CN1589790A - Abedol slow release tablet and its preparation method - Google Patents
Abedol slow release tablet and its preparation method Download PDFInfo
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- CN1589790A CN1589790A CNA031592228A CN03159222A CN1589790A CN 1589790 A CN1589790 A CN 1589790A CN A031592228 A CNA031592228 A CN A031592228A CN 03159222 A CN03159222 A CN 03159222A CN 1589790 A CN1589790 A CN 1589790A
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- abiduoer
- slow releasing
- releasing tablet
- waxiness
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Abstract
A slow-release tablet of Abiduoer as an antivirus medicine features that in order to make it be dissolved in water, it can contain the hydrophilic gel skeleton (hydroxypropylmethyl cellulose) or the wax skeleton (glyceride behenate). Its preparing process is also disclosed.
Description
Technical field
The present invention relates to the slow releasing tablet of antiviral drugs arbidol HCl.
Background technology
Arbidol HCl (Arbidol hydrochloride) is a kind of novel antiviral medicine.It is the most remarkable to the antiviral activity with A, the antigenic influenza virus of Type B, can suppress A, Type B influenza virus duplicating in cell culture medium by selectivity.Abiduoer has immunoregulation effect simultaneously, can induce the generation interferon, and activating macrophage improves the resistance of body to viral infection, is to be used for the treatment of the influenza that A, Type B virus cause and the novel antiviral medicine of acute respiratory viral infection.
Animal pharmacokinetics experiment shows, rat oral gavage gives that Abiduoer (150mg/kg) post-absorption is rapid, and blood plasma tmax is 20min, and t1/2 is 6.7h.Because the Abiduoer half-life is shorter, in order to reach optimum therapeuticing effect, common Abiduoer tablet or capsule need administration 3～4 times every day when clinical application, and each 200mg makes troubles for patient's medication.Therefore, be necessary the slow release method of arbidol HCl is studied.
Summary of the invention
Slow releasing preparation can provide suitable blood drug level to human body on demand in the scheduled period, reduce medicining times and can obtain excellent curative.Its important feature is can make human body keep this kind blood drug level to reach the long period, do not descend faster the ordinary preparation and do not resemble, thereby " peak valley " phenomenon that just can avoid the ordinary preparation frequent drug administration to be occurred increases safety, effectiveness and the adaptability of medicine.
Matrix sustained release tablet is to use one of more oral slow-releasing preparation kind clinically at present, and its preparation technology is easy, and the release stable in properties is suitable for suitability for industrialized production.Matrix sustained release tablet can be divided into insoluble matrix sustained release tablet, hydrogel matrix slow releasing tablet, waxiness matrix sustained release tablet etc. by the framework material difference that it adopted.
For this medicine of arbidol HCl,, therefore can not adopt insoluble framework material, and can only be prepared into hydrogel matrix slow releasing tablet and waxiness matrix sustained release tablet because it is water-soluble hardly.
Abiduoer slow releasing tablet of the present invention is a matrix sustained release tablet, is respectively hydrogel matrix slow releasing tablet, waxiness matrix sustained release tablet.
In Abiduoer hydrogel matrix slow releasing tablet, contain 50～400 milligrams of active ingredient hydrochloric acid Abiduoers.
Hydrophilic gel matrix material shared part by weight in prescription can be 5～90% in hydrogel matrix tablet.
Hydrophilic gel matrix material is a hydrophilic polymer, meet water or Digestive system skeleton and expand, thereby can form firm gel barrier control medicine stripping, and protection label depths is not subjected to the influence of dissolution medium and disintegrate takes place.As time goes on, outer gel layer constantly dissolves, and inside forms gel layer again, dissolves until label to be dissolved in the dissolution medium fully again.
If the active component dissolubility is bigger, its releasing mechanism mainly is the diffusion of active component and the continuous corrosion of gel layer; Belong to indissoluble thing in the water as active component, slow release mechanism mainly shows in the corrosion process of gel layer.
The hydrophilic gel matrix material that is used for the Abiduoer slow releasing tablet comprises: natural gum, cellulose derivative, non-cellulosic polysaccharide, ethene polymers, crylic acid resin.
The hydrophilic gel matrix material natural gum comprises sodium alginate, agar, Calculus Bovis from Northwest of China fin glue etc.
The hydrophilic gel matrix material cellulose derivative comprises methylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, hydroxyethylmethyl-cellulose, sodium carboxymethyl cellulose etc.
The hydrophilic gel matrix material non-cellulosic polysaccharide comprises chitin etc.
The hydrophilic gel matrix material ethene polymers comprises polyvinyl alcohol, carbopol etc.
The hydrophilic gel matrix material crylic acid resin comprises Eudragit E, Eudragit RL, Eudragit RS etc.
Above-mentioned hydrophilic gel matrix material is hydroxypropyl emthylcellulose preferably, as the Methocel K series of products of DowChemical.
The preparation of hydrogel matrix tablet can be adopted common wet granulation technology, can add various additive of tablet such as diluent, wetting agent or binding agent, lubricant, fluidizer, stabilizing agent etc. according to different situations.
The character of diluent also can influence the stripping of matrix tablet, and hydrophilic diluents helps medicine to discharge from framework material, and hydrophobic diluents then can delay the release of medicine.Can regulate the rate of release of medicine by adding following different diluent:
Hydrophilic diluents helps the material of moisture penetration in the pharmaceutical preparation as lactose, mannitol, sorbitol, xylitol, starch, microcrystalline Cellulose or other.
Hydrophobic diluents, as glyceryl monostearate, cetylate, hydrogenation or not hydrogenated vegetable oil, wax, list-, two-or tri-substituted glycerol ester, or other can delay the material of moisture penetration in the pharmaceutical preparation.
The optional water of wetting agent or binding agent, ethanol, starch slurry, polyvinylpyrrolidine and various cellulose family.
Lubricant and fluidizer adopt magnesium stearate, stearic acid, Polyethylene Glycol-4000 ,-6000, Talcum, micropowder silica gel etc. usually.
Because Abiduoer is a hydrochlorate, its aqueous solution of 0.07% (g/ml) PH is between 4.85～5.05, and unstable in aqueous solution and under the high temperature, outward appearance is flavescence gradually.And,, can keep the stability of Abiduoer in wet-granulation process as adding acid regulators such as dilute hydrochloric acid, tartaric acid, citric acid, lactic acid in the next stability of improving its aqueous solution of acid condition.
The waxiness matrix sustained release tablet is that framework material is made with materials such as inert fat or wax classes, and along with the corrosion gradually of fat or waxiness, drug slow discharges.
In Abiduoer waxiness matrix sustained release tablet, contain 50～400 milligrams of active ingredient hydrochloric acid Abiduoers.
Waxiness framework material shared weight ratio in prescription is 5～80% in the waxiness matrix tablet.
The waxiness framework material that is used for the Abiduoer slow releasing tablet comprises: hydrogenated vegetable oil, stearic acid, octadecanol, glyceryl stearate, Tridocosanoin etc.
Above-mentioned waxiness framework material is Tridocosanoin preferably, as the COMPRITOL of GATTEFOSSE company
R888 ATO.
Because the arbidol HCl poorly water-soluble, in its waxiness matrix tablet, need to add hydroaropic substance as pore-forming agent promoting the release of medicine, adoptable porogen has polyvinylpyrrolidone, microcrystalline Cellulose, Polyethylene Glycol-1500,4000,6000 etc.
The preparation of waxiness matrix tablet can be adopted direct compression, wet granulation, fusing or melt granulation technology.
Because COMPRITOL
R888 ATO have compressibility and cohesive preferably, with mixing such as diluent such as microcrystalline Cellulose, lactose, mannitol, sorbitol, calcium hydrogen phosphate, make direct compression become possibility with directly compressible.
Work as COMPRITOL
RWhen 888 ATO are used for wet granulation, only need add entry or organic solvent and make wetting agent and get final product.Diluent can adopt the kind that adopts usually in the wet granulation technology.
For wax materials such as hydrogenated vegetable oil, stearic acid, octadecanol, glyceryl stearate, can adopt fusing or melt granulation, waxiness is dissolved in organic solvent or fusion after, add Abiduoer, diluent and porogen, cooling back crushing screening is granulated, and adds the lubricant tabletting.
The specific embodiment
In Abiduoer hydrogel matrix slow releasing tablet, the preferred hydroxypropyl emthylcellulose of hydrophilic gel matrix material, as the Methocel K series of products of Dow Chemical, shared part by weight preferably 15～50% in prescription.
In Abiduoer waxiness matrix sustained release tablet, the waxiness framework material is Tridocosanoin preferably, as the COMPRITOL of GATTEFOSSE company
R888 ATO, shared part by weight preferably 10～40% in prescription.
With following embodiment the present invention is described.
Embodiment 1: arbidol HCl hydrogel matrix slow releasing tablet
Prescription:
200 milligrams of arbidol HCls
110 milligrams of Methocel K4M
130 milligrams of lactose
10% polyvinylpyrrolidone+2% tartaric acid is an amount of
95% alcoholic solution
5 milligrams of magnesium stearate
5 milligrams of Pulvis Talci
Sheet weighs 500 milligrams
Preparation technology:
Arbidol HCl was pulverized 80 mesh sieves, with behind Methocel K4M and the lactose mix homogeneously with granulating after 10% polyvinylpyrrolidone+2% tartaric acid, 95% alcoholic solution moistening, at 45～50 ℃ of dry back granulate, add magnesium stearate and Pulvis Talci, the mix homogeneously tabletting.
The release test:
For investigating the extracorporeal releasing characteristic of arbidol HCl slow releasing tablet, with the release of 2000 editions two appendix XC first methods of Chinese Pharmacopoeia (basket method) working sample.With water 900ml is solvent, and rotating speed is that per minute 100 changes, and respectively at sampling in 1,2,4,6,8 hour, according to spectrophotography (2000 editions two appendix IVA of Chinese Pharmacopoeia), measures trap, the release of calculation sample at the wavelength place of 257nm.
Result of the test sees Table one.
| Time (hour) | Release (%) |
| ????1 | ????12.3 |
| ????2 | ????21.5 |
| ????4 | ????37.4 |
| ????6 | ????46.7 |
| ????8 | ????58.6 |
| ????10 | ????67.7 |
| ????12 | ????75.3 |
| ????16 | ????86.9 |
| ????20 | ????94.7 |
| ????24 | ????99.5 |
Active substance can sustained release in about 20 hours.
Embodiment 2: arbidol HCl hydrogel matrix slow releasing tablet
Prescription:
200 milligrams of arbidol HCls
80 milligrams of Methocel K15M
160 milligrams of microcrystalline Cellulose
10% polyvinylpyrrolidone+2% tartaric acid is an amount of
95% alcoholic solution
5 milligrams of magnesium stearate
5 milligrams of Pulvis Talci
Sheet weighs 500 milligrams
Preparation technology:
Arbidol HCl was pulverized 80 mesh sieves, with behind Methocel K15M and the microcrystalline Cellulose mix homogeneously with granulating after 10% polyvinylpyrrolidone+2% tartaric acid, 95% alcoholic solution moistening, at 45～50 ℃ of dry back granulate, add magnesium stearate and Pulvis Talci, the mix homogeneously tabletting.
Embodiment 3: arbidol HCl hydrogel matrix slow releasing tablet
Prescription:
100 milligrams of arbidol HCls
50 milligrams of sodium alginates
70 milligrams of microcrystalline Cellulose
0.5% hydroxypropyl emthylcellulose+2% winestone is an amount of
Acid
60% alcoholic solution
2.5 milligrams of magnesium stearate
2.5 milligrams of Pulvis Talci
Sheet weighs 250 milligrams
Preparation technology:
Arbidol HCl was pulverized 80 mesh sieves, with behind sodium alginate and the microcrystalline Cellulose mix homogeneously with granulating after 0.5% hydroxypropyl emthylcellulose+2% tartaric acid, 60% alcoholic solution moistening, granulate after 45～50 dryings adds magnesium stearate and Pulvis Talci, the mix homogeneously tabletting.
Embodiment 4: arbidol HCl waxiness matrix sustained release tablet
Prescription:
200 milligrams of arbidol HCls
COMPRITOL
R35 milligrams of 888 ATO
65 milligrams of microcrystalline Cellulose
Water is an amount of
Sheet weighs 300 milligrams
Preparation technology:
Arbidol HCl was pulverized 80 mesh sieves, with COMPRITOL
RBehind 888 ATO and the microcrystalline Cellulose mix homogeneously with granulating after the water-wet, at 40～45 ℃ of dry back granulate, tabletting.
Embodiment 5:
Prescription:
200 milligrams of arbidol HCls
50 milligrams of glyceryl stearate
20 milligrams of polyvinylpyrrolidones
77.5 milligrams of microcrystalline Cellulose
2.5 milligrams of magnesium stearate
Sheet weighs 350 milligrams
Preparation technology:
Arbidol HCl was pulverized 80 mesh sieves, with glyceryl stearate fusion in 65 water-baths, the mixture that slowly adds arbidol HCl, polyvinylpyrrolidone and microcrystalline Cellulose while stirring, continuing to stir slowly cools off it, solidifying body is crossed 18 mesh sieves granulate, add the magnesium stearate tabletting.
Claims (16)
1, a kind of Abiduoer slow releasing tablet is characterized in that containing Abiduoer, also contains hydrophilic gel matrix material or waxiness framework material.
2, Abiduoer slow releasing tablet according to claim 1 is characterized in that hydrophilic gel matrix material comprises: natural gum, cellulose derivative, non-cellulosic polysaccharide, ethene polymers, crylic acid resin.
3, Abiduoer slow releasing tablet according to claim 1 and 2 is characterized in that containing 50～400 milligrams of active ingredient hydrochloric acid Abiduoers, and hydrophilic gel matrix material shared part by weight in prescription can be 5～90% in hydrogel matrix tablet.
4, Abiduoer slow releasing tablet according to claim 2 is characterized in that natural gum comprises sodium alginate, agar, Calculus Bovis from Northwest of China fin glue etc.
5, Abiduoer slow releasing tablet according to claim 2 is characterized in that cellulose derivative comprises methylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, hydroxyethylmethyl-cellulose, sodium carboxymethyl cellulose etc.
6, Abiduoer slow releasing tablet according to claim 2 is characterized in that non-cellulosic polysaccharide comprises chitin etc.
7, Abiduoer slow releasing tablet according to claim 2 is characterized in that ethene polymers comprises polyvinyl alcohol, carbopol etc.
8, Abiduoer slow releasing tablet according to claim 2 is characterized in that crylic acid resin comprises Eudragit E, Eudragit RL, Eudragit RS etc.
9, Abiduoer slow releasing tablet according to claim 3 is characterized in that the preferred hydroxypropyl emthylcellulose of hydrophilic gel matrix material, and shared part by weight preferably 15～50% in prescription.
10, Abiduoer slow releasing tablet according to claim 5 is characterized in that the preferred hydroxypropyl emthylcellulose of hydrophilic gel matrix material, and shared part by weight preferably 15～50% in prescription.
11, Abiduoer slow releasing tablet according to claim 1 is characterized in that the waxiness framework material comprises: hydrogenated vegetable oil, stearic acid, octadecanol, glyceryl stearate, Tridocosanoin.
12, according to claim 1 or 11 described Abiduoer slow releasing tablet, it is characterized in that containing 50～400 milligrams of active ingredient hydrochloric acid Abiduoers in the waxiness matrix sustained release tablet, waxiness framework material shared weight ratio in prescription is 5～80% in the waxiness matrix tablet.
13, Abiduoer slow releasing tablet according to claim 11 is characterized in that preferably Tridocosanoin of waxiness framework material, and shared part by weight preferably 10～40% in prescription.
14, Abiduoer slow releasing tablet according to claim 12 is characterized in that preferably Tridocosanoin of waxiness framework material, and shared part by weight preferably 10～40% in prescription.
15, a kind of preparation method of Abiduoer slow releasing tablet is characterized in that the Abiduoer hydrogel matrix tablet adopts common wet granulation technology.
16, a kind of preparation method of Abiduoer slow releasing preparation is characterized in that Abiduoer waxiness matrix tablet adopts direct compression, wet granulation, fusing or melt granulation technology.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031592228A CN100402027C (en) | 2003-09-04 | 2003-09-04 | Abedol slow release tablet and its preparation method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031592228A CN100402027C (en) | 2003-09-04 | 2003-09-04 | Abedol slow release tablet and its preparation method |
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| Publication Number | Publication Date |
|---|---|
| CN1589790A true CN1589790A (en) | 2005-03-09 |
| CN100402027C CN100402027C (en) | 2008-07-16 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031592228A Expired - Fee Related CN100402027C (en) | 2003-09-04 | 2003-09-04 | Abedol slow release tablet and its preparation method |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102357093A (en) * | 2011-09-01 | 2012-02-22 | 湖北丽益医药科技有限公司 | Medicinal composition of methanesulfonic acid arbidol oral solid preparation |
| CN105395504A (en) * | 2015-11-26 | 2016-03-16 | 郑州瑞启生物技术有限公司 | Flunarizine hydrochloride matrix sustained-release tablets and preparing method thereof |
-
2003
- 2003-09-04 CN CNB031592228A patent/CN100402027C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102357093A (en) * | 2011-09-01 | 2012-02-22 | 湖北丽益医药科技有限公司 | Medicinal composition of methanesulfonic acid arbidol oral solid preparation |
| CN102357093B (en) * | 2011-09-01 | 2013-03-20 | 湖北丽益医药科技有限公司 | Medicinal composition of methanesulfonic acid arbidol oral solid preparation |
| CN105395504A (en) * | 2015-11-26 | 2016-03-16 | 郑州瑞启生物技术有限公司 | Flunarizine hydrochloride matrix sustained-release tablets and preparing method thereof |
| CN105395504B (en) * | 2015-11-26 | 2019-06-28 | 郑州百瑞动物药业有限公司 | A kind of flunarizine hydrochloride matrix sustained release tablet and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100402027C (en) | 2008-07-16 |
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Effective date of registration: 20140617 Address after: 050035 No. 226, the Yellow River Avenue, hi tech Industrial Development Zone, Hebei, Shijiazhuang Patentee after: Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. of CSPC Group Patentee after: Shijiazhuang Pharmaceutical Group Ouyi Pharma Co., Ltd. Address before: 050051 No. 276 West Zhongshan Road, Hebei, Shijiazhuang Patentee before: Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. of CSPC Group |
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