CN102204910A - Pharmaceutical composition of moxifloxacin hydrochloride, and preparation method thereof - Google Patents
Pharmaceutical composition of moxifloxacin hydrochloride, and preparation method thereof Download PDFInfo
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- CN102204910A CN102204910A CN2011100743852A CN201110074385A CN102204910A CN 102204910 A CN102204910 A CN 102204910A CN 2011100743852 A CN2011100743852 A CN 2011100743852A CN 201110074385 A CN201110074385 A CN 201110074385A CN 102204910 A CN102204910 A CN 102204910A
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- moxifloxacin hydrochloride
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Abstract
The invention provides a pharmaceutical composition of moxifloxacin hydrochloride, and a preparation method thereof. The composition mainly comprises moxifloxacin hydrochloride, a melting agent polyethylene glycol 6000 and other excipients. The preparation method mainly comprises the steps of: preparing drug particles by a hot melt granulating technology, and then tabletting or encapsulating.
Description
[technical field]
The invention belongs to technical field of medicine, more specifically, the present invention relates to a kind of pharmaceutical composition that contains moxifloxacin hydrochloride and fusing agent, also relates to described preparation of drug combination method.
[background technology]
Moxifloxacin hydrochloride (Moxifloxacin Hydrochloride), its chemistry 1-cyclopropyl-7-(S by name, S-2,8-diazonium-bicyclo-[4.3.0] nonane-8-yl)-6-fluoro-8-methoxy-1,4-dihydro-4-oxygen-3-quinoline carboxylic acid hydrochloride is the efficient fluoroquinolone antibacterial agent thing of New-type wide-spectrum of German Bayer company research and development, and commodity are called " visiing multiple pleasure ", in JIUYUE, 1999 is gone on the market in Germany, and the same year, December obtained FDA approval listing in the U.S..That uses clinically at present is mainly tablet.
The moxifloxacin hydrochloride raw material is a crystalline powder, and flowability and compressibility are all relatively poor, and the said preparation specification is bigger, needs the adjuvant space of interpolation limited, is not suitable for dry powder direct tabletting, and preparation technology is wet method system granule tabletting.Traditional wet granulation, need consider factors such as addition, the particle drying time of adhesive, the time of sieving of granulating, the machine quantity that production needs is many, the space is big, and owing to some factor need the dependence experience be judged, therefore may cause unstable product quality, batch differences is big etc.And, may cause the problem such as slack-off of dissolution in addition along with the prolongation of resting period.
And dry method system granule arts demand is used special installations such as dry granulation machine; also need by compress, pulverize, sieve, process such as granulate just can finish; operating process is loaded down with trivial details, time-consuming; artificially increased cost; and " taking off lid " phenomenon appears behind the tabletting easily; or the tablet friability is defective, occurs fragment easily in the coating process of postorder, makes tablet quality defective.
Hot melt system granule method is external in recent years emerging a kind of granulation technique.This technology is different from hot melt extrusion granulator technology, and the latter need use special and expensive equipment such as hot melt extrusion granulator machine, and hot melt system granule method only needs fluid bed to realize, and fluid bed is the common equipment that generally uses in the modern pharmaceutical factory.This technology is time saving and energy saving, and quickness and high efficiency adapts to the development in modern pharmaceutical field.
[summary of the invention]
[technical problem that will solve]
Purpose of the present invention, be to overcome the potential risk that prior art is brought to product stability in wet granule compression tablet technology, a kind of technology of preparing-hot melt granulation technique of time saving and energy saving, quickness and high efficiency is proposed, this The Application of Technology has not only reduced production cost of products, has also guaranteed the quality of product simultaneously.
[technical scheme]
The present invention is achieved through the following technical solutions.
The present invention relates to a kind of pharmaceutical composition of moxifloxacin hydrochloride, it is characterized in that it is made up of at pharmaceutically acceptable carrier with comprising fusing agent and other the effective ingredient moxifloxacin hydrochloride, and the tablet of making by the hot melt granulation technique, wherein used fusing agent is a polyethylene glycol 6000.
The invention provides a kind of method that adopts the hot melt granulation technique to prepare the moxifloxacin hydrochloride pharmaceutical composition, promptly adopt fluid bed heat to found grain.Preparation technology is easy for this technology, and is time saving and energy saving, uniform particles, and good fluidity, tablet hardness is better, and friability is lower, and dissolution obviously is better than wet granulation.
Moxifloxacin hydrochloride is wide spectrum and the 8-methoxy fluoroquinolone class antimicrobial drug with antibacterial activity.Moxifloxacin hydrochloride is to gram positive bacteria, gram-negative bacteria, and anaerobe, acid fast bacteria and atypical microorganism such as mycoplasma, chlamydia and legionella have broad spectrum antibiotic activity.Antibacterial action mechanism is for disturbing II, IV topoisomerase.Topoisomerase is the key enzyme of control DNA topological sum at dna replication dna, in repairing and transcribing.Its killing curve shows that Moxifloxacin is the bactericidal activity with concentration dependent.We know, medicine with concentration dependent, refer to be blood drug level in the body, so the stripping of medicine is fast, can make the absorption of medicine fast, reach blood drug level effectively very soon, bring into play drug effect rapidly, and if dissolution is slack-off, then absorb slack-off accordingly, onset is slack-off, even may can not reach effective concentration because of medicine elimination and metabolic problems, thereby curative effect is very poor.
The hot melt granulation technique is different from hot melt extrusion granulator technology; the latter need use special and expensive equipment such as hot melt extrusion granulator machine; and hot melt system granule method only needs fluid bed to realize; its operation principle is the material in material trough; the abundant mixed melting of adjuvant; be delivered to the second-rate bromhidrosis streaming nozzle at refrigerating chamber top by the constant pressure and flow device; the small droplet of compressed air atomizing becoming that in refrigerating chamber, is produced by air compressor; fully contact with air through cryotherapy; the exchange of conducting heat; finish solidification process; product after partly solidified is deposited in the powder cup of hothouse bottom; the tail gas of discharging from the atomization refrigeration chamber is finished gas solid separation in cyclone separator; product is captured down and collects in the powder cup, and tail gas enters atmosphere by air-introduced machine.Fluid bed is the common equipment that generally uses in the modern pharmaceutical factory.This technology is time saving and energy saving, and quickness and high efficiency adapts to the development in modern pharmaceutical field.
Contain moxifloxacin hydrochloride in the compositions of the present invention, fusing agent polyethylene glycol 6000 and other are at pharmaceutically acceptable carrier.
Wherein pharmaceutically acceptable carrier should be meant the conventional medicine carrier in pharmaceutical field, for example disintegrating agent, lubricant etc., disintegrating agent such as carboxymethyl starch sodium, hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose; Fluidizer such as silicon dioxide, gel silicon dioxide; Lubricant such as Pulvis Talci, calcium stearate, magnesium stearate, micropowder silica gel etc.
Preferably, described pharmaceutical composition is made by following raw material,
More preferably, described pharmaceutical composition is made by following raw material,
According to another kind of preferred implementation of the present invention, described preparation is tablet or capsule.
According to another kind of preferred implementation of the present invention, be that one or more are selected from the carrier of normally used disintegrating agent, lubricant pharmaceutically at pharmaceutically acceptable carrier.
Described disintegrating agent is selected from carboxymethyl starch sodium, hyprolose, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose.
Described lubricant is selected from Pulvis Talci, calcium stearate and magnesium, micropowder silica gel.
The invention still further relates to described preparation of drug combination method.This method step is as follows: moxifloxacin hydrochloride, polyethylene glycol 6000, disintegrating agent, fluidizer are put in the fluid bed, carry out hot melt and granulate.
The granule that the present invention further can obtain the hot melt granulation is prepared into pharmaceutical preparation with the galenic pharmacy routine techniques, as tablet, and capsule.And the preparation of each unit contains the moxifloxacin hydrochloride of 250mg, 500mg or 1000mg.
Therefore preferred manufacturing procedure of the present invention is as follows:
Moxifloxacin hydrochloride, polyethylene glycol 6000, cross-linking sodium carboxymethyl cellulose and silicon dioxide are put in the fluid bed, carry out hot melt and granulate.
Particularly preferred preparation method is as follows: the moxifloxacin hydrochloride, 4-6 weight portion cross-linking sodium carboxymethyl cellulose, 40-60 weight portion polyethylene glycol 6000 and the 10 weight portion silicon dioxide that take by weighing 1000 weight portions are put in the fluid bed, air intake frequency 30-40Hz, temperature of charge are set are parameter such as 55-75 ℃ carries out hot melt and granulates, mix adding magnesium stearate behind the granule granulate that makes, tabletting, the bag film-coat.
It is to obtain through screening that the present invention preferably fills a prescription, and is particularly conducive to commercial production.
In the present invention, the method and apparatus that generally uses that the those of ordinary skill in employing pharmaceutical technology field is known, with the granule that obtains can with make tablet in pharmaceutically acceptable carrier combinations, employed these carriers or excipient all are to determine easily for the those of ordinary skill in pharmaceutical technology field, also are conspicuous.
[beneficial effect]
The present invention has following beneficial effect: the present invention adopts hot melt method of granulating pharmaceutical compositions, and its advantage is, compares with prior art, preparation technology is easy, time saving and energy saving, uniform particles, good fluidity, the tablet hardness of compacting is better, friability is lower, also fragment can not occur in the coating process, easily control, this tablet stability is good simultaneously, and dissolution and wet granulation relatively have a clear superiority in accelerated stability test simultaneously.See accompanying drawing and subordinate list.
[description of drawings]
The tablet dissolution with the wet granulation compacting of Fig. 1 embodiment 1-4 compares
After 6 months, condition determination is: slurry method, 900ml water, 50rpm, 37 ℃ through accelerated test.The tablet dissolution of the visible wet granulation of result is considerably slower than the tablet that embodiment obtains.The tablet dissolution of the product of Fig. 2 embodiment and wet granulation compacting relatively
Condition determination is: slurry method, 0.1NHCl, 50rpm, 37 ℃.After 6 months, the product dissolution of the visible wet granulation of result is slower than embodiment through accelerated test.
[specific embodiment]
Further specify the present invention by the following examples, but not as limitation of the present invention.
Embodiment 1:
The Polyethylene Glycol-6000 and the 10 weight portion silicon dioxide that take by weighing moxifloxacin hydrochloride 1000 weight portions, cross-linking sodium carboxymethyl cellulose 10 weight portions, 200 weight portions are put in the fluid bed, it is that 30Hz, temperature of charge are 75 ℃ that the air intake frequency is set, carrying out hot melt granulates, with the granule that makes with in the rearmounted mixer of 18 mesh sieve granulate, adding 1 weight portion magnesium stearate mixed 5 minutes, be pressed into 1000, reuse
The bag film-coat.
Embodiment 2:
Taking by weighing moxifloxacin hydrochloride 1000 weight portions, cross-linking sodium carboxymethyl cellulose 1 weight portion, 10 weight portion Polyethylene Glycol-6000 and silicon dioxide 2 weight portions puts in the fluid bed, it is that 40Hz, temperature of charge are 65 ℃ that the air intake frequency is set, carrying out hot melt granulates, with the granule that makes with in the rearmounted mixer of 18 mesh sieve granulate, adding magnesium stearate 0.5 weight portion mixed 5 minutes, be pressed into 1000, reuse
The bag film-coat.
Embodiment 3:
Taking by weighing moxifloxacin hydrochloride 1000 weight portions, cross-linking sodium carboxymethyl cellulose 5 weight portions, Polyethylene Glycol-6000100 weight portion and silicon dioxide 5 weight portions puts in the fluid bed, it is that 30Hz, temperature of charge are 55 ℃ that the air intake frequency is set, carrying out hot melt granulates, with the granule that makes with in the rearmounted mixer of 18 mesh sieve granulate, adding magnesium stearate 0.1 weight portion mixed 5 minutes, be pressed into 1000, reuse
The bag film-coat.
Embodiment 4:
Taking by weighing moxifloxacin hydrochloride 1000 weight portions, cross-linking sodium carboxymethyl cellulose 7 weight portions, Polyethylene Glycol-600050 weight portion and silicon dioxide 7 weight portions puts in the fluid bed, it is that 40Hz, temperature of charge are 65 ℃ that the air intake frequency is set, carrying out hot melt granulates, with the granule that makes with in the rearmounted mixer of 18 mesh sieve granulate, add magnesium stearate 0.5 weight portion and mixed 1000 capsules of packing into 5 minutes.
Further specify the advantage of pharmaceutical composition of the present invention below by data.
The comparison of table 1 embodiment of the invention and dry granulation technical result
As seen from the above table, from the character aspect comparison of operating time and labor intensity etc. and product intermediate, the present invention has remarkable advantages than dry granulation technology and wet granulation technique.
Table 2 embodiment of the invention and wet granulation technique are placed the comparison of stripping result after 6 months
Condition determination is: slurry method, 900ml water, 50rpm, 37 ℃.
As seen from the above table, from 6 months results of wet granulation product and accelerated test of the present invention relatively, the dissolution of wet granulation is considerably slower than the present invention, and the present invention and relatively do not have significant difference in 0 month.The present invention has remarkable advantages than wet granulation technique on product quality.
Claims (10)
1. the pharmaceutical composition of a moxifloxacin hydrochloride is characterized in that it is made up of effective ingredient moxifloxacin hydrochloride and polyethylene glycol 6000 and other pharmaceutically acceptable carrier,
2. pharmaceutical composition according to claim 1 is characterized in that other pharmaceutically acceptable carrier is one or more carriers that are selected from disintegrating agent, lubricant or fluidizer.
3. pharmaceutical composition according to claim 2 is characterized in that described disintegrating agent is selected from one or more of carboxymethyl starch sodium, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose.
4. pharmaceutical composition according to claim 2 is characterized in that described lubricant or fluidizer are selected from one or more of silicon dioxide, colloidal silica, magnesium stearate, stearic acid, calcium stearate, Pulvis Talci, sodium lauryl sulphate, hydrogenated vegetable oil, sodium stearyl fumarate, mountain Yu acid glycerol.
5. pharmaceutical composition according to claim 1 is characterized in that each set of dispense of described composition is such as following:
6. pharmaceutical composition according to claim 5 is characterized in that each set of dispense of described composition is such as following:
7. pharmaceutical composition according to claim 1 is characterized in that, makes after granulating with the hot melt granulation technique.
8. pharmaceutical composition according to claim 1 is characterized in that, temperature of charge is 55-75 ℃ during granulation.
9. preparation of drug combination method according to claim 1 is characterized in that preparation method is as follows: moxifloxacin hydrochloride, polyethylene glycol 6000, cross-linking sodium carboxymethyl cellulose and silicon dioxide are put in the fluid bed, carry out hot melt and granulate.
10. preparation method according to claim 9, it is characterized in that, preparation method is as follows: the moxifloxacin hydrochloride, 40-60 weight portion polyethylene glycol 6000,4-6 weight portion cross-linking sodium carboxymethyl cellulose and the 10 weight portion silicon dioxide that take by weighing 1000 weight portions are put in the fluid bed, air intake frequency 30-40Hz, temperature of charge are set are parameter such as 55-75 ℃ carries out hot melt and granulates, the magnesium stearate that adds 0.5 weight portion behind the granule granulate that makes is mixed, tabletting, the bag film-coat.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201110074385.2A CN102204910B (en) | 2011-03-25 | 2011-03-25 | Pharmaceutical composition of moxifloxacin hydrochloride, and preparation method thereof |
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| CN201110074385.2A CN102204910B (en) | 2011-03-25 | 2011-03-25 | Pharmaceutical composition of moxifloxacin hydrochloride, and preparation method thereof |
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| CN102204910B CN102204910B (en) | 2014-10-29 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013097003A1 (en) * | 2011-12-26 | 2013-07-04 | Ems S/A. | Solid pharmaceutical composition comprising an antibiotic from the quinolone family and method for the production thereof |
| CN108371655A (en) * | 2018-03-29 | 2018-08-07 | 重庆华邦制药有限公司 | Include the solid drugs and preparation method thereof of razaxaban |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1762357A (en) * | 2005-09-21 | 2006-04-26 | 深圳市天一时科技开发有限公司 | Oral medicinal formulation of moxifloxacin and its preparation method |
| CN101732233A (en) * | 2009-11-19 | 2010-06-16 | 浙江工业大学 | Method for preparing solid dispersion |
-
2011
- 2011-03-25 CN CN201110074385.2A patent/CN102204910B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1762357A (en) * | 2005-09-21 | 2006-04-26 | 深圳市天一时科技开发有限公司 | Oral medicinal formulation of moxifloxacin and its preparation method |
| CN101732233A (en) * | 2009-11-19 | 2010-06-16 | 浙江工业大学 | Method for preparing solid dispersion |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013097003A1 (en) * | 2011-12-26 | 2013-07-04 | Ems S/A. | Solid pharmaceutical composition comprising an antibiotic from the quinolone family and method for the production thereof |
| CN108371655A (en) * | 2018-03-29 | 2018-08-07 | 重庆华邦制药有限公司 | Include the solid drugs and preparation method thereof of razaxaban |
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| CN102204910B (en) | 2014-10-29 |
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Address after: 100021 Beijing city Chaoyang District West business center boziwan Jinhai rich 402 (A) 21 storey building Applicant after: China Resources Saike Pharmaceutical Co., Ltd. Address before: 100021 Beijing city Chaoyang District West business center boziwan Jinhai rich 402 (A) 21 storey building Applicant before: Saike Pharmaceutical Co., Ltd., Beijing |
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