CN105616355A - Solid dispersion of glycyrol and preparation of solid dispersion - Google Patents
Solid dispersion of glycyrol and preparation of solid dispersion Download PDFInfo
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- CN105616355A CN105616355A CN201410586777.0A CN201410586777A CN105616355A CN 105616355 A CN105616355 A CN 105616355A CN 201410586777 A CN201410586777 A CN 201410586777A CN 105616355 A CN105616355 A CN 105616355A
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Abstract
The invention discloses a solid dispersion of glycyrol, wherein the solid dispersion consists of the glycyrol and povidone which serves as a carrier material. Furthermore, the invention discloses a pharmaceutical preparation and a preparation method of the solid dispersion. Experiments show that the solid dispersion disclosed by the invention has made significant technical progress in such technical indicators as dissolution rate, stability, water solubility, bioavailability and the like.
Description
Technical field
The invention discloses the solid dispersion of a kind of glycyrol, comprise glycyrol and the polyvidone as carrier, belong to field of medicaments.
Background technology
Radix Glycyrrhizae is the root of glycyrrhizic legume GlycyrrhizauralensisFisch., is one of the most frequently used Chinese medicine, has effect of invigorating the spleen and replenishing QI, heat-clearing and toxic substances removing, nourishing the lung to arrest cough, relieving spasm to stop pain, coordinating the actions of various ingredients in a prescription. Its main chemical compositions has triterpene saponin, coumarin and flavone etc. And the multiple chemical composition of Radix Glycyrrhizae is all very important natural active matter, therefore the pharmacologically active of Radix Glycyrrhizae extract and some of them monomer is successively conducted in-depth research by Chinese scholars, and achieves some gratifying achievements.
Glycyrol (glycyrol) is the class coumarin kind compound in Radix Glycyrrhizae, domestic also it have been reported that this compound is neoglycyrol (Wang Cailan, Zhang Ruyi etc., the chemical research of novel coumarin in Glycyrrhiza uralensis Fisch., Acta Pharmaceutica Sinica,, 1991:26 (2): 147-151) Chinese scholars to the pharmacology activity research of this compound and the like achieved with a lot of valuable achievements. Hattori, Masao report that glycyrol and some other coumarin kind compound can be reasonably resistant to the antibacterial of causing dental caries-turn sugar chain coccus; Glycyrol can also suppress melanic generation simultaneously, the cosmetics of some skin whitenings all contain this kind of monomer, Saki, Tokimasa etc. point out that again including glycyrol Multiple components all shows (Glycyrrhizaextractsas ��-the glucosidaseinhibitors of the inhibitory action to alpha-glucosidase, Patent, Application:JP2002-5190920020227), and alpha-glucosidase activity is relevant to hyperglycemia. In Chinese patent 200710003022.3, inventor have found that this compound has immunosuppressive activity, can as the immunosuppressant of a kind of novelty.
Glycyrol is Coumestrol compounds, and containing ��, ��-unsaturated six-membered cyclic lactone and two aromatic rings, its structural formula is: different thiazolinyl-7 of defending of 5-methoxyl group-6-, 12-dihydroxy tonkabean phenylate, and structural formula is as follows:
Due to the difficult capacitive material of glycyrol, it is difficult to dissolve, therefore make preparation extremely difficult, it is the report of not yet effective preparation up till now.
Solid dispersion (SolidDispersion, SD) being the solid dispersion system of the high degree of dispersion being mixed by medicine and carrier, insoluble drug is dispersed in the carrier material of another kind of water solublity, slightly solubility or enteric solubility the dispersion formed with molecule, colloidal state, crystallite or unformed state. Since Sekiguchi and Obi in 1961 adopts fusion method that insoluble drug and water-soluble material are made solid dispersion first, since improve the dissolution rate of insoluble drug, the research application of solid dispersion technology is constantly expanded. Solid dispersion has the dissolubility and dissolution rate that increase insoluble drug, improves bioavailability. Delay or Drug controlled release, there is slow release and enteric characteristics. Delay hydrolysis and oxidation, improve medicine stability. Cover bad taste and the zest of smelling of medicine, reduce toxic and side effects. Make the advantages such as liquid medicine solidification.
Summary of the invention
Solid dispersion is a kind of technological means solving insoluble drug dissolution and drug bioavailability. In solid dispersion, insoluble drug molecule is distributed in polymer carrier with amorphous form. But for different medicines, it is necessary to solid dispersion carrier material is screened, and prepare into solid dispersion according to the carrier material filtered out by suitable preparation method. It is multiple that solid dispersion carrier material conventional in prior art includes cellulose, microcrystalline Cellulose, beta-schardinger dextrin-, alpha-cyclodextrin, Polyethylene Glycol etc., and the peptizaiton difference in different solid dispersion of these carrier materials is very big.
Inventor is according to the method (Wang Cailan of document, Zhang Ruyi etc., the chemical research of novel coumarin in Glycyrrhiza uralensis Fisch., Acta Pharmaceutica Sinica, 1991:26 (2): 147-151) by effective extract and separate obtain glycyrol, it is found by the applicant that these carrier materials above-mentioned are used for preparing its dissolution of glycyrol solid dispersion improves inconspicuous after obtaining glycyrol.
Through lot of experiments, applicant is surprisingly it has been found that select polyvidone as carrier material for glycyrol, compared with selecting other solid dispersion carrier material, prepared glycyrol solid dispersion has the effect that unexpected, dissolution significantly improves, and obtained solid dispersion has good stability, bioavailability high. Finding based on this, applicant completes the present invention.
The invention provides a kind of glycyrol solid dispersion, comprise glycyrol and the polyvidone as solid dispersion carrier material, solid dispersion stable in properties of the present invention, dissolution, bioavailability significantly improve. The present invention still further provides the pharmaceutical preparation containing the acceptable adjuvant of above solid dispersion and other pharmacy. Finally, present invention also offers the corresponding preparation method of said medicine.
In the present invention, described polyvidone can disperse glycyrol so as to be dissolved in water or other solvent, it is preferred that polyvidone mean molecule quantity is 5000D-50000D, more preferably 30 POVIDONE K 30 BP/USP 15, PVP K30,30 POVIDONE K 30 BP/USP 90 or its mixture.
In the present invention, glycyrol can from oryzanol raw material purification, it is also possible to be adopt chemical industry method synthesis.
In the present invention, the mass ratio of polyvidone and glycyrol is 1:100-100:1, it is preferred to 2:1-40:1, it is most preferred that for 4:1-20:1.
In the present invention, in order to improve the effect of solid dispersion further, it is possible to adding synergist, applicable synergist may is that
Poloxamer in Pluronic F68, it is preferable that PLURONICS F87;
Vitamin and derivant thereof, it is preferable that vitamin E, vitamin E polyethylene glycol succinic acid ester;
Lecithin, including egg yolk lecithin, soybean phospholipid, it is preferable that soybean lecithin;
Polyalcohols, including the organic polyhydric alcohol of liquid under room temperature, it is preferable that propylene glycol, glycerol, ethylene glycol or its mixture;
Tweens, it is preferable that polysorbate40, polysorbate60, Tween 80, it is most preferred that Tween 80;
Polyoxyl stearate, it is preferable that polyoxyethylene stearate (40) ester;
Preferably, the synergist for solid dispersion of the present invention is polyhydric alcohol and tween.
In the glycyrol solid dispersion containing synergist, glycyrol, polyvidone, synergist mass ratio be 1:2-20:0.2-5.
The relative glycyrol raw materials such as test shows, glycyrol solid dispersion result of extraction of the present invention is good, dissolubility also have the raising of highly significant.
On the other hand, the preparation method that present invention also offers glycyrol solid dispersion.
Glycyrol, polyvidone are dissolved in organic solvent, organic solvent are reclaimed and dries and obtain glycyrol solid dispersion. Wherein, organic solvent used can be any organic compound that can dissolve glycyrol, polyvidone, for instance alcohol, acetonitrile, oxolane, dichloromethane, chloroform, ethyl acetate, acetone or its any mixture. Being actually needed of bound drug safety and preparation, the preferred organic solvent of preparation method of the present invention is alcohol, ethyl acetate, acetone and/or its mixture. When with alcohol as organic solvent, the present invention is preferably with dehydrated alcohol, absolute methanol, ethanol water, methanol aqueous solution. In above-mentioned course of dissolution, can heating to accelerate dissolution velocity, the temperature of heating is at 30-85 DEG C.
The solid dispersion of the present invention is not limited to adopt said method to prepare, and other all can adopt suitable preparation parameter for preparing the solid dispersion of the present invention for preparing the method such as fusion method of solid dispersion, melted-solvent method etc.
In above-mentioned preparation method, the drying means adopted is not subjected to special restriction, the preparation method that industrial conventional drying means such as drying under reduced pressure, spray drying, constant pressure and dry are used equally to the present invention. For example, it is possible to the distillation of gained solution decompression to be obtained the co-precipitation thing of paste, it is dried pulverizing; Gained solution can be passed through spray drying machine, thus directly collecting the dried powder of solid dispersion; Then gained paste precipitate can be pulverized by heating, drying organic solvent at ambient pressure.
Solid dispersion of the present invention can pass through the route of administration of any appropriate and enter human body, it is common that oral or parenteral route. In order to carry out this kind of application, the solid dispersion of the present invention can pass through to add suitable pharmaceutic adjuvant preparation for acceptable dosage form on pharmaceutics. When being used for treating as active component, it is possible to be administered orally directly to the glycyrol solid dispersion powder simple with patient or direct fill capsulae vacuus. It is all occur with the medicine type containing pharmaceutic adjuvant during glycyrol solid dispersion practical application of the present invention, therefore the invention provides the pharmaceutical preparation of glycyrol solid dispersion.
Can be tablet, capsule, pill, granule, suspensoid, powder, oral liquid, injectable or can infusion solution or suspensoid, suppository etc. by the medicament oral, non-bowel, topical that is suitable for that is mixed with pharmaceutic adjuvant, preferred dosage form is peroral dosage form in actual applications, it is easy to patient uses.
Solid dispersion of the present invention can be combined with adjuvant prepares into various peroral dosage form, such as tablet, capsule, granule, drop pill etc., the method of preparation used can be the conventional method of drug world, such as tablet, it is possible to make mixture then tabletting by adding suitable additive to the glycyrol solid dispersion of the present invention; Capsule, it is possible to make by being processed in the granule addition capsule shells of powder or specific standard to the glycyrol solid dispersion of present invention addition pharmaceutic adjuvant. Preferred dosage form is tablet and capsule, and these dosage forms can adopt routine techniques and regular machinery to prepare.
Difference according to pharmaceutical dosage form, it is possible to optionally with the pharmaceutic adjuvant that other is suitable. Adaptable pharmaceutically common adjuvant includes but not limited to:
One or more pharmaceutically useful filleies, include but not limited to sucrose, lactose, microcrystalline Cellulose, starch etc.;
One or more disintegrating agents, include but not limited to polyvinylpolypyrrolidone, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose;
One or more lubricants, include but not limited to magnesium stearate, colloidal silica;
One or more, for improving the adjuvant (flavoring agent, coloring agent) of abnormal smells from the patient, perception, include but not limited to Herba Menthae, essence, beta-carotene;
One or more stabilizers, antioxidant, include but not limited to butylated hydroxytoluene, alpha-tocopherol, propylgallate, malonic acid, vitamin C, sodium sulfite, sodium sulfite, sodium pyrosulfite.
As required, production process can also add other suitable adjuvant.
In foregoing, described filler, disintegrating agent, lubricant, coloring agent, flavoring agent etc. belong to pharmaceutics category, are that those skilled in the art are familiar with or should be familiar with. " including but not limited to " used by applicant refers to one or several in described concrete material but it also may be described outside well known to those skilled in the art, play the material of same purpose effect. Such as described disintegrating agent, except polyvinylpolypyrrolidone, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, it will be obvious to one with ordinary skill in the art that such as carboxymethylcellulose calcium, low-substituted hydroxypropyl cellulose can also as disintegrating agent.
It will be appreciated by those skilled in the art that the process that solid dispersion preparation obtained for the present invention adopts it is that pharmaceutical field is common. Such as, knowledge according to galenic pharmacy, glycyrol solid dispersion of the present invention and its pharmaceutic adjuvant it is dissolved in after the system such as alcohol, aqueous solution stirs or is fully ground to go out solvent and dries, thus obtaining dry suspension or the powder of solid dispersion of the present invention, then further tabletting or encapsulated. This preparation technique is it is well established in the art, the technical scheme that those skilled in the art adopt on formulation method has no effect on protection scope of the present invention. Specifically prepare into any dosage form and adopt which type of preparation process to determine according to concrete production requirement.
The glycyrol solid dispersion and the preparations thereof that obtain the present invention carry out dissolution in vitro test, accelerated stability test, solubility test, result shows that the glycyrol solid dispersion prepared by disclosure can make glycyrol reach significantly high dispersity in polyvidone, substantially increase the dissolution in vitro of glycyrol, thus improve its bioavailability.
Detailed description of the invention
Embodiment 1
By 4g glycyrol, 15g PVP K30, mixed grinding 20min, gained abrasive flour is joined stirring 10min in 80ml ethanol, gained solution pours Rotary Evaporators into, take out in baking oven dry when being concentrated into 10ml, 80 mesh sieves pulverized by gained solid, obtained glycyrol solid dispersion composition of the present invention.
Embodiment 2
Measure 150ml ethyl acetate, add 7g 30 POVIDONE K 30 BP/USP 90 wherein and fully vibrate dissolving. Being subsequently adding glycyrol 1g, heated and stirred about 15 minutes at 70 DEG C, gained solution pours Rotary Evaporators into, takes out in baking oven dry when being concentrated into 20ml, and 80 mesh sieves pulverized by gained solid, obtained glycyrol solid dispersion of the present invention.
Embodiment 3
Measuring 50ml ethanol, add 20g PVP K30,1g propylene glycol, 1g glycyrol, 0.2g egg yolk lecithin wherein, in 50 DEG C of water-baths, heating is sufficiently stirred for dissolving. Gained solution pours Rotary Evaporators into, takes out in baking oven dry when being concentrated into 15ml, and 80 mesh sieves pulverized by gained solid, obtained glycyrol solid dispersion of the present invention.
Embodiment 4
10g glycyrol, 100g 30 POVIDONE K 30 BP/USP 90,5g glycerol are dissolved in 99% ethanol, again solution spray drying device spray drying is prepared glycyrol solid dispersion, being further dried at 60 DEG C 2 hours, remove residual solvent, gained powder is glycyrol solid dispersion of the present invention.
Embodiment 5
Glycyrol 5g, 30 POVIDONE K 30 BP/USP 1515g are dissolved in acetone, then solution spray drying device spray drying is prepared glycyrol solid dispersion, be further dried at 60 DEG C 2 hours, remove residual solvent.
Embodiment 6
Measure the ethanol of 100ml95%, addition propylene glycol 2ml, PVP K30 8g fully vibrate after dissolving and add glycyrol 1.5g, heated and stirred about 10 minutes at 75 DEG C, gained solution pours Rotary Evaporators into, take out in baking oven dry when being concentrated into 15ml, 80 mesh sieves pulverized by gained solid, obtained glycyrol solid dispersion of the present invention.
Embodiment 7
Measure the ethanol of 100ml95%, addition 3ml glycerol, 28g 30 POVIDONE K 30 BP/USP 15 fully vibrate after dissolving and add 4g glycyrol, heated and stirred about 10 minutes at 80 DEG C, gained solution pours Rotary Evaporators into, take out in baking oven dry when being concentrated into 18ml, 80 mesh sieves pulverized by gained solid, obtained glycyrol solid dispersion of the present invention.
Embodiment 8
Measure the ethanol of 200ml95%, addition 3ml Tween 80,30g 30 POVIDONE K 30 BP/USP 32 fully vibrate after dissolving and add 5g glycyrol, heated and stirred about 20 minutes at 70 DEG C, gained solution pours Rotary Evaporators into, take out in baking oven dry when being concentrated into 15ml, 80 mesh sieves pulverized by gained solid, obtained glycyrol solid dispersion of the present invention.
Embodiment 9
Take the ethanol of 100ml95%, addition 2ml polysorbate60,20g 30 POVIDONE K 30 BP/USP 15 fully vibrate to dissolve and add 5g glycyrol, heated and stirred about 10 minutes at 80 DEG C, gained solution pours Rotary Evaporators into, take out in baking oven dry when being concentrated into about 15ml, 80 mesh sieves pulverized by gained solid, obtained glycyrol solid dispersion of the present invention.
Embodiment 10
Measure the ethanol of 100ml95%, addition 5ml propylene glycol, 50g 30 POVIDONE K 30 BP/USP 15 fully vibrate after dissolving and add 6g glycyrol, heated and stirred about 10 minutes at 80 DEG C, gained solution pours Rotary Evaporators into, take out in baking oven dry when being concentrated into about 15ml, 80 mesh sieves pulverized by gained solid, obtained glycyrol solid dispersion of the present invention.
Embodiment 11
| The glycyrol solid dispersion of embodiment 6 | 9g |
| Microcrystalline Cellulose | 8g |
| Polyvinylpolypyrrolidone | 3g |
| Magnesium stearate | 0.5g |
The glycyrol solid dispersion of embodiment 6, microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate are crossed respectively 80 mesh sieves standby. Weigh glycyrol solid dispersion, microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, tabletting according to above table, obtain Tablets, totally 100.
Embodiment 12
| The glycyrol solid dispersion of embodiment 8 | 16g |
| Starch | 80g |
| Magnesium stearate | 1g |
| 5% starch slurry | In right amount |
By the glycyrol solid dispersion of the embodiment of the present invention 8 and starch Homogeneous phase mixing, add 5% appropriate starch slurry and granulate, dry, add magnesium stearate mixing, then gained is joined in capsule, totally 200.
Embodiment 13
| The glycyrol solid dispersion of embodiment 4 | 15g |
| Microcrystalline Cellulose | 8g |
| Lactose | 35g |
| Magnesium stearate | 10g |
By the glycyrol solid dispersion of the embodiment of the present invention 4 and microcrystalline Cellulose, lactose Homogeneous phase mixing, granulate with dehydrated alcohol, dry, it is subsequently adding magnesium stearate and mixes, the direct bag distribution packaging of granule, totally 140 bags.
Embodiment 14
| The glycyrol solid dispersion of embodiment 10 | 3g |
| Macrogol 2000 | 40g |
Being mixed with cetomacrogol 1000 by the glycyrol solid dispersion of the embodiment of the present invention 10, heating, to 80 DEG C, mixes up pill dripping machine, is added dropwise in dimethylsilane, obtain glycyrol solid dispersion drop pill of the present invention, totally 30.
Embodiment 15
| The glycyrol solid dispersion of embodiment 6 | 15g |
| Microcrystalline Cellulose | 20g |
| Low-substituted hydroxypropyl cellulose | 3g |
| Magnesium stearate | 0.5g |
The glycyrol solid dispersion of embodiment 6, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, magnesium stearate are crossed respectively 80 mesh sieves standby. Weigh glycyrol solid dispersion, microcrystalline Cellulose, polyvinylpolypyrrolidone, magnesium stearate mix homogeneously, tabletting according to above table, obtain Tablets, totally 500.
Comparative example 1
Measure 150ml ethyl acetate, be added thereto to 7g microcrystalline Cellulose and fully vibrate and make it be completely dissolved. Adding 1g glycyrol, at 70 DEG C, within about 15 minutes, to dissolving fully, gained solution pours Rotary Evaporators into heated and stirred, takes out in baking oven dry, dry gained solid was pulverized 80 mesh sieves, to obtain final product when adopting decompression distillation and concentration to 20ml.
Comparative example 2
Measure 150ml ethyl acetate, be added thereto to 7g PLURONICS F87 and fully vibrate and make it be completely dissolved. Adding 1g glycyrol, at 70 DEG C, within about 15 minutes, to dissolving fully, gained solution pours Rotary Evaporators into heated and stirred, takes out in baking oven dry, dry gained solid was pulverized 80 mesh sieves, to obtain final product when adopting decompression distillation and concentration to 20ml.
Comparative example 3
Measure 150ml ethyl acetate, be added thereto to 7g polyethylene glycol 6000 and fully vibrate and make it be completely dissolved. Adding 1g glycyrol, at 70 DEG C, within about 20 minutes, to dissolving fully, gained solution pours Rotary Evaporators into heated and stirred, takes out in baking oven dry, dry gained solid was pulverized 80 mesh sieves, to obtain final product when adopting decompression distillation and concentration to 20ml.
Comparative example 4
By 1g glycyrol, 7g PVP K30, mixing shakes up, and obtains glycyrol polyvidone common mixt.
Experimental example 1 accelerated stability test
The solid dispersion prepare the embodiment of the present invention 6,11 and tablet thereof are placed in 40 DEG C, preserve six months in the calorstat of 75% relative humidity, respectively 0 month, January, February, March, June its dissolution of sampling and measuring and content.
High-efficient liquid phase chromatogram condition: be filler with octadecylsilane chemically bonded silica; Mobile phase A is methanol-oxolane (10:23), and Mobile phase B is acetonitrile-water (55:15), and flow velocity is 1.0ml/min, gradient elution; Column temperature is 45 DEG C; Detection wavelength is 325nm.
According to two annex VD of China's coastal port, take appropriate amount of sample (being equivalent to containing glycyrol 10mg), accurately weighed, finely ground, put in 100ml measuring bottle, add that mobile phase is ultrasonic to be made dissolving and be diluted to scale, shake up, filtering, precision measures filtrate 10 �� l and injects chromatograph of liquid, records chromatogram; Another extracting liquorice alcohol reference substance 10mg, accurately weighed, put in 100ml measuring bottle, add mobile phase A liquid and dissolve and be diluted to scale. By the external standard method content with calculated by peak area glycyrol.
According to 2005 editions two annex �� C the second subtraction units of Chinese Pharmacopoeia, with water 500ml for solvent, precision weighs appropriate amount of sample (being equivalent to containing glycyrol 10mg). Operate in sampling during 45min, with its dissolution of high effective liquid chromatography for measuring in accordance with the law.
The data obtained is following table
Table 1 solid dispersion stability of the present invention and dissolution are investigated
As it can be seen from table 1 the solid dispersion of the present invention and tablet thereof are when accelerated test, dissolution and content are substantially free of change, describe glycyrol solid dispersion of the present invention and tablet stability is good.
Experimental example 2 solubility test is tested
Solid dispersion of the present invention not only substantially increases the dissolution of glycyrol, also improves its water solublity.
Take appropriate glycyrol solid dispersion, with Purified Water q. s so as to form saturated solution, filter with 0.45um filter membrane, by spectrophotometric determination 320 place trap after dilution, by the concentration that absorptance (ECM1%) is 250 calculating saturated solutions of glycyrol thus obtaining the dissolubility of glycyrol in glycyrol solid dispersion.
At normal temperatures and pressures, glycyrol dissolubility in water is less than 1mg/ml.
Glycyrol solid dispersion of the present invention is at glycyrol: during PVP K30 (1:2), the dissolubility of glycyrol is more than 5mg/ml.
Glycyrol solid dispersion of the present invention is at glycyrol: during PVP K30 (1:3), the dissolubility of glycyrol is more than 8mg/ml.
Glycyrol solid dispersion of the present invention is at glycyrol: during PVP K30 (1:5), the dissolubility of glycyrol is more than 9mg/ml.
From above-mentioned data, glycyrol solid dispersion of the present invention has remarkable effect to improving glycyrol dissolubility.
Experimental example 4 different carriers material, preparation method dissolution contrast test
According to 2005 editions two annex �� C the second subtraction units of Chinese Pharmacopoeia, with water 500ml for solvent, precision weighs appropriate amount of sample (being equivalent to containing glycyrol 10mg). Operate in sampling during 45min, with its dissolution of high effective liquid chromatography for measuring in accordance with the law.
High-efficient liquid phase chromatogram condition: be filler with octadecylsilane chemically bonded silica; Mobile phase A is methanol-oxolane (10:23), and Mobile phase B is acetonitrile-water (55:15), and flow velocity is 1.0ml/min, gradient elution; Column temperature is 45 DEG C; Detection wavelength is 325nm.
Measure embodiment 2, comparative example 1, comparative example 2, comparative example 3, comparative example 4 dissolution at room temperature respectively, be respectively labeled as sample 1, sample 2, sample 3, sample 4, sample 5.
| Sample number | 45min dissolution (%) |
| Sample 1 | 91.5 |
| Sample 2 | 37.0 |
| Sample 3 | 40.2 |
| Sample 4 | 39.0 |
| Sample 5 | 1.2 |
From above-mentioned data, compared with other conventional carrier materials of solid dispersion, application polyvidone can obviously improve the dissolution of glycyrol.
The mensuration of experimental example 5 bioavailability
Take 10 mices, give the tablet of the embodiment of the present invention 11 preparation, every dosage 10mg.
Without, under meal situation, putting into the oral cavity of mice with the dosage of 10mg so that it is swallow. Give polishing purification water 20ml. Before administration, after administration 0,0.25h, 0.5h, 1h, 2h, 4h, 6h, 8h, 12h, 24h, 48h, 72h glycyrol content of drawing blood respectively and measuring in blood.
Testing result shows, solid dispersion tablet bioavailability of the present invention is good, is 64%.
Claims (15)
1. a glycyrol solid dispersion, comprises glycyrol and the polyvidone as solid dispersion carrier.
2. solid dispersion according to claim 1, described polyvidone molecular weight is 5000D��50000D.
3. solid dispersion according to claim 2, described polyvidone is one or more the mixture in 30 POVIDONE K 30 BP/USP 15, PVP K30,30 POVIDONE K 30 BP/USP 90.
4. the mass ratio of solid dispersion according to claim 1, polyvidone and glycyrol is 2:1��40:1.
5. the mass ratio of solid dispersion according to claim 3, polyvidone and glycyrol is 4:1��20:1.
6. the solid dispersion according to any of the above-described claim, also comprises synergist, the described synergist one or more mixture in polyhydric alcohol, poloxamer, vitamin E, lecithin, polyoxyl stearate, tween.
7. solid dispersion according to claim 6, glycyrol, polyvidone, synergist mass ratio be 1:2��20:0.2��5.
8. solid dispersion according to claim 6, described polyhydric alcohol is one or more the mixture in ethylene glycol, propylene glycol, glycerol.
9. solid dispersion according to claim 6, described tween is one or more the mixture in polysorbate40, polysorbate60, Tween 80.
10. the method preparing the solid dispersion of any of the above-described claim, including glycyrol, polyvidone are dissolved in organic solvent, reclaims organic solvent dry step.
11. method according to claim 10, the described organic solvent one or more mixture in alcohol, ethyl acetate, acetone.
12. method according to claim 11, described alcohol is ethanol or ethanol water.
13. a pharmaceutical preparation, the glycyrol solid dispersion containing claim 1.
14. preparation according to claim 13, it it is oral formulations.
15. preparation according to claim 14, described peroral dosage form is capsule, tablet, granule, powder or drop pill.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109568309A (en) * | 2019-01-09 | 2019-04-05 | 中国农业大学 | New application of the glycyrol as PBK/TOPK kinase inhibitor |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101235038A (en) * | 2007-01-31 | 2008-08-06 | 北京师范大学 | Immunity inhibitor glycyrol |
| CN102058515A (en) * | 2009-11-18 | 2011-05-18 | 北京世纪博康医药科技有限公司 | Solid dispersion of 24-methylene cycloartanol ferulic acid eater and preparation thereof |
-
2014
- 2014-10-28 CN CN201410586777.0A patent/CN105616355A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101235038A (en) * | 2007-01-31 | 2008-08-06 | 北京师范大学 | Immunity inhibitor glycyrol |
| CN102058515A (en) * | 2009-11-18 | 2011-05-18 | 北京世纪博康医药科技有限公司 | Solid dispersion of 24-methylene cycloartanol ferulic acid eater and preparation thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109568309A (en) * | 2019-01-09 | 2019-04-05 | 中国农业大学 | New application of the glycyrol as PBK/TOPK kinase inhibitor |
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