CN102106842B - Levofloxacin hydrochloride micropill capsule and preparation method thereof - Google Patents
Levofloxacin hydrochloride micropill capsule and preparation method thereof Download PDFInfo
- Publication number
- CN102106842B CN102106842B CN200910156969.7A CN200910156969A CN102106842B CN 102106842 B CN102106842 B CN 102106842B CN 200910156969 A CN200910156969 A CN 200910156969A CN 102106842 B CN102106842 B CN 102106842B
- Authority
- CN
- China
- Prior art keywords
- micropill
- levofloxacin hydrochloride
- pill
- release
- micro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- CAOOISJXWZMLBN-PPHPATTJSA-N htn0d03vrz Chemical compound Cl.C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 CAOOISJXWZMLBN-PPHPATTJSA-N 0.000 title claims abstract description 47
- 239000002775 capsule Substances 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000006187 pill Substances 0.000 claims abstract description 40
- 239000011248 coating agent Substances 0.000 claims abstract description 26
- 238000000576 coating method Methods 0.000 claims abstract description 26
- 239000010410 layer Substances 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 22
- 238000013268 sustained release Methods 0.000 claims abstract description 13
- 239000012730 sustained-release form Substances 0.000 claims abstract description 13
- 239000011230 binding agent Substances 0.000 claims abstract description 10
- 239000011247 coating layer Substances 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 4
- 239000000725 suspension Substances 0.000 claims description 30
- 230000001476 alcoholic effect Effects 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 14
- 229930006000 Sucrose Natural products 0.000 claims description 13
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 13
- 239000005720 sucrose Substances 0.000 claims description 13
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 12
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 12
- 239000012530 fluid Substances 0.000 claims description 11
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 8
- 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 6
- 229960003376 levofloxacin Drugs 0.000 claims description 6
- 229960001699 ofloxacin Drugs 0.000 claims description 6
- 229920003163 Eudragit® NE 30 D Polymers 0.000 claims description 3
- -1 levofloxacin hydrochlorides Chemical class 0.000 claims description 2
- 229920003134 Eudragit® polymer Polymers 0.000 claims 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 7
- 238000005516 engineering process Methods 0.000 abstract description 5
- 239000004014 plasticizer Substances 0.000 abstract description 5
- 239000000843 powder Substances 0.000 abstract description 4
- 239000000428 dust Substances 0.000 abstract description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 230000000638 stimulation Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 7
- 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 5
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000001069 triethyl citrate Substances 0.000 description 5
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 5
- 235000013769 triethyl citrate Nutrition 0.000 description 5
- 239000001856 Ethyl cellulose Substances 0.000 description 4
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 229920001249 ethyl cellulose Polymers 0.000 description 4
- 235000019325 ethyl cellulose Nutrition 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000003361 porogen Substances 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 3
- 238000007922 dissolution test Methods 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000013112 stability test Methods 0.000 description 3
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 2
- 150000007660 quinolones Chemical class 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 241000588624 Acinetobacter calcoaceticus Species 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000459479 Capsula Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 241000588923 Citrobacter Species 0.000 description 1
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
- 241000588914 Enterobacter Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010070840 Gastrointestinal tract irritation Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000607764 Shigella dysenteriae Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 210000000959 ear middle Anatomy 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 210000001187 pylorus Anatomy 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
Images
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a levofloxacin hydrochloride micropill capsule and a preparation method thereof. The levofloxacin hydrochloride micropill capsule comprises a pill core, a medicament-containing layer, a sustained-release coating layer and a quick-release layer, wherein levofloxacin hydrochloride is contained in the medicament-containing layer and the quick-release layer; and the sustained-release coating layer comprises the following materials in percentage by weight: 20 to 60 percent of levofloxacin hydrochloride, 30 to 55 percent of pill core, 10 to 25 percent of binding agent, 3 to 5 percent of sustained-release coating material, 0.3 to 3 percent of pore-forming agent and 0.1 to 1 percent of plasticizer. The levofloxacin hydrochloride micropill capsule has the advantages of high stability, small local stimulation of medicaments, high bioavailability and the like. Due to the adoption of a fluidized bed, the problems of large dust and low yield in a method of powder agglomerating in the background technology are solved.
Description
Technical field
The present invention relates to field of medicaments, relate in particular to a kind of levofloxacin hydrochloride micro-pill capsule and preparation method thereof.
Background technology
Levofloxacin hydrochloride is the levo form of ofloxacin S configuration, is white or micro-yellow crystalline powder, and odorless, bitter in the mouth, meet light gradient color, is a third generation quinolones broad spectrum antibiotic.Glucose fungus, streptococcus, streptococcus pneumoniae, gonococcus, escherichia coli, citrobacter, bacillus dysenteriae, Fei Yankeleishi bacillus, Enterobacter, hemophilus influenza, acinetobacter calcoaceticus, pylori etc. are had to good antibacterial action.Bacillus pyocyaneus, chlamydia trachomatis, tubercule bacillus etc. are had to certain antibacterial activity.And toxicity is low, be quinolones toxic and side effects minimum in marketed drug, side reaction rate is lower than 3%.Be used for the treatment of clinically the infection such as acute and chronic gram negative bacteria at the positions such as respiratory tract, throat, tonsil, urinary tract, skin and soft tissue, gallbladder and bile duct, middle ear, intestinal.
The levofloxacin hydrochloride oral formulations of listing is mainly Tablet and Capsula agent at present, and its capsule mostly is powder and fills.The present invention is to provide first crude drug is prepared into micropill, then filled capsules, has bioavailability high, little to GI irritation, and medicine stability is good.
The preparation of levofloxacin hydrochloride micro-pill and quality control (Chinese Pharmaceutical, the 14th volume o. 11th in 2005,54-55 page) a kind of levofloxacin hydrochloride micro-pill capsule is disclosed, its micropill adopts centrifugal granulating preparation, its technique is that powder plays the initial ball core of female preparation 60-80 order, then amplifies.Its main deficiency has been that female dust is larger, yield low (only having 77.8%), and another levofloxacin hydrochloride is met light gradient color, its effectively shading.CN100361660C discloses levofloxacin slow release micropill preparation, it is characterized in that being comprised of the plain particles of 0-40% or the slow release pastille micropill of micropill and 60-100%.Its deficiency is how to guarantee mixing uniformity.
Patent publication No. is the disclosed a kind of ofloxacin control-sustained releasing medicinal composition of CN1552327, comprises following composition: 50～300mg levofloxacin; With cellulose esters or esters, wherein cellulose esters or esters are selected from 5～200mg hydroxypropyl emthylcellulose, 5～200mg carboxymethyl cellulose and 5～200mg polyvinylpyrrolidone; With 5～150mg fat acid, fatty acid.This patent of invention has solved the slow release problem of levofloxacin hydrochloride.
Summary of the invention
The object of the present invention is to provide a kind of good stability, medicine local excitation is little, bioavailability is high levofloxacin hydrochloride micro-pill capsule.
Another object of the present invention is to provide the preparation method of the levofloxacin hydrochloride micro-pill capsule that a kind of dust is little, yield is high.
In order to realize foregoing invention object, the present invention adopts following technical scheme:
A kind of levofloxacin hydrochloride micro-pill capsule, comprise ball core, medicated layer, sustained release coating layer and release layer, levofloxacin hydrochloride is included in medicated layer and release layer wherein, sustained release coating layer comprises sustained release coating material, porogen, plasticizer, comprise by weight percentage following material: levofloxacin hydrochloride 20%～60%, ball core 30%～55%, binding agent 10%～25%, sustained release coating material 3%～5%, porogen 0.3%～3%, plasticizer 0.1%～1%.
The coating material of described sustained release coating layer is a kind of or its mixing in ethyl cellulose, acrylic resin.
Described porogen is one or more in Polyethylene Glycol, polyvidone, hydroxypropyl methylcellulose, methylcellulose, sucrose.
Described plasticizer is one or more mixing in Polyethylene Glycol, triethyl citrate, dibutyl sebacate, diethyl phthalate.
The preparation method that the invention also discloses a kind of levofloxacin hydrochloride micro-pill capsule, comprises the steps:
(1) contain the preparation of pill core:
The binding agent of getting recipe quantity 30%～60% is dissolved in and in alcoholic solution, obtains binding agent alcoholic solution, then the levofloxacin hydrochloride of recipe quantity 30%～60% is dissolved in binding agent alcoholic solution, stirs and makes it form uniform suspension; The ball core of recipe quantity is placed in to fluidised bed granulator, fluid bed parameter is set, above-mentioned suspension is sparged to ball wicking surface, treat that suspension adds, be dried to obtain micropill;
(2) slow release layer coating:
Sustained release coating material, porogen, the plasticizer configuration coating solution of getting recipe quantity, the micropill that step (1) is obtained is placed in fluid bed, carries out coating; The dry slow-release micro-pill that obtains after coating;
(3) release layer coating:
Remaining levofloxacin hydrochloride and binding agent are dissolved in alcoholic solution, stir into suspension, the slow-release micro-pill that step (2) is obtained is placed in fluid bed, suspension is sparged to slow-release micro-pill surface, dry after suspension is finished, dried micropill cover capsule shells is obtained to levofloxacin hydrochloride micro-pill capsule.
The present invention compared with prior art tool has the following advantages:
1, the size of levofloxacin micropill of the present invention is even, and good fluidity is easy to process, as divided dose, filled capsules etc.
2, medicine local irritation is little, because micropill is distributed in widely in gastrointestinal tract and discharges medicine with unit piller, has effectively avoided medicine local concentration excessive, has reduced the zest of medicine.
3,, because particle diameter is little, be subject to the digestive tract conveying food rhythm and pace of moving things to affect little (as pylorus is closed etc.).
4, large at gastrointestinal tract distribution area, bioavailability is high.
5, improve medicine stability, cover disagreeable taste.
6, levofloxacin micropill skin of the present invention is release layer, reaches very soon effective blood drug concentration, and internal layer is slow release layer, maintains effective blood drug concentration, effectively reduces administration number of times.
7, levofloxacin micropill slow release layer of the present invention and release layer are on same micropill, and divided dose is accurate, good uniformity in batch.
Accompanying drawing explanation
Fig. 1: the release curve of the embodiment of the present invention 1;
Fig. 2: the release curve of the embodiment of the present invention 2;
Fig. 3: the release curve of the embodiment of the present invention 3.
The specific embodiment
Below by specific embodiment, the present invention is described further.
Embodiment 1: the present embodiment adopts following prescription:
Levofloxacin hydrochloride (by ofloxacin) 200g
Sucrose ball core 153.4g
Polyvidone k30 18.4g
Ethyl cellulose 11.2g
Triethyl citrate 2.2g
Polyethylene glycol 6000 3.3g
Pulvis Talci is appropriate
Make 1000
Preparation technology:
(1) contain the preparation of pill core:
First 9.2g polyvidone k30 is dissolved in alcoholic solution, the levofloxacin hydrochloride of 100g is added in polyvidone alcoholic solution, and constantly stir and become uniform suspension; 153.4g sucrose ball core is placed in to fluidized bed pelletizer, above-mentioned even suspension is sparged to blank sucrose ball wicking surface, carry out micropill preparation, treat that suspension all adds, be dried, screen and to obtain micropill;
(2) sustained release coating layer:
9.2g ethyl cellulose is dissolved in alcoholic solution, adds 2.2g triethyl citrate, 3.3g Polyethylene Glycol and appropriate Pulvis Talci, stir to obtain coating solution; The micropill obtaining in step () is placed in to fluid bed, controls the coating that parameter is carried out slow release layer, after coating completes, be dried to obtain slow-release micro-pill;
(3) release layer coating:
3.7g binding agent is dissolved in alcoholic solution, again remaining 100g levofloxacin hydrochloride is joined in solution, constantly stir and obtain uniform suspension, the slow-release micro-pill that step (two) is prepared is placed in fluid bed, controls parameter, above-mentioned even suspension is sparged to micropill surface and add medicine to, treat that whole suspensions add, medicine-feeding completes, and the dry micropill that obtains is filled in micropill in capsule shells, to obtain levofloxacin hydrochloride micro-pill capsule.
The levofloxacin hydrochloride micro-pill capsule of the present embodiment gained is carried out to dissolution test, release curve is shown in Fig. 1, and from release curve, the levofloxacin hydrochloride micro-pill capsule of the present embodiment discharged fast in 2 hours, then Stable Release, maintains necessary blood drug level.
Embodiment 2: the present embodiment adopts following prescription:
Levofloxacin hydrochloride (by ofloxacin) 400g
Sucrose ball core 300g
Polyvidone k30 36g
Eudragit NE30D 122g
Pulvis Talci 36.8g
Make 1000
Preparation technology:
(1) contain the preparation of pill core:
First 21.6g polyvidone k30 is dissolved in alcoholic solution, the levofloxacin hydrochloride of 240g is added in polyvidone alcoholic solution, and constantly stir and become uniform suspension; 300g sucrose ball core is placed in to fluidized bed pelletizer, above-mentioned even suspension is sparged to blank sucrose ball wicking surface, carry out micropill preparation, treat that suspension all adds, be dried, screen and to obtain micropill;
(2) sustained release coating layer:
Eudragit NE30D and the Pulvis Talci of recipe quantity is water-soluble, stir to obtain coating solution; The micropill obtaining in step () is placed in to fluid bed, controls the coating that parameter is carried out slow release layer, after coating completes, be dried to obtain slow-release micro-pill;
(3) release layer coating:
Remaining binding agent is dissolved in alcoholic solution, again remaining levofloxacin hydrochloride is joined in solution, constantly stir and obtain uniform suspension, the slow-release micro-pill that step (two) is prepared is placed in fluid bed, controls parameter, above-mentioned even suspension is sparged to micropill surface and add medicine to, treat that whole suspensions add, medicine-feeding completes, and the dry micropill that obtains is filled in micropill in capsule shells, to obtain levofloxacin hydrochloride micro-pill capsule.
The levofloxacin hydrochloride micro-pill capsule of the present embodiment gained is carried out to dissolution test, release curve is shown in Fig. 2, and from release curve, the levofloxacin hydrochloride micro-pill capsule of the present embodiment discharged fast in 2 hours, then Stable Release, maintains necessary blood drug level.
Embodiment 3: the present embodiment adopts following prescription:
Levofloxacin hydrochloride (by ofloxacin) 100g
Sucrose ball core 80g
Hydroxypropyl methylcellulose 20g
Ethyl cellulose 8g
Triethyl citrate 1.6g
Polyethylene glycol 6000 2.4g
Pulvis Talci is appropriate
Make 1000
Preparation technology:
(1) contain the preparation of pill core:
First 8g hydroxypropyl methylcellulose is dissolved in alcoholic solution, the levofloxacin hydrochloride of 40g is added in polyvidone alcoholic solution, and constantly stir and become uniform suspension; 80g sucrose ball core is placed in to fluidized bed pelletizer, above-mentioned even suspension is sparged to blank sucrose ball wicking surface, carry out micropill preparation, treat that suspension all adds, be dried, screen and to obtain micropill;
(2) sustained release coating layer:
8g base cellulose dissolution, in alcoholic solution, is added to triethyl citrate, Polyethylene Glycol and appropriate Pulvis Talci, stir to obtain coating solution; The micropill obtaining in step () is placed in to fluid bed, controls the coating that parameter is carried out slow release layer, after coating completes, be dried to obtain slow-release micro-pill;
(3) release layer coating:
Remaining binding agent is dissolved in alcoholic solution, again remaining levofloxacin hydrochloride is joined in solution, constantly stir and obtain uniform suspension, the slow-release micro-pill that step (two) is prepared is placed in fluid bed, controls parameter, above-mentioned even suspension is sparged to micropill surface and add medicine to, treat that whole suspensions add, medicine-feeding completes, and the dry micropill that obtains is filled in micropill in capsule shells, to obtain levofloxacin hydrochloride micro-pill capsule.
The levofloxacin hydrochloride micro-pill capsule of the present embodiment gained is carried out to dissolution test, release curve is shown in Fig. 3, and from release curve, the levofloxacin hydrochloride micro-pill capsule of the present embodiment discharged fast in 2 hours, then Stable Release, maintains necessary blood drug level.
The levofloxacin hydrochloride micro-pill capsule of the embodiment of the present invention 1,2,3 gained under illumination, high temperature, super-humid conditions, the relative data recording for the tenth day: character, content, related substance etc.
Table 1 embodiment 1 primary stability test
Table 2 embodiment 2 primary stability tests
Table 3 embodiment 3 primary stability tests
Claims (1)
1. a levofloxacin hydrochloride micro-pill capsule, it is characterized in that preparing 1000 levofloxacin hydrochloride micro-pill capsules and adopt levofloxacin hydrochlorides by ofloxacin 400g, sucrose ball core 300g, polyvidone k3036g, Eudragit NE30D122g, Pulvis Talci 36.8g, and adopt and be prepared as follows method and prepare:
(1) contain the preparation of pill core:
First 21.6g polyvidone k30 is dissolved in alcoholic solution, the levofloxacin hydrochloride of 240g is added in polyvidone alcoholic solution, and constantly stir and become uniform suspension; 300g sucrose ball core is placed in to fluidized bed pelletizer, above-mentioned even suspension is sparged to blank sucrose ball wicking surface, carry out micropill preparation, treat that suspension all adds, be dried, screen and to obtain micropill;
(2) sustained release coating layer:
Eudragit NE30D and the Pulvis Talci of recipe quantity is water-soluble, stir to obtain coating solution; The micropill obtaining in step () is placed in to fluid bed, controls the coating that parameter is carried out slow release layer, after coating completes, be dried to obtain slow-release micro-pill;
(3) release layer coating:
Remaining binding agent is dissolved in alcoholic solution, again remaining levofloxacin hydrochloride is joined in solution, constantly stir and obtain uniform suspension, the slow-release micro-pill that step (two) is prepared is placed in fluid bed, controls parameter, above-mentioned even suspension is sparged to micropill surface and add medicine to, treat that whole suspensions add, medicine-feeding completes, and the dry micropill that obtains is filled in micropill in capsule shells, to obtain levofloxacin hydrochloride micro-pill capsule.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910156969.7A CN102106842B (en) | 2009-12-24 | 2009-12-24 | Levofloxacin hydrochloride micropill capsule and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910156969.7A CN102106842B (en) | 2009-12-24 | 2009-12-24 | Levofloxacin hydrochloride micropill capsule and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102106842A CN102106842A (en) | 2011-06-29 |
| CN102106842B true CN102106842B (en) | 2014-03-05 |
Family
ID=44171198
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910156969.7A Active CN102106842B (en) | 2009-12-24 | 2009-12-24 | Levofloxacin hydrochloride micropill capsule and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102106842B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102488660A (en) * | 2011-12-15 | 2012-06-13 | 西安天一秦昆制药有限责任公司 | Sustained-release pellet containing pirfeudone |
| CN109330995B (en) * | 2018-12-05 | 2021-05-18 | 河北医科大学 | Pellet coated with short-acting hypoglycemic agent and preparation method thereof |
| CN115227677A (en) * | 2022-08-12 | 2022-10-25 | 苏州弘森药业股份有限公司 | Levofloxacin hydrochloride capsule and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1552327A (en) * | 2003-06-03 | 2004-12-08 | 江苏豪森药业股份有限公司 | Oral ofloxacin control-sustained releasing medicinal composition |
| CN1554346A (en) * | 2003-12-23 | 2004-12-15 | 广州市医药工业研究所 | Diltiazem hydrochloride control release capsule and its preparing method |
| CN1813758A (en) * | 2005-12-07 | 2006-08-09 | 范敏华 | Levofloxacin hydrochloride micro-pill capsule and its preparing method |
| CN1994285A (en) * | 2006-01-04 | 2007-07-11 | 上海医药工业研究院 | Sustained release micro-pellet of guaifenesin and preparation process thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4290381B2 (en) * | 2002-04-11 | 2009-07-01 | 学校法人 聖マリアンナ医科大学 | Emulsion containing pyridonecarboxylic acid compound |
-
2009
- 2009-12-24 CN CN200910156969.7A patent/CN102106842B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1552327A (en) * | 2003-06-03 | 2004-12-08 | 江苏豪森药业股份有限公司 | Oral ofloxacin control-sustained releasing medicinal composition |
| CN1554346A (en) * | 2003-12-23 | 2004-12-15 | 广州市医药工业研究所 | Diltiazem hydrochloride control release capsule and its preparing method |
| CN1813758A (en) * | 2005-12-07 | 2006-08-09 | 范敏华 | Levofloxacin hydrochloride micro-pill capsule and its preparing method |
| CN1994285A (en) * | 2006-01-04 | 2007-07-11 | 上海医药工业研究院 | Sustained release micro-pellet of guaifenesin and preparation process thereof |
Non-Patent Citations (3)
| Title |
|---|
| Antidepressant, anxiogenic, and antinociceptive properties of levofloxacin in rats and mice;B.F. Erden, 等;《Pharmacology Biochemistry and Behavior》;20011231;第68卷;第435-441页 * |
| B.F. Erden, 等.Antidepressant, anxiogenic, and antinociceptive properties of levofloxacin in rats and mice.《Pharmacology Biochemistry and Behavior》.2001,第68卷第435-441页. |
| JP特开2003-300882A 2003.10.21 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102106842A (en) | 2011-06-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MX2007010889A (en) | Gastroresistant pharmaceutical formulations containing rifaximin. | |
| CN107007616A (en) | Antisense composition and its preparation and application | |
| EP3498264B1 (en) | Pharmaceutical preparation for oral administration with controlled dissolution rate, the preparation comprising tamsulosin hydrochloride-containing sustained-release pellets | |
| EP1602362B1 (en) | Drug composition having active ingredient adhered at high concentration to spherical core | |
| WO2018229641A1 (en) | Solid preparation of cariprazine for oral administration | |
| WO2006040779A2 (en) | Controlled release gastric floating matrix formulation containing imatinib | |
| CN103919715A (en) | Controlled Release Drug Combination Containing Choline Alfoscerate Or Salt Thereof And Method For Preparing Same | |
| AU2016398029B2 (en) | Palatable compositions including sodium phenylbutyrate and uses thereof | |
| JP6401270B2 (en) | Sustained release solid oral composition | |
| TW201442712A (en) | Formulations of organic compounds | |
| CN102106842B (en) | Levofloxacin hydrochloride micropill capsule and preparation method thereof | |
| AU2014349782A1 (en) | Slow-release solid oral compositions | |
| KR20110007255A (en) | A solid pharmaceutical formulation | |
| JP2017530162A (en) | Oral administration preparation of A-nor-5α androstane compound | |
| TW200808380A (en) | Enteric-coated preparation for site-specific delivery of drug to site within the small intestine | |
| RU2390332C2 (en) | Solid pharmaceutical composition | |
| CN107412198A (en) | Duloxetine hydrochloride enteric slow release granule and preparation method thereof | |
| CN103417483B (en) | memantine hydrochloride slow-release dry suspension and preparation method thereof | |
| CN1813758A (en) | Levofloxacin hydrochloride micro-pill capsule and its preparing method | |
| JP2008044927A (en) | Enteric-coated preparation covered with enteric coating material for site-specific delivery of drug to site within small intestine | |
| US20210290557A1 (en) | Multi-particulate pharmaceutical composition, immediate release pellets, sustained release pellets, enteric release pellets and use thereof | |
| JP7419333B2 (en) | Pharmaceutical composition containing metaarsenite and manufacturing method | |
| CN102552214A (en) | Ilaprazole enteric capsule and preparation method thereof | |
| JP2017530143A (en) | A pharmaceutical composition comprising alpericept | |
| CN102579358B (en) | A kind of drug sustained-release pellet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Address after: West Building in Hangzhou City, Zhejiang province 310052 Binjiang District Lake Road 1180 Huaye hi tech Industrial Park Building No. 2 Applicant after: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Applicant after: Hainan Poly Pharm Co.,Ltd. Applicant after: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Address before: West Building in Hangzhou City, Zhejiang province 310052 Binjiang District Lake Road 1180 Huaye hi tech Industrial Park Building No. 2 Applicant before: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Applicant before: Hainan Poly Pharm Co.,Ltd. Applicant before: Zhejiang Ruida Pharm Co.,Ltd. |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: West Building in Hangzhou City, Zhejiang province 310052 Binjiang District Lake Road 1180 Huaye hi tech Industrial Park Building No. 2 Patentee after: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Patentee after: HAINAN POLY PHARM. Co.,Ltd. Patentee after: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Address before: West Building in Hangzhou City, Zhejiang province 310052 Binjiang District Lake Road 1180 Huaye hi tech Industrial Park Building No. 2 Patentee before: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Patentee before: Hainan Poly Pharm Co.,Ltd. Patentee before: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20230118 Address after: 571127 Guilin Ocean Economic Development Zone, Meilan District, Haikou City, Hainan Province Patentee after: HAINAN POLY PHARM. Co.,Ltd. Patentee after: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Address before: West Building in Hangzhou City, Zhejiang province 310052 Binjiang District Lake Road 1180 Huaye hi tech Industrial Park Building No. 2 Patentee before: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Patentee before: HAINAN POLY PHARM. Co.,Ltd. Patentee before: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| DD01 | Delivery of document by public notice |
Addressee: Zhu Xulei Document name: Notification of Conformity |
|
| DD01 | Delivery of document by public notice |