CN102526748B - Oral tablet containing Valsartan, Hydrochioro and Amlodipine Besylate Tablet - Google Patents
Oral tablet containing Valsartan, Hydrochioro and Amlodipine Besylate Tablet Download PDFInfo
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Abstract
The invention discloses a kind of oral tablet containing Valsartan, Hydrochioro and Amlodipine Besylate Tablet, it is made up of Valsartan, Hydrochioro, Amlodipine Besylate Tablet and pharmaceutic adjuvant, wherein containing pregelatinized starch in the pharmaceutic adjuvant.Valsartan/Hydrochioro/amlodipine besylate tablets that the present invention is provided are unilateral attractive in appearance, and steady quality, dissolution is rapid.The present invention also provides the preparation method of the oral tablet, and process is simple, cost is relatively low, is adapted to industrialized production.
Description
Technical field
The invention belongs to pharmaceutical technology field, it is specifically related to a kind of containing Valsartan, Hydrochioro and benzene sulfonic acid ammonia
The oral tablet of Flordipine.
Background technology
Valsartan is a kind of angiotensins (AT) II receptor antagonists of orally active high specificity, and it is optionally
Act on AT1 receptor subtypes, chemical name：(S)-N- valeryls-N- { [2 '-(1H- tetrazole -5- bases) [1,1 '-phenylbenzene] -4-
Base] methyl }-valine.
Amlodipine is cerebrocrast.The sustainer contraction for suppressing calcium induction is 2 times of nifedipine.It is special
Point is slower with acceptor association and dissociation speed, therefore medicine acts on appearance length of holding time late.Choosing to vascular smooth muscle
The effect of selecting property is more than nifedipine.Can increase cardiac output and coronary flow in myocardial ischemia person this product, increase myocardial oxygen delivery and
Lower oxygen consumption, improve locomitivity.Chemical name：3- ethyl -5- methyl -2- (2- ammonia ethoxymethyl) -4- (2- chlorphenyls)-Isosorbide-5-Nitrae -
Dihydro -6- methyl -3,5- pyridine dicarboxylate benzene sulfonates.Conventional is its benzene sulfonate, maleate etc..
WO97/49394 describes the preparation side of Valsartan and its pharmaceutically acceptable salt and hydrochlorothiazide Compound preparation
Method, mixes by Valsartan, Hydrochioro and in addition to part of stearic acid magnesium, carries out dry granulation, and adding magnesium stearate is carried out
Compressing tablet.And disclose PVPP ratio has relatively good result of extraction 10~20%.
WO2007/022113 describes solid dosage forms of Valsartan and Amlodipine and preparation method thereof, is made using dry method
Grain technique.By Valsartan, Amlodipine, PVPP, microcrystalline cellulose, superfine silica gel powder, the mixing such as magnesium stearate.Using rolling
Platen press non-slurry pelletizing, particle after rolling is mixed with magnesium stearate, and compressing tablet obtains valsartan amlodipine piece.Or by figured silk fabrics
Sha Tan is granulated with auxiliary material, is granulated by Amlodipine, is then pressed into double-layer tablets, to avoid two kinds of active components phase
Mutually influence.
CN1331590A, discloses the preparation method of Valsartan piece, using roll-in method, by Valsartan and auxiliary material mixing granulation
After carry out compressing tablet, open microcrystalline cellulose consumption prescription more than 30%.
Mean disclosed above does not mention the preparation method of valsartan amlodipine hydrochlorothiazide tablets or capsule, and figured silk fabrics is husky
It is smooth be in water it is insoluble, its dissolubility is relevant with pH value, can make Valsartan rapid dissolution in the phosphate of pH6.8
(such as 10min ＞ 85%) is highly difficult, it usually needs use substantial amounts of PVPP, as the consumption of PVPP is carried
Height, due to the easy moisture absorption of the material, therefore product under acceleration conditions in, slice, thin piece disintegration effect is deteriorated, and dissolution suppression ratio is more,
And then influence the dissolution stability of product.Simultaneously in valsartan amlodipine hydrochlorothiazide Compound preparation containing three activity into
Point, influence each other, dissolution and the bioavilability of Valsartan and Amlodipine are particularly influenceed, therefore prepare qualified Valsartan
Amlodipine hydrochlorothiazide tablets are highly difficult.
CN101478956A, discloses Valsartan and Amlodipine, the preparation of Hydrochioro tripartite and preparation method thereof.Bag
Include to mix three kinds of active medicines with auxiliary material and carry out roll pressing grain, then carry out compressing tablet, form single-layer sheet, or by Valsartan with
Hydrochioro mixing granulation, is pressed into double-layer tablets together with Amlodipine, and by Amlodipine and Hydrochioro mixing granulation,
Double-layer tablets are pressed into together with particle obtained in Valsartan dry method.But tablet disclosed in patent contains substantial amounts of super-disintegrant
(such as 13.5% Crospovidone), and substantial amounts of super-disintegrant can cause tablet easily moisture absorption during production and storage,
Adverse effect is brought to the production of product；And moisture absorption can cause product quality to be deteriorated during storage.
Therefore at present it is still necessary to providing a kind of new technical scheme to overcome disadvantage mentioned above so that Valsartan, esodrix
Piperazine and amlodipine besylate tablets are unilateral attractive in appearance, up-to-standard, while Valsartan, Hydrochioro and Amlodipine Besylate Tablet have
Good dissolved corrosion, and it is cheap, be conducive to industrialized production.
The content of the invention
It is a kind of containing Valsartan, Hydrochioro, Amlodipine Besylate Tablet composite tablet, it is characterised in that contain pregelatinated
Starch.
A kind of compound preparation of Valsartan contains following ingredients：
Wherein：
Filler is selected from microcrystalline cellulose, lactose, mannitol etc., preferably microcrystalline cellulose, and microcrystalline cellulose consumption≤
30%.
Disintegrant is selected from sodium carboxymethyl starch, Ac-Di-Sol, PVPP etc., is preferably crosslinked poly- dimension
Ketone, PVPP consumption≤10%.
Lubricant is selected from magnesium stearate, talcum powder, sodium stearyl fumarate, superfine silica gel powder etc., wherein it is preferred that magnesium stearate.
What all auxiliary materials and the consumption of bulk drug mentioned according to the present invention, the present invention referred to is mass percent.
According to the present invention, active component is micronizing, and the particle diameter of wherein Hydrochioro is D90≤ 50 μm, the grain of Valsartan
Footpath D90Between 30~320 μm, preferably 90~250 μm, more preferably 120~200 μm, the particle diameter D of Amlodipine9050
Between~250 μm.
According to the present invention, D90Represent that particle diameter presses volume distributed median, cumulative volume reaches the particle diameter corresponding to 90%, such as D90
=100 μm represent by volume, and the grain diameter for having 90% is less than or equal to 100 μm.
The present inventor has found to be added in advance in containing Valsartan, Hydrochioro, the compound preparation of Amlodipine by experiment
Gelling starch can effectively increase dissolution, improve the bioavilability of preparation, while being also found surprisingly that, be formed sediment using pregelatinated
The compound preparation of powder can reduce the consumption of super-disintegrant, and then improve the stability of product.For example it is pre- relative to not containing
The sample of gelling starch, the dissolution of sample Valsartan and Amlodipine containing pregelatinized starch can improve more than 10%.And
In the increase along with pregelatinized starch consumption, can also further increase by three kinds of dissolutions of active component.Contain pre- glue simultaneously
The dissolution under acceleration conditions of the sample of change starch is better than not containing the sample of pregelatinized starch, in 40 DEG C, the condition of 75%RH
Lower to place 3 months, the sample dissolution without pregelatinized starch have dropped about 20%, and the sample containing pregelatinized starch does not have then
Significant change.This be because under acceleration conditions, the easy moisture absorption of super-disintegrant causes the disintegrating property of super-disintegrant to decline,
The lower three kinds of active component dissolutions of acceleration environment are ultimately resulted in decline.And pregelatinized starch can effectively completely cut off super-disintegrant and water
The contact for dividing, maintains the disintegration effect of super-disintegrant, while pregelatinized starch also has certain calving disaggregation in itself, can promote
Enter the dissolution of medicine, it is ensured that the stability of product.
It has also been found that, the particle diameter of Hydrochioro has large effect to dissolution in such a composition.Hydrochioro
As insoluble drug, with certain hydrophobicity, insoluble drug is crushed the surface area for being conducive to increasing medicine, increase medicine
The dissolution rate of thing.By the Hydrochioro particle diameter D after air-flow crushing90≤ 50 microns of dissolutions are complete, and without air-flow crushing
Hydrochioro dissolution is incomplete.
According to the present invention can with the Valsartan of selective freezing form, or non-crystalline forms Valsartan, it is preferably unformed.
The invention also discloses it is a kind of containing Valsartan, Hydrochioro, Amlodipine compound preparation preparation method：
1. Valsartan is mixed with medical additive, and granulated；
2. Amlodipine is mixed with medical additive；
3. Hydrochioro is mixed with medical additive；
4., by a, the mixing of the part of b, c tri- is pressed into single-layer sheet.
Or：
1. Valsartan, Amlodipine and medical additive are mixed, and granulated；
2. Hydrochioro is mixed with medical additive；
3. a and b are mixed, be then pressed into single-layer sheet.
Or：
1. Valsartan, Hydrochioro and medical additive are mixed, and granulated；
2. Amlodipine is mixed with medical additive；
3. a and b are mixed, be then pressed into single-layer sheet.
Three of the above method is improved and produced it is possible to prevente effectively from influencing each other for three kinds of active components, promotes product dissolution
The stability of product.
Specific embodiment
By specific examples below, reader can be helped to be better understood from the present invention, but example below does not make sense
It is for limiting the present invention.
Embodiment 1
| A | Valsartan | 160g | 41.4% |
| B | Hydrochioro | 12.5g | 3.2% |
| C | Amlodipine Besylate Tablet | 6.9g | 1.8% |
| D | Microcrystalline cellulose | 150g | 38.9% |
| E | PVPP | 50g | 12.9% |
| F | Magnesium stearate (I) | 3.4g | 0.9% |
| G | Magnesium stearate (II) | 3.4g | 0.9% |
| Summation | 386.2g | 100% |
The wherein amlodipine free base containing 5g in 6.9g Amlodipine Besylate Tablets.
Correspondence material is weighed by above-mentioned prescription, A~F is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, is adding G to be mixed, and compressing tablet is carried out using rotary pelleting machine, is coated, and then using aluminum-plastic packaged, investigates dissolution rate
With acceleration environment stability inferior.
Embodiment 2
| A | Valsartan | 160g | 41.4% |
| B | Hydrochioro | 12.5g | 3.2% |
| C | Amlodipine Besylate Tablet | 6.9g | 1.8% |
| D | Microcrystalline cellulose | 130g | 33.7% |
| E | Pregelatinized starch | 20g | 5.2% |
| F | PVPP | 50g | 12.9% |
| G | Magnesium stearate (I) | 3.4g | 0.9% |
| H | Magnesium stearate (II) | 3.4g | 0.9% |
| Summation | 386.2g | 100.0% |
The wherein amlodipine free base containing 5g in 6.9g Amlodipine Besylate Tablets.
Correspondence material is weighed by above-mentioned prescription, A~G is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, is adding H to be mixed, and compressing tablet is carried out using rotary pelleting machine, is coated.Wherein Hydrochioro D90=51 μm, Valsartan
D90=215 μm, D90=156 μm of Amlodipine.
Embodiment 3
| A | Valsartan | 160g | 41.4% |
| B | Hydrochioro | 12.5g | 3.2% |
| C | Microcrystalline cellulose | 110g | 28.5% |
| D | Pregelatinized starch | 20g | 5.2% |
| E | PVPP | 40g | 10.4% |
| F | Magnesium stearate (I) | 3.4g | 0.9% |
| G | Amlodipine Besylate Tablet | 6.9g | 1.8% |
| H | PVPP | 10g | 2.6% |
| I | Microcrystalline cellulose | 20g | 5.2% |
| J | Magnesium stearate (II) | 3.4g | 0.9% |
| Summation | 386.2g | 100.0% |
The wherein amlodipine free base containing 5g in 6.9g Amlodipine Besylate Tablets.
Correspondence material is weighed by above-mentioned prescription, A~F is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, G~I is mixed, and the particle with above A~F is mixed, and is being mixed after adding J, then using rotary pelleting machine
Carry out compressing tablet.Wherein Hydrochioro D90=31 μm, Valsartan D90=158 μm, D90=156 μm of Amlodipine.
Embodiment 4
| A | Valsartan | 160g | 41.4% |
| B | Amlodipine Besylate Tablet | 6.9g | 1.8% |
| C | Microcrystalline cellulose | 110g | 28.5% |
| D | Pregelatinized starch | 20g | 5.2% |
| E | PVPP | 40g | 10.4% |
| F | Magnesium stearate (I) | 3.4g | 0.9% |
| G | Hydrochioro | 12.5g | 3.2% |
| H | PVPP | 10g | 2.6% |
| I | Microcrystalline cellulose | 20g | 5.2% |
| J | Magnesium stearate (II) | 3.4g | 0.9% |
| Summation | 386.2g | 100.0% |
The wherein amlodipine free base containing 5g in 6.9g Amlodipine Besylate Tablets.
Correspondence material is weighed by above-mentioned prescription, A~F is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, G~I is mixed, and the particle with above A~F is mixed, and is being mixed after adding J, then using rotary pelleting machine
Carry out compressing tablet.Wherein Hydrochioro D90=31 μm, Valsartan D90=158 μm, D90=103 μm of Amlodipine.
Embodiment 5
| A | Valsartan | 160g | 41.4% |
| B | Microcrystalline cellulose | 110g | 28.5% |
| C | Pregelatinized starch | 20g | 5.2% |
| D | PVPP | 40g | 10.4% |
| E | Magnesium stearate (I) | 3.4g | 0.9% |
| F | Amlodipine Besylate Tablet | 6.9g | 1.8% |
| G | Hydrochioro | 12.5g | 3.2% |
| H | PVPP | 10g | 2.6% |
| I | Microcrystalline cellulose | 20g | 5.2% |
| J | Magnesium stearate (II) | 3.4g | 0.9% |
| Summation | 386.2g | 100.0% |
The wherein amlodipine free base containing 5g in 6.9g Amlodipine Besylate Tablets.
Correspondence material is weighed by above-mentioned prescription, A~E is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, F~I is mixed, and the particle with above A~E is mixed, and is remixed after adding J, then using rotary pelleting machine
Carry out compressing tablet.Wherein Hydrochioro D90=31 μm, Valsartan D90=158 μm, D90=103 μm of Amlodipine.
Embodiment 6
| A | Valsartan | 160.0g | 44.4% |
| B | Amlodipine Besylate Tablet | 6.9g | 1.9% |
| C | Microcrystalline cellulose | 67.2g | 18.7% |
| D | Pregelatinized starch | 44g | 12.2% |
| E | PVPP | 20.2g | 5.6% |
| F | Magnesium stearate (I) | 3.5g | 1.0% |
| G | Hydrochioro | 12.5g | 3.5% |
| H | Pregelatinized starch | 44.0g | 12.2% |
| I | Magnesium stearate (II) | 1.7g | 0.5% |
| Summation | 360.0g | 100.0% |
The wherein amlodipine free base containing 5g in 6.9g Amlodipine Besylate Tablets.
Correspondence material is weighed by above-mentioned prescription, A~F is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, is adding G~H to be mixed, and compressing tablet is carried out using rotary pelleting machine, is coated.Wherein Hydrochioro D90=31 μm, figured silk fabrics is husky
Smooth D90=158 μm, D90=103 μm of Amlodipine.
Embodiment 7
| A | Valsartan | 160 | 44.44% |
| B | Amlodipine Besylate Tablet | 6.9 | 1.92% |
| C | Microcrystalline cellulose (I) | 60 | 16.67% |
| D | PVPP | 25.2 | 7.00% |
| E | Pregelatinized starch | 54 | 15.00% |
| F | Magnesium stearate (I) | 3.5 | 0.97% |
| H | Hydrochioro | 12.5 | 3.47% |
| I | Microcrystalline cellulose (II) | 36.2 | 10.06% |
| J | Magnesium stearate (II) | 1.7 | 0.47% |
| Summation | 360.0 | 100.0% |
The wherein amlodipine free base containing 5g in 6.9g Amlodipine Besylate Tablets, Hydrochioro is using after air-flow crushing
D90It is 50 microns.
Correspondence material is weighed by above-mentioned prescription, A~F is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, is adding H~J to be mixed, and compressing tablet is carried out using rotary pelleting machine, is coated.Then using aluminum-plastic packaged, dissolution is investigated
Degree and acceleration environment stability inferior.Wherein Hydrochioro D90=50 μm, Valsartan D90=158 μm, Amlodipine D90=103 μ
m。
Embodiment 8
| A | Valsartan | 160 | 44.44% |
| B | Amlodipine Besylate Tablet | 6.9 | 1.92% |
| C | Microcrystalline cellulose (I) | 60 | 16.67% |
| D | PVPP | 25.2 | 7.00% |
| E | Pregelatinized starch | 54 | 15.00% |
| F | Magnesium stearate (I) | 3.5 | 0.97% |
| H | Hydrochioro | 12.5 | 3.47% |
| I | Microcrystalline cellulose (II) | 36.2 | 10.06% |
| J | Magnesium stearate (II) | 1.7 | 0.47% |
| Summation | 360.0 | 100.0% |
The wherein amlodipine free base containing 5g in 6.9g Amlodipine Besylate Tablets.Wherein Hydrochioro is used without gas
Stream crushes D90It is 122 microns.
Correspondence material is weighed by above-mentioned prescription, A~F is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, is adding H~J to be mixed, and compressing tablet is carried out using rotary pelleting machine, is coated.Then using aluminum-plastic packaged, dissolution is investigated
Degree and acceleration environment stability inferior.
Embodiment 9
| A | Valsartan | 160 | 44.4% |
| B | Amlodipine Besylate Tablet | 13.8 | 3.8% |
| C | Microcrystalline cellulose (I) | 49 | 13.6% |
| D | PVPP | 25.2 | 7.0% |
| E | Pregelatinized starch | 70 | 19.4% |
| F | Magnesium stearate (I) | 3.5 | 1.0% |
| H | Hydrochioro | 12.5 | 3.5% |
| I | Microcrystalline cellulose (II) | 24.3 | 6.8% |
| J | Magnesium stearate (II) | 1.7 | 0.5% |
| Summation | 360 | 100.00% |
The wherein amlodipine free base containing 10g in 13.8g Amlodipine Besylate Tablets, Hydrochioro uses air-flow crushing
D afterwards90It is 50 microns.
Correspondence material is weighed by above-mentioned prescription, A~F is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, is adding H~J to be mixed, and compressing tablet is carried out using rotary pelleting machine, is coated.
Embodiment 10
| A | Valsartan | 160 | 44.4% |
| B | Amlodipine Besylate Tablet | 13.8 | 3.8% |
| C | Microcrystalline cellulose (I) | 35 | 9.7% |
| D | PVPP | 15 | 4.2% |
| E | Pregelatinized starch | 98.5 | 27.4% |
| F | Magnesium stearate (I) | 3.5 | 1.0% |
| H | Hydrochioro | 12.5 | 3.5% |
| I | Microcrystalline cellulose (II) | 20 | 5.6% |
| J | Magnesium stearate (II) | 1.7 | 0.5% |
| Summation | 360.0 | 100.0% |
The wherein amlodipine free base containing 10g in 13.8g Amlodipine Besylate Tablets, Hydrochioro uses air-flow crushing
D afterwards90It is 50 microns.
Correspondence material is weighed by above-mentioned prescription, A~F is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, is adding H~J to be mixed, and compressing tablet is carried out using rotary pelleting machine, is coated.
Embodiment 11
| A | Valsartan | 160 | 44.4% |
| B | Amlodipine Besylate Tablet | 13.8 | 3.8% |
| C | Microcrystalline cellulose (I) | 49 | 13.6% |
| D | PVPP | 25.2 | 7.0% |
| E | Pregelatinized starch | 66.8 | 18.6% |
| F | Magnesium stearate (I) | 3.5 | 1.0% |
| H | Hydrochioro | 25 | 6.9% |
| I | Microcrystalline cellulose (II) | 15 | 4.2% |
| J | Magnesium stearate (II) | 1.7 | 0.5% |
| Summation | 360 | 100.00% |
The wherein amlodipine free base containing 10g in 13.8g Amlodipine Besylate Tablets, Hydrochioro uses air-flow crushing
D afterwards90=42 μm, Valsartan D90=54 μm, D90=69 μm of Amlodipine.
Correspondence material is weighed by above-mentioned prescription, A~F is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, is adding H~J to be mixed, and compressing tablet is carried out using rotary pelleting machine, is coated.
Testing result：
Using 2010 editions dissolution determination methods of Chinese Pharmacopoeia, with pH6.8 phosphate buffers as dissolution medium, 50rpm oars
Method, dissolution rate is determined in 30min.
| Valsartan dissolution % | Amlodipine dissolution % | Hydrochioro dissolution % | |
| Embodiment 1 | 79 | 65 | 80 |
| Embodiment 2 | 88 | 75 | 85 |
| Embodiment 3 | 87 | 74 | 90 |
| Embodiment 4 | 89 | 78 | 95 |
| Embodiment 5 | 90 | 76 | 95 |
| Embodiment 6 | 97 | 88 | 98 |
| Embodiment 7 | 95 | 85 | 96 |
| Embodiment 8 | 95 | 85 | 81 |
| Embodiment 9 | 92 | 87 | 96 |
Embodiment 1 does not contain pregelatinized starch, and, than relatively low, embodiment 2 has used pre- glue for three dissolutions of active component
Change starch, dissolution is substantially accelerated.Compared with Example 2, one of which or two kinds of active components are not involved in granulation, can be effective
Increase dissolution.Embodiment 6 shows that the consumption for improving pregelatinized starch can reduce the consumption of PVPP.
Embodiment 7 and 8 shows that the particle diameter of Hydrochioro has large effect to dissolution, more thin more be conducive to Hydrochioro
Dissolution.Embodiment 10 is consistent with 11 dissolution situations.
Embodiment 1 and embodiment 7 are carried out into study on the stability, 40 DEG C under acceleration conditions, under the conditions of 75%RH, 3 months
After determine dissolution：
Testing result：
Using 2010 editions dissolution determination methods of Chinese Pharmacopoeia, with pH6.8 phosphate buffers as dissolution medium, 50rpm oars
Method, dissolution rate is determined in 30min.
| Valsartan dissolution % | Amlodipine dissolution % | Hydrochioro dissolution % | |
| Embodiment 1 | 53 | 50 | 70 |
| Embodiment 7 | 96 | 81 | 97 |
Be can be seen that from the dissolution data of Acceleration study and do not contain the prescription dissolution rate of pregelatinized starch and be decreased obviously,
And contain pregelatinized starch prescription and have no significant change, illustrate to be conducive to keeping the stability of product using pregelatinized starch.
Embodiment 12
| A | Valsartan | 160 | 37.8% |
| B | Amlodipine Besylate Tablet | 13.8 | 3.3% |
| C | Microcrystalline cellulose (I) | 49 | 11.6% |
| D | Ac-Di-Sol | 25.2 | 6.0% |
| E | Pregelatinized starch | 130 | 30.7% |
| F | Magnesium stearate (I) | 3.5 | 0.8% |
| H | Hydrochioro | 25 | 5.9% |
| I | Microcrystalline cellulose (II) | 15 | 3.5% |
| J | Magnesium stearate (II) | 1.7 | 0.4% |
| Summation | 423.2 | 100.00% |
The wherein amlodipine free base containing 10g in 13.8g Amlodipine Besylate Tablets, Hydrochioro uses air-flow crushing
D afterwards90It is 50 microns.
Correspondence material is weighed by above-mentioned prescription, A~F is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, is adding H~J to be mixed, and compressing tablet is carried out using rotary pelleting machine, is coated.Then using aluminum-plastic packaged, dissolution is investigated
Degree and acceleration environment stability inferior.
Embodiment 13
| A | Valsartan | 160 | 58.39% |
| B | Amlodipine Besylate Tablet | 13.8 | 5.04% |
| C | Microcrystalline cellulose (I) | 20 | 7.30% |
| D | Ac-Di-Sol | 10 | 3.65% |
| E | Pregelatinized starch | 30 | 10.95% |
| F | Magnesium stearate (I) | 3.5 | 1.28% |
| H | Hydrochioro | 25 | 9.12% |
| I | Microcrystalline cellulose (II) | 10 | 3.65% |
| J | Magnesium stearate (II) | 1.7 | 0.62% |
| Summation | 274 | 100.00% |
The wherein amlodipine free base containing 10g in 13.8g Amlodipine Besylate Tablets, Hydrochioro uses air-flow crushing
D afterwards90It is 50 microns.
Correspondence material is weighed by above-mentioned prescription, A~F is mixed in total mixed machine, then carried out with dry granulating machine
Granulation, is adding H~J to be mixed, and compressing tablet is carried out using rotary pelleting machine, is coated.Then using aluminum-plastic packaged, dissolution is investigated
Degree and acceleration environment stability inferior.
Likewise, the product stability of both examples above is same as Example 7.
Claims (7)
1. a kind of oral tablet, comprising：
It is characterized in that filler be selected from microcrystalline cellulose, lactose, one or more in mannitol, disintegrant be selected from carboxymethyl
Sodium starch, Ac-Di-Sol, one or more of PVPP.
2. oral tablet according to claim 1, it is characterised in that filler is selected from microcrystalline cellulose, microcrystalline cellulose is used
Amount≤30%.
3. oral tablet according to claim 1, it is characterised in that disintegrant is selected from PVPP, PVPP is used
Amount≤10%.
4. oral tablet according to claim 1, it is characterised in that active component is micronizing, the particle diameter of Hydrochioro
It is D90≤ 50 μm, the particle diameter D of Valsartan90Between 30~320 μm, the particle diameter D of Amlodipine90Between 50~250 μm.
5. a kind of preparation method of oral tablet as claimed in claim 1, specifically includes following steps：
A. Valsartan is mixed with medical additive, and is granulated；
B. Amlodipine is mixed with medical additive；
C. Hydrochioro is mixed with medical additive；
D. by a, the mixing of the part of b, c tri- is pressed into single-layer sheet.
6. a kind of preparation method of oral tablet as claimed in claim 1, specifically includes following steps：
A. Valsartan, Amlodipine and medical additive are mixed, and is granulated；
B. Hydrochioro is mixed with medical additive；
C. a and b are mixed, is then pressed into single-layer sheet.
7. a kind of preparation method of oral tablet as claimed in claim 1, specifically includes following steps：
A. Valsartan, Hydrochioro and medical additive are mixed, and is granulated；
B. Amlodipine is mixed with medical additive；
C. a and b are mixed, is then pressed into single-layer sheet.
Priority Applications (1)
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| CN201110462594.4A CN102526748B (en) | 2011-12-27 | 2011-12-27 | Oral tablet containing Valsartan, Hydrochioro and Amlodipine Besylate Tablet |
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| CN201110462594.4A CN102526748B (en) | 2011-12-27 | 2011-12-27 | Oral tablet containing Valsartan, Hydrochioro and Amlodipine Besylate Tablet |
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| CN102526748A CN102526748A (en) | 2012-07-04 |
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| CN103479643A (en) * | 2013-10-10 | 2014-01-01 | 沈阳药科大学 | Preparation method of compound preparation for treating high blood pressure |
| CN106511289A (en) * | 2015-09-10 | 2017-03-22 | 湖北生物医药产业技术研究院有限公司 | Benzenesulfonicacid lapatinib tablets and preparing method thereof |
| CN109498626A (en) * | 2017-09-14 | 2019-03-22 | 北京万全德众医药生物技术有限公司 | A kind of stable compound preparation valsartan amlodipine prescription and preparation method thereof |
| CN107823170B (en) * | 2017-12-15 | 2020-07-07 | 湖南千金协力药业有限公司 | Valsartan amlodipine tablet and preparation method thereof |
| CN107951849B (en) * | 2017-12-15 | 2020-07-07 | 湖南千金协力药业有限公司 | Amlodipine besylate tablet and preparation method thereof |
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| CN101744813A (en) * | 2010-01-21 | 2010-06-23 | 扬子江药业集团有限公司 | Compound amlodipine and valsartan solid preparation and preparation method thereof |
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| CN101744813A (en) * | 2010-01-21 | 2010-06-23 | 扬子江药业集团有限公司 | Compound amlodipine and valsartan solid preparation and preparation method thereof |
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