CN104257612A - Long-acting ofloxacin sustained-release pellet for veterinary use and preparation method thereof - Google Patents
Long-acting ofloxacin sustained-release pellet for veterinary use and preparation method thereof Download PDFInfo
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- CN104257612A CN104257612A CN201410447678.4A CN201410447678A CN104257612A CN 104257612 A CN104257612 A CN 104257612A CN 201410447678 A CN201410447678 A CN 201410447678A CN 104257612 A CN104257612 A CN 104257612A
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- ofloxacin
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- 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 title claims abstract description 55
- 229960001699 ofloxacin Drugs 0.000 title claims abstract description 55
- 238000013268 sustained release Methods 0.000 title claims abstract description 27
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title abstract description 19
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- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of a pharmaceutical preparation for veterinary use, relates to a sustained-release preparation and in particular relates to a long-acting ofloxacin sustained-release pellet for veterinary use and a preparation method thereof. The pellet sequentially comprises a medicated pellet core and a sustained-release coating layer, and is characterized in that the sustained-release coating layer accounts for 5-20% of mass of the medicated pellet core; and the sustained-release coating layer comprises the following ingredients: 4.5-9 parts of a sustained-release coating material, 0.1-2 parts of an anti-sticking agent, 0-2 parts of a plasticizer, 0-0.6 part of a pore-forming agent and 0.1-1 part of a gastrointestinal adhesive. The long-acting ofloxacin sustained-release pellet for veterinary use disclosed by the invention is beneficial for improving a stability of preparation and capable of masking poor taste of ofloxacin; the pellet is uniform in size, high in sphericity, small in difference between batches, stable in quality, simple and reliable in preparation process and low in production cost.
Description
technical field
The invention belongs to pharmaceutic preparation for livestock technical field, relate to a kind of slow releasing preparation, be specifically related to a kind of long-acting veterinary ofloxacin slow-release micropill and preparation method thereof.
background technology
Ofloxacin is a kind of fluoroquinolone antibiotics, there is broad-spectrum antibacterial action, antibacterial action is strong, to most enterobacteriaceae lactobacteriaceae, as the gram-negative bacterias such as escherichia coli, Klebsiella, Proteus, Salmonella, Shigella and hemophilus influenza, legionella pneumophilia, Diplococcus gonorrhoeae have stronger antibacterial activity.Also antibacterial action is had to the gram positive bacterias such as staphylococcus aureus, streptococcus pneumoniae, micrococcus scarlatinae and mycoplasma pneumoniae, Chlamydia pneumoniae, its mechanism of action is the activity by anti-bacteria DNA gyrase, stops the synthesis of DNA of bacteria and copies and cause bacterial death.Ofloxacin is widely used on veterinary clinic, is mainly used to prevent and treat swine dysentery, baby pig diarrhoea, calf diarrhea, calf paratyphoid fever, yellow scour of piglet, Hakuri etc., especially have unique curative effect to Sanguis sus domestica La caused by treponema, and relapse rate is low.
Although being widely used of ofloxacin, in use due to ofloxacin poorly water-soluble, need acid adding or alkali to regulate pH to dissolve when it is water-soluble, though ofloxacin liquid preparation is easy to use, poor stability, carries transport inconvenience.The patent of current ofloxacin application for animals mostly is injection, though injection is rapid-action, easily to trouble poultry cause stress, be unfavorable for the quick improvement of disease.
summary of the invention
The invention provides a kind of long-acting veterinary ofloxacin slow-release micropill and preparation method thereof.
The present invention is by the following technical solutions:
A kind of long-acting veterinary ofloxacin slow-release micropill, is followed successively by containing pill core and sustained-release coating layer from inside to outside, and the quality of sustained-release coating layer is containing pill core 5 ~ 20%; With parts by weight, composition containing pill core is: ofloxacin 10 ~ 25 parts, filler 10 ~ 60 parts and binding agent 10 ~ 15 parts, the composition of sustained-release coating layer is: Sustained release coating materials 4.5 ~ 9 parts, antiplastering aid 0.1 ~ 2 part, plasticizer 0 ~ 2 part, porogen 0 ~ 0.6 part and gastrointestinal tract adhesive agent 0.1 ~ 1 part, the total amount containing pill core and sustained-release coating layer is 100 parts.
Filler is at least one in lactose, mannitol, microcrystalline Cellulose, sodium bicarbonate, calcium carbonate, pregelatinized Starch, medicinal dextrin.
Binding agent is at least one in sodium carboxymethyl cellulose, hypromellose, Polyethylene Glycol, polyvidone, sucrose.
Gastrointestinal tract adhesive agent is at least one in carbomer, hypromellose, methylcellulose, gelatin, pectin, sodium carboxymethyl cellulose.
Coating material be Sulisi, especially strange, hydroxypropyl cellulose, Lac, ethyl cellulose, Opadry, acrylic resin, refined gram should at least one.
Antiplastering aid is at least one in Pulvis Talci, corn starch, micropowder silica gel, magnesium stearate.
Plasticizer is at least one in triethyl citrate, dimethyl phthalate, triacetyl glycerine, liquid Paraffin.
Porogen is at least one in sucrose, sodium chloride, mannitol, PEG6000.
Prepare the method for long-acting veterinary ofloxacin slow-release micropill, comprise the following steps: (1) prepares ball core: ofloxacin, filler, binding agent are sieved, mixing, carry out extruding after the material of mixing and wetting agent again being mixed-round as a ball, then dry, sieve, obtain containing pill core; (2) coating: take Sustained release coating materials, antiplastering aid, plasticizer, porogen, the mixing of gastrointestinal tract adhesive agent, add solvent and be mixed with coating solution, coating solution is forming coatings containing coating direct on pill core.
Ofloxacin slow-release micropill for animals of the present invention, adopt film controlling type or matrix type slow release principle, utilize Sustained release coating materials will wrap up evenly containing pill core, gastrointestinal tract adhesive agent such as the carbomer etc. added in the present invention can adhere to gastrointestinal tract mucosa epithelium position, can not only the stop of prolong drug at this position and release time, reach the administration object of slow release and targeting, the contact of medicine and absorbing film can also be increased, change the mobility of cell membrane, increase medicine to the penetration power of intestinal epithelial cell, thus the absorption of medicine can be promoted, improve the bioavailability of medicine.Ofloxacin is made long-acting slow-release preparation by the present invention, makes it maintain slowly uniform release, reduces active ingredient delivery rate, postpone peak time, make blood drug level keep steady statue for a long time, reduce administration frequency and drug residue, drug effect is not fully exerted, reduces aquaculture cost.The ofloxacin slow-release micropill for animals that the present invention obtains is conducive to the stability improving preparation, cover the poor taste of ofloxacin, size is even, and proper sphere degree is high, and between batch, the difference of micropill is little, steady quality, and the good fluidity of micropill, is easy to mix homogeneously, coating process favorable reproducibility, preparation technology is simple and reliable, low production cost.
accompanying drawing explanation
Fig. 1 is the In-vitro release curves of the ofloxacin slow-release micropill of embodiment 1;
Fig. 2 is the In-vitro release curves of the ofloxacin slow-release micropill of embodiment 2;
Fig. 3 is the In-vitro release curves of the ofloxacin slow-release micropill of embodiment 3.
detailed description of the invention
embodiment 1
A kind of ofloxacin slow-release micropill, comprise following component: containing pill core: ofloxacin (active component) 10g, hypromellose (binding agent) 20g, corn starch (filler) 20g, microcrystalline Cellulose (filler) 40g, coating material: Sulisi (Sustained release coating materials) 7.2g, Pulvis Talci (antiplastering aid) 2.0g, triethyl citrate (plasticizer) 0.5g, sucrose (porogen) 0.1g, carbomer (gastrointestinal tract adhesive agent) 0.2g.
Preparation method: (1) is containing the preparation of pill core: take ofloxacin, binding agent, filler sieve, mix homogeneously, do wetting agent by purified water and the material of mix homogeneously made soft material, by extruding-round as a ball, and dry under 60 DEG C of conditions, sieve obtained containing pill core; (2) sustained release coating: take Sustained release coating materials, antiplastering aid, plasticizer, porogen and gastrointestinal tract adhesive agent, add ethanol, stirring makes it dissolve completely, form the coating solution of solid content 10wt%, hydrojet coating is carried out to containing pill core in fluid bed, by obtained ofloxacin micropill aging 24h under 40 DEG C of conditions, obtain slow-release micro-pill.
embodiment 2
A kind of ofloxacin slow-release micropill, comprise following component: containing pill core: ofloxacin (active component) 15g, sodium carboxymethyl cellulose (binding agent) 15g, mannitol (filler) 20g, microcrystalline Cellulose (filler) 40g, coating material: especially strange NE 30D(Sustained release coating materials) 6.0g, Pulvis Talci (antiplastering aid) 2.0g, dimethyl phthalate (plasticizer) 1.5g, sodium chloride (porogen) 0.3g, hypromellose (gastrointestinal tract adhesive agent) 0.2g.
Preparation method is with embodiment 1.
embodiment 3
A kind of ofloxacin slow-release micropill, comprise following component: containing pill core: ofloxacin (active component) 20g, polyvidone (binding agent) 10g, pregelatinized Starch (filler) 40g, sodium bicarbonate (filler) 18g, coating material: ethyl cellulose (Sustained release coating materials) 8.5g, micropowder silica gel (antiplastering aid) 1.0g, triacetyl glycerine (plasticizer) 1.5g, Polyethylene Glycol (porogen) 0.6g, sodium carboxymethyl cellulose (gastrointestinal tract adhesive agent) 0.4g.
Preparation method is with embodiment 1.
embodiment 4
A kind of ofloxacin slow-release micropill, comprise following component: containing pill core: ofloxacin (active component) 25, hypromellose (binding agent) 15g, calcium carbonate (filler) 20g, medicinal dextrin (filler) 27g, coating material: hydroxypropyl cellulose (Sustained release coating materials) 8.5g, Pulvis Talci (antiplastering aid) 2.0g, triethyl citrate (plasticizer) 1.5g, mannitol (porogen) 0.6g, methylcellulose (gastrointestinal tract adhesive agent) 0.4g.
Preparation method is with embodiment 1.
Experiment one: vitro release measures
Sample: three batches of ofloxacin slow-release micropill samples for animals (specification is respectively 10%, 15%, 20%, obtains respectively according to the method for embodiment 1,2,3)
Assay method, carry out according to the assay method of 2010 editions veterinary drug allusion quotations annex release, take appropriate ofloxacin slow-release micropill (being equivalent to ofloxacin 0.225g) and be placed in stripping rotor, release medium is 0.1mol/L HCl, setting speed is 100r/min, and temperature is 37 DEG C, in 1,2,4,6,9,12,15,18,21,25h time sample, adopt the content of determined by ultraviolet spectrophotometry ofloxacin, calculate Accumulation dissolution.Release profiles, as shown in Fig. 1 ~ 3, can be found out that micropill of the present invention effective ingredient release when 2h is 70% less than release during 10%, 15h, extend 20 times, can postpone peak time than ordinary preparation dissolution time, extends medication interval, plays long-acting object.
Experiment two: pharmacokinetic studies
Experiment material: ofloxacin slow-release micropill (10%, obtain according to embodiment 1, lot number: 20140312), (10%, after being mixed according to mass ratio 1:5:4 with corn starch, microcrystalline Cellulose by ofloxacin, conveniently pill making craft obtains ofloxacin common pellets, lot number: 20140310), healthy SD rat 11 (male, about body weight 200g, is provided by Zhengzhou University's laboratory animal center of cultivating).
Method: 10 laboratory animals are divided into two groups at random, fasting 12h before experiment, by test medicine (ofloxacin slow-release micropill) and reference agent (ofloxacin common pellets) 0.2g gastric infusion, respectively 0.5,1,2,3,4,6,8,10,12,16,24,36,48h gets blood 0.5ml in rat eyeground vein clump, blood sample is in the centrifugal 1min of 12000r/min, get blood plasma 150 μ l, with the blood plasma of not administration rat for blank, according to determined by ultraviolet spectrophotometry blood drug level, data acquisition pharmacokinetics software Pksolver process.
Experimental result shows, and test medicine meets one-compartment model, and reference agent meets two-compartment model, and adopt t inspection to compare analysis to two groups of data, result shows, test medicine and reference agent
k a ,
t max ,
c max ,
t 1/2Ka , all there were significant differences (p<0.05) for mean residence time (MRT), and test medicine is than reference agent
t max significant prolongation,
c max obvious reduction.Result is as shown in table 1.
The pharmacokinetic data available of table 1. ofloxacin slow-release micropill
Note: * P<0.05, compares with reference agent.
Claims (9)
1. a long-acting veterinary ofloxacin slow-release micropill, is followed successively by from inside to outside containing pill core and sustained-release coating layer, it is characterized in that, the quality of sustained-release coating layer is containing pill core 5 ~ 20%; With parts by weight, composition containing pill core is: ofloxacin 10 ~ 25 parts, filler 10 ~ 60 parts and binding agent 10 ~ 15 parts, the composition of sustained-release coating layer is: Sustained release coating materials 4.5 ~ 9 parts, antiplastering aid 0.1 ~ 2 part, plasticizer 0 ~ 2 part, porogen 0 ~ 0.6 part and gastrointestinal tract adhesive agent 0.1 ~ 1 part, the total amount containing pill core and sustained-release coating layer is 100 parts.
2. long-acting veterinary ofloxacin slow-release micropill as claimed in claim 1, it is characterized in that, filler is at least one in lactose, mannitol, microcrystalline Cellulose, sodium bicarbonate, calcium carbonate, pregelatinized Starch, medicinal dextrin.
3. long-acting veterinary ofloxacin slow-release micropill as claimed in claim 1, it is characterized in that, binding agent is at least one in sodium carboxymethyl cellulose, hypromellose, Polyethylene Glycol, polyvidone, sucrose.
4. long-acting veterinary ofloxacin slow-release micropill as claimed in claim 1, it is characterized in that, gastrointestinal tract adhesive agent is at least one in carbomer, hypromellose, methylcellulose, gelatin, pectin, sodium carboxymethyl cellulose.
5. long-acting veterinary ofloxacin slow-release micropill as claimed in claim 1, is characterized in that, Sustained release coating materials be Sulisi, especially strange, hydroxypropyl cellulose, Lac, ethyl cellulose, Opadry, acrylic resin, refined gram should at least one.
6. long-acting veterinary ofloxacin slow-release micropill as claimed in claim 1, it is characterized in that, antiplastering aid is at least one in Pulvis Talci, corn starch, micropowder silica gel, magnesium stearate.
7. long-acting veterinary ofloxacin slow-release micropill as claimed in claim 1, it is characterized in that, plasticizer is at least one in triethyl citrate, dimethyl phthalate, triacetyl glycerine, liquid Paraffin.
8. long-acting veterinary ofloxacin slow-release micropill as claimed in claim 1, it is characterized in that, porogen is at least one in sucrose, sodium chloride, mannitol, PEG6000.
9. prepare the method for long-acting veterinary ofloxacin slow-release micropill described in any one of claim 1-8, it is characterized in that comprising the following steps: (1) prepares ball core: ofloxacin, filler, binding agent are sieved respectively, mixing, carry out extruding after the material of mixing and wetting agent again being mixed-round as a ball, then dry, sieve, obtain containing pill core; (2) coating: take Sustained release coating materials, antiplastering aid, plasticizer, porogen, the mixing of gastrointestinal tract adhesive agent, add solvent and be mixed with coating solution, coating solution is forming coatings containing coating direct on pill core.
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| CN201410447678.4A CN104257612A (en) | 2014-09-04 | 2014-09-04 | Long-acting ofloxacin sustained-release pellet for veterinary use and preparation method thereof |
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| CN201410447678.4A CN104257612A (en) | 2014-09-04 | 2014-09-04 | Long-acting ofloxacin sustained-release pellet for veterinary use and preparation method thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106619572A (en) * | 2016-12-22 | 2017-05-10 | 乐山市瑞和祥动物保健药业有限公司 | Quinocetone sustained-release pellet and preparation method thereof |
| CN106880659A (en) * | 2017-03-07 | 2017-06-23 | 青岛科技大学 | A kind of kuh-seng seed flavones sustained release pellet for animals and its preparation |
| CN107929252A (en) * | 2017-11-23 | 2018-04-20 | 湖北龙翔药业科技股份有限公司 | A kind of Marbofloxacin sustained-release pellet tablet and preparation method thereof |
| CN109157519A (en) * | 2018-06-12 | 2019-01-08 | 刘登 | A kind of preparation method of Ofloxacin Hydrochloride Tablet in Vitro |
| 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 |
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| CN1839846A (en) * | 2006-01-10 | 2006-10-04 | 中国药科大学 | Levofloxacin sustained-release pellets, preparation method and use thereof |
| CN103301069A (en) * | 2012-03-15 | 2013-09-18 | 杭州赛利药物研究所有限公司 | Levofloxacin granule and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1839846A (en) * | 2006-01-10 | 2006-10-04 | 中国药科大学 | Levofloxacin sustained-release pellets, preparation method and use thereof |
| CN103301069A (en) * | 2012-03-15 | 2013-09-18 | 杭州赛利药物研究所有限公司 | Levofloxacin granule and preparation method thereof |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106619572A (en) * | 2016-12-22 | 2017-05-10 | 乐山市瑞和祥动物保健药业有限公司 | Quinocetone sustained-release pellet and preparation method thereof |
| CN106619572B (en) * | 2016-12-22 | 2019-11-26 | 乐山市瑞和祥动物保健药业有限公司 | A kind of quinocetone sustained release pellet and preparation method thereof |
| CN106880659A (en) * | 2017-03-07 | 2017-06-23 | 青岛科技大学 | A kind of kuh-seng seed flavones sustained release pellet for animals and its preparation |
| CN107929252A (en) * | 2017-11-23 | 2018-04-20 | 湖北龙翔药业科技股份有限公司 | A kind of Marbofloxacin sustained-release pellet tablet and preparation method thereof |
| CN109157519A (en) * | 2018-06-12 | 2019-01-08 | 刘登 | A kind of preparation method of Ofloxacin Hydrochloride Tablet in Vitro |
| CN109157519B (en) * | 2018-06-12 | 2021-01-26 | 刘登 | Preparation method of ofloxacin tablets |
| 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 |
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Application publication date: 20150107 |