CN1404832A - Gliclazide oral tablet capable of quickly disintegrating and dissolving out and its preparation technology - Google Patents
Gliclazide oral tablet capable of quickly disintegrating and dissolving out and its preparation technology Download PDFInfo
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- CN1404832A CN1404832A CN 02114329 CN02114329A CN1404832A CN 1404832 A CN1404832 A CN 1404832A CN 02114329 CN02114329 CN 02114329 CN 02114329 A CN02114329 A CN 02114329A CN 1404832 A CN1404832 A CN 1404832A
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Abstract
The present invention relates to a gliclazide oral tablet capable of quickly disintegrating and dissolving out and its preparation process. Said oral tablet preparation is made up by using (by weight portion) 1 portion of gliclazide as raw material medicine, 0.625-0.75 portion of disintegration assistant, 0.75-1.125 portions of disintegrating agent, 0.125-0.25 portions of surfactant and 2-2.375 portions of binding agent as auxiliary material through a certain preparation process. Said preparation can be quickly disintegrated in water, and the gliclazide can be quickly dissolved out, so that the resolvability of the medicine and its biological utilization rate can be greatly raised, and its action for curing diabetes can be greatly raised.
Description
Technical field
The present invention relates to a kind of pharmaceutical product and preparation technology, specifically, is the Gliclazide oral tablet and the preparation technology thereof of the quick disintegrate of a kind of energy, stripping.
Technical background
Diabetes are No. second diseases that are only second to cardiovascular disease, and the WHO survey result shows that there are several hundred million diabeticss in the whole world at present, wherein is the type ii diabetes patient more than 90%.China Epidemiological study result shows that among the general crowd, type ii diabetes patient proportion is 1～2%, and proportion is up to 10% among the crowd more than 50 years old, and the patient through being diagnosed as type ii diabetes surpasses 30,000,000 people in China.Along with the raising of people's living standard, diabetes prevalence is quick growth in recent years, obese type type ii diabetes patient showed increased especially, and such patient is poor to insulin sensitivity, becomes the difficult problem in the clinical practice always.
Diabetes are except that disease own, and even more serious harm also is its various complication, and comparatively serious is cardiovascular, kidney, nervous system, ocular complications, the equal grievous injury patient's of each complication quality of life.
The present treatment of type ii diabetes is divided into diet and exercise therapy, oral antidiabetic drug treatment and insulinize.Diet and exercise therapy are the bases of various treatments, are applicable to all type ii diabetes patients, but exhausted big number patient only depends on diet and exercise therapy to be difficult to get a desired effect.Insulinize does not generally advocate to be used for the first-line treatment of type ii diabetes, and mainly is the treatment that is used for the unmanageable hyperglycemia of other medicines or severe infections or ketoacidosis acute stage.Present gone on the market clinical uses more orally-taken blood sugar reducing medicine to be sulphanylureas, biguanides and alpha-glucosidase inhibitor.Because special mechanism of action of alpha-glucosidase inhibitor and expensive price are therefore general not separately as the first-line treatment medicine of diabetes, clinical use is maximum remains sulphanylureas and biguanides.
First generation sulphanylureas orally-taken blood sugar reducing medicine begins to be applied to clinical the 1950's, as tolbutamide and chlorpropamide, but because their side effect is big and the quality instability, at present clinical few use the to the utmost.Second filial generation sulphanylureas orally-taken blood sugar reducing types of drugs is more, and the new varieties listing is also constantly arranged in recent years.
Gliclazide is a second filial generation sulfonylurea blood sugar lowering, acts on byer force, and its mechanism of action is optionally to act on beta Cell of islet, promotes insulin secretion, and the insulin that improves behind the feed glucose discharges, and glycogen is generated and output is suppressed.Zoopery and clinical use prove that also gliclazide can reduce hematoblastic gathering and adhesion, prevents that fibrin deposition from wall of micrangium, having preventive and therapeutic effect to diabetic microvascular complication.Zoopery is the result show, the life-time service gliclazide is cholesterol reducing, triglyceride reducing and fatty acid obviously.Histological examination shows, it can suppress the tremulous pulse, the especially coronary artery injury that are caused by high-cholesterol diet, and is favourable to reducing cardiovascular complication and improving retinopathy.
Pharmacokinetic is the result show, the Gliclazide oral administration absorbs rapidly at gastrointestinal tract, can reach plasma peaks in 3-4 hour, and plasma protein binding rate is 92%, and the half-life is 10-12 hour, oral after mainly at liver metabolism, through homaluria.
Gliclazide is applicable to type ii diabetes, is specially adapted to obese diabetic, senile diabetes and with the glycemic control of the diabetes of cardiovascular complication.Also can try out in insulin-dependent diabetes, treat with insulin combination.
Yet gliclazide has shortcomings such as poorly water-soluble, dissolution rate and bioavailability are low.
Summary of the invention
Purpose of the present invention is exactly by improving the water solublity of this type of medicine, make rapid disintegrate of preparation and homodisperse, thereby improve the dissolution rate and the bioavailability of medicine, more effectively bring into play 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: with gliclazide as crude drug, with micropowder silica gel, microcrystalline Cellulose, crospolyvinylpyrrolidone, cross-linking sodium carboxymethyl cellulose, tween-80, poloxamer, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose etc. as adjuvant.In per 1 weight portion gliclazide, allocate 0.625～0.75 weight portion into and help and collapse agent, 0.75～1.125 weight portion disintegrating agent, 0.125～0.25 weight portion surfactant and 2～2.375 weight portion binding agents.
Above-mentionedly help that to collapse agent be micropowder silica gel, disintegrating agent is crospolyvinylpyrrolidone and/or cross-linking sodium carboxymethyl cellulose and/or carboxymethyl starch sodium, surfactant is tween-80 and/or poloxamer, and binding agent is microcrystalline Cellulose, polyvinylpyrrolidone K30 and/or low-substituted hydroxypropyl cellulose.
The preparation technology of the Gliclazide oral tablet of the quick disintegrate of described energy, dispersion and stripping is with after carrying out micropowder processing (grinding to form 200 orders-500 purpose fine powder) behind gliclazide and the abundant mix homogeneously of filler (lactose or mannitol), with the disintegrating agent and helping of 2/3 amount collapse agent, binding agent allocate into described in the fine powder of micronization processes (in disintegrating agent) mixing, surfactant is dissolved in the wetting agent, stir, be used to make and add in addition granulate (adding disintegrating agent) after the 1/3 amount disintegrating agent and lubricant mixing after soft material, granulation, the drying again.
Below through detecting: one, detect index and method to beneficial effect of the present invention as directed:
1. disintegration: 6 of sample thiefs, detect according to two appendix XA of Chinese Pharmacopoeia version in 2000 inspection technique disintegration.
2. dispersing uniformity: 2 of sample thiefs, put (20 ± 1 ℃) jolting in the 100ml water, detect according to two appendix IA of Chinese Pharmacopoeia version in 2000 dispersing uniformity inspection technique.
3. dissolution rate: detect according to two appendix XC of Chinese Pharmacopoeia version in 2000, the second method dissolution method.
900ml is a solvent with phosphate buffer (pH7.4), and rotating speed is that per minute 100 changes, operation in accordance with the law.Got solution and filter in right amount in the time of 5,10,20,30,45 minutes, precision is measured subsequent filtrate 5ml, puts in the 25ml measuring bottle, is diluted to scale with phosphate buffer, shakes up; It is an amount of that precision takes by weighing the gliclazide reference substance in addition, (pH7.4) makes the solution that contains 8 μ g among every 1ml with phosphate buffer, (two appendix IVA of Chinese Pharmacopoeia version in 2000) measure trap respectively in the wavelength place of 226nm according to spectrophotography, by the stripping quantity of every of the ratio calculation of the two trap.Two, gliclazide 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 rate: see Table 1.
The commercially available gliclazide ordinary tablet of table 1. dissolution rate testing result
Three, example 1 sample detection result:
| Time (minute) | ????5???????10??????20??????30??????45 |
| Stripping quantity (%) | ????31.4????49.6????63.5????86.7????95.2 |
1. disintegration time: 12 seconds
2. dispersing uniformity: expansion homodisperse rapidly in ℃ water of 100ml20 ± 1, and all sieve by No. 2.
3. dissolution rate: see Table 2.
Table 2. example 1 sample dissolution rate testing result
Four, example 2 sample detection results:
| Time (minute) | ????5???????10??????20??????30??????45 |
| Stripping quantity (%) | ????96.4????98.6????99.3????99.6????98.9 |
1. disintegration time: 68 seconds
2. dispersing uniformity: expansion homodisperse rapidly in ℃ water of 100ml20 ± 1, and all sieve by No. 2.
3. dissolution rate: see Table 3.
Table 3. example 2 sample dissolution rate testing results
Five, example 3 sample detection results:
| Time (minute) | ????5???????10??????20??????30??????45 |
| Stripping quantity (%) | ????93.2????97.5????99.3????98.6????99.2 |
1. disintegration time: 72 seconds
2. dispersing uniformity: expansion homodisperse rapidly in ℃ water of 100ml20 ± 1, and all sieve by No. 2.
3. dissolution rate: see Table 4.
Table 4. example 3 sample dissolution rate testing results
Six, example 4 sample detection results: 1. disintegration time: 46 seconds are dispersing uniformity 2.: expansion homodisperse rapidly in 100ml20 ± 1 water, and all sieve by No. 2.3. dissolution rate: see Table 5.
| Time (minute) | ????5???????10??????20??????30??????45 |
| Stripping quantity (%) | ????91.7????98.6????99.2????99.7????98.1 |
Table 5. example 4 sample dissolution rate testing results
Seven, example 5 sample detection results:
| Time (minute) | ????5???????10??????20??????30??????45 |
| Stripping quantity (%) | ????89.6????95.3????97.2????99.6????98.3 |
1. disintegration time: 50 seconds
2. dispersing uniformity: expansion homodisperse rapidly in ℃ water of 100ml20 ± 1, and all sieve by No. 2.
3. dissolution rate: see Table 6.
Table 6. example 5 sample dissolution rate testing results
| Time (minute) | ????5???????10??????20??????30??????45 |
| Stripping quantity (%) | ????93.6????99.8????98.9????97.8????97.1 |
More than detect as directed, the present invention and commercially available common gliclazide 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
Gliclazide 40g
Lactose 80g
Mannitol 30g
Micropowder silica gel 30g
Microcrystalline Cellulose 80g
Crospolyvinylpyrrolidone 20g
Carboxymethyl starch sodium 10g
Tween 80 5g
Poloxamer 5g
Magnesium stearate 1g
900% ethanol 2000ml
Make 1000 (two) examples 2
Gliclazide 40g
Lactose 100g
Low-substituted hydroxypropyl cellulose 40g
Micropowder silica gel 25g
Microcrystalline Cellulose 55g
Crospolyvinylpyrrolidone 15g
Cross-linking sodium carboxymethyl cellulose 15g
Tween 80 5g
Poloxamer 5g
Magnesium stearate 1.5g
9n% ethanol 200ml
Make 1000 (three) examples 3
Gliclazide 40g
Lactose 80g
Micropowder silica gel 30g
Microcrystalline Cellulose 95g
Crospolyvinylpyrrolidone 20g
Cross-linking sodium carboxymethyl cellulose 25g
Tween 80 4g
Poloxamer 5g
Polyvinylpyrrolidone K30 1g
50% ethanol 210ml
Magnesium stearate 2g
Make 1000 (four) examples 4
Gliclazide 40g
Lactose 80g
Micropowder silica gel 30g
Microcrystalline Cellulose 95g
Crospolyvinylpyrrolidone 20g
Cross-linking sodium carboxymethyl cellulose 25g
Tween 80 4g
Poloxamer 5g
30% ethanol 200ml
Magnesium stearate 2g
Make 1000 (five) examples 5
Gliclazide 40g
Lactose 80g
Micropowder silica gel 30g
Microcrystalline Cellulose 95g
Crospolyvinylpyrrolidone 20g
Cross-linking sodium carboxymethyl cellulose 25g
Poloxamer 5g
30% ethanol 270ml
Magnesium stearate 1g
Make preparation process thereof in 1000 above-mentioned examples
1. with grinding in the rearmounted high speed powder mill of the abundant mix homogeneously of principal agent (raw material) and filler, carry out micronization processes, get impalpable powder (200 orders-500 order).
2. above impalpable powder is collapsed agent, binding agent and the abundant mix homogeneously of 2/3 amount disintegrating agent with helping.
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 disintegrating agent, the lubricant of 1/3 amount in addition, 16 mesh sieve granulate, mix homogeneously after below 80 ℃ dry 4 hours.
5. tabletting, pressure is 3～4kg/cm
2
Wherein: 1. filler: lactose and/or mannitol.
2. help and collapse agent: micropowder silica gel.
3. binding agent: microcrystalline Cellulose and/or polyvinylpyrrolidone K30 and/or low-substituted hydroxypropyl cellulose.
4. disintegrating agent: crospolyvinylpyrrolidone and/or cross-linking sodium carboxymethyl cellulose and/or carboxymethyl starch sodium etc.
5. surfactant: tween-80 and/or poloxamer.
6. wetting agent: ethanol, water.
7. lubricant: magnesium stearate.
Claims (7)
1. the Gliclazide oral tablet of the quick disintegrate of energy, stripping, it is characterized in that: with gliclazide as crude drug, in per 1 weight portion gliclazide, allocate 0.625～0.75 weight portion into and help and collapse agent, 0.75～1.125 weight portion disintegrating agent, 0.125～0.25 weight portion surfactant and 2～2.375 weight portion binding agents.
2. the Gliclazide oral tablet of the quick disintegrate of energy according to claim 1, stripping is characterized in that: help that to collapse agent be micropowder silica gel.
3. the Gliclazide oral tablet of the quick disintegrate of energy according to claim 1, stripping is characterized in that: disintegrating agent is crospolyvinylpyrrolidone and/or cross-linking sodium carboxymethyl cellulose and/or carboxymethyl starch sodium.
4. the Gliclazide oral tablet of the quick disintegrate of energy according to claim 1, stripping is characterized in that: surfactant is tween-80 and/or poloxamer.
5. the Gliclazide oral tablet of the quick disintegrate of energy according to claim 1, stripping is characterized in that: binding agent is microcrystalline Cellulose and/or polyvinylpyrrolidone K30 and/or low-substituted hydroxypropyl cellulose.
6. the preparation technology of the Gliclazide oral tablet of the quick disintegrate of the described energy of claim 1, stripping, it is characterized in that: handle carrying out micropowder behind gliclazide and the abundant mix homogeneously of filler, grind to form 200 orders-500 purpose fine powder, the disintegrating agent and helping of 2/3 amount is collapsed agent, binding agent allocate described granulate after the 1/3 amount disintegrating agent and lubricant mixing, the tabletting of in the fine powder of micronization processes, adding again after mixing, system soft material, granulation, the drying in addition into.
7. the preparation technology of the Gliclazide oral tablet of the quick disintegrate of energy according to claim 6, stripping, it is characterized in that: above-mentioned filler is lactose and/or mannitol, help that to collapse agent be micropowder silica gel, binding agent is microcrystalline Cellulose and/or polyvinylpyrrolidone K30 and/or low-substituted hydroxypropyl cellulose, disintegrating agent is crospolyvinylpyrrolidone and/or cross-linking sodium carboxymethyl cellulose and/or carboxymethyl starch sodium, surfactant is tween-80 and/or poloxamer, wetting agent is ethanol, water, and lubricant is a magnesium stearate.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02114329 CN1404832A (en) | 2002-08-05 | 2002-08-05 | Gliclazide oral tablet capable of quickly disintegrating and dissolving out and its preparation technology |
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| CN 02114329 CN1404832A (en) | 2002-08-05 | 2002-08-05 | Gliclazide oral tablet capable of quickly disintegrating and dissolving out and its preparation technology |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103690501A (en) * | 2013-12-24 | 2014-04-02 | 江西南昌制药有限公司 | Gliclazide tablet and preparation method thereof |
| CN104784050A (en) * | 2014-01-17 | 2015-07-22 | 南京瑞尔医药有限公司 | Preparation method for gliclazide tablet composition |
| CN104784130A (en) * | 2014-01-17 | 2015-07-22 | 南京瑞尔医药有限公司 | Gliclazide tablet composition |
-
2002
- 2002-08-05 CN CN 02114329 patent/CN1404832A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103690501A (en) * | 2013-12-24 | 2014-04-02 | 江西南昌制药有限公司 | Gliclazide tablet and preparation method thereof |
| CN104784050A (en) * | 2014-01-17 | 2015-07-22 | 南京瑞尔医药有限公司 | Preparation method for gliclazide tablet composition |
| CN104784130A (en) * | 2014-01-17 | 2015-07-22 | 南京瑞尔医药有限公司 | Gliclazide tablet composition |
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