CN102058480A - Oral effervescent tablet and preparation method thereof - Google Patents
Oral effervescent tablet and preparation method thereof Download PDFInfo
- Publication number
- CN102058480A CN102058480A CN2009102284670A CN200910228467A CN102058480A CN 102058480 A CN102058480 A CN 102058480A CN 2009102284670 A CN2009102284670 A CN 2009102284670A CN 200910228467 A CN200910228467 A CN 200910228467A CN 102058480 A CN102058480 A CN 102058480A
- Authority
- CN
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- Prior art keywords
- effervescent
- tablet
- binding agent
- acid
- granulate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- 238000002360 preparation method Methods 0.000 title claims abstract description 35
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- 239000008187 granular material Substances 0.000 claims description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 40
- 239000003826 tablet Substances 0.000 claims description 37
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- 239000000203 mixture Substances 0.000 claims description 34
- 239000000843 powder Substances 0.000 claims description 34
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 15
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- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 6
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Abstract
The invention relates to an oral effervescent tablet and a preparation method thereof, belonging to the field of pharmaceutic preparations. The preparation method of the effervescent tablet provided by the invention comprises the following steps: mixing raw materials, and pelletizing; and tidying particles, tabletting and the like.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to prescription of a kind of oral administration effervescing sheet and preparation method thereof.
Background technology
Effervescent tablet means chemical medicine or Chinese medicine extract and suitable adjuvant (comprising diluent, effervescent, binding agent, lubricant, fluidizer etc.) mix homogeneously, the repressed a kind of solid preparation that forms.2005 editions Pharmacopoeias of People's Republic of China (two ones) regulation, be limited to 5 minutes on effervescent tablet disintegration, oral administration effervescing sheet kinds such as vitamin C effervescent tablet, acetaminophen effervescent tablet, aspirin effervescent tablets have been recorded in 2005 editions Pharmacopoeias of People's Republic of China (two ones), the extract oral effervescent tablet does not also enter the kind of Pharmacopoeia of People's Republic of China, along with the development of preparation technique and pharmaceutical equipment, the oral administration effervescing sheet is on kind and quantitatively all in continuous increase.
The oral administration effervescing sheet is a kind of new dosage form of pharmaceutical field, has some characteristics and the advantage of solid preparation and liquid preparation concurrently, is specially adapted to the patient of child, old people and the solid preparation of can't swallowing, and easy to carry; Because of finally taking with liquid form, drug effect is rapid, bioavailability is high again.Compare with conventional tablet, have characteristics such as disintegrate is fast, bioavailability is high, drug loading is big; Compare with granule, have easy to carry, advantages such as dissolubility good, mouthfeel good, taking convenience; Compare with oral liquid, have easy to carry, good stability, low cost and other advantages.So from being subject to people's attention once occurring, development in recent years is particularly rapid.Effervescent tablet is also very fast in the development of China, is researching and developing, is producing and obtaining clinically using widely.
Mostly the oral administration effervescing sheet is the screening by selecting water miscible pharmaceutical adjunct to fill a prescription at present, the prepared that adopts soda acid to granulate respectively, but the production of oral administration effervescing sheet and application also exist such as the production technology instability, sticking easily takes place, fall problem such as lid, quality stability is poor, be prone to problems such as tablet variable color, distortion, effervescent time-delay.
The traditional pelletizing press sheet technology of the general employing of tablet is to guarantee the flowability and the uniformity of material.But the following problem of pelletizing press sheet technology ubiquity: the disintegration of tablet that obtains is slow, the compressibility of part tablet intermediate powder is bad, and the hardness of tablet is not enough, occurs knocking limit arrisdefect or loose sheet top easily and splits phenomenon, need compression force bigger during tabletting, production equipment is had relatively high expectations; Technology relative complex during granulation, the influence factor who is subjected to is more, and is unfavorable to the control of cost and quality; The addition of adjuvant is big, causes each dose big, is unfavorable for that the patient takes.The granulating process of oral administration effervescing sheet comprises that mainly soda acid granulates two kinds of organic solvent mixing granulations respectively.
Soda acid pelletizing press sheet technology respectively is to prepare granulates and alkali granule respectively, add mix lubricant then after tabletting make.This technology realizes easily aborning, environment and equipment there is not special requirement, problems such as but granulates that this technology is made and alkali granule easily particulate aberration occurs, effervescent speed is slow, and tabletting is prone to colored sheet, sticking, falls lid, poor stability and be difficult in industrialization is produced, realize.
Organic solvent mixing granulation tablet forming technique adopts organic solvent as binding agent, with adjuvants such as crude drug, soda acid mixing granulation in the lump, tabletting is made behind the outer mixed lubricant, though the uniform particles of this technology preparation, water content is low, tabletting is not prone to the sticking problem, the tablet effervescent speed that extrudes is fast, stability better, but carry out in need be between antiknock device and hoolivan, and organic solvent has toxicity more, human body is had injury effect, also will detect the residual of organic solvent in case of necessity, so limitation is obvious.
Powder vertical compression technology is with the direct mixed pressuring plate after pulverization process of all supplementary materials in the oral administration effervescing slice prescription, this technology requires very high to the compressibility of supplementary material and flowability etc., its advantage is that technology is simple, does not need granulation process and relevant device, low cost of manufacture, energy consumption is little, pollute low, the tablet color even of making, effervescent speed is fast, good stability.But this technology is higher to the sheeting equipment requirement on machining accuracy, and adjuvant is had relatively high expectations, and generally need be exclusively used in the adjuvant of direct compression, can not satisfy above-mentioned requirements and the supplementary material in the actual prescription of effervescent tablet is many, thereby its operability is very poor, and particularly the oral Chinese medicine effervescent tablet is infeasible substantially.Mainly be because the compatibility of accessory formula and Chinese medicine extract is relatively poor, behind adjuvant and the medicine mixing, mobile poor, tabletting easily causes tablet weight variation defective, occurs knocking molding problems such as limit arrisdefect during the poor compressibility tabletting easily, so use less.
The people knows in the industry, the sticking problem of oral administration effervescing sheet is the difficult problem that any exploitation effervescent tablet kind can not be avoided, traditional have following several solution, the first adds good lubricants such as a small amount of magnesium stearate, but this series lubricant agent mostly is water-insoluble, adds the product of this series lubricant agent, behind the effervescent, can not form clear solutions, produce to the patient easily and detest psychology; It two is to add soluble oil, but practice shows that how undesirable the lubricant effect of this series lubricant agent is, can only guarantee the lubricant effect at tabletting initial stage, can not thoroughly solve the problem of tabletting sticking; The 3rd, abroad according to above-mentioned two kinds of situations, develop a kind of task equipment, this kind equipment mainly is to substitute the consumption that internal mix reduces water insoluble lubricants magnesium stearate in the effervescent tablet prescription etc. by surface sprinkling, reduce the detest of patient to muddy effervescent solution, but such equipment debugging wants complexity, and comparatively expensive.
So people expect to overcome these deficiencies that traditional oral administration effervescing sheet exists, and provide a kind of disintegrate steady quality fast, the prescription and the production technology of the oral administration effervescing sheet of better tolerance always.
Summary of the invention
The invention provides a kind of preparation method of new effervescent tablet, overcome traditional oral administration effervescing sheet preparation and gone up the deficiency that exists, break traditions and go up the limitation that can not adopt the mixing water method to granulate, solved the multiple deficiency that traditional handicraft prepares effervescent tablet because soda acid meets that waterishlogging is given birth to reaction.
Method of the present invention adopts soda acid mixed fluidized bed method spray granulation; this method comprises being after solvent cement atomizes with water and the fine powder mixing granulation of other compositions in fluidised bed granulator; by reasonable control to spray amount and temperature of charge; the reaction of soda acid is controlled at rational degree, and then reaches granulation, blended purpose.
This method also comprises the step with the freezing back of granule tabletting.The minor amount of water that contains in the effervescent tablet is to cause the effervescent tablet sticking to get a key factor; And the effervescent in the effervescent tablet prescription, filler, soluble oil etc. are along with in the tabletting process, the raising of device temperature, and viscosity raises gradually, finally causes sticking.Address the above problem by refrigerating process.
The method for preparing effervescent tablet of the present invention, preferably adopt following steps:
(1) crude drug and filler, effervescent, correctives and lubricant pulverizing is standby for fine powder.
(2) adjuvant mix homogeneously such as crude drug and filler, effervescent is standby.
(3) with binding agent and strong toner water dissolving becoming aqueous solution, standby after filtering.
(4) in fluidised bed granulator, binding agent is atomized afterwards and the fine powder mix homogeneously in the step (2), granulate, standby.
(5) with the particle drying in the step (4), granulate is standby
(6) with granule and correctives in the step (5), mix lubricant is evenly standby
(7) the freezing back of the mixture in the step (6) is standby
(8) mixture in the step (7) is pressed into tablet.
Wherein,
In the step (1), described crude drug and filler, effervescent, correctives and lubricant are pulverized to fine powder can get by preparation method preparation conventional in the prior art, for example pulverize, and sieve promptly.Described fine powder is preferably 30～120 orders, and crude drug and filler most preferably are 80～100 orders.Effervescent, correctives most preferably are 80 orders, and lubricant most preferably is 120 orders.
In the step (2), crude drug mixes with adjuvants such as filler, effervescents and can carry out total mixing in the machine, also can carry out in fluidised bed granulator.
In the step (3), binding agent and the dissolving of strong toner water are become aqueous solution as binding agent, can select cold water or hot water dissolving for use, making becomes clear solutions, and the concentration of solution is preferably 10～35%, most preferably is 25～30%.Binder solution needs to filter before atomizing, can adopt filter screen or filter cloth to filter, and filters the order number and is preferably 100 orders.
In the step (4), with in the fine powder mix homogeneously process in binding agent atomizing back and the step (2), the fine powder in the step (2) is the motion of fluidisation attitude in fluidised bed granulator in fluidised bed granulator.Binding agent is transported to binding agent in the fluid bed by equipment such as peristaltic pump or screw pumps.Binding agent is transported to when passing through spray gun in the fluid bed, is atomized into tiny droplet under compressed-air actuated effect.Atomizing pressure is preferably 0.1～0.4MPa, most preferably is 0.25～0.35MPa.In fluid bed, the binding agent that is atomized contacts with the fine powder of fluidisation attitude and forms granule, simultaneously under the effect of the air inducing of heating, and granule rapid draing.The air inducing temperature is preferably 30～60 ℃, most preferably is 35～50 ℃.
Particulate dry fluid bed drying or the vacuum drying of adopting in the step (5), temperature is preferably 40～70 ℃, and vacuum is preferably and is not less than 0.08MPa, most preferably is 40～65 ℃, and vacuum is preferably and is not less than 0.085MPa.Granulate can select granulate pulverizer or oscillating granulator granulate for use, the back of can sieving is to the oversize granulate, arrangement order number is preferably 10 orders.
Granule and correctives in the step (6), mix lubricant is carried out in mixer, always does time to be preferably 5 minutes.
Mixture freezing means mixture and as in refrigerator-freezer or the cold closet material temperature to be reduced in the step (7), and material temperature is preferably-20～15 ℃, most preferably is-10～10 ℃
Mixture is pressed into tablet in the step (8), is meant to pass through pressure on tablet machine, and material is pressed into difform tablet, the general heavy preferred 1～5g/ sheet of sheet, and hardness is preferably 5～10KN.
Method of the present invention is fit to any effervescent tablet prescription, is particularly suitable for the following effervescent tablet prescription of the present invention:
For this reason, the invention provides a kind of new effervescent tablet prescription, its prescription is as follows:
Wherein:
Described active constituents of medicine is water miscible chemical medicine or Chinese medicine extract, and its weight portion is preferably 3～45.
Described filler is a water-soluble material, easily molten in water (1g is dissolved in 1ml～10ml water), be preferably polymerization sugar, sucrose, xylitol, mannitol, sorbitol, lactose, maltodextrin, anhydrous glucose, sodium chloride etc. and their combination etc., most preferably maltodextrin, xylitol, the combination of mannitol.Its weight portion is preferably 5～50.
Described effervescent is that organic acid and carbonic acid or the bicarbonate that acid-base reaction produces carbon dioxide takes place in water, and organic acid is preferably citric acid, tartaric acid, fumaric acid, malic acid, succinic acid etc., citric acid most preferably, tartaric acid; The preferred potassium carbonate of carbonic acid or bicarbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate etc., most preferably sodium bicarbonate.Its weight portion is preferably 30～55.
Described binding agent is preferably the aqueous solution of PVP K30, PVP K15, PEG 6000, PEG 4000, HPMC E5 etc., most preferably is the aqueous solution of PVP K15, PEG 6000.Its weight portion is preferably 1.5～3.
It is the general designation of correctives and strong toner that described flavoring is rectified toner, even the solution behind tablet and the tablet effervescent has pigment, sweeting agent and the essence etc. of good color and mouthfeel, it is preferably lemon yellow, sunset yellow, bata-carotene, aspartame, steviosin, sucralose, Fructus Citri sinensis flavor essence, fresh milk essence etc., most preferably is bata-carotene, aspartame, sucralose, Fructus Citri sinensis flavor essence.Its weight portion is preferably 0.3～2, most preferably is 0.3～1.
Described lubricant is selected from stearic acid, stearate, sodium stearyl fumarate, leucine, PEG 6000, sodium benzoate, sodium lauryl sulphate, hydrogenated vegetable wet goods, be preferably stearate, sodium stearyl fumarate, leucine, PEG 6000 most preferably are leucine, PEG 6000.Its weight portion is preferably 0.5～1.
Therefore, effervescent tablet of the present invention, optimizing prescriptions is as follows:
The present invention finds, adopting soda acid of the present invention to mix the fluidisation water law granulates, can make effervescents such as soda acid under fluidized state with other supplementary material high degree of dispersion, under the binder aqueous solution effect of high atomisation, a small amount of soda acid generation neutralization reaction generates a spot of salt and water, and is that core forms granule with this minor amount of water, and the heated air inducing of the moisture that acid-base reaction is emitted is taken away rapidly, form dried granules, finish the granulation dry run.
In the granulation dry run, temperature of charge raises and can make the dispersive binding agent of prescription camber (for low melting point water-soluble, film-forming adjuvant such as PEG 6000, PVP K15) melt film forming (phase transformation to a certain degree takes place), bronsted lowry acids and bases bronsted lowry is played to a certain degree parcel buffer action, thereby reach the effect that increases tablet stability.Its diffluent characteristic can be impelled the rapid disintegrate of tablet, and effervescent reaches the requirement of target level of product quality.In addition, this type of adjuvant generally has certain lubricity and cohesive, can reduce slice power, reduces the consumption of lubricant in the tablet formulation, to reach the generation of avoiding lid, sticking phenomenon.
The inventor finds, will treat that the tabletting material is refrigerated to uniform temperature (20～15 ℃) after, the viscosity of material obviously reduces, especially temperature of charge reduce to subzero after, the water of trace exists with solid state in the material, and the also obviously reduction of the viscosity of other material, can thoroughly solve the sticking problem.
The present invention is on the basis of water solublity effervescent tablet pharmaceutical formulation, utilize soda acid to mix water law fluidized granulation dry technology, form granule fast, soda acid is wrapped up, and utilize freezing pressed-disc technique, reduce the viscosity of material, thereby solve technology and quality problems in the effervescent tablet production process, its principle is different with present existing effervescent tablet pelletizing press sheet technology.
Effervescent tablet of the present invention can be selected according to the different of patient, disease and its Chinese medicine in use, and effervescent tablet of the present invention can be taken by doctor's advice, or each 1-3 sheet, every day 1～3 time.
Beneficial effect of the present invention is:
1, the present invention is based on water solublity effervescent tablet pharmaceutical formulation, mix water law fluidized granulation dry technology and freezing pressed-disc technique by soda acid, for effervescent tablet particularly the production preparation technique of Chinese medicine effervescent tablet provide new, had the prescription and the manufacturing process of general relatively significance of application.Can realize the industrialization production of Chinese medicine effervescent tablet.
2, effervescent tablet stay in grade of the present invention, quality does not change with the storage cycle.
3, effervescent tablet prescription of the present invention is one glass of transparent, that mouthfeel is good liquid behind the effervescent for the full water-soluble prescription, and clear and bright solution is given the good impression of people.
4, production technology is simple, and operating process is simplified, and has reduced the production input of artificial, equipment etc.; The production favorable reproducibility.
5, by the accessory formula screening, the tablet hardness of compacting is good, and the quality densification is not easy powder delivery and falls slag; The surface is moist, appearance looks elegant.
The specific embodiment
The present invention is further illustrated below in conjunction with specific embodiment, but not as limitation of the present invention.
Embodiment 1: isatis root effervescence tablet
1, the extraction of extract dry powder:
Get Radix Isatidis and decoct with water 2 times, 2 hours for the first time, 1 hour for the second time, merge decoction liquor, filter, filtrate is concentrated into relative density 1.20 (50 ℃), adds 95% ethanol and makes that to contain the alcohol amount be 60%, leave standstill and make precipitation, get supernatant, reclaim ethanol, be condensed into the thick paste shape to relative density 1.20～1.25 (50～60 ℃), 70 ℃ of drying under reduced pressure then, dry extract is broken into fine powder, crosses 100 mesh sieves promptly.
2, the preparation of isatis root effervescence tablet:
(1) prescription:
(2) preparation technology
A. with 1540 parts of extract dry powder, 1155 parts of tartaric acid and sodium bicarbonate, 425 parts of xylitol, 45 parts aspartame, mixed sieving, standby as bed material.
B. with 135 parts PEG 6000, be dissolved in water, it is standby as slurry to sieve.
C. in fluidised bed granulator, the b slurry is sprayed onto on a bed material fluidized granulation, granulate, drying.
D. the dried granule of granulate is added 45 parts of leucines, mix homogeneously.
E. the above-mentioned material that mixes is refrigerated to 0～10 ℃, standby.
F. above-mentioned material is added tabletting in the tablet machine, sheet is heavily controlled about 4.5g, and hardness is at 8～10 kilograms.
G. with the tablet check of wrapping, packing is promptly taken 1, every day 3 times at every turn
The heavy 4.5g of sheet, 3 minutes disintegrations (80 ℃ of water temperatures).
Adopt the moistureproof combined bottle cap packing of the medicinal low density polyethylene (LDPE) of the medicinal high-density polyethylene bottle of oral administration solid/solid medicinal Aluminum Bottle and oral administration solid; Every bottled 10, under middle acceleration environment (30 ± 2 ℃ of temperature, relative humidity 65 ± 5%), quality was stable in 6 months, and room temperature following 24 months quality of condition that keep sample are stable.
Embodiment 2: the Salvia miltiorrhiza and Panax notoginseng effervescent tablet
1, the extraction of extract dry powder:
Get Radix Salviae Miltiorrhizae, Radix Notoginseng decocts with water 3 times, 2 hours for the first time, the 2nd, 3 time each one hour, merge decoction liquor, filter, filtrate concentrates, and adds the ethanol of 2 times of amounts 95%, leaves standstill 24 hours, filter, reclaim ethanol, be condensed into the thick paste shape to relative density 1.20～1.25 (50～60 ℃), be spray dried to fine powder then, cross 100 mesh sieves promptly.
2, the preparation of Salvia miltiorrhiza and Panax notoginseng effervescent tablet:
(1) prescription:
(2) preparation technology
A. with 50 parts of extract dry powder, 450 parts of citric acids, 400 parts of sodium bicarbonate, 650 parts of maltodextrins, mixed sieving, standby as bed material.
B. with 26 parts PVP K15, be dissolved in water, it is standby as slurry to sieve.
C. in fluidised bed granulator, the b slurry is sprayed onto on a bed material fluidized granulation, granulate, drying.
D. the dried granule of granulate is added 8 parts of sucralose, 16 parts of leucines, mix homogeneously.
E. the above-mentioned material that mixes is refrigerated to 0～10 ℃, standby.
F. above-mentioned material is added tabletting in the tablet machine, sheet is heavily controlled about 1.6g, and hardness is at 5～8 kilograms.
G. with the tablet check of wrapping, packing is promptly taken 1, every day 3 times at every turn
The heavy 1.6g of sheet, 4 minutes disintegrations.
Adopt the moistureproof combined bottle cap packing of the medicinal low density polyethylene (LDPE) of the medicinal high-density polyethylene bottle of oral administration solid/solid medicinal Aluminum Bottle and oral administration solid; Every bottled 10, under middle acceleration environment (30 ± 2 ℃ of temperature, relative humidity 65 ± 5%), quality was stable in 6 months, and room temperature following 24 months quality of condition that keep sample are stable.
Embodiment 3: the Flos Trollii effervescent tablet
1, the preparation of extract dry powder:
The depletion Flos Nelumbinis decocts with water 3 times, and each 1.5 hours, collecting decoction filtered, and filtrate decompression concentrates, and leaves standstill, and gets supernatant, filters, and filtrate is concentrated into relative density 1.20-1.25 (50 ℃), and 70 ℃ of drying under reduced pressure, dry extract are broken into 100 order fine powders.
2, the preparation of Flos Trollii effervescent tablet:
(1) prescription:
(2) preparation technology:
A. with 1350 parts of extract dry powder, 750 parts of tartaric acid and sodium bicarbonate, 197 parts of xylitol, 25 parts aspartame, mixed sieving, standby as bed material.
B. with 96 parts PEG 6000, be dissolved in water, it is standby as slurry to sieve.
C. in fluidised bed granulator, the b slurry is sprayed onto on a bed material fluidized granulation, granulate, drying.
D. the dried granule of granulate is added 32 parts of leucines, mix homogeneously.
E. the above-mentioned material that mixes is refrigerated to 0～10 ℃, standby.
F. above-mentioned material is added tabletting in the tablet machine, sheet is heavily controlled about 3.2g, and hardness is at 6～9 kilograms.
G. with the tablet check of wrapping, packing is promptly taken 1, every day 3 times at every turn
The heavy 3.2g of sheet, 5 minutes disintegrations (80 ℃ of water temperatures).
Adopt the moistureproof combined bottle cap packing of the medicinal low density polyethylene (LDPE) of the medicinal high-density polyethylene bottle of oral administration solid/solid medicinal Aluminum Bottle and oral administration solid; Every bottled 10, under middle acceleration environment (30 ± 2 ℃ of temperature, relative humidity 65 ± 5%), quality was stable in 6 months, and room temperature following 24 months quality of condition that keep sample are stable.
Embodiment 4 ANTIWEI effervescent tablets
1, the extraction of extract dry powder:
Get Rhizoma Imperatae, Radix Puerariae (open country), Semen Armeniacae Amarum (stir-fry), Herba Ephedrae, Ramulus Cinnamomi, Rhizoma Zingiberis, each medical material of Radix Glycyrrhizae, water extraction is twice respectively, extracted respectively 30 minutes and 20 minutes, and filtered merging filtrate, after directly being concentrated into 1: 1, add 95% alcoholic solution and transfer to 60% concentration of alcohol precipitate with ethanol, left standstill 24 hours, filter, decompression recycling ethanol, being concentrated into density is D
60=1.20-1.25, extractum.Vacuum drying is ground into fine powder then, crosses 100 mesh sieves promptly.
2, the preparation of ANTIWEI effervescent tablet:
(1) prescription:
(2) preparation technology
A. with 1220 parts of extract dry powder, 670 parts of citric acids, 300 parts of sodium bicarbonate, 858 parts of maltodextrins, mixed sieving, standby as bed material.
B. with 108 parts PEG 6000, be dissolved in water, it is standby as slurry to sieve.
C. in fluidised bed granulator, the b slurry is sprayed onto on a bed material fluidized granulation, granulate, drying.
D. the dried granule of granulate is added 12 parts of sucralose, 32 parts of leucines, mix homogeneously.
E. the above-mentioned material that mixes is refrigerated to 0～10 ℃, standby.
F. above-mentioned material is added tabletting in the tablet machine, sheet is heavily controlled about 3.2g, and hardness is at 7～9 kilograms.
G. with the tablet check of wrapping, packing is promptly taken 1, every day 3 times at every turn
The heavy 3.2g of sheet, 4 minutes disintegrations (80 ℃ of water temperatures).
Adopt the moistureproof combined bottle cap packing of the medicinal low density polyethylene (LDPE) of the medicinal high-density polyethylene bottle of oral administration solid/solid medicinal Aluminum Bottle and oral administration solid; Every bottled 10, under middle acceleration environment (30 ± 2 ℃ of temperature, relative humidity 65 ± 5%), quality was stable in 6 months, and room temperature following 24 months quality of condition that keep sample are stable.
Embodiment 5 vitamin C effervescent tablets
1, the processing of crude drug:
Get the vitamin C crystal, be ground into fine powder, cross 80 mesh sieves promptly.
2, the preparation of ANTIWEI effervescent tablet:
(1) prescription:
(2) preparation technology
A. with 1000 parts of vitamin C fine powders, 450 parts of citric acids, 600 parts of sodium bicarbonate, 818 portions of mannitol, mixed sieving, standby as bed material.
B. with being dissolved in water of 6000,2 parts of beta-carotene of PEG of 90 parts, it is standby as slurry to sieve.
C. in fluidised bed granulator, the b slurry is sprayed onto on a bed material fluidized granulation, granulate, drying.
D. the dried granule of granulate is added 10 parts of sucralose, 30 parts of leucines, mix homogeneously.
E. the above-mentioned material that mixes is refrigerated to 0～10 ℃, standby.
F. above-mentioned material is added tabletting in the tablet machine, sheet is heavily controlled about 3.0g, and hardness is at 7～9 kilograms.
G. with the tablet check of wrapping, packing is promptly taken 1, every day 3 times at every turn
The heavy 3.0g of sheet, 5 minutes disintegrations.
Adopt the moistureproof combined bottle cap packing of the medicinal low density polyethylene (LDPE) of the medicinal high-density polyethylene bottle of oral administration solid/solid medicinal Aluminum Bottle and oral administration solid; Every bottled 10, under middle acceleration environment (30 ± 2 ℃ of temperature, relative humidity 65 ± 5%), quality was stable in 6 months, and room temperature following 24 months quality of condition that keep sample are stable.
Embodiment 6 vitamin C effervescent tablets
Preparation method is with embodiment 1
Embodiment 7 vitamin C effervescent tablets
Preparation method is with embodiment 1
Embodiment 8
Process among the above embodiment and traditional pressed-disc technique compare, and the effervescent tablet that traditional pressed disc method obtains exists pitted skin and sticking phenomenon, and present embodiment does not then have.
Embodiment 9
Prescription among the above embodiment and the conventional formulation that does not add maltodextrin, xylitol or mannitol compare, and the effervescent tablet that conventional formulation obtains exists pitted skin and sticking phenomenon, and present embodiment does not then have.
Claims (10)
1. the preparation method of an oral administration effervescing sheet; comprise mixed material; granulate; granulate; the step of tabletting; it is characterized in that described method comprises the atomize fine powder mixing granulation of back and compositions such as other soda acids of aqueous binder in fluidised bed granulator, and with the step of the freezing back of the granule that makes tabletting.
2. the preparation method of claim 1 is characterized in that, adopts following steps:
It is (1) crude drug and filler, effervescent, correctives and lubricant pulverizing is standby for fine powder,
It is (2) adjuvant mix homogeneously such as crude drug and filler, effervescent is standby,
It is (3) with binding agent and strong toner water dissolving becoming aqueous solution, standby after filtering,
(4) in fluidised bed granulator, binding agent is atomized afterwards and the fine powder mix homogeneously in the step (2), granulate, standby,
(5) with the particle drying in the step (4), granulate is standby,
(6) with granule and correctives in the step (5), mix lubricant is evenly standby,
It is (7) the freezing back of the mixture in the step (6) is standby,
(8) mixture in the step (7) is pressed into tablet.
3. the preparation method of claim 2 is characterized in that, wherein,
In the step (1), described crude drug and filler, effervescent, correctives and lubricant are pulverized to fine powder is 30～120 orders,
In the step (2), crude drug mixes with adjuvants such as filler, effervescents and can carry out in the machine or carry out in stream flower beds granulator total mixing,
In the step (3), binding agent and the dissolving of strong toner water are become aqueous solution as binding agent, or select cold water or hot water dissolving for use, making becomes clear solutions, and the concentration of solution is 10～35%,
In the step (4); in fluidised bed granulator with in the fine powder mix homogeneously process in binding agent atomizing back and the step (2); fine powder in the step (2) is the motion of fluidisation attitude in fluidised bed granulator; binding agent is transported to binding agent in the fluid bed by equipment such as peristaltic pump or screw pumps; binding agent is transported to when passing through spray gun in the fluid bed; under compressed-air actuated effect, be atomized into tiny droplet; atomizing pressure is 0.1～0.4MPa; in fluid bed; the binding agent that is atomized contacts with the fine powder of fluidisation attitude and forms granule, simultaneously under the effect of the air inducing of heating, and granule rapid draing; the air inducing temperature is 30～60 ℃
Particulate dry fluid bed drying or the vacuum drying of adopting in the step (5), temperature is 40～70 ℃, vacuum is for being not less than 0.08MPa, granulate can select granulate pulverizer or oscillating granulator granulate for use, can sieve afterwards to the oversize granulate,
Granule and correctives in the step (6), mix lubricant is carried out in mixer, and always doing time is 5 minutes,
Mixture freezing means mixture and as in refrigerator-freezer or the cold closet material temperature to be reduced in the step (7), and material temperature is-20～15 ℃,
Mixture is pressed into tablet in the step (8), is meant to pass through pressure on tablet machine, and material is pressed into difform tablet, and general sheet weighs 1～5g/ sheet, and hardness is 5～10KN.
4. the preparation method of claim 3 is characterized in that, wherein,
In the step (1), described fine powder is 80～100 orders,
In the step (3), the concentration of solution is 25～30%, and filtering the order number is 100 orders,
In the step (4), atomizing pressure is 0.25～0.35MPa, and the air inducing temperature is 35～50 ℃,
Baking temperature is 40～65 ℃ in the step (5), and vacuum is for being not less than 0.085MPa, and arrangement order number is 10 orders,
The refrigerated temperature of mixture is-10～10 ℃ in the step (7).
5. the preparation method of claim 1 is characterized in that, wherein,
Fine powder effervescent described in the step (1), correctives are 80 orders, and lubricant is 120 orders.
6. an effervescent tablet pharmaceutical composition is characterized in that, its prescription is as follows:
7. the pharmaceutical composition of claim 6 is characterized in that,
Wherein:
Described active constituents of medicine is water miscible chemical medicine or Chinese medicine extract,
Described filler is a water-soluble material, and is easily molten in water, is selected from polymerization sugar, sucrose, and xylitol, mannitol, sorbitol, lactose, maltodextrin, anhydrous glucose, sodium chloride and their combination,
Described effervescent is that organic acid and carbonic acid or the bicarbonate that acid-base reaction produces carbon dioxide takes place in water, organic acid is selected from citric acid, tartaric acid, fumaric acid, malic acid, succinic acid etc., carbonic acid or bicarbonate are selected from potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate
Described binding agent is selected from PVP K30, PVP K15, PEG 6000, PEG 4000, HPMC E5,
Described flavoring is rectified color and is pigment, sweeting agent and the essence that makes the solution behind tablet and the tablet effervescent have good color and mouthfeel, be selected from lemon yellow, sunset yellow, bata-carotene, aspartame, steviosin, sucralose, Fructus Citri sinensis flavor essence, fresh milk essence
Described lubricant is selected from stearic acid, stearate, sodium stearyl fumarate, leucine, PEG 6000, sodium benzoate, sodium lauryl sulphate, hydrogenated vegetable oil.
8. the pharmaceutical composition of claim 7 is characterized in that,
Wherein:
Described filler is maltodextrin, xylitol, the combination of mannitol,
Described effervescent is selected from citric acid, tartaric acid; Sodium bicarbonate, its weight portion are 30～55,
Described binding agent is selected from PVP K15, PEG 6000,
Described flavoring is rectified toner and is selected from bata-carotene, aspartame, sucralose, Fructus Citri sinensis flavor essence, and its weight portion is 0.3～2,
Described lubricant is selected from stearate, sodium stearyl fumarate, leucine, PEG 6000.
9. the pharmaceutical composition of claim 8 is characterized in that,
Wherein:
Described filler is selected from maltodextrin, xylitol or mannitol, and its weight portion is 5～50,
Described effervescent is selected from sodium bicarbonate, and its weight portion is 30～55,
Described binding agent is selected from PVP K15, PEG 6000, and its weight portion is 1.5～3,
Described flavoring is rectified toner and is selected from bata-carotene, aspartame, sucralose, Fructus Citri sinensis flavor essence, and its weight portion is 0.3～1,
Described lubricant is selected from leucine, PEG 6000, and its weight portion is 0.5～1.
10. the pharmaceutical composition of claim 9 is characterized in that,
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