CN104586810A - Acipimox sustained-release tablet and preparation method thereof - Google Patents
Acipimox sustained-release tablet and preparation method thereof Download PDFInfo
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- CN104586810A CN104586810A CN201510033991.8A CN201510033991A CN104586810A CN 104586810 A CN104586810 A CN 104586810A CN 201510033991 A CN201510033991 A CN 201510033991A CN 104586810 A CN104586810 A CN 104586810A
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Abstract
The invention relates to an acipimox sustained-release tablet. The prepared sustained-release tablet consists of a compressed tablet and sustained-release coating, wherein the compressed tablet comprises acipimox, hydroxypropyl methyl cellulose and microcrystalline cellulose, and the sustained-release coating films comprise Eurdragit NE 30D, talcum powder, polyethylene glycol 6000 and sodium lauryl sulfate. The prepared acipimox sustained-release tablets disclosed by the invention are stable in medicine release, do not have the problem of residual organic solvents, are simple in process and convenient to operate, and ensure that remarkable economic and social benefits can be achieved.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of slow-releasing acipimox tablet agent and preparation method thereof.
Background technology
In recent years, along with dietary habit change, living standard raising, operating pressure increase, hyperlipemia and hyperproteinemia patient get more and more, and patient group is rejuvenation more and more.Hyperlipemia and hyperproteinemia are one group of clinical common lipid metabolism disorder diseases, and become hyperlipemia in limited time when the concentration of blood plasma lipide exceedes normal value height, in blood plasma, lipoprotein exceedes normal value height and is called hyperlipoproteinemia in limited time.Epidemiological study shows, increasing of plasma low density lipoprotein and Very Low Density Lipoprotein, is the key factor of early starting pulse atherosclerosis and coronary heart disease.Statistical analysis shows, serum cholesterol often reduces by 1%, and the pathogenetic risk of coronary disease will reduce by 2%.Therefore, rational diet, motion and Drug therapy are very important to hyperlipemia and patients with hyperlipoproteinemia.
Acipimox is nicotinic acid derivates, this medicine mainly acts on fatty tissue, by suppressing fatty tissue release free fatty, reduce the synthesis of plasma low density lipoprotein and very low density lipoprotein (VLDL), thus the level of plasma low density lipoprotein and very low density lipoprotein (VLDL) in reduction blood plasma, reduce the decomposition of plasma high density lipoprotein level by suppressing hepatic lipase active simultaneously.Clinically, acipimox effectively can be treated increased TG, hypercholesterolemia and high triglyceride and be merged hypercholesterolemia, is a kind of lipid regulating agent of safe, effective, better tolerance.This medicine oral absorption is rapid, and blood drug level of taking medicine in latter 2 hours can peaking, and the half-life is shorter.This medicine is not combined with plasma protein, not by metabolism, mainly discharges through urine with original shape.Because the half-life is short, not only bring inconvenience to patient, the needs such as growing life and medicinal application can not be met.Therefore acipimox is developed to slow releasing agent.Slow-releasing acipimox tablet can reduce medicining times, reduces side effect, improves the compliance of patient.
Chinese patent CN03130362.5 discloses a kind of delayed releasing Acipimox prepn, in order to ensure long effective blood drug concentration further in invention, improve the compliance of patient, increase the consumption of slow-release material, but the increase of slow-release material brings certain potential safety hazard to clinical application.
Chinese patent CN02129443.7A discloses a kind of slow-releasing acipimox capsule, and it is made up of acipimox, celphere, slow releasing agent, plasticizer, antiplastering aid, and dissolution is better, but slow-release time only has 8 hours.
Chinese patent CN103211785A discloses a kind of acipimox film-controlled slow-release pellet capsule, discloses ball core prescription and extended release coatings film prescription, and said preparation release in early stage is slower, but the later stage has significantly to dash forward releases phenomenon, cause the later stage to discharge very fast, release is unstable, and pharmaceutical release time is shorter.
Existing delayed releasing Acipimox prepn, slow-release time is shorter, has significant difference and the prominent of medicine releases phenomenon before and after rate of release.
Summary of the invention
Based on the above-mentioned shortcoming of prior art, the object of the present inventor is intended to obtain that a kind of release is steady, the persistent period is long, the simple delayed releasing Acipimox prepn of technique.
Hydroxypropyl emthylcellulose containing water-swellable in plain sheet of the present invention, hydroxypropyl emthylcellulose obviously can expand after absorbing water and play a supporting role, inventor finds, acipimox and hydroxypropyl emthylcellulose do not react, above being well attached to, there is the effect of hydroxypropyl emthylcellulose, label is glomeration in an aqueous medium, among being wrapped up by appropriate acipimox, plays certain slow releasing function, avoid the prominent of medicine later stage and release phenomenon, the medicine later stage is steadily discharged.
In the selection of extended release coatings film, inventor finds, Polyethylene Glycol, the Pulvis Talci of selection appropriate components mix with Eurdragit NE30D, gained formulation products has good stability, can long term storage, use sodium lauryl sulphate as porogen, the steady release of medicine can be maintained further.
By above technology, the present invention produces that a kind of production efficiency is high, release is steady, technique is simple, cost is low, the slow-releasing acipimox tablet of organic solvent-free residue problem.
The invention provides a kind of slow releasing tablet comprising acipimox.The content of slow-releasing acipimox tablet of the present invention is plain sheet, and it is composed as follows:
1) plain sheet, composed of the following components:
Be preferably:
2) extended release coatings film, composed of the following components:
Be preferably:
Wherein coat weight is the 10-20% of plain sheet, and preferably, coat weight is the 13-17% of plain sheet, most preferably is 15%.
The present invention additionally provides the preparation method of above-mentioned slow releasing tablet simultaneously, comprises the following steps:
(1) by acipimox, microcrystalline Cellulose, hydroxypropyl methylcellulose mixing;
(2) 50% alcoholic solution is added to gained mixture appropriate;
(3) granulation, drying, obtain dry granule;
(4) dry granule is mixed homogeneously with appropriate silicon dioxide (weight is 1% of dry granule), tabletting;
(5) polyethylene glycol 6000 and sodium lauryl sulphate are dissolved in the water, add EurdragitNE 30D and Pulvis Talci, obtain sustained release coating liquid;
(6) with coating solution, coating is carried out to plain sheet, obtain slow releasing tablet;
The content of described silicon dioxide is 1% of dry granule.
2 hours releases of the slow-releasing acipimox tablet obtained by the present invention can control within 30% effectively, improve the slow release effect of medicine greatly.In slow-releasing acipimox tablet preparation method of the present invention, Sustained release coating materials does not need with an organic solvent to make solvent, and equipment needed thereby is simple, makes the method have the features such as economy, safety, environmental protection.
Detailed description of the invention
Further illustrate the present invention by the following examples, but these embodiments do not limit the present invention in any way.
1, the Eurdragit NE 30D of different content is explored on the impact of sustained drug release effect:
Element sheet composition:
Acipimox 250g, microcrystalline Cellulose 150g, hydroxypropyl methylcellulose 10g, silicon dioxide is appropriate;
Sustained release coating forms:
The Eurdragit NE 30D of 48g, 60g, 75g, 96g, 105g five kinds of different amounts, Pulvis Talci 18g, polyethylene glycol 6000 12g, sodium lauryl sulphate 6g, preparation method is:
(1) by acipimox, microcrystalline Cellulose, hydroxypropyl methylcellulose mixing;
(2) 50% appropriate amount of ethanol soft material is added to gained mixture;
(3) granulation, drying, obtain dry granule;
(4) dry granule is mixed homogeneously with silicon dioxide (weight is 1% of dry granule), tabletting;
(5) polyethylene glycol 6000 and sodium lauryl sulphate are dissolved in the water, add EurdragitNE 30D and Pulvis Talci, obtain sustained release coating liquid;
(6) with coating solution, coating is carried out to plain sheet, obtain slow releasing tablet;
Coat weight is 13% of plain sheet.
Experimental result is as follows:
Table 1. different Eurdragit NE 30D consumption is on the impact of release
From above-mentioned data, Eurdragit NE 30D has larger impact to release, and the preferred content of the present invention is 48-96g, most preferably is 60g, within the scope of this, all can reach its slow release requirement.
2, the impact of sustained release coating weightening finish on drug release is explored:
Element sheet composition:
Acipimox 250g, microcrystalline Cellulose 150g, hydroxypropyl methylcellulose 10g, silicon dioxide is appropriate;
Sustained release coating forms:
Eurdragit NE 30D 60g, Pulvis Talci 18g, polyethylene glycol 6000 12g, sodium lauryl sulphate 6g.Coating weight gain is respectively 8%, 10%, 13%, 15%, 17%, 20% of plain sheet.Preparation method is with 1.
Experimental result is as follows
The different coating weight gain of table 2. is on the impact of release
From above-mentioned data, coating weight gain all can reach its slow release requirement within the scope of 10-20%, and during coating weight gain 15%, release is the most stable.
3, hydroxypropyl methylcellulose proportion of composing is explored on the impact of drug release:
Embodiment 1
Element sheet composition:
Acipimox 250g, microcrystalline Cellulose 150g, hydroxypropyl methylcellulose 5.0g, silicon dioxide is appropriate;
Sustained release coating forms:
Eurdragit NE 30D 60g, Pulvis Talci 18g, polyethylene glycol 6000 12g, sodium lauryl sulphate 6g, coating weight gain is 15% of plain sheet, has following preparation method to make:
(1) by acipimox, microcrystalline Cellulose, hydroxypropyl methylcellulose mixing;
(2) 50% appropriate amount of ethanol soft material is added to gained mixture;
(3) granulation, drying, obtain dry granule;
(4) dry granule is mixed homogeneously with silicon dioxide (weight is 1% of dry granule), tabletting;
(5) polyethylene glycol 6000 and sodium lauryl sulphate are dissolved in the water, add EurdragitNE 30D and Pulvis Talci, obtain sustained release coating liquid;
(6) with coating solution, coating is carried out to plain sheet, obtain slow releasing tablet;
Embodiment 2
Element sheet composition:
Acipimox 250g, microcrystalline Cellulose 150g, hydroxypropyl methylcellulose 7.0g, silicon dioxide is appropriate;
Sustained release coating forms:
Eurdragit NE 30D 60g, Pulvis Talci 18g, polyethylene glycol 6000 12g, sodium lauryl sulphate 6g, coating weight gain is 15% of plain sheet, and preparation method is with embodiment 1.
Embodiment 3
Element sheet composition:
Acipimox 250g, microcrystalline Cellulose 150g, hydroxypropyl methylcellulose 10g, silicon dioxide is appropriate;
Sustained release coating forms:
Eurdragit NE 30D 60g, Pulvis Talci 18g, polyethylene glycol 6000 12g, sodium lauryl sulphate 6g; Coating weight gain is 15% of plain sheet, and preparation method is with embodiment 1.
Embodiment 4
Element sheet composition:
Acipimox 250g, microcrystalline Cellulose 150g, hydroxypropyl methylcellulose 15g, silicon dioxide is appropriate;
Sustained release coating forms:
Eurdragit NE 30D 60g, Pulvis Talci 18g, polyethylene glycol 6000 12g, sodium lauryl sulphate 6g, coating weight gain is 15% of plain sheet, and preparation method is with embodiment 1.
Embodiment 5
Element sheet composition:
Acipimox 250g, microcrystalline Cellulose 150g, hydroxypropyl methylcellulose 20g, silicon dioxide is appropriate;
Sustained release coating forms:
Eurdragit NE 30D 60g, Pulvis Talci 18g, polyethylene glycol 6000 12g, sodium lauryl sulphate 6g, coating weight gain is 15% of plain sheet, and preparation method is with embodiment 1.
Embodiment 6:
Element sheet composition:
Acipimox 250g, microcrystalline Cellulose 100g, hydroxypropyl methylcellulose 10g, silicon dioxide is appropriate;
Sustained release coating forms:
Eurdragit NE 30D 60g, Pulvis Talci 18g, polyethylene glycol 6000 12g, sodium lauryl sulphate 6g, coating weight gain is 15% of plain sheet, and preparation method is with embodiment 1.
Embodiment 7:
Element sheet composition:
Acipimox 250g, microcrystalline Cellulose 200g, hydroxypropyl methylcellulose 10g, silicon dioxide is appropriate;
Sustained release coating forms:
Eurdragit NE 30D 60g, Pulvis Talci 18g, polyethylene glycol 6000 12g, sodium lauryl sulphate 6g, coating weight gain is 15% of plain sheet, and preparation method is with embodiment 1.
Comparative example 1
The prescription of 1000 slow releasing tablet
General tabletting method is adopted to carry out tabletting.
Comparative example 2
Element sheet composition:
Acipimox 250g, microcrystalline Cellulose 150g, 1% sodium carboxymethyl cellulose is appropriate, and silicon dioxide is appropriate;
Sustained release coating forms:
Eurdragit NE 30D60g, Pulvis Talci 18g, polyethylene glycol 6000 12g, sodium lauryl sulphate 6g, coating weight gain is 15% of plain sheet;
Preparation method is with embodiment 1.
Comparative example 3
Element sheet composition:
Acipimox 250g, microcrystalline Cellulose 150g, hydroxypropyl methylcellulose 30g, silicon dioxide is appropriate;
Sustained release coating forms:
Eurdragit NE 30D60g, Pulvis Talci 18g, polyethylene glycol 6000 12g, sodium lauryl sulphate 6g, coating weight gain is 15% of plain sheet;
Preparation method is with embodiment 1.
Comparative example 4
The micropill prescription of acipimox film-controlled slow-release pellet capsule is as follows:
One, ball core prescription (1000)
Two, extended release coatings film prescription
Acipimox is crossed 60 mesh sieves; with microcrystalline Cellulose PH101, lactose, put mix homogeneously in wet granulator, 1% sodium carboxymethyl cellulose 10% alcoholic solution soft material; extrusion spheronization is also dried in fluid bed; sieve, get the ball core between 16 ~ 30 orders, then coating; coating weight gain is 14.8%; to the micropill of extended release coatings be wrapped in fluid bed, heat treatment under 40 DEG C/2h condition, by coated micropill filling capsule and get final product.
Checking embodiment:
Drug release determination: according to dissolution method (Chinese Pharmacopoeia version in 2010 two annex XC second methods), with the hydrochloric acid solution of 900ml 0.1mol/L for dissolution medium, rotating speed 50rpm, release is surveyed in different time sampling, and concrete outcome is in table 3:
The drug release determination result of each embodiment of table 3
As can be seen from Table 3:
The release of embodiment 1-7 can control within 30%, and the highest release reaches 99.17%;
Comparative example 1 is matrix sustained release tablet, and within 8 hours, release is complete substantially;
Comparative example 2 is not containing hydroxypropyl methylcellulose, and not to medicine parcel, medicine later stage rate of release is very fast;
The hydroxypropyl methylcellulose that comparative example 3 is contained is too much, and rate of release is excessively slow;
The change of comparative example 4 ball core prescription, causes quick release.
Discharge result from embodiment and comparative example to find out, acipimox, microcrystalline Cellulose, hydroxypropyl methylcellulose as the key component of ball core, are not only increased the sustained level of medicine by the present invention, and drug release process is steady, obtains good technique effect.
Claims (9)
1. a slow-releasing acipimox tablet, is made up of plain sheet and extended release coatings film, it is characterized in that, the component of plain sheet comprises acipimox, microcrystalline Cellulose, hydroxypropyl methylcellulose and silicon dioxide; The component of sustained release coating comprises Eurdragit NE 30D, Pulvis Talci, polyethylene glycol 6000 and lauryl sulphate acid.
2. slow-releasing acipimox tablet as claimed in claim 1, it is characterized in that, plain sheet each component percentage by weight is:
3. slow-releasing acipimox tablet as claimed in claim 2, it is characterized in that, plain sheet each component percentage by weight is:
4. slow-releasing acipimox tablet as claimed in claim 1, it is characterized in that, extended release coatings film each component percentage by weight is:
5. slow-releasing acipimox tablet as claimed in claim 4, it is characterized in that, extended release coatings film each component percentage by weight is:
6. slow-releasing acipimox tablet as claimed in claim 1, it is characterized in that, coat weight is the 10-20% of plain sheet.
7. slow-releasing acipimox tablet as claimed in claim 6, it is characterized in that, coat weight is the 13-17% of plain sheet.
8. slow-releasing acipimox tablet as claimed in claim 7, it is characterized in that, coat weight is 15% of plain sheet.
9. the preparation method of slow-releasing acipimox tablet as claimed in claim 1, is characterized in that, comprise the steps:
(1) by acipimox, microcrystalline Cellulose, hydroxypropyl methylcellulose mixing;
(2) 50% alcoholic solution is added to gained mixture appropriate;
(3) granulation, drying, obtain dry granule;
(4) dry granule is mixed homogeneously with appropriate silicon dioxide, tabletting;
(5) polyethylene glycol 6000 and sodium lauryl sulphate are dissolved in the water, add Eurdragit NE 30D and Pulvis Talci, obtain sustained release coating liquid;
(6) with coating solution, coating is carried out to plain sheet, obtain slow releasing tablet.
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| CN201510033991.8A CN104586810B (en) | 2015-01-22 | 2015-01-22 | A kind of slow-releasing acipimox tablet and preparation method thereof |
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| CN201510033991.8A CN104586810B (en) | 2015-01-22 | 2015-01-22 | A kind of slow-releasing acipimox tablet and preparation method thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1395928A (en) * | 2002-08-26 | 2003-02-12 | 鲁南制药股份有限公司 | Slow-releasing acipimox tablet |
| CN1486695A (en) * | 2003-07-04 | 2004-04-07 | 天津万斯瑞医药科技有限公司 | Delayed releasing Acipimox prepn |
| CN102188431A (en) * | 2011-05-09 | 2011-09-21 | 浙江九旭药业有限公司 | Doxazosin mesylate sustained-release tablets and preparation method thereof |
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2015
- 2015-01-22 CN CN201510033991.8A patent/CN104586810B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1395928A (en) * | 2002-08-26 | 2003-02-12 | 鲁南制药股份有限公司 | Slow-releasing acipimox tablet |
| CN1486695A (en) * | 2003-07-04 | 2004-04-07 | 天津万斯瑞医药科技有限公司 | Delayed releasing Acipimox prepn |
| CN102188431A (en) * | 2011-05-09 | 2011-09-21 | 浙江九旭药业有限公司 | Doxazosin mesylate sustained-release tablets and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 潘卫三等: "阿昔莫司缓释片的体外释放度及释放机制的初步研究", 《中国新药杂志》 * |
| 郝贵周等: "星点设计－效应面法优化阿昔莫司控释片处方研究", 《齐鲁药事》 * |
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