CN102784121A - Levofloxacin composition freeze-dried orally disintegrating tablets and preparation method thereof - Google Patents
Levofloxacin composition freeze-dried orally disintegrating tablets and preparation method thereof Download PDFInfo
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- CN102784121A CN102784121A CN2012103012410A CN201210301241A CN102784121A CN 102784121 A CN102784121 A CN 102784121A CN 2012103012410 A CN2012103012410 A CN 2012103012410A CN 201210301241 A CN201210301241 A CN 201210301241A CN 102784121 A CN102784121 A CN 102784121A
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Abstract
The invention provides levofloxacin composition freeze-dried orally disintegrating tablets and a preparation method of the orally disintegrating tablets, relates to the field of a medicine and a medicine preparation method technology and mainly solves the problems in the prior art that the ordinary preparation prepared by levofloxacin is poor in curative effect and not suitable for children and the patients who are difficult to swallow. The levofloxacin composition freeze-dried orally disintegrating tablets are prepared from the following components by weight: 10-24% of levofloxacin, 24-50% of mannitol, 2-4% of gelatin, 32-74% of hydroxypropyl-beta-cyclodextrin with medium substitution degree, 0.1-0.2% of trichlorosucrose and 50-70% of purified water. The levofloxacin composition freeze-dried orally disintegrating tablets prepared by the above components are easy in preparation process, and simple in components, and mainly meet the administration requirements of children and the patients who are difficult to swallow; moreover, the levofloxacin composition freeze-dried orally disintegrating tablets have the advantages of being fast to disintegrate, convenient to take, and good in taste; and the tablets take effect quickly and are fully absorbed, and the first pass effect of the liver is avoided.
Description
Technical field:
The present invention relates to the method for preparing technical field of medicine and medicine, relate in particular to a kind of levofloxacin composition freeze-drying oral cavity disintegration tablet and preparation method thereof.
Background technology:
Levofloxacin is the effective ingredient levo form in the ofloxacin (racemization), its mechanism of action, the same ofloxacin of antibacterial action characteristics, but its antibacterial action is strong slightly than ofloxacin.Levofloxacin can suppress the DNA gyrase, the duplicating of blocking dna, and antibacterial produces bacteriolyze in being higher than minimum inhibitory concentration several times environment.Levofloxacin all has definite vitro antibacterial activity to Grain-positive and negative bacteria.Levofloxacin is far longer than gram positive bacteria to the antibacterial action of gram negative bacilli.Its vitro antibacterial activity is strong slightly or similar than norfloxacin, and the two antimicrobial spectrum is identical.The extremely sensitive pathogenic bacterium of levofloxacin are had: gram negative bacilli and part gram positive bacteria, like staphylococcus aureus, gonococcus, legion brevibacterium etc.The more sensitive pathogenic bacterium of levofloxacin are had: pseudomonas aeruginosa (bacillus pyocyaneus), Streptococcus etc.
Levofloxacin is complete synthesis the 3rd generation promise ketone broad-spectrum high efficacy antimicrobial drug, and antimicrobial spectrum is extensive and effect is strong, thereby is used in a large number treat the disease by bacterial infection, has the good clinical effect.But its water solublity is relatively poor, and bioavailability is not high.
The levofloxacin dosage form of listing is mainly conventional tablet, capsule, injection at present.Yet regular dosage form such as tablet and capsule etc. are not suitable for the patient of child, gerontal patient and dysphagia to be taken, and makes the patient produce negation to medication, has reduced the compliance of patient's clinical application.
So still lack at present and press for a kind of like this Levaquin, its preparation technology is simple, component is simple.The oral absorption rate is high, and taking convenience, delicious is specially adapted to child, old age, is unable to leave the bed, the severely-disabled patient, and swallows inconvenient patient's medication.
Summary of the invention:
The object of the invention is to overcome the defective of prior art, utilizes cyclodextrin inclusion technique, increases the water solublity of levofloxacin, the stability of improving levofloxacin, reduction GI irritation.Utilize computer molecular simulateo, the best complex ratio and the inventory of Theoretical Calculation levofloxacin and cyclodextrin.
The present invention need not water when a kind of taking is provided, need not to chew, and fast levofloxacin composition freeze-drying oral cavity disintegration tablet of disintegration rate and preparation method thereof in the oral cavity, this method preparation condition is gentle, is easy to control, is fit to industrialized great production.The said composition composition is simple: principal agent is a levofloxacin, also includes skeleton agent (mannitol), forming agent (gelatin), solubilising, odor mask (medium substitution value hydroxypropyl-β-cyclodextrin), correctives (sucralose).
For realizing the object of the invention, technical scheme realizes through following mode:
A kind of levofloxacin compositions is characterized in that: said composition comprises following component and component quantity ratio:
The preferred ingredient quantity ratio of said each component of levofloxacin compositions is:
A kind of levofloxacin composition freeze-drying oral cavity disintegration tablet that contains the levofloxacin compositions is characterized in that, is prepared from following component and component quantity ratio:
The preferred ingredient quantity ratio of each component of preparation levofloxacin composition freeze-drying oral cavity disintegration tablet is:
A kind of method for preparing of levofloxacin composition freeze-drying oral cavity disintegration tablet is characterized in that, the concrete steps of this method for preparing are:
A) the medium substitution value hydroxypropyl-β-cyclodextrin of group component is dissolved in 70%-80% the purified water of component water total amount; Under stirring, be heated to 55 ℃; The levofloxacin that slowly adds group component; Continue to stir 10 hours, treat medium substitution value hydroxypropyl-β-cyclodextrin, add mannitol, the sucralose of group component after the levofloxacin enclose;
B) gelatin with group component is dissolved in the purified water of component water consumption 20%-30%, is heated to dissolving fully;
C) merge two kinds of solution that above-mentioned steps a, step b obtain and stirring;
D) regulate pH value to 5.5-6.5 with sodium bicarbonate;
E) according to levofloxacin composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and puts into freeze drying box, to medicinal liquid carry out freezing, evacuation is dry, the control moisture is no more than 1.0%;
F) treat levofloxacin composition freeze-drying oral cavity disintegration tablet drying after, in freeze drying box, seal;
G) cut drug-containing dish after the medicament that freezes is taken out freeze drying box, and carry out finished product packing.
Said medium substitution value hydroxypropyl-β-cyclodextrin consumption is 200%-600% of levofloxacin quality in the prescription.
Said sucralose consumption is 0.4%-1.0% of levofloxacin quality in the prescription.
Said levofloxacin composition freeze-drying oral cavity disintegration tablet specification is 50mg/ sheet or 100mg/ sheet.
We have formulated relevant detection method for the disintegration rate of levofloxacin composition freeze-drying oral cavity disintegration tablet:
Disintegration
According to inspection technique disintegration (two appendix ⅹ of Chinese Pharmacopoeia version in 2010 A); The stainless steel shaft of hanging basket through the upper end hung on the metal rack; Immerse in the 1000ml beaker; And screen cloth fills temperature and is 37 ℃ ± 1 ℃ water apart from beaker bottom 25mm in the beaker when regulating the hanging basket position it being descended, when regulating height of water level hanging basket being risen screen cloth in the underwater 15mm place.
Except as otherwise herein provided, get 6 groups of test samples (every group of dosage is 100mg), put respectively in the glass tubing of above-mentioned hanging basket, add baffle plate, start disintegration tester and check, each sheet all should all disintegrates in 1.1 seconds.Result such as following table:
Dosage equates, the disintegration time and the medicine of different levofloxacin tablets reach peak concentration
The disintegration rate that can find out levofloxacin composition freeze-drying oral cavity disintegration tablet of the present invention from above experimental result is faster than levofloxacin ordinary tablet.
Advantage of the present invention:
The first, the tablet disintegrate is rapid, and drug effect is fast.Levofloxacin composition freeze-drying oral cavity disintegration tablet of the present invention is disintegrate rapidly in 2 seconds in mouth, is beneficial to the rapid stripping of medicine, shortens dissolution time, accelerates to absorb, and liver first-pass effect is little, makes its performance curative effect fast, and GI irritation is little, and the untoward reaction rate is low.
The second, drug absorption is abundant.Levofloxacin composition freeze-drying oral cavity disintegration tablet of the present invention is disintegrate fully in the oral cavity, makes the absorption of medicine more abundant, helps improving bioavailability of medicament like this.
Three, taking convenience, mouthfeel is good.Levofloxacin composition freeze-drying oral cavity disintegration tablet of the present invention needn't be used water delivery service, and saliva can make its complete disintegrate, and no foreign body sensation in mouthful is owing to wherein add the compliance that the sweet child of helping of suitable correctives cool taste flavor takes medicine.
The selected adjuvant of levofloxacin composition freeze-drying oral cavity disintegration tablet all is the adjuvants that are suitable for this tablet of preparation.Insoluble in water according to the research levofloxacin, for improving its dissolubility, so in prescription, add medium substitution value hydroxypropyl-β-cyclodextrin, consumption is 200%-600% of levofloxacin quality in the prescription.Use medium substitution value hydroxypropyl-β-cyclodextrin in this prescription; Be that to have a haemolysis little because of it, stimulate slightly, advantages such as metabolism take place in human body hardly; And help improving dissolubility, stability and the bioavailability of medicine, and can improve the quality of medicament.
Levofloxacin composition freeze-drying oral cavity disintegration tablet of the present invention has added the correctives sucralose in prescription.In traditional production application, aspartame flavour mouthfeel is pretty good, but is prone to decompose instability; Cyclamate, glucide safety receive dispute to a certain degree, and are prone to produce the back bitterness.And the sucralose sweet feel is very near sucrose, and is very stable, safe to heat, acid, alkali.Simultaneously, sucralose is not utilized by the dental caries pathogenic bacteria, can reduce pathogenic bacteria in the oral cavity, and the acid amount of generation and streptococcus cell effectively play the dental caries effect in the adhesion of dental surface, and useful especially teenager teeth is healthy; The sucralose good stability can long term storage, and in freezing dry process, can not be damaged, and is fit to industrial applications.
Levofloxacin composition freeze-drying oral cavity disintegration tablet component of the present invention is simple, need not water when taking, and need not to chew, and disintegration time was no more than for 2 seconds in human oral cavity; Absorb soon, bioavailability is high, and intestinal is residual few, and side effect is low; Liver first-pass effect is little, and the untoward reaction rate is low, and mouthfeel is good.
The specific embodiment:
For technological means, creation characteristic that the present invention is realized, reach purpose and effect and be easy to understand and understand, below in conjunction with specific embodiment, further set forth the present invention.
Embodiment 1
Prescription: 1000 amounts
Medium substitution value hydroxypropyl-β-the cyclodextrin of recipe quantity is dissolved in 80% of prescription water total amount
In the purified water, under stirring, be heated to 55 ℃, slowly add the levofloxacin of recipe quantity; Continue to stir 10 hours, treat that medium substitution value hydroxypropyl-β-cyclodextrin will add mannitol, the sucralose of recipe quantity to after the levofloxacin enclose; The gelatin of recipe quantity is dissolved in the purified water of prescription water consumption 20%, is heated to dissolving fully, merge above-mentioned two kinds of solution and stir; Regulate pH value to 5.5-6.5 with sodium bicarbonate, according to levofloxacin composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after; Medicinal liquid after merging is pressed in the loading amount packing drug-containing dish, and put into freeze drying box, carry out freezing medicinal liquid; After treating levofloxacin composition freeze-drying oral cavity disintegration tablet drying, in freeze drying box, seal, take out back cutting, packing.
Embodiment 2
Prescription: 1000 amounts
Medium substitution value hydroxypropyl-β-the cyclodextrin of recipe quantity is dissolved in 80% the purified water of prescription water total amount, under stirring, is heated to 55 ℃, slowly add the levofloxacin of recipe quantity; Continue to stir 10 hours, treat medium substitution value hydroxypropyl-β-cyclodextrin, add mannitol, the sucralose of recipe quantity after the levofloxacin enclose; The gelatin of recipe quantity is dissolved in the purified water of prescription water consumption 20%, is heated to dissolving fully, merge above-mentioned two kinds of solution and stir; Regulate pH value to 5.5-6.5 with sodium bicarbonate, according to levofloxacin composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after; Medicinal liquid after merging is pressed in the loading amount packing drug-containing dish; And put into freeze drying box, medicinal liquid is carried out freezing, treat levofloxacin composition freeze-drying oral cavity disintegration tablet drying after; In freeze drying box, seal, take out back cutting, packing.
Embodiment 3
Prescription: 1000 amounts
Medium substitution value hydroxypropyl-β-the cyclodextrin of recipe quantity is dissolved in 80% the purified water of prescription water total amount, under stirring, is heated to 55 ℃, slowly add the levofloxacin of recipe quantity; Continue to stir 10 hours, treat medium substitution value hydroxypropyl-β-cyclodextrin, add mannitol, the sucralose of recipe quantity after the levofloxacin enclose; The gelatin of recipe quantity is dissolved in the purified water of prescription water consumption 20%, is heated to dissolving fully, merge above-mentioned two kinds of solution and stir; Regulate pH value to 5.5-6.5 with sodium bicarbonate, according to levofloxacin composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after; Medicinal liquid after merging is pressed in the loading amount packing drug-containing dish; And put into freeze drying box, medicinal liquid is carried out freezing, treat levofloxacin composition freeze-drying oral cavity disintegration tablet drying after; In freeze drying box, seal, take out back cutting, packing.
More than show and described ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; The present invention is not restricted to the described embodiments; That describes in the foregoing description and the description is merely preference of the present invention, is not used for limiting the present invention, under the prerequisite that does not break away from spirit and scope of the invention; The present invention also has various changes and modifications, and these variations and improvement all fall in the scope of the invention that requires protection.The present invention requires protection domain to be defined by appending claims and equivalent thereof.
Claims (8)
1. a levofloxacin compositions is characterized in that, said composition comprises following component and component quantity ratio:
2. levofloxacin compositions according to claim 1 is characterized in that, the preferred ingredient quantity ratio of said each component of levofloxacin compositions is:
3. a levofloxacin composition freeze-drying oral cavity disintegration tablet that contains the said compositions of claim 1 is characterized in that, is prepared from following component and component quantity ratio:
4. levofloxacin composition freeze-drying oral cavity disintegration tablet according to claim 3 is characterized in that, the preferred ingredient quantity ratio of each component of preparation levofloxacin composition freeze-drying oral cavity disintegration tablet is:
5. the method for preparing of the said levofloxacin composition freeze-drying of claim 3 oral cavity disintegration tablet is characterized in that the concrete steps of this method for preparing are:
A) the medium substitution value hydroxypropyl-β-cyclodextrin of group component is dissolved in 70%-80% the purified water of component water total amount; Under stirring, be heated to 55 ℃; The levofloxacin that slowly adds group component; Continue to stir 10 hours, treat medium substitution value hydroxypropyl-β-cyclodextrin, add mannitol, the sucralose of group component after the levofloxacin enclose;
B) gelatin with group component is dissolved in the purified water of component water consumption 20%-30%, is heated to dissolving fully;
C) merge two kinds of solution that above-mentioned steps a, step b obtain and stirring;
D) regulate pH value to 5.5-6.5 with sodium bicarbonate;
E) according to levofloxacin composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and puts into freeze drying box, to medicinal liquid carry out freezing, evacuation is dry, the control moisture is no more than 1.0%;
F) treat levofloxacin composition freeze-drying oral cavity disintegration tablet drying after, in freeze drying box, seal;
G) cut drug-containing dish after the medicament that freezes is taken out freeze drying box, and carry out finished product packing.
6. the method for preparing of levofloxacin composition freeze-drying oral cavity disintegration tablet according to claim 5 is characterized in that: said medium substitution value hydroxypropyl-β-cyclodextrin consumption is 200%-600% of levofloxacin quality in the prescription.
7. the method for preparing of levofloxacin composition freeze-drying oral cavity disintegration tablet according to claim 5 is characterized in that: said sucralose consumption is 0.4%-1.0% of levofloxacin quality in the prescription.
8. the method for preparing of levofloxacin composition freeze-drying oral cavity disintegration tablet according to claim 5 is characterized in that: said levofloxacin composition freeze-drying oral cavity disintegration tablet specification is 50mg/ sheet or 100mg/ sheet.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2012103012410A CN102784121A (en) | 2012-08-23 | 2012-08-23 | Levofloxacin composition freeze-dried orally disintegrating tablets and preparation method thereof |
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| CN2012103012410A CN102784121A (en) | 2012-08-23 | 2012-08-23 | Levofloxacin composition freeze-dried orally disintegrating tablets and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104586748A (en) * | 2014-12-25 | 2015-05-06 | 海南卫康制药(潜山)有限公司 | Levofloxacin composition freeze-dried tablet as well as preparation method thereof |
| CN114917197A (en) * | 2022-06-16 | 2022-08-19 | 南京正科医药股份有限公司 | Levofloxacin hydrochloride tablet |
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| CN1634073A (en) * | 2004-10-01 | 2005-07-06 | 北京阜康仁生物制药科技有限公司 | Orally disintegrating tablet of levofloxacin and its pharmaceutical salt |
| CN1689649A (en) * | 2004-04-30 | 2005-11-02 | 量子高科（北京）研究院有限公司 | Oral cavity quick dissolving preparation and production method thereof |
| CN101925349A (en) * | 2007-12-21 | 2010-12-22 | 欧兰德股份有限公司 | Orally disintegrating tablet compositions of temazepam |
| CN102631336A (en) * | 2012-02-07 | 2012-08-15 | 海南卫康制药(潜山)有限公司 | Freeze-drying orally disintegrating tablet with vitamin K1 composition for infants and preparation method for freeze-drying orally disintegrating tablet |
-
2012
- 2012-08-23 CN CN2012103012410A patent/CN102784121A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1689649A (en) * | 2004-04-30 | 2005-11-02 | 量子高科（北京）研究院有限公司 | Oral cavity quick dissolving preparation and production method thereof |
| CN1634073A (en) * | 2004-10-01 | 2005-07-06 | 北京阜康仁生物制药科技有限公司 | Orally disintegrating tablet of levofloxacin and its pharmaceutical salt |
| CN101925349A (en) * | 2007-12-21 | 2010-12-22 | 欧兰德股份有限公司 | Orally disintegrating tablet compositions of temazepam |
| CN102631336A (en) * | 2012-02-07 | 2012-08-15 | 海南卫康制药(潜山)有限公司 | Freeze-drying orally disintegrating tablet with vitamin K1 composition for infants and preparation method for freeze-drying orally disintegrating tablet |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104586748A (en) * | 2014-12-25 | 2015-05-06 | 海南卫康制药(潜山)有限公司 | Levofloxacin composition freeze-dried tablet as well as preparation method thereof |
| CN114917197A (en) * | 2022-06-16 | 2022-08-19 | 南京正科医药股份有限公司 | Levofloxacin hydrochloride tablet |
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Application publication date: 20121121 |