CN101606931A - A kind of erdosteine composition and preparation method thereof - Google Patents
A kind of erdosteine composition and preparation method thereof Download PDFInfo
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- CN101606931A CN101606931A CNA2009103052986A CN200910305298A CN101606931A CN 101606931 A CN101606931 A CN 101606931A CN A2009103052986 A CNA2009103052986 A CN A2009103052986A CN 200910305298 A CN200910305298 A CN 200910305298A CN 101606931 A CN101606931 A CN 101606931A
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Abstract
The invention provides a kind of erdosteine composition, described compositions is grouped into by following quality: 130～170 parts of erdosteines, 35～65 parts of lactose, 30～70 parts of microcrystalline Cellulose, 20～40 parts of low-substituted hydroxypropyl celluloses, 1～5 part of acesulfame potassium, 10～30 parts of carboxymethyl starch sodium, 0.1～0.5 part of magnesium stearate; The present invention also provides a kind of preparation method of described erdosteine composition, comprise: get the raw materials ready, granulate: will pulverize behind erdosteine, the low-substituted hydroxypropyl cellulose mix homogeneously, add carboxymethyl starch sodium, add dehydrated alcohol, the wet mixing cutting, dry granulate, tabletting: granule and microcrystalline Cellulose mix homogeneously, add lactose, acesulfame potassium and magnesium stearate and carry out tabletting, packing is promptly.Compositions dispersing uniformity provided by the invention is good, medicine dissolution efficiency height.
Description
Technical field
The present invention relates to field of medicaments, specifically, relate to a kind of erdosteine composition and preparation method thereof.
Background technology
Expectorant is the product of respiratory inflammation, can stimulate respiratory mucosa, causes cough and asthma, and can increase the weight of to infect.When acute/chronic bronchitis or chronic lung diseases respiratory failure, spend height or form the expectorant bolt, can block respiratory tract and cause suffocating as patient's thick sputum.Therefore, use sticking expectorant regulator, make patient's phlegm dissolving, thinning, viscosity reduces, and quickens the respiratory mucosa ciliary movement, improves transport function, has crucial meaning.
At present this is smooth etc. for the sticking expectorant regulator of listing such as bromhexine, mesna, carboxylic first, all has sticking expectorant regulating action in various degree, but its pharmacology or have some defectives clinically.Free sulfydryl can adsorb the gastrointestinal tract mucin in the molecular structure, can produce the gastrointestinal tract local damage after oral, side effect is bigger, can weaken the antibacterial activity of penicillin, cephalosporins, erythromycin, tetracycline etc., unsuitable drug combination is renderd a service not high to the improvement of some respiration parameter such as expectorant viscosity etc.
Erdosteine is a kind of prodrug, the sulfydryl that has non-free sealing in its structure, to local mucin inactive, oral after metabolism produces three and contains the metabolite of free sulfhydryl groups and bring into play pharmacological action, thereby the no obvious gastrointestinal side effect in oral back.Experimental results show that; the erdosteine cylinder metabolism-ure can make mucinous disulfide bonds in the bronchial secretion; and change secretions is formed and rheological property; reduce sputum viscosity; improve downtrod respiratory function; this product can be removed free radical, effectively protects the a1-antitrypsin to avoid the oxidation deactivation that cigarette, dirt bring out, and prevents the damage to elastance of lung albumen and neutrophilic granulocyte.This product can also obviously increase IgA/ albumin, lactoferrin/albuminous ratio, weakens local inflammation, strengthens and improve the osmosis of antibiotic to bronchial mucosa, helps the treatment of the various inflammation of respiratory tract.External clinical clinical studies show: with like product such as acetylcysteine, carboxylic first this is smooth, ambroxol etc. relatively, this product has better curative effect to acute/chronic bronchitis, improvement to some respiratory function parameter is more effective, drug accumulation does not take place in heavy dose of administration, and liver, renal function moderate obstacle do not have obvious change to this product characteristics of pharmacokinetics.
Dispersible tablet claims water dispersion tablet again, and being meant can rapid homodisperse tablet in water.Except that good stability with conventional tablet, be easy to carry, the advantage such as taking convenience, also have the bioavailability advantage of higher, can directly swallow, chew in clothes or the input water and take after the dispersion, be particularly suitable for the patient of difficulty that swallows, and mouthfeel is good, has improved patient's compliance.
Disclose the adjuvant of multiple suitable preparation dispersible tablet as " dispersible tablet prescription, process characteristic and progress thereof " (" medicine evaluation " 2005 the 5th volume the 3rd phase), can be used as disintegrating agent as low-substituted hydroxypropyl cellulose, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose and use.Wherein mentioning the low-substituted hydroxypropyl cellulose optimum amount is 2～5%.
In addition, " Chinese pharmaceutic adjuvant " (Chemical Industry Press, version in 2006, chief editors such as Luo Mingsheng) discloses carboxymethyl starch sodium and adopted outer add mode effect best, and microcrystalline Cellulose is not suitable for using as disintegrating agent usually.
The erdosteine dissolubility is relatively poor, and it is relatively poor to make the general formulation bioavailability, and therefore, the present invention has carried out great deal of experimental on above-mentioned disclosed document basis, proposed erdosteine dispersible tablet of the present invention and preparation method thereof.
Summary of the invention
One of the object of the invention is to provide a kind of erdosteine composition, and the erdosteine composition that is provided prescription is reasonable, and rate of dispersion is faster, and dissolution efficiency is higher.
Two of the object of the invention is to provide a kind of dispersible tablet preparation method that contains described erdosteine composition, and described preparation method can further improve the quality of erdosteine composition dispersible tablet.
For achieving the above object, the present invention takes following technical scheme:
A kind of erdosteine composition, described compositions is grouped into by following quality: 130～170 parts of erdosteines, 35～65 parts of lactose, 30～70 parts of microcrystalline Cellulose, 20～40 parts of low-substituted hydroxypropyl celluloses, 1～5 part of acesulfame potassium, 10～30 parts of carboxymethyl starch sodium, 0.1～0.5 part of magnesium stearate; Be preferably 140～160 parts of erdosteines, 45～55 parts of lactose, 40～60 parts of microcrystalline Cellulose, 25～35 parts of low-substituted hydroxypropyl celluloses, 1～2 part of acesulfame potassium, 15～25 parts of carboxymethyl starch sodium, 0.2～0.4 part of magnesium stearate; More preferably 150 parts of erdosteines, 50 parts of lactose, 50 parts of microcrystalline Cellulose, 30 parts of low-substituted hydroxypropyl celluloses, 1 part of acesulfame potassium, 20 parts of carboxymethyl starch sodium, 0.3 part of magnesium stearate.
A kind of preparation method that contains the dispersible tablet of erdosteine composition noted earlier, described preparation method comprises the steps:
(1) get the raw materials ready: microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium sieve, lactose, acesulfame potassium grinding and sieving;
(2) granulate: will pulverize with ball mill behind erdosteine, the low-substituted hydroxypropyl cellulose mix homogeneously, sieve, add carboxymethyl starch sodium then, use high-speed mixing granulating machine to do and mix, add dehydrated alcohol 15～25ml, be preferably 20ml, wet mixing, and then the wet mixing cutting, the wet granular that makes carries out drying, and the dried granule that obtains after the drying carries out granulate;
(3) tabletting: granule behind the granulate and microcrystalline Cellulose are used the three-dimensional mixer mix homogeneously, add lactose, acesulfame potassium and magnesium stearate mix homogeneously again, carry out tabletting, packing after the assay was approved promptly.
According to foregoing preparation method, step (1) lactose, acesulfame potassium were pulverized 100～140 mesh sieves, and microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 70～90 mesh sieves, and carboxymethyl starch sodium is crossed 100～140 mesh sieves; Be preferably lactose, acesulfame potassium was pulverized 120 mesh sieves, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 80 mesh sieves, carboxymethyl starch sodium is crossed 120 mesh sieves.
According to foregoing preparation method, step (2) is described sieves to crossing 90～110 mesh sieves, is preferably 100 mesh sieves.
According to foregoing preparation method, described dried the mixing of step (2) is to do rotating speed 35～55 commentaries on classics/min and mix 5～15min, is preferably rotating speed 45 commentaries on classics/min, the dried 10min that mixes.
According to foregoing preparation method, the described wet mixing of step (2) is rotating speed 25～35 commentaries on classics/min, and wet mixing 2～5min is preferably rotating speed 30 commentaries on classics/min, wet mixing 3min.
According to foregoing preparation method, the described wet mixing of step (2) clipping time is 1～5min, is preferably 2min.
According to foregoing preparation method, the described drying of step (2) is 60～70 ℃ of down dry 15～30min, is preferably 65 ℃ of down dry 20～25min.
According to foregoing preparation method, step (3) granule and microcrystalline Cellulose are mixed into rotating speed 30～40 commentaries on classics/min, mix 10～20min; Add lactose, acesulfame potassium and magnesium stearate and be mixed into rotating speed 25～35 commentaries on classics/min, mix 8～12min; Preferred particulates and microcrystalline Cellulose are mixed into rotating speed 35 commentaries on classics/min, mix 15min; Add lactose, acesulfame potassium and magnesium stearate and be mixed into rotating speed 30 commentaries on classics/min, mix 10min.
According to foregoing preparation method, the described tabletting pressure of step (3) is 2～5N, is preferably 3N.
Below technical solution of the present invention is described in more detail:
It is low that " Chinese pharmaceutic adjuvant " mentions the microcrystalline Cellulose swellbility, is not suitable for using as disintegrating agent.Yet the present invention is unexpected to be found, uses high carboxymethyl starch sodium of swellbility or low-substituted hydroxypropyl cellulose and microcrystalline Cellulose combination collocation to use, and can well improve dispersing uniformity and dissolution rate.
Analysis may be high swelling property materials such as carboxymethyl starch sodium in aqueous solution after the disintegrate, the Colloidal fluid of formation is wrapped in the outside of drug particles, has hindered the further stripping of granule Chinese medicine powder.
And the present invention uses microcrystalline Cellulose and carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose combination collocation, not only the dispersing uniformity time short, and the effective ingredient dissolution rate is fast.
The present invention adopts lactose as filler in compositions, and the tablet appearance that makes is good, is difficult for dry linting.Effect is significantly better than other filler material.
In addition, note also control microcrystalline Cellulose and low-substituted hydroxypropyl cellulose ratio, when large percentage, can not reach good dispersion effect, jitter time has exceeded the state-promulgated pharmacopoeia standard.
Test is found, when 130～170 parts of erdosteines, 35～65 parts of lactose, 30～70 parts of microcrystalline Cellulose, 20～40 parts of low-substituted hydroxypropyl celluloses, 1～5 part of acesulfame potassium, 10～30 parts of carboxymethyl starch sodium, can reach good dispersion result of extraction during 0.1～0.5 part of magnesium stearate; When more preferably 140～160 parts of erdosteines, 45～55 parts of lactose, 40～60 parts of microcrystalline Cellulose, 25～35 parts of low-substituted hydroxypropyl celluloses, 1～2 part of acesulfame potassium, 15～25 parts of carboxymethyl starch sodium, can improve the dispersion result of extraction again during 0.2～0.4 part of magnesium stearate; When being preferably 150 parts of erdosteines, 50 parts of lactose, 50 parts of microcrystalline Cellulose, 30 parts of low-substituted hydroxypropyl celluloses, 1 part of acesulfame potassium, 20 parts of carboxymethyl starch sodium again, during 0.3 part of magnesium stearate, disperse stripping can reach optimum efficiency.
The preparation of erdosteine composition provided by the present invention can be with reference to any preparation of compositions method of prior art, those skilled in the art can prepare this erdosteine composition by simple experiment in conjunction with the prior art of self grasping after reading the present invention.But in order further to improve the quality of this erdosteine composition, further improve and disperse result of extraction, the present invention provides a kind of preferred manufacturing procedure simultaneously:
A kind of preparation method of erdosteine composition noted earlier, described preparation method comprises the steps:
(1) get the raw materials ready: microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium sieve, lactose, acesulfame potassium grinding and sieving;
Above-mentioned adjuvant sieves earlier, can be in the certain particle scope with control of material, help in the blend step of back, mixing more even like this, and dispersibility is better.Those skilled in the art know described sieving usually cross for how many mesh sieves, sieving of prior art can be prepared up-to-standard compositions, but the present invention preferably lactose, acesulfame potassium pulverized 100～140 mesh sieves, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 70～90 mesh sieves, and carboxymethyl starch sodium is crossed 100～140 mesh sieves; More preferably lactose, acesulfame potassium were pulverized 120 mesh sieves, and microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 80 mesh sieves, and carboxymethyl starch sodium is crossed 120 mesh sieves.
(2) granulate: will pulverize with ball mill behind erdosteine, the low-substituted hydroxypropyl cellulose mix homogeneously, sieve, add carboxymethyl starch sodium then, use high-speed mixing granulating machine to do and mix, add dehydrated alcohol 15～25ml, be preferably 20ml, wet mixing, and then the wet mixing cutting, the wet granular that makes carries out drying, and the dried granule that obtains after the drying carries out granulate;
To pulverize together after erdosteine and the low-substituted hydroxypropyl cellulose mixing, can be so that effect be tightr between low-substituted hydroxypropyl cellulose and the effective ingredient, after the disintegrate of Swertia Tablet chance water goes out drug particles, low-substituted hydroxypropyl cellulose can more effective disintegrate once more, discharge medicine itself, thereby strengthened the dissolution of medicine greatly.This mainly is because the low-substituted hydroxypropyl cellulose surface texture is coarse, can strengthen medicated powder and particulate tessellation.If carboxymethyl starch sodium is added simultaneously, the three pulverizes together, though dissolution increases than commonsense method, can not reach the degree of the inventive method.
Secondly, pulverize together after erdosteine and low-substituted hydroxypropyl cellulose mix, medicine and disintegrating agent better can also be scatter, uniformity is better.
The present invention before granulation and the medicated powder mix homogeneously that crushes, can further strengthen dispersion effect with carboxymethyl starch sodium, quickens rate of dispersion.
Wherein said the sieving of step (2) can be suitable any the sieving of prior art, those skilled in the art know usually cross for how many purpose sieves, but in order to strengthen the homogeneity of medicine, further strengthens dissolution efficiency, the present invention can preferably cross 90～110 mesh sieves, more preferably crosses 100 mesh sieves.
After carboxymethyl starch sodium is added, do mixed, be for before wet mixing with the medicated powder mix homogeneously, prevent to add behind the liquid medicated powder thickness that becomes and be difficult to mix homogeneously.The stirring of doing when mixing can be done the stirring that mixes with reference to prior art, if stirring is too violent, can make compact erdosteine of part and low-substituted hydroxypropyl cellulose separate, and has reduced dissolution rate, but still can meet the requirement of state-promulgated pharmacopoeia.But in order further to improve the dissolution rate of this compositions, the present invention is through overtesting, and preferred described to do the rotating speed that mixes be 35～55 commentaries on classics/min, and dried doing time is 5～15min, rotating speed 45 commentaries on classics/min more preferably, and dried doing time is 10min.
Described wet mixing also can be with reference to any wet mixing operation of prior art, but in order to take into account production efficiency and mixed effect, the present invention can preferred described wet mixing rotating speed be 25～35 commentaries on classics/min, and the wet mixing time is 2～5min, more preferably rotating speed is 30, and the wet mixing time is 3min.
The described wet mixing cutting of step (2) also can be with reference to any wet mixing cutting operation of prior art, and those skilled in the art can formulate described wet mixing cutting according to prior art and by simple experiment.Need not to pay more creative work again, yet can the be preferred described wet mixing of the present invention clipping time is 1～5min, more preferably 2min.
The described drying of step (2) also can be the drying of prior art, and those skilled in the art can determine described drying process according to the character of erdosteine and other adjuvant.The preferred drying of the present invention is 60～70 ℃ of down dry 15～30min, more preferably 65 ℃ of down dry 20～25min.
(3) tabletting: granule behind the granulate and microcrystalline Cellulose are used the three-dimensional mixer mix homogeneously, add lactose, acesulfame potassium and magnesium stearate mix homogeneously again, carry out tabletting, packing after the assay was approved promptly.
Described being mixed into of step (3) uses three-dimensional mixer to carry out, and its concrete operations also can be used the operation of three-dimensional mixer with reference to prior art.But find that through test of many times the breakage of particles that too violent operation can make small part make has caused part tablet outward appearance poor slightly, but does not influence the quality of tablet own.The present invention is in order to improve the whole homogeneity of medicine, and preferred particulates of the present invention and microcrystalline Cellulose are mixed into rotating speed 30～40 commentaries on classics/min, mix 10～20min; Add lactose, acesulfame potassium and magnesium stearate and be mixed into rotating speed 25～35 commentaries on classics/min, mix 8～12min; More preferably granule and microcrystalline Cellulose are mixed into rotating speed 35 commentaries on classics/min, mix 15min; Add lactose, acesulfame potassium and magnesium stearate and be mixed into rotating speed 30 commentaries on classics/min, mix 10min.
The wherein said tabletting of step (3) has certain influence to tablet, and pressure is crossed conference and reduced disintegration rate, crosses the easy dry linting of tabloid.But those skilled in the art know the pressure limit that similar tablet should adopt usually, those skilled in the art can be according to the used supplementary product kind of erdosteine composition provided by the invention, the prior art of grasping in conjunction with himself, and can determine a rational pressure limit by simple experiment.But the present invention is in order to obtain the erdosteine composition dispersible tablet of best in quality, and preferred pressure is 2～5N, more preferably 3N.
Technical scheme of the present invention has following advantage:
(1) erdosteine composition dispersible tablet dispersing uniformity provided by the invention is good, medicine dissolution efficiency height.
(2) preparation method provided by the present invention is simple, is fit to industrial mass production.
(3) preparation method provided by the present invention can further be improved the quality of products, and further improves the administering effect of the erdosteine composition dispersible tablet that makes.
The specific embodiment
The following examples will be done to explain more specifically to the present invention, but the present invention is not limited only to these embodiment, and these embodiment do not limit the present invention in any way yet equally.
Embodiment 1
Erdosteine 150g
Lactose 50g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
Acesulfame potassium 1g
Carboxymethyl starch sodium 20g
Magnesium stearate 0.3g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 80 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 120 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 100 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 45 commentaries on classics/min, mixes 10min; carry out wet mixing after adding dehydrated alcohol 20ml, rotating speed is 30 commentaries on classics/min, mixes 3min; 2min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 65 ℃ of oven dry 20～25 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 35 commentaries on classics/min, mix 15min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 30 commentaries on classics/min, mix 10min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 3N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 2
Erdosteine 150g
Lactose 50g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
Acesulfame potassium 1g
Carboxymethyl starch sodium 20g
Magnesium stearate 0.3g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 70 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 100 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 100 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 35 commentaries on classics/min, mixes 5min; carry out wet mixing after adding dehydrated alcohol 20ml, rotating speed is 30 commentaries on classics/min, mixes 3min; 2min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 60 ℃ of oven dry 15～20 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 35 commentaries on classics/min, mix 15min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 30 commentaries on classics/min, mix 10min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 3N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 3
Erdosteine 150g
Lactose 50g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
Acesulfame potassium 1g
Carboxymethyl starch sodium 20g
Magnesium stearate 0.3g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 80 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 100 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 100 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 45 commentaries on classics/min, mixes 10min; carry out wet mixing after adding dehydrated alcohol 25ml, rotating speed is 30 commentaries on classics/min, mixes 2min; 2min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 60 ℃ of oven dry 15～20 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 30 commentaries on classics/min, mix 15min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 30 commentaries on classics/min, mix 8min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 3N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 4
Erdosteine 150g
Lactose 50g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
Acesulfame potassium 1g
Carboxymethyl starch sodium 20g
Magnesium stearate 0.3g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 90 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 100 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 90 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 35 commentaries on classics/min, mixes 10min; carry out wet mixing after adding dehydrated alcohol 15ml, rotating speed is 35 commentaries on classics/min, mixes 2min; 2min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 60 ℃ of oven dry 25～30 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 30 commentaries on classics/min, mix 10min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 25 commentaries on classics/min, mix 9min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 3N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 5
Erdosteine 150g
Lactose 50g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
Acesulfame potassium 1g
Carboxymethyl starch sodium 20g
Magnesium stearate 0.3g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 70 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 140 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 90 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 45 commentaries on classics/min, mixes 15min; carry out wet mixing after adding dehydrated alcohol 15ml, rotating speed is 35 commentaries on classics/min, mixes 2min; 2min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 60 ℃ of oven dry 25～30 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 30 commentaries on classics/min, mix 12min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 25 commentaries on classics/min, mix 10min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 2N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 6
Erdosteine 140g
Lactose 45g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 25g
Acesulfame potassium 1g
Carboxymethyl starch sodium 15g
Magnesium stearate 0.2g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 80 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 140 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 110 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 35 commentaries on classics/min, mixes 15min; carry out wet mixing after adding dehydrated alcohol 15ml, rotating speed is 35 commentaries on classics/min, mixes 3min; 1min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 70 ℃ of oven dry 20～25 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 40 commentaries on classics/min, mix 13min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 25 commentaries on classics/min, mix 8min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 4N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 7
Erdosteine 160g
Lactose 55g
Microcrystalline Cellulose 60g
Low-substituted hydroxypropyl cellulose 35g
Acesulfame potassium 2g
Carboxymethyl starch sodium 25g
Magnesium stearate 0.4g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 90 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 140 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 110 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 55 commentaries on classics/min, mixes 10min; carry out wet mixing after adding dehydrated alcohol 20ml, rotating speed is 35 commentaries on classics/min, mixes 3min; 1min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 70 ℃ of oven dry 20～25 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 40 commentaries on classics/min, mix 14min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 35 commentaries on classics/min, mix 11min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 4N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 8
Erdosteine 145g
Lactose 52g
Microcrystalline Cellulose 55g
Low-substituted hydroxypropyl cellulose 28g
Acesulfame potassium 1.5g
Carboxymethyl starch sodium 16g
Magnesium stearate 0.3g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 90 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 100 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 100 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 55 commentaries on classics/min, mixes 15min; carry out wet mixing after adding dehydrated alcohol 20ml, rotating speed is 35 commentaries on classics/min, mixes 3min; 3min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 70 ℃ of oven dry 15～20 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 40 commentaries on classics/min, mix 20min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 35 commentaries on classics/min, mix 11min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 5N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 9
Erdosteine 155g
Lactose 47g
Microcrystalline Cellulose 45g
Low-substituted hydroxypropyl cellulose 33g
Acesulfame potassium 2g
Carboxymethyl starch sodium 23g
Magnesium stearate 0.4g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 70 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 100 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 110 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 35 commentaries on classics/min, mixes 5min; carry out wet mixing after adding dehydrated alcohol 20ml, rotating speed is 25 commentaries on classics/min, mixes 3min; 3min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 70 ℃ of oven dry 15～20 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 40 commentaries on classics/min, mix 18min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 25 commentaries on classics/min, mix 12min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 3N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 10
Erdosteine 147g
Lactose 48g
Microcrystalline Cellulose 48g
Low-substituted hydroxypropyl cellulose 26g
Acesulfame potassium 1g
Carboxymethyl starch sodium 18g
Magnesium stearate 0.3g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 80 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 120 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 90 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 35 commentaries on classics/min, mixes 10min; carry out wet mixing after adding dehydrated alcohol 20ml, rotating speed is 25 commentaries on classics/min, mixes 5min; 4min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 68 ℃ of oven dry 25～30 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 40 commentaries on classics/min, mix 19min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 30 commentaries on classics/min, mix 10min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 4N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 11
Erdosteine 130g
Lactose 35g
Microcrystalline Cellulose 30g
Low-substituted hydroxypropyl cellulose 20g
Acesulfame potassium 1g
Carboxymethyl starch sodium 10g
Magnesium stearate 0.1g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 100 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 140 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 90 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 45 commentaries on classics/min, mixes 7min; carry out wet mixing after adding dehydrated alcohol 25ml, rotating speed is 25 commentaries on classics/min, mixes 5min; 4min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 62 ℃ of oven dry 25～30 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 35 commentaries on classics/min, mix 16min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 25 commentaries on classics/min, mix 9min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 3N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 12
Erdosteine 170g
Lactose 65g
Microcrystalline Cellulose 70g
Low-substituted hydroxypropyl cellulose 40g
Acesulfame potassium 5g
Carboxymethyl starch sodium 30g
Magnesium stearate 0.5g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 70 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 120 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 110 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 45 commentaries on classics/min, mixes 12min; carry out wet mixing after adding dehydrated alcohol 25ml, rotating speed is 25 commentaries on classics/min, mixes 4min; 5min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 64 ℃ of oven dry 20～25 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 35 commentaries on classics/min, mix 17min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 25 commentaries on classics/min, mix 11min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 4N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 13
Erdosteine 135g
Lactose 65g
Microcrystalline Cellulose 33g
Low-substituted hydroxypropyl cellulose 37g
Acesulfame potassium 4g
Carboxymethyl starch sodium 28g
Magnesium stearate 0.4g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 70 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 140 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 100 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 55 commentaries on classics/min, mixes 13min; carry out wet mixing after adding dehydrated alcohol 25ml, rotating speed is 25 commentaries on classics/min, mixes 4min; 5min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 69 ℃ of oven dry 15～25 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 30 commentaries on classics/min, mix 15min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 35 commentaries on classics/min, mix 11min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 5N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 14
Erdosteine 168g
Lactose 38g
Microcrystalline Cellulose 68g
Low-substituted hydroxypropyl cellulose 22g
Acesulfame potassium 1g
Carboxymethyl starch sodium 12g
Magnesium stearate 0.2g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 90 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 100 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 110 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 55 commentaries on classics/min, mixes 8min; carry out wet mixing after adding dehydrated alcohol 25ml, rotating speed is 30 commentaries on classics/min, mixes 4min; 5min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 70 ℃ of oven dry 20～30 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 40 commentaries on classics/min, mix 13min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 30 commentaries on classics/min, mix 8min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 3N, and the qualified back of the substrate examination that presses packing promptly.
Embodiment 15
Erdosteine 138g
Lactose 36g
Microcrystalline Cellulose 32g
Low-substituted hydroxypropyl cellulose 38g
Acesulfame potassium 2g
Carboxymethyl starch sodium 28g
Magnesium stearate 0.1g
Make 1000
Recipe quantity microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 70 mesh sieves, and lactose, acesulfame potassium, carboxymethyl starch sodium are crossed 100 mesh sieves.To pulverize with ball mill behind erdosteine and the low-substituted hydroxypropyl cellulose mix homogeneously, cross 110 mesh sieves, add carboxymethyl starch sodium; use high-speed mixing granulating machine to do and mix, rotating speed is 35 commentaries on classics/min, mixes 8min; carry out wet mixing after adding dehydrated alcohol 23ml, rotating speed is 35 commentaries on classics/min, mixes 2min; 2min is cut in wet mixing then, and the wet granular that makes changes in the ebullated dryer, and temperature is controlled at 65 ℃ of oven dry 20～25 minutes; shut down; clear filter bag, blowing, dried granule granulate.Granule behind the granulate adds three-dimensional mixer with suction feeding, adding microcrystalline Cellulose mixes, the mixer rotating speed is 35 commentaries on classics/min, mix 10min, add lactose, acesulfame potassium and magnesium stearate again and continue to mix, rotating speed is 35 commentaries on classics/min, mix 12min, the medicated powder of mix homogeneously carries out tabletting, and tabletting hardness is 2N, and the qualified back of the substrate examination that presses packing promptly.
The present invention also provides following test example, so that the advantage of tablet provided by the present invention and preparation method to be described:
Test example 1
This test example has been investigated the dispersing uniformity and the dissolution of erdosteine dispersible tablet.Detection method be according to " 2005 editions second appendix XA dispersing uniformity detection method of Chinese pharmacopoeia and appendix XC dissolution method:
The screening of table 1, supplementary product kind
| Prescription one | Prescription two | Prescription three | Prescription four | |
| Erdosteine | ??150g | ??150g | ??150g | ??150g |
| Disintegrating agent | ??MCC?50g ??LS-HPS?30g ??CMS-Na?20g | ??MCC?50g ??LS-HPS?30g ??CMS-Na?20g | ??cCMC-Na50g ??MCC?20g ??LS-HPS?30g | ??PVP30g ??LS-HPS?50g |
| Filler | Lactose 50g | Mannitol 50g | Lactose 50g | Lactose 50g |
| Lubricant | Magnesium stearate 0.3g | Magnesium stearate 0.3g | Magnesium stearate 0.3g | Magnesium stearate 0.3g |
| The agent of sedan-chair flavor | Acesulfame potassium 1g | Acesulfame potassium 1g | Acesulfame potassium 1g | Acesulfame potassium 1g |
| Outward appearance | Well | Dry linting | Well | Well |
| Dispersing uniformity | ??60s | ??90s | ??100s | ??130s |
| Dissolution | ??97％ | ??95％ | ??93％ | ??85％ |
Wherein MCC is that microcrystalline Cellulose, LS-HPS are that low-substituted hydroxypropyl cellulose, PVP are that polyvinylpyrrolidone, CMS-Na are that carboxymethyl starch sodium, cCMC-Na are cross-linking sodium carboxymethyl cellulose.Last table prescription one is for adopting embodiment 1 described prescription preparation, and presentation of results adopts kind adjuvant effect of the present invention to be better than other adjuvant.
The screening of table 2, supplementary product consumption
Wherein writing out a prescription one is the erdosteine dispersible tablet according to the preparation of embodiment 1 prescription, and prescription two be the erdosteine dispersible tablet according to embodiment 8 preparations, and prescription three be to write out a prescription according to embodiment 14 to prepare.
The preparation tablets of above-mentioned two tables has adopted identical preparation method, and described preparation method is with reference to the preparation of the common dispersible tablet of prior art, is specially:
Supplementary material was pulverized 100 mesh sieves, got in erdosteine, lactose, microcrystalline Cellulose, hydroxypropyl cellulose, the acesulfame potassium adding high-speed mixing granulating machine, and the sealing high-speed dry was mixed 10 minutes.Add 15～20ml ethanol wet mixing 3 minutes, after the wet mixing, wet mixing cutting 2 minutes, promptly.The wet granular of making is changed in the ebullated dryer, and temperature is controlled at 50～60 ℃ of oven dry 40 minutes, shuts down, clear filter bag, blowing.Dried granule is added pelletizing machine, and start button carries out granulate.Dried granule is added magnesium stearate and carboxymethyl starch sodium, add three-dimensional mixer and mix, tabletting promptly.
Test example 2
This test example has been investigated the influence of preparation method for the dispersible tablet stripping:
| Method | ??1 | ??2 | ??3 | ??4 | ??5 | ??6 |
| Substrate's appearance | Well | Well | Gloss difference | Well | Well | Well |
| Hardness | Well | Well | Well | Well | Well | Well |
| Dispersing uniformity | ??25s | ??53s | ??42s | ??37s | ??33s | ??60s |
| Dissolution | ??99％ | ??97％ | ??98％ | ??98％ | ??99％ | ??97％ |
This test example adopts the prescription proportioning of embodiment 1, and the preparation method of described erdosteine dispersible tablet is investigated, and when a certain factor was investigated, other factors all was consistent, and carried out according to embodiment is described.
Wherein being prepared as according to the method for embodiment 1 of method 1 carried out;
Method 2,3 is investigated for the breaking method of step (2), and what method 2 adopted is with remix behind erdosteine and the low-substituted hydroxypropyl cellulose pulverize separately; What method 3 adopted is to pulverize jointly behind erdosteine, low-substituted hydroxypropyl cellulose and the carboxymethyl starch sodium three mix homogeneously.
Method 4,5 has been investigated step (2) has been done the incorporation time and the mixing velocity of mixing, and wherein the mixing velocity of method 4 is 70 commentaries on classics/min, incorporation time 10min; Method 5 mixing velocities are 45 commentaries on classics/min, incorporation time 20min.
Method 6 is the preparation method described in the test example 1.
Last table data show, take preparation method of the present invention, can further improve the result of extraction of product, the mixing velocity and the incorporation time of do mixing influence to some extent for stripping, but that the product dissolving out capability that exceeds the technical solution of the present invention scope still can reach conventional method is prepared.
Through test, the product dissolving out capability of other parameter combinations also meets the trend of above-mentioned test example in other embodiment of the present invention and the claim, and the present invention sets forth no longer one by one.
Claims (10)
1. erdosteine composition, it is characterized in that, described compositions is grouped into by following quality: 130～170 parts of erdosteines, 35～65 parts of lactose, 30～70 parts of microcrystalline Cellulose, 20～40 parts of low-substituted hydroxypropyl celluloses, 1～5 part of acesulfame potassium, 10～30 parts of carboxymethyl starch sodium, 0.1～0.5 part of magnesium stearate; Be preferably 140～160 parts of erdosteines, 45～55 parts of lactose, 40～60 parts of microcrystalline Cellulose, 25～35 parts of low-substituted hydroxypropyl celluloses, 1～2 part of acesulfame potassium, 15～25 parts of carboxymethyl starch sodium, 0.2～0.4 part of magnesium stearate; More preferably 150 parts of erdosteines, 50 parts of lactose, 50 parts of microcrystalline Cellulose, 30 parts of low-substituted hydroxypropyl celluloses, 1 part of acesulfame potassium, 20 parts of carboxymethyl starch sodium, 0.3 part of magnesium stearate.
2. a dispersible tablet preparation method that contains the described erdosteine composition of claim 1 is characterized in that described preparation method comprises the steps:
(1) get the raw materials ready: microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium sieve, lactose, acesulfame potassium grinding and sieving;
(2) granulate: will pulverize with ball mill behind erdosteine, the low-substituted hydroxypropyl cellulose mix homogeneously, sieve, add carboxymethyl starch sodium then, use high-speed mixing granulating machine to do and mix, add dehydrated alcohol 15～25ml, be preferably 20ml, wet mixing, and then the wet mixing cutting, the wet granular that makes carries out drying, and the dried granule that obtains after the drying carries out granulate;
(3) tabletting: granule behind the granulate and microcrystalline Cellulose are used the three-dimensional mixer mix homogeneously, add lactose, acesulfame potassium and magnesium stearate mix homogeneously again, carry out tabletting, packing after the assay was approved promptly.
3. preparation method according to claim 2 is characterized in that, step (1) lactose, acesulfame potassium were pulverized 100～140 mesh sieves, and microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 70～90 mesh sieves, and carboxymethyl starch sodium is crossed 100～140 mesh sieves; Be preferably lactose, acesulfame potassium was pulverized 120 mesh sieves, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose are crossed 80 mesh sieves, carboxymethyl starch sodium is crossed 120 mesh sieves.
4. preparation method according to claim 2 is characterized in that, step (2) is described sieves to crossing 90～110 mesh sieves, is preferably 100 mesh sieves.
5. preparation method according to claim 2 is characterized in that, described dried the mixing of step (2) is to do rotating speed 35～55 commentaries on classics/min and mix 5～15min, is preferably rotating speed 45 commentaries on classics/min, the dried 10min that mixes.
6. preparation method according to claim 2 is characterized in that, the described wet mixing of step (2) is rotating speed 25～35 commentaries on classics/min, and wet mixing 2～5min is preferably rotating speed 30 commentaries on classics/min, wet mixing 3min.
7. preparation method according to claim 2 is characterized in that, the described wet mixing of step (2) clipping time is 1～5min, is preferably 2min.
8. preparation method according to claim 2 is characterized in that, the described drying of step (2) is 60～70 ℃ of down dry 15～30min, is preferably 65 ℃ of down dry 20～25min.
9. preparation method according to claim 2 is characterized in that, step (3) granule and microcrystalline Cellulose are mixed into rotating speed 30～40 commentaries on classics/min, mixes 10～20min; Add lactose, acesulfame potassium and magnesium stearate and be mixed into rotating speed 25～35 commentaries on classics/min, mix 8～12min; Preferred particulates and microcrystalline Cellulose are mixed into rotating speed 35 commentaries on classics/min, mix 15min; Add lactose, acesulfame potassium and magnesium stearate and be mixed into rotating speed 30 commentaries on classics/min, mix 10min.
10. preparation method according to claim 2 is characterized in that, the described tabletting hardness of step (3) is 2～5N, is preferably 3N.
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| CN104523658A (en) * | 2014-12-11 | 2015-04-22 | 陈长潭 | Erdosteine powder inhalation and preparation method thereof |
| CN104873495A (en) * | 2015-05-15 | 2015-09-02 | 苗怡文 | Erdosteine composition for treating respiratory tract inflammation |
| CN104983693A (en) * | 2015-08-13 | 2015-10-21 | 青岛蓝盛洋医药生物科技有限责任公司 | Medicine erdosteine composition granules for treating respiratory tract infection |
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| CN1323662C (en) * | 2004-06-18 | 2007-07-04 | 江苏恒瑞医药股份有限公司 | Pharmaceutical composition containing ambroxol and erdosteine or acetylcysteine and application thereof |
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| CN104523658A (en) * | 2014-12-11 | 2015-04-22 | 陈长潭 | Erdosteine powder inhalation and preparation method thereof |
| CN104523658B (en) * | 2014-12-11 | 2017-02-22 | 陈长潭 | Erdosteine powder inhalation and preparation method thereof |
| CN104873495A (en) * | 2015-05-15 | 2015-09-02 | 苗怡文 | Erdosteine composition for treating respiratory tract inflammation |
| CN105055348A (en) * | 2015-07-30 | 2015-11-18 | 青岛蓝盛洋医药生物科技有限责任公司 | Medicinal erdosteine composition tablet for treating respiratory tract inflammation and preparation method of tablet |
| CN104983693A (en) * | 2015-08-13 | 2015-10-21 | 青岛蓝盛洋医药生物科技有限责任公司 | Medicine erdosteine composition granules for treating respiratory tract infection |
| CN106038620A (en) * | 2016-07-11 | 2016-10-26 | 山西普德药业有限公司 | Ginkgo leaf tablet preparing method |
| CN106038620B (en) * | 2016-07-11 | 2019-09-17 | 山西普德药业有限公司 | A kind of preparation method of Folium Ginkgo |
| CN106176642A (en) * | 2016-07-19 | 2016-12-07 | 山东罗欣药业集团股份有限公司 | A kind of dispersible tablet treating respiratory system disease and preparation method thereof |
| CN106176642B (en) * | 2016-07-19 | 2019-08-13 | 山东罗欣药业集团股份有限公司 | A kind of Disket and preparation method thereof for treating respiratory disease |
| CN115137693A (en) * | 2021-03-31 | 2022-10-04 | 成都倍特药业股份有限公司 | Carbocisteine oral preparation and preparation method thereof |
| KR20220148616A (en) | 2021-04-29 | 2022-11-07 | 대봉엘에스 주식회사 | Individual co-crystal of l, d-erdosteine |
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