CN104546769A - Amlodipine besylate solid oral tablet and preparation method thereof - Google Patents
Amlodipine besylate solid oral tablet and preparation method thereof Download PDFInfo
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- CN104546769A CN104546769A CN201410841605.3A CN201410841605A CN104546769A CN 104546769 A CN104546769 A CN 104546769A CN 201410841605 A CN201410841605 A CN 201410841605A CN 104546769 A CN104546769 A CN 104546769A
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Abstract
The invention discloses an amlodipine besylate solid oral tablet and a preparation method thereof. The amlodipine besylate solid oral tablet comprises amlodipine besylate, filler, a disintegrant and a lubricant, wherein the disintegrant adopts sodium carboxymethyl starch which contains less than 2% by mass of sodium chloride. The preparation method comprises the steps of premixing, auxiliary adding, tableting and the like. The amlodipine besylate solid oral tablet and the preparation method have the following benefits: the content of sodium chloride on the surface of the sodium carboxymethyl starch serving as the disintegrant is reduced, so that the disintegration performance of the disintegrant is improved, the release speed of medicine is increased, and the dissolution performance of the medicine is optimal.
Description
Technical field
The invention belongs to technical field of pharmaceutical chemistry, be specifically related to a kind of Amlodipine Besylate Tablet solid oral tablet and preparation method thereof.
Background technology
Amlodipine Besylate Tablet (amlodipine besylate) is dihydropyridine type calcium antagonists, chemistry is by name: 3-ethyl-5-methyl-2-(the amino ethoxymethyl of 2-)-4-(2-chlorphenyl)-1,4-dihydro-6-methyl-3,5-pyridine dicarboxylate benzene sulfonate, structural formula is as follows:
The contraction of cardiac muscle and smooth muscle depends on extracellular calcium and enters cell by specific ion passage.And Amlodipine Besylate Tablet Selective depression calcium ion cross-film can enter smooth muscle cell and myocardial cell, cardiac muscle is greater than to the effect of smooth muscle.Its bioavailability is high, drug effect is slow lastingly, side effect is little, evident in efficacy, can be used for treating hypertension, coronary heart disease.As the oral tablet of commodity " Norvasc " by name, its specification has 2.5mg, 5mg and 10mg etc. several, and its adjuvant comprises microcrystalline Cellulose, calcium phosphate dibasic anhydrous, Sodium Hydroxymethyl Stalcs and magnesium stearate etc.
Carboxymethyl starch sodium is conventional in Amlodipine Besylate Tablet solid orally ingestible cooks disintegrating agent.Carboxymethyl starch sodium belongs to the derivant of low degree of substitution potato starch, is that glucose molecule is interconnective by Isosorbide-5-Nitrae-α-glycosidic bond, and approximately every 100 glucose units introduce 25 carboxymethyls.There is water absorption, water swellability, mobility, compressibility, granularity subcircular.In American Pharmacopeia USP35-NF30, carboxymethylstach sodium is divided into A type and Type B, and is divided into A, B and C type in European Pharmacopoeia EP8.0.Its molecular weight generally between 5 × 105 ~ 1 × 106, good fluidity (< 36 ° angle of repose).A and Type B are mainly through the crosslinked preparation of sodium thiosulfate, and C type is standby mainly through Dehydration.
The synthetic method of existing carboxymethyl starch sodium is mainly divided into: hydrophily method, solid method, organic solvent method.Product is obtained through carboxy methylation, washing, drying, pulverization process.After industrial general employing sodium chloroacetate and carboxymethyl starch react in anhydrous solvent, then neutralize with acid, then dry, pulverizing obtains target product.In dry run, solution evaporation causes particle surface to contain the inorganic salts such as a large amount of sodium chloride, sodium glycollate.The carboxymethyl starch sodium quality standard of current domestic production is mainly as the criterion with " Chinese Pharmacopoeia " 2010 editions.Domestic manufacturer as Chaozhou, Guangdong prospect Science and Technology Ltd., Liaocheng A Hua pharmaceutical Co. Ltd, upper Hydron be in its quality standard of carboxymethyl starch sodium of producing such as medical auxiliary materials Technology Co., Ltd. about sodium chloride content standard gauge be decided to be≤6%(calculates by dry product), actual detection limit is about 4% ~ 6%.In its quality standard of carboxymethyl starch sodium that foreign vendor produces as Explotab, Primojel, Vivastar P etc. about sodium chloride content standard gauge be decided to be≤7%, actual detection limit is about 4% ~ 6.5%.
The disintegrating property of carboxymethyl starch sodium directly affects the drug-eluting performance of Amlodipine Besylate Tablet solid oral tablet, therefore wishing to find can the key parameter of carboxymethyl starch sodium of appreciable impact drug releasing rate, thus obtains best drug-eluting performance.Carboxymethyl starch sodium has a lot of performance, such as: density, specific surface area, particle diameter, the degree of polymerization (DP), substitution value (DS), swelling degree, crystal formation, pattern, impurity content, pH value, solution viscosity, draw moist, powder bulk properties (as aerated flow kinetic energy (Aerated Energy, AE), cohesive strength (Cohesion), unconfined yield strength (UYS) and the basic energy of flow (BFE) etc.
Summary of the invention
The object of this invention is to provide a kind of Amlodipine Besylate Tablet solid oral tablet and preparation method thereof, overcome the deficiency that currently available technology exists.
The object of the invention is to be achieved through the following technical solutions:
A kind of Amlodipine Besylate Tablet solid oral tablet, comprise Amlodipine Besylate Tablet, filler, disintegrating agent, lubricant, described disintegrating agent is carboxymethyl starch sodium, and described carboxymethyl starch sodium contains the sodium chloride that mass content is less than 2%.
Further, described filler is one or more in lactose, microcrystalline Cellulose, starch, mannitol, pregelatinized Starch, calcium phosphate dibasic anhydrous, preferably microcrystalline cellulose and calcium phosphate dibasic anhydrous.
Further, described lubricant is one or more in magnesium stearate, Pulvis Talci, micropowder silica gel, preferred magnesium stearate.
The preparation method of above-mentioned Amlodipine Besylate Tablet solid oral tablet, comprises the steps:
(1) active component Amlodipine Besylate Tablet and filler (as microcrystalline Cellulose, calcium phosphate dibasic anhydrous etc.) are carried out premixing;
(2) in compound, add filler and disintegrating agent (as microcrystalline Cellulose, calcium phosphate dibasic anhydrous etc. and carboxymethyl starch sodium) proceed mixing, wherein, by high speed disintegrator, carboxymethyl starch sodium is pulverized, then screening obtains the disintegrating agent carboxymethyl base Starch Sodium of low sodium chloride content, and described sodium chloride mass content is lower than 2%;
(3) in compound, add lubricant (as magnesium stearate etc.) to mix; With
(4) tablet machine is adopted to carry out tabletting above-mentioned compound.
Beneficial effect of the present invention is: provide a kind of method preparing Amlodipine Besylate Tablet solid oral tablet newly, the method is pulverized disintegrating agent carboxymethyl base Starch Sodium, its surface chlorination sodium content is reduced, improve the disintegrating property of carboxymethyl starch sodium, improve the rate of release of medicine, make the dissolving out capability of medicine reach best.
Accompanying drawing explanation
In order to be illustrated more clearly in the embodiment of the present invention or technical scheme of the prior art, be briefly described to the accompanying drawing used required in embodiment below, apparently, accompanying drawing in the following describes is only some embodiments of the present invention, for those of ordinary skill in the art, under the prerequisite not paying creative work, other accompanying drawing can also be obtained according to these accompanying drawings.
Fig. 1 is the stereoscan photograph of not beating the carboxymethyl starch sodium of powder according to the embodiment of the present invention;
Fig. 2 is the stereoscan photograph of beating carboxymethyl starch sodium after powder 30s according to the embodiment of the present invention.
Detailed description of the invention
Be clearly and completely described the technical scheme in the embodiment of the present invention, obviously, described embodiment is only the present invention's part embodiment, instead of whole embodiments.Based on the embodiment in the present invention, the every other embodiment that those of ordinary skill in the art obtain, all belongs to the scope of protection of the invention.
According to the embodiment of the present invention, provide a kind of Amlodipine Besylate Tablet solid oral tablet and preparation method thereof.
Embodiment 1:
Calculate by 1000 plain sheets, each constituent content is as follows:
Amlodipine Besylate Tablet 7g
Microcrystalline Cellulose (PH102) 126g
Calcium phosphate dibasic anhydrous 60g
Carboxymethyl starch sodium (pulverizing) 5g
Magnesium stearate 2g
The preparation method of above-mentioned Amlodipine Besylate Tablet solid oral tablet is as follows:
(1) Amlodipine Besylate Tablet and microcrystalline Cellulose (30%) are added feed bin and carry out premix;
(2) microcrystalline Cellulose (70%), calcium phosphate dibasic anhydrous, carboxymethyl starch sodium (pulverizing) to be added in above-mentioned compound mixing till evenly;
(3) magnesium stearate is added mix homogeneously in above-mentioned compound;
(4) tablet machine is adopted to carry out tabletting above-mentioned compound;
(5) tablet made is measured stripping curve in four kinds of media, the results are shown in Table shown in 1, Fig. 1 is the stereoscan photograph of the carboxymethyl starch sodium not beating powder.
Embodiment 2:
Calculate by 1000 plain sheets, each constituent content is as follows:
Amlodipine Besylate Tablet 7g
Microcrystalline Cellulose (PH102) 126g
Calcium phosphate dibasic anhydrous 60g
Carboxymethyl starch sodium (pulverizing) 5g
Magnesium stearate 2g
The preparation method of above-mentioned Amlodipine Besylate Tablet solid oral tablet is as follows:
(1) Amlodipine Besylate Tablet and microcrystalline Cellulose (30%) are added feed bin and carry out premix;
(2) joined in high speed disintegrator by carboxymethyl starch sodium (pulverizing) and pulverize 30s, cross 200 eye mesh screens screening 10s after pulverizing and get sample on screen cloth, before and after pulverizing, particle diameter and sodium chloride content situation of change are shown in Table 2;
(3) by microcrystalline Cellulose (70%), calcium phosphate dibasic anhydrous, to add in above-mentioned compound mixing till evenly through the carboxymethyl starch sodium that pulverizes and sieves;
(4) magnesium stearate is added mix homogeneously in above-mentioned compound;
(5) tablet machine is adopted to carry out tabletting above-mentioned compound;
(6) tablet made is measured stripping curve in four kinds of media, the results are shown in Table shown in 1, Fig. 2 is the stereoscan photograph of carboxymethyl starch sodium after dozen powder 30s.
Embodiment 3:
Stripping curve is measured: utilize the gloomy digestion instrument of the Chinese to survey the stripping curve of Amlodipine Besylate Tablet solid oral tablet, its leaching condition is as follows:
A. dissolution medium: 900ml;
B. device: slurry processes;
C. rotating 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 (simultaneously adding isothermal equal-volume dissolution medium);
G. sample treatment: filter with 0.45 μm of general filter of Town in Shanghai, discard just filtrate 5ml, get subsequent filtrate and do respective handling.
Embodiment 4:
Grain diameter measurement: use Malvern 2000 type laser particle analyzer to carry out dry method granulometry, dry method injector model is Scirocco 2000(A), adopt Gneral analysis pattern, granule refractive index is 1.530, granule absorbance is 0.1, gas dispersion pressure is 2MPa, and sample rate is 75%, and applied sample amount is 1g.
Embodiment 5:
Sodium chloride content is measured: with reference to " Chinese Pharmacopoeia 2005 version two the 915th page of detection methods about sodium chloride in carboxymethylstach sodium: get this product and be about 0.5g, accurately weighed, be placed in 250ml conical flask, add water 150ml, shake up, add Neutral potassium chromate indicator 1ml, with silver nitrate titration liquid (0.1mol/L) titration.Every 1ml silver nitrate titration liquid (0.1mol/L) is equivalent to the sodium chloride of 5.844mg.
Table 1
Table 2
The carboxymethyl starch sodium disintegrating property that the present invention contrasts the different sodium chloride content of same producer different batches carries out in research process, find when the sodium chloride content in carboxymethyl starch sodium is lower, in the tablet obtained, Amlodipine Besylate Tablet shows better rate of release, thus find in dry run, to cause a large amount of sodium salt of particle surface to cover further by the preparation method analyzing carboxymethyl starch sodium, finally cause the disintegrating property of tablet to reduce.Undertaken by using high speed disintegrator pulverizing and can obtain particle diameter and have almost no change but the product removed in a large number of sodium salt that covers of particle surface, after pulverizing, carboxymethyl starch sodium disintegrating property significantly improves.
The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (9)
1. an Amlodipine Besylate Tablet solid oral tablet, comprise active component Amlodipine Besylate Tablet, filler, disintegrating agent, lubricant, it is characterized in that: described disintegrating agent is carboxymethyl starch sodium, and described carboxymethyl starch sodium contains the sodium chloride that mass content is less than 2%.
2. Amlodipine Besylate Tablet solid oral tablet according to claim 1, is characterized in that: described filler is one or more in lactose, microcrystalline Cellulose, starch, mannitol, pregelatinized Starch, calcium phosphate dibasic anhydrous.
3. Amlodipine Besylate Tablet solid oral tablet according to claim 2, is characterized in that: described filler is microcrystalline Cellulose or calcium phosphate dibasic anhydrous.
4. Amlodipine Besylate Tablet solid oral tablet according to claim 2, is characterized in that: described lubricant is one or more in magnesium stearate, Pulvis Talci, micropowder silica gel.
5. Amlodipine Besylate Tablet solid oral tablet according to claim 4, is characterized in that: described lubricant is magnesium stearate.
6. a preparation method for Amlodipine Besylate Tablet solid oral tablet, is characterized in that, comprises the steps:
(1) active component Amlodipine Besylate Tablet and filler are carried out premixing;
(2) in compound, add filler and disintegrating agent carboxymethyl base Starch Sodium proceed mixing, wherein, by high speed disintegrator, carboxymethyl starch sodium is pulverized, then screening obtain sodium chloride mass content lower than 2% disintegrating agent carboxymethyl base Starch Sodium;
(3) in compound, add lubricant to mix; With
(4) tablet machine is adopted to carry out tabletting above-mentioned compound.
7. the preparation method of Amlodipine Besylate Tablet solid oral tablet according to claim 6, is characterized in that, the filler in step (1) is microcrystalline Cellulose or calcium phosphate dibasic anhydrous.
8. the preparation method of Amlodipine Besylate Tablet solid oral tablet according to claim 6, is characterized in that, the filler in step (2) is microcrystalline Cellulose or calcium phosphate dibasic anhydrous.
9. the preparation method of Amlodipine Besylate Tablet solid oral tablet according to claim 6, is characterized in that, the lubricant in step (3) is magnesium stearate.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108464972A (en) * | 2018-07-02 | 2018-08-31 | 福州大学 | A kind of anti-pulmonary hypertension oral tablet and preparation method thereof containing Snopori |
| 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 |
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| 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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2014
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| 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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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108464972A (en) * | 2018-07-02 | 2018-08-31 | 福州大学 | A kind of anti-pulmonary hypertension oral tablet and preparation method thereof containing Snopori |
| 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 |
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