CN104666260A - Ezetimibe tablet - Google Patents
Ezetimibe tablet Download PDFInfo
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- CN104666260A CN104666260A CN201510055735.9A CN201510055735A CN104666260A CN 104666260 A CN104666260 A CN 104666260A CN 201510055735 A CN201510055735 A CN 201510055735A CN 104666260 A CN104666260 A CN 104666260A
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- ezetimibe
- tablet
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- polyvidone
- aerosil
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Abstract
The invention belongs to the technical field of drugs and in particular relates to an ezetimibe tablet. The ezetimibe tablet comprises ezetimibe, hydroxypropyl cellulose, diethylene glycol monoethyl ether, fumed silica, filling agents, disintegrating agents and lubricating agents. The tablet is prepared by dissolving ezetimibe and hydroxypropyl cellulose in diethylene glycol monoethyl ether, adding fumed silica for adsorption, then mixing the materials with pharmaceutically acceptable auxiliary materials uniformly and pressing the mixture by adopting a direct tabletting process. Compared with the prior art, the ezetimibe tablet is high in drug dissolution speed and simple in process and dispenses with addition of surfactants and micronization treatment.
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of Ezetimibe tablet.
Background technology
Ezetimibe is white crystalline powder, easily molten in ethanol, methanol and acetone, almost insoluble in water, and Ezetimibe fusing point about 163 DEG C, at room temperature stablizes.Ezetimibe is clinical is mainly used in primary hypercholesterolemia, this product is as the auxiliary treatment beyond diet control, can separately or with HMG-CoA reductase inhibitor as Statins be united and applied in treatment hypercholesterolemia, T-CHOL (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB) can be reduced, or as the complementary therapy (as LDL-C Apheresis) of other lipid-lowering therapies, can also when other lipid-lowering therapies are invalid for reducing TC and the LDL-C level of HoFH patient.
Ezetimibe is water insoluble, and when oral administration uses the solid dosage forms of Ezetimibe, this medicine must be dissolved in gastric juice, could be played curative effect by absorption.The solid oral dosage form of compacting, as the common preparations such as tablet usually limit its bioavailability because of its rate of dissolution, thus have impact on the curative effect of medicine.Reducing granularity is one of method of the increase dissolubility that this area is commonly used, and in fact reduction granularity is improved deliquescent method and is used to Ezetimibe.But, reduce granularity and can not effectively make the raising of the dissolution rate of Ezetimibe reach gratifying scope.So how granularity to be further improved, thus improve the dissolubility of preparation, increase bioavailability, become the demand that in Ezetimibe research one is urgent.
CN103655481A provides a kind of oral formulations preparation method of Ezetimibe.Adopt ball milling solid dispersion technology, Ezetimibe and pharmaceutically acceptable adjuvant are prepared into solid orally ingestible, improve the dissolution of preparation.But medicine and milling material are ground, milling material may be brought in medicine ball milling fine powder, brings safety concerns during patient medication.This is also the potential risk that ball grinding technique is generally acknowledged.
CN102292072A discloses the method with drug microparticles coating carrier.Coating carrier can obtain in one-step method, the method need from the solution droplets comprising API evaporating solvent to obtain dry microgranule, then by its coating on carrier.But need special production equipment, industrialization is comparatively difficult, and stripping that can not be quick and complete.
CN 103877051A provides a kind of preparation method of Ezetimibe sheet, and hydroxypropyl cellulose and Ezetimibe are dissolved in ethanol, carrier material mannitol dissolves in aqueous.Supercritical carbon dioxide fluid and above-mentioned two kinds of solution are passed into a coaxial three-channel nozzle respectively; utilize the solvent resistant effect of supercritical carbon dioxide fluid; the ultra-fine grain obtained containing Ezetimibe, hydroxypropyl cellulose and mannitol mixes powder, ultra-fine grain is mixed powder and pharmaceutically acceptable adjuvant direct compression forms.The method needs to use supercritical equipment, expensive, and operation with high pressure, is not suitable for suitability for industrialized production.
Summary of the invention
The object of the present invention is to provide that a kind of preparation technology is simple, utilization ratio of drug is high, physical property is stable and the water miscible tablet of Ezetimibe can be significantly improved.Solid dispersions technique is combined with solubilizing agent and adsorbent by inventor, first prepare solid dispersion solubilize drugs, the dispersion solution aerosil of medicine is adsorbed, then mixs homogeneously with pharmaceutically acceptable adjuvant, tabletting, the stripping of gained tablet is rapid.
Specifically, the present invention is achieved through the following technical solutions:
The invention provides a kind of Ezetimibe tablet, this tablet is made up of Ezetimibe, polyvidone, TC, aerosil, filler, disintegrating agent and lubricant.Described Ezetimibe tablet, the weight ratio of Ezetimibe and TC is 1:4-10.Preferably, weight ratio is 1:7.
Described Ezetimibe tablet, be prepared from by the following method: Ezetimibe, polyvidone are dissolved in TC, add aerosil absorption, then even with filler, disintegrating agent and mix lubricant, adopt the compacting of direct compression technique to form.
Described Ezetimibe tablet, the weight ratio of Ezetimibe and polyvidone is 1:1-3.Preferably, weight ratio is 1:2.
Described Ezetimibe tablet, the weight ratio of Ezetimibe and aerosil is 1:20-35.Preferably, weight ratio is 1:25.
Described filler be selected from microcrystalline Cellulose, lactose, mannitol, starch and dextrin one or more.
Described disintegrating agent be selected from carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone and low-substituted hydroxypropyl cellulose one or more.
Described lubricant be selected from magnesium stearate, sodium stearyl fumarate, Pulvis Talci and silicon dioxide one or more.
Compared with prior art, drug-eluting speed is fast in the present invention, and technique is simple, does not need to add surfactant, does not also need micronization processes.Accelerated test result shows, Ezetimibe tablet stability prepared by the present invention is good.
Detailed description of the invention
Following examples further describe beneficial effect of the present invention, embodiment is only for the object of illustration, do not limit the scope of the invention, the simultaneously apparent change made according to the present invention of those of ordinary skill in the art and modification are also contained within the scope of the invention.
Embodiment 1
Preparation technology:
Ezetimibe is dissolved in TC, adds polyvidone, be stirred to dissolve, then add the aerosil absorption of recipe quantity, then with lactose, carboxymethyl starch sodium, magnesium stearate mix homogeneously, adopt the compacting of direct compression technique to form.
Embodiment 2
Preparation technology:
Ezetimibe is dissolved in TC, add polyvidone, be stirred to dissolve, then add the aerosil absorption of recipe quantity, then with microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, the compacting of direct compression technique is adopted to form.
Embodiment 3
Preparation technology:
Ezetimibe is dissolved in TC, add polyvidone, be stirred to dissolve, then add the aerosil absorption of recipe quantity, then with microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, the compacting of direct compression technique is adopted to form.
Embodiment 4
Preparation technology:
By Ezetimibe comminution by gas stream, particle diameter is D90=17.8 μm, add the polyvidone of recipe quantity, aerosil, microcrystalline Cellulose, polyvinylpolypyrrolidone mix homogeneously, add TC, granulate, then add magnesium stearate, mix homogeneously, adopt the compacting of direct compression technique to form.
Embodiment 5
Preparation technology:
By Ezetimibe comminution by gas stream, particle diameter is D90=17.1 μm, add the polyvidone of recipe quantity, aerosil, microcrystalline Cellulose, polyvinylpolypyrrolidone mix homogeneously, add TC, granulate, then add magnesium stearate, mix homogeneously, adopt the compacting of direct compression technique to form.
Embodiment 6
Preparation technology:
Take Ezetimibe and the lactose mix homogeneously of recipe quantity.Ezetimibe milk-sugar mixture is added in pulverizer and pulverizes 3 minutes, then with the polyvidone of recipe quantity, aerosil, crosslinked carboxylic polyvidone, mix homogeneously, add TC, granulate, then add magnesium stearate, mix homogeneously, adopt the compacting of direct compression technique to form.
Embodiment 7
Preparation technology:
Take Ezetimibe and the lactose mix homogeneously of recipe quantity.Ezetimibe milk-sugar mixture is added in pulverizer and pulverizes 3 minutes, then with the polyvidone of recipe quantity, aerosil, crosslinked carboxylic polyvidone, mix homogeneously, add TC, granulate, then add magnesium stearate, mix homogeneously, adopt the compacting of direct compression technique to form.
Comparative example 1
Preparation technology:
Ezetimibe is dissolved in TC, then adds the aerosil absorption of recipe quantity, then with microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, adopt the compacting of direct compression technique to form.
Comparative example 2
Preparation technology:
By Ezetimibe comminution by gas stream, particle diameter is D90=16.3 μm, then with microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, adopts the compacting of direct compression technique to form.
Checking embodiment
Dissolution determination: measure according under Chinese Pharmacopoeia version in 2010 two annex items, paddle method, rotating speed is with 50 revs/min, dissolution medium be 900ml contain 0.45% sodium lauryl sulphate acetate buffer in, detect under 234nm with UV detector, 5min stripping limit is 80%.
The each embodiment measurement result of table 1
As seen from the table, embodiment of the present invention 1-3 stripping is rapid, and after accelerating, stripping is substantially unchanged; Embodiment 4-7, granulate by TC, because raw material can not fully dissolve in a solvent, therefore stripping is slightly slow; Comparative example 1, do not add polyvidone in solvent, and when stripping measures, medicine is separated out, therefore stripping is unhappy; Comparative example 2, raw material micronization processes, and stripping comparatively the present invention is slow.
Claims (7)
1. an Ezetimibe tablet, is characterized in that, this tablet is made up of Ezetimibe, polyvidone, TC, aerosil, filler, disintegrating agent and lubricant; The weight ratio of described Ezetimibe and TC is 1:4-10; Described Ezetimibe tablet is prepared from by following method: be dissolved in TC by Ezetimibe, polyvidone, add aerosil absorption, then with pharmaceutically acceptable adjuvant mix homogeneously, the compacting of direct compression technique is adopted to form.
2. Ezetimibe tablet according to claim 1, is characterized in that, the weight ratio of Ezetimibe and TC is 1:7.
3. Ezetimibe tablet according to claim 1, is characterized in that, the weight ratio of Ezetimibe and polyvidone is 1:1-3.
4. Ezetimibe tablet according to claim 1, is characterized in that, the weight ratio of Ezetimibe and polyvidone is 1:2.
5. Ezetimibe tablet according to claim 1, is characterized in that, the weight ratio of Ezetimibe and aerosil is 1:20-35.
6. Ezetimibe tablet according to claim 1, is characterized in that, the weight ratio of Ezetimibe and aerosil is 1:25.
7. Ezetimibe tablet according to claim 1, is characterized in that, described filler be selected from microcrystalline Cellulose, lactose, mannitol, starch, dextrin one or more; Described disintegrating agent be selected from carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose one or more; Described lubricant be selected from magnesium stearate, sodium stearyl fumarate, Pulvis Talci, silicon dioxide one or more.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510055735.9A CN104666260B (en) | 2015-02-03 | 2015-02-03 | A kind of Ezetimibe tablet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510055735.9A CN104666260B (en) | 2015-02-03 | 2015-02-03 | A kind of Ezetimibe tablet |
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| Publication Number | Publication Date |
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| CN104666260A true CN104666260A (en) | 2015-06-03 |
| CN104666260B CN104666260B (en) | 2018-01-19 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106822020A (en) * | 2017-02-21 | 2017-06-13 | 鲁南制药集团股份有限公司 | A kind of Ezetimibe tablet |
| CN112190580A (en) * | 2020-09-22 | 2021-01-08 | 太阳升(亳州)生物医药科技有限公司 | Method for preparing ezetimibe tablets and ezetimibe tablets |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101048180A (en) * | 2004-10-25 | 2007-10-03 | 日本烟草产业株式会社 | Solid formulation with improved solubility and stability, and method for producing said formulation |
| WO2008063766A2 (en) * | 2006-10-10 | 2008-05-29 | Isp Investments Inc. | Amorphous ezetimibe and the production thereof |
| CN102657598A (en) * | 2012-05-09 | 2012-09-12 | 上海交通大学 | Porous inorganic material based oral preparation of secondary-dispersion insoluble drug and preparation method thereof |
-
2015
- 2015-02-03 CN CN201510055735.9A patent/CN104666260B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101048180A (en) * | 2004-10-25 | 2007-10-03 | 日本烟草产业株式会社 | Solid formulation with improved solubility and stability, and method for producing said formulation |
| WO2008063766A2 (en) * | 2006-10-10 | 2008-05-29 | Isp Investments Inc. | Amorphous ezetimibe and the production thereof |
| CN102657598A (en) * | 2012-05-09 | 2012-09-12 | 上海交通大学 | Porous inorganic material based oral preparation of secondary-dispersion insoluble drug and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 罗明生等: "《中国药用辅料》", 30 April 2006, 化学工业出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106822020A (en) * | 2017-02-21 | 2017-06-13 | 鲁南制药集团股份有限公司 | A kind of Ezetimibe tablet |
| CN112190580A (en) * | 2020-09-22 | 2021-01-08 | 太阳升(亳州)生物医药科技有限公司 | Method for preparing ezetimibe tablets and ezetimibe tablets |
Also Published As
| Publication number | Publication date |
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| CN104666260B (en) | 2018-01-19 |
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