CN100588394C - Compound tablet capable of controlling release of effective component after oral administration, and preparation method thereof - Google Patents
Compound tablet capable of controlling release of effective component after oral administration, and preparation method thereof Download PDFInfo
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- CN100588394C CN100588394C CN03133386A CN03133386A CN100588394C CN 100588394 C CN100588394 C CN 100588394C CN 03133386 A CN03133386 A CN 03133386A CN 03133386 A CN03133386 A CN 03133386A CN 100588394 C CN100588394 C CN 100588394C
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- water soluble
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Abstract
The present invention provides a compound tablet capable of controlling release of effective component after oral administration, and makes it possible to control the release of water soluble medicineand water insoluble medicine. The compound orally administrated tablet contains both water soluble medicine and water insoluble medicine, the water soluble medicine is coated with polymer material toform delayed released granules the slow release n certain rule, and the water insoluble medicine is released fast. The preparation process of the present invention includes the first preparation of delayed released granules of water soluble medicine, the subsequent preparation of fast released water insoluble medicine, and final mixing and tabletting in a conventional rotary tabletting machine.
Description
Technical field:
The present invention relates to medical technical field, exactly it is compound recipe sheet of energy sustained release active ingredient behind the oral administration and preparation method thereof.
Background technology:
So far can sustained release behind the oral administration the existing listing of compound tablet of active ingredient, in order to reach the different drug release behaviors of water soluble drug and poorly water soluble drugs in the compound recipe sheet, the general at present method of two (many) synusia of compacting that adopts prepares such product.But two (many) synusia of preparation must use special tablet machine, and this must increase extraordinary tablet machine equipment when making this class compound tablet of manufacturer's Development and Production, has increased investment, thereby, limited the exploitation and the production of this class compound tablet.
Summary of the invention:
The purpose of this invention is to provide behind the oral administration compound recipe sheet that can the sustained release active ingredient and preparation method thereof, it can use conventional rotary tablet machine (or one-shot formula tablet machine) once to suppress such product.This process can reduce the phase mutual interference between the different drug release behaviors of each component in the compound recipe sheet.Can be used for preparing behind the oral administration can the sustained release active ingredient the compound recipe sheet, make the prepared compound recipe sheet that goes out according to certain rule continue, the water soluble drug in the releasing piece slowly, the poorly water soluble drugs in the releasing piece rapidly simultaneously.And the release rule of medicine is reproducible, is associated with the blood drug level that is measured in human body after the administration.
Among the mechanism that control various active composition discharges, the selected mechanism of the present invention be according to the release request that active ingredient will reach prepare independently, the granule of non-interfering each active ingredient, then in flakes with these granule compactings, and in sheet, add binding agent (or disintegrating agent), with the mouldability that guarantees slice, thin piece and particulate interference not mutually.The slice, thin piece of preparing according to this principle keeps portable, good surface appearance before use, then be dispersed into the granule of each active ingredient in release medium (external) or the stomach-intestinal juice (in the body), different activities composition granule is according to own release characteristic diffusion release.
For the water soluble drug that requires slowly to discharge, there be many being fit to that it is prepared into the method for slow-releasing granules.Main have the granule that utilizes macromolecular compound that medicine and excipient combination are made to carry out enclose or directly medicine and the macromolecular compound methods such as making granule that mixes.These macromolecular compounds mainly are particularly cellulose ethers, for example hydroxypropyl cellulose, hydroxyethyl-cellulose, methylcellulose, ethyl cellulose and hydroxypropyl emthylcellulose such as cellulosic cpd and resinae chemical compound.And for the poorly water soluble drugs that requires to discharge rapidly, then can adopt methods such as its enclose, micronization, adding surfactants to quicken its release.Can discharge the process of the compound recipe sheet of water soluble drug and poorly water soluble drugs by different rates to preparation.The compound recipe sheet that adopts this process to make, water soluble drug wherein continues, discharges slowly with certain rule, and poorly water soluble drugs then is to discharge rapidly.And the made compound recipe sheet of this process is that disposable compacting is in blocks.This oral contains water soluble drug and poorly water soluble drugs simultaneously.Water soluble drug is to continue, discharge slowly with certain rule in this compound recipe sheet, and poorly water soluble drugs then is rapid release.Described water soluble drug can be metformin hydrochloride, nicotinic acid, acetaminophen, pseudoephedrine hydrochloride etc., and poorly water soluble drugs can be glibenclamide, glipizide, hydroxyl first glutaryl CoA reductase inhibitor (statins) etc.Water soluble drug is the slow-releasing granules that adopts the water soluble drug of macromolecular material packaging technique preparation.The coating macromolecular material that is adopted can be cellulosic cpd or resinae chemical compound.Described poorly water soluble drugs is the granule that can discharge medicine rapidly that is prepared into by poorly water soluble drugs.Behind the immediate-release granules mix homogeneously of the slow-releasing granules of water soluble drug and poorly water soluble drugs, disposable compacting is in blocks.
Advantage of the present invention is: can make up above-mentioned present adjuvant commonly used and preparation method by the different active ingredient compound recipe of sustained release sheet behind the oral administration of preparation, make sustained release water soluble drug and poorly water soluble drugs become possibility.Even this sustained release makes the different activities composition be pressed into non-interfering release of characteristics that a slice, thin piece also can be as requested.The technology that is provided is simple, is easy to realize, and can uses conventional rotary tablet machine once to suppress in flakes.When developing this class compound tablet, alleviated cost, convenience is provided for manufacturer.
Description of drawings:
Fig. 1 represents to adopt this method to prepare the release profiles of nicotinic acid in the nicotinic acid lovastatin compound slow-release tablet.
Fig. 2 represents to adopt this method to prepare the release profiles of lovastatin in the nicotinic acid lovastatin compound slow-release tablet.
Fig. 3 represents to adopt this method to prepare the release profiles of metformin hydrochloride in the metformin hydrochloride glibenclamide compound slow-release tablet.
Fig. 4 represents to adopt this method to prepare the release profiles of glibenclamide in the metformin hydrochloride glibenclamide compound slow-release tablet.
Has visibly different release in vitro kinetics by two kinds of efficacy components in the visible example 1 compound recipe sheet of the curve of Fig. 1 and 2.Water soluble drug nicotinic acid wherein is for continuing, slowly discharging; The poorly water soluble drugs lovastatin is a rapid release.
Has visibly different release in vitro kinetics by two kinds of efficacy components in the visible example 2 compound recipe sheets of the curve of Fig. 3 and 4.Water soluble drug metformin hydrochloride wherein is for continuing, slowly discharging; The poorly water soluble drugs glibenclamide is a rapid release.
The specific embodiment:
The present invention relates to prepare behind the oral administration can the different active ingredient compound recipe of sustained release sheet method mainly divided for three steps.The first step prepares the slow-releasing granules of water soluble drug; The immediate-release granules of second step preparation poorly water soluble drugs; It is in blocks that the 3rd step was mixed the disposable compacting of above-mentioned granule.
Following example is introduced the present invention, but is not to limit the present invention by any way.
The preparation method of the different active ingredient compound recipe of energy sustained release sheet behind the oral administration:
Step a:
The mixture of macromolecular compound, filler and water soluble drug adds suitable amount of adhesive system soft material, and resulting soft material is through granulation, drying, the granule that obtains having the good physical feature;
Step b:
An amount of coating is dissolved in certain amount of organic solvent-water mixed solution with macromolecular material, adds suitable manufacturing methods simultaneously, dissolving is uniformly dispersed, as coating solution;
Step c:
With the made coating solution of step b step a gained granule is carried out coating, obtain the slow-releasing granules of the water soluble drug of good release characteristic;
Steps d:
Mixing water insoluble drug and necessary adjuvant add an amount of binding agent system soft material, and resulting soft material is through granulation, drying, obtain having the immediate-release granules of the poorly water soluble drugs of good physical feature and release characteristic;
Step e:
Step c and the made granule of steps d are fully mixed, look concrete condition and add adjuvants such as dry method binding agent, use tablet machine granule to be pressed into slice, thin piece with good physical feature.
Embodiment 1:
Embodiment 1 shows that employing this method prepares nicotinic acid lovastatin compound slow-release tablet.The prescription of concrete tablet is as follows, is prepared according to steps A to the program that E describes.
Prescription (g/1000 sheet)
Nicotinic acid 500.00g
Lovastatin 20.00g
Ethyl cellulose (10cp) 275.00g
Starch 140.00g
S-630 46.75g
PEG1500 0.03g
Magnesium stearate 4.68g
Embodiment 2:
Embodiment 2 shows that employing this method prepares metformin hydrochloride glibenclamide compound slow-release tablet.The prescription of concrete tablet is as follows, is prepared according to steps A to the program that E describes.
Prescription (g/1000 sheet)
Metformin hydrochloride 500.00g
Glibenclamide 2.50g
Ethyl cellulose (10cp) 300.00g
Microcrystalline Cellulose (pH101) 80.00g
Beta-schardinger dextrin-25.00g
S-630 45.00g
PEG1500 0.03g
Magnesium stearate 4.50g.
Claims (2)
1, the compound recipe sheet of energy sustained release active ingredient behind the oral administration, this oral contains water soluble drug and poorly water soluble drugs simultaneously, water soluble drug is the slow-releasing granules that adopts the water soluble drug of macromolecular material packaging technique preparation, poorly water soluble drugs is the granule that can discharge medicine rapidly that is prepared into by poorly water soluble drugs, it is characterized in that: described water soluble drug is a metformin hydrochloride, poorly water soluble drugs is a glibenclamide, and its prescription of 1000 is composed as follows:
Metformin hydrochloride 500.00g
Glibenclamide 2.50g
Ethyl cellulose 10cp 300.00g
Microcrystalline Cellulose pH101 80.00g
Beta-schardinger dextrin-25.00g
S-630 45.00g
PEG1500 0.03g
Magnesium stearate 4.50g.
2, the preparation method of the compound recipe sheet of energy sustained release active ingredient behind a kind of oral administration as claimed in claim 1, it is characterized in that: it comprises the following steps:
Step a:
The mixture of microcrystalline Cellulose and metformin hydrochloride adds an amount of S-630 system soft material, and resulting soft material is through granulation, drying, the granule that obtains having the good physical feature;
Step b:
Coating is dissolved in organic solvent-water mixed solution with ethyl cellulose, adds plasticizer P EG1500 simultaneously, dissolving is uniformly dispersed, as coating solution;
Step c:
With the made coating solution of step b step a gained granule is carried out coating, obtain the slow-releasing granules of the water soluble drug of good release characteristic;
Steps d:
Mix glibenclamide and beta-schardinger dextrin-, adds an amount of S-630 system soft material, resulting soft material is through granulation, drying, obtains having the immediate-release granules of the poorly water soluble drugs of good physical feature and release characteristic;
Step e:
Step c and the made granule of steps d are fully mixed, add magnesium stearate, use tablet machine granule to be pressed into slice, thin piece with good physical feature.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN03133386A CN100588394C (en) | 2003-05-28 | 2003-05-28 | Compound tablet capable of controlling release of effective component after oral administration, and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN03133386A CN100588394C (en) | 2003-05-28 | 2003-05-28 | Compound tablet capable of controlling release of effective component after oral administration, and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1457768A CN1457768A (en) | 2003-11-26 |
| CN100588394C true CN100588394C (en) | 2010-02-10 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN03133386A Expired - Fee Related CN100588394C (en) | 2003-05-28 | 2003-05-28 | Compound tablet capable of controlling release of effective component after oral administration, and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100588394C (en) |
-
2003
- 2003-05-28 CN CN03133386A patent/CN100588394C/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| 药用辅料手册. 罗明生,高天惠，73，四川科学技术出版社. 1993 |
| 药用辅料手册. 罗明生,高天惠，73，四川科学技术出版社. 1993 * |
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| Publication number | Publication date |
|---|---|
| CN1457768A (en) | 2003-11-26 |
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Granted publication date: 20100210 Termination date: 20140528 |