a kind of amoxicillin clavulanate potassium tablets, composed of the following components according to mass percent: amoxicillin 15% ~ 30%, clavulanate potassium mixture 5% ~ 15%, filler 30% ~ 65%, polyvinylpolypyrrolidone 1.5% ~ 8%, PVP K30 0.6% ~ 3%, silica 1 % ~ 3%, Glyceryl Behenate 1% ~ 5%; The mass ratio of described amoxicillin and clavulanate potassium is 1: 1 to 10: 1.Clavulanate potassium mixture is the mixture mixed according to mass ratio 1: 1 by clavulanate potassium and microcrystalline Cellulose.
In order to make the Color uniformity of tablet good, have color and luster, surface is speckless, and a kind of preferred technical scheme is: also comprising toner in said components, the mass percentage content of described coloring agent is 0.05% ~ 1%.
During in order to make this tablet as animal chew sheet, having taste preferably, facilitating animal to take, a kind of preferred technical scheme is: the mass percentage content of above-mentioned essence is 1% ~ 5%.
In order to make the compressing stability of this tablet higher, a kind of preferred technical scheme is: above-mentioned filler is one or both in microcrystalline Cellulose and calcium hydrogen phosphate, and the mass ratio of described amoxicillin and clavulanate potassium is 4: 1.
The present invention is the technical scheme solving another technical problem above-mentioned proposition: a kind of preparation method of amoxicillin clavulanate potassium tablets, comprises the following steps:
A. prepare burden: take raw material, described tablet is composed of the following components according to mass percent: amoxicillin 15% ~ 30%, clavulanate potassium mixture 5% ~ 15%, filler 30% ~ 65%, polyvinylpolypyrrolidone 1.5% ~ 8%, PVP K30 0.6% ~ 3%, silica 1 % ~ 3%, Glyceryl Behenate 1% ~ 5%; The mass ratio of described amoxicillin and clavulanate potassium is 1: 1 to 10: 1; Described PVP K30 all adds abundant dissolving in dehydrated alcohol and is configured to binding agent, and the gross mass of described binding agent accounts for 25% ~ 30% of raw material gross mass;
B. granulate in amoxicillin: amoxicillin, filler, polyvinylpolypyrrolidone added in granulator and mix 3 to 8 minutes, add the binding agent configured, carry out drying, granulate, make amoxicillin granules after completing granulation in mixed process;
C. always mix: the amoxicillin granules prepared and clavulanate potassium mixture, silicon dioxide and Glyceryl Behenate are added in mixer, mix discharging after 8 to 12 minutes;
D. tabletting.
In order to make the Color uniformity of tablet good, there is color and luster, surface is speckless, a kind of preferred technical scheme is: also comprising toner in the component of above-mentioned tablet, the mass percentage content of described coloring agent is 0.05% ~ 1%, coloring agent, when configuring binding agent, all adds in binding agent, and fully dissolves.
During in order to make this tablet as animal chew sheet, there is taste preferably, animal is facilitated to take, a kind of preferred technical scheme is: also comprise essence in the component of above-mentioned tablet, the mass percentage content of described essence is 1% ~ 5%, and described essence together adds mixer when total mixing with amoxicillin granules, clavulanate potassium mixture, silicon dioxide and Glyceryl Behenate and mixes.
In order to make the compressing stability of this tablet higher, a kind of preferred technical scheme is: above-mentioned filler is one or both in microcrystalline Cellulose and calcium hydrogen phosphate, and the mass ratio of described amoxicillin and clavulanate potassium is 4: 1.
In order to ensure the quality of tablet, a kind of preferred technical scheme is: when drying is carried out in amoxicillin granulation, be dried to moisture and be less than 3.0%.
Being preferably further of technical scheme: above-mentioned coloring agent is a red ferric oxide, and described essence is beef flavor, chicken meat flavor or essence with pork taste, preferably beef taste essence.
The good effect that the present invention has:
(1) add lubricant in amoxicillin clavulanate potassium tablets of the present invention, lubricant refers to and can reduce granule or the adjuvant of frictional force between tablet and die wall.Tablet of the present invention is as adopted magnesium stearate as lubricant, because magnesium stearate has stronger hydrophobicity, contact angle is 121 °, as improper use, the hydrophobicity of tablet can be made to strengthen, affect water-wet tablet, slow down the disintegrate of tablet and the dissolution of medicine, also can increase the hardness of tablet, so there is certain limitation when magnesium stearate is used for amoxicillin clavulanate potassium tablets.Tablet of the present invention adopts Glyceryl Behenate as lubricant, when relative incorporation time is shorter, Glyceryl Behenate has adhesion characteristic, still effectively can reduce tablet and release required power by nib, improve the compressibility in tablet and capsule manufacture, and on disintegration time and drug release without impact.Glyceryl Behenate can prevent frictional force large and make tabletting difficulty; When making tabletting, pressure distribution is even, and makes the even density of tablet; Tablet is reduced by releasing required power in nib; The outward appearance of tablet can also be improved in addition, make tablet surface bright, smooth.
(2) granulate and adopt wet granulation technology in the amoxicillin in amoxicillin clavulanate potassium tablets of the present invention, binding agent adds configuration in dehydrated alcohol by PVP K30 and forms, dehydrated alcohol volatilizees in preparation process, therefore the preparation technology of this tablet is more succinct, and Forming Quality is better.
(3) formula of amoxicillin clavulanate potassium tablets of the present invention is by selecting appropriate polyvinylpolypyrrolidone as disintegrating agent, appropriate PVP K30 as binding agent, appropriate silicon dioxide is as fluidizer, appropriate Glyceryl Behenate is as lubricant, reduce clavulanate potassium to degrade when wet granulation, tablet yield rate is high, tablet quality is stablized, and stability of drug products is high.
(4) disintegrating agent, filler and amoxicillin powder are first made amoxicillin granules by wet granulation by the preparation method of amoxicillin clavulanate potassium tablets of the present invention, again amoxicillin granules, clavulanate potassium mixture, fluidizer and mix lubricant are carried out tabletting, technique is simple, easy and simple to handle, raw material incorporation time is shorter, the more important thing is the degraded that effectively can control clavulanate potassium simultaneously, ensure the stability of medicine, the outward appearance of tablet, moisture, tablet weight variation and stability thereof are also more excellent compared with dry method direct compression.
Detailed description of the invention
(embodiment 1)
During the amoxicillin clavulanate potassium tablets tabletting of the present embodiment, the quality control of every sheet is at 180 ± 13.5mg, and every sheet tablet forms according to following component and consumption configuration:
Clavulanate potassium mixture is the mixture mixed according to mass ratio 1: 1 by clavulanate potassium and microcrystalline Cellulose.Polyvinylpolypyrrolidone, red ferric oxide and dehydrated alcohol are configured to binding agent and add in tablet manufacture, and dehydrated alcohol volatilizees in tablet manufacture, become kind without residue at tablet.
The preparation method of the amoxicillin clavulanate potassium tablets of the present embodiment, comprises following concrete steps:
A. prepare burden: take appropriate amoxicillin powder, clavulanate potassium mixture, microcrystalline Cellulose, calcium hydrogen phosphate, polyvinylpolypyrrolidone, silicon dioxide, Glyceryl Behenate and beef flavor according to formula consumption, and sieve respectively.The binding agent of configuration 50mg, binding agent is solvent with dehydrated alcohol, adds the PVP K-30 that accounts for binding agent gross mass 5% and account for binding agent gross mass 0.2% red ferric oxide to stir, for subsequent use after PVP K-30 and red ferric oxide fully dissolve.
B. granulate in amoxicillin: the amoxicillin powder configured, microcrystalline Cellulose, calcium hydrogen phosphate, polyvinylpolypyrrolidone added in granulator and mix 5 minutes; the binding agent configured is added lentamente in mixed process; drying is carried out after completing granulation; until moisture is less than 3.0%; finally carry out granulate, make amoxicillin granules.
C. always mix: the amoxicillin granules prepared and clavulanate potassium mixture, silicon dioxide, Glyceryl Behenate and the beef flavor configured are added in three-dimensional motion mixer, mixes discharging after 10 minutes.
D. tabletting: according to the cubage sheet weight of principal agent composition in granule, raw material is pressed into the tablet of 180 ± 13.5mg.
E. pack: adopt two aluminium foil to pack.
Between the mixing in strict production control process, granulate between, between tabletting, the humidity and temperature of make-up room.
(embodiment 2)
The remainder of the amoxicillin clavulanate potassium tablets of the present embodiment is identical with embodiment 1, and difference is:
During tabletting, the quality control of every sheet is at 900 ± 45mg, and every sheet tablet forms according to following component and consumption configuration:
The remainder of the preparation method of the amoxicillin clavulanate potassium tablets of the present embodiment is identical with embodiment 1, and difference is: be the amoxicillin powder configured, microcrystalline Cellulose, calcium hydrogen phosphate, polyvinylpolypyrrolidone added in granulator to mix 8 minutes in step B.Be that the amoxicillin granules prepared and clavulanate potassium mixture, silicon dioxide, Glyceryl Behenate and the beef flavor configured are added in three-dimensional motion mixer in step C, mix discharging after 12 minutes.In step D, raw material is pressed into the tablet of 900 ± 45mg.
(embodiment 3)
The remainder of the amoxicillin clavulanate potassium tablets of the present embodiment is identical with embodiment 1, and difference is:
During tabletting, the quality control of every sheet is at 1800 ± 36mg, and every sheet tablet forms according to following component and consumption configuration:
The remainder of the preparation method of the amoxicillin clavulanate potassium tablets of the present embodiment is identical with embodiment 1, and difference is: be the amoxicillin powder configured, microcrystalline Cellulose, calcium hydrogen phosphate, polyvinylpolypyrrolidone added in granulator to mix 3 minutes in step B.Be that the amoxicillin granules prepared and clavulanate potassium mixture, silicon dioxide, Glyceryl Behenate and the beef flavor configured are added in three-dimensional motion mixer in step C, mix discharging after 8 minutes.In step D, raw material is pressed into the tablet of 1800 ± 36mg.
(embodiment 4)
The remainder of the amoxicillin clavulanate potassium tablets of the present embodiment is identical with embodiment 1, and difference is:
Every sheet tablet forms according to following component and consumption configuration:
Embodiment 5
The remainder of the amoxicillin clavulanate potassium tablets of the present embodiment is identical with embodiment 1, and difference is:
Every sheet tablet forms according to following component and consumption configuration:
(comparative example 1)
During the amoxicillin clavulanate potassium tablets tabletting of this comparative example, the quality control of every sheet is at 180 ± 13.5mg, and every sheet tablet forms according to following component and consumption configuration:
Clavulanate potassium mixture is the mixture mixed according to mass ratio 1: 1 by clavulanate potassium and microcrystalline Cellulose.
The preparation method of the amoxicillin clavulanate potassium tablets of this comparative example, comprises following concrete steps:
A. take appropriate amoxicillin powder, clavulanate potassium mixture, microcrystalline Cellulose, polyvinylpolypyrrolidone, silicon dioxide, Glyceryl Behenate and beef flavor according to formula consumption, and sieve respectively.
B. the amoxicillin powder configured and clavulanate potassium mixture are mixed into major ingredient, microcrystalline Cellulose, calcium hydrogen phosphate, polyvinylpolypyrrolidone to be progressively increased method mixing according to equivalent, then progressively increase to drop in granulator with major ingredient equivalent and mix more than 30 minutes.
C. discharging, tabletting, packaging.
(comparative example 2)
During the amoxicillin clavulanate potassium tablets tabletting of this comparative example, the quality control of every sheet is at 180 ± 13.5mg, and every sheet tablet forms according to following component and consumption configuration:
The preparation method of the amoxicillin clavulanate potassium tablets of this comparative example, comprises following concrete steps:
A. take appropriate amoxicillin powder, clavulanate potassium mixture, microcrystalline Cellulose, calcium hydrogen phosphate, polyvinylpolypyrrolidone, silicon dioxide, Glyceryl Behenate and beef flavor according to formula consumption, and sieve respectively.The binding agent of configuration 50ml, binding agent is solvent with dehydrated alcohol, adds the PVP K-30 that accounts for binding agent gross mass 5% and account for binding agent gross mass 0.2% red ferric oxide to stir, for subsequent use after PVP K-30 and red ferric oxide fully dissolve.
B. the amoxicillin powder configured, clavulanate potassium mixture, microcrystalline Cellulose, calcium hydrogen phosphate, polyvinylpolypyrrolidone are added in granulator and mix 5 minutes; the binding agent configured is added lentamente in mixed process; drying is carried out after completing granulation; until moisture is less than 3.0%, finally carry out granulate.
C. always mix, the granule prepared and silicon dioxide, Glyceryl Behenate and the beef flavor configured are added in three-dimensional motion mixer, mixes discharging after 10 minutes.
D. tabletting, packaging.
(comparative example 3)
This comparative example the remainder of amoxicillin clavulanate potassium tablets identical with embodiment 1, difference is: the lubricant in formula adopts magnesium stearate to instead of Glyceryl Behenate.
During tabletting, the quality control of every sheet is at 180 ± 13.5mg, and every sheet tablet forms according to following component and consumption configuration:
The preparation method of the amoxicillin clavulanate potassium tablets of the present embodiment is identical with embodiment 1.
According to " the project of " crude drug and pharmaceutical preparation stability important investigation Item Reference table " listed corresponding dosage form in Chinese Pharmacopoeia 2005 (two editions) annex XIXC, the sample of each embodiment and comparative example is placed on 40 DEG C, the accelerated test of 3 months is carried out under the environment of relative humidity 65%, detect the outward appearance of sample, tablet weight variation, content, related substance and dissolution, and compared with the data of 0 day.Each embodiment and comparative example the results are shown in Table 1.
The result of the test of the sample of each embodiment of table 1 and comparative example
Comparative example 3 and each embodiment are carried out contrast known, in owing to have employed magnesium stearate as lubricant, cause in the sheet hardness of this formula large, the dissolution of medicine is slow, and have employed Glyceryl Behenate as lubricant, add the effect that appropriate Glyceryl Behenate has binding agent concurrently, effectively can improve the compressibility of tablet, on disintegration time and drug release without impact.
Comparative example 2 and each embodiment are carried out contrast known, the impurity in the tablet of comparative example 2 is obviously many than the impurity of each embodiment, and after the accelerated test of 3 months, the impurity in the tablet of comparative example 2 is more obvious.In addition, the clavulanic acid dissolution of comparative example 2 is starkly lower than the clavulanic acid dissolution of each embodiment, after the accelerated test of 3 months, the content of clavulanic acid significantly reduces, and degraded is very serious, it can thus be appreciated that, wet granulation directly results in clavulanic acid and easily degrades, and stability of drug products declines.
Comparative example 1 and each embodiment are carried out contrast known, adopt dry method direct compression, easily produce sliver, and tablet weight variation is large, the content heterogeneity of clavulanic acid and amoxicillin in sample.And the result of the sample appearance of embodiment 1 to 5, moisture, tablet weight variation and stability thereof is obviously better than comparative example 1, show the superiority of composition and engineering.
Amoxicillin clavulanate potassium tablets of the present invention and preparation method thereof is not limited to the various embodiments described above, and above-described embodiment is only for example of the present invention is clearly described, and is not the restriction to embodiments of the present invention.For those of ordinary skill in the field, can also make other changes in different forms on the basis of the above description.Here exhaustive without the need to also giving all embodiments.And these belong to spirit institute's apparent change of extending out of the present invention or change and are still among protection scope of the present invention.
Claims (4)
1. a preparation method for amoxicillin clavulanate potassium tablets, is characterized in that, comprises the following steps:
A. prepare burden: take raw material, described tablet is composed of the following components according to mass percent: amoxicillin 15% ~ 30%, clavulanate potassium mixture 5% ~ 15%, filler 30% ~ 65%, polyvinylpolypyrrolidone 1.5% ~ 8%, PVP K30 0.6% ~ 3%, silica 1 % ~ 3%, Glyceryl Behenate 1% ~ 5%, coloring agent 0.05% ~ 1%; Described clavulanate potassium mixture is the mixture mixed according to mass ratio 1: 1 by clavulanate potassium and microcrystalline Cellulose; The mass ratio of described amoxicillin and clavulanate potassium is 1: 1 to 10: 1; Described PVP K30 and coloring agent all add abundant dissolving in dehydrated alcohol and are configured to binding agent, and the gross mass of described binding agent accounts for 25% ~ 30% of raw material gross mass;
B. granulate in amoxicillin: amoxicillin, filler, polyvinylpolypyrrolidone added in granulator and mix 3 to 8 minutes, add the binding agent configured, carry out drying, granulate, make amoxicillin granules after completing granulation in mixed process;
C. always mix: the amoxicillin granules prepared and clavulanate potassium mixture, silicon dioxide and Glyceryl Behenate are added in mixer, mix discharging after 8 to 12 minutes;
D. tabletting.
2. the preparation method of amoxicillin clavulanate potassium tablets according to claim 1, is characterized in that: described filler is one or both in microcrystalline Cellulose and calcium hydrogen phosphate, and the mass ratio of described amoxicillin and clavulanate potassium is 4: 1.
3. the preparation method of amoxicillin clavulanate potassium tablets according to claim 1 and 2, is characterized in that: when drying is carried out in amoxicillin granulation, be dried to moisture and be less than 3.0%.
4. the preparation method of amoxicillin clavulanate potassium tablets according to claim 1 and 2, is characterized in that: described coloring agent is red ferric oxide.
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| CN201410822886.8A CN104546838B (en) | 2013-07-16 | 2013-07-16 | Tablet and preparation method thereof |
| CN201410822889.1A CN104473922B (en) | 2013-07-16 | 2013-07-16 | Composite tablet and preparation method thereof |
| CN201310297361.2A CN103340855B (en) | 2013-07-16 | 2013-07-16 | Compound amoxicillin and clavulanate potassium tablet and preparation method thereof |
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| CN108904455B (en) * | 2018-07-20 | 2021-04-02 | 汤臣倍健股份有限公司 | A method for preparing tablet containing high-dose oil ester component |
| CN112006994B (en) * | 2020-08-10 | 2022-10-25 | 瑞普（天津）生物药业有限公司 | Amoxicillin and clavulanate potassium preparation and preparation method thereof |
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| CN1681497A (en) * | 2002-07-16 | 2005-10-12 | 兰贝克赛实验室有限公司 | Dispersible tablets for oral administration |
| WO2006066930A1 (en) * | 2004-12-24 | 2006-06-29 | Lek Pharmaceuticals D.D. | Stable pharmaceutical composition comprising amoxicillin and clavulanic acid |
| CN101502511A (en) * | 2008-09-09 | 2009-08-12 | 山东淄博新达制药有限公司 | Amoxicillin/clavulanate potassium tablet and preparation method thereof |
| CN101897701A (en) * | 2009-05-27 | 2010-12-01 | 华北制药集团制剂有限公司 | Preparation method of amoxicillin and clavulanate potassium tablets |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1681497A (en) * | 2002-07-16 | 2005-10-12 | 兰贝克赛实验室有限公司 | Dispersible tablets for oral administration |
| WO2006066930A1 (en) * | 2004-12-24 | 2006-06-29 | Lek Pharmaceuticals D.D. | Stable pharmaceutical composition comprising amoxicillin and clavulanic acid |
| CN101502511A (en) * | 2008-09-09 | 2009-08-12 | 山东淄博新达制药有限公司 | Amoxicillin/clavulanate potassium tablet and preparation method thereof |
| CN101897701A (en) * | 2009-05-27 | 2010-12-01 | 华北制药集团制剂有限公司 | Preparation method of amoxicillin and clavulanate potassium tablets |
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