CN1309387C - Cresol powder with dissolution increased and its preparing method-analgesic, antipyretic and anti-inflammatory agent - Google Patents
Cresol powder with dissolution increased and its preparing method-analgesic, antipyretic and anti-inflammatory agent Download PDFInfo
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- CN1309387C CN1309387C CNB031100597A CN03110059A CN1309387C CN 1309387 C CN1309387 C CN 1309387C CN B031100597 A CNB031100597 A CN B031100597A CN 03110059 A CN03110059 A CN 03110059A CN 1309387 C CN1309387 C CN 1309387C
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- mefenamic acid
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Abstract
The present invention relates to a formula for enhancing the dissolution of a mefenamic acid dispersive tablet and a preparation method thereof. The mefenamic acid dispersive tablet is a dispersive tablet prepared by using non-steroid analgesia, refrigeration and anti-inflammatory medicine-mefenamic acid as an active ingredient and a filling agent, adhesive, a disintegrating agent and/or a disintegrating assistance agent, an adsorbing agent, glidant, a suspension and/or suspending agent, corrigent, a surface active agent, a wetting agent and a lubricating agent as the preparation formula. Compared with a mefenamic acid common tablet, the mefenamic acid dispersive tablet of the present invention has obviously enhanced dissolution.
Description
Technical field
The present invention relates to the preparation of the analgesia of a kind of non-steroidal, analgesic, anti-inflammatory agent, specifically, is a kind of mefenamic acid dispersible tablets prescription that can improve dissolution and preparation method thereof.
Technical background
Mefenamic acid is non-steroidal analgesia, analgesic, anti-inflammatory agent.Have analgesia, analgesic and antiinflammatory action, its antiinflammatory action is stronger.
The acute toxicity tests shows, mefenamic acid rat and mice oral administration gavage administration LD
50Be respectively 780mg/kg and 630mg/kg.
Pharmacokinetic is the result show, reaches the peak in blood drug level 2-4 hour behind the oral 1g of mefenamic acid, and peak value is 10 μ g/ml.Oral 4 times on the one, can reach stable state (plasma concentration is 20 μ g/ml) on 2nd.By liver biotransformation, T
1/2It is 2 hours.67% by the kidney discharge, and 25% by bile, feces discharge.
Mefenamic acid is clinical to be used for slightly reaching medium degree pain, as dentistry, the postoperative pain of obstetrics or orthopedic section, and soft tissue injury pain and skeleton, arthralgia.
In addition, also be used for dysmenorrhea, vascular headache and cancerous pain etc.Chinese Pharmacopoeia two ones of versions in 2000 have been recorded mefenamic acid and conventional tablet and capsule.
Mefenamic acid is water insoluble, and the dissolution of conventional tablet and capsule is low, and weak curative effect makes the clinical practice of mefenamic acid be subjected to very big restriction.
Summary of the invention
Purpose of the present invention is exactly by making the method for mefenamic acid dispersible tablets, the dissolution of mefenamic acid is improved, thereby improve the bioavailability of mefenamic acid, give full play to its therapeutical effect, also make simultaneously gerontal patient, dysphagia patients and taking medicine in water-stressed conditions become more convenient.
For achieving the above object, the present invention adopts following technical scheme: be active component with the mefenamic acid, with filler, binding agent, disintegrating agent and/or help collapse agent, adsorbent, fluidizer, suspensoid and/or suspending agent, correctives, surfactant, wetting agent, lubricant is the dispersible tablet that pharmaceutical formulation is made.
The used filler of mefenamic acid dispersible tablets prescription of the present invention includes but not limited to low-substituted hydroxypropyl cellulose, lactose, sucrose, glucose, mannitol, xylitol, sorbitol, calcium sulfate, calcium gluconate, calcium hydrogen phosphate, calcium phosphate, calcium carbonate, calcium bicarbonate, starch, carboxymethyl starch, pregelatinized Starch, microcrystalline Cellulose etc.
The used wetting agent of mefenamic acid dispersible tablets prescription of the present invention includes but not limited to water, ethanol etc.
The used binding agent of mefenamic acid dispersible tablets prescription of the present invention includes but not limited to starch, pregelatinized Starch, gelatin, dextrin, the maltose dextrin, sucrose, arabic gum, polyvinylpyrrolidone, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, sodium carboxymethyl cellulose, various viscosity methylcellulose, microcrystalline Cellulose, low viscosity carboxymethyl cellulose, various viscosity ethyl celluloses, various viscosity polyvinyl alcohol, polyethylene glycol 6000,50mpa.s following hydroxypropyl emthylcellulose etc.
The disintegrating agent that mefenamic acid dispersible tablets of the present invention prescription is used and/or help and collapse agent and include but not limited to starch, pregelatinized Starch, microcrystalline Cellulose, alginic acid, pure lignocellulose, carboxymethyl starch sodium, guar gum, crospolyvinylpyrrolidone, ion exchange resin, methylcellulose, sodium carboxymethyl cellulose etc.
The used fluidizer of mefenamic acid dispersible tablets prescription of the present invention includes but not limited to micropowder silica gel.
The used lubricant of mefenamic acid dispersible tablets prescription of the present invention includes but not limited to magnesium stearate, calcium stearate, zinc stearate, Pulvis Talci, glyceryl monostearate, Macrogol 4000, polyethylene glycol 6000, Polyethylene Glycol 8000, sodium benzoate, adipic acid, fumaric acid, boric acid, sodium chloride, enuatrol, triacetyl glycerine, polyoxyethylene monostearate, single Laurel sucrose acid ester, sodium chloride, sodium laurylsulfate, magnesium laurylsulfate etc.
The used adsorbent of mefenamic acid dispersible tablets prescription of the present invention includes but not limited to micropowder silica gel, crospolyvinylpyrrolidone, micropowder silica gel, Kaolin, alkali or magnesium carbonate, light magnesium oxide, aluminium hydroxide desiccant gel etc.
The used surfactant of mefenamic acid dispersible tablets prescription of the present invention comprises but is not limited to sodium lauryl sulphate, poloxamer, Tween 80, bromination hexadecane trimethylamine, sodium laurylsulfate, stearyl alcohol sodium sulfonate, polyoxyethylene high fatty alcohol, sucrose ester, sorbitol fatty ester, soybean phospholipid etc.
The used correctives of mefenamic acid dispersible tablets prescription of the present invention includes but not limited to steviosin, fructose, glucose, high fructose syrup, Mel, aspartame, protein sugar, xylitol, mannitol, lactose, sorbitol, maltose alcohol, glycyrrhizin, phyllodulcin, Sodium Cyclamate, flavoring banana essence, flavoring pineapple essence, Fructus Citri tangerinae essence, Herba Menthae essence, Fructus Foeniculi, vanillin, Fructus Citri Limoniae essence, cherry essence, rose essence etc.
Used suspensoid and/or the suspending agent of mefenamic acid dispersible tablets prescription of the present invention includes but not limited to crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, the poly-ethoxy ethanol of hot phenoxy group, alevaire, the sorbitol anhydride polyethylene glycol monooleate, polyoxyethylene monostearate, polyoxyethylene deriv, Tween 80, the polyoxyethylene alkylphenyl sodium sulfonate, sodium lauryl sulfate, arabic gum, polyvinylpyrrolidone, the tragakanta, pectin, gelatin, carboxymethyl cellulose, methylcellulose, sodium carboxymethyl cellulose, guar gum, micropowder silica gel, Magnesiumaluminumsilicate, hydroxyethyl-cellulose, Kaolin, sodium alginate, kieselguhr, aluminium hydroxide etc.
The preparation method of the mefenamic acid dispersible tablets that described dissolution is improved is with after carrying out the processing of high speed abrasive micropowder behind mefenamic acid and the abundant mix homogeneously of filler, with the disintegrating agent and/or help of 2/3 amount collapse agent, binding agent, adsorbent, fluidizer, suspensoid and/or suspending agent allocate into described in the fine powder of micronization processes mixing, surfactant is dissolved in the wetting agent, stir, be used to make soft material, granulation, add in addition 1/3 amount disintegrating agent after the drying again and/or help and collapse agent, lubricant, correctives mixing, granulate, tabletting, promptly.
Below through detecting to beneficial effect of the present invention as directed:
One, detect index and method:
1. disintegration: 6 of sample thiefs, detect according to two appendix X of Chinese Pharmacopoeia version in 2000 A inspection technique disintegration.
2. dispersing uniformity: 2 of sample thiefs, put (20 ± 1 ℃) jolting in the 100ml water, detect according to two appendix I of Chinese Pharmacopoeia version in 2000 A dispersing uniformity inspection technique.
3. dissolution: detect according to two appendix X of Chinese Pharmacopoeia version in 2000 C, the second method dissolution method.
Sample thief is used ethanol 40ml, and adding phosphate buffer (pH8.0) is solvent to 800ml, and rotating speed is that per minute 75 changes, operation in accordance with the law in the time of 45 minutes, is got solution and is filtered, and precision is measured subsequent filtrate 3ml, put in the 100ml measuring bottle, add phosphate acid and be diluted to scale, shake up towards liquid (pH8.0); Precision takes by weighing mefenamic acid reference substance 20mg in addition, puts in the 100ml measuring bottle, adds ethanol 5ml and makes dissolving, add phosphate buffer (pH8.0) and be diluted to scale, shake up, precision is measured in right amount, and (pH8.0) is diluted to the solution that contains mefenamic acid 10 μ g among every 1ml with phosphate buffer.Get above-mentioned two kinds of solution,, measure trap respectively, calculate every stripping quantity at the wavelength of 286nm according to spectrophotography (two appendix IV of Chinese Pharmacopoeia version in 2000 A).
Two, mefenamic acid sheet (commercially available conventional tablet) index of correlation testing result
1. disintegration time: 26 minutes
2. dispersing uniformity: can not homodisperse after the jolting in 20 ± 1 ℃ of water of 100ml, can not be all by No. 2 sieves.
3. dissolution: 67.4%.
Three, example 1 sample detection result:
1. disintegration time: 26 seconds
2. dispersing uniformity: expansion homodisperse rapidly in 20 ± 1 ℃ of water of 100ml, and all sieve by No. 2.
3. dissolution: 98.6%.
Four, example 2 sample detection results:
1. disintegration time: 35 seconds
2. dispersing uniformity: expansion homodisperse rapidly in 20 ± 1 ℃ of water of 100ml, and all sieve by No. 2.
3. dissolution: 95.2%.
Five, example 3 sample detection results:
1. disintegration time: 44 seconds
2. dispersing uniformity: expansion homodisperse rapidly in 20 ± 1 ℃ of water of 100ml, and all sieve by No. 2.
3. dissolution: 97.3%.
Six, example 4 sample detection results:
1. disintegration time: 53 seconds
2. dispersing uniformity: expansion homodisperse rapidly in 20 ± 1 ℃ of water of 100ml, and all sieve by No. 2.
3. dissolution: 96.2.
More than detect as directed, mefenamic acid dispersible tablets of the present invention and commercially available common mefenamic acid tablet compare, and this product has quick disintegrate, stripping, is uniformly dispersed, and improves the dissolution of medicine and the advantage of bioavailability.
The specific embodiment
(1) example 1
Mefenamic acid 250g
Lactose 30g
Low-substituted hydroxypropyl cellulose 20g
Micropowder silica gel 20g
Microcrystalline Cellulose 80g
Crospolyvinylpyrrolidone 20g
Carboxymethyl starch sodium 30g
Tween 80 5g
Poloxamer 5g
Correctives is an amount of
Magnesium stearate 1.5g
60% ethanol is an amount of
Make 1000
(2) example 2
Mefenamic acid 250g
Lactose 80g
Micropowder silica gel 30g
Microcrystalline Cellulose 100g
Crospolyvinylpyrrolidone 20g
Cross-linking sodium carboxymethyl cellulose 20g
Tween 80 4g
Poloxamer 5g
Polyvinylpyrrolidone K30 1g
50% ethanol is an amount of
Correctives is an amount of
Magnesium stearate 2g
Make 1000
(3) example 3
Mefenamic acid 250g
Lactose 100g
Micropowder silica gel 30g
Microcrystalline Cellulose 60g
Crospolyvinylpyrrolidone 35g
Cross-linking sodium carboxymethyl cellulose 15g
Tween 80 5g
Poloxamer 5g
30% ethanol is an amount of
Correctives is an amount of
Magnesium stearate 2g
Make 1000
(4) example 4
Mefenamic acid 250g
Lactose 100g
Micropowder silica gel 20g
Microcrystalline Cellulose 80g
Crospolyvinylpyrrolidone 15g
Cross-linking sodium carboxymethyl cellulose 20g
Poloxamer 5g
30% ethanol is an amount of
Correctives is an amount of
Magnesium stearate 1g
Make 1000
Formulation preparation method in the above-mentioned example:
1. with grinding in active component and the rearmounted high speed powder mill of the abundant mix homogeneously of filler, carry out micronization processes, get impalpable powder (200 orders-500 order).
2. with above impalpable powder and binding agent, adsorbent, fluidizer, suspensoid and/or suspending agent and 2/3 amount disintegrating agent and/or help and collapse the abundant mix homogeneously of agent.
3. surfactant is dissolved in the wetting agent, stirs, be used for mixed powder system soft material 2., 18 mesh sieves are granulated.
4. the granule of making added the disintegrating agent of 1/3 amount in addition and/or helps and collapses agent, lubricant, correctives, 16 mesh sieve granulate, mix homogeneously after below 80 ℃ dry 4 hours.
5. tabletting, pressure is 3～4kg/cm
2
Claims (4)
1. the mefenamic acid dispersible tablets that is improved of dissolution is characterized in that it is is active component with non-steroidal analgesia, analgesic, anti-inflammatory agent mefenamic acid, and per 1000 active component and adjuvants by following proportioning are formed: mefenamic acid 250g, lactose 30g, low-substituted hydroxypropyl cellulose 20g, micropowder silica gel 20g, microcrystalline Cellulose 80g, crospolyvinylpyrrolidone 20g, carboxymethyl starch sodium 30g, tween 80 5g, poloxamer 5g, magnesium stearate 1.5g, 60% ethanol, correctives are an amount of.
2. the mefenamic acid dispersible tablets that is improved of dissolution is characterized in that it is is active component with non-steroidal analgesia, analgesic, anti-inflammatory agent mefenamic acid, and per 1000 active component and adjuvants by following proportioning are formed: mefenamic acid 250g, lactose 80g, micropowder silica gel 30g, microcrystalline Cellulose 100g, crospolyvinylpyrrolidone 20g, cross-linking sodium carboxymethyl cellulose 20g, tween 80 4g, poloxamer 5g, polyvinylpyrrolidone K30 1g, magnesium stearate 2g, 50% ethanol, correctives are an amount of.
3. the mefenamic acid dispersible tablets that is improved of dissolution, it is characterized in that it is is active component with non-steroidal analgesia, analgesic, anti-inflammatory agent mefenamic acid, per 1000 active component and adjuvants by following proportioning are formed: mefenamic acid 250g, lactose 100g, micropowder silica gel 30g, microcrystalline Cellulose 60g, crospolyvinylpyrrolidone 35g, cross-linking sodium carboxymethyl cellulose 15g, tween 80 5g, poloxamer 5g, magnesium stearate 2g, 30% ethanol, correctives are an amount of.
4. the mefenamic acid dispersible tablets that is improved of dissolution, it is characterized in that it is is active component with non-steroidal analgesia, analgesic, anti-inflammatory agent mefenamic acid, per 1000 active component and adjuvants by following proportioning are formed: mefenamic acid 250g, lactose 100g, micropowder silica gel 20g, microcrystalline Cellulose 80g, crospolyvinylpyrrolidone 15g, cross-linking sodium carboxymethyl cellulose 20g, poloxamer 5g, magnesium stearate 1g, 30% ethanol, correctives are an amount of.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031100597A CN1309387C (en) | 2003-04-15 | 2003-04-15 | Cresol powder with dissolution increased and its preparing method-analgesic, antipyretic and anti-inflammatory agent |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031100597A CN1309387C (en) | 2003-04-15 | 2003-04-15 | Cresol powder with dissolution increased and its preparing method-analgesic, antipyretic and anti-inflammatory agent |
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| Publication Number | Publication Date |
|---|---|
| CN1444940A CN1444940A (en) | 2003-10-01 |
| CN1309387C true CN1309387C (en) | 2007-04-11 |
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| CNB031100597A Expired - Fee Related CN1309387C (en) | 2003-04-15 | 2003-04-15 | Cresol powder with dissolution increased and its preparing method-analgesic, antipyretic and anti-inflammatory agent |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| BRPI1008422A2 (en) * | 2009-02-13 | 2016-03-01 | Ipsen Pharma Sas | solid pharmaceutical composition, process for preparing a solid pharmaceutical composition, and polymorphic compound |
| US8691281B2 (en) | 2009-02-13 | 2014-04-08 | Ipsen Pharma S.A.S. | Solid pharmaceutical composition containing 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta (C)chromen-3-yl sulfamate and polymorphs thereof |
| CN102218041B (en) * | 2010-04-15 | 2015-08-05 | 江苏联环药业股份有限公司 | Ebastine solid dispersion and Ebastine tablets prepared therefrom |
| CN102475689B (en) * | 2010-11-30 | 2015-04-01 | 杭州赛利药物研究所有限公司 | Suspension dispersible tablets and preparation method |
| CN106924713A (en) * | 2017-04-14 | 2017-07-07 | 福建汇天生物药业有限公司 | A kind of leflunomide tablet of high bioavilability and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5055306A (en) * | 1987-10-22 | 1991-10-08 | Aps Research Limited | Sustained-release formulations |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5055306A (en) * | 1987-10-22 | 1991-10-08 | Aps Research Limited | Sustained-release formulations |
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Granted publication date: 20070411 Termination date: 20100415 |