CN106176646B - Tosufloxacin tosylate dispersible tablets and preparation method thereof - Google Patents
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Abstract
The invention discloses a tosufloxacin tosylate dispersible tablet, which comprises the following components: 20-45 parts of tosufloxacin tosylate, 35-44 parts of microcrystalline cellulose, 7-20 parts of pregelatinized starch, 2-10 parts of mannitol, 1-5 parts of silicon dioxide, 300.8-1.2 parts of povidone K, 1-4 parts of sodium carboxymethyl starch, 1-4 parts of aspartame, 0.8-1.2 parts of magnesium stearate and 0.8-1.2 parts of strawberry essence. The tosufloxacin tosylate dispersible tablet has the advantages of shorter disintegration time, high dissolution rate, good stability and good antibacterial effect.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a tosufloxacin tosylate dispersible tablet and a preparation method thereof.
Background
Tosufloxacin tosylate, its chemical name is: 7- [ 3-amino-1- (pyrrolidinyl)]-1- (2, 4-difluorophenyl) -6-fluoro-1, 4-dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid p-toluenesulfonate monohydrate with the molecular formula C26H23F3N4O6S·H2O, molecular weight 594.57, is a quinolone broad-spectrum antibacterial drug, is white to light yellow powder, has no odor, slightly bitter taste, hygroscopicity, and gradually deepening color when exposed to light, is slightly soluble in sodium hydroxide test solution, is hardly soluble in water or chloroform, and is easily soluble in dimethylformamide or glacial acetic acid.
Tosufloxacin tosylate, a quinolone antibacterial agent, was developed by Nippon Fushan chemical industry, Inc., and first introduced into the market in Japan in 1990, it was reported that Tosufloxacin tosylate has a strong bactericidal activity against gram-positive bacteria, gram-negative bacteria, mycoplasma anaerobe, chlamydia, etc., and is suitable for treating various systemic infections caused by Tosufloxacin-sensitive bacteria in adult patients, such as superficial and deep skin infections, secondary infections such as trauma or thermal injury and surgical injury, osteomyelitis, arthritis, acute bronchitis, pneumonia, pyelonephritis, prostatitis, urethritis, etc.
Kohno carries out investigation and arrangement on the clinical application of tosufloxacin tosylate, wherein the investigation is mainly aimed at the antibacterial capacity of respiratory tract infection, some germs show drug resistance to antibacterial drugs such as cephalosporins and carbapenems, the tosufacin tosylate is more important in future application, the tosufacin tosylate belongs to an insoluble drug, and the tosufacin tosylate has the defects of poor water solubility, slow generation of drug effect, low bioavailability and the like when being prepared into a common tablet, so that the application of the tosufacin tosylate is limited.
Chinese patent CN104546735A discloses a tosufloxacin tosylate granule for children, wherein the main drug is tosufloxacin tosylate, and the auxiliary materials comprise sucrose, aspartame, hydroxypropyl cellulose SSL, silicon dioxide and the like, wherein the sucrose is a diluent and a sweetening agent, the aspartame is a sweetening agent, the hydroxypropyl cellulose SSL is an adhesive, the fresh orange powder essence is a flavoring agent, the silicon dioxide is a flow aid, and the carmine is a coloring agent to jointly form the formula.
The present invention has been made in view of the above circumstances.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides the tosufloxacin tosylate dispersible tablet which has the advantages of good stability, high bioavailability, short disintegration time and good antibacterial effect.
The invention provides a tosufloxacin tosylate dispersible tablet, which comprises the following components:
the tosufloxacin tosylate dispersible tablet of the invention adopts microcrystalline cellulose, pregelatinized starch and mannitol as fillers, the microcrystalline cellulose is crystalline cellulose with smaller polymerization degree prepared by partial hydrolysis of the cellulose, has good compressibility and stronger adhesive force, the pressed tablet has larger hardness, the pregelatinized starch has good fluidity, compressibility, self-lubricating property and dry adhesiveness and better disintegration effect, the mannitol is in the form of particles or powder, the sodium carboxymethyl starch is used as a disintegrant, is colorless and fixed powder, has very obvious water absorption and expansion effects, can expand to 300 times of the original volume after absorbing water, and is a disintegrant with excellent performance.
Preferably, the dispersible tablet of tosufloxacin tosylate comprises the following components:
the inventor finds that the composition of various medicines has better stability, dissolution and shorter disintegration time in the proportion through a large number of experiments.
Further, the tosufloxacin tosylate is tosufloxacin tosylate crystal, the structural formula is shown as formula I, and an X-ray powder diffraction spectrogram obtained by Cu-Kalpha ray measurement is shown as figure 1:
due to the fact that the solid medicine has polymorphism, the same solid medicine can exist in an amorphous form or in different crystal structure forms, different crystal forms of the same medicine can have obvious differences in solubility, thermal stability and the like, and X-ray powder diffraction of the tosufloxacin tosylate crystal has characteristic peaks at the positions of 10.13 degrees, 10.61 degrees, 13.21 degrees, 15.42 degrees, 15.81 degrees, 18.49 degrees, 21.84 degrees, 22.32 degrees, 23.04 degrees, 25.96 degrees, 26.42 degrees and 30.16 degrees of 2 theta.
Tests show that the tosufloxacin tosylate composition consisting of the tosufloxacin tosylate crystals prepared by the invention has better stability, short disintegration time and high dissolution rate.
The second object of the invention provides a preparation method of the tosufloxacin tosylate crystal, which comprises the following steps:
(1) dissolving the crude tosufloxacin tosylate in a mixed solution of an organic solvent and water at the temperature of 40-80 ℃, preferably 45 ℃, and uniformly mixing, stirring and dissolving;
(2) adding active carbon into the solution, decarbonizing and filtering;
(3) cooling, standing and crystallizing;
(4) and after the crystal is completely separated out, washing and drying to obtain the tosufloxacin tosylate crystal.
Further, in the step (1), the mass volume ratio of the tosufloxacin tosylate to the mixed solution of the organic solvent and the water is 1:5g-15 ml.
Further, the organic solvent is ethanol with a volume fraction of 95%, and the volume ratio of ethanol to water is 10-1:1, preferably 1: 1.
Furthermore, the mass fraction of the activated carbon is 0.1-0.3%.
Further, the temperature in the step (3) is reduced to 28-32 ℃, and the standing time is 10-20 hours.
Further, the drying temperature in the step (4) is 40-60 ℃.
The third object of the invention provides a preparation method of the tosufloxacin tosylate dispersible tablet, which comprises the following steps:
(1) preparing an adhesive, namely stirring and dissolving povidone K-30 by using ethanol, clarifying the solution without condensate, and adding purified water for mixing for later use;
(2) granulating; weighing tobathiacin tosylate, microcrystalline cellulose, pregelatinized starch, mannitol and silicon dioxide according to a formula ratio, putting into a granulator for granulation, stirring and mixing, pouring the prepared adhesive solution into the mixed raw and auxiliary materials to prepare a soft material, continuously stirring, and then preparing into granules;
(3) drying, sieving and granulating;
(4) mixing, namely uniformly mixing the whole dried granules with the carboxymethyl starch sodium, the aspartame, the magnesium stearate and the strawberry essence according to the prescription amount;
(5) tabletting, encapsulating and warehousing.
The tosufloxacin tosylate dispersible tablet is prepared by the process, and has better dissolution rate and stability.
Compared with the prior art, the invention has the beneficial effects that: the tosufloxacin tosylate dispersible tablet has the advantages of shorter disintegration time, high dissolution rate, good stability and good antibacterial effect.
Drawings
FIG. 1X-ray powder diffraction pattern of tobramfloxacin tosylate crystals of example 1 of the invention.
Detailed Description
Example 1
(1) Dissolving the crude tosufloxacin tosylate in a mixed solution of ethanol and water with the volume fraction of 95% at the temperature of 40 ℃, and uniformly mixing, stirring and dissolving, wherein the volume ratio of the ethanol to the water is 1:1, and the mass volume ratio of the tosufloxacin tosylate to the mixed solution of the ethanol and the water is 1g:10 ml.
(2) Adding a proper amount of 0.2 percent of activated carbon by mass into the solution, and then filtering;
(3) cooling the filtered solution to 30 ℃, standing for 15 hours, and crystallizing;
(4) and after the crystal is completely separated out, washing and drying at 50 ℃ to obtain the tosufloxacin tosylate crystal.
The obtained tosufloxacin tosylate crystal has an X-ray powder diffraction spectrum measured by Cu-Kalpha ray, as shown in figure 1, and the X-ray powder diffraction of the tosufloxacin tosylate crystal has characteristic peaks at 2 theta of 10.13 degrees, 10.61 degrees, 13.21 degrees, 15.42 degrees, 15.81 degrees, 18.49 degrees, 21.84 degrees, 22.32 degrees, 23.04 degrees, 25.96 degrees, 26.42 degrees and 30.16 degrees.
Example 2
(1) Dissolving the crude tosufloxacin tosylate in a mixed solution of ethanol and water with the volume fraction of 95% at the temperature of 45 ℃, and uniformly mixing, stirring and dissolving, wherein the volume ratio of the ethanol to the water is 10:1, and the mass volume ratio of the tosufloxacin tosylate to the mixed solution of the ethanol and the water is 1g:5 ml.
(2) Adding a proper amount of 0.1 percent of activated carbon by mass into the solution, and then filtering;
(3) cooling the filtered solution to 28 ℃, standing for 10 hours, and crystallizing;
(4) and after the crystal is completely separated out, washing and drying at 40 ℃ to obtain the tosufloxacin tosylate crystal.
The obtained tosufloxacin tosylate crystal has an X-ray powder diffraction pattern substantially in accordance with example 1, which is measured by using Cu-Ka rays.
Example 3
(1) Dissolving the crude tosufloxacin tosylate in a mixed solution of ethanol and water with the volume fraction of 95% at the temperature of 80 ℃, and uniformly mixing, stirring and dissolving, wherein the volume ratio of the ethanol to the water is 5:1, and the mass volume ratio of the tosufloxacin tosylate to the mixed solution of the ethanol and the water is 1g:3 ml.
(2) Adding a proper amount of 0.3 percent of activated carbon by mass into the solution, and then filtering;
(3) cooling the filtered solution to 32 ℃, standing for 20 hours, and crystallizing;
(4) and after the crystal is completely separated out, washing and drying at 60 ℃ to obtain the tosufloxacin tosylate crystal.
The obtained tosufloxacin tosylate crystal has an X-ray powder diffraction pattern substantially in accordance with example 1, which is measured by using Cu-Ka rays.
Example 4 prescription of dispersible tablet of tosufloxacin tosylate
The preparation method of the tosufloxacin tosylate dispersible tablet comprises the following steps:
(1) preparing an adhesive, namely stirring and dissolving povidone K-30 by using ethanol, clarifying the solution without condensate, and adding purified water for mixing for later use;
(2) granulating; weighing tobathiacin tosylate, microcrystalline cellulose, pregelatinized starch, mannitol and silicon dioxide according to a formula ratio, putting into a granulator for granulation, stirring and mixing, pouring the prepared adhesive solution into the mixed raw and auxiliary materials to prepare a soft material, continuously stirring, and then preparing into granules;
(3) transferring the granulated particles into a fluidized bed dryer for drying, and sieving and granulating the dried particles;
(4) totally mixing, namely putting the whole dried granules, the sodium carboxymethyl starch, the aspartame, the magnesium stearate and the strawberry essence in a formula amount into a multidirectional motion mixer, and starting a mixing key to uniformly mix the granules;
(5) tabletting the mixed granules by using a rotary tablet press, packaging by using an aluminum plastic packaging machine, and warehousing finished products after the inspection is qualified.
Example 5 prescription of dispersible tablets of tosufloxacin tosylate
Wherein, the preparation method of the tosufloxacin tosylate dispersible tablet is the same as the example 4.
Example 6 prescription of dispersible tablets of tosufloxacin tosylate
Wherein, the preparation method of the tosufloxacin tosylate dispersible tablet is the same as the example 4.
Example 7
The prescription and preparation method of the tosufloxacin tosylate dispersible tablet in this example are the same as example 5, except that the tosufloxacin tosylate is the tosufloxacin tosylate crystal prepared in example 1.
Example 8
The prescription and preparation method of the tosufloxacin tosylate dispersible tablet in this example are the same as example 5, except that the tosufloxacin tosylate is the tosufloxacin tosylate crystal prepared in example 2.
Test example 1 dissolution measurement
Test drugs 1 to 5 were tosufloxacin tosylate dispersible tablets prepared in examples 4 to 8, respectively;
control 1: tolsufloxacin tosylate particles prepared according to the formulation and method of example 3 of patent CN 104546735A;
according to a dissolution rate measuring method (XC second method which is an appendix of the second part of the Chinese pharmacopoeia 2005 version), 1000ml of phosphate buffer solution (pH value is 2.0) is used as a dissolution medium, the rotating speed is 75 revolutions per minute, the method is operated, when the rotating speed is 30 minutes, 10ml of solution is taken, the solution is filtered, 3ml to 50ml of subsequent filtrate is accurately taken, the solution is diluted to a scale by the dissolution medium, the solution is shaken evenly, the absorbance is measured at the wavelength of 270nm according to an ultraviolet-visible spectrophotometry method (IVA which is an appendix of the second part of the Chinese pharmacopoeia 2005 version), a proper amount of tosufloxacin tosylate reference substance is taken, precisely weighed, dissolved and diluted into a solution with corresponding concentration, the absorbance is measured by the same method, the dissolution rate of each tablet is calculated, and the test.
Table 1 dissolution results
| Sample (I) | 5 |
10 minutes | 15 |
30 minutes | 45 minutes |
| Test drug 1 | 92.5 | 94.9 | 96.3 | 97.8 | 98.6 |
| Test drug 2 | 93.4 | 95.1 | 97.2 | 98.5 | 99.0 |
| Test drug 3 | 92.6 | 94.8 | 96.6 | 97.4 | 98.7 |
| Test drug 4 | 93.4 | 95.9 | 97.8 | 99.1 | 99.5 |
| Test drug 5 | 93.6 | 95.8 | 97.9 | 99.0 | 99.4 |
| Control drug 1 | 90.6 | 92.8 | 94.1 | 95.6 | 96.4 |
As can be seen from Table 1, the tobathiacin tosylate dispersible tablets prepared by the invention have better dissolution rate and improved bioavailability, and the dissolution rate data of the experimental medicaments 1-3 and the experimental medicaments 3 and 4 show that the tobathiacin tosylate dispersible tablets prepared by the tobathiacin tosylate crystals prepared by the invention have better dissolution rate because the tobathiacin tosylate crystals have brand new molecular arrangement structures, and compared with the bulk drugs, the molecular binding force of the crystal lattice to the tobathiacin tosylate is weakened, so that the tobathiacin tosylate is easier to break out of the crystal lattice into a solvent, and the dissolution rate is higher. As can be seen from the experimental medicines 1-5 and the contrast medicine 1, the dispersible tablet of tosufloxacin tosylate of the invention has better dissolution rate compared with the prior art.
Test example 2 stability test
Test drugs 1: the dispersible tablet of tosufloxacin tosylate prepared in example 5;
test drugs 2: the dispersible tablet of tosufloxacin tosylate prepared in example 7;
control 1: tolsufloxacin tosylate particles prepared according to the formulation and method of patent CN104546735A example 3.
The test drugs 1 and 2 and the control drug 1 were placed in a clean plate, spread to a thin layer of 5mm or less, placed under strong light (4500lx), high temperature (60 ℃), and high humidity (RH 92.5%, RH 75%) for 10 days, sampled on days 0, 5, and 10, respectively, and the results of the measurements were shown in table 2 below.
TABLE 2 stability results
As can be seen from table 2, the test drugs 1 and 2 have better dissolution rate, less impurities and less content change under the action of high temperature, high humidity and strong light compared with the control drug 1, and as can be seen from the test drugs 1 and 2, the dispersible tablets prepared by using the tobramoxacin tosylate crystals prepared by the invention have better effect because the tobramfloxacin tosylate crystals have better stability.
The inventor also conducted the above-mentioned tests on the dispersible tablets of tosufloxacin tosylate prepared in other examples, and the results are similar to this, and are not listed because of space limitation.
Test example 3 antibacterial test
(1) Test drug
Test drugs 1: the dispersible tablet of tosufloxacin tosylate prepared in example 5;
test drugs 2: the dispersible tablet of tosufloxacin tosylate prepared in example 7;
control 1: tolsufloxacin tosylate particles prepared according to the formulation and method of patent CN104546735A example 3.
(2) Test strains: streptococcus pneumoniae, haemophilus influenzae and gram-positive bacteria.
(3) Culture medium: three groups of Streptococcus pneumoniae, Haemophilus influenzae and gram-positive bacteria in the same amount were cultured in the medium for 24 hours, and then the test drug and the control drug in the same concentration were added to the three groups, respectively.
(4) Determination of Minimum Inhibitory Concentration (MIC)
The MICs of the test drug and the control drug were determined as shown in Table 3:
TABLE 3 determination of minimum inhibitory concentration
As can be seen from Table 3, the minimum inhibitory concentration of the test drug is lower than that of the control drug, which indicates that the Toshifloxacin tosylate dispersible tablet of the invention has better inhibitory effect than that of the control drug, and the dispersible tablet prepared by the Toshifloxacin tosylate crystal has better inhibitory effect.
The inventor also conducted the above-mentioned tests on the dispersible tablets of tosufloxacin tosylate prepared in other examples, and the results are similar to this, and are not listed because of space limitation.
The embodiments in the above embodiments can be further combined or replaced, and the embodiments are only used for describing the preferred embodiments of the present invention, and do not limit the concept and scope of the present invention, and various changes and modifications made to the technical solution of the present invention by those skilled in the art without departing from the design idea of the present invention belong to the protection scope of the present invention.
Claims (10)
1. The tosufloxacin tosylate dispersible tablet is characterized by comprising the following components:
the tosufloxacin tosylate is tosufloxacin tosylate crystal, the structural formula is shown as formula I, and an X-ray powder diffraction spectrogram obtained by Cu-K alpha ray measurement is shown as figure 1:
2. the dispersible tablet of tosufloxacin tosylate according to claim 1, wherein the preparation method of the tosufloxacin tosylate crystal comprises the following steps:
(1) dissolving the crude tosufloxacin tosylate in a mixed solution of an organic solvent and water at the temperature of 40-80 ℃, and uniformly mixing, stirring and dissolving;
(2) adding active carbon into the solution, decarbonizing and filtering;
(3) cooling, standing and crystallizing;
(4) and after the crystal is completely separated out, washing and drying to obtain the tosufloxacin tosylate crystal.
3. The tobathiacin tosylate dispersible tablet according to claim 2, wherein the mass volume ratio of the tobathiacin tosylate to the mixed solution of the organic solvent and water in the step (1) is 1 to 5 g: 15 ml.
4. The dispersible tablet of tosufloxacin tosylate according to claim 2, characterised in that the temperature in step (1) is 45 ℃.
5. The tosufloxacin tosylate dispersible tablet according to claim 2, wherein the organic solvent is ethanol with a volume fraction of 95%, and the volume ratio of ethanol to water is 10-1: 1.
6. The dispersible tablet of tosufloxacin tosylate according to claim 5, wherein the volume ratio of ethanol to water is 1: 1.
7. The dispersible tablet of tosufloxacin tosylate according to claim 2, wherein the mass fraction of the activated carbon is 0.1-0.3%.
8. The tobathiacin tosylate dispersible tablet according to claim 2, wherein the temperature reduction in step (3) is to a temperature of 28-32 ℃ and the standing time is 10-20 hours.
9. The dispersible tablet of tosufloxacin tosylate according to claim 2, characterized in that the drying temperature in step (4) is 40-60 ℃.
10. A process for the preparation of the dispersible tablet of tosufloxacin tosylate according to claim 1 or 2, characterized in that it comprises the following steps:
(1) preparing an adhesive, namely stirring and dissolving povidone K-30 by using ethanol, clarifying the solution without condensate, and adding purified water for mixing for later use;
(2) granulating; weighing tobathiacin tosylate, microcrystalline cellulose, pregelatinized starch, mannitol and silicon dioxide according to a formula ratio, putting into a granulator for granulation, stirring and mixing, pouring the prepared adhesive solution into the mixed raw and auxiliary materials to prepare a soft material, continuously stirring, and then preparing into granules;
(3) drying, sieving and granulating;
(4) mixing, namely uniformly mixing the whole dried granules with the carboxymethyl starch sodium, the aspartame, the magnesium stearate and the strawberry essence according to the prescription amount;
(5) tabletting, encapsulating and warehousing.
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| JP6647395B2 (en) * | 2016-04-27 | 2020-02-14 | 富士フイルム富山化学株式会社 | Tablets containing tosfloxacin tosylate |
| WO2017188362A1 (en) * | 2016-04-27 | 2017-11-02 | 富山化学工業株式会社 | Tablet containing tosufloxacin tosilate, disintegrator and acidic amino acid |
| CN107519145B (en) * | 2017-08-24 | 2021-04-30 | 正大制药（青岛）有限公司 | Tosufloxacin tosylate effervescent tablet for children and preparation method thereof |
| CN110041329B (en) * | 2019-05-27 | 2021-08-10 | 天地恒一制药股份有限公司 | Preparation method of tosufloxacin tosylate monohydrate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004066910A2 (en) * | 2003-01-31 | 2004-08-12 | Glenmark Pharmaceuticals Ltd. | Controlled release modifying complex and pharmaceutical compositions thereof |
| CN101948471A (en) * | 2010-10-11 | 2011-01-19 | 赤峰万泽制药有限责任公司 | Refining process of tosufloxacin tosylate |
| CN104546735A (en) * | 2014-12-22 | 2015-04-29 | 青岛正大海尔制药有限公司 | Pediatric tosufloxacin tosilate granule and preparation method thereof |
-
2016
- 2016-08-19 CN CN201610694265.5A patent/CN106176646B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004066910A2 (en) * | 2003-01-31 | 2004-08-12 | Glenmark Pharmaceuticals Ltd. | Controlled release modifying complex and pharmaceutical compositions thereof |
| CN101948471A (en) * | 2010-10-11 | 2011-01-19 | 赤峰万泽制药有限责任公司 | Refining process of tosufloxacin tosylate |
| CN104546735A (en) * | 2014-12-22 | 2015-04-29 | 青岛正大海尔制药有限公司 | Pediatric tosufloxacin tosilate granule and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| "甲苯磺酸妥舒沙星分散片工艺研究";何碧泉等;《中外健康文摘》;20130131;第10卷(第2期);第37-39页 * |
| "甲苯磺酸妥舒沙星分散片的研制和质量控制";王金香等;《海峡药学》;20101231;第22卷(第7期);第72-75页 * |
| 何碧泉等."甲苯磺酸妥舒沙星分散片工艺研究".《中外健康文摘》.2013,第10卷(第2期),第37-39页. * |
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