CN100484530C - Azithromycin mix suspension grain and method for preparing the same - Google Patents
Azithromycin mix suspension grain and method for preparing the same Download PDFInfo
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Abstract
The invention relates to an azithromycin suspension granule and a preparation method thereof. The invention adopts appropriate auxiliary materials and dosages thereof to prepare the azithromycin suspension granules by using an appropriate preparation method. The azithromycin suspension granule provided by the invention is characterized in that: the components of the azithromycin suspension granule is (by weight portion): azithromycin 100-250, sucrose 500-1250, starch 60-150, mannite 16-40, steviosin 20-50, appropriate ethanol with a mass percentage of 95 percent and appropriate coconut flavor. The azithromycin suspension granule provided by the invention tastes good and the bitterness thereof is effectively covered, thus ensuring the compliance of the sufferer to take the medicine; the azithromycin suspension granule also has the advantages of good suspension homogeneity, high formability and stability.
Description
Technical field
The present invention relates to a kind of Azithromycin mix suspension grain and preparation method thereof, belong to medical technical field.
Background technology
Azithromycin be off-white color crystalline powder, odorless, bitter in the mouth, little have draw moistly, more easily decompose under the acid condition.Its chemical name is: (2R, 3S, 4R, 5R, 8R, 10R, 11R, 12S, 13S, 14R)-13-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-nuclear-own pyrans glycosyl) oxygen]-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-seven methyl isophthalic acid 1-[[3,4,6-three deoxidations-3-(dimethylamino)-β-D-wood-own pyrans glycosyl] oxygen]-1-oxa--6-azacyclo-pentadecane-15-ketone.
Its structural formula is as follows:
Molecular formula: C
38H
72N
2O
12
Molecular weight: 749.00
The development of azithromycin starts from the discovery of the erythromycin of phase early 1950s, is the most frequently used clinically anti-infective, and to the infection that multiple sensitive strain causes, the treatment works well.Erythromycin is in clinical practice many decades.But unstable to acid because of it, blood concentration is low, dosage is big, to characteristics such as liver are toxic, so relevant scientist by its chemical constitution of transformation, develops a series of new derivative of macrolides.Azithromycin has, long half time stable to acid, and drug level height, evident in efficacy in infection site tissue and the cell, advantages such as safety and better tolerance.
Azithromycin reaches antibacterial action by suppressing ribosome 50s protein subunit matter surface.G-coccus, G-bacillus and anaerobe there is stronger antibacterial action.Antibacterial action to mucositis brinell ball bacterium, Neisseria gonorrhoeae, salmonella, shigella dysenteriae, pneumobacillus, Campylobacter, hemophilus influenza, legionella pneumophilia, aerogenesis folder film clostridium and anaerobic cocci is also strong than erythromycin.To pasteurella multocida, yersinia, mycoplasma pneumoniae, chlamydia psittaci, mycin spirillum, borrelia vincentii and organize entamoeba etc. that obvious effect is also arranged.Azithromycin also has the obvious sterilization effect to some antibacterial.Experiment shows, Azithromycin 4 is hour internal energy kills 99.9% hemophilus influenza fast, can kill that alveolar is huge has a liking for intracellular legionella pneumophilia, and erythromycin only has bacteriostasis.Observe from animal infection modal, azithromycin all presents bactericidal activity in the body to streptococcus pneumoniae, pneumobacillus, hemophilus influenza and escherichia coli etc. when high concentration.
Compare with other Macrolidees, azithromycin has the influenza bacillus of height, the activity of moraxelle catarrhalis, easily enter in the phagocyte such as tissue and neutrophilic granulocyte, macrophage, 1 logotype on the 1st got final product on the 3rd, advanced age, dosed administration routinely still when person and renal dysfunction seldom had characteristics such as interaction with other medicine as other Macrolidees.Azithromycin plays a significant role in the upper and lower respiratory infection diseases of treatment.Azithromycin in American-European pneumonia diagnosis and treatment guide as choice drug, in the community acquired pneumonia diagnosis and treatment guide of Japan then as the choice drug of atypical pneumonia.
Azithromycin can be absorbed by macrophage and assemble in cell, but azithromycin can not destroy the function of macrophage, and macrophage is transported to infection site with azithromycin, thereby the drug level in causing organizing is more than 100 times of serum Chinese medicine concentration.Ordinary preparation was taken the 0.5g azithromycin in first day, took the 0.25g azithromycin later every day, and the 5th day blood drug level is lower than the 5th day blood drug level of the disposable 2.0g of taking azithromycin.A kind of high dose release oral azithromycin preparation can be widely used in the single dose azithromycin treatment, and therefore obviously improves the compliance and the convenience of administration, is a kind of preparation with clinical meaning.
Disclose in the Chinese patent application 200510061861.1 that a kind of suitable dysphagia patien uses, stability is better, good absorbing, rapid-action, Azithromycin for Suspension that bioavailability is high, comprise azithromycin 0.1～20% in this dry suspension, lubricated fluidizer 1～10%, pH value regulator 0.1～10%, polymer binder 10～40%, sweeting agent 50～85% and fragrant correctives 0.5～15%.
Disclose a kind of Azithromycin slow-release dry suspension and preparation method thereof among the Chinese patent application 200610091077.X, the Azithromycin slow-release microsphere described in this application is to form with spray drying method for preparation; Wherein the capsule material of packaging medicine azithromycin can adopt medicinal macromolecule viscous material or macromolecule poorly soluble pharmaceutical adjuvant, as gelatin, arabic gum, carboxymethyl cellulose salt, hydroxypropyl emthylcellulose, ethyl cellulose or acrylate copolymer etc.; Be preferably the acrylate copolymer class.The dry suspension of the high dose release oral azithromycin of this application has obviously improved the compliance of administration and convenience, bioavailability height.
Shenzhen Zhijun Pharmaceutical Co., Ltd discloses a kind of oral azithromycin resin suspension and preparation method thereof in Chinese patent application 200610157604.2, the w/v component of each component is: per 100 milliliters contain azithromycin 0.25～4.0 gram, ion exchange resin 0.5～8.0 gram, all the other are water.Its preparation method: with azithromycin, mineral acid is or/and organic acid adds purified water; Add ion exchange resin, get mixed liquor; Suspending agent, surfactant and purified water are made suspension medium, add complexing of metal ion agent, antiseptic, correctives and coloring agent, mixing; Add mixed liquor.The present invention compared with prior art, azithromycin and ion exchange resin are carried out ion-exchange reactions, form drug-resin complex, ion exchange resin has been sheltered the bitterness of active constituents of medicine azithromycin wherein well, make it have good mouthfeel, and preparation method is simple, adopts ordinary preparation equipment to get final product, and is suitable for suitability for industrialized production.
Pfizer Products Inc discloses a kind of powder that is used for oral administration mixed suspension in Chinese patent application 200480020329.9, and oral administration mixed suspension prepared therefrom, it comprises the excipient of non-dihydrate azithromycin and the conversion of stable azithromycin, and azithromycin was by the conversion of a kind of form to another form when wherein said excipient had reduced in being in suspension.Also relate in this patent application and reduce the method that the non-dihydrate azithromycin form transforms in oral administration mixed suspension, it is to reduce the capillary reduction surface tension of aqueous carrier excipient by adding.And present patent application further relates to the method that reduces the non-dihydrate azithromycin conversion, and it is the viscosity by increase oral administration mixed suspension in unseasoned oral administration mixed suspension, and the viscosity that reduces oral administration mixed suspension in the oral administration mixed suspension of seasoning is arranged.
200410034010.3 disclose a kind of azithromycin granule, its raw material is an azithromycin, adjuvant is microcrystalline Cellulose, hyprolose, cross-linked pvp.Its preparation method is: (1) takes by weighing azithromycin, microcrystalline Cellulose, low substituent group cellulose, the cross-linked pvp 80-100 mesh sieve that sieves respectively, mixing; (2) make soft material with the 5%PVP aqueous solution after, cross the 24-40 mesh sieve and make granule; (3) put granule in 40-60 ℃, aeration-drying 2-4 hour; (4) cross 24-40 mesh sieve granulate, promptly get azithromycin granule.The inventor finds that it is serious to reunite with azithromycin in the process of 5%PVP aqueous solution system soft material, and suspendible uniformity, grain forming and stability are all bad, and can not cover the bitterness of medicine azithromycin effectively, and mouthfeel is bad, and patient's compliance is poor.
Oral Azithromycin dosage forms commonly used at present has tablet, capsule, granule etc.The patient that tablet and capsule are not suitable for child, old people and dysphagia takes, and to the child, dosage is not accurate enough when taking; Though being fit to the patient of child, old people and dysphagia, granule and dry suspension take, but because Macrolide antibiotics multi-flavor road is extremely bitter, though flavoring in addition when preparation, but still can not cover the bitterness of medicine effectively, thereby patient's compliance is poor.In addition, for hydrophobic azithromycin, the microparticulate degree is big in its suspension, and system plays pendulum, thereby its suspendible uniformity and less stable.
Mix suspension grain is a kind of quick-effective preparation that development in recent years is got up, because its distinctive advantage more and more is subjected to people's attention.Mix suspension grain means that insoluble drug and proper auxiliary materials make the dried particles agent of certain particle size.Facing the time spent adds water or other appropriate liquid jolting and can be dispersed into suspension for oral.Mix suspension grain require water-soluble or other appropriate liquid after suspendible evenly, good stability, good mouthfeel.
In addition and since azithromycin little have draw moistly, when the design of the prescription of Azithromycin mix suspension grain agent, also need to consider to improve moist, preparations shaping of drawing of azithromycin etc.
Therefore, how can cover effectively bitterness with the drug compliance of guaranteeing the patient, improve mix suspension grain suspendible uniformity and stability, to improve moist and preparations shaping of drawing of Azithromycin mix suspension grain be the key issue of the oral Azithromycin mix suspension grain agent of preparation.Though disclosing, Chinese patent application 200510061861.1 use sweeting agent and aromatic to cover bitterness with the drug compliance of guaranteeing the patient and use polymer binder to strengthen the method for the stability of Azithromycin for Suspension; but; how not cover bitterness effectively to guarantee patient's drug compliance in instruction or the agent of hint Azithromycin mix suspension grain; improve the suspendible uniformity of mix suspension grain and the method for stability; do not provide in the prior art yet and be suitable for covering bitterness to guarantee patient's drug compliance; improve the suspendible uniformity of mix suspension grain and the adjuvant and the consumption thereof of the Azithromycin mix suspension grain agent of stability, more do not provide any and draw moist about being suitable for improving azithromycin; the adjuvant of preparations shaping and consumption thereof.
In view of this, special proposition the present invention.
Summary of the invention
Main purpose of the present invention be to provide a kind of mouthfeel good, can cover all good Azithromycin mix suspension grains of the bitterness of azithromycin, the drug compliance of guaranteeing the patient and suspendible uniformity and stability effectively; and Azithromycin mix suspension grain provided by the present invention can improve moist and preparations shaping of drawing of azithromycin, good fluidity effectively.
For the present invention clearly is described, below carry out some explanations with regard to thinking of the present invention earlier.
Mix suspension grain of the present invention means that insoluble drug and proper auxiliary materials make the dried particles agent of certain particle size.Facing the time spent adds water or other appropriate liquid jolting and can be dispersed into suspension for oral.
Mix suspension grain normal sucrose, Herba Menthae, edible essences etc. of adding in preparation process are suitable for child administration to adjust taste, make mix suspension grain for the medicine of disintegrate difficulty and can help absorbing.Specification requirement: (1) mouthfeel, epigranular are good; (2) dissolubility and good dispersion property; (3) other should meet general rule requirement under the granule item.
Since mix suspension grain requires water-soluble or other appropriate liquid after suspendible evenly, good stability, good mouthfeel, to the oral mucosa nonirritant.Therefore the selection to supplementary product kind and performance thereof is the key of preparation mix suspension grain.
For hydrophobic azithromycin, the microparticulate degree is big in its suspension, so system plays pendulum.And the viscosity that increases medium can reduce the sedimentation velocity of microgranule, improves the stability of suspension.
In addition, azithromycin has very bitter taste, needs suitable flavoring agent to guarantee the vomiting after patient's compliance and minimizing are swallowed.
And azithromycin is little to be had and draws moistly, need consider to improve moist and preparations shaping of drawing of azithromycin when concrete prescription design and technological design.
Based on described consideration, the invention provides a kind of suspendible evenly, good stability, preparations shaping is good, mouthfeel is good, guarantee the take medicine Azithromycin mix suspension grain of compliance of patient.
The component of Azithromycin mix suspension grain provided by the present invention is as follows:
Azithromycin 100-250 weight portion
Sucrose 500-1250 weight portion
Starch 60-150 weight portion
Mannitol 16-40 weight portion
Steviosin 20-50 weight portion
95% ethanol is an amount of
Cocoanut flavour is an amount of
Preferably, the component of Azithromycin mix suspension grain provided by the present invention is as follows:
Azithromycin 100-200 weight portion
Sucrose 500-1000 weight portion
Starch 60-120 weight portion
Mannitol 16-32 weight
Steviosin 20-40 weight
95% ethanol is an amount of
Cocoanut flavour is an amount of.
In the present invention, the bitterness of azithromycin is sheltered by the composition of flavoring agent.Used correctives steviosin of the present invention and cocoanut flavour make preparation of the present invention produce fragrant and sweet happy people's mouthfeel, the cocoanut flavour fragrant odour, use has the effect that reduces bitterness time of staying in the oral cavity, and correctives has not only played the important function of flavoring, also played stronger taste masking effect, cover the bad bitterness of azithromycin, improved the mouthfeel of mix suspension grain greatly, thereby Azithromycin mix suspension grain of the present invention has improved patient's drug compliance especially easily.
Also added adjuvant sucrose and mannitol pharmaceutically commonly used among the present invention, not only can play the effect of seasoning, and at the viscosity that preparation of the present invention can also be increased medium after water-soluble or other appropriate liquid, and the viscosity that increases medium can reduce the sedimentation velocity of microgranule, improves the stability of suspension.
Among the present invention, 95% ethanol is used as binding agent, as long as its consumption can satisfy the amount that supplementary material can reach the system soft material, this point can both be expected for those skilled in the art.
In addition, select for use among the present invention hygroscopicity preferably starch be filler, effectively improved moist problem of drawing of azithromycin, the good moldability of gained preparation.
The more important thing is, in the prior art when preparation azithromycin granule agent and dry suspension usually all from improving mouthfeel, cover the bitterness of azithromycin and improve and start with aspect suspension stable, but azithromycin itself has and draws moist and grain forming that bring is difficult to solution.In view of above defective, the present invention mainly considers to improve the bad sense of taste of azithromycin when writing out a prescription design, when concrete prescription and technological design, consider to improve aspects such as moist and preparations shaping of drawing of azithromycin, suspension ability, and prescription is screened from aspects such as the mouthfeel of the granule of each prescription and technology gained thereof, grain forming, flowability, suspension abilities.
Screening test is (consumption in table 1, table 2 and the table 3 is per 1000 bags consumption) shown in following table 1, table 2 and table 3:
The test of table 1. prescription screening
| The present invention | CN200510061861.1 | CN200410034010.3 | |
| Supplementary material and consumption thereof | An amount of cocoanut flavour of azithromycin 100g sucrose 500g starch 60g mannitol 16g steviosin 20g 95% ethanol is an amount of | 4000 milliliters of azithromycin 100g IV acrylic resin 400g sodium carboxymethylcellulose 25g xanthans 25g sodium phosphate 11g silica 30g sucrose 700g sweet mellow wine 689g orange flavor essence 20g ethanol | Azithromycin 100g microcrystalline Cellulose 500g hyprolose 60g cross-linked pvp 36g 5%PVP aqueous solution is an amount of |
| Mouldability | Well | Difference | Difference |
| Mobile | Well | Difference | Difference |
| Suspension ability | Well | Well | Good |
| Air draws moist | Do not have | Have | Have |
| Mouthfeel | Better, bitterness improves | Better, bitterness improves | Bad |
Table 2. binding agent screening test
Table 3. supplementary product consumption screening test
As can be seen from the above table, not only mouthfeel is good for the Azithromycin mix suspension grain for preparing by prescription of the present invention, and its mouldability, flowability, suspension ability are all good than prior art, have also solved effectively to draw moist problem.
Another object of the present invention is to provide the preparation method of Azithromycin mix suspension grain of the present invention, it is characterized in that described method comprises azithromycin, sucrose, mannitol pulverize separately, sieves, again starch is sieved, then mixing granulation, drying, granulate, packing.
In the above-mentioned preparation method, described azithromycin, sucrose, mannitol are crossed 100 mesh sieves, and described starch is crossed 120 mesh sieves.The purpose of screening is in order to obtain the material than uniform particle size.This all has an important meaning smoothly to drug quality and preparation production.Screening all has tangible influence to the flowability of degree of mixing, particle, filling, tablet weight variation etc. in unit operationss such as mixing, granulation, tabletting.The back remix of earlier former, adjuvant being pulverized, sieved among the present invention can make former, adjuvant be evenly distributed, mix more even, thereby improved mixing uniformity, dispersibility and dissolubility.
Above-mentioned being mixed into done mixed wet mixing more earlier.Married operation is a purpose with the content uniformity.Mixing resultant influences the presentation quality and the inherent quality of preparation.Mix bad meeting and speckle occurs, disintegration, intensity are defective, influence drug effect etc., and it is inhomogeneous to mix the inhomogeneous drug content that causes, and bioavailability and therapeutic effect are all brought great influence.Do earlier among the present invention and mix wet mixing again, make supplementary material mix more evenly, drug content is more even, thereby makes its particulate dispersive property and solubility property better.
Wherein said doing mixed to sealing dried mixing.Because it is Powdered that blended supplementary material is, therefore can produce bigger dust pollution, can staff's health be worked the mischief to a certain extent, also can cause certain pollution simultaneously to environment.Under the condition of sealing, do among the present invention and mix, reduced powder and flown upward, help labor protection.
Above-mentioned drying is for being dried to moisture≤4%.Described drying can adopt drying means pharmaceutically commonly used, preferably adopts at the ebullated dryer inner drying.Drying is an indispensable unit operations during preparation is produced.The purpose of drying is to make material to be convenient to processing, transportation, storage and use, guarantees the quality of medicine and improves stability of drug.Drying of the present invention preferably at the ebullated dryer inner drying to moisture≤4%, so not only can make material reach preferable drying effect, moisture reaches standard, but also can prevent adhesion phenomenon effectively.
Preferred manufacturing procedure comprises the steps:
(1) take by weighing former, the adjuvant of recipe quantity, with azithromycin, sucrose, mannitol pulverize separately, cross 100 mesh sieves, starch is crossed 120 mesh sieves, obtains former, adjuvant powder;
(2) will go up the supplementary material powder that goes on foot gained and place the interior sealing of mixer to do mixed 5-15 minute, and add 95% ethanol, soft material was made in wet mixing in 30～150 seconds, and granulation obtains wet granular;
(3) will go up prepared wet granular of step and evenly place the ebullated dryer inner drying, obtain dried granule to moisture≤4%;
(4) dried granule and cocoanut flavour are added the pelletizing machine granulate, cross 14～40 mesh sieves, determine according to content that loading amount is packed after the assay was approved and promptly get mix suspension grain of the present invention.
Step in the said method (2) is to be no more than 25 ℃, relative humidity in ambient temperature to be no more than under 40% the condition and to carry out.Azithromycin is little have draw moist, the difficulty of granulating.Though draw moist lessly, those skilled in the art often ignores and does not consider, and can cause that all azithromycin makes moist if the ambient temperature in the pelletization is too high, humidity is too high, makes that its preparations shaping is bad.The inventor adjusts environmental condition through a large amount of tests, has obtained being suitable for ambient temperature and the humidity that product Azithromycin mix suspension grain of the present invention is granulated, and has well solved and has drawn the moist preparations shaping problem of bringing.
The invention provides the pharmaceutic adjuvant and the consumption thereof that are fit to Azithromycin mix suspension grain, wherein used correctives steviosin and cocoanut flavour make preparation of the present invention produce fragrant and sweet happy people's mouthfeel, and correctives has not only played the important function of flavoring, also played stronger taste masking effect, covered the bad bitterness of azithromycin, improved the mouthfeel of mix suspension grain greatly, thereby Azithromycin mix suspension grain of the present invention improves patient's drug compliance especially easily; Added adjuvant sucrose and mannitol pharmaceutically commonly used among the present invention, not only can play the effect of seasoning, and after preparation of the present invention is water-soluble or other appropriate liquid, can also increase the viscosity of medium, and the viscosity that increases medium can reduce the sedimentation velocity of microgranule, improve the stability of suspension, thereby Azithromycin mix suspension grain of the present invention in the stability that adds the suspension that forms after water or other appropriate liquid better.In addition, in the preparation method provided by the present invention screening, drying have all been carried out strict process control, guaranteed that granularity, dispersive property and the solubility property of Azithromycin mix suspension grain and moisture all reach good.
Azithromycin mix suspension grain provided by the present invention prescription and technology have not only well been improved mouthfeel, have improved the suspendible uniformity and the stability of azithromycin, and it is moist also to have improved drawing of azithromycin, and the gained molding particles is good.
The specific embodiment
Below be the specific embodiment of the present invention, described embodiment is in order to further describe the present invention rather than restriction the present invention.
Embodiment 1
1, specification: 0.1g
2, prescription:
3, preparation process:
(1) take by weighing former, the adjuvant of recipe quantity, with azithromycin, sucrose, mannitol pulverize separately, cross 100 mesh sieves, starch is crossed 120 mesh sieves, obtains former, adjuvant powder;
(2) will go up resulting supplementary material powder of step and place the interior sealing of mixer to do mixed 10 minutes, and add 95% ethanol, 30 seconds systems of wet mixing soft material is granulated under the condition of 25 ℃ of ambient temperatures, relative humidity 45%, obtains wet granular;
(3) will go up prepared wet granular of step and evenly place in the ebullated dryer, and regulate 60 ℃ of inlet temperature, dry 40 minutes, moisture was 3.5%, shut down then, clear filter bag, and blowing obtains dried granule;
(4) dried granule and cocoanut flavour are added the pelletizing machine granulate, cross 14 mesh sieves, determine according to content that loading amount is packed after the assay was approved and promptly get mix suspension grain of the present invention.
Embodiment 2
1, specification: 0.25g
2, prescription:
3, preparation process
(1) take by weighing former, the adjuvant of recipe quantity, with azithromycin, sucrose, mannitol pulverize separately, cross 100 mesh sieves, starch is crossed 120 mesh sieves, obtains former, adjuvant powder;
(2) will go up the supplementary material powder that goes on foot gained and place the interior sealing of mixer to do mixed 5 minutes, and add 95% ethanol, wet mixing was made soft material in 150 seconds, granulated under the condition of 20 ℃ of ambient temperatures, relative humidity 25%, obtained wet granular;
(3) will go up prepared wet granular of step and evenly place in the ebullated dryer, and regulate 70 ℃ of inlet temperature, dry 50 minutes, moisture was 4%, shut down then, clear filter bag, and blowing obtains dried granule;
(4) dried granule and cocoanut flavour are added the pelletizing machine granulate, cross 40 mesh sieves, determine according to content that loading amount is packed after the assay was approved and promptly get mix suspension grain of the present invention.
Embodiment 3
1, prescription:
2, preparation process:
(1) take by weighing former, the adjuvant of recipe quantity, with azithromycin, sucrose, mannitol pulverize separately, cross 100 mesh sieves, starch is crossed 120 mesh sieves, obtains former, adjuvant powder;
(2) will go up the supplementary material powder that goes on foot gained and place the interior sealing of mixer to do mixed 15 minutes, and add 95% ethanol, soft material was made in wet mixing in 100 seconds, and granulation obtains wet granular;
(3) will go up prepared wet granular of step and evenly place in the ebullated dryer, and regulate 65 ℃ of inlet temperature, dry 45 minutes, moisture was 3.8%, shut down then, clear filter bag, and blowing obtains dried granule;
(4) dried granule and cocoanut flavour are added the pelletizing machine granulate, cross 20 mesh sieves, determine according to content that loading amount is packed after the assay was approved and promptly get mix suspension grain of the present invention.
Embodiment 4
1, prescription:
2, preparation process:
(1) take by weighing former, the adjuvant of recipe quantity, with azithromycin, sucrose, mannitol pulverize separately, cross 100 mesh sieves, starch is crossed 120 mesh sieves, obtains former, adjuvant powder;
(2) will go up the supplementary material powder that goes on foot gained and place the interior sealing of mixer to do mixed 10 minutes, and add 95% ethanol, soft material was made in wet mixing in 80 seconds, and granulation obtains wet granular;
(3) will go up prepared wet granular of step under 65 ℃ condition dry 40 minutes, moisture is 3.5%, obtains dried granule then;
(4) dried granule and cocoanut flavour are added the pelletizing machine granulate, cross 18 mesh sieves, determine according to content that loading amount is packed after the assay was approved and promptly get mix suspension grain of the present invention.
Below routine by experiment and comparative example illustrates the beneficial effect of product Azithromycin mix suspension grain of the present invention.The dissolubility and the dispersibility test of [test example 1] Azithromycin mix suspension grain
Requirement according to Chinese Pharmacopoeia version in 2005 two appendix IX E second method (two sieve method), the summation of an oversize and No. five siftage must not surpass for 15% of examination amount, above-mentioned granule sample check result all meets the pharmacopeia regulation, thereby can fully guarantee the homogeneity of granule particle diameter, granule being lumpd because of making moist or pulverize in transportation and storage influences quality.
Get above-mentioned granule sample 10g, add hot water 200ml, stir 5min, observe this product melting, check result shows the sample off-bottom, does not see foreign body.Meet two appendix IN regulations of Chinese Pharmacopoeia version in 2005.The solubility Azithromycin mix suspension grain of above-mentioned preparation can be dispersed or dissolved in the water fully, thereby can guarantee the bioavailability of granule, makes things convenient for the patient to take.
[test example 2] Azithromycin mix suspension grain agent study on the stability of the present invention
According to two regulations of Chinese Pharmacopoeia version in 2000 about the medicine stability test guideline, to the embodiment of the invention 1 and according to the prepared Azithromycin mix suspension grain of 200510061861.1 method under temperature, humidity effect, time dependent rule is investigated, thereby its stability is compared.
One, accelerated test
Get the embodiment of the invention 1 and, press commercially available back,, placed 6 months under the condition of relative humidity 75% ± 5% 40 ℃ ± 2 ℃ of temperature according to the prepared Azithromycin mix suspension grain of 200510061861.1 method.In 0th month, the 1st month, 2 months, 3 months, 6 each sampling at the end of month of duration of test once, detect by stable high spot reviews project.Testing result sees Table 1.
The Azithromycin for Suspension accelerated test study on the stability result of table 1. the present invention and prior art relatively
Annotate: A and B are respectively the Azithromycin for Suspension of Azithromycin mix suspension grain of the present invention and prior art
Conclusion (of pressure testing): Azithromycin mix suspension grain accelerated test of the present invention is stable, 40 ℃ ± 2 ℃ of temperature, placed 6 months under the condition of relative humidity 75% ± 5%, every index all with test preceding no significant change.Illustrate that Azithromycin mix suspension grain of the present invention has good stability.Compare with the Azithromycin for Suspension of prior art, its stability is better than prior art.
Two, long term test
Long term test is to carry out under the actual storage requirement near medicine.Get the embodiment of the invention 1 and, press commercially available back,, place under the condition of relative humidity 60% ± 10% and observe 25 ℃ ± 2 ℃ of temperature according to the prepared Azithromycin mix suspension grain of 200510061861.1 method.In 3rd month, 6 months, 9 months, 12 months, 18 each sampling at the end of month of duration of test once, detect by stable high spot reviews project.Its testing result sees Table 2.
The Azithromycin for Suspension long term test study on the stability result of table 1. the present invention and prior art relatively
Annotate: A and B are respectively the Azithromycin for Suspension of Azithromycin mix suspension grain of the present invention and prior art
Conclusion (of pressure testing): show by above data, Azithromycin mix suspension grain of the present invention in long term test, every index all with test before no significant difference, steady quality, and compare with the Azithromycin for Suspension of prior art, stability better.
Claims (2)
1, a kind of Azithromycin mix suspension grain is characterized in that: the raw material of described mix suspension grain is composed as follows:
Azithromycin 100-250 weight portion
Sucrose 500-1250 weight portion
Starch 60-150 weight portion
Mannitol 16-40 weight portion
Steviosin 20-50 weight portion
95% ethanol is an amount of
Cocoanut flavour is an amount of.
2, Azithromycin mix suspension grain according to claim 1 is characterized in that: the raw material of described mix suspension grain is composed as follows:
Azithromycin 100-200 weight portion
Sucrose 500-1000 weight portion
Starch 60-120 weight portion
Mannitol 16-32 weight
Steviosin 20-40 weight
95% ethanol is an amount of
Cocoanut flavour is an amount of.
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| CN113262208B (en) * | 2015-01-29 | 2023-05-23 | 北京科信聚润医药科技有限公司 | Azithromycin taste-masking dry suspension granule and preparation method thereof |
| CN114010605A (en) * | 2021-11-26 | 2022-02-08 | 广东百澳药业有限公司 | Acetylcysteine granules and preparation method thereof |
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| CN1813683A (en) * | 2005-12-07 | 2006-08-09 | 范敏华 | Azithromycin for suspension and its preparing method |
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| CN1813683A (en) * | 2005-12-07 | 2006-08-09 | 范敏华 | Azithromycin for suspension and its preparing method |
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