CN1864679A - A composite bergenin dispersible tablet and preparation method thereof - Google Patents
A composite bergenin dispersible tablet and preparation method thereof Download PDFInfo
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- CN1864679A CN1864679A CN 200510043482 CN200510043482A CN1864679A CN 1864679 A CN1864679 A CN 1864679A CN 200510043482 CN200510043482 CN 200510043482 CN 200510043482 A CN200510043482 A CN 200510043482A CN 1864679 A CN1864679 A CN 1864679A
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Abstract
The compound bergenin disperser tablet consists of bergenin in 82.0-90.0 wt%, chlorphenamine maleate 1.0-2.0 wt%, carboxymethyl starch sodium 5.0-10.0 wt%, magnesium stearate 0.5-2.0 wt%, superfine silica gel powder 0.5-1.5 wt%, sodium dodecyl sulfate 0.1-0.5 wt%, polyvinyl pyrrolidone 1.0-3.0 wt% and aspartame 0.1-0.5 wt%. The compound bergenin disperser tablet is prepared through micronizing the components, mixing, wet pelletizing and tabletting. It may be disintegrated fast within 2 min and has high bergenin and chlorphenamine maleate leaching speed.
Description
Affiliated technical field:
The present invention relates to a kind of compound medicinal formulation, more particularly, is the improvement technology about a kind of bergenini compositae tabellae oral formulations.
Technical background:
Bergeninum, claim arolisic acid B, bergenin, Rodgersia podophylla A. Gray element, bergenit again, mostly be to belong to the active ingredient that extracts the plants such as (Bergenia) phytolith Chinese cabbage, Myrsinacea plant Herba Ardisiae Japonicae, astilbe Herba astilbes chinensis from the Saxifragaceae Rhizoma Seu Herba Bergeniae, belong to the isocoumarin compounds, it mainly acts on is eliminating phlegm and stopping cough, untoward reaction is little, and use does not produce drug resistance continuously.
Chlorphenamine maleate is H
1The receptor blocker, its antihistaminic effect is stronger, central inhibitory action and cholinolytic effect all a little less than, so few side effects, and consumption is few.Its excited bronchus of energy and gastrointestinal smooth muscle, increase capillary permeability, reduce secretion of bronchus body of gland and blood vessel dilating etc., it has satisfactory effect to some asthmatic patient recent clinical studies proof, can strengthen asthmatic bronchitis and bronchiolitis therapeutic effect, improve to breathe heavily and suppress, promote wheezing sound to disappear and shorten the course of disease.
The bergenini compositae tabellae determined curative effect, safety is good, and clinical practice is extensive.But disintegrate is slower, and medicine needs the long period could stripping from preparation, and onset is slow.Bergeninum is the dewatering medicament of slightly solubility, and it is absorbed in the influence that is subjected to preparation process to a great extent.The Bergeninum tablet (containing the plain 125mg/ sheet of Rhizoma Seu Herba Bergeniae) of different lot numbers is carried out dissolution and the test of rabbit bioavailability, and the result shows, the tablet of different lot numbers, its disintegration, dissolution parameters T
50Significant difference is all arranged, but disintegration time and T
50Significant positive correlation is arranged, and pharmacokinetic parameter AUC and T
50Between significant positive correlation is arranged, illustrate and inquire into the key that factor influence disintegration is a raising Bergeninum sheet bioavailability.
Because Bergeninum conventional tablet bioavailability is lower, focus mostly on aspect the bioavailability that improves dissolution and tablet in the technical study of Bergeninum preparation.Once the someone carried out the research of Bergeninum solid dispersion, and the PVP coprecipitate of Bergeninum is pressed into tablet, and its dissolution has improved 20% than the bergenini compositae tabellae ordinary tablet.Bergeninum and beta-schardinger dextrin-are made inclusion complex, make the nearly molecularity of Bergeninum high degree of dispersion, dissolubility increases 2 times, and dissolution is significantly increased.But because this class methods cost height, complex process is not carried out suitability for industrialized production.
Chlorphenamine maleate in the compound bergenin pills agent every only contain 2mg, its uniformity of dosage units and dissolution are the key factors that influences its bioavailability and clinical efficacy.Ceng Renjie etc. compare for the dissolution of 4 producer's Allergies, the dissolution difference that found that 4 producers is bigger, dissolution is low then to be to cause that curative effect of medication is undesirable, especially clinical effect one of major reason slowly, and different preparation process is that the reason that causes its dissolution difference bigger is (referring to " China Dispensary ", 2001,12 (9): 554-555).
Summary of the invention:
The object of the present invention is to provide a kind of taking convenience, disintegration rate is fast, dissolution is high, absorption is fast, bioavailability is high, untoward reaction is low bergenini compositae tabellae dispersible tablet formulation and preparation method thereof.
Because Bergeninum is insoluble in water, therefore, the present invention promotes the absorption of human body to Bergeninum and chlorphenamine maleate to shorten the disintegration of tablet time, to improve its dissolution speed and start with, and makes it to reach fast effective blood drug concentration, onset rapidly.In addition, at the problem of old and child patient dysphagia, solution of the present invention is that Bergeninum is mixed with a kind of clothes of can directly swallowing, chew, or the bergenini compositae tabellae dispersible tablet of taking after the aqueous dispersion, the convenient use both can be accelerated dissolution rate, helped the rapid onset of medicine again.
Because the difference of principal agent character has very big influence for the disintegration rate of dispersible tablet, therefore the component of every kind of dispersible tablet will design according to the characteristic of principal agent.Dispersible tablet of the present invention is made up of components such as Bergeninum, chlorphenamine maleate, disintegrating agent carboxymethyl base Starch Sodium, polyvinyl pyrrolidone, fluidizer micropowder silica gel, magnesium stearate lubricant, surfactant sodium lauryl sulphate and correctives aspartames.Its constituent content, be by weight percentage: the Bergeninum of 82.0-90.0wt%, the chlorphenamine maleate of 1.0-2.0wt%, the carboxymethyl starch sodium of 5.0-10.0wt%, the magnesium stearate of 0.5-2.0wt%, 0.5-1.5wt% micropowder silica gel, the sodium lauryl sulphate of 0.1-0.5wt%, the polyvinylpyrrolidone of 1.0-3.0wt% and the aspartame of 0.1-0.5wt%.
The character of principal agent and proportion have determined the selection of adjuvant, and be all better because of the compressibility and the flowability of Bergeninum, weighs for reducing sheet as much as possible, do not design filler in the prescription of this product.Therefore in the present invention, the content of Bergeninum is higher, accounts for 82.0-90.0wt% in prescription, and promptly tablet is under the situation of same size content, and it is heavy that the present invention has alleviated sheet as much as possible, thereby made things convenient for the patient to take.
The disintegration of dispersible tablet and disintegrating agent performance are closely related, the mechanism of action of disintegrating agent is still not exclusively clear and definite, it is generally acknowledged and be subjected to the effect of following two aspects to make disintegration of tablet: (1) expansion: disintegrating agent mostly is the high molecular weight hydrophilic material, after the compacting in flakes, meet water and be easy to wetted and expand make disintegration of tablet by self; (2) capillarity: some disintegrating agents and filler, mostly be spheroidal hydrophilic aggregation body, form countless holes and capillary tube adding to depress, have intensive water absorption, hydrone is entered rapidly among the tablet, make whole tablet moistening and disintegrate.Suction back powder expands and does not dissolve, and does not form colloid solution, is unlikely to hinder the continuation infiltration of hydrone, makes the further disintegrate of tablet.
The present invention is disintegrating agent with the carboxymethyl starch sodium, and Bergeninum is 8.2 with the relative weight ratio of carboxymethyl starch sodium: 1-18.0: 1.Carboxymethyl starch sodium is formed by glucose polymerisation, has good water absorption and imbibition.The back volume that fully expands can increase 200-300 doubly, has good compressibility, can improve the mouldability of tablet, increases the hardness of tablet and does not influence its disintegrative.Its degree of exchange of the carboxymethyl starch sodium of selecting for use among the present invention is generally about 0.3-0.5, and swellbility is 5ml/g, all can use as commercial goods Primojel, Explotab or DST etc.
The polyvinylpyrrolidone hydrophilic is strong, can make particle surface become hydrophilic with it as binding agent, and moisture is moistening behind the tabletting penetrates, and disintegration of tablet is accelerated, and also helps the stripping of medicine.The molecular weight of the polyvinylpyrrolidone of selecting for use is 25000-40000, as PVPK
25Or PVPK
30All can use Deng the commercial goods.Data shows that the concentration difference of polyvinylpyrrolidone aqueous solution is also influential to disintegration rate, and along with the minimizing of polyvinylpyrrolidone ratio, particulate disintegration rate is accelerated.The present invention adopts 5% polyvinylpyrrolidone aqueous solution, and the dispersible tablet that makes all can disintegrate within 3min, meets the regulation of Chinese Pharmacopoeia.
For increasing the wettability of supplementary material, make it to form suspension rapidly after the disintegrate, and increase the dissolution of principal agent among the present invention, promote it to absorb, adopted surfactant sodium lauryl sulphate with solubilization.Sodium lauryl sulphate is water-soluble, use simultaneously with binder solution, can promote the disintegrate of tablet and the stripping of medicine.The principle that surfactant promotes tablet medicine to absorb under low concentration has aspect two: surfactant can influence biomembrane on the one hand, changes the character of gastrointestinal barrier, makes medicine be easy to see through; Surfactant is because of reducing surface tension on the other hand, so its solution is the surface of wet medicated particle effectively, reduce the gas phase on the liquid and the surface of solids, improve the hygroscopicity of medicine, drug particle is had more nearly with liquid contact, this effect can make stripping and infiltration rate increase.
Lubricant and fluidizer are selected magnesium stearate, micropowder silica gel etc. for use, and correctives can be selected aspartame, saccharin sodium, stevioside, essence etc. for use, and consumption is 0.1-0.5%.
Carboxymethyl starch sodium is bigger to the disintegration time influence, and the present invention has done the selection test of disintegrating agent carboxymethyl base Starch Sodium use amount, the carboxymethyl starch sodium consumption is designed in the scope of 5.0-10.0wt%, and compare disintegration by measuring.
The assay method of dispersing uniformity: get 2 of dispersible tablets, add in the 100ml water, jolting, complete to disintegrate, the record disintegration time.Test data with the results are shown in Table 1.
The screening of table 1 carboxymethyl starch sodium consumption
| The test lot number | 1 | 2 | 3 | 4 | 5 | 6 |
| (%) micropowder silica gel of Bergeninum (g) chlorphenamine maleate (g) carboxymethyl starch sodium (g) (g) magnesium stearate (g) | 12.5 0.2 0.5 3.7 0.15 0.1 | 12.5 0.2 0.7 5.1 0.15 0.1 | 12.5 0.2 0.9 6.5 0.15 0.1 | 12.5 0.2 1.1 7.8 0.15 0.1 | 12.5 0.2 1.3 9.1 0.15 0.1 | 12.5 0.2 1.5 10.4 0.15 0.1 |
| Dispersing uniformity (second) | 188 | 119 | 98 | 107 | 115 | 117 |
As can be seen from Table 1, the addition of test lot number 3 carboxymethyl starch sodium is the most suitable, and disintegration is the shortest.
The present invention also screens as binding agent the solution of 5%PVP different ethanol concentration, and test data sees Table 2.
The screening of table 2 binding agent
| The test lot number | 7 | 8 | 9 | 10 | 11 |
| Concentration of alcohol | 80％ | 60％ | 40％ | 20％ | 0％ |
| Dispersing uniformity (second) | 165 | 147 | 136 | 128 | 105 |
As can be seen from Table 2, the solution of 5%PVP different ethanol concentration is made binding agent, and with the minimizing of proportion of ethanol, disintegrate is accelerated, and reaches the fastest during to aqueous solution.
Because of Bergeninum and chlorphenamine maleate flavor is all bitter, for improving the mouthfeel of dispersible tablet, intend adding aspartame as correctives, based on test lot number 3, the aspartame of adding different amounts, test data and the results are shown in Table 3.
The screening of table 3 correctives (aspartame) consumption
| The test lot number | 12 | 13 | 14 | 15 | 16 | 17 |
| Bergeninum, (g) chlorphenamine maleate, (g) carboxymethyl starch sodium, (g) micropowder silica gel, (g) magnesium stearate, (g) aspartame, (g), (%) | 12.5 0.2 0.9 0.15 0.1 0.00 0.00 | 12.5 0.2 0.9 0.15 0.1 0.01 0.07 | 12.5 0.2 0.9 0.15 0.1 0.03 0.22 | 12.5 0.2 0.9 0.15 0.1 0.05 0.36 | 12.5 0.2 0.9 0.15 0.1 0.07 0.50 | 12.5 0.2 0.9 0.15 0.1 0.09 0.65 |
| Dispersing uniformity (second) | 95 | 92 | 103 | 96 | 100 | 110 |
| Mouthfeel | Bitter in the mouth | Mouthfeel is general | Good mouthfeel | Good mouthfeel | Good mouthfeel | It is sweet to distinguish the flavor of |
The compound method of bergenini compositae tabellae dispersible tablet of the present invention is: at first Bergeninum, chlorphenamine maleate, carboxymethyl starch sodium, magnesium stearate, micropowder silica gel are micronized to and all cross 100 mesh sieves; Polyvinylpyrrolidone is water-soluble, be mixed with 5% polyvinylpyrrolidone aqueous solution, add sodium lauryl sulphate again, make that its concentration is 1%, make both mixed solutions, preserve standby.
Then with chlorphenamine maleate earlier with carboxymethyl starch sodium with the equivalent method mixing that progressively increases, with the Bergeninum mixing, then add aspartame again, sieve mixing.
Then, add the mixed aqueous solution of a certain amount of polyvinylpyrrolidone, sodium lauryl sulphate, make soft material.With 20 mesh sieves with wet granulation, 60 ℃ of oven dry, reuse 20 mesh sieve granulate.Thereafter with above-mentioned dried particles and magnesium stearate, micropowder silica gel mix homogeneously, detect the percentage composition of principal agent in the mixed material, the heavy and pressure of adjustment sheet, tabletting makes the tablet among the present invention.
Before an important feature of the present invention was film-making, the component in the tablet was all carried out micronization processes, made it all by 100 mesh sieves.Because Bergeninum is insoluble in water, can improve particulate specific surface area after the micronization, make the dispersible tablet disintegrate after medicine can contact with body fluid more fully, accelerate absorption.
Another important feature of the present invention is that principal agent is at first made less disintegrate granule, and then is pressed into the dispersible tablet that is easy to disintegrate.Include components such as Bergeninum, chlorphenamine maleate, carboxymethyl starch sodium, aspartame, polyvinylpyrrolidone, sodium lauryl sulphate in the said disintegrate microgranule; Except that above-mentioned disintegrate microgranule, also add micropowder silica gel, magnesium stearate in the dispersible tablet.
Like this bergenini compositae tabellae dispersible tablet that constitutes, after taking, the very fast disintegrate of tablet becomes less disintegrate microgranule, and then disintegrate is fine powder, thereby has improved the disintegration rate of tablet, has shortened disintegration time.And because the solubilization of surfactant sodium lauryl sulphate in the disintegrate microgranule, improved the dissolution of principal agent.
For showing progressive of the present invention, we have also done the dissolution test of bergenini compositae tabellae dispersible tablet of the present invention, and contrast with ordinary tablet.Ordinary tablet is selected from the compound bergenin pills that commercially available Jianjiang Pharmaceutical Factory produces, batch number: 030902.Assay method adopts two appendix XC of Chinese Pharmacopoeia version in 2000 three therapeutic methods of traditional Chinese medicine.Result of the test sees Table 4.
Bergeninum stripping curve comparing result in table 4 bergenini compositae tabellae dispersible tablet and the ordinary tablet
| Lot number | Time (minute) | 1 | 2 | 3 | 4 | 5 | 6 | On average ± SD (%) |
| Bergenini compositae tabellae dispersible tablet 040806 | 5 | 70.1 | 71.6 | 77.9 | 74.2 | 76.0 | 75.7 | 74.2±2.92 |
| 10 | 95.8 | 98.5 | 101.8 | 99.3 | 99.8 | 99.3 | 99.1±1.95 | |
| 20 | 106.6 | 107.4 | 110.6 | 110.4 | 106.2 | 107.2 | 108.1±1.93 | |
| 30 | 107.6 | 109.7 | 110.0 | 109.8 | 107.9 | 107.8 | 108.4±1.14 | |
| 45 | 111.9 | 112.7 | 112.2 | 108.4 | 106.8 | 107.3 | 109.9±2.67 | |
| Bergenini compositae tabellae dispersible tablet 040807 | 5 | 78.7 | 75.5 | 71.7 | 76.1 | 70.2 | 60.9 | 72.2±6.3 |
| 10 | 99.5 | 98.4 | 99.9 | 101.8 | 95.9 | 99.3 | 99.1±1.94 | |
| 20 | 107.5 | 113.0 | 106.3 | 106.3 | 107.7 | 112.5 | 108.8±3.06 | |
| 30 | 109.6 | 108.2 | 109.2 | 109.7 | 109.0 | 107.5 | 108.9±0.88 | |
| 45 | 112.5 | 112.7 | 112.1 | 111.7 | 106.6 | 109.8 | 110.9±2.35 | |
| Bergenini compositae tabellae dispersible tablet 040808 | 5 | 71.7 | 77.8 | 75.6 | 71.8 | 78.8 | 74.3 | 75.0±2.98 |
| 10 | 85.3 | 101.1 | 99.4 | 85.2 | 99.6 | 99.3 | 95.0±7.6 | |
| 20 | 106.6 | 109.5 | 108.1 | 106.1 | 109.6 | 112.2 | 108.7±2.24 | |
| 30 | 108.9 | 108.1 | 111.3 | 109.0 | 109.7 | 108.1 | 109.2±1.2 | |
| 45 | 111.0 | 112.7 | 112.3 | 111.2 | 112.0 | 108.4 | 111.3±1.55 | |
| Bergenini compositae tabellae ordinary tablet 030902 | 5 | 45.4 | 45.4 | 44.0 | 45.3 | 48.9 | 45.3 | 45.7±1.7 |
| 10 | 64.4 | 64.4 | 64.3 | 64.2 | 79.5 | 79.1 | 68.6±8.4 | |
| 20 | 78.5 | 78.6 | 96.8 | 96.4 | 92.9 | 92.7 | 89.3±8.51 | |
| 30 | 99.8 | 105.4 | 103.4 | 103.4 | 108.3 | 108.1 | 104.7±3.24 | |
| 45 | 110.0 | 109.3 | 108.3 | 108.4 | 112.6 | 112.4 | 110.2±1.91 |
Chlorphenamine maleate stripping curve contrast in table 5 bergenini compositae tabellae dispersible tablet and the ordinary tablet
| Lot number | Time (minute) | 1 | 2 | 3 | 4 | 5 | 6 | On average ± SD (%) |
| Bergenini compositae tabellae dispersible tablet 040806 | 5 | 51.3 | 66.3 | 53.9 | 69.7 | 68.0 | 49.7 | 59.8±9.13 |
| 10 | 77.5 | 77.3 | 77.2 | 80.2 | 76.6 | 77.5 | 77.7±1.26 | |
| 20 | 86.7 | 88.3 | 87.4 | 94.6 | 86.9 | 86.7 | 88.4±3.08 | |
| 30 | 100.6 | 102.7 | 101.9 | 101.1 | 97.9 | 95.8 | 100.0±2.63 | |
| 45 | 93.9 | 104.8 | 104.2 | 97.3 | 98.8 | 96.0 | 99.2±4.44 | |
| Bergenini compositae tabellae dispersible tablet 040807 | 5 | 51.9 | 49.4 | 63.3 | 66.4 | 51.6 | 66.4 | 58.2±8.01 |
| 10 | 76.6 | 79.9 | 77.7 | 80.1 | 79.3 | 77.8 | 78.1±1.37 | |
| 20 | 85.3 | 82.6 | 88.4 | 87.7 | 88.1 | 91.6 | 82.7±5.32 | |
| 30 | 96.1 | 102.4 | 105.8 | 98.1 | 101.0 | 103.1 | 98.9±1.43 | |
| 45 | 97.1 | 100.9 | 99.6 | 97.5 | 98.9 | 99.6 | 98.9±1.43 | |
| Bergenini compositae tabellae dispersible tablet 040808 | 5 | 51.6 | 51.3 | 71.1 | 71.7 | 69.2 | 57.0 | 62.0±9.76 |
| 10 | 74.4 | 74.2 | 82.9 | 79.8 | 79.1 | 74.5 | 77.5±3.65 | |
| 20 | 83.7 | 90.6 | 86.9 | 85.2 | 95.4 | 85.1 | 82.4±5.82 | |
| 30 | 97.4 | 103.3 | 98.7 | 103.0 | 105.9 | 102.6 | 101.8±3.17 | |
| 45 | 91.6 | 92.2 | 92.9 | 100.4 | 95.1 | 101.3 | 95.6±4.26 | |
| Bergenini compositae tabellae ordinary tablet 030902 | 5 | 17.7 | 17.6 | 18.6 | 21.2 | 19.1 | 21.2 | 19.2±1.6 |
| 10 | 23.4 | 22.4 | 23.5 | 22.7 | 23.5 | 26.0 | 23.6±1.3 | |
| 20 | 40.2 | 45.1 | 43.9 | 54.6 | 45.5 | 54.6 | 47.3±5.94 | |
| 30 | 68.9 | 75.4 | 64.3 | 80.3 | 83.2 | 79.4 | 75.2±7.30 | |
| 45 | 92.3 | 94.2 | 88.4 | 94.2 | 93.8 | 90.0 | 92.2±2.44 |
From table 4, table 5 as can be seen, the dissolution homogeneity of the present invention's three batch samples is good, individual variation is little in batch, favorable reproducibility between batch, the all more commercially available ordinary tablet of the dissolution of three batches of dispersible tablets is obviously accelerated, the average dissolution of 5 minutes Bergeninums is 73.8%, has improved more than 28.0% than the dissolution of ordinary tablet 5 minutes the time; The average dissolution of chlorphenamine maleate is 60.0%, has improved more than 40.0% than the dissolution of ordinary tablet 5 minutes the time.In a word, advantage of the present invention is clearly, and made dispersible tablet can directly be swallowed, chew clothes, or takes after the aqueous dispersion.Absorb soon, the bioavailability height, it is suitable with oral suspensions, especially be fit to old man, paralytic and the patient of difficulty that swallows, and the patient under special environment that can obtain water, can make things convenient for patient's medication, improve the compliance of clinical application, meet clinical needs better.
The specific embodiment:
The invention will be further described with by way of example more below, provides implementation detail of the present invention, but be not to be intended to limit protection scope of the present invention.
With micronizations such as Bergeninum, chlorphenamine maleate, aspartame, carboxymethyl starch sodium, magnesium stearate, micropowder silica gels, make it all to cross 100 mesh sieves earlier;
Take by weighing the 3.0g polyvinylpyrrolidone and make 5% aqueous solution, add surfactant sodium lauryl sulphate 0.6g (its concentration is 1%) again, standby.
Take by weighing chlorphenamine maleate 2.0g, earlier with the 9.0g carboxymethyl starch sodium with the equivalent method mixing that progressively increases, then add the abundant mixing of 125.0g Bergeninum after, add the 0.5g aspartame and sieve, mixing adds above-mentioned mixed solution and makes soft material.With 20 mesh sieves with wet granulation, and 60 ℃ of down oven dry, again with 20 mesh sieve granulate.Add 1.0g magnesium stearate and 1.5g micropowder silica gel mixing then.Detect the percentage composition of principal agent in the mixed material, after the calculating sheet is heavy, regulate pressure, compacting in flakes.So can suppress 1000 dispersible tablets.
Its disintegration time is 93.0 seconds, and the dissolution of 5 minutes Bergeninums is 71.2%, and the dissolution of chlorphenamine maleate is 60.9%.
The several examples of following reuse further specify the present invention, and following example is to produce the Formulation Example of 1000 dispersible tablets.
Embodiment 1 wt wt%
Bergeninum 125.0g 87.6
Chlorphenamine maleate 1.9g 1.3
Carboxymethyl starch sodium 9.0g 6.3
Magnesium stearate 1.0g 0.7
Micropowder silica gel 1.6g 1.1
Aspartame 0.6g 0.4
Sodium lauryl sulphate 0.6g 0.4
Polyvinylpyrrolidone 3.0g 2.1
Make 1000
With micronizations such as Bergeninum, chlorphenamine maleate, aspartame, carboxymethyl starch sodium, magnesium stearate, micropowder silica gels, make it all to cross 100 mesh sieves earlier;
Take by weighing the 3.0g polyvinylpyrrolidone and make 5% aqueous solution, add surfactant sodium lauryl sulphate 0.6g (its concentration is 1%) again, standby.
Take by weighing chlorphenamine maleate 1.9g, earlier with the 9.0g carboxymethyl starch sodium with the equivalent method mixing that progressively increases, then add the abundant mixing of 125.0g Bergeninum after, add the 0.6g aspartame and sieve, mixing adds above-mentioned mixed solution and makes soft material.With 20 mesh sieves with wet granulation, and 60 ℃ of down oven dry, again with 20 mesh sieve granulate.Add 1.0g magnesium stearate and 1.6g micropowder silica gel mixing then.Detect the percentage composition of principal agent in the mixed material, after the calculating sheet is heavy, regulate pressure, compacting in flakes.So can suppress 1000 dispersible tablets.
Its disintegration time is 95.0 seconds, and the dissolution of 5 minutes Bergeninums is 70.9%, and the dissolution of chlorphenamine maleate is 62.3%.
Embodiment 2 wt wt%
Bergeninum 125.0g 84.5
Chlorphenamine maleate 3.0g 2.0
Carboxymethyl starch sodium 14.5g 9.8
Magnesium stearate 2.2g 1.5
Micropowder silica gel 0.7g 0.5
Aspartame 0.7g 0.5
Sodium lauryl sulphate 0.3g 0.2
Polyvinylpyrrolidone 1.5g 1.0
Make 1000
With micronizations such as Bergeninum, chlorphenamine maleate, aspartame, carboxymethyl starch sodium, magnesium stearate, micropowder silica gels, make it all to cross 100 mesh sieves earlier;
Take by weighing the 1.5g polyvinylpyrrolidone and make 5% aqueous solution, add surfactant sodium lauryl sulphate 0.3g (its concentration is 1%) again, standby.
Take by weighing chlorphenamine maleate 3.0g, earlier with the 14.5g carboxymethyl starch sodium with the equivalent method mixing that progressively increases, then add the abundant mixing of 125.0g Bergeninum after, add the 0.7g aspartame and sieve, mixing adds above-mentioned mixed solution and makes soft material.With 20 mesh sieves with wet granulation, and 60 ℃ of down oven dry, again with 20 mesh sieve granulate.Add 2.2g magnesium stearate and 0.7g micropowder silica gel mixing then.Detect the percentage composition of principal agent in the mixed material, after the calculating sheet is heavy, regulate pressure, compacting in flakes.So can suppress 1000 dispersible tablets.
Its disintegration time is 101.0 seconds, and the dissolution of 5 minutes Bergeninums is 69.9%, and the dissolution of chlorphenamine maleate is 60.5%.
Embodiment 3 wt wt%
Bergeninum 125.0g 88.9
Chlorphenamine maleate 1.4g 1.0
Carboxymethyl starch sodium 7.1g 5.0
Magnesium stearate 0.7g 0.5
Micropowder silica gel 2.1g 1.5
Aspartame 0.1g 0.1
Sodium lauryl sulphate 0.7g 0.5
Polyvinylpyrrolidone 3.5g 2.5
Make 1000
With micronizations such as Bergeninum, chlorphenamine maleate, aspartame, carboxymethyl starch sodium, magnesium stearate, micropowder silica gels, make it all to cross 100 mesh sieves earlier.
Take by weighing the 3.5g polyvinylpyrrolidone and make 5% aqueous solution, add surfactant sodium lauryl sulphate 0.7g (its concentration is 1%) again, standby.
Take by weighing chlorphenamine maleate 1.4g, earlier with the 7.1g carboxymethyl starch sodium with the equivalent method mixing that progressively increases, then add the abundant mixing of 125.0g Bergeninum after, add the 0.1g aspartame and sieve, mixing adds above-mentioned mixed solution and makes soft material.With 20 mesh sieves with wet granulation, and 60 ℃ of down oven dry, again with 20 mesh sieve granulate.Add 0.7g magnesium stearate and 2.1g micropowder silica gel mixing then.Detect the percentage composition of principal agent in the mixed material, after the calculating sheet is heavy, regulate pressure, compacting in flakes.So can suppress 1000 dispersible tablets.
Its disintegration time is 98.0 seconds, and the dissolution of 5 minutes Bergeninums is 72.5%, and the dissolution of chlorphenamine maleate is 61.7%.
Embodiment 4 wt wt%
Bergeninum 125.0g 86.4
Chlorphenamine maleate 2.3g 1.6
Carboxymethyl starch sodium 10.3g 7.1
Magnesium stearate 2.9g 2.0
Micropowder silica gel 1.2g 0.8
Aspartame 0.3g 0.2
Sodium lauryl sulphate 0.4g 0.3
Polyvinylpyrrolidone 2.2g 1.5
Make 1000
With micronizations such as Bergeninum, chlorphenamine maleate, aspartame, carboxymethyl starch sodium, magnesium stearate, micropowder silica gels, make it all to cross 100 mesh sieves earlier.
Take by weighing the 2.2g polyvinylpyrrolidone and make 5% aqueous solution, add surfactant sodium lauryl sulphate 0.44g (its concentration is 1%) again, standby.
Take by weighing chlorphenamine maleate 2.3g, earlier with the 10.3g carboxymethyl starch sodium with the equivalent method mixing that progressively increases, then add the abundant mixing of 125.0g Bergeninum after, add the 0.3g aspartame and sieve, mixing adds above-mentioned mixed solution and makes soft material.With 20 mesh sieves with wet granulation, and 60 ℃ of down oven dry, again with 20 mesh sieve granulate.Add 2.9g magnesium stearate and 1.2g micropowder silica gel mixing then.Detect the percentage composition of principal agent in the mixed material, after the calculating sheet is heavy, regulate pressure, compacting in flakes.So can suppress 1000 dispersible tablets.
Its disintegration time is 95.2 seconds, and the dissolution of 5 minutes Bergeninums is 71.8%, and the dissolution of chlorphenamine maleate is 62.0%.
Claims (4)
1. bergenini compositae tabellae dispersible tablet, by the active ingredient Bergeninum, chlorphenamine maleate and disintegrating agent, binding agent, surfactant, fluidizer, component such as lubricant and correctives is formed, the particle diameter of constituent that it is characterized in that said dispersible tablet is below 75 microns, it forms content, be by weight percentage: the Bergeninum of 82.0-90.0wt%, the chlorphenamine maleate of 1.0-2.0wt%, the carboxymethyl starch sodium of 5.0-10.0wt%, the magnesium stearate of 0.5-2.0wt%, the 0.5-1.5wt% micropowder silica gel, the sodium lauryl sulphate of 0.1-0.5wt%, the polyvinylpyrrolidone of 1.0-3.0wt% and the aspartame of 0.1-0.5wt%.
2. according to the described dispersible tablet of claim 1, the Bergeninum, chlorphenamine maleate, carboxymethyl starch sodium, micropowder silica gel, magnesium stearate, the aspartame that it is characterized in that being used for film-making are all crossed 100 mesh sieves, and particle diameter is below 75 microns.
3. according to the described dispersible tablet of claim 1, it is characterized in that the Bergeninum and the relative weight ratio of carboxymethyl starch sodium are 8.2: 1-18.0: 1.
4. according to the described dispersible tablet of claim 1, it is characterized in that adopting wet granulation, comprise following main preparation steps:
(1), makes it all to cross 100 mesh sieves with micronizations such as Bergeninum, chlorphenamine maleate, micropowder silica gel, carboxymethyl starch sodium, magnesium stearate, aspartames;
(2) preparation disintegrate microgranule:
I) with chlorphenamine maleate earlier with carboxymethyl starch sodium with the equivalent method mixing that progressively increases, again with Bergeninum with the equivalent method mixing that progressively increases, then add aspartame, sieve, mixing, standby;
Ii) that polyvinylpyrrolidone is water-soluble, make 5% polyvinylpyrrolidone aqueous solution, add the surfactant sodium lauryl sulphate again, make that its concentration is 1%, make both mixed aqueous solutions;
Iii) mixed aqueous solution is added i) mixture in, make soft material, granulate with 20 eye mesh screens, 60 ℃ of oven dry, with 20 mesh sieve granulate, make the disintegrate microgranule again;
(3) preparation bergenini compositae tabellae dispersible tablet: with magnesium stearate and micropowder silica gel and exsiccant bergenini compositae tabellae disintegrate microgranule mix homogeneously; after detecting the percentage composition of principal agent in the mixed material; heavy and the pressure of adjustment sheet, tabletting is made bergenini compositae tabellae dispersible tablet of the present invention.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN 200510043482 CN1864679A (en) | 2005-05-16 | 2005-05-16 | A composite bergenin dispersible tablet and preparation method thereof |
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| CN 200510043482 CN1864679A (en) | 2005-05-16 | 2005-05-16 | A composite bergenin dispersible tablet and preparation method thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101797253A (en) * | 2010-03-18 | 2010-08-11 | 四川大学 | Bergenin and cetirizine dihydrochloride compound oral administration preparation |
| CN101991554B (en) * | 2009-08-24 | 2012-07-11 | 成都医学院 | Bergenin osmotic pump tablet and preparation method thereof |
| CN106880608A (en) * | 2015-12-15 | 2017-06-23 | 北大方正集团有限公司 | A kind of teriflunomide dispersible tablet and preparation method thereof |
| CN106880610A (en) * | 2015-12-15 | 2017-06-23 | 北大方正集团有限公司 | A kind of ramelteon dispersible tablet and preparation method thereof |
| US20220031679A1 (en) * | 2010-04-07 | 2022-02-03 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl) benzoic acid and administration thereof |
-
2005
- 2005-05-16 CN CN 200510043482 patent/CN1864679A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101991554B (en) * | 2009-08-24 | 2012-07-11 | 成都医学院 | Bergenin osmotic pump tablet and preparation method thereof |
| CN101797253A (en) * | 2010-03-18 | 2010-08-11 | 四川大学 | Bergenin and cetirizine dihydrochloride compound oral administration preparation |
| US20220031679A1 (en) * | 2010-04-07 | 2022-02-03 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl) benzoic acid and administration thereof |
| CN106880608A (en) * | 2015-12-15 | 2017-06-23 | 北大方正集团有限公司 | A kind of teriflunomide dispersible tablet and preparation method thereof |
| CN106880610A (en) * | 2015-12-15 | 2017-06-23 | 北大方正集团有限公司 | A kind of ramelteon dispersible tablet and preparation method thereof |
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