CN102440993A - Amlodipine benazepril tablet and preparation method thereof - Google Patents
Amlodipine benazepril tablet and preparation method thereof Download PDFInfo
- Publication number
- CN102440993A CN102440993A CN201110407064XA CN201110407064A CN102440993A CN 102440993 A CN102440993 A CN 102440993A CN 201110407064X A CN201110407064X A CN 201110407064XA CN 201110407064 A CN201110407064 A CN 201110407064A CN 102440993 A CN102440993 A CN 102440993A
- Authority
- CN
- China
- Prior art keywords
- amlodipine
- tablet
- benazepril
- lactose
- batch mixing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to an amlodipine benazepril tablet and a preparation method thereof. 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 a kind of amlodipine benazepril tablet and preparation method thereof.
Background technology
Hypertension is a main hazard factor in the cardiovascular disease death incident, and it is adult 10%～30% that its prevalence accounts for, and single drug is treated hypertensive effective percentage and is merely 40%; Can improve curative effect though increase dosage; But also increased incidence rate of adverse reaction simultaneously,, reduced the incidence rate of cardiovascular event for improving curative effect; Reduce target organ damage; Usually with angiotensin converting enzyme inhibitor and calcium antagonist drug combination treatment hypertension, safe and effective, have good tolerability.
Amlodipine Besylate Tablet (amlodipine besylate) is a long lasting bihydropyridine type calcium antagonists of the 2nd generation, but diastole coronary vasodilator and whole body blood vessel, and coronary blood flow increasing brings high blood pressure down, and is mainly used in treatment hypertension and angina pectoris clinically.Be hydrolyzed to benazeprilat in benazepril hydrochloride (benazepril hydrochloride) liver; Become a kind of emulative angiotensin converting enzyme inhibitor; Vascular resistance is reduced, and the aldosterone secretion reduces, and serum renin activity increases; Also vascular resistance is reduced, produce hypotensive effect through suppressing the Kallidin I degraded.Amlodipine benazepril sheet is two kinds of highly effectively compound formulations of antihypertensive drugs, and antihypertensive effect is superior to single leading medicine.
Mostly the preparation technology of existing amlodipine benazepril sheet is wet granule compression tablet.Also have and prepare the amlodipine compositions through wet granulation benazepril compositions, dry process earlier; The back is mixed and is added the technology that pharmaceutical excipient is processed amlodipine/benazepril compound preparation; But at present, domestic do not have the direct powder compression of employing technology to prepare amlodipine benazepril sheet as yet.
Mainly there is following defective in the amlodipine benazepril sheet that existing prepared obtains:
1, the dissolution of Amlodipine Besylate Tablet is lower in the amlodipine benazepril sheet for preparing, and is inappropriate for the medicine quick acting, and clinical practice is had certain influence.Thereby, need to adopt improved method to prepare amlodipine benazepril sheet, for example; Can improve its stripping through micronization, when actual fabrication, after the hydrophobicity material is pulverized; Along with reducing of particle diameter, surface free energy increases, the easy phenomenon that reassembles of particle; So the actual benefit of pulverizing is not high; On the other hand,, the hydrophobicity of tablet is strengthened, be unfavorable for the stripping of tablet on the contrary because the hydrophobicity material particular diameter is too little, the increase of specific surface area;
2, general preparation technology adopts magnesium stearate as lubricant; Magnesium stearate is a lyophobic dust, after the excessive or excessive agitation of consumption, can cover the infiltration that particle surface influences 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 pelletizing press sheet prepared amlodipine benazepril sheet: process is complicated; Consider factors such as adhesive addition, particle drying time, the pure time of sieving of granulating; The machine quantity that production needs is many, the space is big; And because some factor need the dependence experience judge that therefore possibly cause unstable product quality, batch differences is big etc.
Summary of the invention
It is high that one of the object of the invention provides a kind of dissolution, the amlodipine benazepril tablet that disintegrative is good.
The technical scheme that realizes above-mentioned purpose is following:
A kind of amlodipine benazepril tablet; With Amlodipine Besylate Tablet and benazepril hydrochloride is 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:
Sodium Hydroxymethyl Stalcs 1%-5%, more than the summation of each component be 100%.
Preferably, the percentage by weight of said each raw material components is:
Sodium Hydroxymethyl Stalcs 1.5%-2.5%, more than the summation of each component be 100%.
Most preferably, the percentage by weight of said each raw material components is:
Preferably, the weight ratio of lactose and microcrystalline Cellulose is 1-4 in the said filler: 1.
Another object of the present invention provides a kind of method for preparing of above-mentioned amlodipine benazepril tablet.
The technical scheme that realizes above-mentioned purpose is following:
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 Amlodipine Besylate Tablet, benazepril hydrochloride, micropowder silica gel, lactose, microcrystalline Cellulose and Sodium Hydroxymethyl Stalcs in proportion respectively;
B, the 15-20% that gets said lactose total amount and Amlodipine Besylate Tablet place the high efficient mixed machine to rotate mix homogeneously, obtain batch mixing I;
C, in mixture I, be sequentially added into remaining lactose and benazepril hydrochloride, rotate mix homogeneously, obtain batch mixing II;
D, place automatic lifting hopper mixer to rotate mix homogeneously batch mixing II, microcrystalline Cellulose, Sodium Hydroxymethyl Stalcs, micropowder silica gel successively in order, obtain whole batch mixing III;
E, whole batch mixing III direct compression promptly get described amlodipine benazepril tablet;
Preferably, high efficient mixed machine and the rotating speed that promotes the hopper mixer automatically are 12r/min in said 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,, can not form big 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 owing to do not carry out the granule tabletting.Therefore technique of direct powder compression provided by the invention has improved the 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 mix, directly compacting was 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, its possess hydrophilic property does not influence the profit of invading of water with micropowder silica gel, and the stripping of medicine is had great facilitation.
The specific embodiment
Below in conjunction with embodiment the present invention is done further elaboration.
Embodiment 1
Each raw material components amount that present embodiment prepares amlodipine benazepril tablet is:
Micropowder silica gel 1kg, total amount is 100Kg, prepares 500,000 of amlodipine benazepril sheets altogether.
The concrete steps that present embodiment prepares amlodipine benazepril tablet are following:
A, with Amlodipine Besylate Tablet and benazepril hydrochloride crushing screening, take by weighing Amlodipine Besylate Tablet, benazepril hydrochloride, micropowder silica gel, lactose, microcrystalline Cellulose and Sodium Hydroxymethyl Stalcs in proportion respectively;
B, in the lactose that is taken by weighing, get wherein 20% lactose and Amlodipine Besylate Tablet mix homogeneously in the high efficient mixed machine, the rotating speed of high efficient mixed machine is 12r/min; Mix 5min; The uniformity of sampling detection level, uniformity of dosage units is up to standard, finishes to mix promptly to obtain batch mixing I;
C, add remaining lactose and benazepril hydrochloride in the mixture I successively, mix homogeneously, the rotating speed of high efficient mixed machine are 12r/min, mix 13min, the uniformity of sampling and testing content, and uniformity of dosage units is up to standard, finishes to mix promptly 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 mixed machine is 12r/min; Mix 13min; The uniformity of sampling and testing content, uniformity of dosage units is up to standard, finishes to mix promptly to obtain whole batch mixing III;
E, get the content detection that whole batch mixing III carries out benazepril hydrochloride and amlodipine, confirm that sheet is heavy, whole batch mixing III tabletting on tablet machine, content uniformity is ± 5%, hardness >=23N promptly gets described amlodipine benazepril tablet;
In above-mentioned steps b, c, d, every to efficient mixing machine or automatically promote add a kind of raw material in the 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:
Micropowder silica gel 1.5kg, total amount is 100Kg, prepares 500,000 of amlodipine benazepril sheets altogether.
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:
Micropowder silica gel 0.5kg, total amount is 100Kg, prepares 500,000 of amlodipine benazepril sheets altogether.
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:
Micropowder silica gel 0.1kg, total amount is 100Kg, prepares 500,000 of amlodipine benazepril sheets altogether.
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:
Micropowder silica gel 3kg, total amount is 100Kg, prepares 500,000 of amlodipine benazepril sheets altogether.
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 following 6 months of the condition of 40 ℃+2 ℃ of temperature, relative humidity 75%+5% respectively.Investigate each item index respectively at the 1st, 2,3,6 sampling at the end of month, the result sees the following form:
Table 1 amlodipine benazepril tablet stability is measured the result
Can be known that by last table the prepared amlodipine benazepril tablet of the present invention has good stability, places after 6 months, its each item performance indications still remain unchanged basically, 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 with 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 the amlodipine benazepril tablet that four kinds of different modes obtain respectively; Wherein compressing dry granulation and wet method tabletting add micropowder silica gel the sample proportioning raw materials with embodiment 1; Other proportion of raw materials of sample that does not add micropowder silica gel is identical, and placing temperature is following 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:
Test result contrasts as follows:
Table 2 amlodipine benazepril tablet dissolution and disintegration comparing result
Test comparison result by last table can know; Technique of direct powder compression provided by the present invention effectively raises the 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 bigger fine powder of surface area ratio, effectively improve the dispersed homogeneous degree and the dissolution of tablet.And under the same preparation technology; The adding of micropowder silica gel effectively raises the stripping property and the disintegrative of amlodipine benazepril tablet, because micropowder silica gel is as the fluidizer of direct powder compression, possess hydrophilic property; Therefore do not influence 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 technique of direct powder compression micropowder silica gel as a result, the energy-and time-economizing, and the amlodipine benazepril tablet quality for preparing is stable, dissolution is high, disintegrative good.
More than be merely specific embodiment of the present invention, do not limit protection scope of the present invention with this; Any replacement and the improvement on the basis of not violating the present invention's design, done all belong to protection scope of the present invention.
Claims (6)
1. amlodipine benazepril tablet; It is characterized in that; With Amlodipine Besylate Tablet and benazepril hydrochloride is 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:
Sodium Hydroxymethyl Stalcs 1%-5%, more than the summation of each component be 100%.
2. a kind of amlodipine benazepril tablet according to claim 1 is characterized in that the percentage by weight of wherein said each raw material components is:
Sodium Hydroxymethyl Stalcs 1.5%-2.5%, more than the summation of each component be 100%.
3. a kind of amlodipine benazepril tablet according to claim 1 and 2 is characterized in that the percentage by weight of wherein said each raw material components is:
4. according to each described a kind of amlodipine benazepril tablet of claim 1-3, it is characterized in that the weight ratio of lactose and microcrystalline Cellulose is 1-4 in the filler: 1.
5. a method for preparing like each described amlodipine benazepril tablet of claim 1-4 is characterized in that, may further comprise the steps:
A, with Amlodipine Besylate Tablet and benazepril hydrochloride crushing screening, take by weighing Amlodipine Besylate Tablet, benazepril hydrochloride, micropowder silica gel, lactose, microcrystalline Cellulose and Sodium Hydroxymethyl Stalcs in proportion respectively;
B, the 15-20% that gets said lactose total amount and Amlodipine Besylate Tablet place the high efficient mixed machine to rotate mix homogeneously, obtain batch mixing I;
C, in mixture I, be sequentially added into remaining lactose and benazepril hydrochloride, rotate mix homogeneously, 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, obtain whole batch mixing III;
E, with whole batch mixing III direct compression, hardness >=23N promptly gets described amlodipine benazepril tablet;
6. a kind of method for preparing amlodipine benazepril tablet according to claim 4 is characterized in that, high efficient mixed machine and the rotating speed that promotes the hopper mixer automatically are 12r/min in said step b, c, the d mixed process.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110407064 CN102440993B (en) | 2011-12-08 | 2011-12-08 | Amlodipine benazepril pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110407064 CN102440993B (en) | 2011-12-08 | 2011-12-08 | Amlodipine benazepril pharmaceutical composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102440993A true CN102440993A (en) | 2012-05-09 |
| CN102440993B CN102440993B (en) | 2013-04-17 |
Family
ID=46004253
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110407064 Active CN102440993B (en) | 2011-12-08 | 2011-12-08 | Amlodipine benazepril pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102440993B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109674794A (en) * | 2017-10-19 | 2019-04-26 | 上海复星星泰医药科技有限公司 | A kind of Amlodipine benazepil pulsatile tablets and preparation method thereof |
Citations (5)
| 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 |
| WO2007040511A1 (en) * | 2005-09-28 | 2007-04-12 | Teva Pharmaceutical Industries Ltd. | Stable combinations of amlodipine besylate and benazepril hydrochloride |
| 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 |
-
2011
- 2011-12-08 CN CN 201110407064 patent/CN102440993B/en active Active
Patent Citations (5)
| 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 |
| WO2007040511A1 (en) * | 2005-09-28 | 2007-04-12 | Teva Pharmaceutical Industries Ltd. | Stable combinations of amlodipine besylate and benazepril hydrochloride |
| 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 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109674794A (en) * | 2017-10-19 | 2019-04-26 | 上海复星星泰医药科技有限公司 | A kind of Amlodipine benazepil pulsatile tablets and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102440993B (en) | 2013-04-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101327213B (en) | Irbesartan and hydrochlorothiazide pharmaceutical composition and preparation method thereof | |
| CN102266300A (en) | Gefitinib dispersible tablet and preparation method and application thereof | |
| CN104523640A (en) | Ticagrelor tablets and preparation method thereof | |
| CN105147614B (en) | A kind of solid pharmaceutical preparation and preparation method thereof including BIBW 2992MA2 | |
| CN103040774B (en) | Granulating and coating process of esomeprazole magnesium contained in esomeprazole magnesium enteric-coated tablet | |
| CN103610677A (en) | Repaglinide troche and preparation method thereof | |
| CN102793682A (en) | Rapid-release compound omeprazole tablet and preparation method thereof | |
| Ofori-Kwakye et al. | Formulation and quality evaluation of two conventional release tablet formulations | |
| CN109875972A (en) | A kind of olmesartan medoxomil/amlodipinepharmaceutical pharmaceutical composition | |
| CN102526748B (en) | Oral tablet containing Valsartan, Hydrochioro and Amlodipine Besylate Tablet | |
| CN102440993B (en) | Amlodipine benazepril pharmaceutical composition | |
| CN110354086B (en) | Preparation method of candesartan cilexetil tablets | |
| CN102462663A (en) | Felodipine pharmaceutical composition based on dry process granulation | |
| CN105456209A (en) | Topiroxostat tablet and preparation method thereof | |
| CN110237073B (en) | Olmesartan medoxomil amlodipine tablet and preparation method thereof | |
| CN106983726A (en) | Azilsartan piece and preparation method thereof | |
| CN102058872B (en) | Medicinal composition containing Lysinopril and amlodipine besilate and preparation method thereof | |
| CN102764254A (en) | Levetiracetam drug composition and preparation method thereof | |
| CN102697778A (en) | Valsartan amlodipine compound solid preparation and preparation method thereof | |
| CN103933004A (en) | Letrozole troche and preparation method of letrozole troche | |
| CN106822155B (en) | Piece and preparation method thereof in three Compound Tablet of efavirenz, Lamivudine and tenofovir disoproxil fumarate | |
| CN106420637A (en) | Ketotifen fumarate tablets and preparation method thereof | |
| CN111150710A (en) | Medicament composition of high-load lubricant and preparation method thereof | |
| CN103181905A (en) | Process for preparing pramipexole dihydrochloride tablets | |
| CN103142604A (en) | Acetaminophen and caffeine dispersible tablet, and its preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C53 | Correction of patent of invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Shi Meng Inventor after: Xia Chunsen Inventor after: Peng Wang Inventor before: Peng Wang |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: PENG WANG TO: SHI MENG XIA CHUNSEN PENG WANG |