CN104546769B - A kind of Amlodipine Besylate Tablet solid oral tablet and preparation method thereof - Google Patents
A kind of Amlodipine Besylate Tablet solid oral tablet and preparation method thereof Download PDFInfo
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- CN104546769B CN104546769B CN201410841605.3A CN201410841605A CN104546769B CN 104546769 B CN104546769 B CN 104546769B CN 201410841605 A CN201410841605 A CN 201410841605A CN 104546769 B CN104546769 B CN 104546769B
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Abstract
The invention discloses a kind of Amlodipine Besylate Tablet solid oral tablet and preparation method thereof, the tablet includes Amlodipine Besylate Tablet, filler, disintegrating agent, lubricant, and the disintegrating agent is sodium carboxymethyl starch, and sodium chloride mass content is less than 2%.Preparation method include: premixing, be added auxiliary material and tabletting and etc. be made.The invention has the benefit that disintegrating agent carboxymethyl base sodium starch surface chlorination sodium content of the present invention reduces, the disintegrating property of sodium carboxymethyl starch is improved, the rate of release of drug is improved, the dissolving out capability of drug is made to reach best.
Description
Technical field
The invention belongs to chemical pharmaceutical technology fields, and in particular to a kind of Amlodipine Besylate Tablet solid oral tablet and its
Preparation method.
Background technique
Amlodipine Besylate Tablet (amlodipine besylate) is dihydropyridine type calcium antagonists, chemical name are as follows: 3- second
Base -5- methyl -2- (2- amino ethoxymethyl) -4- (2- chlorphenyl)-Isosorbide-5-Nitrae-dihydro -6- methyl -3,5- pyridine dicarboxylate benzene
Sulfonate, structural formula are as follows:
The contraction of cardiac muscle and smooth muscle enters cell by specific ion channel dependent on extracellular calcium.And benzene sulphur
Sour Amlodipine can selective depression calcium ion cross-film enter smooth muscle cell and cardiac muscle cell, the effect of smooth muscle is greater than
Cardiac muscle.Its bioavilability is high, drug effect slowly persistently, it is Small side effects, significant in efficacy, can be used for treating hypertension, coronary heart disease.Such as
The oral tablet of trade name " Amlodipine Besylate Tablet ", specification have 2.5mg, 5mg and 10mg etc. several, and auxiliary material includes microcrystalline cellulose
Element, calcium phosphate dibasic anhydrous, Sodium Hydroxymethyl Stalcs and magnesium stearate etc..
Sodium carboxymethyl starch is commonly used in Amlodipine Besylate Tablet solid orally ingestible and cooks disintegrating agent.Sodium carboxymethyl starch category
It is that glucose molecule is interconnected by Isosorbide-5-Nitrae-α-glycosidic bond, every about 100 in the derivative of low degree of substitution potato starch
A glucose unit introduces 25 carboxymethyls.With water imbibition, water swellability, mobility, compressibility, granularity subcircular.Beauty
Carboxyrnethyl starch sodium is divided into A type and Type B in state pharmacopeia USP35-NF30, and is divided into A, B and c-type in European Pharmacopoeia EP8.0.Its point
Son amount is generally between 5 × 105 ~ 1 × 106, good fluidity (36 ° of angle of repose <).A and Type B are mainly handed over by sodium thiosulfate
Connection preparation, c-type mainly pass through dehydration preparation.
The synthetic method of existing sodium carboxymethyl starch is broadly divided into: water-borne method, solid method, organic solvent method.Through carboxymethyl
Change, wash, dry, pulverization process obtains product.It is industrial generally to use sodium chloroacetate and carboxymethyl starch in anhydrous solvent
After reaction, then neutralized with acid, it is then dry, crush and obtain target product.Solution evaporation causes particle surface to contain in drying process
There are the inorganic salts such as a large amount of sodium chloride, sodium glycollate.The sodium carboxymethyl starch quality standard of domestic production at present is mainly with " middle traditional Chinese medicines
Allusion quotation " subject to 2010 editions.Science and Technology Ltd., Liaocheng A Hua pharmaceutical Co. Ltd, upper Hydron are looked forward in such as Guangdong Chaozhou by domestic manufacturer
To be provided in its quality standard of the sodium carboxymethyl starch of the productions such as medical auxiliary materials Technology Co., Ltd. about sodium chloride content standard
Calculated for≤6%(by dry product), actually detected amount is about 4% ~ 6%.Foreign vendor such as Explotab, Primojel, Vivastar
It is defined as≤7% about sodium chloride content standard in its quality standard of the sodium carboxymethyl starch of the productions such as P, actually detected amount is about
4%~6.5%。
The disintegrating property of sodium carboxymethyl starch directly affects the drug dissolution of Amlodipine Besylate Tablet solid oral tablet
Can, therefore, it is desirable to find the key parameter that can significantly affect the sodium carboxymethyl starch of drug releasing rate, to obtain best
Drug-eluting performance.Sodium carboxymethyl starch has many performances, such as: density, partial size, the degree of polymerization (DP), replaces specific surface area
Degree (DS), crystal form, pattern, impurity content, pH value, solution viscosity, draws moist, powder bulk properties (such as aerated flow at dilation
Kinetic energy (Aerated Energy, AE), cohesive strength (Cohesion), unconfined yield strength (UYS) and basic flowing energy
(BFE) etc..
Summary of the invention
The object of the present invention is to provide a kind of Amlodipine Besylate Tablet solid oral tablets and preparation method thereof, overcome mesh
Preceding the shortcomings of the prior art.
The purpose of the present invention is be achieved through the following technical solutions:
A kind of Amlodipine Besylate Tablet solid oral tablet, including Amlodipine Besylate Tablet, filler, disintegrating agent, lubrication
Agent, the disintegrating agent is sodium carboxymethyl starch, and the sodium carboxymethyl starch contains sodium chloride of the mass content less than 2%.
Further, the filler is lactose, microcrystalline cellulose, starch, mannitol, pregelatinized starch, anhydrous phosphoric acid
One of hydrogen calcium is a variety of, preferably microcrystalline cellulose and calcium phosphate dibasic anhydrous.
Further, the lubricant is one or more of magnesium stearate, talcum powder, superfine silica gel powder, preferably tristearin
Sour magnesium.
The preparation method of above-mentioned Amlodipine Besylate Tablet solid oral tablet, includes the following steps:
(1) active constituent Amlodipine Besylate Tablet and filler (such as microcrystalline cellulose, calcium phosphate dibasic anhydrous) are carried out
Premixing；
(2) filler and disintegrating agent (such as microcrystalline cellulose, calcium phosphate dibasic anhydrous and carboxymethyl are added into mixture
Sodium starch) continue to mix, wherein sodium carboxymethyl starch is crushed by high speed disintegrator, then screening obtains low
The disintegrating agent carboxymethyl base sodium starch of sodium chloride content, the sodium chloride mass content are lower than 2%；
(3) lubricant (such as magnesium stearate) is added into mixture to be mixed；With
(4) above-mentioned mixture is subjected to tabletting using tablet press machine.
The invention has the benefit that providing a kind of new side for preparing Amlodipine Besylate Tablet solid oral tablet
Method, this method crush disintegrating agent carboxymethyl base sodium starch, make the reduction of its surface chlorination sodium content, improve carboxymethyl starch
The disintegrating property of sodium improves the rate of release of drug, and the dissolving out capability of drug is made to reach best.
Detailed description of the invention
It in order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, below will be to institute in embodiment
Attached drawing to be used is needed to be briefly described, it should be apparent that, the accompanying drawings in the following description is only some implementations of the invention
Example, for those of ordinary skill in the art, without creative efforts, can also obtain according to these attached drawings
Obtain other attached drawings.
Fig. 1 is the stereoscan photograph of the sodium carboxymethyl starch for not beating powder described according to embodiments of the present invention；
Fig. 2 is the described stereoscan photograph for beating sodium carboxymethyl starch after powder 30s according to embodiments of the present invention.
Specific embodiment
Technical scheme in the embodiment of the invention is clearly and completely described, it is clear that described embodiment is only
It is a part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, ordinary skill people
Member's every other embodiment obtained, shall fall within the protection scope of the present invention.
According to embodiments of the present invention, a kind of Amlodipine Besylate Tablet solid oral tablet and preparation method thereof is provided.
Embodiment 1:
It is calculated by 1000 plain pieces, each component content is as follows:
Amlodipine Besylate Tablet 7g
Microcrystalline cellulose (PH102) 126g
Calcium phosphate dibasic anhydrous 60g
Sodium carboxymethyl starch (does not crush) 5g
Magnesium stearate 2g
Above-mentioned Amlodipine Besylate Tablet solid oral tablet the preparation method is as follows:
(1) feed bin is added in Amlodipine Besylate Tablet and microcrystalline cellulose (30%) to premix；
(2) above-mentioned mixture is added in microcrystalline cellulose (70%), calcium phosphate dibasic anhydrous, sodium carboxymethyl starch (not crushing)
Middle mixing is until uniformly；
(3) magnesium stearate is added in above-mentioned mixture and is uniformly mixed；
(4) above-mentioned mixture is subjected to tabletting using tablet press machine；
(5) manufactured tablet is measured into dissolution curve in four kinds of media, the results are shown in Table 1, and Fig. 1 is the carboxylic for not beating powder
The stereoscan photograph of methyl starch sodium.
Embodiment 2:
It is calculated by 1000 plain pieces, each component content is as follows:
Amlodipine Besylate Tablet 7g
Microcrystalline cellulose (PH102) 126g
Calcium phosphate dibasic anhydrous 60g
Sodium carboxymethyl starch (does not crush) 5g
Magnesium stearate 2g
Above-mentioned Amlodipine Besylate Tablet solid oral tablet the preparation method is as follows:
(1) feed bin is added in Amlodipine Besylate Tablet and microcrystalline cellulose (30%) to premix；
(2) sodium carboxymethyl starch (not crushing) is added in high speed disintegrator and crushes 30s, smash it through 200 mesh screens
Screening 10s takes sample on sieve, crushes front and back partial size and sodium chloride content situation of change is shown in Table 2；
(3) it is added by microcrystalline cellulose (70%), calcium phosphate dibasic anhydrous, by the sodium carboxymethyl starch to pulverize and sieve above-mentioned
Mixing is until uniformly in mixture；
(4) magnesium stearate is added in above-mentioned mixture and is uniformly mixed；
(5) above-mentioned mixture is subjected to tabletting using tablet press machine；
(6) manufactured tablet is measured into dissolution curve in four kinds of media, the results are shown in Table 1, and Fig. 2 is after beating powder 30s
The stereoscan photograph of sodium carboxymethyl starch.
Embodiment 3:
Dissolution curve measurement: surveying the dissolution curve of Amlodipine Besylate Tablet solid oral tablet using Hansen digestion instrument,
Leaching condition is as follows:
A. dissolution medium: 900ml；
B. device: slurry processes；
C. revolving speed: 50 turns/min；
D. temperature: 37 ± 0.5 DEG C；
E. sample time: 5min, 10 min, 15 min, 30 min, 45 min；
F. sampling amount: 10ml uses glass syringe (while adding the isometric dissolution medium of isothermal)；
G. sample treatment: with the general filter filtering of 0.45 μm of Town in Shanghai, primary filtrate 5ml is discarded, subsequent filtrate is taken to do respective handling.
Embodiment 4:
Grain diameter measurement: dry method granulometry, dry method sample injector model are carried out using 2000 type laser particle analyzer of Malvern
Scirocco 2000(A), using Gneral analysis mode, particle refractive index is 1.530, granule absorbance 0.1, gas dispersion
Pressure is 2MPa, sample rate 75%, applied sample amount 1g.
Embodiment 5:
Sodium chloride content measurement: with reference to " two page 915 of Chinese Pharmacopoeia 2005 version about chlorination in carboxyrnethyl starch sodium
The detection method of sodium: taking this product about 0.5g, accurately weighed, is placed in 250ml conical flask, adds water 150ml, shake up, add potassium chromate
Indicator 1ml is titrated with silver nitrate titration liquid (0.1mol/L).Every 1ml silver nitrate titration liquid (0.1mol/L) is equivalent to
5.844mg sodium chloride.
Table 1
Table 2
The sodium carboxymethyl starch disintegrating property that the present invention compares same producer's different batches difference sodium chloride content is ground
During studying carefully, the Amlodipine Besylate Tablet in obtained tablet when the sodium chloride content in sodium carboxymethyl starch is lower is found
Better rate of release is shown, to further find meeting in drying process by the preparation method of analysis sodium carboxymethyl starch
The a large amount of sodium salt coverings of particle surface are caused, the disintegrating property for ultimately causing tablet reduces.Powder is carried out by using high speed disintegrator
It is broken that the product that partial size has almost no change but the sodium salt of particle surface covering largely removes, sodium carboxymethyl starch after crushing can be obtained
Disintegrating property significantly improves.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Within mind and principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Claims (8)
1. a kind of Amlodipine Besylate Tablet solid oral tablet, including active constituent Amlodipine Besylate Tablet, filler, disintegration
Agent, lubricant, it is characterised in that: the disintegrating agent is sodium carboxymethyl starch, and the sodium carboxymethyl starch contains mass content
Sodium chloride less than 2%, the filler are lactose, microcrystalline cellulose, starch, mannitol, pregelatinized starch, anhydrous phosphoric acid hydrogen
One of calcium is a variety of.
2. Amlodipine Besylate Tablet solid oral tablet according to claim 1, it is characterised in that: the filler is micro-
Crystalline cellulose or calcium phosphate dibasic anhydrous.
3. Amlodipine Besylate Tablet solid oral tablet according to claim 1, it is characterised in that: the lubricant is hard
One or more of fatty acid magnesium, talcum powder, superfine silica gel powder.
4. Amlodipine Besylate Tablet solid oral tablet according to claim 3, it is characterised in that: the lubricant is hard
Fatty acid magnesium.
5. a kind of preparation method of Amlodipine Besylate Tablet solid oral tablet, which comprises the steps of:
(1) active constituent Amlodipine Besylate Tablet is pre-mixed with filler；
(2) filler is added into mixture and disintegrating agent carboxymethyl base sodium starch continues to mix, wherein crushed by high speed
Machine crushes sodium carboxymethyl starch, and then screening obtains the disintegrating agent carboxymethyl base starch that sodium chloride mass content is lower than 2%
Sodium；
(3) lubricant is added into mixture to be mixed；
(4) above-mentioned mixture is subjected to tabletting using tablet press machine.
6. the preparation method of Amlodipine Besylate Tablet solid oral tablet according to claim 5, which is characterized in that step
(1) filler in is microcrystalline cellulose or calcium phosphate dibasic anhydrous.
7. the preparation method of Amlodipine Besylate Tablet solid oral tablet according to claim 5, which is characterized in that step
(2) filler in is microcrystalline cellulose or calcium phosphate dibasic anhydrous.
8. the preparation method of Amlodipine Besylate Tablet solid oral tablet according to claim 5, which is characterized in that step
(3) lubricant in is magnesium stearate.
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| CN110215436A (en) * | 2019-07-04 | 2019-09-10 | 沈阳达善医药科技有限公司 | A kind of preparation method improving amlodipine besylate tablets intermediate mixture homogeneity |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1686121A (en) * | 2005-04-19 | 2005-10-26 | 昆明金殿制药有限公司 | Phenylsulfonic acid amido chloro diping dispersion tablet and its preparation method |
| CN102846565A (en) * | 2011-06-28 | 2013-01-02 | 扬子江药业集团上海海尼药业有限公司 | Preparation method of Levamlodipine besylate tablet |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1686121A (en) * | 2005-04-19 | 2005-10-26 | 昆明金殿制药有限公司 | Phenylsulfonic acid amido chloro diping dispersion tablet and its preparation method |
| CN102846565A (en) * | 2011-06-28 | 2013-01-02 | 扬子江药业集团上海海尼药业有限公司 | Preparation method of Levamlodipine besylate tablet |
Non-Patent Citations (2)
| Title |
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| 一种优良的片剂崩解剂——羧甲基淀粉钠;刘丽娟等;《山东医药工业》;19991231;第18卷(第3期);参见全文 |
| 国产梭甲基淀粉钠的崩解性能考查;高崇凯等;《沈阳药学院学报》;19890131;第6卷(第1期);参见全文 |
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