CN102688245A - Stable amlodipine and benazepril medicinal composition and preparation method thereof - Google Patents
Stable amlodipine and benazepril medicinal composition and preparation method thereof Download PDFInfo
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- CN102688245A CN102688245A CN201210192076XA CN201210192076A CN102688245A CN 102688245 A CN102688245 A CN 102688245A CN 201210192076X A CN201210192076X A CN 201210192076XA CN 201210192076 A CN201210192076 A CN 201210192076A CN 102688245 A CN102688245 A CN 102688245A
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- benazepril
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Abstract
The invention relates to a medicinal composition subjected to physical separation and capable of improving the compatibility and stability of amlodipine and benazepril and a preparation method thereof. The amlodipine and benazepril or the medicinal salts of the two medicines are used as active ingredients, the physical separation of the amlodipine and benazepril can be realized by multiple medicinal preparation means such as by pressing into bi-layer tablets, adding the pellets of one medicine into the tablets of the other substance, integrating the pellets of various substances coated respectively into the same tablet or capsule, adopting a dual-cavity or multi-cavity drug delivery system and the like, and finally the compatibility of the two active ingredients and the stability of the medicinal composition are improved. According to the technical means adopted in the invention, the bi-layer tablets, pellet tablets, single-cavity or dual-cavity (pellet) capsules, orally disintegrating tablets and the like can be developed. The medicinal composition provided by the invention can be used for treating various types of hypertension.
Description
Technical field
The present invention relates to a kind of Pharmaceutical composition that contains amlodipine and benazepril and preparation method thereof, belong to medical technical field.
Background technology
The change of Along with people's growth in the living standard and diet structure, life style, the incidence rate of hypertension has the trend that progressively increases in recent years.Hypertension can cause organ injuries such as patient's heart, brain, kidney, and with sugar, lipid metabolic disorder and diabetes substantial connection is arranged, and obviously reduces patients ' life quality, when serious even threat to life.Therefore, more and more cause the attention of Chinese scholars about the research of hypertension incidence mechanism and medicine.
The sulfonic acid amlodipine is a calcium ion antagonist, stops flow of calcium ions, directly acts on vascular smooth muscle, diastole coronary vasodilator and whole body blood vessel, and coronary blood flow increasing brings high blood pressure down.Amlodipine is on the basis that keeps the calcium antagonist advantage; Overcome the defective of calcium antagonist pharmacokinetics in the past preferably, had blood drug level and reach mild, the long half time in peak, characteristics such as bioavailability height; Therefore, external expert is with its representative medicine as third generation calcium antagonist.Amlodipine has been regarded as the typical case's representative that possesses above-mentioned characteristic.
Benazepril can suppress the Angiotensin-Converting activity, reduces the Angiotensin II level, diastole small artery blood vessel.Polytype hypertension is all had tangible hypotensive effect, and can improve the cardiac function of patients with congestive heart failure.Its pharmacological action is mainly reflected in two aspects.(1) blood pressure lowering: these article are hydrolyzed to benazeprilat in liver, become a kind of emulative angiotensin converting enzyme inhibitor, and the prevention angiotensin i-converting is an Angiotensin II, and vascular resistance is reduced, and the aldosterone secretion reduces, and plasma renin activity increases.Benazeprilat also suppresses the degraded of Kallidin I, and vascular resistance is reduced, and produces hypotensive effect.(2) lower cardiac load: these article expansion artery and vein, reduce peripheral vascular resistance or cardiac afterload, reduce PC embedding pressure or cardiac preload, also reduce pulmonary vascular resistance, thereby improve cardiac output, make exercise tolerance and time lengthening.
The Combined application of these two kinds of active ingredients of amlodipine and benazepril can either play vasodilator, can reduce angiotensin again, and the two plays the collaborative effect that brings high blood pressure down from different aspects.
Summary of the invention
Although amlodipine and benazepril have good synergistic, benazepril is incompatible with the amlodipine physical property.If the two is joined in the single dosage form their bad stability.For overcoming this defective, must guarantee that the two keeps the physics to separate in preparation.Can reach this purpose through multiple means; Join in the tablet of other a kind of material like double-layer tablet, with a kind of micropill of medicine, the micropill of the various materials of coating is incorporated in same tablet or the capsule respectively, utilizes dual cavity or multi-cavity chamber drug-supplying system etc.
In external the two compound preparation that has gone on the market; Adopt benazepril tablet and the amlodipine powder same capsular method of packing into; This technical process comprises: technologies such as benazepril preparation tablets, benazepril label coating and amlodipine pastille powder preparation, production simultaneously needs special capsule pad device.This promotes to suitability for industrialized production and causes very big obstruction.
The inventor discovers: can realize that the physics of these two kinds of active compositions separates through other galenic pharmacy means; And, can further this Pharmaceutical composition be developed to double-layer tablet, pellet tablet, single chamber or the dosage forms such as two-chamber (micropill) capsule, oral cavity disintegration tablet of pro ore.
Preparation double-layer tablet, pellet tablet, single chamber or the used adjuvants of dosage form such as two-chamber (micropill) capsule, oral cavity disintegration tablet are selected from the adjuvant that the insider knows, and include but are not limited to filler, binding agent, disintegrating agent, wetting agent, lubricant, fluidizer, film-coat material, opacifier, antiplastering aid etc.The technological means that realizes preparation production also is a method commonly used in the pharmaceutical field, like wet granulation, dry granulation, fluid bed drying, hot air drying etc., micropill, tablet coating, fill, packing etc.
The specific embodiment
Come the preparation of amlodipine of the present invention and benazepril or the pharmaceutical salts of the two (following consumption is all in amlodipine and benazepril) done further specifying through following instance, but be not limited in following instance.
Embodiment 1 amlodipine and benazepril pellet tablet
The micropill prescription:
The coating prescription
Method for preparing:
1. Amlodipine Besylate Tablet medicine carrying micropill preparation
With Amlodipine Besylate Tablet, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose pulverize separately, cross 100 mesh sieves, behind the mix homogeneously; Add suitable quantity of water and prepare software, this soft material is presented to extrudes in the spheronizator, be extruded into bar after; Be presented in the shot-blasting machine ball blast, control medicine carrying micropill moisture; The gained micropill can wrap or not wrap the HPMC film-coat, and is subsequent use;
2. benazepril hydrochloride medicine carrying micropill preparation
With benazepril hydrochloride, starch, sucrose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose pulverize separately, cross 100 mesh sieves, behind the mix homogeneously; Add suitable quantity of water and prepare software, this soft material is presented to extrudes in the spheronizator, be extruded into bar after; Be presented in the shot-blasting machine ball blast, control medicine carrying micropill moisture; The gained micropill can wrap or not wrap the HPMC film-coat, and is subsequent use;
3. micropill film coating
Get 03K19229 type gastric solubleness Opadry coating powder, add water and stir, process the suspension of 10% concentration, promptly get contagion gown liquid.Get and contain pill core in the fluidized bed coating pot, regulate atomizing pressure and solution spray speed, controlling ball core temperature is 30 ℃～45 ℃; Carry out fluid bed bag contagion gown; Increase to a certain amount of back (about 3%),, sieve after sampling detection moisture is qualified in dry 30 minutes of 30 ℃～45 ℃ continuation.
4. get microcrystalline Cellulose PH200, mix, add carboxymethyl starch sodium, magnesium stearate, be pressed into the micropill tablet with above-mentioned an amount of two kinds of micropills.
The present invention adopts ball heart medicine carrying mode to be written into active constituents of medicine, still, in the practical application, also can adopt modes such as the medicine-feeding of blank pill heart lamination, drug suspension spraying medicine-feeding, all can realize similar purpose.
Embodiment 2 amlodipines and benazepril pellet tablet
Prescription:
The coating prescription
Method for preparing:
1. Amlodipine Besylate Tablet medicine carrying preparation of granules
With Amlodipine Besylate Tablet, microcrystalline Cellulose pulverize separately, cross 100 mesh sieves, behind the mix homogeneously, add suitable quantity of water system soft material, 24 mesh sieves are granulated, drying, 24 mesh sieve granulate, subsequent use;
2. benazepril hydrochloride medicine carrying micropill preparation
With benazepril hydrochloride, lactose, microcrystalline Cellulose, polyvinylpolypyrrolidone pulverize separately, cross 100 mesh sieves, behind the mix homogeneously; Add suitable quantity of water and prepare soft material, this soft material is presented to extrudes in the spheronizator, be extruded into bar after; Be presented in the shot-blasting machine ball blast, control medicine carrying micropill moisture; The gained micropill can wrap or not wrap the HPMC film-coat, and is subsequent use;
3. micropill film coating (optional)
Get 03K19229 type gastric solubleness Opadry coating powder, add water and stir, process the suspension of 10% concentration, promptly get contagion gown liquid.Get and contain pill core in the fluidized bed coating pot, regulate atomizing pressure and solution spray speed, controlling ball core temperature is 30 ℃～45 ℃; Carry out fluid bed bag contagion gown; Increase to a certain amount of back (about 3%),, sieve after sampling detection moisture is qualified in dry 30 minutes of 30 ℃～45 ℃ continuation.
4. get step 1 gained Amlodipine Besylate Tablet medicine carrying granule and step 2 gained benazepril hydrochloride medicine carrying micropill, add microcrystalline Cellulose PH200, carboxymethyl starch sodium, magnesium stearate again, behind the mix homogeneously, tabletting, but gained tablet coating or coating not.
5. tablet thin film coating (optional)
Get 03K19229 type gastric solubleness Opadry coating powder, add water and stir, process the suspension of 10% concentration, promptly get contagion gown liquid.Get the pastille label in the fluidized bed coating pot, regulate atomizing pressure and solution spray speed, control ball core temperature is 30 ℃～45 ℃; Carry out fluid bed bag contagion gown; Increase to a certain amount of back (about 2%), in dry 30 minutes of 30 ℃～45 ℃ continuation, after sampling detection moisture is qualified.
Embodiment 3: amlodipine and benazepril pellt capsule
Prescription:
The coating prescription
Method for preparing:
1. Amlodipine Besylate Tablet medicine carrying micropill preparation
With Amlodipine Besylate Tablet, microcrystalline Cellulose, polyvinylpolypyrrolidone pulverize separately, cross 100 mesh sieves, behind the mix homogeneously; Add an amount of PVPk30 (5%) aqueous solution and prepare software, this soft material is presented to extrudes in the spheronizator, be extruded into bar after; Be presented in the shot-blasting machine ball blast, control medicine carrying micropill moisture; The gained micropill can wrap or not wrap the HPMC film-coat, and is subsequent use;
2. benazepril hydrochloride medicine carrying micropill preparation
With benazepril hydrochloride, microcrystalline Cellulose, lactose, polyvinylpolypyrrolidone pulverize separately, cross 100 mesh sieves, behind the mix homogeneously; Add an amount of PVPk30 (5%) aqueous solution and prepare software, this soft material is presented to extrudes in the spheronizator, be extruded into bar after; Be presented in the shot-blasting machine ball blast, control medicine carrying micropill moisture; The gained micropill can wrap or not wrap the HPMC film-coat, and is subsequent use;
3. micropill film coating (optional)
Get the Opadry coating powder, add water and stir, process the suspension of 10% concentration, promptly get contagion gown liquid.Get and contain pill core in the fluidized bed coating pot, regulate atomizing pressure and solution spray speed, controlling ball core temperature is 30 ℃～45 ℃; Carry out fluid bed bag contagion gown, increase to a certain amount of back (about 2-3%), continued dry 30 minutes in 30 ℃～45 ℃; Sampling detects the qualified back of moisture mistake, sieves.
4. get above-mentioned an amount of two kinds of micropills, behind the mix homogeneously, the suitable capsule of packing into promptly gets.
Embodiment 4: amlodipine and benazepril double-layer tablet
Prescription:
Method for preparing:
1. Amlodipine Besylate Tablet medicine carrying preparation of granules
With Amlodipine Besylate Tablet, microcrystalline Cellulose pulverize separately, cross 100 mesh sieves, behind the mix homogeneously, add suitable quantity of water system soft material, 24 mesh sieves are granulated, drying, 24 mesh sieve granulate, subsequent use;
2. benazepril hydrochloride medicine carrying micropill preparation
With benazepril hydrochloride, lactose, microcrystalline Cellulose, polyvinylpolypyrrolidone pulverize separately, cross 100 mesh sieves, behind the mix homogeneously, add suitable quantity of water and prepare soft material, drying, 24 mesh sieve granulate, subsequent use;
With above two kinds of granules according to certain mixed, add polyvinylpolypyrrolidone, magnesium stearate, mix homogeneously.
4. tabletting is suppressed bilayer tablet on bi-layer tablet press
Embodiment 5: amlodipine and benazepril microplate capsule
Prescription:
Method for preparing:
1. Amlodipine Besylate Tablet medicine carrying preparation of granules
With Amlodipine Besylate Tablet, microcrystalline Cellulose pulverize separately, cross 100 mesh sieves, behind the mix homogeneously, add suitable quantity of water system soft material, 24 mesh sieves are granulated, drying, 24 mesh sieve granulate, subsequent use;
2. benazepril hydrochloride medicine carrying micropill preparation
With benazepril hydrochloride, lactose, microcrystalline Cellulose, polyvinylpolypyrrolidone pulverize separately, cross 100 mesh sieves, behind the mix homogeneously, add suitable quantity of water and prepare soft material, drying, 24 mesh sieve granulate, subsequent use;
With above two kinds of granules according to certain mixed, add polyvinylpolypyrrolidone, magnesium stearate, mix homogeneously.
4. respectively above two kinds of granules are pressed into micro tablet, successively fill is in capsule.
Embodiment 6: amlodipine and benazepril tablet composite packaging
Prescription:
Method for preparing:
1. Amlodipine Besylate Tablet medicine carrying preparation of granules
With Amlodipine Besylate Tablet, microcrystalline Cellulose, carboxymethyl starch sodium pulverize separately, cross 100 mesh sieves, behind the mix homogeneously, add an amount of 3%HPMC aqueous solution system soft material, 24 mesh sieves are granulated, drying, 24 mesh sieve granulate, subsequent use;
2. benazepril hydrochloride medicine carrying micropill preparation
With benazepril hydrochloride, lactose, microcrystalline Cellulose, carboxymethyl starch sodium pulverize separately, cross 100 mesh sieves, behind the mix homogeneously, add an amount of 3%HPMC aqueous solution and prepare soft material, drying, 24 mesh sieve granulate, subsequent use;
With above two kinds of granules according to certain mixed, add polyvinylpolypyrrolidone, magnesium stearate, mix homogeneously.
4. respectively above two kinds of granules are pressed into suitable tablet, are filled in the composite packaging of two blister aperture.
Embodiment 6: stability study
Above embodiment 1-6 gained preparation is placed the plastic bottle (high density polyethylene (HDPE) that contains desiccant; HDPE) in the bottle; At 25 ℃; Launch stability test under 60% condition, the main degradation product benazeprilat of total impurities percent, benazepril and the two kinds of active component that the index of investigating is mainly active component content, amlodipine dissolution of 30 minutes in 0.1N hydrochloric acid dissolution medium.The result is as follows:
The result shows that all the prescription preparations in the embodiment of the invention all have excellent stability, and this physics who directly has benefited from two kinds of active substances separates.Therefore, adopt physics's separation means of the present invention, can successfully realize set objective, keep the stability of two kinds of active component, avoid incompatible phenomenon to take place.
Claims (4)
1. the present invention is a kind of Pharmaceutical composition that contains amlodipine and benazepril; It is characterized in that: the physics through realizing two kinds of main active separates, thereby improves the compatibility of these two kinds of active component and the stability of this Pharmaceutical composition.
2. the described Pharmaceutical composition of claim 1; It is characterized in that; Realize that two kinds of isolating technological means of main active physics join in the tablet of other a kind of material for the compacting double-layer tablet, with a kind of micropill of medicine, the micropill of the various materials of coating is incorporated in same tablet or the capsule respectively, utilizes dual cavity or multi-cavity chamber drug-supplying system etc.
3. the described Pharmaceutical composition of claim 1 is characterized in that, according to described galenic pharmacy technological means, can be developed into double-layer tablet, pellet tablet, single chamber or dosage forms such as two-chamber (micropill) capsule, oral cavity disintegration tablet.
4. the described Pharmaceutical composition of claim 1 is characterized in that, the application of said composition in preparation treatment all kinds hypertension drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210192076XA CN102688245A (en) | 2012-06-11 | 2012-06-11 | Stable amlodipine and benazepril medicinal composition and preparation method thereof |
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| CN201210192076XA CN102688245A (en) | 2012-06-11 | 2012-06-11 | Stable amlodipine and benazepril medicinal composition and preparation method thereof |
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| CN102688245A true CN102688245A (en) | 2012-09-26 |
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| CN201210192076XA Pending CN102688245A (en) | 2012-06-11 | 2012-06-11 | Stable amlodipine and benazepril medicinal composition and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103908456A (en) * | 2012-12-29 | 2014-07-09 | 安徽贝克生物制药有限公司 | Disoproxil fumarate, lamivudine and efavirenz tri-combination compound mini-pill tablet and preparation method thereof |
| CN108066347A (en) * | 2016-11-16 | 2018-05-25 | 深圳万和制药有限公司 | Orally disintegrating tablet medicament composition comprising Tamsulosin and dutasteride |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1814290A (en) * | 2005-12-05 | 2006-08-09 | 苏州东瑞制药有限公司 | Multi-layer tablet containing calsium-path receptor retarder and ACE inhibitor, and preparing method |
| CN101137367A (en) * | 2003-10-20 | 2008-03-05 | 诺瓦提斯公司 | Benazapril and amlodipine besylate for reducing cardiovascular morbidity |
| CN101653440A (en) * | 2008-08-18 | 2010-02-24 | 北京瑞康医药技术有限公司 | Treatment composition containing amlodipine series salt and pril medicament |
-
2012
- 2012-06-11 CN CN201210192076XA patent/CN102688245A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101137367A (en) * | 2003-10-20 | 2008-03-05 | 诺瓦提斯公司 | Benazapril and amlodipine besylate for reducing cardiovascular morbidity |
| CN1814290A (en) * | 2005-12-05 | 2006-08-09 | 苏州东瑞制药有限公司 | Multi-layer tablet containing calsium-path receptor retarder and ACE inhibitor, and preparing method |
| CN101653440A (en) * | 2008-08-18 | 2010-02-24 | 北京瑞康医药技术有限公司 | Treatment composition containing amlodipine series salt and pril medicament |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103908456A (en) * | 2012-12-29 | 2014-07-09 | 安徽贝克生物制药有限公司 | Disoproxil fumarate, lamivudine and efavirenz tri-combination compound mini-pill tablet and preparation method thereof |
| CN108066347A (en) * | 2016-11-16 | 2018-05-25 | 深圳万和制药有限公司 | Orally disintegrating tablet medicament composition comprising Tamsulosin and dutasteride |
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Application publication date: 20120926 |
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