CN101966156A - Azithromycin for suspension and preparation method thereof - Google Patents
Azithromycin for suspension and preparation method thereof Download PDFInfo
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- CN101966156A CN101966156A CN2010102940475A CN201010294047A CN101966156A CN 101966156 A CN101966156 A CN 101966156A CN 2010102940475 A CN2010102940475 A CN 2010102940475A CN 201010294047 A CN201010294047 A CN 201010294047A CN 101966156 A CN101966156 A CN 101966156A
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Abstract
The invention discloses an azithromycin for suspension and a preparation method thereof. The azithromycin for suspension is prepared by mixing azithromycin particles and sugar particles, wherein, the azithromycin particle is a composite comprising the following components in parts by weight: 1.5-4.5 parts of xanthan gum, 1 part of silk fibroin and 1 part of aerosol. The invention also provides the preparation method of the azithromycin for suspension, avoids drug burst release, reduces adverse effect, and improves the compliance of patients, thus avoiding the gastrointestinal tract symptoms of stomachache, nausea, vomiting, gastro spasm, diarrhea and the like, the skin eruption and transaminase transiency promotion, and occurrence of adverse reactions, such as transient neutropenia and the like.
Description
Technical field
The present invention relates to a kind of dried mixed suspension preparation and preparation method thereof, relate in particular to the dried mixed suspension preparation of a kind of azithromycin, belong to medical technical field.
Background technology
Azithromycin (Azithromycin) is a kind of antibiotic that belongs to macrolide, change the peptide process by hindering antibacterial, thereby suppress the synthetic of bacterioprotein, be applicable to the caused infection of responsive pathogenic bacterium, as by Chlamydia pneumoniae, the microbial community acquired pneumonia that need at first take the intravenous drip treatment of hemophilus influenza, legionella pneumophilia, mucositis mora bacterium, staphylococcus aureus or pneumonia streptococcus; The needs that caused by chlamydia trachomatis, gonorrhea diplococcus, mycoplasma hominis are at first taked the pelvic inflammatory disease of intravenous drip treatment.Main different of azithromycin and other macrolide antibiotics one can be used for the treatment of nongonococcal urethritis such as sexually transmitted disease (STD) and syphilis exactly.Special advantages makes international market demand increase day by day, and the increase of international demand has then directly promoted the increase of azithromycin clinical application, thereby promotes the market growth, has also established the leading position of azithromycin in macrolide antibiotics simultaneously.Because azithromycin reaches nearly 100% to non-complex gonorrhea and chlamydia urethritis and cervicitis cure rate, therefore U.S. FDA infection Advisory Board has recommended azithromycin to be used for infection such as the caused respiratory tract of sensitive bacterial, urogenital tract, skin and soft tissue, so also can stimulate the market demand of azithromycin, and the azithromycin future market prospect also will be more good.
In present clinical experimental study and existing process of clinical application, the azithromycin main adverse reactions for stomachache, feel sick, gastrointestinal symptoms such as vomiting, stomach spasm and diarrhoea, and erythra etc., the temporary rising of accidental transaminase, the Ceng Jianyi property crossed neutrophilic granulocyte reduces, the same with other Macrolidees such as erythromycin, severe anaphylactic reaction such as periodic edema and anaphylactic shock etc. are rare, but must note.
Therefore, research and development azithromycin new formulation improves patient's compliance, reduces even stops untoward reaction, becomes problem demanding prompt solution.
Summary of the invention
Technical problem to be solved by this invention provides the dried mixed suspension preparation of a kind of azithromycin, and said preparation can significantly promote drug compliance, thereby reduces untoward reaction, and the present invention also provides the preparation method of said preparation in addition.
Technical problem of the present invention is realized by following technical scheme.
The dried mixed suspension preparation of a kind of azithromycin, mix by azithromycin granule and sugared granule, contain xanthan gum-fibroin albumen-micropowder silica gel compositions in the described azithromycin granule, the weight portion of xanthan gum is 1.5～4.5 in the said composition, the weight portion of fibroin albumen is 1, and the weight portion of micropowder silica gel is 1; Described azithromycin granule and sugared particulate mixed proportion are 2: 1.
The dried mixed suspension preparation of above-mentioned azithromycin, in the described azithromycin granule, the weight portion of azithromycin is 20～25, the weight portion of xanthan gum-fibroin albumen-micropowder silica gel compositions is 1.
The dried mixed suspension preparation of above-mentioned azithromycin, the weight portion of described xanthan gum are 3, and the weight portion of fibroin albumen is 1, and the weight portion of micropowder silica gel is 1.
The dried mixed suspension preparation of above-mentioned azithromycin, the weight portion of described azithromycin are 23, and the weight portion of xanthan gum-fibroin albumen-micropowder silica gel compositions is 1.
The dried mixed suspension preparation of above-mentioned azithromycin, described azithromycin granule also contains the component of following weight portion:
Microcrystalline Cellulose 4～4.5
Sodium carbonate 1～1.2
20% arabic gum aqueous solution 11～11.5.
The dried mixed suspension preparation of above-mentioned azithromycin, described azithromycin granule is made of the component of following weight portion:
Azithromycin 23
Xanthan gum-fibroin albumen micropowder silica gel compositions 1
Microcrystalline Cellulose 4.24
Sodium carbonate 1.056
20% arabic gum aqueous solution 11.2.
The dried mixed suspension preparation of azithromycin of the present invention, described sugared granule is made of the component of following weight portion:
Cane sugar powder 20～21
Mannitol 8～9
A Siba sweet 0.5～1
Lemon yellow 0.05～0.1
1％HPMC 1.5～2。
The dried mixed suspension preparation of above-mentioned azithromycin, described sugared granule is made of the component of following weight portion:
Cane sugar powder 20.47
Mannitol 8.77
A Siba sweet 0.75
Lemon yellow 0.09
1％HPMC 1.7。
The dried mixed suspension preparation of above-mentioned azithromycin, described azithromycin granule is made of the component of following weight portion:
Azithromycin 23
Xanthan gum-fibroin albumen-micropowder silica gel compositions 1
Microcrystalline Cellulose 4.24
Sodium carbonate 1.056
20% arabic gum aqueous solution 11.2;
Described sugared granule is made of the component of following weight portion:
Cane sugar powder 20.47
Mannitol 8.77
A Siba sweet 0.75
Lemon yellow 0.09
1％HPMC 1.7。
The method of the dried mixed suspension preparation preparation of azithromycin of the present invention may further comprise the steps:
Granulating process:
A, with xanthan gum with after fibroin albumen mixes by usage ratio, under 55～60 ℃ of conditions, stir fusion and insulation, slowly add micropowder silica gel while stirring, micropowder silica gel is uniformly dispersed, compositions is standby;
B, be that 3: 1: 8 ratio makes microemulsion, in emulsion, add azithromycin or its officinal salt, place 40～60 ℃ of water-baths according to propoxylation methyl glucoside weight, isobutanol volume, ethyl acetate volume ratio; Described weight, volume unit are respectively g and ml;
C, adding resulting composition among the step a in microemulsion, be stirred to evenly, as reactant liquor, is that pH value that 10% NaOH solution regulate this reactant liquor be 8.0～10.0 with weight concentration with this solution, adding 20～30ml methanol, isothermal reaction 1～2 hour;
D, reactant liquor is cooled to 0 ℃, the glutaraldehyde that adds 0.08～0.125 times of reactant liquor volume continues to stir 30 minutes, slowly is warming up to 40～60 ℃ again, and adding glacial acetic acid to the value of pH is 2.0～4.0, obtains suspension;
E, treat that sedimentation is complete after static, the supernatant that inclines filters, and washes with water to no aldehyde to distinguish the flavor of, and drains.
F, sodium carbonate is crossed 80 mesh sieves, take by weighing d, gained precipitum, microcrystalline Cellulose, sodium carbonate, put into high speed granulator, do and mixed 1 minute, add 20% arabic gum aqueous solution, stirred discharging 5 minutes, 18 order nylon mesh are granulated, airpillow-dry, 65 ℃ of inlet temperature, 38.5 ℃ of drop temperatures, pellet moisture is 3.68%, 16 order iron wire sieve granulate; Granule is crossed 40 mesh sieves sift out fine powder, get coarse granule;
The sugar granule preparing process:
Cane sugar powder is crossed 100 mesh sieves, take by weighing lemon yellow and add in the 1%HPMC solution and stir, take by weighing Icing Sugar, mannitol, the sweet high speed granulator of putting into of A Siba, do and mixed 1 minute, pour the 1%HPMC solution that adds lemon yellow into stir about 5 minutes, 150 rev/mins of mixing speeds, 18 order nylon mesh are granulated, airpillow-dry, 65 ℃ of inlet temperature, drop temperature is controlled at 30 ℃-40 ℃, 16 order iron wire sieve granulate, discharging;
Mix:
Measure medicine-containing particle content, even with sugared granule by 2: 1 mixed, be up to the standards, packing, promptly.Wherein:
Described granulating process, melt temperature is preferred 57 ℃ among the step a;
Bath temperature is 50 ℃ among the described step b;
The pH value of reactant liquor is 9.0 among the described step c; Isothermal reaction 1.5 hours;
The glutaraldehyde consumption is 0.1 times of reactant liquor volume in the described steps d, slowly is warming up to 50 ℃, and the glacial acetic acid adjust pH is 3.0.
The dried mixed suspension preparation of azithromycin provided by the present invention is a lapping with xanthan gum-fibroin albumen-micropowder silica gel compositions, usage ratio by investigating xanthan gum-fibroin albumen-micropowder silica gel and various factors are to the influence of preparation, determined preparation condition: the amount ratio of xanthan gum, fibroin albumen and micropowder silica gel is 1.5～4.5: 1: 1, and 55～60 ℃ of melt temperatures and insulation; The complex coacervation pH value is 8.0～10.0; The complex coacervation time is 1～2 hour; The amount of cross-linking agent is 0.08～0.125 times of a reactant liquor volume; Crosslinking time is 30 minutes.Especially the amount ratio when xanthan gum, fibroin albumen and micropowder silica gel is 3: 1: 1,57 ℃ of melt temperatures and insulation; The complex coacervation pH value is 9.0; The complex coacervation time is 1.5 hours; The amount of cross-linking agent is 0.1 times of a reactant liquor volume; When crosslinking time was 30 minutes, envelop rate reached more than 95% especially.The present invention has avoided that medicine is prominent to be released, reduced untoward reaction, improved patient's compliance, thereby avoided stomachache, feel sick, gastrointestinal symptoms such as vomiting, stomach spasm and diarrhoea, and erythra, the temporary rising of transaminase, are crossed the generation of untoward reaction such as property neutrophilic granulocyte minimizing.
The specific embodiment
The invention will be further described below in conjunction with the specific embodiment.
The preparation of the dried mixed suspension preparation of embodiment 1 azithromycin
Granulating process:
A, with xanthan gum 15g, after fibroin albumen 10g mixes, under 55 ℃ of conditions, stir fusion and insulation, slowly add micropowder silica gel 10g while stirring, micropowder silica gel is uniformly dispersed, compositions is standby;
B, make microemulsion, in emulsion, add azithromycin dihydrochloride 700g (in azithromycin), place 40 ℃ of water-baths with propoxylation methyl glucoside 15g, isobutanol 5ml, ethyl acetate 40ml;
C, add resulting composition among a in microemulsion, be stirred to evenly, as reactant liquor, the pH value of regulating this reactant liquor with 10% NaOH solution is 8.0 with this solution, adding 20ml methanol, isothermal reaction 1 hour;
D, reactant liquor is cooled to 0 ℃, the glutaraldehyde that adds 0.08 times of reactant liquor volume continues to stir 30 minutes, slowly is warming up to 40 ℃ again, and adding glacial acetic acid to pH value is 2.0, obtains suspension;
E, treat that sedimentation is complete after static, the supernatant that inclines filters, and washes with water to no aldehyde to distinguish the flavor of, and drains, promptly.
F, sodium carbonate is crossed 80 mesh sieves, get d, gained precipitum, 4g microcrystalline Cellulose, 1g sodium carbonate, put into high speed granulator, do and mixed 1 minute, add 11g 20% arabic gum aqueous solution, stirred discharging 5 minutes, 18 order nylon mesh are granulated, airpillow-dry, 65 ℃ of inlet temperature, 38.5 ℃ of drop temperatures, pellet moisture is 3.68%, 16 order iron wire sieve granulate; Granule is crossed 40 mesh sieves sieve fine powder, get coarse granule;
The sugar granule preparing process:
Cane sugar powder is crossed 100 mesh sieves, take by weighing the 0.05g lemon yellow and add in the 1.5g1%HPMC solution and stir, take by weighing 20g Icing Sugar, 8g mannitol, the sweet high speed granulator of putting into of 0.5g A Siba, do and mixed 1 minute, pour the 1%HPMC solution that adds lemon yellow into stir about 5 minutes, 150 rev/mins of mixing speeds, 18 order nylon mesh are granulated, airpillow-dry, 65 ℃ of inlet temperature, drop temperature is controlled at 30 ℃-40 ℃, 16 order iron wire sieve granulate, discharging;
Mix:
Measure medicine-containing particle content, even with sugared granule by 2: 1 mixed, be up to the standards, packing, promptly.
The preparation of the dried mixed suspension preparation of embodiment 2 azithromycins
Granulating process:
A, with xanthan gum 45g, after fibroin albumen 10g mixes, under 60 ℃ of conditions, stir fusion and insulation, slowly add micropowder silica gel 10g while stirring, micropowder silica gel is uniformly dispersed, compositions is standby;
B, make microemulsion, in emulsion, add lactobionic acid azithromycin 1625g (in azithromycin), place 60 ℃ of water-baths with propoxylation methyl glucoside 120g, isobutanol 40ml, ethyl acetate 320ml;
C, add resulting composition among a in microemulsion, be stirred to evenly, as reactant liquor, the pH value of regulating this reactant liquor with 10% NaOH solution is 10.0 with this solution, adding 30ml methanol, isothermal reaction 2 hours;
D, reactant liquor is cooled to 0 ℃, the glutaraldehyde that adds 0.125 times of reactant liquor volume continues to stir 30 minutes, slowly is warming up to 60 ℃ again, and adding glacial acetic acid to pH value is 4.0, obtains suspension;
E, treat that sedimentation is complete after static, the supernatant that inclines filters, and washes with water to no aldehyde to distinguish the flavor of, and drains, promptly.
F, sodium carbonate is crossed 80 mesh sieves, get d, gained precipitum, 4.5g microcrystalline Cellulose, 1.2g sodium carbonate, put into high speed granulator, do and mixed 1 minute, add 11.5g 20% arabic gum aqueous solution, stirred discharging 5 minutes, 18 order nylon mesh are granulated, airpillow-dry, 65 ℃ of inlet temperature, 38.5 ℃ of drop temperatures, pellet moisture is 3.68%, 16 order iron wire sieve granulate; Granule is crossed 40 mesh sieves sieve fine powder, get coarse granule;
The sugar granule preparing process:
Cane sugar powder is crossed 100 mesh sieves, take by weighing the 0.1g lemon yellow and add in the 2g1%HPMC solution and stir, take by weighing 21g Icing Sugar, 9g mannitol, the sweet high speed granulator of putting into of 1g A Siba, do and mixed 1 minute, pour the 1%HPMC solution that adds lemon yellow into stir about 5 minutes, 150 rev/mins of mixing speeds, 18 order nylon mesh are granulated, airpillow-dry, 65 ℃ of inlet temperature, drop temperature is controlled at 30 ℃-40 ℃, 16 order iron wire sieve granulate, discharging;
Mix:
Measure medicine-containing particle content, even with sugared granule by 2: 1 mixed, be up to the standards, packing, promptly.
The preparation of the dried mixed suspension preparation of embodiment 3 azithromycins
Granulating process:
A, with xanthan gum 25g, after fibroin albumen 10g mixes, under 58 ℃ of conditions, stir fusion and insulation, slowly add micropowder silica gel 10g while stirring, micropowder silica gel is uniformly dispersed, compositions is standby;
B, make microemulsion with propoxylation methyl glucoside 60g, isobutanol 20ml, ethyl acetate 160ml and in emulsion, add azithromycin 990g, place 50 ℃ of water-baths;
C, add resulting composition among a in microemulsion, be stirred to evenly, as reactant liquor, the pH value of regulating this reactant liquor with 10% NaOH solution is 9.0 with this solution, adding 25ml methanol, isothermal reaction 1.5 hours;
D, reactant liquor is cooled to 0 ℃, the glutaraldehyde that adds 0.1 times of reactant liquor volume continues to stir 30 minutes, slowly is warming up to 50 ℃ again, and adding glacial acetic acid to pH value is 3.0, obtains suspension;
E, treat that sedimentation is complete after static, the supernatant that inclines filters, and washes with water to no aldehyde to distinguish the flavor of, and drains, promptly.
F, sodium carbonate is crossed 80 mesh sieves, get d, gained precipitum, 4.2g microcrystalline Cellulose, 1.1g sodium carbonate, put into high speed granulator, do and mixed 1 minute, add 11.2g 20% arabic gum aqueous solution, stirred discharging 5 minutes, 18 order nylon mesh are granulated, airpillow-dry, 65 ℃ of inlet temperature, 38.5 ℃ of drop temperatures, pellet moisture is 3.68%, 16 order iron wire sieve granulate; Granule is crossed 40 mesh sieves sieve fine powder, get coarse granule;
The sugar granule preparing process:
Cane sugar powder is crossed 100 mesh sieves, take by weighing the 0.08g lemon yellow and add in the 2g1%HPMC solution and stir, take by weighing 20.5g Icing Sugar, 8.5g mannitol, the sweet high speed granulator of putting into of 0.7g A Siba, do and mixed 1 minute, pour the 1%HPMC solution that adds lemon yellow into stir about 5 minutes, 150 rev/mins of mixing speeds, 18 order nylon mesh are granulated, airpillow-dry, 65 ℃ of inlet temperature, drop temperature is controlled at 30 ℃-40 ℃, 16 order iron wire sieve granulate, discharging;
Mix:
Measure medicine-containing particle content, even with sugared granule by 2: 1 mixed, be up to the standards, packing, promptly.
The preparation and the external stripping of the dried mixed suspension preparation of embodiment 4 azithromycins
One, the preparation of the dried mixed suspension preparation of azithromycin
Granulating process:
A, with xanthan gum 30g, after fibroin albumen 10g mixes, under 55 ℃ of conditions, stir fusion and insulation, slowly add micropowder silica gel 10g while stirring, micropowder silica gel is uniformly dispersed, compositions is standby;
B, make microemulsion, in emulsion, add lactobionic acid azithromycin 1150g (in azithromycin), place 50 ℃ of water-baths with propoxylation methyl glucoside 30g, isobutanol 10ml, ethyl acetate 80ml;
C, add resulting composition among a in microemulsion, be stirred to evenly, as reactant liquor, the pH value of regulating this reactant liquor with 10% NaOH solution is 9.0 with this solution, adding 25ml methanol, isothermal reaction 1.5 hours;
D, reactant liquor is cooled to 0 ℃, the glutaraldehyde that adds 0.1 times of reactant liquor volume continues to stir 30 minutes, slowly is warming up to 50 ℃ again, and adding glacial acetic acid to pH value is 3.0, obtains suspension;
E, treat that sedimentation is complete after static, the supernatant that inclines filters, and washes with water to no aldehyde to distinguish the flavor of, and drains, and is standby.
F, sodium carbonate is crossed 80 mesh sieves, get d, gained precipitum, 4.24g microcrystalline Cellulose, 1.056g sodium carbonate, put into high speed granulator, do and mixed 1 minute, add 11.2g 20% arabic gum aqueous solution, stirred discharging 5 minutes, 18 order nylon mesh are granulated, airpillow-dry, 65 ℃ of inlet temperature, 38.5 ℃ of drop temperatures, pellet moisture is 3.68%, 16 order iron wire sieve granulate; Granule is crossed 40 mesh sieves sieve fine powder, get coarse granule;
The sugar granule preparing process:
Cane sugar powder is crossed 100 mesh sieves, take by weighing the 0.09g lemon yellow and add in the 1.7g1%HPMC solution and stir, take by weighing 20.47g Icing Sugar, 8.77g mannitol, the sweet high speed granulator of putting into of 0.75g A Siba, do and mixed 1 minute, pour the 1%HPMC solution that adds lemon yellow into stir about 5 minutes, 150 rev/mins of mixing speeds, 18 order nylon mesh are granulated, airpillow-dry, 65 ℃ of inlet temperature, drop temperature is controlled at 30 ℃-40 ℃, 16 order iron wire sieve granulate, discharging;
Mix:
Measure medicine-containing particle content, even with sugared granule by 2: 1 mixed, be up to the standards, packing specification is 100mg/ bag (in an azithromycin), promptly.
Two, the external stripping of the dried mixed suspension preparation of azithromycin
Dissolution medium is that 100r/min, temperature are 37.0 ℃ ± 0.5 ℃ for pH6.80 phosphate buffer 900ml, the rotating speed of handling through the degassing, respectively at 5,15,30,45,60,120,240,360 and 480min after the 5ml that takes a sample, use filtering with microporous membrane, and benefit is gone into the equivalent medium, get filtrate and measure it, find c (m1), calculate accumulation stripping percentage rate by the standard curve regression equation at wavelength 321nm place, and with the dried mixed suspension preparation of commercially available azithromycin in contrast, see Table 1.
The external stripping experimental result of dried mixed suspension preparation of table 1 azithromycin of the present invention and the dried mixed suspension preparation of commercially available azithromycin
The result shows that the external molten slow releasing function with advantage of dried mixed suspension preparation of azithromycin of the present invention and the dried mixed suspension preparation of commercially available azithromycin has reduced toxic and side effects, has improved patient's compliance.
The dried mixed suspension preparation clinical research of embodiment 6 azithromycins of the present invention untoward reaction situation
100 routine patients have participated in the clinical research of this product, be equally divided into test group and matched group at random, wherein test group is taken the dried mixed suspension preparation of lactobionic acid azithromycin of the present invention, matched group is taken the common slow release dry suspension composition preparation of commercially available lactobionic acid azithromycin, the dried mixed suspension preparation specification of above lactobionic acid azithromycin is the 100mg/ bag, and day obeys once, each 1 bag, took for 2 weeks continuously, see Table 2.
The untoward reaction of dried mixed suspension preparation of the present invention and commercially available common dried mixed suspension preparation in table 2 clinical research
Because preparation of the present invention has tangible slow releasing function, having avoided medicine to dash forward releases, improved patient's compliance, reduced stomachache, felt sick, gastrointestinal symptoms such as vomiting, stomach spasm and diarrhoea, and erythra, the temporary rising of transaminase, one cross the generation of the generation untoward reaction of untoward reaction such as property neutrophilic granulocyte minimizing, has significant clinical meaning.
Obviously, the foregoing description only is the example of enumerating for clearly demonstrating, and the variation of other form of making on the basis of the above still is among protection scope of the present invention.
Claims (10)
1. dried mixed suspension preparation of azithromycin, it is mixed by azithromycin granule and sugared granule, it is characterized in that, contain xanthan gum-fibroin albumen-micropowder silica gel compositions in the described azithromycin granule, the weight portion of xanthan gum is 1.5～4.5 in the said composition, the weight portion of fibroin albumen is 1, and the weight portion of micropowder silica gel is 1; Described azithromycin granule and sugared particulate mixed proportion are 2: 1.
2. the dried mixed suspension preparation of azithromycin according to claim 1 is characterized in that the weight portion of described xanthan gum is 3, and the weight portion of fibroin albumen is 1, and the weight portion of micropowder silica gel is 1.
3. the dried mixed suspension preparation of azithromycin according to claim 2 is characterized in that, in the described azithromycin granule, the weight portion of azithromycin is 20～25, and the weight portion of xanthan gum-fibroin albumen-micropowder silica gel compositions is 1.
4. the dried mixed suspension preparation of azithromycin according to claim 3 is characterized in that the weight portion of described azithromycin is 23, and the weight portion of xanthan gum-fibroin albumen-micropowder silica gel compositions is 1.
5. the dried mixed suspension preparation of azithromycin according to claim 4 is characterized in that described azithromycin granule also contains the component of following weight portion:
Microcrystalline Cellulose 4～4.5
Sodium carbonate 1～1.2
20% arabic gum aqueous solution 11～11.5.
6. the dried mixed suspension preparation of azithromycin according to claim 5 is characterized in that described azithromycin granule is made of the component of following weight portion:
Azithromycin 23
Xanthan gum-fibroin albumen micropowder silica gel compositions 1
Microcrystalline Cellulose 4.24
Sodium carbonate 1.056
20% arabic gum aqueous solution 11.2.
7. the dried mixed suspension preparation of azithromycin according to claim 6 is characterized in that, described sugared granule is made of the component of following weight portion:
Cane sugar powder 20～21
Mannitol 8～9
A Siba sweet 0.5～1
Lemon yellow 0.05～0.1
1％HPMC 1.5～2。
8. the dried mixed suspension preparation of azithromycin according to claim 7 is characterized in that, described sugared granule is made of the component of following weight portion:
Cane sugar powder 20.47
Mannitol 8.77
A Siba sweet 0.75
Lemon yellow 0.09
1％HPMC 1.7。
9. the dried mixed suspension preparation of azithromycin according to claim 8 is characterized in that described azithromycin granule is made of the component of following weight portion:
Azithromycin 23
Xanthan gum-fibroin albumen-micropowder silica gel compositions 1
Microcrystalline Cellulose 4.24
Sodium carbonate 1.056
20% arabic gum aqueous solution 11.2;
Described sugared granule is made of the component of following weight portion:
Cane sugar powder 20.47
Mannitol 8.77
A Siba sweet 0.75
Lemon yellow 0.09
1％HPMC 1.7。
10. method for preparing as the dried mixed suspension preparation of azithromycin as described in the claim 1,2,3,4,5,6,7,8 or 9 is characterized in that it prepares according to the following steps:
Granulating process:
A, with xanthan gum with after fibroin albumen mixes by usage ratio, under 55～60 ℃ of conditions, stir fusion and insulation, slowly add micropowder silica gel while stirring, micropowder silica gel is uniformly dispersed, compositions is standby;
B, be that 3: 1: 8 ratio makes microemulsion, in emulsion, add azithromycin or its officinal salt, place 40～60 ℃ of water-baths according to propoxylation methyl glucoside weight, isobutanol volume, ethyl acetate volume ratio; Described weight, volume unit are respectively g and ml;
C, adding resulting composition among the step a in microemulsion, be stirred to evenly, as reactant liquor, is that pH value that 10% NaOH solution regulate this reactant liquor be 8.0～10.0 with weight concentration with this solution, adding 20～30ml methanol, isothermal reaction 1～2 hour;
D, reactant liquor is cooled to 0 ℃, the glutaraldehyde that adds 0.08～0.125 times of reactant liquor volume continues to stir 30 minutes, slowly is warming up to 40～60 ℃ again, and adding glacial acetic acid to the value of pH is 2.0～4.0, obtains suspension;
E, treat that sedimentation is complete after static, the supernatant that inclines filters, and washes with water to no aldehyde to distinguish the flavor of, and drains.
F, sodium carbonate is crossed 80 mesh sieves, take by weighing d, gained precipitum, microcrystalline Cellulose, sodium carbonate, put into high speed granulator, do and mixed 1 minute, add 20% arabic gum aqueous solution, stirred discharging 5 minutes, 18 order nylon mesh are granulated, airpillow-dry, 65 ℃ of inlet temperature, 38.5 ℃ of drop temperatures, pellet moisture is 3.68%, 16 order iron wire sieve granulate; Granule is crossed 40 mesh sieves sieve fine powder, get coarse granule;
The sugar granule preparing process:
Cane sugar powder is crossed 100 mesh sieves, take by weighing lemon yellow and add in the 1%HPMC solution and stir, take by weighing Icing Sugar, mannitol, the sweet high speed granulator of putting into of A Siba, do and mixed 1 minute, pour the 1%HPMC solution that adds lemon yellow into stir about 5 minutes, 150 rev/mins of mixing speeds, 18 order nylon mesh are granulated, airpillow-dry, 65 ℃ of inlet temperature, drop temperature is controlled at 30 ℃-40 ℃, 16 order iron wire sieve granulate, discharging;
Mix:
Measure medicine-containing particle content, even with sugared granule by 2: 1 mixed, be up to the standards, packing, promptly.
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| CN104825409A (en) * | 2015-04-27 | 2015-08-12 | 四川制药制剂有限公司 | Preparation process of azithromycin dry suspension |
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