CN1301108C - Metaducine dispersion tablet and its preparation method - Google Patents
Metaducine dispersion tablet and its preparation method Download PDFInfo
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- CN1301108C CN1301108C CNB2004100359415A CN200410035941A CN1301108C CN 1301108 C CN1301108 C CN 1301108C CN B2004100359415 A CNB2004100359415 A CN B2004100359415A CN 200410035941 A CN200410035941 A CN 200410035941A CN 1301108 C CN1301108 C CN 1301108C
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- Prior art keywords
- metadoxine
- dispersible tablet
- preparation
- tablet
- white tablets
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- 238000002360 preparation method Methods 0.000 title abstract description 18
- 239000006185 dispersion Substances 0.000 title abstract 4
- RYKKQQUKJJGFMN-HVDRVSQOSA-N 4,5-bis(hydroxymethyl)-2-methylpyridin-3-ol;(2s)-5-oxopyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCC(=O)N1.CC1=NC=C(CO)C(CO)=C1O RYKKQQUKJJGFMN-HVDRVSQOSA-N 0.000 claims abstract description 89
- 239000007919 dispersible tablet Substances 0.000 claims description 39
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 24
- 108010011485 Aspartame Proteins 0.000 claims description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000000605 aspartame Substances 0.000 claims description 12
- 235000010357 aspartame Nutrition 0.000 claims description 12
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 12
- 229960003438 aspartame Drugs 0.000 claims description 12
- 235000019359 magnesium stearate Nutrition 0.000 claims description 12
- 239000000741 silica gel Substances 0.000 claims description 12
- 229910002027 silica gel Inorganic materials 0.000 claims description 12
- 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 description 10
- 229930195725 Mannitol Natural products 0.000 claims description 10
- 239000000594 mannitol Substances 0.000 claims description 10
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- 239000003795 chemical substances by application Substances 0.000 abstract description 12
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- 239000000463 material Substances 0.000 abstract 1
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- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
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- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 2
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- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
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- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 1
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- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- 102000057288 Tryptophan 2,3-dioxygenases Human genes 0.000 description 1
- 108700016257 Tryptophan 2,3-dioxygenases Proteins 0.000 description 1
- LXNHXLLTXMVWPM-UHFFFAOYSA-N Vitamin B6 Natural products CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
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- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
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- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
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- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
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- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The present invention provides a metadoxine dispersion tablet and a preparation method thereof. The metadoxine dispersion tablet comprises the following components: metadoxine, a filling agent, a disintegrating agent, corrigent, glidant and a lubricating agent. The preparation method comprises the following steps: raw materials and auxiliary materials are respectively ground by a sieve with 60 meshes for standby; the metadoxine, the filling agent, the disintegrating agent and the corrigent are evenly mixed; the lubricating agent and the glidant are added for evenly mixing; the metadoxine dispersion tablet is obtained through tabletting operation.
Description
Affiliated technical field
The present invention relates to a kind of dispersible tablet that contains metadoxine (Metadoxine) and preparation method thereof.
Background technology
Fatty liver, alcoholic liver become the second largest killer of hepatopathy after viral hepatitis.U.S. hepatopathy professional investigation mechanism found alcoholic liver crowd follow-up investigation through 4 years, the mortality rate of suffering from alcoholic liver and alcoholic fatty liver patient is much higher than the general population, serious symptom alcoholic fatty liver such as untimely treatment, most patients may be dead in some months.At present, owing to drink, the sickness rate of alcoholic liver and alcoholic fatty liver is also in rising trend in China.Its fearful part is that alcoholic liver and alcoholic fatty liver if untimely control meeting constantly worsens, make the patient go on the dead trilogy of alcoholic liver and alcoholic fatty liver → liver cirrhosis → hepatocarcinoma.
Metadoxine is developed by Italian LABORATORI BALDACCI S.P.A. company the earliest, has better curative effect for acute and chronic alcoholism of treatment and alcoholic liver disease.Metadoxine is an ion pair, has Benadon (vitamin B6) and 2-pyrrolidone-5-carboxylic acid (pyroglutamic acid: salt and covalently bound some characteristic of forming the cyclisation derivant of glutamic acid).Metadoxine is an aldehyde dehydrogenase activator, and the active of aldehyde dehydrogenase obviously increased.Experimental results show that in the presence of this product, acetaldehyde metabolism and the speed that changes into acetate are obviously accelerated, and can reduce the interact generation of the long-acting macromolecular complex that causes the tool cytotoxic activity of albumin and acetaldehyde, improve liver ATP concentration, accelerate amino acid whose transhipment in the cell, antagonism ethanol is to the inhibitory action of tryptophan pyrrolase, thereby accelerates the elimination of ethanol and acetaldehyde in blood and the urine, recovers liver function.Clinical acute and chronic alcoholism and the alcoholic liver disease of being used for the treatment of.
At present, the oral formulations that metadoxine goes on the market abroad has ordinary tablet and oral liquid, and specification is 500mg.The domestic preparation listing of still not having metadoxine.There is following problem in the metadoxine conventional tablet: the ordinary tablet volume is not big for (1) metadoxine, for the patient who swallows dysmasesis, uses inconvenience; (2) metadoxine is usually used in treating acute alcoholism, and ordinary tablet oral after, the disintegrate of medicine and principal agent stripping need a period of time, so onset is slow, bioavailability is low, thereby the metadoxine ordinary tablet is not suitable for the acute alcoholism patient; (3) metadoxine is usually used in treating alcoholic liver disease, needs long-term prescription, because metadoxine has intensive tart flavour, the ordinary tablet mouthfeel is bad, causes the long-term prescription difficulty, patient's poor compliance.Though there are not the problems referred to above in the metadoxine oral liquid, because volume is bigger, and glass bottle packing is frangible, and the patient carries inconvenience.It seems that generally existing metadoxine oral formulations can not satisfy treatment alcoholic liver disease and acute and chronic crapulent demand.Thereby needing a kind of new formulation of metadoxine, said preparation should have following characteristics: volume is little, is easy to carry; Be applicable to the patient who swallows dysmasesis; Rapid-action, bioavailability is high; Mouthfeel is good, is suitable for patient's long-term prescription.
As metadoxine being made dispersible tablet the problems referred to above are resolved, but have following difficulty: the very easily moisture absorption of (1) metadoxine, the dispersible tablet that adopts common preparation technology to make is against regulation disintegration, and easy moisture absorption deliquescence, is difficult for preserving; (2) the metadoxine crude drug is mobile poor, adopts common adjuvant to be difficult for making dispersible tablet; (3) the metadoxine specification is bigger, every 500mg, as adopt common adjuvant and prepared dispersible tablet, and need to add more adjuvant, cause the problem that tablet volume is big, cost is high.
The present invention makes dispersible tablet with metadoxine, and the problems referred to above are resolved.The metadoxine dispersible tablet is put into the low amounts of water jolting before use, and very fast disintegrate is dispersed into solution state, has the following advantages: (1) conveniently swallows patient's medication of dysmasesis; (2) solution state easily absorbs, and the bioavailability height is rapid-action, applicable to the acute alcoholism patient; (3) mouthfeel is good, is beneficial to improve patient's compliance; (4) volume is little, is easy to carry; (5) adopt Technology of the present invention to prepare the metadoxine dispersible tablet, used adjuvant amount reduces, and simplifies production technology, can reduce production costs.
Summary of the invention
The objective of the invention is at the deficiencies in the prior art, overcome the limitation of existing metadoxine preparation, provide a kind of absorptions soon, bioavailability height, application and metadoxine dispersible tablet easy to carry and preparation method thereof.
Purpose of the present invention is achieved by following testing program.
Metadoxine dispersible tablet of the present invention is composed of the following components: metadoxine 50～1000mg, filler 20～600mg, disintegrating agent 3～200mg, correctives 2～50mg, lubricant 0.2～40mg, fluidizer 0.5～20mg.
Described filler is selected from one of following formula or any two kinds or arbitrarily two or more mixture:
1. 2. 3. 4. microcrystalline Cellulose of mannitol of lactose of pregelatinized Starch.
Described disintegrating agent is selected from one of following formula or any two kinds or arbitrarily two or more mixture:
1. 2. 3. 4. 5. 6. 7. sodium lauryl sulphate of tween 80 of carboxymethyl starch sodium of crospolyvinylpyrrolidone of interlinkage sodium carboxymethyl cellulose of L-hydroxypropyl cellulose of microcrystalline Cellulose.
Described correctives is selected from one of following formula or any two kinds or arbitrarily two or more mixture:
1. 2. 3. 4. saccharin sodium of glycyrrhizin of aspartame of steviosin.
Described lubricant and fluidizer are selected from one of following formula or any two kinds or arbitrarily two or more mixture:
1. 2. 3. 4. 5. 6. stearic acid of sodium lauryl sulphate of Stepanol MG of micropowder silica gel of Pulvis Talci of magnesium stearate.
The preferred composition of metadoxine dispersible tablet of the present invention is:
Metadoxine 50～1000mg
Mannitol 20～600mg
Crospolyvinylpyrrolidone 3～200mg
Aspartame 2～50mg
Micropowder silica gel 0.2～40mg
Magnesium stearate 0.5～20mg
Preferred each set of dispense ratio was during above-mentioned metadoxine dispersible tablet was formed:
Metadoxine 500mg
Mannitol 250mg
Crospolyvinylpyrrolidone 50mg
Aspartame 16mg
Micropowder silica gel 24mg
Magnesium stearate 8mg
The composition of tablet can carry out suitable adjustment as required in the prescription, and the shape of tablet also can be adjusted as required, can be circle, ellipse, polygon or other special-shaped tablets.
The preparation method of above-mentioned metadoxine dispersible tablet, can adopt following two kinds of technologies to carry out:
1. direct powder compression, the preparation method of above-mentioned metadoxine dispersible tablet, carry out according to the following steps order:
(1) former, adjuvant is crossed 60 mesh sieves respectively, and is standby;
(2) with metadoxine, filler, disintegrating agent, correctives mix homogeneously;
(3) add lubricant and fluidizer, mixing;
(4) tabletting.Figure of tablet can be circle, ellipse, polygon or other all rational shapes.
2. compressing dry granulation, the preparation method of above-mentioned metadoxine dispersible tablet, carry out according to the following steps order:
(1) former, adjuvant is crossed 100 mesh sieves respectively, and is standby;
(2) with metadoxine, filler, disintegrating agent, correctives mix homogeneously;
(3) adopt rolling process or double compression to be pressed into sheet;
(4) sheet is pulverized, crossed 20 mesh sieves;
(5) add disintegrating agent, lubricant and fluidizer, mixing;
(6) tabletting.Figure of tablet can be circle, ellipse, polygon or other all rational shapes.
Metadoxine dispersible tablet of the present invention and preparation method thereof can produce following beneficial effect:
(1) the metadoxine dispersible tablet is put into the low amounts of water jolting before use, and very fast disintegrate is dispersed into solution state, conveniently swallows patient's medication of dysmasesis;
(2) solution state easily absorbs, and the bioavailability height is rapid-action, also is applicable to the acute alcoholism patient;
(3) mouthfeel is good, is beneficial to improve patient's compliance;
(4) volume is little, is easy to carry;
(5) adopt technique of direct powder compression or dry granulation tablet forming technique, avoid using organic solvents such as ethanol, and production technology is simple, is beneficial to suitability for industrialized production;
(6) adopt this method to prepare the metadoxine dispersible tablet, can reduce supplementary product consumption, reduce cost.
The specific embodiment
Can further clearly understand the present invention by specific embodiment given below and Application Example, but they not limitation of the invention.
Embodiment 1
Calculate by 1000 metadoxine dispersible tablet inventorys of preparation, the consumption of supplementary material is as follows:
Metadoxine 500g
Mannitol 250g
Crospolyvinylpyrrolidone 50g
Aspartame 16g
Micropowder silica gel 24g
Magnesium stearate 8g
Prepare the metadoxine dispersible tablet of above-mentioned prescription, carry out according to following steps:
(1) adjuvant is crossed 60 mesh sieves respectively, and is standby;
(2) with metadoxine, filler, disintegrating agent, correctives mix homogeneously;
(3) add lubricant and fluidizer, mixing;
(4) tabletting, promptly.Every contains metadoxine 500mg, and sheet heavily is about 0.7g.
Differentiate: contain similar phenolic hydroxyl structure in the metadoxine structure, can produce color reaction with ferric chloride.Method: get 20 of this product, porphyrize takes by weighing fine powder an amount of (being equivalent to metadoxine 100mg approximately), makes the principal agent dissolving with distilled water 10ml jolting, with 0.8 μ m filtering with microporous membrane, gets subsequent filtrate 1.0ml, adds 1 of FeCl3 test solution, and it is orange red that test solution shows.
Check:
Two appendix I of dispersing uniformity Chinese Pharmacopoeia version in 2000 A regulation dispersible tablet dispersing uniformity inspection method is as follows: gets two of dispersible tablets, puts jolting in the 100ml water, and in 20 ± 1 ℃ of water, all disintegrates and sieve (aperture 850 μ m) in 3 minutes by No. 2.
Other should meet pertinent regulations under the tablet item (two appendix I of Chinese Pharmacopoeia version in 2000 A)
Assay:
Chromatographic condition and system suitability test:
Chromatographic column: C18 post 250mm * 4.6mm, φ 5 μ m;
Mobile phase: second eyeball: 0.2% phosphoric acid (1: 99);
Detect wavelength: 205nm;
Flow velocity: 1ml/min;
Number of theoretical plate calculates by VB6 component peaks (peak 1) and pyroglutamic acid component peaks (peak 2) respectively all must not be lower than 3000.
Assay method: get 20 of this product, porphyrize, precision takes by weighing in right amount (being equivalent to metadoxine 50mg approximately), puts in the 100ml measuring bottle, adds mobile phase to scale, dissolving in ultrasonic 30 minutes, filter, precision is measured subsequent filtrate 10ml and is put in the 100ml measuring bottle, adds mobile phase and is diluted to scale, shake up, as need testing solution.It is an amount of that in addition precision takes by weighing the metadoxine that is dried to constant weight, is diluted to the solution of 50 μ g/ml, liquid in contrast with mobile phase.Precision is measured each 20 μ l of reference substance solution and need testing solution and is injected chromatograph of liquid, the record chromatogram, by external standard method with two component peaks areas with calculate content.Should be 90%～110% of labelled amount.
Indication: acute and chronic alcoholism, alcoholic liver disease.
Usage and dosage: put into before taking and take after the jolting of an amount of eliminating cold for resuscitation water is uniformly dispersed or oral, every day 2 times, each 1.
Specification: 500mg
Storage: lucifuge, protection against the tide, airtight preservation.
Embodiment 2
Except that prescription changed following composition into, other were with embodiment 1.
Prescription consists of:
Metadoxine 250g
Mannitol 150g
Crospolyvinylpyrrolidone 10g
Aspartame 6g
Magnesium stearate 6g
Micropowder silica gel 6g
Embodiment 3
Except that prescription changed following composition into, other were with embodiment 1.
Prescription consists of:
Metadoxine 500g
Mannitol 150g
Crospolyvinylpyrrolidone 20g
Aspartame 9g
Micropowder silica gel 14g
Magnesium stearate 8g
Embodiment 4
Except that prescription changed following composition into, other were with embodiment 1.
Prescription consists of:
Metadoxine 500g
Lactose 250g
Crospolyvinylpyrrolidone 50g
Aspartame 16g
Micropowder silica gel 24g
Magnesium stearate 8g
Embodiment 5
Except that preparation technology implemented according to the following steps, other were with embodiment 1.
Preparation technology presses step and implements:
(1) adjuvant is crossed 100 mesh sieves respectively, and is standby;
(2) with metadoxine, filler, disintegrating agent, correctives mix homogeneously;
(3) adopt rolling process or double compression to be pressed into sheet;
(4) sheet is pulverized, crossed 20 mesh sieves;
(5) add disintegrating agent, lubricant and fluidizer, mixing;
(6) tabletting, promptly.
Embodiment 6
Except that prescription changed following composition into, other were with embodiment 5.
Prescription consists of:
Metadoxine 250g
Mannitol 150g
Crospolyvinylpyrrolidone 10g
Aspartame 6g
Micropowder silica gel 6g
Magnesium stearate 6g
Embodiment 7
Except that prescription changed following composition into, other were with embodiment 5.
Prescription consists of:
Metadoxine 500g
Mannitol 150g
Crospolyvinylpyrrolidone 20g
Aspartame 9g
Micropowder silica gel 14g
Magnesium stearate 8g
Embodiment 8
Except that prescription changed following composition into, other were with embodiment 5.
Prescription consists of:
Metadoxine 500g
Lactose 250g
Crospolyvinylpyrrolidone 50g
Aspartame 16g
Micropowder silica gel 24g
Magnesium stearate 8g
Embodiment 9 metadoxine dispersible tablets and metadoxine sheet dispersing uniformity and dissolving out capability are relatively
1. get embodiment 1 metadoxine dispersible tablet and metadoxine sheet (Italian LABORATORIBALDACCI S.P.A. company, trade name: METADOXIL), check according to the dispersing uniformity inspection method: get two of this product, put jolting in the 100ml water, in 20 ± 1 ℃ of water, all disintegrates and in 3 minutes with crossing sieve No. 2.Write down complete disintegration time, the results are shown in Table 1.
Table 1 metadoxine dispersible tablet and metadoxine sheet dispersing uniformity check result
| Preparation | Disintegration |
| The metadoxine dispersible tablet | 29 seconds |
| The metadoxine sheet | 600 seconds |
2. get embodiment 1 metadoxine dispersible tablet and metadoxine sheet (Italian LABORATORIBALDACCI S.P.A. company, trade name: METADOXIL), carry out the dissolution test according to following dissolution test method: sample thief, be dissolution medium with 900ml degassing distilled water respectively, temperature is 37 ℃, rotating speed is 50 rev/mins, operation in accordance with the law, and in 2,5,10,20,30,5ml (replenishing equality of temperature distilled water 5ml simultaneously) took a sample respectively in 45 minutes, 0.8 μ m microporous filter membrane filters, adopt the HPLC method to measure after getting subsequent filtrate dilution suitable multiple, calculate accumulative total stripping percentage rate relatively.Result of the test sees Table 2:
Table 2 metadoxine dispersible tablet and metadoxine sheet dissolution test result
| Time (minute) | 2 | 5 | 10 | 20 | 30 | 45 |
| The metadoxine dispersible tablet | 92.3 | 97.8 | 98.0 | 98.1 | 98.1 | 98.1 |
| The metadoxine sheet | 9.2 | 20.6 | 31.3 | 47.9 | 60.8 | 80.3 |
The above results shows: the disintegrate of metadoxine dispersible tablet of the present invention and dissolving out capability obviously are better than the metadoxine sheet, and disintegrate and stripping are the speed limit processes that oral formulations absorbs, so the metadoxine dispersible tablet can improve the infiltration rate and the bioavailability of medicine, thereby reach quick-acting, purpose efficiently.
Embodiment 10 metadoxine dispersible tablet stability tests
Get embodiment 1 metadoxine dispersible tablet and carry out stability study, comprising: accelerated test and long term test.
1. accelerated test
Sample was placed 6 months under 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5% condition by listing packing, respectively at 0,1,2,3, the every index of sampling and measuring in June, and with compared in 0 month.The results are shown in Table 3.
Table 1 accelerated test result
| Lot number | Time (moon) | Appearance character | Content (%) | Related substance (%) | Dispersing uniformity | Dissolution (%) |
| 030706 | 0 1 2 3 6 | White tablets white tablets white tablets white tablets white tablets | 100.24 100.79 99.56 101.21 100.07 | 0.27 0.25 0.30 0.20 0.24 | Up to specification up to specification | 98.03 97.48 96.72 96.91 96.50 |
| 030707 | 0 1 2 3 6 | White tablets white tablets white tablets white tablets white tablets | 98.50 99.12 99.37 98.16 99.09 | 0.31 0.30 0.26 0.33 0.19 | Up to specification up to specification | 97.06 97.46 97.23 96.63 96.55 |
| 030708 | 0 1 2 3 6 | White tablets white tablets white tablets white tablets white tablets | 101.48 100.16 101.69 100.75 100.91 | 0.33 0.22 0.35 0.23 0.26 | Up to specification up to specification | 98.19 97.33 97.56 96.76 95.68 |
The result shows: this product is compared with 0 month through accelerated test 6 months, and the every index of three batch samples has no significant change.
2. long term test
Sample was placed 6 months down in room temperature condition by listing packing, respectively at 0,3, the every index of sampling and measuring in June, and with compared in 0 month.The results are shown in Table 2.
Table 2 long-term test results
| Lot number | Time (moon) | Appearance character | Content (%) | Related substance (%) | Dispersing uniformity | Dissolution (%) |
| 030706 | 0 3 6 | White tablets white tablets white tablets | 100.24 101.03 100.70 | 0.27 0.20 0.33 | Up to specification up to specification | 98.03 97.15 97.60 |
| 030707 | 0 3 6 | White tablets white tablets white tablets | 98.50 99.15 98.76 | 0.31 0.23 0.27 | Up to specification up to specification | 97.06 97.20 96.96 |
| 030708 | 0 3 6 | White tablets white tablets white tablets | 101.48 101.02 100.97 | 0.33 0.26 0.23 | Up to specification up to specification | 98.19 97.83 96.57 |
The result shows: this product is through long term test 6 months, with 0 month relatively, the every index of three batch samples has no significant change.
Stability test is the result show, metadoxine dispersible tablet of the present invention has good stability.
Claims (2)
1, a kind of metadoxine dispersible tablet is characterized in that described metadoxine dispersible tablet is composed of the following components:
Metadoxine 50～1000mg
Mannitol 20～600mg
Crospolyvinylpyrrolidone 3～200mg
Aspartame 2～50mg
Micropowder silica gel 0.2～40mg
Magnesium stearate 0.5～20mg.
2, metadoxine dispersible tablet as claimed in claim 1 is characterized in that described metadoxine dispersible tablet is composed of the following components:
Metadoxine 500mg
Mannitol 250mg
Crospolyvinylpyrrolidone 50mg
Aspartame 16mg
Micropowder silica gel 24mg
Magnesium stearate 8mg.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| IL187159A0 (en) * | 2007-07-03 | 2009-02-11 | Gur Megiddo | Use of metadoxine in relief of alcohol intoxication |
| WO2010013242A1 (en) | 2008-07-29 | 2010-02-04 | Alcobra Ltd. | Substituted pyridoxine-lactam carboxylate salts |
| NZ597319A (en) | 2009-06-25 | 2014-06-27 | Alcobra Ltd | A method for the treatment, alleviation of symptoms of, relieving, improving and preventing a cognitive disease, disorder or condition |
| BR112015006642B1 (en) * | 2012-09-26 | 2022-08-02 | Eurodrug Laboratories B.V | PROLONGED RELEASE PHARMACEUTICAL COMPOSITION COMPRISING METHADOXINE AND PREDNISONE |
| CN103099794B (en) * | 2013-02-19 | 2014-07-30 | 青岛正大海尔制药有限公司 | Vitamin C clathrate dispersible tablet |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1359680A (en) * | 2001-12-26 | 2002-07-24 | 成都康弘制药有限公司 | Prescription of preparing moxapride citrate |
| CN1449757A (en) * | 2003-04-30 | 2003-10-22 | 江西省药物研究所 | Domperidone oral disintegrating tablet and preparation process thereof |
| CN1490006A (en) * | 2003-08-20 | 2004-04-21 | 杭州容立医药科技有限公司 | Melazocine masticatory and its preparation |
| CN1528350A (en) * | 2003-09-29 | 2004-09-15 | 武汉健民中药工程有限责任公司 | Dispersion tablet containing ginkgo leaf extract |
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2004
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1359680A (en) * | 2001-12-26 | 2002-07-24 | 成都康弘制药有限公司 | Prescription of preparing moxapride citrate |
| CN1449757A (en) * | 2003-04-30 | 2003-10-22 | 江西省药物研究所 | Domperidone oral disintegrating tablet and preparation process thereof |
| CN1490006A (en) * | 2003-08-20 | 2004-04-21 | 杭州容立医药科技有限公司 | Melazocine masticatory and its preparation |
| CN1528350A (en) * | 2003-09-29 | 2004-09-15 | 武汉健民中药工程有限责任公司 | Dispersion tablet containing ginkgo leaf extract |
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