CN101530399A - Silibinin solid self-emusifying tablet and preparation method thereof - Google Patents
Silibinin solid self-emusifying tablet and preparation method thereof Download PDFInfo
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- CN101530399A CN101530399A CN200910030758A CN200910030758A CN101530399A CN 101530399 A CN101530399 A CN 101530399A CN 200910030758 A CN200910030758 A CN 200910030758A CN 200910030758 A CN200910030758 A CN 200910030758A CN 101530399 A CN101530399 A CN 101530399A
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- silibinin
- emusifying
- tablet
- poloxamer
- glyceryl monostearate
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- SEBFKMXJBCUCAI-UHFFFAOYSA-N NSC 227190 Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-UHFFFAOYSA-N 0.000 title claims abstract description 57
- 235000014899 silybin Nutrition 0.000 title claims abstract description 57
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 title claims abstract description 56
- 229950000628 silibinin Drugs 0.000 title claims abstract description 55
- 239000007787 solid Substances 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title abstract description 15
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims abstract description 60
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 30
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims abstract description 28
- 229960000502 poloxamer Drugs 0.000 claims abstract description 28
- 229920001983 poloxamer Polymers 0.000 claims abstract description 28
- 239000000741 silica gel Substances 0.000 claims abstract description 24
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 24
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 21
- 239000008187 granular material Substances 0.000 claims abstract description 21
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- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 18
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 18
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 18
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 18
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims abstract description 18
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims abstract description 18
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims abstract description 18
- 239000000843 powder Substances 0.000 claims abstract description 15
- 229940079593 drug Drugs 0.000 claims abstract description 12
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 27
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 27
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- 239000000594 mannitol Substances 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
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- 238000000034 method Methods 0.000 claims description 6
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- 238000010521 absorption reaction Methods 0.000 abstract description 8
- 239000000969 carrier Substances 0.000 abstract 1
- 238000002483 medication Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 13
- 239000004530 micro-emulsion Substances 0.000 description 9
- 238000012377 drug delivery Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
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- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
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- 206010008909 Chronic Hepatitis Diseases 0.000 description 2
- FDQAOULAVFHKBX-UHFFFAOYSA-N Isosilybin A Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC(=CC=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 FDQAOULAVFHKBX-UHFFFAOYSA-N 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- VLGROHBNWZUINI-UHFFFAOYSA-N Silybin Natural products COc1cc(ccc1O)C2OC3C=C(C=CC3OC2CO)C4Oc5cc(O)cc(O)c5C(=O)C4O VLGROHBNWZUINI-UHFFFAOYSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
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- 210000003494 hepatocyte Anatomy 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
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- 238000002347 injection Methods 0.000 description 2
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- -1 silibinin phospholipid Chemical class 0.000 description 2
- 229940043175 silybin Drugs 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- DUVVGYBLYHSFMV-YGEZULPYSA-N 4-methyl-n-[[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]carbamoyl]benzamide Chemical compound C1=CC(C)=CC=C1C(=O)NC(=O)N[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DUVVGYBLYHSFMV-YGEZULPYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 206010070840 Gastrointestinal tract irritation Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
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- 210000001124 body fluid Anatomy 0.000 description 1
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- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007957 coemulsifier Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000004064 cosurfactant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
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- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
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- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000008855 peristalsis Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention relates to a silibinin solid self-emusifying tablet and a preparation method thereof. The silibinin solid self-emusifying tablet comprises silibinin, poloxamer F68, glycerin monostearate, microcrystalline cellulose, mannite, polyvinylpolypyrrolidone, superfine silica gel powder and magnesium stearate; the mass ratio of the silibinin to the poloxamer F68+the glycerin monostearate to the microcrystalline cellulose+the mannite+the polyvinylpolypyrrolidone+the superfine silica gel powder+the magnesium stearate= from 1:1:3 to 1:6:20; the silibinin solid self-emusifying tablet exists in an amorphous state, and medical granules are enclosed by soluble carriers; and the mass ratio of the poloxamer F68 to the glycerin monostearate= from 1:11 to 1:1. The silibinin solid self-emusifying tablet has good absorption, increases the effectiveness and safety of medications, and obviously reduces the treatment cost of the patient.
Description
Technical field
The present invention relates to a kind of silibinin solid self-emusifying tablet and preparation method thereof, specifically contain the self-emusifying tablet of silibinin, be used for acute and chronic hepatitis, the recovery of the abnormal liver function of fatty liver.
Background technology
Silibinin, English name: silibinin; Chemical name: 2 α-[2,3-is trans-2,3-dihydro-3-(4-hydroxy 3-methoxybenzene base)-2-methylol-1,4-benzodioxane-6-yl]-2,3-dihydro-3 β, 5,7-trihydroxy-4H-1-.alpha.-5:6-benzopyran-4-ketone-hydrate.Molecular formula: C25H22010.H2O; Molecular weight: 500.47.
The silibinin preparation is the listing history of existing nearly half a century at home and abroad.Clinical research confirmation, silibinin has liver protection function preferably to chronic hepatitis patient, even 2/3 hepatocyte is destroyed by hepatitis virus in patient's liver, still can guarantee all the other 1/3 hepatocyte liver function of can bringing into normal play as long as adhere to taking silibinin.
The own poor solubility of silibinin (its water solublity, fat-soluble all bad), oral difficult absorption causes bioavailability low, is difficult to arrive site of action.Someone studies, and silibinin is become ester with succinic acid, makes silibinin succinic acid monoester sodium drug administration by injection, and effect is fine.But its shortcoming is the medication inconvenience and costs an arm and a leg, is difficult to meet clinical needs.Existing market Herba Silybi mariani preparation relatively has the kind of striving power unexpectedly that import preparation, silybin meglumine preparation, silibinin phospholipid complex formulation are arranged, allow silibinin is the same with other drug fully to be absorbed by human body, need research and solve the problem that preparation absorbs.Because the curative effect and the safety of silibinin itself are very definite, and the delivery system that changes, so degree of absorption and speed are the matters of utmost importance that needs solution.
The preparation of silibinin mainly contains tablet, capsule and injection etc.Because silibinin is insoluble in water, oral absorption is poor, bioavailability is low, influences its clinical practice.For this reason, positive active development is developed its novel form both at home and abroad, increases its dissolution velocity or changes its stripping and absorption characteristic, to improve bioavailability.Except that its meglumine salt commonly used or bis-bias succinate sodium salt.Additive method has employing Polyethylene Glycol (PEG), polyvinylpyrrolidone adjuvants such as (PVP) to make solid dispersion, cyclodextrin clathrate, fabaceous lecithin, liposome, phosphatidylcholine complex etc.
After proposing the microemulsion notion in 1940, played the carrier that microemulsion begins to be used as hydrophobic drug in 1970, this year is along with research gos deep into, self-microemulsifying drug delivery system (Self-microemulsifying drug deliverysystem, SMEDDS) notion of this newtype drug transmission system have been proposed.The definition of self-microemulsifying drug delivery system and characteristics: the homogeneous that microemulsion is made up of emulsifying agent, co-emulsifier, oil and water, isotropic transparent or semitransparent dispersion, Thermodynamically stable, particle size distribution is in 10-100nm.Its advantage: particle diameter is little, the solution clear, and medicine increase-volume amount is big, and preparation is more stable.Self-microemulsifying drug delivery system comprises oil phase, surfactant and cosurfactant (or containing low amounts of water), and pharmaceutical pack is rolled in the oil droplet, and the spontaneous O/W type microemulsion that is dispersed into of body fluid (common 37 ℃) under gastrointestinal peristalsis is met in oral back.Self-microemulsifying drug delivery system can be used as the carrier of hydrophobicity, difficult absorption, facile hydrolysis medicine, oral back contacts with gastro-intestinal Fluid and forms the little emulsion droplet of medicine carrying, increased the long-pending and dissolubility of medical surfaces,, fast distribution even at gastrointestinal tract, surfactant can reduce surface tension, has overcome the obstacle when macromole passes through the gastrointestinal tract epithelial cell film, and medicine is easy to be delivered to absorption site by the gastrointestinal wall hydrated sheath, improve dissolution and permeability, reduced the medicine peak of curve/paddy ratio and untoward reaction for the moment.Self-microemulsifying drug delivery system also can absorb through lymphatic vessel and overcome first pass effect, can avoid to a certain extent medicine in gastrointestinal tract by enzyme hydrolysis, help to improve bioavailability.
Summary of the invention
1, technical problem to be solved:
The objective of the invention is to overcome above-mentioned weak point, thereby thereby provide a kind of medicine gastrointestinal that promotes to absorb, improve bioavailability of medicament raising curative effect, Tabules taking convenience, the oral self emulsifying of silibinin, i.e. a kind of silibinin solid self-emusifying tablet and preparation method thereof.
2, technical scheme:
Silibinin solid self-emusifying tablet of the present invention comprises silibinin, poloxamer F68, glyceryl monostearate, microcrystalline Cellulose, mannitol, polyvinylpolypyrrolidone, micropowder silica gel, magnesium stearate, mass ratio between them is: silibinin: poloxamer F68+ glyceryl monostearate: mannitol+microcrystalline Cellulose+polyvinylpolypyrrolidone+micropowder silica gel+magnesium stearate=1:1:3 to 1:6:20, it exists with amorphous state, is surrounded by soluble carrier around the drug particles.Mass ratio between poloxamer F68 and the glyceryl monostearate is: poloxamer F68: glyceryl monostearate=1:11 to 1:1.Glyceryl monostearate is the self emulsifying glyceryl monostearate.
A kind of method for preparing silibinin solid self-emusifying tablet, adopt following processing step:
(1), with half of silibinin, poloxamer F68, glyceryl monostearate and micropowder silica gel, add anhydrous alcohol solution, solution temperature is: 40-70 ℃, reserve liquid.
(2), again with microcrystalline Cellulose, mannitol, polyvinylpolypyrrolidone and remaining 1/2 micropowder silica gel mix homogeneously in mixer, spread in dish, put and be dried to powder in the baking oven, baking temperature is: 60-85 ℃, be drying time: 4-5 hour, standby; Mixer rotating speed: 10～15r/min.
(3), the reserve liquid of step 1 gained is joined in the powder of step 2 gained, and it is added wet granulation in granulator, spread in dish, put and carry out drying in the baking oven, baking temperature is: 50-60 ℃, be drying time: 4-5 hour, and granulate, standby.
(4), add magnesium stearate again in the above-mentioned granule, fully mix homogeneously joins tabletting in the tablet machine hopper, gets product tablet machine rotating speed: 8～12r/min.
Wet granulation order number is: 16 orders-30 order; Granulate order number is: 16 orders-40 order.
3, beneficial effect:
Silibinin self-emusifying tablet of the present invention, silibinin, poloxamer F68, mannitol, glyceryl monostearate is for forming solid self-emulsifying microemulsion system, wherein silibinin is a principal agent, poloxamer is a surfactant, mannitol is auxiliary agent, glyceryl monostearate is an oil phase, because component is solid,, add filler with this system so can form solid self-emulsifying microemulsion system, disintegrate prepares tablet, production equipment with conventional tablet is simple, be convenient to packing, the advantage that stores and transport and carry, taking convenience of the present invention, absorbability is good, GI irritation is littler, and medicine loses little in the whole absorption process of human body; Owing to used solid self-emulsifying technology (nanotechnology) dexterously, obviously can increase the effectiveness and the safety of medication, obviously reduced patient's treatment cost.Pharmacoeconomics studies show that using silybin nanostructured Emulsion can reduce dosage 10%～15%, the general practice expense can reduce about 20%, can bring great social benefit and economic benefit, preparation has good stability, meets water stripping rapidly, forms characteristics such as even Emulsion, bioavailability height; Preparation technology is simple, and equipment is not had specific (special) requirements, is fit to large-scale production.
The specific embodiment
Following the present invention will be further described in conjunction with the embodiments:
Any ratio between glyceryl monostearate=1:11 to 1:1), 105 grams are to 700 grams (mannitol+microcrystalline Cellulose+polyvinylpolypyrrolidone+micropowder silica gel+magnesium stearate) the present invention suppresses and gets 35 gram silibinin, 35 grams in 1000 Herba Silybi mariani self-emusifying tablets prescription (mass ratio between poloxamer F68 and the glyceryl monostearate is: poloxamer F68: to 210 gram poloxamer F68 and glyceryl monostearate, wherein mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, micropowder silica gel, magnesium stearate are the conventional amount used ratio, and dehydrated alcohol is a convention amount;
Micropowder silica gel with silibinin, poloxamer F68, glyceryl monostearate and 1/2, add anhydrous alcohol solution and add the micropowder silica gel mix homogeneously powder wet granulation of microcrystalline Cellulose, mannitol, polyvinylpolypyrrolidone and 1/2, dry granulate, add magnesium stearate and mix the back tabletting, get product.
The preparation method of silibinin self-emusifying tablet of the present invention adopts following processing step:
(1), with the micropowder silica gel of silibinin, poloxamer F68, glyceryl monostearate and 1/2, add anhydrous alcohol solution, solution temperature is: 40-70 ℃, reserve liquid;
(2), again with micropowder silica gel mix homogeneously in mixer of microcrystalline Cellulose, mannitol, polyvinylpolypyrrolidone and 1/2, spread in dish, put and be dried to powder in the baking oven, baking temperature is 60-85 ℃, be drying time: 4-5 hour, standby; Mixer rotating speed: 10～15r/min;
(3), the reserve liquid of step 1 gained is joined in the powder of step 2 gained, and it is added wet granulation in granulator, wet granulation order number is: 16 orders-30 order; Spread in dish, put and carry out drying in the baking oven, baking temperature is: 50-60 ℃, be drying time: 4-5 hour, and granulate, standby, granulate order number is: 16 orders-40 order;
(4), add magnesium stearate again in the above-mentioned granule, fully mix homogeneously joins tabletting in the tablet machine hopper, gets product tablet machine rotating speed: 8～12r/min.
Embodiment one:
The present invention get 35 gram silibinin, 52.5 gram poloxamer F68,50 gram mannitol, 200 gram microcrystalline Cellulose, _ 52.5 gram glyceryl monostearates, 50 gram polyvinylpolypyrrolidone, 50 gram micropowder silica gels, 5 gram magnesium stearate, 100 gram dehydrated alcohol;
(1), with the micropowder silica gel of silibinin, poloxamer F68, glyceryl monostearate and 1/2, add anhydrous alcohol solution, solution temperature is: 50 ℃, reserve liquid.
(2), again with micropowder silica gel mix homogeneously in mixer of microcrystalline Cellulose, mannitol, polyvinylpolypyrrolidone and 1/2, spread in dish, put and be dried to powder in the baking oven, baking temperature is: 60 ℃, be drying time: 4 hours, standby; Mixer rotating speed: 10～15r/min.
(3), the reserve liquid of step 1 gained is joined in the powder of step 2 gained, and it is added wet granulation in granulator, wet granulation order number is: 18 orders; Spread in dish, put and carry out drying in the baking oven, baking temperature is: 50 ℃, be drying time: 5 hours, and granulate, standby.Granulate order number is: 16 orders.
(4), add magnesium stearate again in the above-mentioned granule, fully mix homogeneously joins tabletting in the tablet machine hopper, gets product.Tablet machine rotating speed: 10r/min.
Embodiment two:
The present invention gets 35 gram silibinin, 140 gram poloxamer F68,50 gram mannitol, 200 gram microcrystalline Cellulose, 70 gram glyceryl monostearates, 100 gram polyvinylpolypyrrolidone, 100 gram micropowder silica gels, 7 gram magnesium stearate, 200 gram dehydrated alcohol;
(1), with the micropowder silica gel of silibinin, poloxamer F68, glyceryl monostearate and 1/2, add anhydrous alcohol solution, solution temperature is: 50 ℃, reserve liquid.
(2), again with micropowder silica gel mix homogeneously in mixer of microcrystalline Cellulose, mannitol, polyvinylpolypyrrolidone and 1/2, spread in dish, put and be dried to powder in the baking oven, baking temperature is: 60 ℃, be drying time: 4 hours, standby; Mixer rotating speed: 10～15r/min.
(3), the reserve liquid of step 1 gained is joined in the powder of step 2 gained, and it is added wet granulation in granulator, wet granulation order number is: 18 orders; Spread in dish, put and carry out drying in the baking oven, baking temperature is: 50 ℃, be drying time: 5 hours, and granulate, standby.Granulate order number is: 16 orders.
(4), add magnesium stearate again in the above-mentioned granule, fully mix homogeneously joins tabletting in the tablet machine hopper, gets product.Tablet machine rotating speed: 8r/min.
Embodiment three:
The present invention gets 35 gram silibinin, 96.25 gram poloxamer F68,100 gram mannitol, 150 gram microcrystalline Cellulose, 8.75 gram glyceryl monostearates, 50 gram polyvinylpolypyrrolidone, 50 gram micropowder silica gels, 5 gram magnesium stearate, 100 gram dehydrated alcohol;
(1), with the micropowder silica gel of silibinin, poloxamer F68, glyceryl monostearate and 1/2, add anhydrous alcohol solution, solution temperature is: 50 ℃, must reach liquid fully;
(2), again with micropowder silica gel mix homogeneously in mixer of microcrystalline Cellulose, mannitol, polyvinylpolypyrrolidone and 1/2, spread in dish, put and be dried to powder in the baking oven, baking temperature is: 60 ℃, be drying time: 4 hours, standby; Mixer rotating speed: 10～15r/min.
(3), the reserve liquid of step 1 gained is joined in the powder of step 2 gained, and it is added wet granulation in granulator, wet granulation order number is: 18 orders; Spread in dish, put and carry out drying in the baking oven, baking temperature is: 50 ℃, be drying time: 5 hours, and granulate, standby.Granulate order number is: 16 orders.
(4), add magnesium stearate again in the above-mentioned granule, fully mix homogeneously joins tabletting in the tablet machine hopper, gets product.Tablet machine rotating speed: 8r/min.
Poloxamer F68 has another name called general stream sieve 188, and glyceryl monostearate is the self emulsifying glyceryl monostearate.
Adopt the self-emusifying tablet of solid self-microemulsion technology development among three embodiment of the present invention, micropowder silica gel by principal agent silibinin and poloxamer F68, glyceryl monostearate and 1/2 is dissolved in the ethanol together, cooperate mannitol to make whole system form the system of self-emulsifying microemulsion, then this delivery system is disperseed to be adsorbed on solid adjuvant material, form silibinin solid self-microemulsion sheet.
Medicine exists with amorphous state in the silibinin self-emusifying tablet, is surrounded by soluble carrier around the drug particles, makes the medical surfaces of hydrophobicity slightly solubility have good wettability, and drug microparticles is easily wetted, has accelerated dissolution and trap.
The present invention has adopted 1/2 micropowder silica gel to add in the solid self-emulsifying body, does not influence the stripping of silibinin, makes that the solid self-emulsifying body disperses easily, drying and granulate, helps big production practical operation.
The equipment that adopts among the present invention is conventional common apparatus, for example: one-step-granulating method; 35 towards full-automatic tablet machine etc., and the raw material that uses is purchased by market.
Claims (5)
1, a kind of silibinin solid self-emusifying tablet, it is characterized in that: comprise silibinin, poloxamer F68, glyceryl monostearate, microcrystalline Cellulose, mannitol, polyvinylpolypyrrolidone, micropowder silica gel, magnesium stearate, mass ratio between them is: silibinin: poloxamer F68+ glyceryl monostearate: mannitol+microcrystalline Cellulose+polyvinylpolypyrrolidone+micropowder silica gel+magnesium stearate=1:1:3 to 1:6:20, it exists with amorphous state, is surrounded by soluble carrier around the drug particles.
2, a kind of silibinin solid self-emusifying tablet according to claim 1, it is characterized in that: the mass ratio between poloxamer F68 and the glyceryl monostearate is: poloxamer F68: glyceryl monostearate=1:11 to 1:1.
3, a kind of silibinin solid self-emusifying tablet according to claim 1 and 2 is characterized in that: glyceryl monostearate is the self emulsifying glyceryl monostearate.
4, a kind of method for preparing the described a kind of silibinin solid self-emusifying tablet of claim 1 is characterized in that: adopt following processing step:
(1), with half of silibinin, poloxamer F68, glyceryl monostearate and micropowder silica gel, add anhydrous alcohol solution, solution temperature is: 40-70 ℃, reserve liquid;
(2), again with microcrystalline Cellulose, mannitol, polyvinylpolypyrrolidone and remaining 1/2 micropowder silica gel mix homogeneously in mixer, spread in dish, put and be dried to powder in the baking oven, baking temperature is: 60-85 ℃, be drying time: 4-5 hour, standby; Mixer rotating speed: 10～15r/min;
(3), the reserve liquid of step 1 gained is joined in the powder of step 2 gained, and it is added wet granulation in granulator, spread in dish, put and carry out drying in the baking oven, baking temperature is: 50-60 ℃, be drying time: 4-5 hour, and granulate, standby;
(4), add magnesium stearate again in the above-mentioned granule, fully mix homogeneously joins tabletting in the tablet machine hopper, gets product tablet machine rotating speed: 8～12r/min.
5, a kind of method for preparing silibinin solid self-emusifying tablet according to claim 4, it is characterized in that: wet granulation order number is: 16 orders-30 order; Granulate order number is: 16 orders-40 order.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012006965A1 (en) * | 2010-07-16 | 2012-01-19 | Zhong Shuguang | Tablet with improved comprehensive performance and preparation method therefor |
| CN105853374A (en) * | 2016-04-26 | 2016-08-17 | 江苏中兴药业有限公司 | Preparation method of silybin-phospholipid complex |
| CN111494564A (en) * | 2020-04-30 | 2020-08-07 | 江苏中兴药业有限公司 | Preparation method of compound liver-protecting and alcohol-dispelling tablet |
| US11142517B2 (en) | 2016-11-16 | 2021-10-12 | H. Lundbeck A/S | Crystalline forms of a MAGL inhibitor |
| US11273159B2 (en) | 2016-11-16 | 2022-03-15 | H. Lundbeck A/S | Pharmaceutical formulations |
| RU2775232C1 (en) * | 2016-11-16 | 2022-06-28 | Абайд Терапьютикс, Инк. | Pharmaceutical compositions |
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| CN100348199C (en) * | 2002-12-19 | 2007-11-14 | 王登之 | Silicibinin-N-methylglucamine disperser for treating hepatitis, and its prepn. method |
| CN1311822C (en) * | 2004-12-16 | 2007-04-25 | 中国药科大学 | Preparation of slowly releasing silybum mariamum |
| CN1957936A (en) * | 2005-11-05 | 2007-05-09 | 安徽中医学院 | Silybin tiny pellets and preparation method |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012006965A1 (en) * | 2010-07-16 | 2012-01-19 | Zhong Shuguang | Tablet with improved comprehensive performance and preparation method therefor |
| CN105853374A (en) * | 2016-04-26 | 2016-08-17 | 江苏中兴药业有限公司 | Preparation method of silybin-phospholipid complex |
| US11142517B2 (en) | 2016-11-16 | 2021-10-12 | H. Lundbeck A/S | Crystalline forms of a MAGL inhibitor |
| US11273159B2 (en) | 2016-11-16 | 2022-03-15 | H. Lundbeck A/S | Pharmaceutical formulations |
| RU2775232C1 (en) * | 2016-11-16 | 2022-06-28 | Абайд Терапьютикс, Инк. | Pharmaceutical compositions |
| US11993588B2 (en) | 2016-11-16 | 2024-05-28 | H. Lundbeck A/S | Crystalline forms of a MAGL inhibitor |
| CN111494564A (en) * | 2020-04-30 | 2020-08-07 | 江苏中兴药业有限公司 | Preparation method of compound liver-protecting and alcohol-dispelling tablet |
| CN111494564B (en) * | 2020-04-30 | 2021-07-27 | 江苏中兴药业有限公司 | Preparation method of compound liver-protecting and alcohol-dispelling tablet |
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| CN101530399B (en) | 2011-01-26 |
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Denomination of invention: Silibinin solid self-emusifying tablet and preparation method thereof Effective date of registration: 20130106 Granted publication date: 20110126 Pledgee: Zhenjiang Jiangsu rural commercial bank Limited by Share Ltd Zhongshan Road branch Pledgor: Jiangsu Zhongxing Pharmaceutical Co., Ltd. Registration number: 2012320000002 |
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Address after: 212143 Zhenjiang City, Jiangsu province high tech Industrial Park of Dantu District No. 86 Leng Yu Lu Patentee after: Jiangsu Zhongxing Pharmaceutical Co., Ltd. Address before: 212009 No. three, No. 6, weft Road, Zhenjiang, Jiangsu Patentee before: Jiangsu Zhongxing Pharmaceutical Co., Ltd. |
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Correction item: Patentee|Address Correct: Jiangsu Zhongxing Pharmaceutical Co., Ltd|No.6 Weisan Road, Zhenjiang City, Jiangsu Province, 212009 False: Jiangsu Zhongxing Pharmaceutical Co., Ltd|No.86 lengfu Road, high tech Industrial Park, Dantu District, Zhenjiang City, Jiangsu Province 212143 Number: 43-02 Volume: 33 |
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Address after: 212143 Zhenjiang City, Jiangsu province high tech Industrial Park of Dantu District No. 86 Leng Yu Lu Patentee after: ZHONGXING PHARM Co.,Ltd. JIANGSU Address before: 212009 No. three, No. 6, weft Road, Jiangsu, Zhenjiang Patentee before: ZHONGXING PHARM Co.,Ltd. JIANGSU |