CN104825408A - Azithromycin dispersible tablet and preparation method and use thereof - Google Patents
Azithromycin dispersible tablet and preparation method and use thereof Download PDFInfo
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- azithromycin
- dispersible tablet
- silica gel
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- 229960004099 azithromycin Drugs 0.000 title claims abstract description 72
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 title claims abstract description 72
- 239000007919 dispersible tablet Substances 0.000 title claims abstract description 67
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 35
- 239000000741 silica gel Substances 0.000 claims abstract description 35
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 35
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims abstract description 31
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 31
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims abstract description 31
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 31
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 31
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 31
- 239000008101 lactose Substances 0.000 claims abstract description 27
- 239000003826 tablet Substances 0.000 claims abstract description 22
- 239000000945 filler Substances 0.000 claims abstract description 16
- 239000000843 powder Substances 0.000 claims abstract description 13
- 229920000881 Modified starch Polymers 0.000 claims abstract description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 58
- 235000019359 magnesium stearate Nutrition 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 18
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 8
- 238000010348 incorporation Methods 0.000 claims description 7
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 5
- 238000007907 direct compression Methods 0.000 claims description 4
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 4
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 4
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 4
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 4
- 239000011812 mixed powder Substances 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 2
- 238000011017 operating method Methods 0.000 claims description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 12
- 238000004090 dissolution Methods 0.000 abstract description 10
- 239000003795 chemical substances by application Substances 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 abstract description 2
- 229920001353 Dextrin Polymers 0.000 abstract description 2
- 239000004375 Dextrin Substances 0.000 abstract description 2
- 229930195725 Mannitol Natural products 0.000 abstract description 2
- 229920002472 Starch Polymers 0.000 abstract description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 abstract description 2
- 230000015556 catabolic process Effects 0.000 abstract description 2
- 238000006731 degradation reaction Methods 0.000 abstract description 2
- 235000019425 dextrin Nutrition 0.000 abstract description 2
- 239000006185 dispersion Substances 0.000 abstract description 2
- 239000000594 mannitol Substances 0.000 abstract description 2
- 235000010355 mannitol Nutrition 0.000 abstract description 2
- 238000011160 research Methods 0.000 abstract description 2
- 239000008107 starch Substances 0.000 abstract description 2
- 235000019698 starch Nutrition 0.000 abstract description 2
- 235000000346 sugar Nutrition 0.000 abstract description 2
- 238000005336 cracking Methods 0.000 abstract 1
- 239000000314 lubricant Substances 0.000 abstract 1
- 238000009702 powder compression Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 4
- 108010011485 Aspartame Proteins 0.000 description 3
- 239000000605 aspartame Substances 0.000 description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 3
- 235000010357 aspartame Nutrition 0.000 description 3
- 229960003438 aspartame Drugs 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 2
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 2
- 239000004376 Sucralose Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 239000003120 macrolide antibiotic agent Substances 0.000 description 2
- 229940085605 saccharin sodium Drugs 0.000 description 2
- 235000019408 sucralose Nutrition 0.000 description 2
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229960001866 silicon dioxide Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- -1 wherein Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention provides an azithromycin dispersible tablet which is composed of the following raw materials by weight: 10-16 parts of micro powder silica gel, 60-120 parts of microcrystalline cellulose, 20-40 parts of low-substituted hydroxypropyl cellulose, 8-15 parts of a tablet agent lubricant and 0-50 parts of a filling agent; the filling agent is one of or a combination of two or more of the following components: lactose, pregelatinized starch, starch, dextrin, mannitol, sugar powder and calcium carbonate. The present invention also provides a preparation method and use of the dispersible tablet, by a large number of experimental researches of the dispersible tablet prescription, the azithromycin dispersible tablet prescription suitable for powder direct tableting can be finally obtained, the phenomenon such as sticking and picking, cracking, cover removing and the like in the powder direct tableting process of the azithromycin can be solved, the dispersible tablet with uniform dispersion and good dissolution and other performances can be obtained, and the obtained dispersible tablet can guarantee the stability of main medicines, avoids the degradation of the main medicines, and provides more secure selection for clinical medication.
Description
This divisional application is denomination of invention is " a kind of Azithromycin dispersible tablet and its production and use ", and application number is 2012105902402, and the applying date is the divisional application of in December, the 2012 original invention patent application of 31 days.
Technical field
The present invention relates to a kind of Azithromycin dispersible tablet and its production and use.
Background technology
Azithromycin, belongs to macrolide antibiotics, and have unique pharmacokinetic characteristics, biological half-life is long, and tissue permeability is high, chemical and biological stability is good, has a broad antifungal spectrum, the advantages such as untoward reaction is little, better tolerance.Be widely used in respiratory tract, skin soft tissue and urogenital infections clinically.This kind dosage form of current domestic listing includes ordinary tablet, dispersible tablet, capsule, granule, dry suspension etc.
Due to azithromycin poorly water-soluble, ordinary tablet stripping in vivo and absorption are greatly affected.Dispersible tablet is the novel quick-effective preparation of one in recent years developed rapidly, both can directly take, also can be quickly dispersed in after in water and drink, it is slow that the appearance of this dosage form solves solid preparation disintegrate, stripping is poor, the problems such as bioavailability is not high, are particularly suitable for the medicine that infection, antipyretic-antalgic etc. need quick acting.This dosage form had clear and definite definition and requirement in 2010 in version " Chinese Pharmacopoeia ", and " dispersible tablet means in water can disintegrate homodisperse tablet rapidly.Medicine in dispersible tablet should be indissoluble.Dispersible tablet can add aqueous dispersion deutostoma clothes, also dispersible tablet can be contained in mouth and suck clothes or swallow.
Existing research worker is by azithromycin prepared composition discrete piece at present, achieves good therapeutic effect.But, there is following problem in the Azithromycin dispersible tablet of listing: existing Azithromycin dispersible tablet preparation method is all tablettings after wet granulation, but azithromycin is macrolide antibiotics, unstable under wet heat condition, inevitably be exposed in hygrothermal environment in wet-granulation process, principal agent can be degraded, and related substance can obviously increase, and makes medicine may there is certain potential safety hazard.
If the method for powder formulation tabletting can be adopted to prepare dispersible tablet, then can solve the problem.But inventor studies discovery, because the compressibility of azithromycin own is poor, and have viscosity, be easy to cause sticking, sliver, the problems such as friability is defective in the process of carrying out tabletting, this phenomenon more highlights when adopting technique of direct powder compression.
Summary of the invention
For above-mentioned defect, the object of the present invention is to provide a kind of Azithromycin dispersible tablet being suitable for direct pressed powder, and the preparation method of Azithromycin dispersible tablet and purposes.
The invention provides a kind of Azithromycin dispersible tablet, it is the preparation be prepared from by the supplementary material of following weight proportion:
Azithromycin 250 parts;
Micropowder silica gel 10 ~ 16 parts, microcrystalline Cellulose 60 ~ 120 parts, low-substituted hydroxypropyl cellulose 20 ~ 40 parts, with lubricator 8 ~ 15 parts, tablet, filler 0 ~ 50 part; Described filler is one or more the combination in lactose, pregelatinized Starch, starch, dextrin, mannitol, Icing Sugar, calcium carbonate.
Further, described micropowder silica gel is 12 ~ 16 parts, and low-substituted hydroxypropyl cellulose is 25 ~ 40 parts.
Further, described microcrystalline Cellulose is 70 ~ 120 parts.
Further, described filler is that lactose is or/and pregelatinized Starch; Described tablet is with lubricator one or more the combination in magnesium stearate, sodium stearyl fumarate, Pulvis Talci, glyceryl monostearate.
Further preferably, it is the preparation be prepared from by the supplementary material of following weight proportion:
Azithromycin 250 parts;
Micropowder silica gel 12 ~ 14 parts, microcrystalline Cellulose 70 ~ 90 parts, low-substituted hydroxypropyl cellulose 25 ~ 40 parts, with lubricator 8 ~ 10 parts, tablet, filler 30 ~ 50 parts; Wherein, tablet is with lubricator magnesium stearate, and filler is lactose.
Further preferably, it is the preparation be prepared from by the supplementary material of following weight proportion:
Azithromycin 250 parts, micropowder silica gel 14 parts, microcrystalline Cellulose 90 parts, lactose 30 parts, low-substituted hydroxypropyl cellulose 25 parts, magnesium stearate 10 parts;
Or, azithromycin 250 parts, micropowder silica gel 16 parts, microcrystalline Cellulose 110 parts, lactose 20 parts, pregelatinized Starch 20 points, low-substituted hydroxypropyl cellulose 25 parts, magnesium stearate 15 parts;
Or, azithromycin 250 parts, micropowder silica gel 14 parts, microcrystalline Cellulose 80 parts, lactose 40 parts, low-substituted hydroxypropyl cellulose 25 parts, magnesium stearate 10 parts;
Or, azithromycin 250 parts, micropowder silica gel 12 parts, microcrystalline Cellulose 70 parts, lactose 50 parts, low-substituted hydroxypropyl cellulose 40 parts, magnesium stearate 8 parts;
Or, azithromycin 250 parts, micropowder silica gel 15 parts, microcrystalline Cellulose 120 parts, low-substituted hydroxypropyl cellulose 40 parts, magnesium stearate 8 parts;
Or, azithromycin 250 parts, micropowder silica gel 16 parts, microcrystalline Cellulose 90 parts, lactose 30 parts, low-substituted hydroxypropyl cellulose 25 parts, Pulvis Talci 15 parts;
Or, azithromycin 250 parts, micropowder silica gel 14 parts, microcrystalline Cellulose 90 parts, lactose 30 parts, low-substituted hydroxypropyl cellulose 25 parts, magnesium stearate 5 parts, Pulvis Talci 10 parts;
Or, azithromycin 250 parts, micropowder silica gel 14 parts, microcrystalline Cellulose 90 parts, lactose 30 parts, low-substituted hydroxypropyl cellulose 25 parts, sodium stearyl fumarate 15 parts;
Or, azithromycin 250 parts, micropowder silica gel 16 parts, microcrystalline Cellulose 90 parts, lactose 30 parts, low-substituted hydroxypropyl cellulose 25 parts, glyceryl monostearate 15 parts.
Wherein, described adjuvant also comprises 1-3 part correctives.
Further, described correctives is aspartame, steviosin, saccharin sodium or sucralose.
Present invention also offers the preparation method of above-mentioned Azithromycin dispersible tablet, it comprises following operating procedure:
(1) supplementary material is taken by weight ratio;
(2) after getting other supplementary materials except magnesium stearate, sieve, mixing, then add magnesium stearate mix homogeneously, direct compression, obtain dispersible tablet.
Further, the concrete operations of step (2) are as follows:
A, get azithromycin and micropowder silica gel, mixed 80 ~ 100 mesh sieves, mix homogeneously, and obtained powder a;
B, other adjuvants got except magnesium stearate and micropowder silica gel, mix homogeneously, obtains powder b;
C, powder a, b are crossed 40 ~ 60 mesh sieves, after mix homogeneously, then add magnesium stearate mixing, incorporation time is within 30min, and gained mixed-powder direct compression, obtains dispersible tablet.
Further, in step C, after adding magnesium stearate, incorporation time is 5 ~ 30min.
The present invention is by studying the lot of experiments of dispersible tablet prescription, finally obtain the Azithromycin dispersible tablet prescription of applicable direct powder compression, not only solve sticking, sliver that azithromycin occurs in direct powder compression process, take off the phenomenons such as lid, obtain be uniformly dispersed, the dispersible tablet of good performance such as dissolution, simultaneously, gained dispersible tablet ensure that the stability of principal agent, avoids the degraded of principal agent, for clinical application provides safer selection.
Detailed description of the invention
The preparation method of embodiment 1 Azithromycin dispersible tablet of the present invention
Prescription
Preparation method:
1, get azithromycin and mix 80 mesh sieves with micropowder silica gel, mix homogeneously;
2, by lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, aspartame mix homogeneously;
3, above two kinds of powder are crossed 60 mesh sieves, after mix homogeneously, add magnesium stearate and mix 5-10min in mixer;
4, regulate tablet machine pressure and sheet weight, get above-mentioned mixed powder and carry out tabletting, obtain 1000 dispersible tablets.
The present invention, except use aspartame is as except correctives, can also use sucrose, steviosin, saccharin sodium, sucralose, edible essence and their compositions etc.
The preparation method of embodiment 2 Azithromycin dispersible tablet of the present invention
Prepare dispersible tablet according to the prescription of embodiment 1 and preparation method, wherein step 1,3 the whole incorporation time crossing grit number and step 3 with reference to following table, gained dispersible tablet result is as follows:
Table 1
From the above results, after reaching 30min when combined, slice, thin piece hardness significantly declines, and in order to ensure the concordance of product quality, the present invention can preferred incorporation time 5-30min.
Embodiment 3 Azithromycin dispersible tablet of the present invention prescription preferred
Because the compressibility of azithromycin own is poor, and have viscosity, be easy to cause sticking, sliver, the problems such as friability is defective in the process of carrying out tabletting, this phenomenon more highlights when adopting technique of direct powder compression.
In order to obtain the Azithromycin dispersible tablet of high-quality, the present invention screens dispersible tablet prescription, and wherein, prescription proportioning and incorporation time are all according to table 2, and preparation method is with reference to embodiment 1.
Table 2
Brief summary:
(1) from prescription 1-13 relatively, if do not add micropowder silica gel in prescription, then dispersible tablet sticking phenomenon is comparatively obvious; If adopt pregelatinized Starch and cross-linking sodium carboxymethyl cellulose in prescription, replace lactose and low-substituted hydroxypropyl cellulose, the then easy sliver of dispersible tablet, friability is undesirable;
By the screening to supplementary product kind, the supplementary product kind that the present invention finally determines is: micropowder silica gel, microcrystalline Cellulose, lactose, low-substituted hydroxypropyl cellulose, magnesium stearate, and appropriate correctives and pregelatinized Starch, finally obtaining substantially qualified dispersible tablet supplementary material proportioning is:
Azithromycin 250 parts; Micropowder silica gel 10 ~ 16 parts, microcrystalline Cellulose 60 ~ 120 parts, low-substituted hydroxypropyl cellulose 20 ~ 40 parts, with lubricator 8 ~ 15 parts, tablet, filler 0 ~ 50 part.
(2) from prescription 2-4,7-18 relatively, even if having selected supplementary product kind, but different supplementary product consumptions still plays crucial effect to the performance of dispersible tablet, wherein, dispersible tablet under prescription 2 supplementary product consumption proportioning, disintegration is longer, dispersing uniformity and dissolution poor; The dispersed homogeneous degree of prescription 3 adjuvant is general; The feature eligibility such as the dissolution of prescription 11, but disintegration is longer, more than 1min.Therefore, the present invention determines that standard compliant dispersible tablet supplementary material proportioning is:
Azithromycin 250 parts; Micropowder silica gel 12 ~ 16 parts, microcrystalline Cellulose 60 ~ 120 parts, low-substituted hydroxypropyl cellulose 25 ~ 40 parts, with lubricator 8 ~ 15 parts, tablet, filler 0 ~ 50 part.
(3) in order to improve the dissolution (more than 90%) of dispersible tablet further, the present invention can be preferably as follows supplementary material proportioning:
Azithromycin 250 parts; Micropowder silica gel 12 ~ 16 parts, microcrystalline Cellulose 70 ~ 120 parts, low-substituted hydroxypropyl cellulose 25 ~ 40 parts, with lubricator 8 ~ 15 parts, tablet, filler 0 ~ 50 part.
(4) in order to ensure that dissolution is more than 90%, can reduce again the friability of tablet further, ensure that tablet is at transport, intact in storage, the present invention is finally also preferably as follows supplementary material proportioning:
Azithromycin 250 parts; Micropowder silica gel 12 ~ 14 parts, microcrystalline Cellulose 70 ~ 90 parts, low-substituted hydroxypropyl cellulose 25 ~ 40 parts, with lubricator 8 ~ 10 parts, tablet, filler 30 ~ 50 parts; Wherein, tablet is with lubricator magnesium stearate, and filler is lactose.
Beneficial effect of the present invention is illustrated below by way of test example.
The tablet properties of test example 1 Azithromycin dispersible tablet of the present invention measures
The dissolution of Azithromycin dispersible tablet of the present invention (prepared by embodiment 1), friability, disintegration and dispersing uniformity is measured by " Chinese Pharmacopoeia " 2010 editions correlation techniques.Result is see table 3,4.
Table 3 Azithromycin dispersible tablet dissolution (%) of the present invention testing result (n=6)
| Sample name | 3min | 10min |
| Embodiment 1 sample 1 | 93.2 | 99.7 |
| Embodiment 1 sample 2 | 94.3 | 99.5 |
| Embodiment 1 sample 3 | 92.7 | 100.3 |
Other testing results of table 4 Azithromycin dispersible tablet of the present invention (n=6)
| Sample name | Embodiment 1 sample 1 | Embodiment 1 sample 2 | Embodiment 1 sample 3 |
| Friability | 0.13％ | 0.15％ | 0.11％ |
| Disintegration | 25s | 30s | 27s |
| Dispersing uniformity | Conform with the regulations (< 1min) | Conform with the regulations (< 1min) | Conform with the regulations (< 1min) |
From the above results, Azithromycin dispersible tablet prepared by the present invention, overcome sticking, sliver that azithromycin occurs in direct powder compression process, take off the problems such as lid, prepare the dispersible tablet that dissolution, friability, disintegration and dispersing uniformity are all good.
Test example 2 Azithromycin dispersible tablet of the present invention is on the impact of feed degradation
Its related substances in Azithromycin dispersible tablet of the present invention (prepared by embodiment 1) and Azithromycin Raw Material is measured, in order to determine whether the preparation of dispersible tablet of the present invention causes degraded to raw material by " Chinese Pharmacopoeia " 2010 editions correlation techniques.The results are shown in Table 5.
Table 5 Azithromycin Raw Material and dispersible tablet related substance testing result
| Sample name | Maximum unknown single assorted % | Total assorted % |
| Raw material | 0.54 | 2.58 |
| Embodiment 1 sample 1 | 0.55 | 2.57 |
| Embodiment 1 sample 2 | 0.54 | 2.58 |
| Embodiment 1 sample 3 | 0.55 | 2.58 |
From the above results, in dispersible tablet finished product of the present invention, its related substances and raw material are consistent, and namely show, in production process, principal agent composition keeps stable, does not occur degraded.
The present invention is by studying the lot of experiments of dispersible tablet prescription, finally obtain the Azithromycin dispersible tablet prescription of applicable direct powder compression, not only solve sticking, sliver that azithromycin occurs in direct powder compression process, take off the phenomenons such as lid, obtain be uniformly dispersed, the dispersible tablet of good performance such as dissolution, simultaneously, gained dispersible tablet ensure that the stability of principal agent, avoids the degraded of principal agent, for clinical application provides safer selection.
In addition, compared with existing wet granule compression tablet, the present invention does not adopt binding agent to granulate, drying, saves operation and energy consumption, reduces the CCP in whole technique, reduce the difficulty of quality control.
Claims (8)
1. an Azithromycin dispersible tablet, is characterized in that: it is the preparation be prepared from by the supplementary material of following weight proportion:
Azithromycin 250 parts;
Micropowder silica gel 12 ~ 16 parts, microcrystalline Cellulose 60 ~ 120 parts, low-substituted hydroxypropyl cellulose 25 ~ 40 parts, with lubricator 8 ~ 15 parts, tablet, filler 0 ~ 50 part; Described filler is the compositions of lactose or lactose and pregelatinized Starch, and described tablet is with lubricator one or more the combination in magnesium stearate, sodium stearyl fumarate, Pulvis Talci, glyceryl monostearate.
2. Azithromycin dispersible tablet according to claim 1, is characterized in that: described microcrystalline Cellulose is 70 ~ 120 parts.
3. the Azithromycin dispersible tablet according to claim 1-2 any one, is characterized in that: it is the preparation be prepared from by the supplementary material of following weight proportion:
Azithromycin 250 parts;
Micropowder silica gel 12 ~ 14 parts, microcrystalline Cellulose 70 ~ 90 parts, low-substituted hydroxypropyl cellulose 25 ~ 40 parts, with lubricator 8 ~ 10 parts, tablet, filler 30 ~ 50 parts; Wherein, tablet is with lubricator magnesium stearate, and filler is lactose.
4. the Azithromycin dispersible tablet according to claim 1-3 any one, is characterized in that: it is the preparation be prepared from by the supplementary material of following weight proportion:
Azithromycin 250 parts, micropowder silica gel 14 parts, microcrystalline Cellulose 90 parts, lactose 30 parts, low-substituted hydroxypropyl cellulose 25 parts, magnesium stearate 10 parts;
Or, azithromycin 250 parts, micropowder silica gel 16 parts, microcrystalline Cellulose 110 parts, lactose 20 parts, pregelatinized Starch 20 points, low-substituted hydroxypropyl cellulose 25 parts, magnesium stearate 15 parts;
Or, azithromycin 250 parts, micropowder silica gel 14 parts, microcrystalline Cellulose 80 parts, lactose 40 parts, low-substituted hydroxypropyl cellulose 25 parts, magnesium stearate 10 parts;
Or, azithromycin 250 parts, micropowder silica gel 12 parts, microcrystalline Cellulose 70 parts, lactose 50 parts, low-substituted hydroxypropyl cellulose 40 parts, magnesium stearate 8 parts;
Or, azithromycin 250 parts, micropowder silica gel 15 parts, microcrystalline Cellulose 120 parts, low-substituted hydroxypropyl cellulose 40 parts, magnesium stearate 8 parts;
Or, azithromycin 250 parts, micropowder silica gel 16 parts, microcrystalline Cellulose 90 parts, lactose 30 parts, low-substituted hydroxypropyl cellulose 25 parts, Pulvis Talci 15 parts;
Or, azithromycin 250 parts, micropowder silica gel 14 parts, microcrystalline Cellulose 90 parts, lactose 30 parts, low-substituted hydroxypropyl cellulose 25 parts, magnesium stearate 5 parts, Pulvis Talci 10 parts;
Or, azithromycin 250 parts, micropowder silica gel 14 parts, microcrystalline Cellulose 90 parts, lactose 30 parts, low-substituted hydroxypropyl cellulose 25 parts, sodium stearyl fumarate 15 parts;
Or, azithromycin 250 parts, micropowder silica gel 16 parts, microcrystalline Cellulose 90 parts, lactose 30 parts, low-substituted hydroxypropyl cellulose 25 parts, glyceryl monostearate 15 parts.
5. the Azithromycin dispersible tablet according to claim 1-4 any one, is characterized in that: described adjuvant also comprises 1-3 part correctives.
6. the preparation method of Azithromycin dispersible tablet described in claim 1-5 any one, is characterized in that: it comprises following operating procedure:
(1) supplementary material is taken by weight ratio;
(2) after getting other supplementary materials except magnesium stearate, sieve, mixing, then add magnesium stearate mix homogeneously, direct compression, obtain dispersible tablet.
7. preparation method according to claim 6, is characterized in that: the concrete operations of step (2) are as follows:
A, get azithromycin and micropowder silica gel, mixed 80 ~ 100 mesh sieves, mix homogeneously, and obtained powder a;
B, other adjuvants got except magnesium stearate and micropowder silica gel, mix homogeneously, obtains powder b;
C, powder a, b are crossed 40 ~ 60 mesh sieves, after mix homogeneously, then add magnesium stearate mixing, incorporation time is within 30min, and gained mixed-powder direct compression, obtains dispersible tablet.
8. preparation method according to claim 7, is characterized in that: in step C, and after adding magnesium stearate, incorporation time is 5 ~ 30min.
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| CN106279312A (en) * | 2016-08-16 | 2017-01-04 | 珠海同源药业有限公司 | A kind of azithromycin compound and combinations thereof thing |
| CN112315924A (en) * | 2020-11-10 | 2021-02-05 | 迪沙药业集团有限公司 | Azithromycin composition and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103550181B (en) * | 2013-11-04 | 2015-06-17 | 深圳致君制药有限公司 | Azithromycin dispersible tablet and preparation method thereof |
| CN103655496A (en) * | 2013-12-10 | 2014-03-26 | 山东淄博新达制药有限公司 | Azithromycin dispersible tablet and preparation process thereof |
| CN113559073A (en) * | 2021-07-20 | 2021-10-29 | 海南海神同洲制药有限公司 | Azithromycin tablet and preparation method thereof |
| CN114983954B (en) * | 2022-06-15 | 2023-09-12 | 广州新济药业科技有限公司 | Folic acid tablet and preparation method thereof |
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| CN101129398A (en) * | 2007-09-13 | 2008-02-27 | 天津药业集团新郑股份有限公司 | Azithromycin dispersible tablet and method of preparing the same |
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| WO2005009447A1 (en) * | 2003-07-24 | 2005-02-03 | Pliva - Research And Development Ltd. | Single dose fast dissolving azithromycin |
| CN102018679A (en) * | 2009-09-11 | 2011-04-20 | 上海天龙药业有限公司 | Azithromycin dispersing tablet with improved mouthfeel and preparation method of same |
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| CN101129398A (en) * | 2007-09-13 | 2008-02-27 | 天津药业集团新郑股份有限公司 | Azithromycin dispersible tablet and method of preparing the same |
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| CN106279312A (en) * | 2016-08-16 | 2017-01-04 | 珠海同源药业有限公司 | A kind of azithromycin compound and combinations thereof thing |
| CN106279312B (en) * | 2016-08-16 | 2019-08-20 | 珠海同源药业有限公司 | A kind of azithromycin compound and combinations thereof |
| CN112315924A (en) * | 2020-11-10 | 2021-02-05 | 迪沙药业集团有限公司 | Azithromycin composition and preparation method thereof |
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