CN110151712A - A kind of lavo-ofloxacin hydrochloride dripping pill and preparation method thereof - Google Patents
A kind of lavo-ofloxacin hydrochloride dripping pill and preparation method thereof Download PDFInfo
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- CN110151712A CN110151712A CN201910399297.6A CN201910399297A CN110151712A CN 110151712 A CN110151712 A CN 110151712A CN 201910399297 A CN201910399297 A CN 201910399297A CN 110151712 A CN110151712 A CN 110151712A
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- ofloxacin
- ofloxacin hydrochloride
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- 229960001699 ofloxacin Drugs 0.000 title claims abstract description 63
- 239000006187 pill Substances 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000000843 powder Substances 0.000 claims abstract description 16
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 claims abstract description 11
- 239000008118 PEG 6000 Substances 0.000 claims abstract description 8
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 claims abstract description 8
- 239000000463 material Substances 0.000 claims abstract description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 60
- 239000003814 drug Substances 0.000 claims description 28
- 229940079593 drug Drugs 0.000 claims description 24
- 239000011159 matrix material Substances 0.000 claims description 12
- 238000001816 cooling Methods 0.000 claims description 11
- 239000006185 dispersion Substances 0.000 claims description 10
- 238000002844 melting Methods 0.000 claims description 10
- 230000008018 melting Effects 0.000 claims description 10
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 claims description 4
- UIOFUWFRIANQPC-JKIFEVAISA-N Floxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl UIOFUWFRIANQPC-JKIFEVAISA-N 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 229960004273 floxacillin Drugs 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 238000002347 injection Methods 0.000 abstract description 7
- 239000007924 injection Substances 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 230000001154 acute effect Effects 0.000 abstract description 2
- 230000002924 anti-infective effect Effects 0.000 abstract description 2
- 208000015181 infectious disease Diseases 0.000 abstract description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 31
- 239000007788 liquid Substances 0.000 description 29
- 238000000034 method Methods 0.000 description 25
- 238000004090 dissolution Methods 0.000 description 23
- 239000013558 reference substance Substances 0.000 description 16
- 239000004677 Nylon Substances 0.000 description 8
- 239000002826 coolant Substances 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 229920001778 nylon Polymers 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 239000012085 test solution Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000002835 absorbance Methods 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000013441 quality evaluation Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000003556 assay Methods 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 239000012738 dissolution medium Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 238000010812 external standard method Methods 0.000 description 4
- 239000004744 fabric Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000002386 leaching Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 238000005374 membrane filtration Methods 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 239000011148 porous material Substances 0.000 description 4
- 238000004321 preservation Methods 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 229910001220 stainless steel Inorganic materials 0.000 description 4
- 239000010935 stainless steel Substances 0.000 description 4
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 3
- 229960003376 levofloxacin Drugs 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 241000202934 Mycoplasma pneumoniae Species 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 201000005010 Streptococcus pneumonia Diseases 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to biomedicine technical fields, more particularly to a kind of preparation method of lavo-ofloxacin hydrochloride dripping pill, the pill prescription contains following pharmaceutical grade component: PEG-4000, PEG-6000, lavo-ofloxacin hydrochloride fine powder, and mass ratio of the above-mentioned material in prescription is followed successively by 0.4-0.8 ︰ 0.4-0.8 ︰ 0.2-0.4.For the lavo-ofloxacin hydrochloride novel form that the present invention refers to other than acute infection disease needs to be injected intravenously lavo-ofloxacin hydrochloride injection, the faster lavo-ofloxacin hydrochloride dripping pill that works is can be selected in the anti-infective therapy of other indications.
Description
Technical field
The present invention relates to lavo-ofloxacin hydrochloride preparation technique fields, and in particular to a kind of lavo-ofloxacin hydrochloride dripping pill.
Background technique
Lavo-ofloxacin hydrochloride is the laevoisomer of quinolone drugs ofloxacin hydrochloride, and there is broad-spectrum antiseptic to make
With if had to most gram-negative bacteria escherichia coli, Proteus, Salmonella, haemophilus influenzae etc. stronger
Antibacterial activity.To the gram positive bacterias such as staphylococcus aureus, micrococcus scarlatinae, streptococcus pneumonia and mycoplasma pneumoniae, clothing
Substance also has certain inhibitory activity, but poor to anaerobic bacteria and enterococcal effect.Suitable for urinary system caused by sensitive bacteria
The diseases such as system, respiratory system, digestive system, skin soft-tissue infection.
The antibacterial activity of lavo-ofloxacin hydrochloride is about twice of ofloxacin hydrochloride raceme, and adverse reaction is compared with racemization
Body is few, is one of common Antibiotics drug.The preparation type of lavo-ofloxacin hydrochloride is at present with injection, capsule, piece
Based on agent, but there are shortcomings, for example injection needs drug administration by injection, and patient compliance is poor, and security risk is big；Production link ring
Border and equipment requirement height, quality requirement are high, lead to high production cost；Transportational process is easily broken, and stability is general etc. during storage；
Capsule and tablet drug release rate are slow, work slow, preparation process is relative complex.Selecting the dripping pill of water-soluble base preparation has mouth
Clothes absorption is fast, patient compliance is good；Production link environmental requirement is relatively low, and preparation process is simple, and production cost is low.Therefore, originally
Dripping pill is made in lavo-ofloxacin hydrochloride by invention, to overcome the upper of existing lavo-ofloxacin hydrochloride injection, capsule and tablet
State deficiency.
Summary of the invention
A kind of preparation method of lavo-ofloxacin hydrochloride dripping pill proposed by the present invention, solve injection compliance it is poor, peace
Full property is low, at high cost；The problem of capsule and tablet drug release are slow, work slow, opposite high production cost.
To achieve the goals above, the present invention adopts the following technical scheme:
A kind of lavo-ofloxacin hydrochloride dripping pill, pill prescription contain following component: PEG-4000, PEG-6000 and hydrochloric acid are left
Ofloxacin fine powder, mass ratio of the above-mentioned material in prescription are followed successively by 0.4-0.8 ︰ 0.4-0.8 ︰ 0.2-0.4.
Preferably, the mass ratio of PEG-4000, PEG-6000 and lavo-ofloxacin hydrochloride fine powder in prescription is 0.6g:
0.6g:0.3g.
Preferably, average ball weight is 50mg, wherein lavo-ofloxacin hydrochloride content is 9.0-11.0mg.
Preferably, average ball weight is 50mg, wherein lavo-ofloxacin hydrochloride content is 10.0mg.
A kind of preparation method of lavo-ofloxacin hydrochloride dripping pill, preparation process include: the melting of matrix, the dispersion of drug,
Dripping, cooling and net ball.
The preparation step of pill of the present invention includes the melting of matrix, the dispersion of drug, dripping, cooling, net ball etc.；
In addition, also having carried out quality evaluation to made dripping pill.It is described in detail below:
(1) melting of matrix: taking recipe quantity PEG and is placed in evaporating dish by a certain percentage, and 80-90 DEG C of water-bath heating is molten
Melt, stirs evenly.
(2) dispersion of drug: recipe quantity lavo-ofloxacin hydrochloride fine powder (crossing 100 mesh nylon medicines sieve) is taken, is added above-mentioned molten
Melt in matrix, stir evenly, so that medicaments uniformity disperses or/and is dissolved in matrix.
(3) dripping: gained molten liquid is moved in the liquid reservoir of heat preservation, and the temperature in liquid reservoir need to remain to 80-85 DEG C,
Regulating dropping head instills cooling atoleine at a distance from coolant liquid, by drug containing molten liquid (temperature is controlled at 4 DEG C or less)；Drop speed
Control is in 30-35 drop/min.Coolant liquid cannot be shaken during dripping, in case viscous stick occurs for uncured dripping pill.
(4) net ball: the dripping pill of cooling forming is taken out, and is placed in nylon and is shone on the net, drips net atoleine；It is wiped again with gauze
The atoleine of surface attachment is placed in and air-dries in heating container, it is dry to get.
(5) quality evaluation:
1. appearance: ball shape, size, color, whether there is or not be adhered phenomenon.
2. weight differential: taking 20 ball of piller, accurately weighed total weight after acquiring average ball weight (about 50mg), then distinguishes essence
The weight of close weighed each ball, for every ball weight compared with average ball heavy phase, the pill beyond limit test of weight variation must not be more than 2 balls,
And there must not be 1 ball beyond one times of weight limit.
Regulation of " Chinese Pharmacopoeia " version in 2015 about pill weight differential
3. leaching time limit measurement: according to being advised under pill disintegration time limit test item in " Chinese Pharmacopoeia " version annex in 2015
It is fixed, 0.425mm should be using the sieve pore internal diameter of tablet disintegration time limit device, but stainless steel cloth；Unless otherwise specified, dripping pill is taken
It 6, checks according to the above method, all dripping pills should all leach in 30min；It cannot all be leached if any one, should separately take 6
Grain, according to the above method retrial should all meet regulation.
4. dissolution rate: this product is taken, according to dissolution rate and drug release determination method (0,931 first method of general rule), with hydrochloric acid solution (9-
1000) 900mL is dissolution medium, and revolving speed is 50 turns per minute, operates according to methods, when through 30min, takes dissolution fluid 10mL, filter, uses
Hydrochloric acid solution is quantitatively diluted to 100mL, is made in every l mL containing about lavo-ofloxacin (by C18H20FN3O4Meter) 22.2 μ g it is molten
Liquid measures absorbance according to UV-VIS spectrophotometry (general rule 0401) at 294nm wavelength；Another precision weighs levofloxacin
Star reference substance is appropriate, add hydrochloric acid solution to dissolve and quantify dilution be made in every lmL containing about the solution of 22.2 μ g, be measured in the same method, count
Calculate every the amount of dissolution.Dissolution limit is 80% or more labelled amount, should meet regulation.
5. assay:
The preparation of reference substance solution: taking lavo-ofloxacin hydrochloride reference substance appropriate, accurately weighed, adds 0.1mol/L hydrochloric acid molten
The hydrochloric lavo-ofloxacin reference substance 0.1mg of every 1mL is made in liquid, mixed solution to get.
The preparation of test solution: taking this product appropriate, finely ground, weighs the fine powder for being equivalent to 1.0g, is equivalent to levofloxacin
Star presses C18H20FN3O4Meter, about 0.2g), it sets in 100mL measuring bottle, adds 0.1mol/L hydrochloric acid solution to leach and be diluted to scale, shake
Even, 0.45 μm of filter membrane filtration, precision measures subsequent filtrate 5mL, sets in 100mL measuring bottle, be diluted to quarter with 0.lmol/L hydrochloric acid solution
Degree, shakes up, as test solution.
According to UV-VIS spectrophotometry (general rule 0401), absorbance is measured at the wavelength of 294nm；A bit by external standard
Method calculates to get lavo-ofloxacin hydrochloride content.
Possessed by of the invention the utility model has the advantages that
A kind of lavo-ofloxacin hydrochloride dripping pill of the invention absorbs fastly, in addition to acute infection disease needs to be injected intravenously hydrochloric acid
Outside levofloxacin, the faster lavo-ofloxacin hydrochloride drop that works is can be selected in the anti-infective therapy of other indications
Ball.Because its pill is administered orally, patient compliance is greatly increased than injection, and the safety is improved；Dripping pill production equipment is simple,
It is lower than capsule and tablet cost, so that the market competitiveness is stronger.On lavo-ofloxacin hydrochloride pill also be can yet be regarded as simultaneously
State a kind of supplement dosage form of dosage form；For patients, a kind of more selections of medication wish.
Specific embodiment
Combined with specific embodiments below, the present invention is further clarified.The experiment of actual conditions is not specified in embodiment
Method, usually according to normal condition and condition described in handbook, or according to the normal condition proposed by manufacturer；Used is logical
With equipment, material, reagent etc., it is commercially available unless otherwise specified.
By pharmaceutical grade PEG-4000, PEG-6000,0.4 ︰ of lavo-ofloxacin hydrochloride fine powder mass ratio, 0.4 ︰ 0.2, amounts to and claim
Take raw material 10g.It prepares according to the following steps:
(1) melting of matrix: recipe quantity PEG-4000, PEG-6000 are weighed, and is placed in evaporating dish by a certain percentage, water
80-90 DEG C of heating melting is bathed, is stirred evenly.
(2) dispersion of drug: recipe quantity lavo-ofloxacin hydrochloride fine powder (crossing 100 mesh nylon medicines sieve) is taken, is added above-mentioned molten
Melt in matrix, stir evenly, so that medicaments uniformity dispersion or/and dissolution.
(3) dripping: gained molten liquid is moved in the liquid reservoir of heat preservation, and the temperature in liquid reservoir need to remain to 80-85 DEG C,
Regulating dropping head instills cooling atoleine at a distance from coolant liquid, by drug containing molten liquid (temperature is controlled at 4 DEG C or less)；Drop speed
Control is in 30 drops/min.Coolant liquid cannot be shaken during dripping, in case viscous stick occurs for uncured dripping pill.
(4) net ball: the dripping pill of cooling forming is taken out, and is placed in nylon and is shone on the net, drips net atoleine；It is wiped again with gauze
The atoleine of surface attachment is placed in and air-dries in heating container, it is dry to get.Every grain ball weighs about 50mg.
(5) quality evaluation:
1. appearance: near-white spherical shape dripping pill.
2. weight differential: take 20 ball of piller, accurately weighed total weight, after acquiring average ball weight, then it is accurately weighed each respectively
The weight of ball, every ball weight is compared with average ball heavy phase, 1 ball of pill beyond limit test of weight variation, but without departing from weight limit
One times.
3. leaching time limit measurement: according to being advised under pill disintegration time limit test item in " Chinese Pharmacopoeia " version annex in 2015
It is fixed, 0.425mm should be using the sieve pore internal diameter of tablet disintegration time limit device, but stainless steel cloth；Unless otherwise specified, dripping pill is taken
It 6, checks according to the above method, all dripping pills should all leach in 30min.
4. dissolution rate: this product is taken, according to " Chinese Pharmacopoeia " version annex dissolution rates in 2015 and drug release determination method (general rule 0931
First method), using hydrochloric acid solution (9-1000) 900mL as dissolution medium, revolving speed is 50 turns per minute, is operated according to methods, through 30min
When, dissolution fluid 10mL is taken, is filtered, is quantitatively diluted to 100mL with hydrochloric acid solution, is made in every lmL and (is pressed containing about lavo-ofloxacin
C18H20FN3O4Meter) solution of 22.2 μ g measured at 294nm wavelength and inhaled according to UV-VIS spectrophotometry (general rule 0401)
Luminosity；It is appropriate that another precision weighs lavo-ofloxacin reference substance, add hydrochloric acid solution to dissolve and quantify dilution be made in every lmL containing about
The solution of 22.2 μ g, is measured in the same method, and calculates every the amount of dissolution.Dissolution limit is 90.5% or more labelled amount, meets regulation.
5. assay:
The preparation of reference substance solution: taking lavo-ofloxacin hydrochloride reference substance appropriate, accurately weighed, adds 0.1mol/L hydrochloric acid molten
The hydrochloric lavo-ofloxacin reference substance 0.1mg of every 1mL is made in liquid, mixed solution to get.
The preparation of test solution: taking 30 ball of this product, finely ground, weigh be equivalent to average ball weigh 20 times fine powder it is appropriate (about
1.0g is equivalent to lavo-ofloxacin by C18H20FN3O4Meter, about 0.2g), it sets in 100mL measuring bottle, adds 0.1mol/L hydrochloric acid solution molten
Scale is dissipated and be diluted to, is shaken up, 0.45 μm of filter membrane filtration, precision measures subsequent filtrate 5mL, sets in 100mL measuring bottle, use 0.lmol/L
Hydrochloric acid solution is diluted to scale, shakes up, as test solution.
According to UV-VIS spectrophotometry (general rule 0401), absorbance is measured at the wavelength of 294nm；A bit by external standard
Method calculates, and every hydrochloric lavo-ofloxacin of ball is (10.16 ± 0.72) mg.
Embodiment 2
According to PEG-4000, PEG-6000,0.6 ︰ of lavo-ofloxacin hydrochloride fine powder mass ratio, 0.6 ︰ 0.3, accurately weigh each
Raw material amounts to 10g.It prepares according to the following steps:
(1) melting of matrix: recipe quantity PEG-4000, PEG-6000 are weighed, and is placed in evaporating dish by a certain percentage, water
80-90 DEG C of heating melting is bathed, is stirred evenly.
(2) dispersion of drug: recipe quantity lavo-ofloxacin hydrochloride fine powder (crossing 100 mesh nylon medicines sieve) is taken, is added above-mentioned molten
Melt in matrix, stir evenly, so that medicaments uniformity dispersion or/and dissolution.
(3) dripping: gained molten liquid is moved in the liquid reservoir of heat preservation, and the temperature in liquid reservoir need to remain to 80-85 DEG C,
Regulating dropping head instills cooling atoleine at a distance from coolant liquid, by drug containing molten liquid (temperature is controlled at 4 DEG C or less)；Drop speed
Control is in 30 drops/min.Coolant liquid cannot be shaken during dripping, in case viscous stick occurs for uncured dripping pill.
(4) net ball: the dripping pill of cooling forming is taken out, and is placed in nylon and is shone on the net, drips net atoleine；It is wiped again with gauze
The atoleine of surface attachment is placed in and air-dries in heating container, it is dry to get.Every grain ball weighs about 50mg.
(5) quality evaluation:
1. appearance: near-white spherical shape dripping pill.
2. weight differential: taking 20 ball of piller, accurately weighed total weight acquires average ball weight, then accurately weighed each ball respectively
Weight, every ball weight is compared with average ball heavy phase, 1 ball of pill beyond limit test of weight variation, but without departing from weight limit
One times.
3. leaching time limit measurement: according to being advised under pill disintegration time limit test item in " Chinese Pharmacopoeia " version annex in 2015
It is fixed, 0.425mm should be using the sieve pore internal diameter of tablet disintegration time limit device, but stainless steel cloth；Unless otherwise specified, dripping pill is taken
It 6, checks according to the above method, all dripping pills should all leach in 30min.
4. dissolution rate: this product is taken, according to " Chinese Pharmacopoeia " version annex dissolution rates in 2015 and drug release determination method (general rule 0931
First method), using hydrochloric acid solution (9-1000) 900mL as dissolution medium, revolving speed is 50 turns per minute, is operated according to methods, through 30min
When, dissolution fluid 10mL is taken, is filtered, is quantitatively diluted to 100mL with hydrochloric acid solution, is made in every lmL and (is pressed containing about lavo-ofloxacin
C18H20FN3O4Meter) solution of 22.2 μ g measured at 294nm wavelength and inhaled according to UV-VIS spectrophotometry (general rule 0401)
Luminosity；It is appropriate that another precision weighs lavo-ofloxacin reference substance, add hydrochloric acid solution to dissolve and quantify dilution be made in every lmL containing about
The solution of 22.2 μ g, is measured in the same method, and calculates every the amount of dissolution.Dissolution limit is 90.5% or more labelled amount, meets regulation.
5. assay:
The preparation of reference substance solution: taking lavo-ofloxacin hydrochloride reference substance appropriate, accurately weighed, adds 0.1mol/L hydrochloric acid molten
The hydrochloric lavo-ofloxacin reference substance 0.1mg of every 1mL is made in liquid, mixed solution to get.
The preparation of test solution: taking 30 ball of this product, finely ground, weigh be equivalent to average ball weigh 20 times fine powder it is appropriate (about
1.0g is equivalent to lavo-ofloxacin by C18H20FN3O4Meter, about 0.2g), it sets in 100mL measuring bottle, adds 0.1mol/L hydrochloric acid solution molten
Scale is dissipated and be diluted to, is shaken up, 0.45 μm of filter membrane filtration, precision measures subsequent filtrate 5mL, sets in 100mL measuring bottle, use 0.lmol/L
Hydrochloric acid solution is diluted to scale, shakes up, as test solution.
According to UV-VIS spectrophotometry (general rule 0401), absorbance is measured at the wavelength of 294nm；A bit by external standard
Method calculates, and every hydrochloric lavo-ofloxacin of ball is (9.84 ± 0.71) mg.
Embodiment 3
According to PEG-4000, PEG-6000,0.8 ︰ of lavo-ofloxacin hydrochloride fine powder mass ratio, 0.8 ︰ 0.4, accurately weigh each
Raw material amounts to 10g.It prepares according to the following steps:
(1) melting of matrix: recipe quantity PEG-4000, PEG-6000 are weighed, and is placed in evaporating dish by a certain percentage, water
80-90 DEG C of heating melting is bathed, is stirred evenly.
(2) dispersion of drug: recipe quantity lavo-ofloxacin hydrochloride fine powder (crossing 100 mesh nylon medicines sieve) is taken, is added above-mentioned molten
Melt in matrix, stir evenly, so that medicaments uniformity dispersion or/and dissolution.
(3) dripping: gained molten liquid is moved in the liquid reservoir of heat preservation, and the temperature in liquid reservoir need to remain to 80-85 DEG C,
Regulating dropping head instills cooling atoleine at a distance from coolant liquid, by drug containing molten liquid (temperature is controlled at 4 DEG C or less)；Drop speed
Control is in 30 drops/min.Coolant liquid cannot be shaken during dripping, in case viscous stick occurs for uncured dripping pill.
(4) net ball: the dripping pill of cooling forming is taken out, and is placed in nylon and is shone on the net, drips net atoleine；It is wiped again with gauze
The atoleine of surface attachment is placed in and air-dries in heating container, it is dry to get.Every grain ball weighs about 50mg.
(5) quality evaluation:
1. appearance: near-white spherical shape dripping pill.
2. weight differential: taking 20 ball of piller, accurately weighed total weight after acquiring average ball weight (about 50mg), then distinguishes essence
The weight of close weighed each ball, every ball weight is compared with average ball heavy phase, 1 ball of pill beyond limit test of weight variation, but without departing from
One times of weight limit.
3. leaching time limit measurement: according to being advised under pill disintegration time limit test item in " Chinese Pharmacopoeia " version annex in 2015
It is fixed, 0.425mm should be using the sieve pore internal diameter of tablet disintegration time limit device, but stainless steel cloth；Unless otherwise specified, dripping pill is taken
It 6, checks according to the above method, all dripping pills should all leach in 30min.
4. dissolution rate: this product is taken, according to " Chinese Pharmacopoeia " version annex dissolution rates in 2015 and drug release determination method (general rule 0931
First method), using hydrochloric acid solution (9-1000) 900mL as dissolution medium, revolving speed is 50 turns per minute, is operated according to methods, through 30min
When, dissolution fluid 10mL is taken, is filtered, is quantitatively diluted to 100mL with hydrochloric acid solution, is made in every lmL and (is pressed containing about lavo-ofloxacin
C18H20FN3O4Meter) solution of 22.2 μ g measured at 294nm wavelength and inhaled according to UV-VIS spectrophotometry (general rule 0401)
Luminosity；It is appropriate that another precision weighs lavo-ofloxacin reference substance, add hydrochloric acid solution to dissolve and quantify dilution be made in every lmL containing about
The solution of 22.2 μ g, is measured in the same method, and calculates every the amount of dissolution.Dissolution limit is 90.5% or more labelled amount, meets regulation.
5. assay:
The preparation of reference substance solution: taking lavo-ofloxacin hydrochloride reference substance appropriate, accurately weighed, adds 0.1mol/L hydrochloric acid molten
The hydrochloric lavo-ofloxacin reference substance 0.1mg of every 1mL is made in liquid, mixed solution to get.
The preparation of test solution: taking 30 ball of this product, finely ground, weigh be equivalent to average ball weigh 20 times fine powder it is appropriate (about
1.0g is equivalent to lavo-ofloxacin by C18H20FN3O4Meter, about 0.2g), it sets in 100mL measuring bottle, adds 0.1mol/L hydrochloric acid solution molten
Scale is dissipated and be diluted to, is shaken up, 0.45 μm of filter membrane filtration, precision measures subsequent filtrate 5mL, sets in 100mL measuring bottle, use 0.lmol/L
Hydrochloric acid solution is diluted to scale, shakes up, as test solution.
According to UV-VIS spectrophotometry (general rule 0401), absorbance is measured at the wavelength of 294nm；A bit by external standard
Method calculates, and every hydrochloric lavo-ofloxacin of ball is (9.93 ± 0.85) mg.
The above content is a further detailed description of the present invention in conjunction with specific preferred embodiments, and it cannot be said that
Specific implementation of the invention is only limited to these instructions.For those of ordinary skill in the art to which the present invention belongs, exist
Under the premise of not departing from present inventive concept, a number of simple deductions or replacements can also be made, all shall be regarded as belonging to of the invention
Protection scope.
Claims (5)
1. a kind of lavo-ofloxacin hydrochloride dripping pill, pill prescription contains following component: PEG-4000, PEG-6000 and the left oxygen of hydrochloric acid
Flucloxacillin fine powder, mass ratio of the above-mentioned material in prescription are followed successively by 0.4-0.8 ︰ 0.4-0.8 ︰ 0.2-0.4.
2. lavo-ofloxacin hydrochloride dripping pill as described in claim 1, is characterized in that: PEG-4000, PEG-6000 and hydrochloric acid are left
Mass ratio of the Ofloxacin fine powder in prescription is 0.6 g:0.6 g:0.3 g.
3. lavo-ofloxacin hydrochloride dripping pill as described in claim 1, is characterized in that: average ball weight is 50 mg, wherein hydrochloric acid
Lavo-ofloxacin content is 9.0-11.0 mg.
4. lavo-ofloxacin hydrochloride dripping pill as claimed in claim 3, is characterized in that: average ball weight is 50 mg, wherein hydrochloric acid
Lavo-ofloxacin content is 10.0 mg.
5. a kind of preparation method of the lavo-ofloxacin hydrochloride dripping pill as described in claim 1-4, is characterized in that: preparation process packet
It includes: the melting of matrix, the dispersion of drug, dripping, cooling and net ball.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1634004A (en) * | 2004-10-01 | 2005-07-06 | 耿燕 | Ambroxol hydrochloride drop pills and its preparation method |
| CN1634072A (en) * | 2003-12-28 | 2005-07-06 | 彭红 | Levofloxacin dripping pills and its preparing process |
| CN103393543A (en) * | 2013-08-02 | 2013-11-20 | 魏雪纹 | Method using 3D printing technology to prepare dropping pills |
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2019
- 2019-05-14 CN CN201910399297.6A patent/CN110151712A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1634072A (en) * | 2003-12-28 | 2005-07-06 | 彭红 | Levofloxacin dripping pills and its preparing process |
| CN1634004A (en) * | 2004-10-01 | 2005-07-06 | 耿燕 | Ambroxol hydrochloride drop pills and its preparation method |
| CN103393543A (en) * | 2013-08-02 | 2013-11-20 | 魏雪纹 | Method using 3D printing technology to prepare dropping pills |
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