CN102440993B - Amlodipine benazepril pharmaceutical composition - Google Patents
Amlodipine benazepril pharmaceutical composition Download PDFInfo
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- CN102440993B CN102440993B CN 201110407064 CN201110407064A CN102440993B CN 102440993 B CN102440993 B CN 102440993B CN 201110407064 CN201110407064 CN 201110407064 CN 201110407064 A CN201110407064 A CN 201110407064A CN 102440993 B CN102440993 B CN 102440993B
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- SRTZYSFUFGOMFR-FKLPMGAJSA-N 2-[(3s)-3-[[(2s)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl]acetic acid;3-o-ethyl 5-o-methyl 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl.C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 SRTZYSFUFGOMFR-FKLPMGAJSA-N 0.000 title claims abstract description 47
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 14
- 239000000203 mixture Substances 0.000 claims abstract description 44
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 30
- 239000008101 lactose Substances 0.000 claims abstract description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 17
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 17
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 17
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 17
- 239000011734 sodium Substances 0.000 claims abstract description 16
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 16
- 229960000528 amlodipine Drugs 0.000 claims abstract description 15
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 claims abstract description 9
- 229960004530 benazepril Drugs 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims description 51
- ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 claims description 39
- 229960003619 benazepril hydrochloride Drugs 0.000 claims description 30
- VPSRQEHTHIMDQM-FKLPMGAJSA-N benazepril hydrochloride Chemical compound Cl.C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 VPSRQEHTHIMDQM-FKLPMGAJSA-N 0.000 claims description 30
- 229960004005 amlodipine besylate Drugs 0.000 claims description 25
- 238000005070 sampling Methods 0.000 claims description 23
- 239000000741 silica gel Substances 0.000 claims description 21
- 229910002027 silica gel Inorganic materials 0.000 claims description 21
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 20
- 238000012360 testing method Methods 0.000 claims description 15
- 238000001514 detection method Methods 0.000 claims description 13
- 238000005303 weighing Methods 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 238000012216 screening Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 abstract description 17
- 238000005516 engineering process Methods 0.000 abstract description 6
- 230000008901 benefit Effects 0.000 abstract description 4
- 239000000314 lubricant Substances 0.000 abstract description 4
- 239000000843 powder Substances 0.000 abstract description 4
- 239000000945 filler Substances 0.000 abstract description 3
- 229910002012 Aerosil® Inorganic materials 0.000 abstract 1
- 229920002472 Starch Polymers 0.000 abstract 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 abstract 1
- SJSNKICFTZWKLT-KEHAGZLWSA-N benzenesulfonic acid;2-[(3s)-3-[[(2s)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-2-oxo-4,5-dihydro-3h-1-benzazepin-1-yl]acetic acid;3-o-ethyl 5-o-methyl 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate;hydrochloride Chemical compound Cl.OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl.C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 SJSNKICFTZWKLT-KEHAGZLWSA-N 0.000 abstract 1
- 239000007884 disintegrant Substances 0.000 abstract 1
- 239000008107 starch Substances 0.000 abstract 1
- 235000019698 starch Nutrition 0.000 abstract 1
- 239000002994 raw material Substances 0.000 description 13
- 239000003814 drug Substances 0.000 description 12
- 238000009702 powder compression Methods 0.000 description 9
- 238000004090 dissolution Methods 0.000 description 7
- 239000008187 granular material Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- 206010020772 Hypertension Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 description 2
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
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- 230000002950 deficient Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
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- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- 229940042746 amlodipine / benazepril Drugs 0.000 description 1
- -1 amlodipine/benazepril compound Chemical class 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 229960004067 benazeprilat Drugs 0.000 description 1
- MADRIHWFJGRSBP-ROUUACIJSA-N benazeprilat Chemical compound C([C@H](N[C@H]1CCC2=CC=CC=C2N(C1=O)CC(=O)O)C(O)=O)CC1=CC=CC=C1 MADRIHWFJGRSBP-ROUUACIJSA-N 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
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- 238000003825 pressing Methods 0.000 description 1
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- 239000000126 substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an amlodipine and benazepril composition which is a tablet. The amlodipine benazepril tablet is obtained by treating amlodipine besylate and benazepril hydrochloride as active components, aerosil as a lubricant, lactose and microcrystalline cellulose as fillers and sodium carboxymethyl starch as a disintegrant and adopting a direct powder tabletting technology. The method has the advantages of simple process, and energy and time saving; and the prepared tablet has the advantages of stable quality, high dissolvability, and good disintegration.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to the pharmaceutical composition of a kind of amlodipine and benazepril, described pharmaceutical composition is tablet.
Background technology
Hypertension is a Major Risk Factors in the cardiovascular disease death incident, its prevalence accounts for adult's 10%～30%, it only is 40% that single drug is treated hypertensive effective percentage, can improve curative effect although increase dosage, but also increased the incidence rate of untoward reaction simultaneously, for improving curative effect, reduce the incidence rate of cardiovascular event, reduce target organ damage, usually with angiotensin converting enzyme inhibitor and calcium antagonist drug combination treatment hypertension, safe and effective, have good toleration.
Amlodipine Besylate Tablet (amlodipine besylate) is the long-acting bihydropyridine type calcium antagonists of 2nd generation, but diastole coronary vasodilator and whole body blood vessel increase coronary flow, reduce blood pressure, and are mainly used in clinically treating hypertension and angina pectoris.Be hydrolyzed to benazeprilat in benazepril hydrochloride (benazepril hydrochloride) liver, become a kind of emulative angiotensin converting enzyme inhibitor, vascular resistance is reduced, Aldosterone Secretion reduces, serum renin activity increases, also by suppressing the Kallidin I degraded vascular resistance is reduced, produce hypotensive effect.Amlodipine benazepril sheet is two kinds of highly effectively compound formulations of antihypertensive drugs, and antihypertensive effect is better than single leading medicine.
The preparation technology of existing amlodipine benazepril sheet mostly is wet granule compression tablet.Also have first by wet granulation prepare the benazepril compositions, dry process prepares the amlodipine compositions, rear mixing adds the technique that pharmaceutical excipient is made amlodipine/benazepril compound preparation, but at present, domestic not yet have the direct powder compression of employing technology to prepare amlodipine benazepril sheet.
Mainly there is following defective in the amlodipine benazepril sheet that existing technique prepares:
1, the dissolution of Amlodipine Besylate Tablet is lower in the amlodipine benazepril sheet for preparing, and is unsuitable for the medicine quick acting, and clinical practice is had certain influence.Thereby, need to adopt Innovative method to prepare amlodipine benazepril sheet, for example, can improve its stripping by micronization, when reality prepares, behind the hydrophobicity crushing material, along with reducing of particle diameter, surface free energy increases, the phenomenon that particle easily reassembles, so the actual benefit of pulverizing is not high; On the other hand, because the hydrophobicity material particular diameter is too little, the increase of specific surface area, the hydrophobicity of tablet is strengthened, be unfavorable on the contrary the stripping of tablet;
2, general preparation technology adopts magnesium stearate as lubricant, magnesium stearate is lyophobic dust, after the excessive or excessive agitation of consumption, can cover particle surface affects the infiltration of water, cause amlodipine benazepril sheet disintegrate (or stripping) to postpone, be unfavorable for that medicine brings into play therapeutic effect fast;
3, adopt traditional wet granule compression tablet technique to prepare amlodipine benazepril sheet: process is complicated, consider the factors such as adhesive addition, particle drying time, the pure time of sieving of granulating, the machine quantity of need of production is many, the space is large, and because some factor need to rely on micro-judgment, therefore may cause unstable product quality, difference is large etc. between batch.
Summary of the invention
It is high that one of purpose of the present invention provides a kind of dissolution, the amlodipine benazepril tablet that disintegrative is good.
The technical scheme that realizes above-mentioned purpose is as follows:
A kind of amlodipine benazepril tablet, take Amlodipine Besylate Tablet and benazepril hydrochloride as active component, with micropowder silica gel as lubricant, with lactose and microcrystalline Cellulose as filler, as disintegrating agent, the percentage by weight of wherein said each raw material components is with Sodium Hydroxymethyl Stalcs:
Preferably, the percentage by weight of described each raw material components is:
Most preferably, the percentage by weight of described each raw material components is:
Preferably, the weight ratio of lactose and microcrystalline Cellulose is 1-4:1 in the described filler.
Another object of the present invention provides a kind of preparation method of above-mentioned amlodipine benazepril tablet.
The technical scheme that realizes above-mentioned purpose is as follows:
A kind of method for preparing amlodipine benazepril tablet may further comprise the steps:
A, with Amlodipine Besylate Tablet and benazepril hydrochloride crushing screening, take by weighing respectively in proportion Amlodipine Besylate Tablet, benazepril hydrochloride, micropowder silica gel, lactose, microcrystalline Cellulose and Sodium Hydroxymethyl Stalcs;
B, the 15-20% that gets described lactose total amount and Amlodipine Besylate Tablet place high efficient mixer to rotate mix homogeneously, obtain the batch mixing I;
C, in the batch mixing I, be sequentially added into remaining lactose and benazepril hydrochloride, rotate mix homogeneously, obtain the batch mixing II;
D, successively batch mixing II, microcrystalline Cellulose, Sodium Hydroxymethyl Stalcs, micropowder silica gel are placed automatic lifting hopper mixer to rotate mix homogeneously in order, obtain whole batch mixing III;
E, whole batch mixing III direct compression namely get described amlodipine benazepril tablet;
Preferably, the rotating speed of high efficient mixer and automatic lifting hopper mixer is 12r/min in described step b, c, the d mixed process.
Advantage of the present invention and good effect
1, the present invention adopts technique of direct powder compression to prepare amlodipine benazepril tablet, and its disintegrating agent is different from the disintegrating agent in the wet granulation, not can owing to early stage contact wetting reduce disintegrating property, thereby guaranteed good disintegration properties.In addition, owing to do not carry out the granule tabletting, can not form large bulk granule behind the disintegration of tablet, but form the relatively large fine powder of specific surface area, can distribute preferably in vivo, improve the dispersed homogeneous degree of tablet, help release, the absorption of medicine.Therefore technique of direct powder compression provided by the invention has improved dissolution and the disintegrative of amlodipine benazepril sheet greatly;
2, technique of direct powder compression provided by the invention, after the powder of medicine sieved respectively with suitable adjuvant and mixing, direct pressing is in blocks without granulating (wet grain or dried granule).Preparation process is simple, the energy-and time-economizing, and mass discrepancy between reducing batch makes medicine more stable;
Therefore 3, amlodipine benazepril tablet provided by the invention, as lubricant, it has hydrophilic with micropowder silica gel, does not affect the profit of invading of water, and the stripping of medicine is had great facilitation.
The specific embodiment
The present invention is further elaborated below in conjunction with embodiment.
Embodiment 1
Each raw material components amount that present embodiment prepares amlodipine benazepril tablet is:
The concrete steps that present embodiment prepares amlodipine benazepril tablet are as follows:
A, with Amlodipine Besylate Tablet and benazepril hydrochloride crushing screening, take by weighing respectively in proportion Amlodipine Besylate Tablet, benazepril hydrochloride, micropowder silica gel, lactose, microcrystalline Cellulose and Sodium Hydroxymethyl Stalcs;
B, in the lactose that takes by weighing, get wherein 20% lactose and Amlodipine Besylate Tablet mix homogeneously in high efficient mixer, the rotating speed of high efficient mixer is 12r/min, mix 5min, the uniformity of sampling detection level, uniformity of dosage units is up to standard, finishes to mix namely to obtain the batch mixing I;
C, add successively remaining lactose and benazepril hydrochloride in the batch mixing I, mix homogeneously, the rotating speed of high efficient mixer are 12r/min, mix 13min, the uniformity of sampling and testing content, and uniformity of dosage units is up to standard, finishes to mix namely to obtain the batch mixing II;
D, successively batch mixing II, microcrystalline Cellulose, Sodium Hydroxymethyl Stalcs, micropowder silica gel are placed automatic lifting hopper mixer mix homogeneously in order, the rotating speed of high efficient mixer is 12r/min, mix 13min, the uniformity of sampling and testing content, uniformity of dosage units is up to standard, finishes to mix namely to obtain whole batch mixing III;
E, get the content detection that whole batch mixing III is carried out benazepril hydrochloride and amlodipine, determine that sheet is heavy, whole batch mixing III tabletting on tablet machine, content uniformity is ± 5%, hardness 〉=23N namely gets described amlodipine benazepril tablet;
In above-mentioned steps b, c, d, every add a kind of raw material in efficient mixing machine or the automatic lifting hopper mixer after, need the material face spread out to pat as far as possible can add next raw material after whole; Before adding raw material, beginning to mix, need the material face spread out to pat as far as possible can begin to mix after whole; Need the sampling detection level uniformity after mix finishing, before sampling, also need the material face spread out to pat as far as possible can begin sampling after whole.
Embodiment 2
Each raw material components amount that present embodiment prepares amlodipine benazepril tablet is:
Present embodiment prepares the concrete steps of amlodipine benazepril tablet with embodiment 1.
Embodiment 3
Each raw material components amount that present embodiment prepares amlodipine benazepril tablet is:
Present embodiment prepares the concrete steps of amlodipine benazepril tablet with embodiment 1.
Embodiment 4
Each raw material components amount that present embodiment prepares amlodipine benazepril tablet is:
Present embodiment prepares the concrete steps of amlodipine benazepril tablet with embodiment 1.
Embodiment 5
Each raw material components amount that present embodiment prepares amlodipine benazepril tablet is:
Present embodiment prepares the concrete steps of amlodipine benazepril tablet with embodiment 1.
Embodiment 6
Stability experiment
According to " chemicals stability study technological guidance principle " and " Chinese pharmacopoeia version in 2010 two ones " appendix XIX C crude drug and pharmaceutical preparation stability test guidelines " is carried out stability test to sample.Get 3 batches in the sample of embodiment 1 preparation, lot number is respectively 11032401,11032402 and 11032403, places respectively lower 6 months of the condition of 40 ℃+2 ℃ of temperature, relative humidity 75%+5%.Investigate indices respectively at the 1st, 2,3,6 sampling at the end of month, the results are shown in following table:
Table 1 amlodipine benazepril tablet stability measurement result
As seen from the above table, the prepared amlodipine benazepril tablet of the present invention has good stability, places after 6 months, and its property indices still remains unchanged substantially, and batch between mass discrepancy very little.
The described amlodipine benazepril of embodiment 2-5 tablet has all been carried out similar experiment, the result is similar to the test result of embodiment 1 sample, show that all amlodipine benazepril tablet provided by the invention has good stability, the mass discrepancy between each batch is also very little.
Embodiment 7
Get respectively the amlodipine benazepril tablet that four kinds of different modes obtain, wherein compressing dry granulation and wet method tabletting add the sample proportioning raw materials of micropowder silica gel with embodiment 1, the proportioning of other raw material of sample that does not add micropowder silica gel is identical, and placing temperature is lower 18 months of 40 ℃+2 ℃, the condition of relative humidity 75%+5%.Respectively at the 1st, 3,6,12,18 the end of month sampling and measuring stripping property and disintegration, carry out stripping property and disintegrative experiment contrast:
The test result contrast is as follows:
Table 2 amlodipine benazepril Dissolution of Tablet and disintegration comparing result
By the test comparison result of upper table as can be known, technique of direct powder compression provided by the present invention effectively raises dissolution and the disintegrating property of medicine, because technique of direct powder compression not can owing to early stage contact wetting guaranteed good disintegrative, in addition, direct powder compression does not carry out granule tabletting process, can not reunite behind the disintegration of tablet and form the larger fine powder of surface area ratio, Effective Raise dispersed homogeneous degree and the dissolution of tablet.And under the same preparation technology, the adding of micropowder silica gel effectively raises stripping property and the disintegrative of amlodipine benazepril tablet, because micropowder silica gel has hydrophilic as the fluidizer of direct powder compression, therefore do not affect the profit of invading of water, promoted the stripping of medicine.
To sum up, the present invention has overcome the defective of prior art with the adding of as a result micropowder silica gel of technique of direct powder compression, the energy-and time-economizing, and the amlodipine benazepril tablet quality for preparing is stable, dissolution is high, disintegrative good.
Be specific embodiments of the invention only below, do not limit protection scope of the present invention with this; Any replacement and the improvement done on the basis of not violating the present invention's design all belong to protection scope of the present invention.
Claims (5)
1. the pharmaceutical composition of an amlodipine and benazepril is characterized in that described pharmaceutical composition is tablet, and the weight of each component is:
Prepare altogether 500,000 of amlodipine benazepril sheets;
The concrete steps of preparation tablet are as follows:
A, with Amlodipine Besylate Tablet and benazepril hydrochloride crushing screening, take by weighing respectively in proportion Amlodipine Besylate Tablet, benazepril hydrochloride, micropowder silica gel, lactose, microcrystalline Cellulose and Sodium Hydroxymethyl Stalcs;
B, in the lactose that takes by weighing, get wherein 20% lactose and Amlodipine Besylate Tablet mix homogeneously in high efficient mixer, the rotating speed of high efficient mixer is 12r/min, mix 5min, the uniformity of sampling detection level, uniformity of dosage units is up to standard, finishes to mix namely to obtain batch mixing I;
C, add successively remaining lactose and benazepril hydrochloride in the batch mixing I, mix homogeneously, the rotating speed of high efficient mixer are 12r/min, mix 13min, the uniformity of sampling and testing content, and uniformity of dosage units is up to standard, finishes to mix namely to obtain batch mixing II;
D, successively batch mixing II, microcrystalline Cellulose, Sodium Hydroxymethyl Stalcs, micropowder silica gel are placed automatic lifting hopper mixer mix homogeneously in order, the rotating speed of high efficient mixer is 12r/min, mix 13min, the uniformity of sampling and testing content, uniformity of dosage units is up to standard, finishes to mix namely to obtain whole batch mixing III;
E, get the content detection that whole batch mixing III carries out benazepril hydrochloride and amlodipine, determine that sheet is heavy, whole batch mixing III tabletting on tablet machine, content uniformity is ± 5%, hardness 〉=23N namely gets described amlodipine benazepril tablet.
2. the pharmaceutical composition of an amlodipine and benazepril is characterized in that described pharmaceutical composition is tablet, and the weight of each component is:
Prepare altogether 500,000 of amlodipine benazepril sheets;
The concrete steps of preparation tablet are as follows:
A, with Amlodipine Besylate Tablet and benazepril hydrochloride crushing screening, take by weighing respectively in proportion Amlodipine Besylate Tablet, benazepril hydrochloride, micropowder silica gel, lactose, microcrystalline Cellulose and Sodium Hydroxymethyl Stalcs;
B, in the lactose that takes by weighing, get wherein 20% lactose and Amlodipine Besylate Tablet mix homogeneously in high efficient mixer, the rotating speed of high efficient mixer is 12r/min, mix 5min, the uniformity of sampling detection level, uniformity of dosage units is up to standard, finishes to mix namely to obtain batch mixing I;
C, add successively remaining lactose and benazepril hydrochloride in the batch mixing I, mix homogeneously, the rotating speed of high efficient mixer are 12r/min, mix 13min, the uniformity of sampling and testing content, and uniformity of dosage units is up to standard, finishes to mix namely to obtain batch mixing II;
D, successively batch mixing II, microcrystalline Cellulose, Sodium Hydroxymethyl Stalcs, micropowder silica gel are placed automatic lifting hopper mixer mix homogeneously in order, the rotating speed of high efficient mixer is 12r/min, mix 13min, the uniformity of sampling and testing content, uniformity of dosage units is up to standard, finishes to mix namely to obtain whole batch mixing III;
E, get the content detection that whole batch mixing III carries out benazepril hydrochloride and amlodipine, determine that sheet is heavy, whole batch mixing III tabletting on tablet machine, content uniformity is ± 5%, hardness 〉=23N namely gets described amlodipine benazepril tablet.
3. the pharmaceutical composition of an amlodipine and benazepril is characterized in that described pharmaceutical composition is tablet, and the weight of each component is:
Prepare altogether 500,000 of amlodipine benazepril sheets;
The concrete steps of preparation tablet are as follows:
A, with Amlodipine Besylate Tablet and benazepril hydrochloride crushing screening, take by weighing respectively in proportion Amlodipine Besylate Tablet, benazepril hydrochloride, micropowder silica gel, lactose, microcrystalline Cellulose and Sodium Hydroxymethyl Stalcs;
B, in the lactose that takes by weighing, get wherein 20% lactose and Amlodipine Besylate Tablet mix homogeneously in high efficient mixer, the rotating speed of high efficient mixer is 12r/min, mix 5min, the uniformity of sampling detection level, uniformity of dosage units is up to standard, finishes to mix namely to obtain batch mixing I;
C, add successively remaining lactose and benazepril hydrochloride in the batch mixing I, mix homogeneously, the rotating speed of high efficient mixer are 12r/min, mix 13min, the uniformity of sampling and testing content, and uniformity of dosage units is up to standard, finishes to mix namely to obtain batch mixing II;
D, successively batch mixing II, microcrystalline Cellulose, Sodium Hydroxymethyl Stalcs, micropowder silica gel are placed automatic lifting hopper mixer mix homogeneously in order, the rotating speed of high efficient mixer is 12r/min, mix 13min, the uniformity of sampling and testing content, uniformity of dosage units is up to standard, finishes to mix namely to obtain whole batch mixing III;
E, get the content detection that whole batch mixing III carries out benazepril hydrochloride and amlodipine, determine that sheet is heavy, whole batch mixing III tabletting on tablet machine, content uniformity is ± 5%, hardness 〉=23N namely gets described amlodipine benazepril tablet.
4. the pharmaceutical composition of an amlodipine and benazepril is characterized in that described pharmaceutical composition is tablet, and the weight of each component is:
Prepare altogether 500,000 of amlodipine benazepril sheets;
The concrete steps of preparation tablet are as follows:
A, with Amlodipine Besylate Tablet and benazepril hydrochloride crushing screening, take by weighing respectively in proportion Amlodipine Besylate Tablet, benazepril hydrochloride, micropowder silica gel, lactose, microcrystalline Cellulose and Sodium Hydroxymethyl Stalcs;
B, in the lactose that takes by weighing, get wherein 20% lactose and Amlodipine Besylate Tablet mix homogeneously in high efficient mixer, the rotating speed of high efficient mixer is 12r/min, mix 5min, the uniformity of sampling detection level, uniformity of dosage units is up to standard, finishes to mix namely to obtain batch mixing I;
C, add successively remaining lactose and benazepril hydrochloride in the batch mixing I, mix homogeneously, the rotating speed of high efficient mixer are 12r/min, mix 13min, the uniformity of sampling and testing content, and uniformity of dosage units is up to standard, finishes to mix namely to obtain batch mixing II;
D, successively batch mixing II, microcrystalline Cellulose, Sodium Hydroxymethyl Stalcs, micropowder silica gel are placed automatic lifting hopper mixer mix homogeneously in order, the rotating speed of high efficient mixer is 12r/min, mix 13min, the uniformity of sampling and testing content, uniformity of dosage units is up to standard, finishes to mix namely to obtain whole batch mixing III;
E, get the content detection that whole batch mixing III carries out benazepril hydrochloride and amlodipine, determine that sheet is heavy, whole batch mixing III tabletting on tablet machine, content uniformity is ± 5%, hardness 〉=23N namely gets described amlodipine benazepril tablet.
5. the pharmaceutical composition of an amlodipine and benazepril is characterized in that described pharmaceutical composition is tablet, and the weight of each component is:
Prepare altogether 500,000 of amlodipine benazepril sheets;
The concrete steps of preparation tablet are as follows:
A, with Amlodipine Besylate Tablet and benazepril hydrochloride crushing screening, take by weighing respectively in proportion Amlodipine Besylate Tablet, benazepril hydrochloride, micropowder silica gel, lactose, microcrystalline Cellulose and Sodium Hydroxymethyl Stalcs;
B, in the lactose that takes by weighing, get wherein 20% lactose and Amlodipine Besylate Tablet mix homogeneously in high efficient mixer, the rotating speed of high efficient mixer is 12r/min, mix 5min, the uniformity of sampling detection level, uniformity of dosage units is up to standard, finishes to mix namely to obtain batch mixing I;
C, add successively remaining lactose and benazepril hydrochloride in the batch mixing I, mix homogeneously, the rotating speed of high efficient mixer are 12r/min, mix 13min, the uniformity of sampling and testing content, and uniformity of dosage units is up to standard, finishes to mix namely to obtain batch mixing II;
D, successively batch mixing II, microcrystalline Cellulose, Sodium Hydroxymethyl Stalcs, micropowder silica gel are placed automatic lifting hopper mixer mix homogeneously in order, the rotating speed of high efficient mixer is 12r/min, mix 13min, the uniformity of sampling and testing content, uniformity of dosage units is up to standard, finishes to mix namely to obtain whole batch mixing III;
E, get the content detection that whole batch mixing III carries out benazepril hydrochloride and amlodipine, determine that sheet is heavy, whole batch mixing III tabletting on tablet machine, content uniformity is ± 5%, hardness 〉=23N namely gets described amlodipine benazepril tablet.
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| CN 201110407064 CN102440993B (en) | 2011-12-08 | 2011-12-08 | Amlodipine benazepril pharmaceutical composition |
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| CN 201110407064 CN102440993B (en) | 2011-12-08 | 2011-12-08 | Amlodipine benazepril pharmaceutical composition |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1526398A (en) * | 2003-09-19 | 2004-09-08 | 启东盖天力药业有限公司 | Compound blood pressure reducing prepn containing angiotonin converzyme inhibitor, calcium ion agonist and Estazolam |
| CN1827111A (en) * | 2006-04-14 | 2006-09-06 | 北京润德康医药技术有限公司 | Pharmaceutical composition using benazepril hydrochloride amlodipine besylate as active ingredients, its preparation method and use |
| CN101137367A (en) * | 2003-10-20 | 2008-03-05 | 诺瓦提斯公司 | Benazapril and amlodipine besylate for reducing cardiovascular morbidity |
| CN102114017A (en) * | 2011-01-05 | 2011-07-06 | 王定豪 | Medicinal composition containing amlodipine and perindopril and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CA2620018A1 (en) * | 2005-09-28 | 2007-04-12 | Mali Kadosh | Stable combinations of amlodipine besylate and benazepril hydrochloride |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1526398A (en) * | 2003-09-19 | 2004-09-08 | 启东盖天力药业有限公司 | Compound blood pressure reducing prepn containing angiotonin converzyme inhibitor, calcium ion agonist and Estazolam |
| CN101137367A (en) * | 2003-10-20 | 2008-03-05 | 诺瓦提斯公司 | Benazapril and amlodipine besylate for reducing cardiovascular morbidity |
| CN1827111A (en) * | 2006-04-14 | 2006-09-06 | 北京润德康医药技术有限公司 | Pharmaceutical composition using benazepril hydrochloride amlodipine besylate as active ingredients, its preparation method and use |
| CN102114017A (en) * | 2011-01-05 | 2011-07-06 | 王定豪 | Medicinal composition containing amlodipine and perindopril and application thereof |
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