CN1254240C - Silibinin meglumine salt oral disintegration tablet preparation and its preparing method - Google Patents
Silibinin meglumine salt oral disintegration tablet preparation and its preparing method Download PDFInfo
- Publication number
- CN1254240C CN1254240C CN 200410069355 CN200410069355A CN1254240C CN 1254240 C CN1254240 C CN 1254240C CN 200410069355 CN200410069355 CN 200410069355 CN 200410069355 A CN200410069355 A CN 200410069355A CN 1254240 C CN1254240 C CN 1254240C
- Authority
- CN
- China
- Prior art keywords
- silybin
- methylglucamine
- meglumine salt
- agent
- disintegration tablet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 238000010579 first pass effect Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical class OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 210000003026 hypopharynx Anatomy 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 229940037627 magnesium lauryl sulfate Drugs 0.000 description 1
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002160 maltose Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229960001462 sodium cyclamate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention relates to an oral disintegration tablet of silibinin meglumine salt which can protect liver cells from being damaged, can stimulate the biosynthesis of protein in the liver cells, can promote damaged liver cells from recovering, can have the direct and indirect anti-fibrosis function, can catch an oxygen free radical, and can have the function for preventing and clearing fat from depositing and soaking on liver. The present invention has the purpose to compensate for the defects of the agent type of the present silibinin meglumine salt preparation agent and to provide an oral silibinin meglumine salt disintegration tablet which has clear chemical component, quick absorption and high biological utilization, avoids the first over effect of liver and is conveniently taken, and preparation process thereof for most patients and medical workers. Silibinin meglumine salt is used as a raw material, a filling agent, a disintegrating agent, a corrective agent, glidant, a lubricating agent, etc. are used as auxiliary materials, an adhesive agent or a coating material can be used according to different conditions, and a proper quantity of effervescent agents are added in according to a detailed situation; furthermore, a mixture is prepared by a specific preparation method, and a finished product is obtained by the tabletting of a tabletting machine. The oral disintegration tablet of the present invention has the characteristics of good friability, quick disintegration, good mouth feel, no sand sensation, unnecessary specific production condition, low production cost, convenient carrying, storage, transportation and taking, etc., is especially suitable for patients who are difficult to swallow or are taken under the condition of no water, improves the dependence of patients, and improves the treating effect of medicine.
Description
[technical field]
The present invention relates to a kind ofly have significant protection and stablize hepatocellular effect; be used for the treatment of the silybin-N-methylglucamine preparation of diseases such as acute, chronic hepatitis, liver cirrhosis, liver poisoning, relate in particular to a kind of silibinin meglumine salt oral disintegration tablet preparation and preparation method thereof with rapid release effect.
[background technology]
Silybin-N-methylglucamine is silibinin and meglumine (1-methylamino-1-deoxidation sorbitol) be combined into, and silybin-N-methylglucamine is soluble in water than silibinin, so the performance of infiltration rate and curative effect is excellent than silibinin all.
Silybin-N-methylglucamine has identical indication and clinical efficacy with silibinin.
The dosage form of silybin-N-methylglucamine preparation mainly contains ordinary tablet and capsule formulation at present.Still find no the orally disintegrating tablet preparation or the relevant document of silybin-N-methylglucamine.Silybin-N-methylglucamine is made oral cavity disintegration tablet, make the patient easy to carry and use, help improving patient's compliance, and then can guarantee the silybin-N-methylglucamine curative effect.
[summary of the invention]
The objective of the invention is to improve existing silybin-N-methylglucamine aspect peroral dosage form deficiency, provide a kind of taking convenience, absorption is rapid-action, bioavailability is high silibinin meglumine salt oral disintegration tablet preparation to extensive patients and medical personnel.Needn't drink water when the present invention relates to take, in the oral cavity, only need get final product rapid disintegrate or dissolving in tens seconds, can finish silibinin meglumine salt oral disintegration tablet of taking medicine and preparation method thereof with saliva hypopharynx.
One, prescription
The silibinin meglumine salt oral disintegration tablet that reaches of the present invention comprises the material medicine silybin-N-methylglucamine, needs following former, the auxiliary material of 9 classes altogether, wherein: when not making Cotton seeds, then do not use coating material, effervescent also can for selecting adjuvant for use as one sees fit.When not making Cotton seeds, prescription is formed: silybin-N-methylglucamine (5-50) %, binding agent (0-5) %, filler (10-80) %, disintegrating agent (2-35) %, correctives (1-40) %, effervescent (0-30) %, fluidizer (0.01-5) %, lubricant (0.3-3) %.When carrying out Cotton seeds, silibinin meglumine salt oral disintegration tablet of the present invention, make silybin-N-methylglucamine powder coating granule by the silybin-N-methylglucamine powder coating, again with other component mixing, tabletting, obtain disintegrating tablet, it is described silibinin meglumine salt oral disintegration tablet, comprise silybin-N-methylglucamine, filler, disintegrating agent, correctives, fluidizer, lubricant and coating material, optional there are binding agent or effervescent, wherein, calculate with weight percentage, silybin-N-methylglucamine 5%～50%, filler 10%～80%, disintegrating agent 2%～35%, correctives 1%～40%, fluidizer 0.01%～5%, lubricant 0.3%～3%, binding agent 0～5%, effervescent 0～30%, coating material is no more than 40%, it is characterized in that: described coating material is a crylic acid resin, and silybin-N-methylglucamine makes silybin-N-methylglucamine powder coating granule by powder coating, again with other component mixing, tabletting makes disintegrating tablet.
Above-mentioned described component, wherein:
Binding agent, include but are not limited to starch, pregelatinized Starch, dextrin, maltodextrin, sucrose, arabic gum, methylcellulose, carboxymethyl cellulose, ethyl cellulose, polyvinyl alcohol, Polyethylene Glycol, polyvinylpyrrolidone (PVP), alginic acid and alginate, xanthan gum and hydroxypropyl emthylcellulose (HPMC), can use use also capable of being combined separately.
Filler includes but are not limited to mannitol (granular or powdery), xylitol, sorbitol, maltose, microcrystalline Cellulose, PROSOLV
SMCC, polymerization sugar (EMDEX
), glucose, lactose, sucrose, dextrin and starch etc., can use separately, also can applied in any combination, consumption is generally (10-80) %.
Disintegrating agent includes but are not limited to microcrystalline Cellulose, PROSOLV
SMCC, crospolyvinylpyrrolidone (PVPP), carboxymethyl starch sodium (CMS-Na), low substituted hydroxy-propyl methylcellulose (L-HPC), cross-linking sodium carboxymethyl cellulose (CCNa) and soybean polysaccharide (EMCOSOY
) etc., can use use also capable of being combined separately.
Correctives, include but are not limited to mannitol, xylitol, stevioside, lactose, fructose, sucrose, protein sugar, maltose alcohol, glycyrrhizin, Sodium Cyclamate, gelatin, aspartame, flavoring banana essence, flavoring pineapple essence, vanillin, fragrant citrus essence, flavoring orange essence, Herba Menthae essence, ginseng essence, strawberry essence, citric acid, citric acid etc., can use use also capable of being combined separately.
Crylic acid resin is homemade acrylic resin I, II, III or IV, perhaps You Teqi (Eudragit
) series, for example strange E100 (Eudragit of You Te
E100).
Fluidizer includes but are not limited to micropowder silica gel, Pulvis Talci, Cab-O-sil, Arosil, hydrated sodium aluminosilicate etc., can use use also capable of being combined separately.
Lubricant, include but are not limited to magnesium stearate, calcium stearate, zinc stearate, glyceryl monostearate, Polyethylene Glycol, hydrogenated vegetable oil, sodium stearyl fumarate, polyoxyethylene monostearate, single Laurel sucrose acid ester, sodium laurylsulfate, magnesium laurylsulfate, Stepanol MG and Pulvis Talci etc., can use use also capable of being combined separately.
Effervescent includes but are not limited to the mixture of malic acid, citric acid or citric acid and sodium bicarbonate or sodium carbonate.
Two, preparation method
The silibinin meglumine salt oral disintegration tablet that reaches of the present invention, its preparation method is a direct compression process, the manufacturer with preparation conventional tablet all can adopt.
The silybin-N-methylglucamine mildly bitter flavor is puckery, and the present invention can adopt two kinds of distinct methods to carry out flavoring or taste masking:
1. adopt the direct flavoring of correctives; 2. in advance silybin-N-methylglucamine is carried out powder coating with taste masking.
The concrete preparation method that powder coating prepares silibinin meglumine salt oral disintegration tablet is as follows:
The first step is got selected coating material, uses the solvent dissolving that adapts with it and be diluted to debita spissitudo standby;
Second goes on foot the Silybin meglumine of fetching water again places ebullated bed to make boiling, sprays into above-mentioned solution with suitable speed then and carries out powder coating, gets silybin-N-methylglucamine powder coating granule, dry back sieving for standby;
The 3rd step made filler, disintegrating agent, correctives, fluidizer, lubricant, optional binding agent or the effervescent mix homogeneously that exists evenly again with through second mixing of materials that goes on foot gained, and is standby;
The 4th step gained material detects through intermediate, determine that sheet is heavy after, send into the tablet machine tabletting promptly.
[beneficial effect]
Tablet is a kind of conventional dosage forms, because of its steady quality, dosage accurately, take, easy to carry, mechanization degree is high, low one of the at present the most frequently used dosage form that becomes of production cost, but because of the tablet extrusion forming, disintegrate is slow, bioavailability is lower, and part patient swallows comparatively difficult, thereby promoting the use of to a certain extent of tablet is restricted.The oral administration solid quick releasing formulation becomes a focus, particularly oral cavity disintegration tablet of new drug development in recent years for this reason, because of its taking convenience, rapid-action, bioavailability is high, the good emphasis that becomes tablet exploitation of mouthfeel.
Oral cavity disintegration tablet is meant not to be needed water or only needs low amounts of water, need not to chew, and tablet places lingual surface, meets after saliva separates rapidly or collapse, and borrows and swallows power, and medicine can be gone into the tablet of stomach onset.The characteristics of oral cavity disintegration tablet are that absorption is fast, bioavailability is high, and intestinal is residual few, and side effect is low, avoids liver first-pass effect etc.
According to the requirement of " formulation characteristic of oral cavity disintegration tablet and quality control meeting summary ", oral cavity disintegration tablet has essential leap than the disintegration rate of drop pill and ordinary tablet, and the disintegrate of oral cavity disintegration tablet generally in 30 seconds, is no more than 1 minute at most.
[specific embodiment]
For the preparation method of silibinin meglumine salt oral disintegration tablet of the present invention better is described, in conjunction with directly flavoring method and powder coating taste masking method are as follows for an embodiment respectively:
Embodiment one direct flavoring method
One. prescription
1. raw material---silybin-N-methylglucamine 100.0g;
2. binding agent---polyvinylpyrrolidone K-301.0g;
3. filler---mannitol 154.0g;
4. correctives---aspartame 3.0g;
Flavoring orange essence 6.0g;
5. disintegrating agent---crospolyvinylpyrrolidone 14.0g;
Cross-linking sodium carboxymethyl cellulose 16.0g;
6. fluidizer---micropowder silica gel 3.0g;
7. lubricant---sodium stearyl fumarate 3.0g.
Gross weight 300g makes 2000 altogether.
Two. preparation method
1) water intaking Silybin meglumine raw material pulverizing is granulated with polyvinylpyrrolidone K-30, and water or ethanol are wetting agent, crosses 26 mesh sieves, and oven dry is standby;
2) with crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, micropowder silica gel, sodium stearyl fumarate, flavoring orange essence and aspartame, cross 40 mesh sieves respectively, mix homogeneously adds the silybin-N-methylglucamine granule of having granulated again, and mix homogeneously is standby;
3) add the mannitol mix homogeneously again;
4) intermediate content detection, determine that sheet is heavy after, send into the tablet machine tabletting promptly.
Embodiment two powder coating taste masking methods
One. prescription
1. raw material---silybin-N-methylglucamine 100.0g;
2. coating material---the strange E100 (Eudragit of You Te
E100) 20.0g;
3. filler---mannitol 132.0g;
4. correctives---aspartame 3.0g;
Flavoring orange essence 6.0g;
5. disintegrating agent---crospolyvinylpyrrolidone 14.0g;
Cross-linking sodium carboxymethyl cellulose 16.0g;
6. fluidizer---micropowder silica gel 6.0g;
7. lubricant---sodium stearyl fumarate 3.0g.
Gross weight 300g makes 2000 altogether.
Two. preparation method
1) gets the strange E100 (Eudragit of You Te
E100) with the dissolving of the medicinal industrial alcohol more than 95% and to be diluted to finite concentration standby;
2) the water intaking Silybin meglumine places ebullated bed to seethe with excitement, and sprays into above-mentioned solution by certain speed and carries out powder coating, makes silybin-N-methylglucamine powder coating granule, and dry back is standby;
3) with mannitol, micropowder silica gel, PVPP, L-HPC, aspartame, sodium stearyl fumarate and flavoring orange essence mix homogeneously, again and sieve after the coated granule mixing standby;
4) intermediate content detection, determine that sheet is heavy after, send into the tablet machine tabletting promptly.
Claims (2)
1. silibinin meglumine salt oral disintegration tablet, it is characterized in that its weight consists of silybin-N-methylglucamine 5～50%, clothing sheet material polyacrylic resin 6.67～40%, disintegrating agent crospolyvinylpyrrolidone 2～35%, filler 10-80%, correctives 1～40%, fluidizer 0.01～5%, lubricant 0.3～3% is formed, wherein filler is selected from mannitol, microcrystalline Cellulose, dextrin, lactose, starch, in maltodextrin and the pregelatinized Starch one or more, correctives is selected from mannitol, lactose, stevioside, gelatin, aspartame, cyclamate, glycyrrhizin, fragrant citrus essence, flavoring orange essence, Herba Menthae essence, ginseng essence, strawberry essence, citric acid, in the citric acid one or more, fluidizer is selected from micropowder silica gel, Pulvis Talci, Cab-O-sil, Arosil, in the hydrated sodium aluminosilicate one or more, lubricant is selected from magnesium stearate, glyceryl monostearate, Stepanol MG, in the Pulvis Talci one or more; After wherein silybin-N-methylglucamine being carried out powder coating with coating material, the gained granule is pressed into disintegrating tablet with other adjuvant.
2. the preparation method of silibinin meglumine salt oral disintegration tablet as claimed in claim 1 is characterized in that being made up of following steps:
The pretreatment of first step silybin-N-methylglucamine; Get selected coating material, with the dissolving of the solvent that adapts with it and to be diluted to debita spissitudo standby, the Silybin meglumine of fetching water again places fluid bed to make boiling, spray into above-mentioned solution with suitable speed then and carry out powder coating, get silybin-N-methylglucamine powder coating granule, dry back sieving for standby;
Second step took by weighing correctives and silybin-N-methylglucamine granule or the feed particles after first step taste masking processing according to quantity, and mix homogeneously is standby;
The 3rd step took by weighing filler, disintegrating agent, fluidizer and mix homogeneously according to quantity, made evenly again with through second mixing of materials that goes on foot gained, added the lubricant mixing, and is standby;
The 4th step gained material detects through intermediate, determine that sheet is heavy after, send into the tablet machine tabletting promptly.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410069355 CN1254240C (en) | 2004-07-19 | 2004-07-19 | Silibinin meglumine salt oral disintegration tablet preparation and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410069355 CN1254240C (en) | 2004-07-19 | 2004-07-19 | Silibinin meglumine salt oral disintegration tablet preparation and its preparing method |
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| CN103768048B (en) * | 2012-10-21 | 2015-11-25 | 江苏中兴药业有限公司 | Silybin meglumine tablets and effect for reducing fat thereof |
| CN111297814A (en) * | 2019-12-18 | 2020-06-19 | 湖南千金协力药业有限公司 | Compound preparation for reducing liver toxicity of tripterygium glycosides tablets and preparation method thereof |
| CN112587488B (en) * | 2020-12-16 | 2022-12-06 | 福建瑞泰来医药科技有限公司 | Silybin composition and preparation method thereof |
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