CN1799543A - Telmisartan dispersible tablet and its preparation method - Google Patents
Telmisartan dispersible tablet and its preparation method Download PDFInfo
- Publication number
- CN1799543A CN1799543A CN 200510130979 CN200510130979A CN1799543A CN 1799543 A CN1799543 A CN 1799543A CN 200510130979 CN200510130979 CN 200510130979 CN 200510130979 A CN200510130979 A CN 200510130979A CN 1799543 A CN1799543 A CN 1799543A
- Authority
- CN
- China
- Prior art keywords
- telmisartan
- agent
- dispersible tablet
- disintegrating agent
- percentage
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Abstract
The invention discloses a samidin dispersion tablet and the method for making same, the component and their weight percentage are: samidin 2%-99%, findings 1%-98%, the findings comprising disintegrating agent, filling agent or diluting agent, binding agent, flow promoting agent or lubricating agent. The preparing method comprises: sifting the samidin with screen of 100 order, sifting the disintegrating agent, filling agent or diluting agent wit hscreen of 80 order; measuring samidin and disintegrating agent, filing agent or diluting agent according to the formular, mixing them uniformly; adding bonding agent to prepare soft material, sifting with screen of 18-20 order, drying the particle in baking box of 50-70 Deg C; sifting the dry particle with screen of 20 order, adding part of disintegrating agent, flow promoting agent or lubricating agent, string uniformly; checking the half-finished product, pressing it; checking the finished product, packing and getting the samidin dispersion tablet. The product is one of the medicine for treating high blood pressure of the newest generation, comparing with other medicine, it is characterized by the uniform distribution, short disintegrating time, fast medicine dissolving out, high bio-availability, and convenient intake, and is particularly suited for the old and dysphagia patients.
Description
Technical field
The present invention relates to a kind of medicine and preparation method thereof, specifically telmisartan dispersible tablet and preparation method thereof.
Background technology
Telmisartan is a kind of angiotensin-ii receptor inhibitor of long-acting, efficient, low toxicity, but the nervous plain AT of highly selective vasoactive
1Receptor is to AT
1The action intensity of receptor is than AT
2Strong about 20000 times, selectivity also is higher than like product.Synthetic Angiotensin II is to AT in the blocking-up body
1Affinity interaction, antagonism is by AT
1Activate arteries contraction, sympathetic activation and physiological effecies such as the increase of pressure receptor sensitivity, increased blood pressure that the back is produced, bring high blood pressure down, weaken myocardial cell and shrink, and retardance AT
1Act on the water-sodium retention that produces behind the kidney.Telmisartan also can reverse by AT
1Cardiac muscle and the proliferation of smooth muscle of arterial blood tube wall and the plumpness of mediation delay the process of myocardial hypertrophy and kidney interstitial fibrosis, reduce the sickness rate and the case fatality rate of heart failure.Telmisartan is one of hypertension treatment medicine of latest generation.But the dosage form of telmisartan mainly contains tablet or capsule at present, and its disintegration time is long, and the medicine dissolution rate is slow, and absorption of human body is also slow, and for old, young and the difficult person that swallows, it is not too convenient to take.
Summary of the invention
Technical problem to be solved by this invention is to propose a kind of disintegration time weak point, the medicine stripping is rapid, absorption is fast, taking convenience also can improve telmisartan dispersible tablet of bioavailability of drugs and curative effect and preparation method thereof.
For solving the problems of the technologies described above, telmisartan dispersible tablet of the present invention comprises following each component, and its weight content percentage ratio is respectively: telmisartan 2%～99%, adjuvant 1%～98%.Be preferably: telmisartan 5～30%, adjuvant 30%～95%.
Above-mentioned telmisartan dispersible tablet, described accessory package contains disintegrating agent, filler or diluent, binding agent, fluidizer or lubricant.Because raw material does not have the bad flavor of smelling, therefore in prescription, can not add correctives.
Telmisartan is white or off-white color crystallization or crystalline powder, and odorless, tasteless dissolves in chloroform, and soluble,very slightly in acetone is almost insoluble in water.Select adjuvant according to feedstock property and preparation characteristic:
Disintegrating agent can select that microcrystalline Cellulose, starch, pregelatinized Starch, modified starch, polyvinylpolypyrrolidone, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose are received, in the carboxymethylcellulose calcium, sodium carboxymethyl cellulose one or more, preferred crospolyvinylpyrrolidone or cross-linking sodium carboxymethyl cellulose.Molecular weight is criterion calculation routinely, and the percentage by weight that disintegrating agent accounts for total prescription is 2%～70%, and preferred 5～20%.The interior dosage of disintegrating agent is to be preferably 2～5 times of outer dosage.
Filler or diluent can be selected dextrin, lactose, sucrose, in Celluloasun Microcrystallisatum, cellulose, calcium sulfate, calcium hydrogen phosphate, calcium phosphate dibasic anhydrous, pregelatinized Starch, the starch one or more, in preferably microcrystalline cellulose, pregelatinized Starch, starch, the lactose one or more, preferred.Molecular weight is criterion calculation routinely, and the percentage by weight that filler or diluent account for total prescription is 2%～85%, and preferred 20～80%.
Binding agent can be selected one or more in starch slurry, syrup, dextrin, purified water, ethanol, sodium carboxymethyl cellulose, hypromellose, the ethyl cellulose, because raw material has extremely strong hydrophobicity, therefore preferred 20-70% ethanol, through screening test, concentration is that 30% o'clock effect is best.Molecular weight is criterion calculation routinely, and the percentage by weight of the total prescription of binder constitutes is 0.1%～65%, and preferred 5～30%.
Fluidizer or lubricant are one or more in stearic acid, magnesium stearate, zinc stearate, calcium stearate, silicon dioxide, micropowder silica gel, Pulvis Talci, the hard paraffin, preferred micropowder silica gel and magnesium stearate.Micropowder silica gel is light-weight white powder, and odorless, tasteless is water insoluble and sour, is dissolved in Fluohydric acid. and hot alkaline solution.Chemical property is stable, and good flowability is arranged, and medicine is had bigger absorption affinity, and hydrophilic is strong, is commonly used for the tablet fluidizer, promoting the flowability of material, but consumption speeding up disintegration of tablet more than 1.0%.Magnesium stearate is a white powder, and fine and smooth easily have good tack, and is not easily separated with being evenly distributed after granule mixes, only with can demonstrating good lubricating property on a small quantity, and the tablet surface smooth and beautiful appearance, be the lubricant of extensive use.Molecular weight is criterion calculation routinely, and the percentage by weight that lubricant accounts for total prescription is 0.1%～20%, and preferred 0.5～5%.
The preparation method of telmisartan dispersible tablet can prepare through the following steps:
1, telmisartan is crossed 100 mesh sieves, disintegrating agent, filler or diluent are crossed 80 mesh sieves, and be standby.
2, take by weighing telmisartan and disintegrating agent, filler or diluent, mix homogeneously by recipe quantity.
3, add binding agent and make soft material, cross 18～20 mesh sieve system granules, granule is dry in 50～70 ℃ of baking ovens.
4, dried granule is crossed 20 mesh sieve granulate, adds part disintegrating agent, fluidizer or lubricant mixing.
5, after the inspection of semifinished product, tabletting.
6, after the product inspection, packing, promptly.
The present invention adds the dispersible tablet that appropriate amount of auxiliary materials is made with telmisartan, and it has the advantage of tablet and fluid preparation concurrently, has to be uniformly dispersed, and disintegration is extremely short, characteristics such as the medicine stripping is fast, bioavailability is high, taking convenience.Can add after the aqueous dispersion orally, also can be contained in and suck clothes in the mouth or swallow, especially be fit to the patient of old people, dysphagia.By the telmisartan dispersible tablet that the inventive method makes, through check, quality index such as its content, character, discriminating, disintegration, dissolution, dispersing uniformity meet " Chinese Pharmacopoeia version in 2000 " and pertinent regulations.General 60 seconds of the disintegration of dispersible tablet of the present invention got final product complete disintegrate, and pharmacopeia requires disintegrate in 3 minutes; The dissolution of dispersible tablet of the present invention is higher than 90%, and the tablet of listing only can reach 80% under the same conditions, illustrates that dispersible tablet of the present invention has produced beyond thought effect.
The specific embodiment
Embodiment one: the prescription screening test of telmisartan dispersible tablet
Select following adjuvant to carry out screening test: filler: pregelatinized Starch, microcrystalline Cellulose; Disintegrating agent: crospolyvinylpyrrolidone (is called for short: PVPP); Binding agent: 30%-70% ethanol; Lubricant: micropowder silica gel, magnesium stearate.Design 6 prescriptions, as follows:
The supplementary product consumption of table 1 prescription is selected (specification: the 40mg/ sheet)
| The prescription number | 1 | 2 | 3 | 4 | 5 | 6 |
| Telmisartan | 4.0g | 4.0g | 4.0g | 4.0g | 4.0g | 4.0g |
| Pregelatinized Starch | 11.2g | 11.2g | 7.2g | 7.2g | 9.2g | 9.2g |
| Microcrystalline Cellulose | 3.0g | 3.0g | 7.0g | 7.0g | 5.0g | 5.0g |
| PVPP (interior) | 2.0g | 1.6g | 2.0g | 1.6g | ||
| Binding agent | 70% ethanol | 30% ethanol | 70% ethanol | 30% ethanol | 70% ethanol | 30% ethanol |
| PVPP (outward) | 2.0g | 0.4g | 2.0g | 0.4g | ||
| Micropowder silica gel | 0.4g | 0.4g | 0.4g | 0.4g | 0.4g | 0.4g |
| Magnesium stearate | 0.2g | 0.2g | 0.2g | 0.2g | 0.2g | 0.2g |
Prescription is investigated the index and the method for inspection thereof: mainly investigating index is: disintegration, dispersing uniformity, dissolution; Less important investigation index is: indexs such as the hardness of particulate flowability, tablet, outward appearance; Measure content, related substance simultaneously, to determine whether adjuvant has interference to mensuration.
Result of the test: see Table 2.
Investigation result (the specification: the 40mg/ sheet) of table 2 prescription
| The prescription number | 1 | 2 | 3 | 4 | 5 | 6 |
| Mobility of particle | Better | Good | Relatively poor | Better | Generally | Good |
| Outward appearance | Better | Generally | Better | Better | Generally | Better |
| Tablet weight variation | Qualified | Qualified | Defective | Qualified | Defective | Qualified |
| Hardness | 8.0kg | 7.0kg | 6.0kg | 6.5kg | 5.0kg | 7.5kg |
| Disintegration time | 90 seconds | 40 seconds | 55 seconds | 75 seconds | 35 seconds | 45 seconds |
| Sieve by 2# | Be | Not | Be | Be | Not | Be |
| Content | 99.24％ | 99.66％ | ||||
| Related substance | 0.359％ | 0.352％ | ||||
| Dissolution | 86.2％ | 95.6％ |
As can be seen from Table 2, all better by the every indexs of sample of prescription 6 preparations, so our 6 optimizing prescriptions as the telmisartan dispersible tablet of 40mg specification of selecting to write out a prescription.
Embodiment two: telmisartan dispersible tablet comprises following each component:
Telmisartan 10.0g 6.5%
Starch 52.0g 34.0%
Lactose 30.0g 19.6%
Add 16.0g 10.5% in the crospolyvinylpyrrolidone
Add 4g 2.6%
30% ethanol 35g 22.9%
Micropowder silica gel 4.0g 2.6%
Magnesium stearate 2.0g 1.3%
Prepare 1000 altogether
It is prepared from through the following steps:
1, telmisartan is crossed 100 mesh sieves, starch, lactose, crospolyvinylpyrrolidone are crossed 80 mesh sieves, and be standby.Take by weighing telmisartan and starch, lactose, crospolyvinylpyrrolidone (in add part), mix homogeneously by recipe quantity.Add binding agent 30% ethanol and make soft material, cross 18～20 mesh sieve system granules, granule is dry in 50～70 ℃ of baking ovens.Dried granule is crossed 20 mesh sieve granulate, adds crospolyvinylpyrrolidone (Extra Section), micropowder silica gel, magnesium stearate mixing.After the inspection of semifinished product, tabletting.After the product inspection, packing, promptly.
Above preparation, through check, quality index such as its content, character, discriminating, disintegration, dissolution, dispersing uniformity not only meet " Chinese Pharmacopoeia version in 2000 " and pertinent regulations, and disintegration time is lower than 1 minute, dissolution is higher than 90%, considerably beyond dispersible tablet generally require standard.
Embodiment three: telmisartan dispersible tablet comprises following each component:
Telmisartan 20.0g 10.4%
Starch 60.0g 31.1%
Microcrystalline Cellulose 40.0g 20.7%
Add 20.0g 10.4% in the cross-linking sodium carboxymethyl cellulose
Add 6g 3.1%
30% ethanol 45g 23.3%
Magnesium stearate 2.0g 1.1%
Prepare 1000 altogether
It is prepared from through the following steps:
1, telmisartan is crossed 100 mesh sieves, starch, cellulose powder, sodium carboxymethyl cellulose are crossed 80 mesh sieves, and be standby.Take by weighing telmisartan and starch, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose (in add part), mix homogeneously by recipe quantity.Add binding agent 30% ethanol and make soft material, cross 18～20 mesh sieve system granules, granule is dry in 50～70 ℃ of baking ovens.Dried granule is crossed 20 sieve granulate, adds cross-linking sodium carboxymethyl cellulose (Extra Section), magnesium stearate mixing.After the inspection of semifinished product, tabletting.After the product inspection, packing, promptly.
Above preparation, through check, quality index such as its content, character, discriminating, disintegration, dissolution, dispersing uniformity not only meet " Chinese Pharmacopoeia version in 2000 " and pertinent regulations, and disintegration time is lower than 1 minute, dissolution is higher than 90%, considerably beyond dispersible tablet generally require standard.
Embodiment four: telmisartan dispersible tablet comprises following each component:
Telmisartan 40.0g 16.1%
Microcrystalline Cellulose 120.0g 48.4%
Add 25.0g 10.1% in the pregelatinized Starch
Add 6g 2.4%
30% ethanol 53g 21.4%
Micropowder silica gel 4.0g 1.6%
Prepare 1000 altogether
It is prepared from through the following steps:
1, telmisartan is crossed 100 mesh sieves, 80 mesh sieves are crossed in microcrystalline Cellulose, pregelatinized Starch, and are standby.Take by weighing telmisartan and microcrystalline Cellulose, pregelatinized Starch (in add part), mix homogeneously by recipe quantity.Add binding agent 30% ethanol and make soft material, cross 18～20 mesh sieve system granules, granule is dry in 50～70 ℃ of baking ovens.Dried granule is crossed 20 mesh sieve granulate, adds pregelatinized Starch (Extra Section), micropowder silica gel mixing.After the inspection of semifinished product, tabletting.After the product inspection, packing, promptly.
Above preparation, through check, quality index such as its content, character, discriminating, disintegration, dissolution, dispersing uniformity not only meet " Chinese Pharmacopoeia version in 2000 " and pertinent regulations, and disintegration time is lower than 1 minute, dissolution is higher than 90%, considerably beyond dispersible tablet generally require standard.
Embodiment five: telmisartan dispersible tablet comprises following each component:
Telmisartan 80.0g 15.6%
Starch 170.0g 33.2%
Microcrystalline Cellulose 110.0g 21.5%
Add 35.0g 6.8% in the cross-linking sodium carboxymethyl cellulose
Add 10.0g 2.0%
30% alcohol 95 g 18.6%
Micropowder silica gel 8.0g 1.6%
Magnesium stearate 4.0g 0.8%
Prepare 1000 altogether
It is prepared from through the following steps:
1, telmisartan is crossed 100 mesh sieves, starch, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose are crossed 80 mesh sieves, and be standby.Take by weighing telmisartan and starch, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose (in add part), mix homogeneously by recipe quantity.Add binding agent 30% ethanol and make soft material, cross 18～20 mesh sieve system granules, granule is dry in 50～70 ℃ of baking ovens.Dried granule is crossed 20 mesh sieve granulate, adds cross-linking sodium carboxymethyl cellulose (Extra Section), micropowder silica gel, magnesium stearate mixing.After the inspection of semifinished product, tabletting.After the product inspection, packing, promptly.
Above preparation, through check, quality index such as its content, character, discriminating, disintegration, dissolution, dispersing uniformity not only meet " Chinese Pharmacopoeia version in 2000 " and pertinent regulations, and disintegration time is lower than 1 minute, dissolution is higher than 90%, considerably beyond dispersible tablet generally require standard.
Embodiment six: telmisartan dispersible tablet comprises following each component:
Specification: 40mg
Telmisartan active component 40.0g 15.5%
Pregelatinized Starch filler 92.0g 35.7%
Microcrystalline Cellulose filler 50.0g 19.4%
Add 16.0g 6.2% in the crospolyvinylpyrrolidone disintegrating agent
Add 4.0g 1.6%
30% ethanol binding agent 50g 19.4%
Micropowder silica gel fluidizer 4.0g 1.6%
Magnesium 2.0g 0.8%
Prepare 1000 altogether
It is prepared from through the following steps:
The preparation binding agent; It is standby that telmisartan was pulverized 100 mesh sieves, and it is standby that crospolyvinylpyrrolidone, pregelatinized Starch, microcrystalline Cellulose are crossed 80 mesh sieves; Take by weighing raw material and adjuvant by recipe quantity; With telmisartan, crospolyvinylpyrrolidone, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, add binding agent and make soft material in right amount, soft material is crossed 20 order nylon sieve series granules, and wet granular is put in the rustless steel pallet in 60 ℃ of baking oven inner dryings; Dried granule is crossed 20 order piano-wire screen granulate, mixing after adding crospolyvinylpyrrolidone, micropowder silica gel, the magnesium stearate; The inspection of semifinished product; Tabletting; Product inspection; Packing promptly.
Above preparation, through check, quality index such as its content, character, discriminating, disintegration, dissolution, dispersing uniformity not only meet " Chinese Pharmacopoeia version in 2000 " and pertinent regulations, and disintegration time is lower than 1 minute, dissolution is higher than 90%, considerably beyond dispersible tablet generally require standard.
Embodiment seven: telmisartan dispersible tablet comprises following each component:
Specification: 80mg
Telmisartan active component 80.0g 16.1%
Pregelatinized Starch filler 166.0g 33.4%
Microcrystalline Cellulose filler 100.0g 20.1%
Add 32.0g 6.4% in the crospolyvinylpyrrolidone disintegrating agent
Add 10.0g 2.0%
30% ethanol binding agent an amount of 19.5%
Micropowder silica gel fluidizer 8.0g 1.6%
Magnesium 4.0g 0.8%
Prepare 1000 altogether
It is prepared from through the following steps:
The preparation binding agent; It is standby that telmisartan was pulverized 100 mesh sieves, and it is standby that crospolyvinylpyrrolidone, pregelatinized Starch, microcrystalline Cellulose are crossed 80 mesh sieves; Take by weighing raw material and adjuvant by recipe quantity; With telmisartan, crospolyvinylpyrrolidone, pregelatinized Starch, microcrystalline Cellulose mix homogeneously, add binding agent and make soft material in right amount, soft material is crossed 20 nylon sieve series granules, and wet granular is put in the rustless steel pallet in 60 ℃ of baking oven inner dryings; Dried granule is crossed 20 order piano-wire screen granulate, mixing after adding crospolyvinylpyrrolidone, micropowder silica gel, the magnesium stearate; The inspection of semifinished product; Tabletting; Product inspection; Packing promptly.
Make the sample of 3 batches of pilot-scales by above-mentioned prescription and method for making, through check, quality index such as its content, character, discriminating, disintegration, dissolution, dispersing uniformity not only meet " Chinese Pharmacopoeia version in 2000 " and pertinent regulations, and disintegration time is lower than 1 minute, dissolution is higher than 90%, considerably beyond dispersible tablet generally require standard.
Embodiment eight: the stability test of telmisartan dispersible tablet
Method by embodiment five and embodiment six respectively prepares 3 batch samples respectively, detects, the line stabilization test of going forward side by side:
1, sample, reference substance, reagent and instrument
Reference substance: telmisartan (lot number: 030802; Press dry product and calculate, content is 99.71%), provide by Qidu Pharmaceutical Co., Ltd., Shandong Prov..
Sample: telmisartan dispersible tablet, self-control, aluminium-plastic bubble plate packing;
Sample specification, lot number and quantity:
40mg: middle test agent: 031113 batch, inspection product quantity is: 9435; 031114 batch, inspection product quantity is: 9527; 031115 batch, inspection product quantity is: 9590;
80mg: middle test agent: 031119 batch, inspection product quantity is: 9630; 031120 batch, inspection product quantity is: 9550; 031121 batch, inspection product quantity is: 9616.
2, investigation project and test basis
2.1, the investigation project: character, dissolution, dispersing uniformity, related substance, sign content.And at accelerated test and long term test end of term increase limit test of microbe.
2.2, test basis: clinical application product quality draft standard.
3, content of the test and condition
3.1 accelerated test: get pilot scale six batch samples of specification 40mg and 80mg respectively,, put under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5% and placed 6 months by intending the listing packing.Respectively at taking a sample 1st month, 2 months, 3 months, 6 the end of month, relatively after the outward appearance, test every index at duration of test, result and comparison in 0 month.Result of the test sees Table 1, table 2, table 3.
Table 1 telmisartan dispersible tablet accelerated test is investigated result's (specification: 40mg)
| Lot number | Time (moon) | Character | Dispersing uniformity | Dissolution (%) | Related substance (%) | Indicate content (%) |
| 031113 | 0 | White tablets | Up to specification | 94.4 | 0.378 | 100.3 |
| 1 | White tablets | Up to specification | 97.2 | 0.389 | 99.92 | |
| 2 | White tablets | Up to specification | 95.3 | 0.471 | 99.46 | |
| 3 | White tablets | Up to specification | 95.0 | 0.530 | 99.24 | |
| 6 | White tablets | Up to specification | 94.9 | 0.568 | 98.47 | |
| 031114 | 0 | White tablets | Up to specification | 95.0 | 0.342 | 99.78 |
| 1 | White tablets | Up to specification | 96.1 | 0.393 | 99.77 | |
| 2 | White tablets | Up to specification | 95.0 | 0.438 | 99.45 | |
| 3 | White tablets | Up to specification | 94.6 | 0.482 | 98.86 | |
| 6 | White tablets | Up to specification | 95.4 | 0.560 | 97.62 | |
| 031115 | 0 | White tablets | Up to specification | 95.5 | 0.351 | 102.0 |
| 1 | White tablets | Up to specification | 95.9 | 0.401 | 100.6 | |
| 2 | White tablets | Up to specification | 95.6 | 0.439 | 99.89 | |
| 3 | White tablets | Up to specification | 95.9 | 0.480 | 99.72 | |
| 6 | White tablets | Up to specification | 97.0 | 0.575 | 99.17 |
Table 2 telmisartan dispersible tablet accelerated test is investigated result's (specification: 80mg)
| Lot number | Time (moon) | Character | Dispersing uniformity | Dissolution (%) | Related substance (%) | Indicate content (%) |
| 031119 | 0 | White tablets | Up to specification | 96.1 | 0.336 | 100.9 |
| 1 | White tablets | Up to specification | 96.5 | 0.383 | 100.2 | |
| 2 | White tablets | Up to specification | 96.3 | 0.421 | 99.92 | |
| 3 | White tablets | Up to specification | 94.8 | 0.460 | 99.51 | |
| 6 | White tablets | Up to specification | 96.4 | 0.564 | 99.28 | |
| 031120 | 0 | White tablets | Up to specification | 95.1 | 0.299 | 99.85 |
| 1 | White tablets | Up to specification | 96.3 | 0.340 | 99.74 | |
| 2 | White tablets | Up to specification | 94.9 | 0.409 | 99.59 | |
| 3 | White tablets | Up to specification | 94.4 | 0.463 | 98.98 | |
| 6 | White tablets | Up to specification | 96.7 | 0.580 | 98.87 | |
| 031121 | 0 | White tablets | Up to specification | 95.5 | 0.328 | 99.91 |
| 1 | White tablets | Up to specification | 94.8 | 0.368 | 99.87 | |
| 2 | White tablets | Up to specification | 95.0 | 0.412 | 99.50 | |
| 3 | White tablets | Up to specification | 96.3 | 0.472 | 99.11 | |
| 6 | White tablets | Up to specification | 96.0 | 0.585 | 98.89 |
Table 3 accelerated test limit test of microbe result at 6 the end of month
| Lot number | 031113 | 031114 | 031115 | 031119 | 031120 | 031121 | |
| Microbial limit | 0 month | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| 6 months | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | |
Conclusion: intending under the listing terms of packing, telmisartan dispersible tablet was placed 6 months under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5%, removing content slightly reduces, related substance has outside the increase slightly, other every indexs have no significant change, at 6 the end of month of accelerated test, limit test of microbe is all up to specification, and result of the test shows that telmisartan dispersible tablet is basicly stable under acceleration environment.
3.2 long term test: get pilot scale six batch samples of specification 40mg and 80mg respectively, lot number is respectively: 031113,031114,031115,031119,031120,031121; By listing packing, put under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10% and placed 36 months.Respectively at 3rd month, 6 months, 9 months, 12 months, 18 months, 24 months, 36 samplings at the end of month, relatively after the outward appearance, test every index, with result and comparison in 0 month.The results are shown in Table 4, table 5, table 6.
Table 4 telmisartan dispersible tablet long term test is investigated result's (specification: 40mg)
| Lot number | Time (moon) | Character | Dispersing uniformity | Dissolution (%) | Related substance (%) | Indicate content (%) |
| 031113 | 0 | White tablets | Up to specification | 94.4 | 0.378 | 100.3 |
| 3 | White tablets | Up to specification | 95.6 | 0.392 | 99.90 | |
| 6 | White tablets | Up to specification | 96.7 | 0.375 | 99.67 | |
| 9 | White tablets | Up to specification | 97.6 | 0.401 | 99.39 | |
| 12 | White tablets | Up to specification | 95.2 | 0.416 | 98.96 | |
| 031114 | 0 | White tablets | Up to specification | 95.0 | 0.342 | 99.78 |
| 3 | White tablets | Up to specification | 96.4 | 0.349 | 99.69 | |
| 6 | White tablets | Up to specification | 94.6 | 0.387 | 99.44 | |
| 9 | White tablets | Up to specification | 95.5 | 0.393 | 99.12 | |
| 12 | White tablets | Up to specification | 95.1 | 0.407 | 98.76 | |
| 031115 | 0 | White tablets | Up to specification | 95.5 | 0.351 | 102.0 |
| 3 | White tablets | Up to specification | 96.5 | 0.357 | 101.0 | |
| 6 | White tablets | Up to specification | 93.7 | 0.378 | 100.7 | |
| 9 | White tablets | Up to specification | 96.0 | 0.382 | 100.2 | |
| 12 | White tablets | Up to specification | 95.8 | 0.403 | 99.94 |
Table 5 long term test limit test of microbe result at 12 the end of month
| Lot number | 031113 | 031114 | 031115 | 031119 | 031120 | 031121 | |
| Microbial limit | 0 month | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| 12 months | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified | |
Table 6 telmisartan dispersible tablet long term test is investigated result's (specification: 80mg)
| Lot number | Time (moon) | Character | Dispersing uniformity | Dissolution (%) | Related substance (%) | Indicate content (%) |
| 031119 | 0 | White tablets | Up to specification | 96.1 | 0.336 | 100.9 |
| 3 | White tablets | Up to specification | 95.7 | 0.372 | 100.6 | |
| 6 | White tablets | Up to specification | 95.6 | 0.379 | 100.1 | |
| 9 | White tablets | Up to specification | 93.7 | 0.392 | 99.89 | |
| 12 | White tablets | Up to specification | 95.0 | 0.456 | 99.75 | |
| 031120 | 0 | White tablets | Up to specification | 95.1 | 0.299 | 99.85 |
| 3 | White tablets | Up to specification | 94.4 | 0.343 | 99.82 | |
| 6 | White tablets | Up to specification | 95.4 | 0.377 | 99.68 | |
| 9 | White tablets | Up to specification | 96.2 | 0.411 | 99.54 | |
| 12 | White tablets | Up to specification | 96.3 | 0.442 | 99.38 | |
| 031121 | 0 | White tablets | Up to specification | 95.5 | 0.328 | 99.91 |
| 3 | White tablets | Up to specification | 95.6 | 0.348 | 99.91 | |
| 6 | White tablets | Up to specification | 96.0 | 0.398 | 99.73 | |
| 9 | White tablets | Up to specification | 96.3 | 0.427 | 99.62 | |
| 12 | White tablets | Up to specification | 96.0 | 0.431 | 99.44 |
Conclusion: intending under the listing terms of packing, telmisartan dispersible tablet was placed 12 months under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10%, every index has no significant change, 12 the end of month of long term test, limit test of microbe is all up to specification, and result of the test shows that telmisartan dispersible tablet is basicly stable under the long term test condition.
4, conclusion
Accelerated test result shows: intending under the listing terms of packing, telmisartan dispersible tablet was placed 6 months under the condition of 40 ℃ ± 2 ℃ of temperature, relative humidity 75% ± 5%, removing content slightly reduces, related substance has outside the increase slightly, other every indexs have no significant change, at 6 the end of month of accelerated test, limit test of microbe is all up to specification, and result of the test shows that telmisartan dispersible tablet is basicly stable under acceleration environment.
Long-term test results shows: intending under the listing terms of packing, telmisartan dispersible tablet was placed 12 months under the condition of 25 ℃ ± 2 ℃ of temperature, relative humidity 60% ± 10%, every index has no significant change, 12 the end of month of long term test, limit test of microbe is all up to specification, and result of the test shows that telmisartan dispersible tablet is basicly stable under the long term test condition.This test is not finished still underway as yet.
Reached a conclusion by above-mentioned investigation result, accelerated test and long term test are investigated, and the result shows that this product is basicly stable.
Among the present invention, each adjuvant is not limited to the kind that embodiment adopts, disintegrating agent can be selected microcrystalline Cellulose, starch, pregelatinized Starch, modified starch, polyvinylpolypyrrolidone, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose is received, carboxymethylcellulose calcium, in the sodium carboxymethyl cellulose one or more, filler or diluent can be selected dextrin, lactose, sucrose, microcrystalline Cellulose, cellulose, calcium sulfate, calcium hydrogen phosphate, calcium phosphate dibasic anhydrous, pregelatinized Starch, in the starch one or more, binding agent can be selected starch slurry, syrup, dextrin, purified water, ethanol, sodium carboxymethyl cellulose, hypromellose, in the ethyl cellulose one or more, fluidizer or lubricant can be selected stearic acid, magnesium stearate, zinc stearate, calcium stearate, silicon dioxide, micropowder silica gel, Pulvis Talci, in the hard paraffin one or more.
Claims (10)
1, telmisartan dispersible tablet is characterized in that, it comprises following each component, and its weight content percentage ratio is respectively: telmisartan 2%～99%, adjuvant 1%～98%.
2, telmisartan dispersible tablet as claimed in claim 1 is characterized in that, described adjuvant includes disintegrating agent, filler or diluent, binding agent, fluidizer or lubricant.
3, telmisartan dispersible tablet as claimed in claim 2, it is characterized in that, described disintegrating agent is that microcrystalline Cellulose, starch, pregelatinized Starch, modified starch, polyvinylpolypyrrolidone, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked carboxymethyl cellulose are received, in the carboxymethylcellulose calcium, sodium carboxymethyl cellulose one or more, and the percentage by weight that accounts for total prescription is 2%～70%; Described filler or diluent are dextrin, lactose, sucrose, one or more in microcrystalline Cellulose, cellulose, calcium sulfate, calcium hydrogen phosphate, calcium phosphate dibasic anhydrous, pregelatinized Starch, the starch, and the percentage by weight that accounts for total prescription is 2%～85%; Described binding agent is one or more in starch slurry, syrup, dextrin, purified water, ethanol, sodium carboxymethyl cellulose, hypromellose, the ethyl cellulose, and the percentage by weight that accounts for total prescription is 0.1%～65%; Described fluidizer or lubricant are one or more in stearic acid, magnesium stearate, zinc stearate, calcium stearate, silicon dioxide, micropowder silica gel, Pulvis Talci, the hard paraffin, and the percentage by weight that accounts for total prescription is 0.1%～20%.
4, telmisartan dispersible tablet as claimed in claim 3 is characterized in that, described binding agent is a 20-70% ethanol.
5, telmisartan dispersible tablet as claimed in claim 2 is characterized in that, described disintegrating agent is a crospolyvinylpyrrolidone; Described filler is microcrystalline Cellulose and pregelatinized Starch; Described binding agent is 30% ethanol; Described fluidizer or lubricant are magnesium stearate and micropowder silica gel.
6, telmisartan dispersible tablet as claimed in claim 3 is characterized in that, the interior dosage of described disintegrating agent is 2～5 times of outer dosage.
7, as each described telmisartan dispersible tablet in the claim 2 to 6, it is characterized in that the percentage by weight that described adjuvant accounts for total prescription is respectively: disintegrating agent 5～20%, filler or diluent 20～80%, binding agent 5～30%, fluidizer or lubricant 0.5～5%.
As each described telmisartan dispersible tablet in the claim 1 to 6, it is characterized in that 8, the percentage by weight that described telmisartan accounts for total prescription is 5～30%, the percentage by weight that described adjuvant accounts for total prescription is 30%～95%.
9, telmisartan dispersible tablet as claimed in claim 8, it is characterized in that, the percentage by weight that the content of described telmisartan and each adjuvant accounts for total prescription is respectively: telmisartan 5～30%, disintegrating agent 5～20%, filler or diluent 20～80%, binding agent 5～30%, fluidizer or lubricant 0.5～5%.
10, the preparation method of telmisartan dispersible tablet is characterized in that, it prepares through the following steps: telmisartan is crossed 100 mesh sieves, and disintegrating agent, filler or diluent are crossed 80 mesh sieves, and be standby; Take by weighing telmisartan and filler or diluent, disintegrating agent (in add part), mix homogeneously by recipe quantity; Add binding agent and make soft material, cross 18～20 mesh sieve system granules, granule is dry in 50～70 ℃ of baking ovens; Dried granule is crossed 20 mesh sieve granulate, adds disintegrating agent (Extra Section), fluidizer or lubricant mixing; The inspection of semifinished product; Tabletting; Product inspection; Packing promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101309795A CN100370984C (en) | 2005-03-11 | 2005-12-15 | Telmisartan dispersible tablet and its preparation method |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510049339 CN1682718A (en) | 2005-03-11 | 2005-03-11 | Telmisartan dispersing tablet and its preparing method |
| CN200510049339.1 | 2005-03-11 | ||
| CNB2005101309795A CN100370984C (en) | 2005-03-11 | 2005-12-15 | Telmisartan dispersible tablet and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1799543A true CN1799543A (en) | 2006-07-12 |
| CN100370984C CN100370984C (en) | 2008-02-27 |
Family
ID=36809903
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005101309795A Active CN100370984C (en) | 2005-03-11 | 2005-12-15 | Telmisartan dispersible tablet and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100370984C (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101219120B (en) * | 2007-12-27 | 2011-02-23 | 江苏万邦生化医药股份有限公司 | Telmisartan dispersible tablet and method for preparing the same |
| CN102512691A (en) * | 2012-01-10 | 2012-06-27 | 广州白云山天心制药股份有限公司 | Telmisartan composition and application thereof |
| CN103110598A (en) * | 2013-02-19 | 2013-05-22 | 青岛正大海尔制药有限公司 | Alfacalcidol dispersible tablet and preparation method thereof |
| CN101467985B (en) * | 2007-12-27 | 2013-08-14 | 万特制药(海南)有限公司 | Bisoprolol fumarate dispersible tablet and preparation method thereof |
| CN103520125A (en) * | 2013-09-28 | 2014-01-22 | 迪沙药业集团有限公司 | Telmisartan composition |
| CN104510720A (en) * | 2014-12-25 | 2015-04-15 | 云南昊邦制药有限公司 | 2-(alpha-hydroxypentyl) benzoate dispersible tablet and preparation method thereof |
| CN108553432A (en) * | 2018-05-28 | 2018-09-21 | 海南赛立克药业有限公司 | Drug and preparation method thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003059327A1 (en) * | 2002-01-16 | 2003-07-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bilayer pharmaceutical tablet comprising telmisartan and a diuretic and preparation thereof |
| DE10244681A1 (en) * | 2002-09-24 | 2004-04-08 | Boehringer Ingelheim International Gmbh | New solid telmisartan-containing pharmaceutical formulations and their preparation |
| US8980870B2 (en) * | 2002-09-24 | 2015-03-17 | Boehringer Ingelheim International Gmbh | Solid telmisartan pharmaceutical formulations |
| US9029363B2 (en) * | 2003-04-30 | 2015-05-12 | Boehringer Ingelheim International Gmbh | Telmisartan sodium salt pharmaceutical formulation |
| CN1548421A (en) * | 2003-05-22 | 2004-11-24 | 上海医药工业研究院 | Tilmisartan salt and its prepn |
-
2005
- 2005-12-15 CN CNB2005101309795A patent/CN100370984C/en active Active
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101219120B (en) * | 2007-12-27 | 2011-02-23 | 江苏万邦生化医药股份有限公司 | Telmisartan dispersible tablet and method for preparing the same |
| CN101467985B (en) * | 2007-12-27 | 2013-08-14 | 万特制药(海南)有限公司 | Bisoprolol fumarate dispersible tablet and preparation method thereof |
| CN102512691A (en) * | 2012-01-10 | 2012-06-27 | 广州白云山天心制药股份有限公司 | Telmisartan composition and application thereof |
| CN103110598A (en) * | 2013-02-19 | 2013-05-22 | 青岛正大海尔制药有限公司 | Alfacalcidol dispersible tablet and preparation method thereof |
| CN103520125A (en) * | 2013-09-28 | 2014-01-22 | 迪沙药业集团有限公司 | Telmisartan composition |
| CN103520125B (en) * | 2013-09-28 | 2019-03-05 | 威海迪素制药有限公司 | A kind of telmisartan composition |
| CN104510720A (en) * | 2014-12-25 | 2015-04-15 | 云南昊邦制药有限公司 | 2-(alpha-hydroxypentyl) benzoate dispersible tablet and preparation method thereof |
| CN108553432A (en) * | 2018-05-28 | 2018-09-21 | 海南赛立克药业有限公司 | Drug and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100370984C (en) | 2008-02-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1215833C (en) | Rapidly disintegrating methylcellulose tablets | |
| CN1799543A (en) | Telmisartan dispersible tablet and its preparation method | |
| CN1642546A (en) | Solid preparation containing single crystal form | |
| CN1698741A (en) | Gingko leaf slow-releasing tablet and preparation process thereof | |
| CN101032489A (en) | Cefprozil dispersible table and the preparing method | |
| CN1823802A (en) | Gastrodin slow release preparation | |
| CN1911209A (en) | Quick-disintegration tablets of calcium atovastatine, and its prepn. method | |
| CN1915216A (en) | New usage of tandospirone and its derivative, and composition containing tandospirone | |
| CN1887277A (en) | Dispersant tablet containing hypolipidemic component and its prepn process | |
| CN1732953A (en) | Dispersible tablet for treating hypertension | |
| CN1806805A (en) | Leponex orally disintegrating tablet and preparation method thereof | |
| CN1757393A (en) | Fosfocina calcium disperser, and its prepn. method | |
| CN100336511C (en) | Release-controlled oral Roxithromycin formulation | |
| CN1771945A (en) | Disperese torasemide tablet and its prepn and application | |
| CN1919185A (en) | Compound ammonium glycyrrhizinato S dispersed tablet and its preparing process | |
| CN1296050C (en) | Acarbose enteric coated tablets and its prepn. method | |
| CN1303990C (en) | Sodium ferulate oral disintegrating tablet and its preparation process | |
| CN1895250A (en) | Gliquilone slow-releasing preparation | |
| CN1272014C (en) | Enteric soluble preparation of Alun phosphorate and its preparing method | |
| CN1868472A (en) | Tablets of Lizakuputan benzoate | |
| CN1726916A (en) | Oral disintegration tablet for dropping blood sugar and preparation method | |
| CN1268327C (en) | Brufen arginine pseudoephedrine hydrochloride compound formulation | |
| CN100340239C (en) | Andrographolide dispersing tablets | |
| CN1899506A (en) | Shenmai oral disintegration tablet and its preparing method | |
| CN1449750A (en) | Gabapentin slow -released composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |