CN101897702B - Amoxicillin sulbactam pivoxil capsule and preparation method thereof - Google Patents
Amoxicillin sulbactam pivoxil capsule and preparation method thereof Download PDFInfo
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- CN101897702B CN101897702B CN200910074605A CN200910074605A CN101897702B CN 101897702 B CN101897702 B CN 101897702B CN 200910074605 A CN200910074605 A CN 200910074605A CN 200910074605 A CN200910074605 A CN 200910074605A CN 101897702 B CN101897702 B CN 101897702B
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Abstract
The invention discloses an amoxicillin sulbactam pivoxil capsule and a preparation method thereof. The preparation method comprises the following steps of: (a) weighing up the following raw materials by mass ratio: 3000 parts of amoxicillin, 3866 parts of sulbactam pivoxil, 32-36 parts of lauryl sodium sulfate, 130-14 parts of crosslinking sodium carboxymethylcellulose and 40-50 parts of magnesium stearate; (b) mixing the amoxicillin, the sulbactam pivoxil and one-second amount of the crosslinking sodium carboxymethylcellulose and uniformly stirring; (c) placing uniformly mixed materials in an extruder for extruding and crushing to obtain dry granules, and mixing the dry granules with the rest crosslinking sodium carboxymethylcellulose, the lauryl sodium sulfate and the magnesium stearate in a mixer to obtain mixed powder; and (d) testing the mixed powder and encapsulating the mixed powder if qualified. The invention adopts less auxiliary materials, has short technological process and simple preparation method, avoids affects of high-temperature and high-humidity to the quality of the products, and increases the stability of the product quality.
Description
Technical field
The present invention relates to field of pharmaceutical preparations.Be specifically related to amoxicillin sulbactam pivoxil capsule and preparation method thereof.
Technical background
The mix preparation that amoxicillin sulbactam pivoxil capsule is made up of amoxicillin and sulbactam (calculating by sulbactam) at 1: 1.Wherein the amoxicillin is a beta-lactam antibiotic; To Streptococcus such as streptococcus pneumoniae, Hemolytic streptococcuss, do not produce aerobic GPCs such as penicillinase staphylococcus, enterococcus faecalis, aerobic gram-negative bacterias such as escherichia coli, proteus mirabilis, Salmonella, hemophilus influenza, NEISSERIA GONORRHOEAE do not produce the beta lactamase bacterial strain and helicobacter pylori has good antibacterial activity.Bacteria cell wall is synthetic brings into play bactericidal action through suppressing in the amoxicillin, can make antibacterial become spheroid rapidly and dissolves, breaks.When antibacterial produces beta-lactamase, can make it lose antibacterial activity.Sulbactam is emulative irreversible beta-lactamase inhibitor, and is main through suppressing the activity of beta-lactamase, makes not that the PCs and the cephalosporins of anti-enzyme exempt from destruction, thereby is able to bring into play synergetic antibacterial effect.Therefore amoxicillin and (Pivaloyloxy)methyl penicillanate S,S-dioxide 5 usefulness have good synergism.
The amoxicillin and sulbactam pivoxyl preparation of using clinically at present is mainly the amoxicillin sulbactam pivoxil oral tablet.Its preparation method generally all is to adopt wet granulation; Method for preparing like CN1969845, the disclosed amoxicillin and sulbactam pivoxyl tablet of CN101317843; Being with the amoxicillin and sulbactam pivoxyl is active component, and repress is processed tablet behind the adjuvant system soft material that interpolation suits.Wet granulation helps improving flowability, dustability, the adhesion of material.Wet granulation carries out under hot and humid condition usually.Advantages such as granule that wet method is processed is through moistened surface, and it is good to have a granular mass, and good looking appearance, wearability are strong, compression forming property is good.But with regard to the amoxicillin and sulbactam pivoxyl preparation, because the amoxicillin is a Beta-lactam medicine, stability decreases under hot and humid condition, and can produce polymer, and then possibly cause a series of anaphylaxis; (Pivaloyloxy)methyl penicillanate S,S-dioxide is an enzyme inhibitor, has stronger hygroscopicity, and degraded easily reduces pharmaceutically active.Therefore in fact, the amoxicillin and sulbactam pivoxyl preparation is suitable adopts wet method to prepare.And dry granulation can be avoided hot and humid operation, therefore can effectively improve damp and hot more sensitive product quality stability.But when this method specifically was applied to the amoxicillin and sulbactam pivoxyl preparation, because amoxicillin and the former powder of sulbactam exist on physical characteristics such as granularity, density than big-difference, therefore big according to general dry granulation products made thereby fill volume, patient's compliance was poor.In addition, adopt its result of extraction of amoxicillin sulbactam pivoxil capsule of existing dry process not good enough.
Summary of the invention
The object of the invention is exactly that a kind of good stability, amoxicillin sulbactam pivoxil capsule that fill volume is little will be provided.Provide a kind of preparation this capsular method simultaneously.
The objective of the invention is to realize like this:
Amoxicillin sulbactam pivoxil capsule provided by the present invention is processed by the raw material of following mass ratio: 3000 parts of amoxicillin, 3866 parts of (Pivaloyloxy)methyl penicillanate S,S-dioxides, sodium lauryl sulphate 32-36 part, cross-linking sodium carboxymethyl cellulose 130-14 part, magnesium stearate 40-50 part.
Capsule of the present invention is an active component with amoxicillin, (Pivaloyloxy)methyl penicillanate S,S-dioxide, and selecting sodium lauryl sulphate, cross-linking sodium carboxymethyl cellulose, magnesium stearate is adjuvant.
The consumption proportion of the adjuvant that the present invention screened and this definite adjuvant has effectively improved the packing density of amoxicillin and the former powder of sulbactam, has reduced the material fill volume, and dry process is achieved.
The present invention has also effectively reduced supplementary product consumption, and its supplementary product consumption only accounts for the 2.86-3.19% of gross weight.So not only can reduce capsular fill amount, also can effectively avoid simultaneously because of the issuable untoward reaction of adjuvant.
Proportion design in view of drug component of the present invention makes the capsular soft gelatin capsule model of the present invention can select capsule for use No. 1.This model is a compact capsule, and its patient that is more convenient for accepts, and has improved patient's compliance thus greatly.
Adopt drug component proportioning of the present invention, every capsules fill amount is controlled at is 0.34-0.36g.
More preferred fill amount is 0.28-0.30g.
The method for preparing of amoxicillin sulbactam pivoxil capsule provided by the invention is that this method may further comprise the steps:
(a) take by weighing the raw material of following mass ratio:
3000 parts of amoxicillin, 3866 parts of (Pivaloyloxy)methyl penicillanate S,S-dioxides, sodium lauryl sulphate 32-36 part,
Cross-linking sodium carboxymethyl cellulose 130-14 part, magnesium stearate 40-50 part;
(b) cross-linking sodium carboxymethyl cellulose with amoxicillin, (Pivaloyloxy)methyl penicillanate S,S-dioxide, 1/2 amount mixes stirring and evenly mixing;
(c) material behind the mixing is put in the extruder extruding, brokenly must be done granule, the dried granule that makes and remaining cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate, magnesium stearate are put to mix in the mixer promptly get mixed powder;
(d) mixed powder is tested qualified back fill.
Adopt said method can be prepared into the amoxicillin sulbactam pivoxil capsule of all size.As: 0.25g/ grain, 0.625g/ grain.
Preferred capsule model of the present invention is No. 1.
The inventive method compared with prior art has the following advantages:
(1) adopts adjuvant few, can reduce patient's dose, and can avoid the side effect that brings by adjuvant.
(2) technological process is short, method for preparing is simple, has avoided the influence of hot and humid condition to product quality, has improved the stability of product quality, simultaneously, has practiced thrift resource.
(3) improve the packing density of active constituents of medicine, can the amoxicillin and sulbactam pivoxyl of effective dose be loaded in the ting model capsule, therefore made things convenient for the patient to take, strengthened patient's compliance.
The specific embodiment
Below in conjunction with embodiment, the present invention further is detailed, but it is not that the present invention is carried out any restriction.
Embodiment 1
Amoxicillin sulbactam pivoxil capsule specification: 250mg
(1) takes by weighing amoxicillin 3kg, (Pivaloyloxy)methyl penicillanate S,S-dioxide 3.866kg, sodium lauryl sulphate 34g.
Cross-linking sodium carboxymethyl cellulose 136g, magnesium stearate 49g.
(Pivaloyloxy)methyl penicillanate S,S-dioxide raw material, magnesium stearate, sodium lauryl sulphate are crossed 80 mesh sieves and weighing respectively; The cross-linking sodium carboxymethyl cellulose of amoxicillin, (Pivaloyloxy)methyl penicillanate S,S-dioxide, 1/2 amount is placed in the mixer; Stirring and evenly mixing; Material behind the mixing is put in the extruder extruding, brokenly must be done granule, the dried granule that makes and remaining cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate, magnesium stearate are put to mix in the mixer promptly get mixed powder.Mixed powder is tested, qualified after, be filled into capsule No. 1.The fill amount is the 0.345g/ grain, and medicament contg is 36.5% (in the amoxicillin.) carry out the capsule after the fill aluminum-plastic packaged.
Embodiment 2
Amoxicillin sulbactam pivoxil capsule specification: 625mg
(1) takes by weighing amoxicillin 12kg, (Pivaloyloxy)methyl penicillanate S,S-dioxide 3.866kg, sodium lauryl sulphate 79g.
Cross-linking sodium carboxymethyl cellulose 316g, magnesium stearate 111g.
(Pivaloyloxy)methyl penicillanate S,S-dioxide raw material, magnesium stearate, sodium lauryl sulphate are crossed 80 mesh sieves and weighing respectively; The cross-linking sodium carboxymethyl cellulose of amoxicillin, (Pivaloyloxy)methyl penicillanate S,S-dioxide, 1/2 amount put to mix in the mixer to stir make its abundant mixing; Material behind the mixing is put in the extruder extruding, brokenly must be done granule, the dried granule that makes and remaining cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate, magnesium stearate are put to mix in the mixer promptly get mixed powder.Mixed powder is tested, qualified after, be filled into capsule No. 0.The fill amount is 0.77g, and medicament contg is 65% (in the amoxicillin.) carry out the capsule after the fill aluminum-plastic packaged.
The comparative example 1
Adopt wet granulation amoxicillin sulbactam pivoxil capsule specification: 250mg
(1) takes by weighing amoxicillin 3kg, (Pivaloyloxy)methyl penicillanate S,S-dioxide 3.866kg, carboxymethyl starch sodium 136g.
The low carboxy-propyl cellulose sodium 136g that replaces, magnesium stearate is an amount of.
Amoxicillin, (Pivaloyloxy)methyl penicillanate S,S-dioxide, carboxymethyl starch sodium, the low carboxy-propyl cellulose sodium that replaces are crossed 80 mesh sieves and weighing respectively; Be placed on to mix in the mixer to stir and make its abundant mixing; Add 5% an amount of polyvidone as binding agent, system soft material, wet granular are dried the back granulate with wet granular; Obtain dried particles, dried granule that makes and an amount of magnesium stearate are put to mix in the mixer promptly get mixed powder.Mixed powder is tested, qualified after, be filled into capsule No. 1.The fill amount is 0.31g, and medicament contg is 36.5% (in the amoxicillin.) carry out the capsule after the fill aluminum-plastic packaged.
The comparative example 2
According to conventional dry process amoxicillin sulbactam pivoxil capsule specification: 625mg
(1) takes by weighing amoxicillin 12kg, (Pivaloyloxy)methyl penicillanate S,S-dioxide 3.866kg, carboxymethyl starch sodium 316g, polyvinylpolypyrrolidone 158g, magnesium stearate 111g.
(Pivaloyloxy)methyl penicillanate S,S-dioxide raw material, magnesium stearate, carboxymethyl starch sodium are crossed 80 mesh sieves and weighing respectively; Amoxicillin, (Pivaloyloxy)methyl penicillanate S,S-dioxide, polyvinylpolypyrrolidone put in the mixer to mix to stir make its abundant mixing; Material behind the mixing is put in the extruder extruding, brokenly must be done granule, dried granule and the carboxymethyl starch sodium, the magnesium stearate that make are put to mix in the mixer promptly get mixed powder.Mixed powder is tested, qualified after, be filled into capsule No. 0.The fill amount is 0.77g, and medicament contg is 65% (in the amoxicillin.) carry out the capsule after the fill aluminum-plastic packaged.
Embodiment 3
Study on the stability
Investigate object: the embodiment of the invention 1 products made thereby and comparative example's 1 products made thereby.
Investigation method:, carry out accelerated test under 40 ℃ ± 2 ℃ conditions of temperature at relative humidity 75% ± 5%.
Investigation project:, character, related substance, content, the dissolution of product are investigated according to " the standard YBHO1472007 of State Food and Drug Administration ".
The result sees table 1, table 2 for details:
The related data of table 1: embodiment 1 products made thereby
Table 2: the related data of comparison example 1 products made thereby
Can find out that from the contrast of the data of table 1, table 2 in accelerated test, after the product of making according to wet method was placed 2 months, its related substance was apparently higher than the product of the inventive method manufacturing, its dissolution and content have not all met the quality standard requirement.And the dissolution of the product of manufacturing of the present invention placement product after 6 months and content of effective are all within the scope that quality standard allowed.Its good stability of amoxicillin sulbactam pivoxil capsule of the inventive method preparation thus.
Embodiment 4
Study on the stability
Investigate object: the embodiment of the invention 2 products made therebies and comparison example 2 products made therebies.
Investigation method:, carry out accelerated test under 40 ℃ ± 2 ℃ conditions of temperature at relative humidity 75% ± 5%.
Investigation project:, character, related substance, content, the dissolution of product are investigated according to " the standard YBHO1472007 of State Food and Drug Administration ".The result sees table 3 for details:
Table 3: embodiment 2, comparison example 2 products made therebies are placed 6 months data of surveying
The contrast of data from table 3 can find out, in accelerated test, after the product of making according to conventional dry method was placed 6 months, the dissolution of product was starkly lower than products made thereby of the present invention.
Embodiment 5
The amoxicillin sulbactam pivoxil capsule fill measures examination, and test result sees table 4. for details
Table 4:
| Specimen | The capsule amount of filling (g/ grain) | Active constituents of medicine content |
| Embodiment 1 | (0.345 No. 1 capsule) | 99.8% of labelled amount |
| Embodiment 2 | (0.77 No. 0 capsule) | 100.2% of labelled amount |
| The comparative example 1 | (0.31 No. 1 capsule) | 89.9% of labelled amount |
| The comparative example 2 | (0.74 No. 0 capsule) | 91.5% of labelled amount |
This shows that in equal volume, the charge weight of products made thereby of the present invention is greater than the charge weight of prior art products made thereby.But so production ting model capsule.
Claims (3)
1. amoxicillin sulbactam pivoxil capsule is characterized in that it is by the raw material of following mass ratio, process according to following method:
3000 parts of amoxicillin, 3866 parts of (Pivaloyloxy)methyl penicillanate S,S-dioxides, 34 parts of sodium lauryl sulphates, 136 parts of cross-linking sodium carboxymethyl celluloses, 49 parts of magnesium stearate;
(a) take by weighing the raw material of above-mentioned mass ratio:
(b) cross-linking sodium carboxymethyl cellulose with amoxicillin, (Pivaloyloxy)methyl penicillanate S,S-dioxide, 1/2 amount mixes stirring and evenly mixing;
(c) material behind the mixing is put in the extruder extruding, brokenly must be done granule, the dried granule that makes and remaining cross-linking sodium carboxymethyl cellulose, sodium lauryl sulphate, magnesium stearate are put to mix in the mixer promptly get mixed powder;
(d) mixed powder is tested qualified back fill.
2. amoxicillin sulbactam pivoxil capsule according to claim 1 is characterized in that said every capsules fill amount is controlled at and is 0.34-0.36g.
3. amoxicillin sulbactam pivoxil capsule according to claim 1 is characterized in that its model of described capsule is No. 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910074605A CN101897702B (en) | 2009-05-27 | 2009-05-27 | Amoxicillin sulbactam pivoxil capsule and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910074605A CN101897702B (en) | 2009-05-27 | 2009-05-27 | Amoxicillin sulbactam pivoxil capsule and preparation method thereof |
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| Publication Number | Publication Date |
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| CN101897702A CN101897702A (en) | 2010-12-01 |
| CN101897702B true CN101897702B (en) | 2012-10-03 |
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| CN200910074605A Expired - Fee Related CN101897702B (en) | 2009-05-27 | 2009-05-27 | Amoxicillin sulbactam pivoxil capsule and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103735529B (en) * | 2014-01-22 | 2015-10-14 | 华北制药股份有限公司 | The preparation method of amoxicillin dry granulation capsule |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1969845A (en) * | 2005-11-23 | 2007-05-30 | 桂勇 | Oral formulation of amoxicillin and sulbactam pivoxyl and preparation method thereof |
| CN101317843A (en) * | 2008-07-18 | 2008-12-10 | 河北智同医药控股集团有限公司 | Amoxicillin sulbactam pivoxil oral preparation and preparation method thereof |
-
2009
- 2009-05-27 CN CN200910074605A patent/CN101897702B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1969845A (en) * | 2005-11-23 | 2007-05-30 | 桂勇 | Oral formulation of amoxicillin and sulbactam pivoxyl and preparation method thereof |
| CN101317843A (en) * | 2008-07-18 | 2008-12-10 | 河北智同医药控股集团有限公司 | Amoxicillin sulbactam pivoxil oral preparation and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 刘新民 等.青霉素类抗生素.《临床药物学》.军事医学科学出版社,2008,(第一版),825-826. * |
| 陈鋆 等.阿莫西林舒巴坦匹酯分散片制备工艺研究.《中国药业》.2009,第18卷(第3期),23-25. * |
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