CN106749174A - A kind of sitafloxacin dihydrate crystal formation, preparation method and combinations thereof tablet - Google Patents
A kind of sitafloxacin dihydrate crystal formation, preparation method and combinations thereof tablet Download PDFInfo
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- CN106749174A CN106749174A CN201611112671.2A CN201611112671A CN106749174A CN 106749174 A CN106749174 A CN 106749174A CN 201611112671 A CN201611112671 A CN 201611112671A CN 106749174 A CN106749174 A CN 106749174A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A61K9/2004—Excipients; Inactive ingredients
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- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- C07B2200/13—Crystalline forms, e.g. polymorphs
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Abstract
The invention belongs to pharmaceutical technology field.Specifically, the present invention relates to sitafloxacin dihydrate crystal formation, preparation method and combinations thereof tablet.Sitafloxacin dihydrate crystal formation provided by the present invention, preparation method include dissolving, crystallization the step of.The present invention also provides the composition containing the crystallization, and the component of following part by weight is included by sitafloxacin dihydrate crystallization active ingredient:Sitafloxacin dihydrate 32 33%, mannitol 38 39%, starch 19 20%, hydroxypropyl cellulose 6 7%, hydroxypropyl methyl cellulose 1.3 1.4%, magnesium stearate 0.9 1%;The method for making above-mentioned Sitafloxacin hydrate tablet, including pulverizing and sieving, pelletizing, dry, the step such as whole grain, total mixed, compressing tablet.Compared with prior art, dissolution rate and bioavilability are improved Sitafloxacin hydrate tablet according to obtained by the present invention.
Description
Technical field
The invention belongs to pharmaceutical technology field, specifically, it is related to a kind of sitafloxacin dihydrate crystal formation, preparation method
And combinations thereof tablet.
Background technology
Sitafloxacin (sitafloxacin), chemical entitled 7- [(7S)-amino -5- azaspiro [2.4] hept- 5- yls] -8-
The chloro- fluoro- 1- of 6- [(1R, 2S)-cis-2- fluorine cyclopropyl]-Isosorbide-5-Nitrae-dihydro -4- oxo -3- quinoline carboxylic acids, are Japanese first pharmacy
The Development of Fluoroquinolone Antibacterials of company's research and development, it is clinical with its 3/2 hydrate.Sitafloxacin is a kind of new oral, with wide
The N-1- fluorine cyclopropyl novel carbostyril antimicrobials of antibacterial activity are composed, to aerobism or anaerobic gram positive bacteria and Ge Lanyin
Property bacterium, Mycoplasma and chlamydiaceae etc. there is broad-spectrum antibacterial action.Sitafloxacin compound has three asymmetric carbon atoms, its
With 1 enantiomter and 6 diastereoisomers, determine that the absolute configuration of its medicinal compound is pacified for ensureing medication
It is complete significant.
Current document report five kinds of different crystal forms [Int.J.Pharm., 2010,402,110-116] of sitafloxacin,
Including anhydride α, β types, 1/2 hydrate, 1 hydrate and 3/2 hydrate, its medicinal crystal formation is 3/2 hydrate, i.e. 7-
[7- (S)-amino -5- azaspiro [2.4] heptane -5- bases] the fluoro- 1- of the chloro- 6- of -8- [the fluoro- 1- cyclopropyl of (1R, 2S) -2-] -1,4-
The hydrate of dihydro -4- Oxoquinoline-3-carboxylic acids 3/2.But, water is dissolved in because sitafloxacin is extremely difficult, it is obtained using existing crystal formation
Tablet, it is oral after dissolve slow in vivo, and be difficult to reach and be completely dissolved, causing the bioavilability of medicine reduces, no
Preferable antibacterial effect can be obtained.Those skilled in the art have been surprisingly found that, using novel crystal forms obtained in sitafloxacin dihydrate,
The suitable auxiliary material of addition is made tablet, surprisingly finds the obtained tablet of the present invention, and dissolution rate and bioavilability are improved, so that
Complete the present invention.
The content of the invention
The first object of the present invention is to provide a kind of sitafloxacin dihydrate crystal formation.
Second object of the present invention is to provide a kind of preparation method of sitafloxacin dihydrate crystal formation, the method work
Skill is simple, easy to operate, and the sitafloxacin dihydrate crystalline stability prepared using the method is good.
A further object of the present invention is to provide one kind containing sitafloxacin dihydrate crystal formation of the present invention or adopt
Tablet composition and preparation method thereof, the present inventor are made with sitafloxacin dihydrate crystal formation obtained in the method for the invention
It was found that using tablet obtained in sitafloxacin dihydrate crystal formation, improving drug dissolution, bioavilability is improve.
To realize the purpose of the present invention, the present invention is adopted the following technical scheme that:
The compound of sitafloxacin dihydrate crystal formation shown in a kind of formula (I), wherein,
Preferably, the X-ray powder that the sitafloxacin dihydrate crystal formation that the present invention is provided is represented with the 2 θ ± 0.2 ° angles of diffraction
Last diffracting spectrum 3.7 °, 5.3 °, 10.3 °, 11.5 °, 15.3 °, 16.8 °, 17.7 °, 19.8 °, 21.7 °, 24.8 °, 27.6 °,
Characteristic diffraction peak is shown at 30.6 °, 34.1 ° and 39.8 °.
Preferably, the X-ray that the sitafloxacin dihydrate crystal formation that the present invention is provided is obtained using Cu-K alpha ray measurements
Powder diagram is as shown in Figure 1.
Second object of the present invention is achieved through the following technical solutions:
A kind of preparation method of the sitafloxacin dihydrate crystal formation described in claim 1, comprises the following steps:
1) sitafloxacin crude product is dissolved in absolute ethyl alcohol, anhydrous propanone and deionized water, is heated to reflux, obtain solution A;
2) 40 DEG C~50 DEG C are cooled to, activated carbon is added, 30min is stirred, filtering obtains solution B, is cooled to 20~25 DEG C
Crystallization 1h, growing the grain 3~12 hours;
3) drip washing is carried out with absolute ethyl alcohol, obtains white solid;
4) by step 3) obtained by solid be placed in vacuum drying chamber, system is vacuumized, dry to constant weight, obtain final product sitafloxacin
Dihydrate crystal formation.
Preferably, by weight, step 1) in sitafloxacin:Absolute ethyl alcohol:Anhydrous propanone is 1:3-8:2-5:5-20, enters
One step preferably, sitafloxacin:Absolute ethyl alcohol:Anhydrous propanone is 1:3-5:2-3:8-10.
Preferably, step 4) described in drying carried out under the conditions of 30-50 DEG C.
The present invention also provides a kind of composition tablet containing sitafloxacin dihydrate, wherein, said composition tablet contains
There is sitafloxacin dihydrate crystal formation obtained in the present invention.
Composition label active ingredient includes following part by weight:Sitafloxacin dihydrate 32-33%, mannitol 38-
39%th, starch 19-20%, hydroxypropyl cellulose 6-7%, hydroxypropyl methyl cellulose 1.3-1.4%, magnesium stearate 0.9-1%.
The present inventor has prepared a kind of sitafloxacin dihydrate crystal formation in the research process of sitafloxacin bulk drug,
Stability of crystal form is good, and the tablet being made is crystallized with sitafloxacin dihydrate of the invention, effective ingredient can with compared with
Fast speed is discharged from medicine, improves the dissolution rate and bioavilability of medicine.
Composition tablet provided by the present invention can preferably be adopted using being prepared from well known to a person skilled in the art method
Prepare with the following method:
(1) pulverize and sieve:80 mesh sieves are crossed after sitafloxacin is crushed, other auxiliary materials cross 80 mesh sieves.
(2) sitafloxacin dihydrate crystal formation is mixed with the supplementary material of size-reduced sieving, is pelletized, dried, whole grain,
Compressing tablet, obtains final product.
Compared with prior art, the invention has the advantages that:
(1) sitafloxacin dihydrate crystal formation provided by the present invention, good stability.
(2) Dissolution of Tablet and bioavilability that sitafloxacin dihydrate crystal formation prepared by the present invention is made are high.(3)
The preparation method process is simple of sitafloxacin dihydrate crystal formation provided by the present invention, it is easy to operate.
Brief description of the drawings
Fig. 1 is the X-ray diffracting spectrum of sitafloxacin dihydrate crystal formation of the invention;
Fig. 2 is the TG collection of illustrative plates of sitafloxacin dihydrate crystal formation of the invention;
After Fig. 3 is for 24 male volunteers multi-dose oral 50mg sitafloxacins test preparations and reference preparation, Xi Tasha
Star mean blood plasma concentration-time graph.
Specific embodiment
The present invention can be conducted further description by the following examples, but invention of the invention is not limited to
The following examples, these embodiments limit the scope of the present invention never in any form.Those skilled in the art will in right
Some done change and adjustment also is regarded as belonging to the scope of the present invention in the range of asking.
Embodiment 1:The preparation of sitafloxacin dihydrate crystal formation
1) sitafloxacin crude product 1kg is dissolved in 3kg absolute ethyl alcohols, 2kg anhydrous propanones and deionized water 5kg, is heated back
Stream, obtains solution A;
2) 40 DEG C~50 DEG C, plus activated carbon 25g are cooled to, 30min is stirred, solution B is obtained, 20~25 DEG C of crystallizations are cooled to
1h, growing the grain 3 hours;
3) drip washing is carried out with 2kg absolute ethyl alcohols, obtains white solid;
4) by step 3) obtained by solid be placed in vacuum drying chamber, system is vacuumized, under the conditions of 30 DEG C dry to constant weight,
Obtain final product sitafloxacin dihydrate crystal formation.
Prepared sitafloxacin dihydrate crystal formation is composed using the X-ray powder diffraction that Cu-K alpha ray measurements are obtained
Figure (see Fig. 1) in characteristic peak 2 θ be 3.7 °, 5.3 °, 10.3 °, 11.5 °, 15.3 °, 16.8 °, 17.7 °, 19.8 °, 21.7 °,
24.8 °, 27.6 °, 30.6 °, 34.1 ° and 39.8 ° displays.
Elementary analysis:
Measured value:C51.21%, H4.98%, Cl7.97%, F8.51%, N9.45%, O17.95%.
Theoretical value:C51.18%, H4.97%, Cl7.95%, F8.52%, N9.42%, O17.94%.
Elementary analysis result is basically identical with theoretical value, and its molecular formula is C19H18ClF2N3O3·2H2O
Using Perkin-Elmer companies of U.S. PEPyrisDiamondTG thermal analyzers, thermogravimetric analysis experiment show (see
Fig. 2):The moisture content 8.079% contained in sitafloxacin dihydrate crystallization prepared by the embodiment, this is (theoretical with containing 2 crystallizations water
Be worth is result 8.084%) within error range.
Embodiment 2:The preparation of sitafloxacin dihydrate crystal formation
1) sitafloxacin crude product 1kg is dissolved in 8kg absolute ethyl alcohols, 5kg anhydrous propanones and deionized water 10kg, is heated back
Stream, obtains solution A;
2) 40 DEG C~50 DEG C, plus activated carbon 25g are cooled to, 30min is stirred, filtering obtains solution B, is cooled to 20~25
DEG C crystallization 1h, growing the grain 6 hours;
3) drip washing is carried out with 3kg absolute ethyl alcohols, obtains white solid;
4) by step 3) obtained by solid be placed in vacuum drying chamber, system is vacuumized, under the conditions of 40 DEG C dry to constant weight,
Obtain final product sitafloxacin dihydrate crystal formation.
According to XPRD data, gained crystal formation is consistent with crystal formation in embodiment 1.Using Perkin-Elmer companies of the U.S.
The thermogravimetric analysis collection of illustrative plates that PEPyrisDiamondTG thermogravimetric analyzers are obtained is consistent with embodiment 1.
Embodiment 3:The preparation of sitafloxacin dihydrate crystal formation
1) sitafloxacin crude product 1kg is dissolved in 5kg absolute ethyl alcohols, 3kg anhydrous propanones and deionized water 20kg, is heated back
Stream, obtains solution A;
2) 40 DEG C~50 DEG C, plus activated carbon 25g are cooled to, 30min is stirred, filtering obtains solution B, is cooled to 20~25
DEG C crystallization 1h, growing the grain 12 hours;
3) drip washing is carried out with 5kg absolute ethyl alcohols, obtains white solid;
4) by step 3) obtained by solid be placed in vacuum drying chamber, system is vacuumized, under the conditions of 50 DEG C dry to constant weight,
Obtain final product sitafloxacin dihydrate crystal formation.
According to XPRD data, gained crystal formation is consistent with crystal formation in embodiment 1.Using Perkin-Elmer companies of the U.S.
The thermogravimetric analysis collection of illustrative plates that PEPyrisDiamondTG thermogravimetric analyzers are obtained is consistent with embodiment 1.
Embodiment 4:The preparation of sitafloxacin dihydrate crystal formation
1) sitafloxacin crude product 1kg is dissolved in 3kg absolute ethyl alcohols, 2kg anhydrous propanones and deionized water 8kg, is heated back
Stream, obtains solution A;
2) 40 DEG C~50 DEG C, plus activated carbon 25g are cooled to, 30min is stirred, filtering obtains solution B, is cooled to 20~25
DEG C crystallization 1h, growing the grain 9 hours;
3) drip washing is carried out with 3kg absolute ethyl alcohols, obtains white solid;
4) by step 3) obtained by solid be placed in vacuum drying chamber, system is vacuumized, under the conditions of 30 DEG C dry to constant weight,
Obtain final product sitafloxacin dihydrate crystal formation.
According to XPRD data, gained crystal formation is consistent with crystal formation in embodiment 1.Using Perkin-Elmer companies of the U.S.
The thermogravimetric analysis collection of illustrative plates that PEPyrisDiamondTG thermogravimetric analyzers are obtained is consistent with embodiment 1.
【Example of formulations】The preparation of sitafloxacin composition tablet
Embodiment 1
The present embodiment provides a kind of sitafloxacin tablet composition, and effective ingredient includes the component of following part by weight:
Label:
Sitafloxacin dihydrate crystal formation 54.39g is (equivalent to 50gC19H18ClF2N3O3);
Mannitol 64.59g;
Starch 33.99g;
Hydroxypropyl cellulose 11.39g;
Hydroxypropyl methyl cellulose 2.38g;
Magnesium stearate 1.52g.
It is coated:Opadry (OPADRYXYWHITE) 4.13g, pure water 30.29g.
The preparation method of the present embodiment sitafloxacin dihydrate tablet composition is comprised the following steps:
A, pulverize and sieve:80 mesh sieves are crossed after sitafloxacin dihydrate crystal formation is crushed, other label auxiliary materials cross 80 mesh
Sieve.
B, granulation:Sitafloxacin, mannitol, starch, hydroxypropyl cellulose are placed in high speed wet mixing pelletizer, are mixed
Close uniform, hydroxypropyl methyl cellulose is configured to the 5% hydroxypropyl methyl cellulose aqueous solution as adhesive, by adhesive
1000 wet granulars are mixed and made into the supplementary material in granulator.
C, drying:Wet granular turns into dry particl in aeration-drying at 55-65 DEG C.
D, whole grain:Dry particl is through 30 mesh sieve whole grains.
It is e, total mixed:Magnesium stearate and surplus hydroxypropyl cellulose are weighed, is placed in mixing in mixer with dry particl one
It is even.
Middle product detecting step:The parameters such as the angle of repose of middle product that the total mixed step of detection is obtained, if meeting standard, enter
Row next step.
F, compressing tablet:Mixed particle carries out compressing tablet.
G, coating:Coating solution is made into pure water and Opadry, coat tablets is coated in and is dried, obtain 1000 finished products, often
Piece contains pure sitafloxacin 50mg.
Embodiment 2
The present embodiment provides a kind of sitafloxacin tablet composition, and effective ingredient includes the component of following part by weight:
Label:
Sitafloxacin dihydrate crystal formation 54.42g is (equivalent to 50gC19H18ClF2N3O3);
Mannitol 64.31g;
Starch 31.33g;
Hydroxypropyl cellulose 11.05g;
Hydroxypropyl methyl cellulose 2.14g;
Magnesium stearate 1.65g
It is coated:Opadry (OPADRYXYWHITE) 4.13g, pure water 30.29g.
The preparation method of the present embodiment sitafloxacin dihydrate tablet composition is comprised the following steps:
A, pulverize and sieve:80 mesh sieves are crossed after sitafloxacin dihydrate crystal formation is crushed, other label auxiliary materials cross 80 mesh
Sieve.
B, granulation:Sitafloxacin, mannitol, starch, hydroxypropyl cellulose are placed in high speed wet mixing pelletizer, are mixed
Close uniform, hydroxypropyl methyl cellulose is configured to the 5% hydroxypropyl methyl cellulose aqueous solution as adhesive, by adhesive
1000 wet granulars are mixed and made into the supplementary material in granulator.
C, drying:Wet granular turns into dry particl in aeration-drying at 55-65 DEG C.
D, whole grain:Dry particl is through 30 mesh sieve whole grains.
It is e, total mixed:Magnesium stearate and surplus hydroxypropyl cellulose are weighed, is placed in mixing in mixer with dry particl one
It is even.
Middle product detecting step:The parameters such as the angle of repose of middle product that the total mixed step of detection is obtained, if meeting standard, enter
Row next step.
F, compressing tablet:Mixed particle carries out compressing tablet.
G, coating:Coating solution is made into pure water and Opadry, coat tablets is coated in and is dried, obtain 1000 finished products, often
Piece contains pure sitafloxacin 50mg.
Test example 1:Accelerated stability is investigated
1.5 crystallizations water of commercially available sitafloxacin, the sitafloxacin dihydrate crystal formation of embodiment 1 are entered in climatic chamber
The row accelerated stability test of 6 months.Experimental condition is:40 DEG C/75% relative humidity (RH), respectively at 0,1,2,3,6 months
Sampling, carries out purity and foreign impurity matters test (high performance liquid chromatography), as a result see the table below 1.
The Acceleration study result of table 1
From upper table result, the stability of sitafloxacin dihydrate crystal formation is better than sitafloxacin 1.5 in the prior art
The individual crystallization water.
Aforementioned stable experiment has been also carried out to the sitafloxacin dihydrate crystal formation prepared by the embodiment of the present invention 2~4,
The result that it is obtained is similar.
Test example 2:Dissolution in vitro compares
Contrast solution compound method:Take the dry sitafloxacin reference substance to constant weight appropriate, it is accurately weighed, use dissolution medium
It is diluted to the solution of about 5 μ g in every 1ml.
The first commercially available pharmacy Sankyo Co., Ltd (trade name is taken respectively:Gracevit) sitafloxacin tablet and preparation reality
Apply sitafloxacin dihydrate tablet obtained in example 1,6 every batch, using water as dissolution medium, according to above-mentioned dissolution and measure side
Method is tested.The appropriate simultaneously fluid infusion of solution is taken respectively at 5min, 10min, 15min, 30min, 45min, 60min, filtration is accurate
Measure subsequent filtrate appropriate, solubilization goes out the solution that WATER AS FLOW MEDIUM is diluted to about 5 μ g in every 1ml, the mensuration absorbance at 288nm is calculated
Dissolution rate, as a result as shown in table 2.
The dissolution rate comparing result of table 2
Contrast item | 5min | 10min | 15min | 30min | 45min | 60min |
Commercially available prod | 25.1 | 46.2 | 62.4 | 74.2 | 83.4 | 91.2 |
The product of embodiment 1 | 60.2 | 81.9 | 90.5 | 95.6 | 97.8 | 98.3 |
Tablet dissolution rate as prepared by upper table result can be seen that the present invention is more than commercially available prod dissolution rate.
Test example 3:Bioavilability compares
Compare by test preparation (the sitafloxacin dihydrate tablet composition of invention formulation embodiment 1) and reference system
Agent (is obtained, except that sitafloxacin used is commercially available original using the prescription and preparation technology of invention formulation embodiment 1
Material) pharmacokinetics.
After 24 male volunteers multi-dose oral 50mg sitafloxacins test preparations and reference preparation, sitafloxacin is average
Blood concentration-time curve is shown in Fig. 3.
The Cmax by test preparation is can be seen that better than reference reagent from the mean blood plasma concentration-time graph of sitafloxacin,
Identical experiment is also carried out to the sitafloxacin tablet prepared by invention formulation embodiment 2, the result that it is obtained is similar.
Claims (8)
1. a kind of sitafloxacin dihydrate crystal formation, it is characterised in that the structural formula of described sitafloxacin dihydrate is as follows:
2. sitafloxacin dihydrate crystal formation as claimed in claim 1, it is characterised in that it is represented with the 2 θ ± 0.2 ° angles of diffraction
X-ray powder diffraction collection 3.7 °, 5.3 °, 10.3 °, 11.5 °, 15.3 °, 16.8 °, 17.7 °, 19.8 °, 21.7 °,
Characteristic diffraction peak is shown at 24.8 °, 27.6 °, 30.6 °, 34.1 ° and 39.8 °.
3. sitafloxacin dihydrate crystal formation as claimed in claim 1, it is characterised in that obtained using Cu-K alpha ray measurements
X-ray powder diffraction figure it is as shown in Figure 1.
4. a kind of preparation method of the sitafloxacin dihydrate crystal formation described in claim 1, it is characterised in that described preparation
Method comprises the following steps:
1) sitafloxacin crude product is dissolved in absolute ethyl alcohol, anhydrous propanone and deionized water, is heated to reflux, obtain solution A;
2) 40 DEG C~50 DEG C are cooled to, activated carbon is added, 30min is stirred, filtering obtains solution B, is cooled to 20~25 DEG C of crystallizations
1h, growing the grain 3~12 hours;
3) drip washing is carried out with absolute ethyl alcohol, obtains white solid;
4) by step 3) obtained by solid be placed in vacuum drying chamber, system is vacuumized, dry to constant weight, obtain final product the water of sitafloxacin two
Compound crystal formation.
5. the preparation method of sitafloxacin dihydrate crystal formation as claimed in claim 4, it is characterised in that by weight, step
It is rapid 1) described in sitafloxacin:Absolute ethyl alcohol:Anhydrous propanone:Deionized water is 1:3-8:2-5:5-20.
6. the preparation method of sitafloxacin dihydrate crystal formation according to claim 4, it is characterised in that by weight,
Step 1) described in sitafloxacin:Absolute ethyl alcohol:Anhydrous propanone:Deionized water is 1:3-5:2-3:8-10.
7. the preparation method of sitafloxacin dihydrate crystal formation as claimed in claim 4, it is characterised in that:Step 4) described in
Drying carried out under the conditions of 30~50 DEG C.
8. a kind of composition tablet containing sitafloxacin dihydrate described in claim 1, it is characterised in that label effectively into
Dividing includes following part by weight:Sitafloxacin dihydrate 32-33%, mannitol 38-39%, starch 19-20%, hydroxypropyl are fine
Dimension element 6-7%, hydroxypropyl methyl cellulose 1.3-1.4%, magnesium stearate 0.9-1%.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN110790744A (en) * | 2018-08-03 | 2020-02-14 | 南京优科生物医药研究有限公司 | Pyridonecarboxylic acid derivatives, process for preparing same and compositions containing same |
CN113181125A (en) * | 2021-04-27 | 2021-07-30 | 海南通用三洋药业有限公司 | Sitafloxacin hydrate tablet and preparation method thereof |
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CN1106006A (en) * | 1993-09-10 | 1995-08-02 | 第一制药株式会社 | Crystals of antimicrobial compound |
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CN1106006A (en) * | 1993-09-10 | 1995-08-02 | 第一制药株式会社 | Crystals of antimicrobial compound |
Non-Patent Citations (2)
Title |
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TETSUYA SUZUKI ET AL.: "Elucidation of the crystal structure–physicochemical property relationship among polymorphs and hydrates of sitafloxacin, a novel fluoroquinolone antibiotic", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
TETSUYA SUZUKI ET AL.: "Studies on mechanism of thermal crystal transformation of sitafloxacin hydrates through melting and recrystallization, yielding different anhydrates depending on initial crystalline forms", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110790744A (en) * | 2018-08-03 | 2020-02-14 | 南京优科生物医药研究有限公司 | Pyridonecarboxylic acid derivatives, process for preparing same and compositions containing same |
CN113181125A (en) * | 2021-04-27 | 2021-07-30 | 海南通用三洋药业有限公司 | Sitafloxacin hydrate tablet and preparation method thereof |
CN113181125B (en) * | 2021-04-27 | 2022-07-19 | 海南通用三洋药业有限公司 | Sitafloxacin hydrate tablet and preparation method thereof |
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