CN102233139B - Acetylcysteine effervescent tablet and preparation method and application thereof - Google Patents
Acetylcysteine effervescent tablet and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses an acetylcysteine effervescent tablet, a preparation method and an application thereof; the effervescent tablet comprises the following pharmaceutical components by weight: 2-6 parts of acetylcysteine, 3.2-13 parts of organic acids, 3-9.5 parts of sodium bicarbonate, 1.5-13.5 parts of filling agents, 3-4 parts of anhydrous alcohol, 0.2-0.6 parts of PVPK30, 0.05-0.25 parts of glycerol, 0.05-0.35 parts of sodium chloride, 0.1-0.75 parts of essence, 0.1-0.4 parts of sweetening agents, and 0.15-0.8 parts of lubricants; the effervescent tablet has low hygroscopicity, and has no sticking and picking problem during tabletting in environment with humidity of less than 55%; and the effervescent tablet is applicable to the preparation of a preoperative adjuvant drug for digestive endoscope examinations and treatment or imaging examinations.
Description
Technical field
The present invention relates to technical field of medicine, be specifically related to a kind of effervescent tablet, method for preparing that contains acetylcysteine, and the application in the adjuvant drug before preparation is as digestive endoscopy inspection and treatment or imaging examination art of this effervescent tablet.
Background technology
Acetylcysteine (Acetylcysteine, N-acetyl group-3-sulfydryl third ammonia) is the precursor of reduced glutathion (GSH), belongs to oxygen free radical scavenger in the body.The mechanism of its liver protection is still not fully aware of, maybe with keep or to recover glutathione level relevant.In addition, acetylcysteine also maybe be through improving hematodinamics and oxygen conveying capacity, expansion microcirculation performance liver protection.
The most of useful effect of acetylcysteine (NAC) comes from it to be had and reduces the extracellular cystine and be converted into the ability of cysteine, and can be used as the metabolic source of sulfydryl.Acetylcysteine can stimulate glutathion (GSH) synthetic, strengthens the activity of GSH-S-based transferase, promotes detoxifcation and to the direct effect of oxygen free radical reaction.Reach external evidence in the body and all point out, acetylcysteine can improve the biosynthesis of GSH in the cell.In cell culture experiments, acetylcysteine promotes the picked-up of cystine from the biosynthetic culture medium of GSH.In vivo, acetylcysteine can improve the level of GSH in the cell of erythrocyte, hepatocyte, lungs cell and replenish the consume that experimental GSH stores.
The GSH concentration that acetylcysteine is corrected the obstruction of biliary tract rat causes the important protective effect to the flowability of film and catalase, SOD2, multi-form GSH peroxidase.These effect prompting acetylcysteines possibly be a kind of active drugs of protecting the patients with biliary liver function.Acetylcysteine is demonstrating the synthetic support to GSH when GSH need increase.Show that acetylcysteine competence exertion under the state that GSH lacks promotes the synthetic effect of GSH.Acetylcysteine can also improve the concentration of single phosphoric acid cyclic guanosine under experiment condition.It is active that Harrison etc. have reported that acetylcysteine shows good hematodinamics through improving endogenous vasodilation nitric oxide level and increase sGC system activity when acute hepatic failure.Report acetylcysteines such as Nagasaki can be protected the GSH hepatic injury in when disappearance, and the integrity of liver can safeguard ischemia/reperfusion injury the time.This effect is as the biosynthetic substrate of GSH but bring into play as direct free radical scavenger, and directly to suppress the Kupffer cell activation relevant with it.There are some researches show that acetylcysteine can block apoptotic process.Its mechanism is that acetylcysteine can be removed reactive oxygen intermediate with participating in the apoptotic signal transduction; Precursor as reduced form GSH provides anti-cell toxic effect; Can also disturb apoptosis the signal in downstream, back to occur.
The preparation of acetylcysteine is used more extensive clinically, and known have an expelling phlegm for arresting cough effect.Also begin to be applied to treat various hepatic disease, particularly liver failure at present.
At present, the preparation of acetylcysteine listing dosage form has: liquid drugs injection, powder pin, granule, eye drop, spray, capsule, effervescent tablet.
Effervescent tablet contains sodium bicarbonate and organic acid, meets water and can produce gas and be the effervescent shape, has dissolving rapidly, and drug effect is fast, and bioavailability is high, easy to carry and low cost and other advantages.But because the used adjuvant of effervescent tablet has stronger hygroscopicity, so be easy to produce the sticking phenomenon in its tabletting process, how solving the sticking problem in the effervescent tablet production process, is one of insoluble problem of pharmaceutical production one line technology personnel.
U.S. Pat 6066335 discloses a kind of acetylcysteine effervescent tablet, and this effervescent tablet prescription is: acetylcysteine, aspartame, cherry essence, propylene glycol, citric acid, sodium bicarbonate, magnesium stearate, and technology is: mixed 3 minutes of acetylcysteine and aspartame, cherry essence; Granulate as binding agent with propylene glycol; After the drying, under less than 25% humidity environment, mixed 10～15 minutes with citric acid, sodium bicarbonate again; Add the magnesium stearate mixing at last, tabletting.This process conditions humidity is less than 25%; Than higher, the GMP workshop to the requirement of temperature, humidity is: 18～26 degrees centigrade of temperature, humidity 45～65% to the requirement of workshop; Humidity is reduced to below 25%; Significantly transform existing workshop, this will inevitably increase production cost, makes troubles to production operation; And the effervescent tablet of preparing according to the method for this patent is when being dissolved in water, and the surface can some materials of come-up, swim on the liquid level, give the sensation of a kind of discomfort of people.
U.S. Pat 5762951 discloses other a kind of acetylcysteine effervescent tablet; This effervescent tablet prescription is: acetylcysteine, through spray-dired sodium dihydrogen citrate, sodium bicarbonate, micronized fatty acid, polyethylene glycol 6000, sodium stearyl fumarate, an amount of flavoring agent; Wherein alkali and organic acid have been controlled particle diameter; And organic acid has passed through processing, spray drying or micronize.Technology is: direct compression.Adjuvant in this prescription will pass through pre-treatment; Spray drying or micronize all will increase new equipment and operation sequence, have increased the prescription difficulty, process using be direct compression; Need special-purpose direct compression machine, workshop tablet machine commonly used can not satisfy the working condition of this technology.
Summary of the invention
The object of the present invention is to provide a kind of acetylcysteine effervescent tablet; This effervescent tablet prescription hygroscopicity is little; Can satisfy humidity less than 55% environment in, particularly in the environment of humidity 50%～55%, can prepare qualified effervescent tablet; Not sticking, and this effervescent tablet disintegration rate is fast, solution is clarified, mouthfeel is good.
Composition and ratio of weight and number that acetylcysteine effervescent tablet prescription of the present invention is contained are: 2～6 parts of acetylcysteines, 3.2～13 parts of organic acid, 3～9.5 parts of sodium bicarbonate, 1.5～13.5 parts of filleies, 3～4 parts of dehydrated alcohol, PVPK
300.2～0.6 part, 0.05～0.25 part of glycerol, 0.05～0.35 part in sodium chloride, 0.1～0.75 part in essence, 0.1～0.4 part of sweeting agent, 0.15～1.55 part of lubricant.
Wherein organic acid is selected from citric acid, tartaric acid or fumaric acid; Filler is selected from mannitol or lactose, sucrose; Essence is selected from cherry essence, orange flavor or Fructus Rubi essence; Sweeting agent is selected from aspartame or cyclamate; Lubricant is selected from sodium stearyl fumarate, polyethylene glycol 6000 or adipic acid.
Another object of the present invention provides the method for preparing of above-mentioned effervescent tablet, and this method contains the following step:
(1) preprocessing raw material and auxiliary material: take by weighing acetylcysteine, organic acid, sodium bicarbonate, the filler of recipe quantity, place mixer to carry out just mixing 3 minutes, put again and beat powder in the Universalpulverizer, cross 80 mesh sieves, get mixed powder I; Take by weighing sodium chloride, essence, sweeting agent, the lubricant of recipe quantity, place mixer to carry out just mixing 1～3 minute, put and beat powder in the Universalpulverizer, cross 80 mesh sieves, 50 ℃ of drying under reduced pressure to moisture get mixed powder II less than 1%;
(2) prepare adhesive slurry: take by weighing recipe quantity PvPk
30Be dissolved in the dehydrated alcohol with glycerol, stirring and dissolving is complete, gets binding agent;
(3) mixed powder I is placed efficient wet granulator, mixed 3 minutes under the stirring at low speed;
(4) granulate: under stirring at low speed, binder solution is added in the efficient wet granulator; Add the cement slurry of about 80% amount in 80 seconds, hang down and cut granulation in 30 seconds, under the stirring at low speed state, add the residue binding agent; The high again height that stirs was cut 30 seconds, then in the stirring at low speed bottom discharge;
(5) dry granulate: 55～60 ℃ of baking temperatures are set, and wind speed 38～45m/s predrying 5 minutes, takes out; Cross 30 mesh sieves (oscillating granulator), continued dry 6 minutes 50～60 ℃ of temperature in advance behind the granulate again; Wind speed 38～45m/s, 30 mesh sieves (oscillating granulator) granulate is crossed in discharging; Measure moisture, control moisture gets granule I less than 1%;
(6) total mixing: humidity less than 55% environment in, mixed powder II is added among the granule I, put in the mixer and mixed 3 minutes, abundant mix homogeneously, sealing is preserved;
(7) tabletting: humidity less than 55% environment in, tablet machine idle running 5 minutes begins tabletting then;
(8) aluminum-plastic packaged, two then aluminum bags pack finished product.
This method for preparing always mixes that the mixed powder compressibility that obtains in the step is good, and hygroscopicity is low, can satisfy humidity less than 55% environment in, suppress qualified effervescent tablet, and sticking not.
A purpose more of the present invention provides the application in the adjuvant drug before preparation is as digestive endoscopy inspection and treatment or imaging examination art of above-mentioned effervescent tablet.
The specific embodiment
Below in conjunction with the specific embodiment the present invention is further described, but should this be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.Adjuvant in following examples can be replaced with acceptable accessories, perhaps reduces, increases.
Embodiment 1
1, prescription:
Acetylcysteine 600g
Citric acid 1045g
Sodium bicarbonate 905g
Mannitol 235g
Dehydrated alcohol 300g
PVPK
30 30g
Glycerol 10g
Sodium chloride 24g
Orange flavor 75g
Aspartame 30g
Polyethylene glycol 6000 45g
Process 1000 altogether
2, processing step:
(1) preprocessing raw material and auxiliary material: take by weighing acetylcysteine, citric acid, sodium bicarbonate, the mannitol of recipe quantity, place mixer to carry out just mixing 3 minutes, put again and beat powder in the Universalpulverizer, cross 80 mesh sieves, get mixed powder I; Take by weighing sodium chloride, orange flavor, aspartame, the polyethylene glycol 6000 of recipe quantity, place mixer to carry out just mixing 2 minutes, put and beat powder in the Universalpulverizer, cross 80 mesh sieves, 50 ℃ of drying under reduced pressure to moisture get mixed powder II less than 1%;
(2) prepare adhesive slurry: take by weighing recipe quantity PvPk
30Be dissolved in the dehydrated alcohol with glycerol, stirring and dissolving is complete, gets binding agent;
(3) mixed powder I is placed efficient wet granulator, mixed 3 minutes under the stirring at low speed;
(4) granulate: under stirring at low speed, binder solution is added in the efficient wet granulator; Add the cement slurry of about 80% amount in 80 seconds, hang down and cut granulation in 30 seconds, under the stirring at low speed state, add the residue binding agent; The high again height that stirs was cut 30 seconds, then in the stirring at low speed bottom discharge;
(5) dry granulate: 55 ℃ of baking temperatures are set, and wind speed 40m/s predrying 5 minutes, takes out; Cross 30 mesh sieves (oscillating granulator), continued dry 6 minutes 55 ℃ of temperature in advance behind the granulate again; Wind speed 38m/s, 30 mesh sieves (oscillating granulator) granulate is crossed in discharging; Measure moisture, control moisture gets granule I less than 1%;
(6) total mixing: in the environment of humidity 45%～50%, mixed powder II is added among the granule I, puts in the mixer and mixes 3 minutes, abundant mix homogeneously, and sealing is preserved;
(7) tabletting: in the environment of humidity 45%～50%, tablet machine idle running 5 minutes begins tabletting then;
(8) aluminum-plastic packaged, two then aluminum bags pack finished product.
Investigate disintegration
Get 6 of present embodiment gained effervescent tablets, according to " inspection of two appendix of 2005 editions Chinese pharmacopoeia inspection technique disintegration, result such as following table:
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods |
| Disintegration (20 ℃) | 18′ | 15′ | 20′ | 17′ | 14′ | 15′ | 17′ |
Discharge great amount of bubbles in the disintegrating procedue, solution clarification after the disintegrate, liquid level does not have floating thing, cup end deposit-free, mouthfeel is fragrant and sweet; Orange flavor in the present embodiment, aspartame, sodium chloride coupling just draw through a large amount of experiment sievings; Three's coupling has obtained well to rectify the flavor effect; Orange flavor tarts up, and aspartame increases sweet taste, and sodium chloride has a bit to become to distinguish the flavor of; Because the mucolyticum acid starting material itself has the foul smell of similar Bulbus Allii, above three's coupling has well overcome the taste of the discomfort that raw material brought.
The value of acetylcysteine effervescent tablet in observing at the bottom of the scope body of stomach stomach
Material and apparatus
The acetylcysteine effervescent tablet, self-control (embodiment 1), specification: 0.6g; Chain protease looses (Japanese first name: プ ロ Na one ゼ looses), and specification: 0.5g/ bag is equivalent to chain protease 20000 units, Japanese scientific research pharmaceutical manufacturing, and its indication is: remove gastric mucus when being used for gastroscopy; Fuji can ∑ 440 electronic gastroscopes.
Clinical data
Chongqing hospital accepts gastroscopy patient (getting rid of residual stomach and liver cirrhosis person) 62 examples as seminar 1 between in March, 2009 to JIUYUE, male's 38 examples wherein, women's 34 examples, 29～51 years old mean age; Accept gastroscopic 58 routine patients the same period as seminar 2, male's 35 examples wherein, women's 33 examples, 30～53 years old mean age.
Method
1+water of seminar's 1 preceding 20 minutes acetylcysteine effervescent tablets of inspection 100ml dissolving back is oral; Preceding 20 minutes chain proteases of seminar 2 inspection loose oral behind the 1 bag+water 100ml mixing.All patients all carry out gastroscopy by the high age and service seniority chief physician special messenger of Gastroenterology dept., are divided into four grades of ABCD according to the degree of getting a clear view, and level evaluation is accomplished by two doctors jointly.The A level: gastric mucosa does not have mucus to adhere to, and gets a clear view; The B level: gastric mucosa has a small amount of mucus to adhere to, and the visual field is still clear; The C level: gastric mucosa has a large amount of mucus to adhere to, and needs 50ml water to go flushing; The D level: gastric mucosa has a large amount of mucus to adhere to, and need go flushing more than 50ml water.Result such as following table:
| A | B | C | D | |
| Seminar 1 | 42(68％) | 11(18％) | 9(14％) | 0 |
| Seminar 2 | 45(76％) | 8(14％) | 5(10％) | 0 |
The result shows that seminar 1 or seminar 2 explain that than the equal definition that can significantly improve in scope body of stomach gastric mucosa is observed of matched group the acetylcysteine effervescent tablet has higher using value in the digestive endoscopy inspection.
More than discover; The acetylcysteine effervescent tablet is taken before digestive endoscopy inspection and treatment or imaging examination art can remove gastral mucus; Thereby when improving digestive endoscopy and treatment or imaging examination; Gastral definition; For the clinical accurate judgement state of an illness provides good approach, the taking dose of acetylcysteine effervescent tablet can be adjusted according to clinical needs, and the acetylcysteine of at every turn taking 600mg under the general situation just can satisfy removes the mucous needs of digestive tract.
Embodiment 2
1, prescription:
Acetylcysteine 600g
Citric acid 320g
Sodium bicarbonate 300g
Mannitol 1545g
Dehydrated alcohol 400g
PVPK
30 60g
Glycerol 15g
Sodium chloride 10g
Cherry essence 75g
Cyclamate 30g
Polyethylene glycol 6000 45g
Process 1000 altogether
2, processing step:
(1) preprocessing raw material and auxiliary material: take by weighing acetylcysteine, citric acid, sodium bicarbonate, the mannitol of recipe quantity, place mixer to carry out just mixing 3 minutes, put again and beat powder in the Universalpulverizer, cross 80 mesh sieves, get mixed powder I; Take by weighing sodium chloride, cherry essence, cyclamate, the polyethylene glycol 6000 of recipe quantity, place mixer to carry out just mixing 2 minutes, put and beat powder in the Universalpulverizer, cross 80 mesh sieves, 50 ℃ of drying under reduced pressure to moisture get mixed powder II less than 1%;
(2) prepare adhesive slurry: take by weighing recipe quantity PvPk
30Be dissolved in the dehydrated alcohol with glycerol, stirring and dissolving is complete, gets binding agent;
(3) mixed powder I is placed efficient wet granulator, mixed 3 minutes under the stirring at low speed;
(4) granulate: under stirring at low speed, binder solution is added in the efficient wet granulator; Add the cement slurry of about 80% amount in 80 seconds, hang down and cut granulation in 30 seconds, under the stirring at low speed state, add the residue binding agent; The high again height that stirs was cut 30 seconds, then in the stirring at low speed bottom discharge;
(5) dry granulate: 55 ℃ of baking temperatures are set, and wind speed 40m/s predrying 5 minutes, takes out; Cross 30 mesh sieves (oscillating granulator), continued dry 6 minutes 55 ℃ of temperature in advance behind the granulate again; Wind speed 38m/s, 30 mesh sieves (oscillating granulator) granulate is crossed in discharging; Measure moisture, control moisture gets granule I less than 1%;
(6) total mixing: in the environment of humidity 45%～50%, mixed powder II is added among the granule I, puts in the mixer and mixes 3 minutes, abundant mix homogeneously, and sealing is preserved;
(7) tabletting: in the environment of humidity 45%～50%, tablet machine idle running 5 minutes begins tabletting then;
(8) aluminum-plastic packaged, two then aluminum bags pack finished product.
Investigate disintegration
Get 6 of present embodiment gained effervescent tablets, according to " inspection of two appendix of 2005 editions Chinese pharmacopoeia inspection technique disintegration, result such as following table:
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods |
| Disintegration (20 ℃) | 48′ | 45′ | 40′ | 47′ | 44′ | 45′ | 45′ |
Discharge great amount of bubbles in the disintegrating procedue, solution clarification after the disintegrate, liquid level does not have floating thing, cup end deposit-free, mouthfeel is fragrant and sweet.
Embodiment 3
1, prescription:
Acetylcysteine 600g
Citric acid 630g
Sodium bicarbonate 570g
Mannitol 950g
Dehydrated alcohol 350g
PVPK
30 55g
Glycerol 15g
Sodium chloride 10g
Fructus Rubi essence 75g
Aspartame 40g
Sodium stearyl fumarate 55g
Process 1000 altogether
2, processing step:
(1) preprocessing raw material and auxiliary material: take by weighing acetylcysteine, citric acid, sodium bicarbonate, the mannitol of recipe quantity, place mixer to carry out just mixing 3 minutes, put again and beat powder in the Universalpulverizer, cross 80 mesh sieves, get mixed powder I; Take by weighing sodium chloride, Fructus Rubi essence, aspartame, the sodium stearyl fumarate of recipe quantity, place mixer to carry out just mixing 2 minutes, put and beat powder in the Universalpulverizer, cross 80 mesh sieves, 50 ℃ of drying under reduced pressure to moisture get mixed powder II less than 1%;
(2) prepare adhesive slurry: take by weighing recipe quantity PvPk
30Be dissolved in the dehydrated alcohol with glycerol, stirring and dissolving is complete, gets binding agent;
(3) mixed powder I is placed efficient wet granulator, mixed 3 minutes under the stirring at low speed;
(4) granulate: under stirring at low speed, binder solution is added in the efficient wet granulator; Add the cement slurry of about 80% amount in 80 seconds, hang down and cut granulation in 30 seconds, under the stirring at low speed state, add the residue binding agent; The high again height that stirs was cut 30 seconds, then in the stirring at low speed bottom discharge;
(5) dry granulate: 55 ℃ of baking temperatures are set, and wind speed 40m/s predrying 5 minutes, takes out; Cross 30 mesh sieves (oscillating granulator), continued dry 6 minutes 55 ℃ of temperature in advance behind the granulate again; Wind speed 38m/s, 30 mesh sieves (oscillating granulator) granulate is crossed in discharging; Measure moisture, control moisture gets granule I less than 1%;
(6) total mixing: in the environment of humidity 40%～45%, mixed powder II is added among the granule I, puts in the mixer and mixes 3 minutes, abundant mix homogeneously, and sealing is preserved;
(7) tabletting: in the environment of humidity 40%～45%, tablet machine idle running 5 minutes begins tabletting then;
(8) aluminum-plastic packaged, two then aluminum bags pack finished product.
Investigate disintegration
Get 6 of present embodiment gained effervescent tablets, according to " inspection of two appendix of 2005 editions Chinese pharmacopoeia inspection technique disintegration, result such as following table:
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods |
| Disintegration (20 ℃) | 28′ | 25′ | 20′ | 27′ | 24′ | 25′ | 25′ |
Discharge great amount of bubbles in the disintegrating procedue, solution clarification after the disintegrate, liquid level does not have floating thing, cup end deposit-free, mouthfeel is fragrant and sweet.
Embodiment 4
1, prescription:
Acetylcysteine 400g
Citric acid 1170g
Sodium bicarbonate 930g
Mannitol 310g
Dehydrated alcohol 300g
PVPK
30 45g
Glycerol 10g
Sodium chloride 30g
Orange flavor 50g
Aspartame 10g
Polyethylene glycol 6000 45g
Process 1000 altogether
2, processing step:
(1) preprocessing raw material and auxiliary material: take by weighing acetylcysteine, citric acid, sodium bicarbonate, the mannitol of recipe quantity, place mixer to carry out just mixing 3 minutes, put again and beat powder in the Universalpulverizer, cross 80 mesh sieves, get mixed powder I; Take by weighing sodium chloride, orange flavor, aspartame, the polyethylene glycol 6000 of recipe quantity, place mixer to carry out just mixing 1 minute, put and beat powder in the Universalpulverizer, cross 80 mesh sieves, 50 ℃ of drying under reduced pressure to moisture get mixed powder II less than 1%;
(2) prepare adhesive slurry: take by weighing recipe quantity PvPk
30Be dissolved in the dehydrated alcohol with glycerol, stirring and dissolving is complete, gets binding agent;
(3) mixed powder I is placed efficient wet granulator, mixed 3 minutes under the stirring at low speed;
(4) granulate: under stirring at low speed, binder solution is added in the efficient wet granulator; Add the cement slurry of about 80% amount in 80 seconds, hang down and cut granulation in 30 seconds, under the stirring at low speed state, add the residue binding agent; The high again height that stirs was cut 30 seconds, then in the stirring at low speed bottom discharge;
(5) dry granulate: 60 ℃ of baking temperatures are set, and wind speed 43m/s predrying 5 minutes, takes out; Cross 30 mesh sieves (oscillating granulator), continued dry 6 minutes 60 ℃ of temperature in advance behind the granulate again; Wind speed 41m/s, 30 mesh sieves (oscillating granulator) granulate is crossed in discharging; Measure moisture, control moisture gets granule I less than 1%;
(6) total mixing: in the environment of humidity 35%～40%, mixed powder II is added among the granule I, puts in the mixer and mixes 3 minutes, abundant mix homogeneously, and sealing is preserved;
(7) tabletting: in the environment of humidity 35%～40%, tablet machine idle running 5 minutes begins tabletting then;
(8) aluminum-plastic packaged, two then aluminum bags pack finished product.
Investigate disintegration
Get 6 of present embodiment gained effervescent tablets, according to " inspection of two appendix of 2005 editions Chinese pharmacopoeia inspection technique disintegration, result such as following table:
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods |
| Disintegration (20 ℃) | 18′ | 22′ | 19′ | 25′ | 24′ | 20′ | 21′ |
Discharge great amount of bubbles in the disintegrating procedue, solution clarification after the disintegrate, liquid level does not have floating thing, cup end deposit-free, mouthfeel is fragrant and sweet.
Embodiment 5
1, prescription:
Acetylcysteine 200g
Citric acid 1296g
Sodium bicarbonate 954g
Lactose 315g
Dehydrated alcohol 300g
PVPK
30 25g
Glycerol 25g
Sodium chloride 35g
Orange flavor 50g
Aspartame 20g
Polyethylene glycol 6000 80g
Process 1000 altogether
2, processing step:
(1) preprocessing raw material and auxiliary material: take by weighing acetylcysteine, citric acid, sodium bicarbonate, the lactose of recipe quantity, place mixer to carry out just mixing 3 minutes, put again and beat powder in the Universalpulverizer, cross 80 mesh sieves, get mixed powder I; Take by weighing sodium chloride, orange flavor, aspartame, the polyethylene glycol 6000 of recipe quantity, place mixer to carry out just mixing 3 minutes, put and beat powder in the Universalpulverizer, cross 80 mesh sieves, 50 ℃ of drying under reduced pressure to moisture get mixed powder II less than 1%;
(2) prepare adhesive slurry: take by weighing recipe quantity PvPk
30Be dissolved in the dehydrated alcohol with glycerol, stirring and dissolving is complete, gets binding agent;
(3) mixed powder I is placed efficient wet granulator, mixed 3 minutes under the stirring at low speed;
(4) granulate: under stirring at low speed, binder solution is added in the efficient wet granulator; Add the cement slurry of about 80% amount in 80 seconds, hang down and cut granulation in 30 seconds, under the stirring at low speed state, add the residue binding agent; The high again height that stirs was cut 30 seconds, then in the stirring at low speed bottom discharge;
(5) dry granulate: 58 ℃ of baking temperatures are set, and wind speed 42m/s predrying 5 minutes, takes out; Cross 30 mesh sieves (oscillating granulator), continued dry 6 minutes 50 ℃ of temperature in advance behind the granulate again; Wind speed 45m/s, 30 mesh sieves (oscillating granulator) granulate is crossed in discharging; Measure moisture, control moisture gets granule I less than 1%;
(6) total mixing: in the environment of humidity 40%～45%, mixed powder II is added among the granule I, puts in the mixer and mixes 3 minutes, abundant mix homogeneously, and sealing is preserved;
(7) tabletting: in the environment of humidity 40%～45%, tablet machine idle running 5 minutes begins tabletting then;
(8) aluminum-plastic packaged, two then aluminum bags pack finished product.
Investigate disintegration
Get 6 of present embodiment gained effervescent tablets, according to " inspection of two appendix of 2005 editions Chinese pharmacopoeia inspection technique disintegration, result such as following table:
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods |
| Disintegration (20 ℃) | 10′ | 11′ | 14′ | 9′ | 13′ | 8′ | 11′ |
Discharge great amount of bubbles in the disintegrating procedue, solution clarification after the disintegrate, liquid level does not have floating thing, cup end deposit-free, mouthfeel is fragrant and sweet.
Embodiment 6
1, prescription:
Acetylcysteine 200g
Tartaric acid 754g
Sodium bicarbonate 615g
Lactose 1326g
Dehydrated alcohol 300g
PVPK
30 20g
Glycerol 5g
Sodium chloride 5g
Orange flavor 10g
Aspartame 15g
Polyethylene glycol 6000 50g
Process 1000 altogether
2, processing step:
(1) preprocessing raw material and auxiliary material: take by weighing acetylcysteine, tartaric acid, sodium bicarbonate, the lactose of recipe quantity, place mixer to carry out just mixing 3 minutes, put again and beat powder in the Universalpulverizer, cross 80 mesh sieves, get mixed powder I; Take by weighing sodium chloride, orange flavor, aspartame, the polyethylene glycol 6000 of recipe quantity, place mixer to carry out just mixing 3 minutes, put and beat powder in the Universalpulverizer, cross 80 mesh sieves, 50 ℃ of drying under reduced pressure to moisture get mixed powder II less than 1%;
(2) prepare adhesive slurry: take by weighing recipe quantity PvPk
30Be dissolved in the dehydrated alcohol with glycerol, stirring and dissolving is complete, gets binding agent;
(3) mixed powder I is placed efficient wet granulator, mixed 3 minutes under the stirring at low speed;
(4) granulate: under stirring at low speed, binder solution is added in the efficient wet granulator; Add the cement slurry of about 80% amount in 80 seconds, hang down and cut granulation in 30 seconds, under the stirring at low speed state, add the residue binding agent; The high again height that stirs was cut 30 seconds, then in the stirring at low speed bottom discharge;
(5) dry granulate: 58 ℃ of baking temperatures are set, and wind speed 42m/s predrying 5 minutes, takes out; Cross 30 mesh sieves (oscillating granulator), continued dry 6 minutes 50 ℃ of temperature in advance behind the granulate again; Wind speed 45m/s, 30 mesh sieves (oscillating granulator) granulate is crossed in discharging; Measure moisture, control moisture gets granule I less than 1%;
(6) total mixing: in the environment of humidity 45%～50%, mixed powder II is added among the granule I, puts in the mixer and mixes 3 minutes, abundant mix homogeneously, and sealing is preserved;
(7) tabletting: in the environment of humidity 50%～55%, tablet machine idle running 5 minutes begins tabletting then;
(8) aluminum-plastic packaged, two then aluminum bags pack finished product.
Investigate disintegration
Get 6 of present embodiment gained effervescent tablets, according to " inspection of two appendix of 2005 editions Chinese pharmacopoeia inspection technique disintegration, result such as following table:
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods |
| Disintegration (20 ℃) | 32′ | 33′ | 30′ | 27′ | 37′ | 35′ | 32′ |
Discharge great amount of bubbles in the disintegrating procedue, solution clarification after the disintegrate, liquid level does not have floating thing, cup end deposit-free, mouthfeel is fragrant and sweet.
Embodiment 7
1, prescription:
Acetylcysteine 400g
Fumaric acid 625g
Sodium bicarbonate 515g
Mannitol 1160g
Dehydrated alcohol 300g
PVPK
30 45g
Glycerol 10g
Sodium chloride 30g
Orange flavor 50g
Aspartame 10g
Adipic acid 155g
Process 1000 altogether
2, processing step:
(1) preprocessing raw material and auxiliary material: take by weighing acetylcysteine, fumaric acid, sodium bicarbonate, the mannitol of recipe quantity, place mixer to carry out just mixing 3 minutes, put again and beat powder in the Universalpulverizer, cross 80 mesh sieves, get mixed powder I; Take by weighing sodium chloride, orange flavor, aspartame, the adipic acid of recipe quantity, place mixer to carry out just mixing 1 minute, put and beat powder in the Universalpulverizer, cross 80 mesh sieves, 50 ℃ of drying under reduced pressure to moisture get mixed powder II less than 1%;
(2) prepare adhesive slurry: take by weighing recipe quantity PvPk
30Be dissolved in the dehydrated alcohol with glycerol, stirring and dissolving is complete, gets binding agent;
(3) mixed powder I is placed efficient wet granulator, mixed 3 minutes under the stirring at low speed;
(4) granulate: under stirring at low speed, binder solution is added in the efficient wet granulator; Add the cement slurry of about 80% amount in 80 seconds, hang down and cut granulation in 30 seconds, under the stirring at low speed state, add the residue binding agent; The high again height that stirs was cut 30 seconds, then in the stirring at low speed bottom discharge;
(5) dry granulate: 60 ℃ of baking temperatures are set, and wind speed 43m/s predrying 5 minutes, takes out; Cross 30 mesh sieves (oscillating granulator), continued dry 6 minutes 60 ℃ of temperature in advance behind the granulate again; Wind speed 41m/s, 30 mesh sieves (oscillating granulator) granulate is crossed in discharging; Measure moisture, control moisture gets granule I less than 1%;
(6) total mixing: in the environment of humidity 45%～50%, mixed powder II is added among the granule I, puts in the mixer and mixes 3 minutes, abundant mix homogeneously, and sealing is preserved;
(7) tabletting: in the environment of humidity 45%～50%, tablet machine idle running 5 minutes begins tabletting then;
(8) aluminum-plastic packaged, two then aluminum bags pack finished product.
Investigate disintegration
Get 6 of present embodiment gained effervescent tablets, according to " inspection of two appendix of 2005 editions Chinese pharmacopoeia inspection technique disintegration, result such as following table:
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | Meansigma methods |
| Disintegration (20 ℃) | 58′ | 55′ | 57′ | 47′ | 56′ | 51′ | 54′ |
Discharge great amount of bubbles in the disintegrating procedue, solution clarification after the disintegrate, liquid level does not have floating thing, cup end deposit-free, mouthfeel is fragrant and sweet.
Wettability test
The mixed powder that obtains in the always mixed step of method for preparing among above-mentioned 7 embodiment carries out wettability test.
Concrete assay method is following:
1. get method for preparing among a certain amount of 7 embodiment always mix the mixed powder that obtains in the step put one precision weigh in the tool plug glass weighing botle (external diameter is 50mm, and height is 15mm) of (m1) precision weigh (m2).
2. uncovered 25 ℃ of the temperature that place of weighing botle, in the thermostatic drier of relative humidity 55%.
3. placed 24 hours.
4. build the weighing botle lid, precision weigh (m3).
Weightening finish percentage rate=(m3-m2) ÷ (m2-m1) * 100%
The result sees the following form:
| Project | (m3-m2)/g | (m2-m1)/g | The weightening finish percentage rate |
| Embodiment 1 | 0.0070 | 5.0155 | 0.14％ |
| Embodiment 2 | 0.0055 | 5.0322 | 0.11％ |
| Embodiment 3 | 0.0045 | 5.0243 | 0.09％ |
| Embodiment 4 | 0.0040 | 5.0334 | 0.08％ |
| Embodiment 5 | 0.0075 | 5.0414 | 0.15％ |
| Embodiment 6 | 0.0035 | 5.0116 | 0.07％ |
| Embodiment 7 | 0.0030 | 5.0242 | 0.06％ |
The result shows that the foregoing description 1～embodiment 7 gained mixed powder hygroscopicity are little, in the environment of humidity 55%, places after 24 hours, and moisture absorption weightening finish percentage rate is all less than 0.2%.
Claims (9)
1. acetylcysteine effervescent tablet, it is characterized in that: composition that is contained and ratio of weight and number are: 2～6 parts of acetylcysteines, 3.2～13 parts of organic acid, 3～9.5 parts of sodium bicarbonate, 1.5～13.5 parts of filleies, 3～4 parts of dehydrated alcohol, PVPK
300.2～0.6 part, 0.05～0.25 part of glycerol, 0.05～0.35 part in sodium chloride, 0.1～0.75 part in essence, 0.1～0.4 part of sweeting agent, 0.15～1.55 part of lubricant.
2. acetylcysteine effervescent tablet according to claim 1 is characterized in that: said organic acid is selected from citric acid, tartaric acid or fumaric acid.
3. acetylcysteine effervescent tablet according to claim 1 is characterized in that: said filler is selected from mannitol, lactose or sucrose.
4. acetylcysteine effervescent tablet according to claim 1 is characterized in that: said essence is selected from cherry essence, orange flavor or Fructus Rubi essence.
5. acetylcysteine effervescent tablet according to claim 1, the spy is characterised in that: said sweeting agent is selected from aspartame or cyclamate.
6. acetylcysteine effervescent tablet according to claim 1 is characterized in that: said lubricant is selected from sodium stearyl fumarate, polyethylene glycol 6000 or adipic acid.
7. the method for preparing of the said acetylcysteine effervescent tablet of claim 1 is characterized in that, contains the following step:
(1) preprocessing raw material and auxiliary material: take by weighing acetylcysteine, organic acid, sodium bicarbonate, the filler of recipe quantity, place mixer to carry out just mixing 3 minutes, put again and beat powder in the Universalpulverizer, cross 80 mesh sieves, get mixed powder I; Take by weighing sodium chloride, essence, sweeting agent, the lubricant of recipe quantity, place mixer to carry out just mixing 1～3 minute, put and beat powder in the Universalpulverizer, cross 80 mesh sieves, 50 ℃ of drying under reduced pressure to moisture get mixed powder II less than 1%;
(2) prepare adhesive slurry: take by weighing recipe quantity PvPk
30Be dissolved in the dehydrated alcohol with glycerol, stirring and dissolving is complete, gets binding agent;
(3) mixed powder I is placed efficient wet granulator, mixed 3 minutes under the stirring at low speed;
(4) granulate: under stirring at low speed, binder solution is added in the efficient wet granulator; Add the cement slurry of about 80% amount in 80 seconds, hang down and cut granulation in 30 seconds, under the stirring at low speed state, add the residue binding agent; The high again height that stirs was cut 30 seconds, then in the stirring at low speed bottom discharge;
(5) dry granulate: 55～60 ℃ of baking temperatures are set, wind speed 38～45m/s, predrying 5 minutes, take out, cross 30 mesh sieves; Continued again dry 6 minutes behind the granulate in advance, 50～60 ℃ of temperature, wind speed 38～45m/s, 30 mesh sieves are crossed in discharging; Granulate is measured moisture, and control moisture gets granule I less than 1%;
(6) total mixing: humidity less than 55% environment in, mixed powder II is added among the granule I, put in the mixer and mixed 3 minutes, abundant mix homogeneously, sealing is preserved;
(7) tabletting: humidity less than 55% environment in, tablet machine idle running 5 minutes begins tabletting then;
(8) aluminum-plastic packaged, two then aluminum bags pack finished product.
8. the described acetylcysteine effervescent tablet of claim 1 application in the adjuvant drug before preparation is as digestive endoscopy inspection and treatment or imaging examination art.
9. acetylcysteine effervescent tablet according to claim 8 is the application in the adjuvant drug before preparation is as digestive endoscopy inspection and treatment or imaging examination art; Be characterised in that: when said acetylcysteine effervescent tablet specification was 600mg, each taking dose was 1.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2010101526942A CN102233139B (en) | 2010-04-21 | 2010-04-21 | Acetylcysteine effervescent tablet and preparation method and application thereof |
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| CN2010101526942A CN102233139B (en) | 2010-04-21 | 2010-04-21 | Acetylcysteine effervescent tablet and preparation method and application thereof |
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| CN103550142A (en) * | 2013-10-15 | 2014-02-05 | 温天文 | Medicinal solution preparation prepared from acetylcysteine clathrate and preparation method thereof |
| CN104758269A (en) * | 2015-02-12 | 2015-07-08 | 北京众盈汇丰科技发展有限责任公司 | Acetylcysteine effervescent tablet |
| CN106692097B (en) * | 2015-07-16 | 2019-10-25 | 北京福元医药股份有限公司 | Reduced glutathione medicine preparation |
| CN113559078A (en) * | 2021-07-02 | 2021-10-29 | 安徽省先锋制药有限公司 | Preparation method of acetylcysteine effervescent tablets |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2192790A (en) * | 1986-07-24 | 1988-01-27 | Inpharzam Int Sa | Acetylcysteine compositions |
| US5762951A (en) * | 1990-09-04 | 1998-06-09 | Bayer Aktiengesellschaft | Effervescent composition and tablet made there from |
| US6066335A (en) * | 1994-06-15 | 2000-05-23 | Horst Machoczek | Method of producing effervescent tablets and effervescent tablet |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1256616B (en) * | 1992-12-02 | 1995-12-12 | Zambon Spa | SYRUP CONTAINING N-ACETYL-CISTEIN |
-
2010
- 2010-04-21 CN CN2010101526942A patent/CN102233139B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2192790A (en) * | 1986-07-24 | 1988-01-27 | Inpharzam Int Sa | Acetylcysteine compositions |
| US5762951A (en) * | 1990-09-04 | 1998-06-09 | Bayer Aktiengesellschaft | Effervescent composition and tablet made there from |
| US6066335A (en) * | 1994-06-15 | 2000-05-23 | Horst Machoczek | Method of producing effervescent tablets and effervescent tablet |
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| CN102233139A (en) | 2011-11-09 |
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