CN104306347A - Carvedilol double-layer sustained release tablet and prepetition method of carvedilol double-layer sustained release tablet - Google Patents
Carvedilol double-layer sustained release tablet and prepetition method of carvedilol double-layer sustained release tablet Download PDFInfo
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- CN104306347A CN104306347A CN201410480492.9A CN201410480492A CN104306347A CN 104306347 A CN104306347 A CN 104306347A CN 201410480492 A CN201410480492 A CN 201410480492A CN 104306347 A CN104306347 A CN 104306347A
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Abstract
The invention relates to a carvedilol double-layer sustained release tablet used for treating congestive heart failures, hypertension and myocardial infarction and a prepetition method of the carvedilol double-layer sustained release tablet. The sustained release tablet comprises a quick release layer and a sustained release layer. The quick release layer in the sustained release tablet can rapidly release medicines and has the effects of being rapid in effect taking and rapidly relieving symptoms; medicines in the sustained release layer are slowly released, the blood concentration is stable, and untoward effects are reduced. The novel preparation of carvedilol and saline of the carvedilol is provided for wide patients and medical workers and is sufficient in medicine therapeutic effect working, small in toxic and side effect, convenient to carry, store and transport and suitable for mass production, and children and the old can conveniently take the preparation in a decrement manner.
Description
Technical field
The present invention relates to a kind of carvedilol double-layer sustained release tablets and preparation method thereof being used for the treatment of heart failure, hypertension, myocardial infarction, this slow releasing tablet comprises release layer and slow release layer is two-layer.Wherein release layer energy rapid delivery of pharmaceuticals, has rapid-action, the effect of quick symptom relief; Slow release layer Chinese medicine slow releasing, blood drug level is steady, reduces untoward reaction.
Background technology
Hypertension is a kind of commonly encountered diseases, frequently-occurring disease, and it is with arteriotony rising for feature, occurs the systemic disease of physiology or pathologic exception with heart, blood vessel, brain and kidney and other organs, very big to human health risk.Hypertension, as do not controlled very well, can damage the internal organs such as the heart, brain, kidney.Hypertension can be divided into two classes clinically: 1. essential hypertension: be a kind of with blood pressure rising for main clinical manifestation and the not yet clear and definite independent disease of the cause of disease.2. secondary hypertension: be also called symptomatic hypertension, in this kind of disease, the cause of disease is clear and definite, and hypertension is only one of clinical manifestation of this kind of disease, and blood pressure can temporary or persistency rising.
Antihypertensive drug can be divided into following a few class according to the effect of various medicine and site of action:
Diuretic antihypertensive medicine: as hydrochlorothiazide etc.
Sympathetic nerve depressant:
(1) central depressor: as clonidine, rilmenidine etc.;
(2) ganglion blocker: as Trimetaphan Camsilate etc.;
(3) noradrenergic nerve tip blocking agent: as reserpine, guanethidine etc.;
(4) adrenoceptor blocking drug: as Propranolol etc.
Renin-angiotensin system depressant:
(1) Angiotensin-Converting (ACE) depressant: as captopril etc.;
(2) Angiotensin Ⅱ receptor blockers: as losartan etc.;
(3) renin inhibitor: as Remikiren etc.Calcium antagonists: as nifedipine etc.
Vasodilator: as hydralazine and sodium nitroprusside etc.
Carvedilol is third generation beta-blocker, has decreased heart rate, reduces the effect of cardiac load.Result of study shows that its toleration is good, and adverse reaction rate is very low, and be easy to after oral absorb, absolute bioavailability (F) is about 25% ~ 35%, has obvious first pass effect, and elimination phase half-life (t1/2b) is about 7 ~ 10 hours.When taking together with food, its absorption is slowed down, but relative bioavailability does not have a significant effect, and can reduce the danger causing postural hypotension.Carvedilol is alkaline lipophilic compound, is greater than 98% with plasma protein binding rate.Its Vdss is approximately 1.5L, and plasma clearance is 500 ~ 700ml/min.Carvedilol metabolism is complete, and its metabolite is first discharged by feces through bile again, discharges with original shape less than 2% with urine.
Existing listing dosage form has conventional tablet and slow releasing capsule, and conventional tablet takes twice every day, and oral absorption is rapid, and its half-life is 7 ~ 10 hours.Slow releasing capsule is taken once every day, effectively decrease medicining times, increase the Compliance of patient, be made up of slow release and fast release micropill in its softgel shell, both rapid absorption can be reached, can ensure again the blood drug level of continued smooth, but coating of pellets technique is loaded down with trivial details, technical costs is high, the present invention is in order to overcome above-mentioned shortcoming, provide a kind of double-layer sustained release tablets, wherein one deck is release layer, and another layer is slow release layer.
By literature search, there are no pertinent literature and the patent report of carvedilol double-layer sustained release tablets and preparation method thereof.
Summary of the invention
The object of the invention is to the deficiency solving the existence of above-mentioned background technology, for providing a kind of quick-acting, long-acting carvedilol economic benefits and social benefits sheet clinically.
Another object of the present invention is to provide the preparation method of above-mentioned carvedilol double-layer sustained release tablets.
The present invention is achieved through the following technical solutions above-mentioned purpose:
A kind of carvedilol double-layer sustained release tablets, be made up of following component:
Immediate release section:
| Phosphoric acid carvedilol | 2%~20% |
| Filler | 10%~30% |
| Disintegrating agent | 2%~15% |
| Correctives | 0%~5% |
| Binding agent | 0%~5% |
| Lubricant | 0.1%~5% |
Slow-released part:
| Phosphoric acid carvedilol | 2%~20% |
| Slow-release material | 20%~30% |
| Filler | 10%~20% |
| Binding agent | 0%~5% |
| Lubricant | 0.1%~5% |
Described release layer is the mixture of one or more in cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose and starch containing disintegrating agent; Filler contained by described release layer is one or more mixture in microcrystalline Cellulose, lactose, starch and mannitol; Described release layer is also containing the mixture of one or more in magnesium stearate, Pulvis Talci, micropowder silica gel, steviosin and Aspartane.
Described slow release layer is the mixture of one or more in hydroxypropyl methylcellulose, carbomer and ethyl cellulose containing slow-release material; Filler contained by described slow release layer is one or more mixture in lactose, calcium hydrogen phosphate, Pulvis Talci or magnesium stearate.
Except above-mentioned material, also may containing one or more in hypromellose, polyvinylpyrrolidone etc. as binding agent.
Present invention also offers a kind of preparation method of carvedilol double-layer sustained release tablets, it is characterized in that immediate release section and slow-released part direct compression or carry out tabletting after granulating respectively, adopting bi-layer tablet press to regulate respectively, each several part sheet is heavy to qualified rear adjustment tabletting hardness to acceptability limit, start tabletting.
In carvedilol double-layer sustained release tablets of the present invention, its immediate release section can rapid delivery of pharmaceuticals, and onset rapidly can relief of symptoms effectively; And drug release in slow-released part is slow, blood drug level can be made steady, less toxic and side effects, and the number of times that can reduce administration improve the compliance of patient's medication.
Detailed description of the invention
Below, in order to technical scheme of the present invention is described better, spy provides following examples, but the present invention is not limited in following instance, in the scope illustrated by the claims in the present invention, can carry out various change or equivalent replacement.
embodiment 1:
Formula 1:
Preparation method:
1, principal agent and all adjuvants are crossed 100 mesh sieves respectively;
2, the principal agent in release layer is mixed homogeneously with other adjuvants in release layer, for subsequent use;
3, the principal agent in slow release layer is mixed homogeneously with other adjuvants in slow release layer, for subsequent use;
4, carvedilol double-layer sustained release tablets is prepared on a bi-layer tablet press, first loading is regulated to be 169mg the materials result of slow-released part mix homogeneously, regulate immediate release section tabletting loading to be 231mg again, and tabletting hardness is adjusted to 60 ~ 100N, start tabletting.
embodiment 2:
Formula 2
Preparation method:
1, principal agent and all adjuvants are crossed 100 mesh sieves respectively;
2, the principal agent in release layer is mixed homogeneously with other adjuvants except magnesium stearate in release layer, 30% ethanol is adopted to do wetting agent, cross 18 eye mesh screens and carry out wet granulation, after drying, arrange to obtain immediate release section granule with 16 mesh sieve choosings, for subsequent use after adding the mixing of immediate release section magnesium stearate;
3, the principal agent in slow release layer is mixed homogeneously with other adjuvants of magnesium stearate that remove in slow release layer, 30% ethanol is adopted to do wetting agent, cross 18 eye mesh screens and carry out wet granulation, after drying, arrange to obtain immediate release section granule with 16 mesh sieve choosings, for subsequent use after adding the mixing of slow-released part magnesium stearate;
4, carvedilol double-layer sustained release tablets is prepared on a bi-layer tablet press, first loading is regulated to be 190mg the materials result of slow-released part mix homogeneously, regulate immediate release section tabletting loading to be 210mg again, and tabletting hardness is adjusted to 60 ~ 100N, start tabletting.
Carvedilol double-layer sustained release tablets prepared by above-described embodiment 2 and commercially available Carvedilol Tablets are carried out Pharmacokinetics in Rat comparative study, adopts non-compartment model to carry out parameter calculating, area under the drug-time curve (AUC) calculates according to trapezoidal method, peak concentration (C
max) and peak time (t
max) be measured value, t
1/2(t is calculated mutually with Drug-time curve end
1/2=0.693/ke).Adopting SPSS software to carry out nonparametric rank test to comparing between pharmacokinetic parameters group, is that difference has statistical significance with P<0.05.
pharmacokinetic parameters (x ± s, n=6) after rat oral single dose administration
| Pharmacokinetic parameters | Embodiment 2 | Commercial preparation |
| AUC 0-12h（μg·h·ml -1） | 16.59±6.14 | 19.32±4.53 |
| AUC 0-∞（μg·h·ml -1） | 17.38±6.73 | 19.64±4.82 |
| MRT 0-t(h) | 2.41±0.66* | 1.38±0.23 |
| MRT 0-∞(h) | 2.96±1.27* | 1.42±0.30 |
| t 1/2(h) | 2.52±1.06* | 0.52±0.06 |
| t max(h) | 0.82±0.19 | 0.96±0.23 |
| C max(μg·ml -1) | 7.54±2.04* | 14.31±5.63 |
Note: compared with reference preparation, * represents P<0.05.
After single oral gives carvedilol double-layer sustained release tablets prepared by embodiment 2 and commercially available ordinary tablet respectively, two preparation main pharmacokinetic parameters adopt nonparametric rank test.Statistical result shows, the AUC of carvedilol double-layer sustained release tablets and commercially available ordinary tablet prepared by embodiment 2
0-12h, AUC
0-∞equal not statistically significant difference, and C
max, MRT
0-tand t
1/2difference has statistical significance.Wherein C
maxcomparatively commercial preparation significantly reduces, and MRT
0-tand t
1/2obvious prolongation, illustrates that carvedilol double-layer sustained release tablets prepared by embodiment 2 has obvious slow releasing function.And owing to containing release layer in double-layer sustained release tablets, so both t
maxand there was no significant difference.
In sum, the carvedilol double-layer sustained release tablets prepared by embodiment 2 compared with commercially available ordinary tablet, t
maxand there was no significant difference, namely its release layer can meet the effect of release relief of symptoms fast; And MRT
0-tand t
1/2obvious prolongation, C
maxremarkable reduction and AUC
0-12h, AUC
0-∞equal not statistically significant difference, namely its slow release layer can delay the release of medicine, makes blood drug level steady, reduces toxic and side effects.
Claims (10)
1. a carvedilol slow releasing preparation, is characterized in that:
(1) release layer and slow release layer is comprised;
(2) wherein active component is carvedilol and pharmaceutical salts thereof.
2. carvedilol double-layer sustained release tablets according to claim 1, is characterized in that described each preparation unit is 5 ~ 100mg containing the amount of active component carvedilol.
3. carvedilol double-layer sustained release tablets according to claim 1, is characterized in that described each preparation unit is 10 ~ 80mg containing the amount of active component carvedilol.
4. carvedilol slow releasing preparation according to claim 1, is characterized in that, its immediate release section forms:
。
5. carvedilol slow releasing preparation according to claim 1, is characterized in that, its slow-released part forms:
。
6. carvedilol slow releasing preparation according to claim 1, is characterized in that: disintegrating agent contained by described release layer is the mixture of one or more in cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose and starch; Filler contained by described release layer is one or more mixture in microcrystalline Cellulose, lactose, starch and mannitol.
7. carvedilol slow releasing preparation according to claim 1, is characterized in that: described slow release layer is the mixture of one or more in hydroxypropyl methylcellulose, carbomer and ethyl cellulose fibre containing slow-release material; Filler contained by described slow release layer is one or more mixture in lactose, calcium hydrogen phosphate, mannitol or microcrystalline Cellulose.
8. carvedilol double-layer sustained release tablets as claimed in claim 1, is characterized in that, described release layer is also containing the mixture of one or more in magnesium stearate, Pulvis Talci, micropowder silica gel, steviosin and Aspartane.
9. the preparation method of carvedilol double-layer sustained release tablets as claimed in claim 1, it is characterized in that, the method comprises:
(1) after the component mixing of release layer, by direct powder compression, or tabletting after dry granulation or wet granulation, prepare described release layer;
(2) after the component mixing of slow release layer, by direct powder compression, or dry granulation, wet granulation, to granulate after melting or tabletting after piller processed, prepare described slow release layer.
10. the preparation method of carvedilol double-layer sustained release tablets as claimed in claim 9, it is characterized in that, immediate release section and slow-released part are granulated respectively, then adopt bi-layer tablet press to carry out tabletting respectively; First press slow-released part granule, after tab coincidence lattice, then add immediate-release granules, pressure testing, be adjusted to qualified weight, then regulate the qualified rear beginning tabletting of hardness, sampling and measuring release, the formal tabletting of beginning after release is qualified.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410480492.9A CN104306347A (en) | 2014-09-19 | 2014-09-19 | Carvedilol double-layer sustained release tablet and prepetition method of carvedilol double-layer sustained release tablet |
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|---|---|---|---|
| CN201410480492.9A CN104306347A (en) | 2014-09-19 | 2014-09-19 | Carvedilol double-layer sustained release tablet and prepetition method of carvedilol double-layer sustained release tablet |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107320462A (en) * | 2016-10-14 | 2017-11-07 | 杨彦玲 | A kind of sustained release preparation of levamlodipine or its salt and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011038683A1 (en) * | 2009-09-29 | 2011-04-07 | 台湾东洋药品工业股份有限公司 | Controlled release formulation of carvedilol |
| CN102548544A (en) * | 2009-10-09 | 2012-07-04 | 永进药品工业株式会社 | Pharmaceutical composition with both immediate and extended release characteristics |
| CN102614130A (en) * | 2011-01-30 | 2012-08-01 | 江苏恒瑞医药股份有限公司 | Carvedilol sulfate sustained release preparation |
| CN102670545A (en) * | 2011-03-09 | 2012-09-19 | 中国药科大学 | Carvedilol push-pull osmotic pump type controlled release preparation and preparation method thereof |
-
2014
- 2014-09-19 CN CN201410480492.9A patent/CN104306347A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011038683A1 (en) * | 2009-09-29 | 2011-04-07 | 台湾东洋药品工业股份有限公司 | Controlled release formulation of carvedilol |
| CN102740838A (en) * | 2009-09-29 | 2012-10-17 | 东生华制药股份有限公司 | Controlled release formulation of carvedilol |
| CN102548544A (en) * | 2009-10-09 | 2012-07-04 | 永进药品工业株式会社 | Pharmaceutical composition with both immediate and extended release characteristics |
| CN102614130A (en) * | 2011-01-30 | 2012-08-01 | 江苏恒瑞医药股份有限公司 | Carvedilol sulfate sustained release preparation |
| CN102670545A (en) * | 2011-03-09 | 2012-09-19 | 中国药科大学 | Carvedilol push-pull osmotic pump type controlled release preparation and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107320462A (en) * | 2016-10-14 | 2017-11-07 | 杨彦玲 | A kind of sustained release preparation of levamlodipine or its salt and preparation method thereof |
| CN107320462B (en) * | 2016-10-14 | 2018-11-13 | 杨彦玲 | A kind of sustained release preparation and preparation method thereof of levamlodipine or its salt |
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Application publication date: 20150128 |