CN104622825A - Azithromycin dispersible tablet - Google Patents
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Abstract
The invention relates to an azithromycin dispersible tablet and a preparation method thereof. The azithromycin dispersible tablet is prepared by the following steps: by adopting a fluid bed bottom spraying technology, coating azithromycin by using a suspension of calcium carbonate and a water-insoluble macromolecular polymer to prepare an azithromycin microcapsule; and then uniformly mixing the azithromycin microcapsule with other pharmaceutically acceptable auxiliary materials of the azithromycin and tabletting, wherein the water-insoluble macromolecular polymer is selected from one or more of acrylic resin, ethyecellulose and hydroxypropyl methylcellulose phthalate. Compared with the prior art, the azithromycin dispersible tablet disclosed by the invention has the advantages of good taste, fast dissolution and simple preparation process.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to a kind of Azithromycin dispersible tablet.
Background technology
Azithromycin (Azithromycin) is white or off-white color crystalline powder, odorless, bitter in the mouth, micro-have draw moist, be soluble in methanol, acetone, chloroform, dehydrated alcohol or dilute hydrochloric acid, almost insoluble in water.Structural formula is as follows:
Molecular formula: C
38h
72n
2o
12
Molecular weight: 749.00
Azithromycin is semisynthetic 15 membered macrolide antibiotic, it is a kind of broad ectrum antibiotic obtained after modifying in erythromycin structure, be applicable to the sexually transmitted disease caused by the respiratory tract caused by sensitive organism, skin soft-tissue infection and chlamydia, pneumonia, ear infection and sexually transmitted disease (STD) can also be treated except treatment bronchitis, its mechanism of action is identical with erythromycin, mainly be combined with the 50S subunit of bacterial ribosome, suppress the albumen synthesis depending on RNA.
Azithromycin concentrates in epithelial cell, fibroblast, macrophage, mononuclear cell and neutrophil cell.In vitro study shows, after hatching 1h in cell/and the ratio of EC is greater than 30.Azithromycin has good pharmaco-kinetic properties, blood and tissue concentration high, and phase of declining long (12 ~ 14h), administration number of times few (every day 1 ~ 2 time), untoward reaction is few.
The dosage form of azithromycin medicine mainly comprises conventional tablet, dispersible tablet, granule, capsule, injection etc.Azithromycin has obvious bitterness, and coated tablet, capsule can cover taste preferably, but is not suitable for children's and has the patient of dysphagia to use.Dispersible tablet can be swallowed, be added to the water be uniformly dispersed after take and suck clothes, relative to conventional tablet, capsule etc., there is taking convenience, disintegrate is rapid, absorption is fast and bioavailability high, have convenient storage, the not easily advantage such as moisture absorption, good stability that granule, dry suspension etc. are not available simultaneously concurrently, be applicable to very much old man child and use.But the same granule of dispersible tablet, dry suspension are the same, be often difficult to solve sensory issues, particularly as the medicine that azithromycin bitterness extremely weighs.
Azithromycin has obvious bitterness, therefore needs to carry out taste masking in production process, especially for the solid preparation of dispersion before taking, as dispersible tablet, oral cavity disintegration tablet, dry suspension.Conventional taste masking technology has: add a large amount of sweeting agents, coating, microencapsulation, cyclodextrin inclusion compound, formation complex, reduce medicine dissolubility in the oral cavity, add blocker and delay drug diffusion etc.
Patent CN101129398A, patent CN102973529A, patent CN103040778A disclose Azithromycin dispersible tablet, all do not carry out taste masking, medicine mouthfeel extreme difference.
Patent CN100490816A, patent CN100484530A, patent CN102824311A, patent CN 103655496A, patent CN103784415A etc. use the sweeting agent of high concentration or the combination of multiple sweeting agent to carry out taste masking, but traditional sweeting agent cannot cover the taste of the azithromycin with strong bitterness effectively, and use sweeting agent can bring side effect undoubtedly in high concentration.
Patent CN102895203A discloses a kind of preparation method of Azithromycin dispersible tablet, and tablet prepared by this invention adopts cellulose acetate, polyacrylic resin Ⅲ coating, and mouthfeel of directly swallowing is better; If but take after dispersion, the effect of taste masking only cannot be reached by the sweeting agent in granule.
Patent CN101926774A reduces azithromycin dissolution degree by hexadecanol and adds a large amount of sweeting agent, orange flavor taste masking, and can alleviate the bitterness of azithromycin to a certain extent, but can not significantly improve, mouthfeel is still poor, and have impact on the stripping of medicine.
Patent CN102018679A carrys out taste masking with the dispersants such as the Kaolin of porosity characteristic, microcrystalline Cellulose and the blocker that can form gel in water, can to slow down to a certain extent the diffusion of azithromycin bitterness, but fundamentally can not cover bitterness, but also cause drug-eluting slack-off, stripping 93% in 45 minutes.
Patent CN101744773A discloses a kind of preparation method of bitter-free azithromycin granular composite, adopt the granulation of azithromycin gelatin solution, dry, pulverizing, add in sodium chloride solution, be prepared into clathrate, add sucrose, pregelatinized Starch, carboxymethyl starch sodium, polyvidone aqueous solution, orange flavor, make azithromycin granule.The carrier material that this invention adopts is gelatin, sodium chloride is water solublity, and when taking, carrier dissolves rapidly, and namely drug release produces stronger bitterness.
Open oral azithromycin resin suspension of patent CN1985842A and preparation method thereof, by azithromycin and ion exchange resin are reacted, form drug-resin complex and cover bitterness, but the release of medicine needs the process of ion exchange again, drug release is slower.
Patent CN1813683A discloses dry suspension of a kind of azithromycin and preparation method thereof, with Eudragit E100 or No. four aqueous acrylic resin dispersion for binding agent, the granulation of fluid bed top spray is carried out to the mixture of azithromycin and other adjuvant, the Azithromycin for Suspension then mixed with other adjuvant.As everyone knows, fluid bed top spray technology is typical granulating process, cannot reach and wrap up completely azithromycin, the main taste masking technology of this invention also derives from the retardance that the large high molecular polymer of viscosity a large amount of in prescription spreads bitterness, can not cover bitterness completely.
Open Azithromycin orally disintegrating tablets of patent CN101112379A and preparation method thereof, with Eudragit E 100 and acrylic resin NE30D for coating material, take silicon dioxide as antiplastering aid, spray coating in the end is carried out, then with other adjuvant mixed pressuring plate to the mixed powder of azithromycin and silicon dioxide.This invention has good taste masking effect, but drug-eluting is comparatively slow, has certain slow release effect.
Patent CN101416945A mono-kind prepares the method for azithromycin fine granule, adopts molten for azithromycin that then spraying dry obtains azithromycin microcapsule with the alcoholic solution of acrylic resin, is then mixed with other sweeting agent.Because employing the method can not reach the parcel completely to azithromycin, the raw material of microcapsule outer layer adheres still has larger bitterness, and taste masking effect is poor.
Patent CN 103054813A provides Azithromycin oral sustained-release dry suspension and preparation method thereof, and azithromycin is prepared into micropill, wraps to cover bitterness layer and slow release layer is made, and mouthfeel is better, has good slow release effect.But azithromycin long half time, takes number of times few, and there is good antibacterial after effect, without the need to making slow releasing preparation.
Patent CN 101966156A relates to a kind of Azithromycin for suspension and preparation method thereof; mixed by azithromycin granule and sugared granule; wherein azithromycin granule is the microcapsule adopting xanthan gum, fibroin albumen etc. to be prepared by complex coacervation; there is good taste masking effect; but drug release is slow; complicated process of preparation simultaneously, and employ a large amount of organic solvents.
Inventor finds by carrying out deep analysis to prior art, and preparing azithromycin microcapsule is the best means covering bitter taste of drug, but also exists: 1. encapsulating not exclusively, can not cover bitterness completely; 2. the problem that drug release is slack-off; The problems such as 3. preparation technology is too complicated.
Therefore, develop a kind of mouthfeel good, stripping is fast, and the azithromycin formulations that preparation is simple is extremely important.
Summary of the invention
In order to develop, a kind of mouthfeel is good, stripping is fast, the simple Azithromycin dispersible tablet of preparation technology, inventors performed a large amount of tests.
Inventor consider dispersible tablet common take mode comprise swallow, be added to the water be uniformly dispersed after take and suck clothes, require high to the mouthfeel of medicine.Because azithromycin is extremely bitter, want to ensure that Azithromycin dispersible tablet has good mouthfeel, guarantee medicine in the oral cavity or disperse in water time be most effective method without drug release.And want to ensure that Azithromycin dispersible tablet stripping is fast, will guarantee that medicine discharges fast in gastric acid.Azithromycin acrylic resin IV is first it is envisioned that carried out powder coating by inventor, dissolves because acrylic resin IV is not dissolved in sour environment in water, just in time can meet above-mentioned requirements.But find when coating weight gain can meet taste masking requirement in test, can not ensure that medicine discharges fast in gastric acid environment.Analysis reason is, drug powder specific surface area is large, and coating weight gain that must be larger just can reach taste masking requirement, and therefore the thickness of coatings increases, and is unfavorable for rapid solution, causes drug release partially slow.
Inventor attempts disintegrating agent to mix with azithromycin powder coating afterwards, but the rate of release of medicine depends primarily on the speed that coating membrane dissolves in gastric acid, disintegrating agent to add impact less.
Inventor attempts again azithromycin to be prepared into coating after granule or piller; so relatively less coating weight gain reaches taste masking requirement; but coated granule or piller are comparatively large due to particle diameter, can be broken in tableting processes, cause medicine to reappear release phenomenon in water.
Inventor attempts in coating material, add the stripping that porogen improves medicine, but is water soluble ingredient due to porogen, and result causes taste masking effect poor.Unexpectedly, inventor expects adding calcium carbonate in coating material, generates solubility calcium chloride, serve the effect of porogen because calcium carbonate reacts with gastric acid in gastric acid environment, the expansion of the carbon dioxide simultaneously produced can impel coating membrane to break sooner, impels medicine to discharge fast.Inventor, by a large amount of tests, further determined that the ratio of acrylic resin IV and calcium carbonate in coating membrane.
Further, acrylic resin in coating membrane IV is changed into all undissolved high molecular polymer in other water, in acid by inventor, due to the utilization of wherein calcium carbonate, also can reach the object of taste masking and rapid release.Inventor, by further test, determines kind and the consumption of usable polymers.
Particularly, technical scheme of the present invention is as follows:
A kind of Azithromycin dispersible tablet, by azithromycin dressing microcapsule, and other pharmaceutically acceptable adjuvant mix homogeneously, tabletting forms, and coating material is the water-insoluble high molecular polymer containing micronization calcium carbonate.
Described Azithromycin dispersible tablet, is prepared by the following method:
1. water-insoluble high molecular polymer is added in appropriate concentration ethanol and dissolve, add micronization calcium carbonate and stir, obtain coating suspensions;
2. sieve 60 ~ 80 object azithromycins, add in fluid bed, adopt the method for end spray coating to spray into the coating suspensions coating 1. prepared, obtain azithromycin dressing microcapsule;
3. sieve 30 ~ 60 object azithromycin dressing microcapsules to mix homogeneously with other pharmaceutically acceptable adjuvant, tabletting, to obtain final product.
Described Azithromycin dispersible tablet, water-insoluble high molecular polymer is selected from one or more in acrylic resin, ethyl cellulose, HP-55.
Described Azithromycin dispersible tablet, water-insoluble high molecular polymer is acrylic resin IV.
Described Azithromycin dispersible tablet, the weight ratio of azithromycin and water-insoluble high molecular polymer is 1 ︰ 0.2 ~ 0.4, is preferably 1 ︰ 0.3.
Described Azithromycin dispersible tablet, the weight ratio of water-insoluble high molecular polymer and calcium carbonate is 1 ︰ 0.3 ~ 0.5, is preferably 1 ︰ 0.4.
Described Azithromycin dispersible tablet, other pharmaceutically acceptable adjuvant comprises filler, disintegrating agent, lubricant and correctives; Wherein, filler is selected from one or more in microcrystalline Cellulose, lactose, mannitol, sorbitol; Disintegrating agent is selected from one or more in polyvinylpolypyrrolidone, polacrilin potassium, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose; Lubricant is selected from one or more in magnesium stearate, sodium stearyl fumarate, Pulvis Talci, zinc stearate, silicon dioxide; Correctives is selected from one or more in saccharin sodium, aspartame, sucralose, steviosin, acesulfame potassium and various taste essence.
The present invention has relative to prior art that mouthfeel is good, stripping is fast, the simple advantage of preparation technology.
Detailed description of the invention
By following examples, Azithromycin dispersible tablet of the present invention is described further, but the present invention is not limited in following examples.The simultaneously apparent change made according to the present invention of those of ordinary skill in the art and modification are also contained within the scope of the invention.
Embodiment 1
Preparation method:
1. ethyl cellulose is added in ethanol and dissolve, add micronization calcium carbonate and stir, obtain coating suspensions;
2. sieve 60 ~ 80 object azithromycins, add in fluid bed, adopt the method for end spray coating to spray into the coating suspensions coating 1. prepared, obtain azithromycin dressing microcapsule;
3. sieve 30 ~ 60 object azithromycin dressing microcapsules to mix homogeneously with microcrystalline Cellulose, lactose, silicon dioxide, polacrilin potassium, sodium stearyl fumarate, saccharin sodium, orange taste essence, tabletting, to obtain final product.
Embodiment 2
Preparation method:
1. acrylic resin I is added in ethanol and dissolve, add micronization calcium carbonate and stir, obtain coating suspensions;
2. sieve 60 ~ 80 object azithromycins, add in fluid bed, adopt the method for end spray coating to spray into the coating suspensions coating 1. prepared, obtain azithromycin dressing microcapsule;
3. sieve 30 ~ 60 object azithromycin dressing microcapsules to mix homogeneously with microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, honey peach taste essence, zinc stearate, tabletting, to obtain final product.
Embodiment 3
Preparation method:
1. acrylic resin IV is added in ethanol and dissolve, add micronization calcium carbonate and stir, obtain coating suspensions;
2. sieve 60 ~ 80 object azithromycins, add in fluid bed, adopt the method for end spray coating to spray into the coating suspensions coating 1. prepared, obtain azithromycin dressing microcapsule;
3. sieve 30 ~ 60 object azithromycin dressing microcapsules to mix homogeneously with mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, strawberry flavor essence, magnesium stearate, tabletting, to obtain final product.
Embodiment 4
Preparation method:
1. acrylic resin III is added in ethanol and dissolve, add micronization calcium carbonate and stir, obtain coating suspensions;
2. sieve 60 ~ 80 object azithromycins, add in fluid bed, adopt the method for end spray coating to spray into the coating suspensions coating 1. prepared, obtain azithromycin dressing microcapsule;
3. sieve 30 ~ 60 object azithromycin dressing microcapsules to mix homogeneously with lactose, cross-linking sodium carboxymethyl cellulose, acesulfame potassium, Fructus Citri sinensis taste essence, magnesium stearate, tabletting, to obtain final product.
Embodiment 5
Preparation method:
1. HP-55 is added in 80% ethanol and dissolve, add micronization calcium carbonate and stir, obtain coating suspensions;
2. sieve 60 ~ 80 object azithromycins, add in fluid bed, adopt the method for end spray coating to spray into the coating suspensions coating 1. prepared, obtain azithromycin dressing microcapsule;
3. sieve 30 ~ 60 object azithromycin dressing microcapsules to mix homogeneously with sorbitol, carboxymethyl starch sodium, polacrilin potassium, sucralose, hami melon taste essence, Pulvis Talci, zinc stearate, tabletting, to obtain final product.
Embodiment 6
Preparation method:
1. acrylic resin IV is added in ethanol and dissolve, add micronization calcium carbonate and stir, obtain coating suspensions;
2. sieve 60 ~ 80 object azithromycins, add in fluid bed, adopt the method for end spray coating to spray into the coating suspensions coating 1. prepared, obtain azithromycin dressing microcapsule;
3. sieve 30 ~ 60 object azithromycin dressing microcapsules to mix homogeneously with mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, strawberry flavor essence, magnesium stearate, tabletting, to obtain final product.
Comparative example 1
Preparation method:
1. acrylic resin IV is added in ethanol and dissolve, for subsequent use;
2. sieve 60 ~ 80 object azithromycins, add in fluid bed, adopt the method for end spray coating to spray into the coating solution coating 1. prepared, obtain azithromycin dressing microcapsule;
3. sieve 30 ~ 60 object azithromycin dressing microcapsules to mix homogeneously with mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, strawberry flavor essence, magnesium stearate, tabletting, to obtain final product.
Comparative example 2
Preparation method:
1. hydroxypropyl cellulose is added in ethanol and dissolve, add micronization calcium carbonate and stir, obtain coating suspensions;
2. sieve 60 ~ 80 object azithromycins, add in fluid bed, adopt the method for end spray coating to spray into the coating suspensions coating 1. prepared, obtain azithromycin dressing microcapsule;
3. sieve 30 ~ 60 object azithromycin dressing microcapsules to mix homogeneously with mannitol, microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, strawberry flavor essence, magnesium stearate, tabletting, to obtain final product.
Comparative example 3
Preparation method:
1. acrylic resin I is added in ethanol and dissolve, for subsequent use;
2. sieve 60 ~ 80 object azithromycins, add in fluid bed, adopt the method for end spray coating to spray into the coating solution coating 1. prepared, obtain azithromycin dressing microcapsule;
3. sieve 30 ~ 60 object azithromycin dressing microcapsules to mix homogeneously with microcrystalline Cellulose, polyvinylpolypyrrolidone, aspartame, honey peach taste essence, zinc stearate, tabletting, to obtain final product.
The preparation of comparative example 4 azithromycin fine granule
7.5kg polyacrylic resin is immersed in stirring and dissolving in 58.3kg ethanol, filtered with 200 eye mesh screens after all dissolving through 2 ~ 3 days, then drop into 2.5kg Azithromycin Raw Material to stir, be uniformly dissolved after 1 day, carry out spraying dry, inlet temperature is 100 ~ 120 DEG C, outlet temperature is 65 ~ 75 DEG C, shower nozzle speed change is 280 ~ 310Hz, feeding viarable speed is 6.00 ~ 12.00Hz, collect microcapsule, sieve microcapsule 100 orders, and sucrose sieves 120 orders, and essence sieves 80 orders.Microcapsule and adjuvant are granulated and is drying to obtain.
Comparative example 5 Azithromycin orally disintegrating tablets
Preparation technology:
Eudragit E 100 is dissolved in ethanol, adds sieved acrylic resin NE30D solid dispersion, be stirred to and dissolve completely; Then silicon dioxide is added, Keep agitation 1 ~ 2 hour; The Azithromycin Raw Material be sieved and silicon dioxide are put into end spray fluidized-bed coating machine, flow down heating at air and coating suspensions is injected on raw material, inlet temperature: 50 DEG C, temperature of charge: 28 DEG C, whiff pressure: 0.15Mpa, hydrojet speed: 6g/ minute, after enrobing processes completes, dry 2 hours; Mannitol, crospolyvinylpyrrolidone, aspartame and flavoring banana essence are crossed respectively 0.5mm to sieve, pour in three-phase mixer and mix 30 minutes, the preliminary mixture that the azithromycin granule of coating and previous step mix is poured in three-phase mixer and mixes 30 minutes, add magnesium stearate again, mix 1 ~ 2 minute, pour in the hopper of tablet machine by mixed material, tabletting obtains.
The preparation of comparative example 6 Azithromycin for Suspension
Preparation technology:
Preparation 10% is strange E100 solution especially; Azithromycin, sucrose, mannitol, sodium phosphate are crossed 80 mesh sieves and are put in fluid bed top spray and mix, and inlet temperature is 40 DEG C, and pressure is 0.25Mpa; Spray especially strange E100 solution; Top spray is dry, and inlet temperature is 50 DEG C, and drying time is 70 minutes; Granulate: take residue sucrose and the granulation of mannitol mix homogeneously alcoholic solution, dry granulate, screening gained granule, selects 30 mesh sieves; Mixing: coating raw material and sucrose and mannitol particles press equal increments method manual mixing, and then with method and the also drying of remaining supplementary material mix homogeneously.
Comparative example 7 Azithromycin dispersible tablet
Preparation method:
First azithromycin is crossed 40 mesh sieves, adjuvant directly sieves with 100 eye mesh screens.Then take azithromycin by recipe quantity, add the carboxymethylstach sodium of cross-linking sodium carboxymethyl cellulose, microcrystalline Cellulose and 3/4 amount, fully mixing 5 minutes, adds the purified water of main ingredient weight about 40%, makes soft material.Inspection soft material quality: make it hands and pinch agglomerating, the namely loose of stranding is advisable.Get above-mentioned soft material to be placed in oscillating granulator and to be granulated by 20 order nylon mesh.Wet grain drying, makes dry granule water content reach prescribed limit.General baking temperature: inlet temperature 60 ~ 65 DEG C, material temperature: 55 ~ 60 DEG C, temperature 30 ~ 35 DEG C during discharging.Dried particles is placed in spin vibration sieve 20 eye mesh screen granulate.Finally granulate granule is placed in V-Mixer, adds magnesium stearate and the silicon dioxide of residue 1/4 amount carboxymethylstach sodium and recipe quantity, mixing, incorporation time is 30 minutes.With special-shaped punch die tabletting after intermediate inspection, THICKNESS CONTROL at 5.2mm, pressure.Pack after Bao Pin is up to the standards.
Checking example 1 jitter time measures
Jitter time measures: adopt testing fixture disintegration, the sieve aperture internal diameter of stainless steel cloth is 710 μm, and water temperature is 15 ~ 25 DEG C; Get test sample 6, record 6 whole disintegrates and by time of screen cloth.The results detailed in Table 1.
Checking example 2 dissolution determination
Chromatographic condition: be filler with octadecylsilane chemically bonded silica; Be mobile phase with phosphate buffer (getting 0.05mol/L dipotassium hydrogen phosphate solution, the phosphoric acid solution adjust ph to 8.2 with adding 20%)-acetonitrile (45:55); Determined wavelength is 210nm.
Dissolution determination: get this product, according to dissolution method (Chinese Pharmacopoeia version in 2010 two annex XC second methods), with pH1.2 hydrochloric acid solution 900ml for dissolution medium, rotating speed is 75 turns per minute, operates in accordance with the law, through 15 minutes time, get solution appropriate, filter, get subsequent filtrate appropriate, the solution made about containing azithromycin 0.2mg in every lml is quantitatively diluted, as need testing solution with dissolution medium; Separately get azithromycin reference substance appropriate, accurately weighed, add ethanol in proper amount (every 2mg about adds ethanol lml) and make dissolving, add dissolution medium and quantitatively dilute the solution made about containing 0.2mg in every lml, product solution in contrast.Precision measures need testing solution and reference substance solution 50 μ l injection liquid chromatography, and record chromatogram, by external standard method with the stripping quantity of the every sheet of calculated by peak area.The results detailed in Table 1.
Checking example 3 medicine leak detection
Detect the amount of leakage of azithromycin in purified water, in order to prove the quality of taste masking effect, medicine discharges fewer in water, then mouthfeel is better.
Chromatographic condition is with checking example 2.
Drug leakage detects: get this product, according to dissolution method (Chinese Pharmacopoeia version in 2010 two annex XC second methods), with purified water 900ml for dissolution medium, rotating speed is 75 turns per minute, operates in accordance with the law, through 30 minutes time, get solution appropriate, filter, get subsequent filtrate appropriate, the solution made about containing azithromycin 0.2mg in every lml is quantitatively diluted, as need testing solution with dissolution medium; Separately get azithromycin reference substance appropriate, accurately weighed, add ethanol in proper amount (every 2mg about adds ethanol lml) and make dissolving, add dissolution medium and quantitatively dilute the solution made about containing 0.2mg in every lml, product solution in contrast.Precision measures need testing solution and reference substance solution 50 μ l injection liquid chromatography, and record chromatogram, by external standard method with the stripping quantity of the every sheet of calculated by peak area.The results detailed in Table 1.
The each embodiment effect of table 1 gathers
| Embodiment | Jitter time (S) | Mouthfeel | Dissolution (%) | Medicine amount of leakage (%) |
| Embodiment 1 | 63 | Well | 98.9 | 3.1 |
| Embodiment 2 | 50 | Well | 99.7 | 2.4 |
| Embodiment 3 | 55 | Well | 100.1 | 1.5 |
| Embodiment 4 | 67 | Well | 99.6 | 1.9 |
| Embodiment 5 | 80 | Well | 98.9 | 1.7 |
| Embodiment 6 | 68 | Well | 85.1 | 1.8 |
| Comparative example 1 | 75 | Well | 71.6 | 2.2 |
| Comparative example 2 | 90 | Extremely bitter | 98.5 | 99.2 |
| Comparative example 3 | 65 | Well | 4.5 | 6.1 |
| Comparative example 4 | Inapplicable | More bitter | 88.9 | 93.2 |
| Comparative example 5 | Inapplicable | Well | 62.3 | 8.5 |
| Comparative example 6 | Inapplicable | More bitter | 95.9 | 97.3 |
| Comparative example 7 | 85 | Extremely bitter | 98.1 | 98.9 |
From above result, embodiment 1 ~ 5 good mouthfeel, dispersion is fast, and in pH1.2 hydrochloric acid, the basic stripping of 15min is complete, and in water, 30min drug release is few, therefore, takes or puts into oral cavity and suck that to take mouthfeel all better after being added to the water dispersion.Embodiment 6, calcium carbonate consumption reduces relatively, and in acid, dissolution rate is slack-off, but calcium carbonate consumption cannot complete coating again too much.Comparative example 1 removes calcium carbonate on the basis of embodiment 3, and in acid, stripping is obviously slack-off, but acrylic resin IV is solvable in acid, and medicine can discharge for a long time completely.Comparative example 2 changes acrylic resin into water miscible hydroxypropyl cellulose, taste bad.Comparative example 3 removes calcium carbonate on the basis of embodiment 2, and acrylic resin I is insoluble in acid, in acid substantially molten not out.Comparative example 4-7 adopts prior art, and then spraying dry obtains azithromycin microcapsule to comparative example 4 with the alcoholic solution of acrylic resin by molten for azithromycin, is then mixed with other sweeting agent.Because employing the method can not reach the parcel completely to azithromycin, the raw material of microcapsule outer layer adheres still has larger bitterness, and taste masking effect is poor.Comparative example 5 for coating material, take silicon dioxide as antiplastering aid with Eudragit E 100 and acrylic resin NE30D, carries out end spray coating, then with other adjuvant mixed pressuring plate to the mixed powder of azithromycin and silicon dioxide.This invention has good taste masking effect, but drug-eluting is comparatively slow, has certain slow release effect.Comparative example 6 for binding agent, carries out the granulation of fluid bed top spray to the mixture of azithromycin and other adjuvant, the Azithromycin for Suspension then mixed with other adjuvant with Eudragit E100.As everyone knows, fluid bed top spray technology is typical granulating process, cannot reach and wrap up completely azithromycin, the main taste masking technology of this invention also derives from the retardance that the large high molecular polymer of viscosity a large amount of in prescription spreads bitterness, can not cover bitterness completely.Comparative example 7 does not carry out taste masking, mouthfeel extreme difference.
Claims (9)
1. an Azithromycin dispersible tablet, is characterized in that, by azithromycin dressing microcapsule, and other pharmaceutically acceptable adjuvant mix homogeneously, tabletting forms, and coating material is the water-insoluble high molecular polymer containing micronization calcium carbonate.
2. Azithromycin dispersible tablet as claimed in claim 1, is characterized in that, be prepared by the following method:
1. water-insoluble high molecular polymer is added in appropriate concentration ethanol and dissolve, add micronization calcium carbonate and stir, obtain coating suspensions;
2. sieve 60 ~ 80 object azithromycins, add in fluid bed, adopt the method for end spray coating to spray into the coating suspensions coating 1. prepared, obtain azithromycin dressing microcapsule;
3. sieve 30 ~ 60 object azithromycin dressing microcapsules to mix homogeneously with other pharmaceutically acceptable adjuvant, tabletting, to obtain final product.
3. Azithromycin dispersible tablet as claimed in claim 1, it is characterized in that, described water-insoluble high molecular polymer is selected from one or more in acrylic resin, ethyl cellulose, HP-55.
4. Azithromycin dispersible tablet as claimed in claim 1, it is characterized in that, described water-insoluble high molecular polymer is acrylic resin IV.
5. Azithromycin dispersible tablet as claimed in claim 1, it is characterized in that, the weight ratio of azithromycin and water-insoluble high molecular polymer is 1 ︰ 0.2 ~ 0.4.
6. Azithromycin dispersible tablet as claimed in claim 1, it is characterized in that, the weight ratio of azithromycin and water-insoluble high molecular polymer is 1 ︰ 0.3.
7. Azithromycin dispersible tablet as claimed in claim 1, it is characterized in that, the weight ratio of water-insoluble high molecular polymer and calcium carbonate is 1 ︰ 0.3 ~ 0.5.
8. Azithromycin dispersible tablet as claimed in claim 1, it is characterized in that, the weight ratio of water-insoluble high molecular polymer and calcium carbonate is 1 ︰ 0.4.
9. Azithromycin dispersible tablet as claimed in claim 1, it is characterized in that, other described pharmaceutically acceptable adjuvant comprises filler, disintegrating agent, lubricant and correctives; Wherein, filler is selected from one or more in microcrystalline Cellulose, lactose, mannitol, sorbitol; Disintegrating agent is selected from one or more in polyvinylpolypyrrolidone, polacrilin potassium, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose; Lubricant is selected from one or more in magnesium stearate, sodium stearyl fumarate, Pulvis Talci, zinc stearate, silicon dioxide; Correctives is selected from one or more in saccharin sodium, aspartame, sucralose, steviosin, acesulfame potassium and various taste essence.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104825419A (en) * | 2015-05-27 | 2015-08-12 | 浙江得恩德制药有限公司 | Low-moisture-absorption colloidal bismuth pectin capsule and preparation technology thereof |
| CN105012262A (en) * | 2015-08-20 | 2015-11-04 | 广东安诺药业股份有限公司 | Azithromycin dispersible tablets with bitterness covering function and preparation method of azithromycin dispersible tablets |
| CN110123788A (en) * | 2019-05-17 | 2019-08-16 | 南京望知星医药科技有限公司 | A kind of Azithromycin slow-release micro-capsule and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104825419A (en) * | 2015-05-27 | 2015-08-12 | 浙江得恩德制药有限公司 | Low-moisture-absorption colloidal bismuth pectin capsule and preparation technology thereof |
| CN104825419B (en) * | 2015-05-27 | 2017-11-21 | 浙江得恩德制药股份有限公司 | A kind of agent of low hygroscopicity Couoidal bismuth pectin capsules agent and its preparation technology |
| CN105012262A (en) * | 2015-08-20 | 2015-11-04 | 广东安诺药业股份有限公司 | Azithromycin dispersible tablets with bitterness covering function and preparation method of azithromycin dispersible tablets |
| CN105012262B (en) * | 2015-08-20 | 2018-04-13 | 广东安诺药业股份有限公司 | Cover Azithromycin dispersible tablet of bitter taste and preparation method thereof |
| CN110123788A (en) * | 2019-05-17 | 2019-08-16 | 南京望知星医药科技有限公司 | A kind of Azithromycin slow-release micro-capsule and preparation method thereof |
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Application publication date: 20150520 |