CN107669646A - Ivermectin tablet and preparation method thereof - Google Patents
Ivermectin tablet and preparation method thereof Download PDFInfo
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- CN107669646A CN107669646A CN201711046903.3A CN201711046903A CN107669646A CN 107669646 A CN107669646 A CN 107669646A CN 201711046903 A CN201711046903 A CN 201711046903A CN 107669646 A CN107669646 A CN 107669646A
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- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- 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
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- 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
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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Abstract
The present invention relates to a kind of ivermectin tablet and preparation method thereof.The ivermectin tablet is mainly prepared by each raw material of following parts by weight：20 parts of 0.5 part of ivermectin 0.1 part, 10 parts of disintegrant 3 part, 91 parts of filler 61 part, 3 parts of lubricant 1 part, 5 parts of adhesive 0.1 part and absolute ethyl alcohol 2 part.The uniformity of the ivermectin tablet is high, dissolution rate is good and using effect is good.
Description
Technical field
The present invention relates to anti-parasite medicine technical field, more particularly to a kind of ivermectin tablet and its preparation side
Method.
Background technology
Ivermectin (IVM) is new wide spectrum, efficient, less toxic antibioticses antiparasitic agent, to internal ectoparasite
Be respectively provided with it is good kill effect, it is preferable especially for the repelling and killing efficacy of nematode and arthropod.
Ivermectin (IVM) is that Merck companies of the U.S. carry out Wilkinson to the double bond between AVMB1 C22 and C23
Catalysis, and the 1st AVM (AVM) the class medicaments derivative obtained after homogeneous system hydrotreating.Ivermectin (IVM)
It is basically identical with the insecticidal activity of AVM (AVM), but IVM has stronger permeability and peace to the body tissue of mammal
Quan Xing.
Ivermectin can increase the release of the inhibitory transmitter γ-aminobutyric acid (GABA) of nematode and arthropod, and
The Cl ion channels of glutamic acid control are opened, strengthen permeability of the neu to Cl, so as to the transmission of block nerves signal, so that
Its neural paralysis, and then muscle cell loses contractility, ultimately results in polypide death.The peripheral neurotransmitter of mammal is
Acetylcholine, though GABA is distributed in central nervous system, because this class medicine is not easy to pass through blood-brain barrier, and pole is influenceed on it
It is small therefore comparatively safe during use.
Ivermectin tablet is mainly made up of ivermectin and auxiliary material.Wherein, ivermectin has preferable permeability, but
It is that commercially available ivermectin is crystalline powder, its dissolubility is poor, and proportion differs larger with other auxiliary materials, and dissolubility is low, therefore passes
The uniformity of ivermectin is poor in the tablet of system, and dissolution rate is low, and then the using effect of tablet is also poor.
The content of the invention
Based on this, it is necessary to provide a kind of uniformity is high and dissolution rate is good, using effect is good ivermectin tablet and its
Preparation method.
A kind of ivermectin tablet, mainly it is prepared by each raw material of following parts by weight：0.1 part -0.5 of ivermectin
Part, 3 parts -10 parts of disintegrant, 61 parts -91 parts of filler, 1 part -3 parts of lubricant, 0.1 part -5 parts of adhesive and absolute ethyl alcohol 2
- 20 parts of part.
In one of the embodiments, in addition to parts by weight are 1 portion of -4 portions of flavor enhancement and parts by weight are 0.01 part -0.04
The preservative of part.
In one of the embodiments, it is prepared by each raw material of following parts by weight：0.3 part -0.4 part of ivermectin,
5 parts -8 parts of disintegrant, 70 parts -85 parts of filler, 1 part -2 parts of lubricant, 1 part -3 parts of adhesive, absolute ethyl alcohol 6-16 parts, seasoning
0.01 part -0.03 part of 1 part -2 parts of agent and preservative.
In one of the embodiments, the disintegrant is sodium carboxymethyl starch, PVPP, cross-linked carboxymethyl fiber
One or more in plain sodium, ethyl cellulose, methylcellulose, lauryl sodium sulfate and polyvinylpyrrolidone.
In one of the embodiments, the filler is anhydrous Icing Sugar, lactose, sucrose, starch, microcrystalline cellulose and wheat
One or more in bud dextrin.
In one of the embodiments, the filler is anhydrous Icing Sugar, microcrystalline cellulose and maltodextrin, wherein, institute
State anhydrous Icing Sugar, the mass ratio of the microcrystalline cellulose and the maltodextrin is (50-80)：(5-10)：(1-10).
In one of the embodiments, the anhydrous Icing Sugar, the mass ratio of the microcrystalline cellulose and the maltodextrin
Example is 60：10：5.
In one of the embodiments, the flavor enhancement is beef flavor and/or chicken essence；The lubricant is tristearin
One or more in sour magnesium, talcum powder and superfine silica gel powder；Described adhesive is sodium carboxymethylcellulose liquid, starch slurry or hydroxypropyl
One or more in methylcellulose；The preservative is parabens, butylated hydroxy anisole or dibutyl hydroxyl
One or more in base toluene.
Ivermectin tablet in the present invention is to pass through the Formulation being processed into by main ingredient and suitable auxiliary material.The master
Medicine is the ivermectin that parts by weight are 0.1 part -0.5 part, and ivermectin has good repelling and killing efficacy to internal epizoa.
Count in parts by weight, auxiliary material mainly including 3 parts -10 parts disintegrant, 61 parts -91 parts of filler, 1 part -3 parts of lubricant,
0.1 part -5 parts of adhesive and 2 parts -20 parts of absolute ethyl alcohol.By using absolute ethyl alcohol, ivermectin can be filled
The dissolving divided.And by controlling the proportioning of other each components in auxiliary material, it is ensured that ivermectin can be uniformly dispersed in auxiliary material.She
The parts by weight for tieing up rhzomorph are 0.1 part -0.5 part, and its accounting in tablets is smaller, but still have in the ivermectin tablet compared with
The high uniformity.Therefore, ivermectin tablet of the invention is by controlling ivermectin, disintegrant, filler, lubricant, viscous
The parts by weight of mixture and absolute ethyl alcohol, each component are used cooperatively jointly, can produce preferable synergy, and it is effectively carried
The high uniformity and dissolution rate of ivermectin tablet, and then there is preferable using effect and security performance.
In addition, the filler in the present invention uses anhydrous Icing Sugar, microcrystalline cellulose and maltodextrin, and it is anhydrous by controlling
The mass ratio of Icing Sugar, microcrystalline cellulose and maltodextrin is (50-80)：(5-10)：(1-10), its filler being collectively forming
With suitable caking property and mobility, it is ensured that ivermectin can be dispersed, and then prepares the ivermectin tablet formed
The uniformity it is preferable.In addition, the hardness for the filler that anhydrous Icing Sugar, microcrystalline cellulose and maltodextrin are formed is suitable, shape is prepared
Into ivermectin tablet in ivermectin dissolving out capability it is preferable, and then the ivermectin tablet using effect and security performance
It is all preferable.
The disintegrant of the present invention is from sodium carboxymethyl starch, PVPP, Ac-Di-Sol, ethyl cellulose
During one or more in element, methylcellulose, lauryl sodium sulfate and polyvinylpyrrolidone, it is preferable that it is disintegrated effect,
The dissolution of ivermectin is helped lend some impetus to, and then further increases the using effect and security performance of ivermectin tablet.
A kind of preparation method of ivermectin tablet is provided in addition, there is a need to.
A kind of preparation method of ivermectin tablet, comprises the following steps：
Ivermectin, disintegrant, filler, lubricant, adhesive and anhydrous second are weighed respectively by above-mentioned parts by weight
Alcohol；
The ivermectin, absolute ethyl alcohol and filler are well mixed, drying and processing, through crushing, sieving middle
Body；
Binder solution is prepared, and binder solution is well mixed with the intermediate, softwood is made；
By the softwood through pelletizing, dry and whole grain, be made particle；
The lubricant is well mixed with the whole grain, through compressing tablet process, produces ivermectin tablet.
In one of the embodiments, the hardness of the ivermectin tablet is 1kgf-7kgf.
By the way that each raw material is crushed respectively and handled through sieving, it is ensured that ivermectin is well mixed in auxiliary material, is had
Effect improves the uniformity of ivermectin tablet.Therefore, by the uniformity of ivermectin tablet made from the preparation method compared with
It is good, and preparation method is simply efficient, is adapted to industrialization to produce, has broad application prospects.
Ivermectin tablet in the present invention can be used for outer expelling parasite inside the animals such as canine.Such as ivermectin tablet
For chewable tablets, animal carries out internal expelling parasite by being swallowed after the ivermectin tablet is chewed.The use of the ivermectin tablet
Effect and security performance are all preferable.
Embodiment
For the ease of understanding the present invention, the present invention is described more fully below in conjunction with embodiment.But this hair
It is bright to realize in many different forms, however it is not limited to embodiment described herein.On the contrary, provide these embodiments
Purpose be to make the understanding more thorough and comprehensive to the disclosure.
Unless otherwise defined, all of technologies and scientific terms used here by the article is with belonging to technical field of the invention
The implication that technical staff is generally understood that is identical.Term used in the description of the invention herein is intended merely to description tool
The purpose of the embodiment of body, it is not intended that in the limitation present invention.Term as used herein "and/or" includes one or more phases
The arbitrary and all combination of the Listed Items of pass.
The test method of unreceipted actual conditions in the following example, conventionally and condition, or said according to commodity
The regulation of bright book suggestion is selected.Agents useful for same or the unreceipted production firm person of instrument, it is that can be obtained by commercially available purchase
Conventional products.
The ivermectin tablet is to pass through the Formulation being processed into by main ingredient and suitable auxiliary material.The ivermectin piece
Agent is mainly prepared by each raw material of following parts by weight：0.1 part -0.5 part of ivermectin, such as can be, but it is not limited to 0.1
Part, 0.2 part, 0.3 part, 0.32 part, 0.4 or 0.5 part；3 parts -10 parts of disintegrant, such as can be, but be not limited to 3 parts, 4 parts, 5
Part, 6 parts, 7 parts, 8 parts or 10 parts；61 parts -91 parts of filler, such as can be, but be not limited to 61 parts, 70 parts, 75 parts, 80 parts,
83.76 parts, 85 parts or 91 parts；1 part -4 parts of flavor enhancement, such as can be, but it is not limited to 1 part, 2 parts, 3 parts, 4 parts；Lubricant 1
- 3 parts of part, such as can be, but it is not limited to 1 part, 2 parts or 3 parts；0.1 part -5 parts of adhesive, such as can be, but it is not limited to 1
Part, 2 parts, 3 parts, 4 parts or 5 parts；0.01 part -0.04 part of preservative, such as can be, but be not limited to 0.01 part, 0.02 part, 0.03
Part, 2 parts -20 parts of the absolute ethyl alcohol of 0.04 part and surplus, such as can be, but be not limited to 2 parts, 6 parts, 10 parts, 16 parts or 20
Part.
In one embodiment, the ivermectin tablet is mainly prepared by each raw material of following parts by weight：Yi Wei
It is 0.3 part -0.4 part of rhzomorph, 5 parts -8 parts of disintegrant, 70 parts -85 parts of filler, 1 part -2 parts of flavor enhancement, 1 part -2 parts of lubricant, viscous
1 part -3 parts of mixture, 0.01 part -0.03 part of preservative and absolute ethyl alcohol 6-16 parts.
In one embodiment, it is prepared by each raw material of following parts by weight：0.32 part of ivermectin, disintegrant 7
Part, 83.76 parts of filler, 1 part of flavor enhancement, 1 part of lubricant, 2 parts of adhesive, 0.02 part of preservative and 6.9 parts of absolute ethyl alcohol.
The disintegrant refers to the material that tablet can be made to split into fine particle rapidly in gastro-intestinal Fluid, so that main ingredient composition
It is rapid to dissolve and absorb, play a role.The disintegrant needs have good water imbibition and dilatancy, so as to realize collapsing for tablet
Solution.Alternatively, the disintegrant is sodium carboxymethyl starch, PVPP, Ac-Di-Sol, ethyl cellulose, first
One or more in base cellulose, lauryl sodium sulfate and polyvinylpyrrolidone etc., its disintegration effect is preferable, contributes to
Promote the dissolution of ivermectin, and then further increase the using effect and security performance of ivermectin tablet.
The weight or volume for being mainly used in filling tablet of the filler, so as to dilute main ingredient, being easy to, which increases volume, helps it
Shaping.Alternatively, the filler be lactose, anhydrous Icing Sugar, sucrose, starch, microcrystalline cellulose, maltodextrin, inorganic salts and
One or more in amylum pregelatinisatum etc..Wherein, sucrose refers to the white that crystallinity sucrose forms after low temperature drying crushes
Powder, its bonding force are strong, by increasing capacitance it is possible to increase the hardness of tablet, and make the surface smooth and beautiful appearance of tablet.The compressibility energy of anhydrous Icing Sugar
Good, property is stable, and chemically reactive, the tablet being pressed into be not bright and clean attractive in appearance with most drug.The property of starch is stable, and most
Number medicine does not work, and price is also relatively cheap, and hygroscopicity is small, appearance luster is good.Microcrystalline cellulose is cellulosic sections hydrolysis
Prepared by the less crystallinity cellulose of the degree of polymerization, there is good compressibility, have stronger adhesion, the tablet being pressed into has
It is larger to have hardness.Amylum pregelatinisatum has good mobility, compressibility, self-lubricity and dry adhesive.Dextrin is starch
The general name of intermediate product is hydrolyzed, maltodextrin forms using starch as raw material through enzyme method technique control hydrolysis.
In one embodiment, the filler is anhydrous Icing Sugar, microcrystalline cellulose and maltodextrin, wherein, this is without molasses sugar
Powder, the mass ratio of the microcrystalline cellulose and the maltodextrin are (50-80)：(5-10)：(1-10).Alternatively, this is without molasses sugar
The mass ratio of powder, the microcrystalline cellulose and the maltodextrin is 60：10：5.Anhydrous Icing Sugar, microcrystalline cellulose and malt paste are altogether
There is suitable caking property and mobility with the filler formed, it is ensured that ivermectin can be dispersed, and then prepares and formed
Ivermectin tablet the uniformity it is preferable.In addition, the filler that anhydrous Icing Sugar, microcrystalline cellulose and maltodextrin are formed is hard
Degree is suitable, and it is preferable to prepare the dissolving out capability of ivermectin in the ivermectin tablet of formation, and then the ivermectin tablet uses
Effect and security performance are all preferable.
The flavor enhancement is used for the organoleptic properties for improving food, makes food tastier, and can promote point of digestive juice
Secrete and orectic food additives.Alternatively, the flavor enhancement be beef flavor, chicken essence, dog taste flavouring agent, milk powder or
One or more in chicken liver meal etc..
The lubricant is used to reduce frictional force between particle, improves powder flowbility；Prevent auxiliary material from sticking at punch head surface；Drop
Frictional force between low tablet and punch die hole wall.Alternatively, the lubricant is one in magnesium stearate, talcum powder and superfine silica gel powder etc.
Kind is a variety of.
The adhesive is the sticking material of tool, and drug material can link together by its viscosity.Alternatively, this is viscous
Mixture is one kind or more in sodium carboxymethylcellulose, starch slurry, hydroxypropyl methylcellulose, methylcellulose or ethyl cellulose etc.
Kind.Wherein, starch slurry is adhesive more common in tablet, and concentration is generally 2% (w/v) -10% (w/v)；When material can press
Poor performance, the starch slurry using higher concentration may be selected；If material compressibility can be good, the starch slurry of low concentration may be selected.Form sediment
The preparation method of slurry mainly has two methods of mashing off and punching slurry, is all the property that homogeneous paste thing is formed after make use of starch heated.
After gelatinization, the viscosity of starch increased dramatically, and be used so as to the adhesive as tablet.Using sodium carboxymethylcellulose, hydroxyl
When third methylcellulose, methylcellulose or ethyl cellulose are as adhesive, the adhesive can be added in the aqueous solution, matched somebody with somebody
The binder solution of concentration needed for being made.During using sodium carboxymethylcellulose as adhesive, its concentration is generally 0.1%
(w/v) -4% (w/v).During using hydroxypropyl methylcellulose as adhesive, its concentration is generally 1% (w/v) -6% (w/v).Should
Preservative is used to keep the drug effect on medicine ground and using quality.Alternatively, the preservative is parabens, butyl hydroxyl
One or more in base anisole or dibutyl hydroxy toluene etc..
The absolute ethyl alcohol is used to dissolve ivermectin.The ivermectin can carry out preferably scattered in absolute ethyl alcohol.Its
In, by the dosage for adjusting absolute ethyl alcohol, it is ensured that ivermectin can be completely dissolved.Alternatively, the dosage of the absolute ethyl alcohol is
20 times -40 times of ivermectin dosage.When absolute ethyl alcohol can be completely dissolved ivermectin, the ivermectin can be equably
Mixed with auxiliary material, the uniformity of the ivermectin tablet of formation is preferable.
Ivermectin tablet in the present invention is to pass through the Formulation being processed into by main ingredient and suitable auxiliary material.The master
Medicine is the ivermectin that parts by weight are 0.1 part -0.5 part, and ivermectin has good repelling and killing efficacy to internal epizoa.
Count in parts by weight, auxiliary material mainly including 3 parts -10 parts disintegrant, 61 parts -91 parts of filler, 1 part -3 parts of lubricant,
0.1 part -5 parts of 2 parts -20 parts of adhesive and absolute ethyl alcohol.By using absolute ethyl alcohol, ivermectin can be carried out abundant
Dissolving.And by controlling the proportioning of other each components in auxiliary material, it is ensured that ivermectin can be uniformly dispersed in auxiliary material.Although
The parts by weight of ivermectin are 0.1 part -0.5 part, and its accounting in tablets is smaller, but still has in the ivermectin tablet
The higher uniformity.Therefore, ivermectin tablet of the invention by control ivermectin, disintegrant, filler, lubricant,
The parts by weight of adhesive and absolute ethyl alcohol, each component are used cooperatively jointly, can produce preferable synergy, and its is effective
The uniformity and dissolution rate of ivermectin tablet are improved, and then there is preferable using effect and security performance.
A kind of preparation method of ivermectin tablet is provided in addition, there is a need to.
A kind of preparation method of ivermectin tablet, comprises the following steps：
1) weigh and sieve：Ivermectin and disintegrant, filler, lubricant, viscous point are weighed by above-mentioned parts by weight
The auxiliary materials such as mixture, the ivermectin weighed and auxiliary material are crushed respectively and handled by the mesh sieve of 60 mesh -120.Can
Selection of land, the auxiliary material also includes flavor enhancement and preservative, and weighs flavor enhancement and preservative respectively by above-mentioned parts by weight.
2) intermediate is prepared：Absolute ethyl alcohol is measured by above-mentioned parts by weight, the ivermectin that step 1) is weighed adds nothing
It is completely dissolved in water-ethanol, the filler added after the sieving of part, is well mixed, drying, is crushed, sieving, in being made
Mesosome.
In one embodiment, the temperature of drying is 50 DEG C -60 DEG C, and the mesh number of sieving is the mesh of 60 mesh -120.
In one embodiment, can also include adding preservative into absolute ethyl alcohol the step dissolved in step 2)
Suddenly.
Specifically, ivermectin, preservative are dissolved in ethanol in tubbing, ensure that dissolving is complete, added part and fill out
Agent mixing is filled, about 4-5 hours is dried in 55 DEG C in baking oven -60 DEG C of drying, crushes, cross the mesh sieve of 60 mesh -120, intermediate is made.
3) binder aqueous solution is prepared：The adhesive that step 1) is weighed is added in purified water, and it is water-soluble to prepare composite adhesives
Liquid.Alternatively, the concentration of the binder aqueous solution is 0.1% (w/v) -10% (w/v).
4) softwood is prepared：Intermediate and step 3) system prepared by the remaining filler of step 1) sieving, step 2)
Standby binder aqueous solution is mixed in preparing tank, and softwood is made.Alternatively, the softwood can be held agglomerating, and light pressure is
Dissipate.
In one embodiment, step 4) also includes flavor enhancement being added to the step of being mixed in preparing tank.
Specifically, by the flavor enhancement, the disintegrant and remaining filler by equivalent progressively increase method input intermediate in mix
Uniformly, and binder aqueous solution is added, softwood is made.
5) pelletize：Softwood prepared by step 4) is pelletized, dry and whole grain, particle is made.Wherein, particle contains
Water is 2%-7%.
Specifically, being placed on 55 DEG C of -60 DEG C of drying about 3-4 hours, drying course in baking oven will stir back and forth, make it heated equal
It is even, the phenomenon of overdrying or overly moist is avoided, makes moisture control 5%.After 24 mesh sieves, particle is made.
6) film-making：Lubricant after step 1) is sieved is added in particle prepared by step 5), and is mixed, tabletting,
Produce ivermectin tablet.Wherein, the hardness of the ivermectin tablet is 1kgf-7kgf.Such as its hardness can be, but not office
Be limited to 1kgf, 1.5kgf, 2kgf, 2.5kgf, 3kgf, 3.5kgf, 4kgf, 4.5kgf, 5kgf, 5.5kgf, 6kgf, 6.5kgf or
7kgf。
Specifically, particle is added lubricant and knocks down two-dimensional motion mixer and always mix timing, then by total mixed particle
It is transferred between tabletting and carries out tabletting, produces ivermectin tablet.
By the way that each raw material is crushed respectively and handled through sieving, it is ensured that ivermectin is well mixed in auxiliary material, is had
Effect improves the uniformity of ivermectin tablet.Therefore, by the uniformity of ivermectin tablet made from the preparation method compared with
It is good, and preparation method is simply efficient, is adapted to industrialization to produce, has broad application prospects.
Ivermectin tablet in the present invention can be used for outer expelling parasite inside the animals such as canine.Such as ivermectin tablet
For chewable tablets, animal carries out internal expelling parasite by being swallowed after ivermectin tablet chewing.The use of the ivermectin tablet
Effect and security performance are all preferable.
It is specific embodiment below：
Embodiment 1
Count in parts by weight, it is 0.32 part of ivermectin, 7 parts of PVPP, 82.26 parts of starch, 1 part of beef flavor, hard
6.4 parts of 1 part of fatty acid magnesium, 2 parts of sodium carboxymethylcellulose, 0.02 part of butylated hydroxy anisole and absolute ethyl alcohol.
1) by the above-mentioned parts by weight weigh respectively ivermectin, PVPP, starch, beef flavor, magnesium stearate,
Sodium carboxymethylcellulose and butylated hydroxy anisole.Each raw material weighed is crushed respectively and by the mesh sieve of 60 mesh -120
Sieving is handled.
2) absolute ethyl alcohol is measured by above-mentioned parts by weight, the ivermectin and butylated hydroxy anisole is added to anhydrous second
It is completely dissolved in alcohol, and is added and is accounted for the starch of gross weight 30% and be well mixed, is finally done at a temperature of 55 DEG C -60 DEG C
Dry processing 4-5 hours, crush, and handled through the mesh sieve of 60 mesh -120, intermediate is made.
3) sodium carboxymethylcellulose by step 1) sieving is added in purified water, is prepared into the carboxylic first that concentration is 3% (w/v)
The base sodium cellulosate aqueous solution.
4) it is by concentration prepared by the remaining starch of step 1) sieving, the intermediate of step 2) preparation and step 3)
3% (w/v) carboxymethylcellulose sodium solution is mixed in preparing tank, and softwood is made.The softwood can hold it is agglomerating, gently
Pressure dissipates.
5) softwood is crossed into the processing of 20 mesh sieves through oscillating granulator, wet granular is made.Wet granular is placed on baking again
55 DEG C of -60 DEG C of dryings -4 hours about 3 hours in case, drying course will stir back and forth, be heated evenly it, avoid overdrying or overly moist
Phenomenon, make moisture control 5%.The particle dried is crossed into 24 mesh sieves again, carries out whole grain, particle is made.
6) magnesium stearate that step 1) is sieved is added in particle, and knocks down two-dimensional motion mixer and always mix, then will be total
Mixed particle carries out tabletting between being transferred to tabletting, produces ivermectin tablet 1.Wherein, the hardness of the ivermectin tablet is
3.5kgf-7.0kgf。
Embodiment 2
Count in parts by weight, 0.1 part of ivermectin, 3 parts of PVPP, 91 parts of starch, 1 part of magnesium stearate, carboxymethyl
3 parts of 1 part of sodium cellulosate and absolute ethyl alcohol.
The preparation method of the ivermectin tablet 2 is same as Example 1.
Embodiment 3
Count in parts by weight, 0.5 part of ivermectin, 10 parts of PVPP, 61 parts of starch, 4 parts of beef flavor, stearic acid
16.5 parts of 3 parts of magnesium, 5 parts of sodium carboxymethylcellulose, 0.04 part of butylated hydroxy anisole and absolute ethyl alcohol.
The preparation method of the ivermectin tablet 3 is same as Example 1.
Embodiment 4
Count in parts by weight, 0.32 part of ivermectin, 5.5 parts of PVPP, 60 parts of anhydrous Icing Sugar, microcrystalline cellulose 10
Part, 5 parts of maltodextrin, 1 part of beef flavor, 1 part of magnesium stearate, 2 parts of sodium carboxymethylcellulose, ethyl-para-hydroxybenzoate 0.02
6.4 parts of part and absolute ethyl alcohol.
1) ivermectin, PVPP, anhydrous Icing Sugar, microcrystalline cellulose, malt are weighed respectively by above-mentioned parts by weight
Dextrin, beef flavor, magnesium stearate, sodium carboxymethylcellulose and ethyl-para-hydroxybenzoate, each raw material weighed is distinguished
Crushed and handled by the mesh sieve of 60 mesh -120.
2) absolute ethyl alcohol is measured by above-mentioned parts by weight, the ivermectin and ethyl-para-hydroxybenzoate is added to necessarily
It is completely dissolved just in the absolute ethyl alcohol of amount, and adds 30% anhydrous Icing Sugar, microcrystalline cellulose, the mixture of maltodextrin
It is well mixed, finally drying process 4-5 hours and handle, be made through the mesh sieve of 60 mesh -120 at a temperature of 55 DEG C -60 DEG C
Intermediate.
3) sodium carboxymethylcellulose for weighing step 1) is added in purified water, is prepared into the carboxylic first that concentration is 3% (w/v)
The base sodium cellulosate aqueous solution.
4) by the beef flavor, the anhydrous Icing Sugar of the PVPP and residue 70%, microcrystalline cellulose, maltodextrin
Mixture by equivalent progressively increase method input intermediate in be well mixed.And add the sodium carboxymethylcellulose water that concentration is 3% (w/v)
Solution, is made softwood, and the softwood can be held agglomerating, and light pressure dissipates.
5) softwood is crossed into the processing of 20 mesh sieves through oscillating granulator, wet granular is made.Wet granular is placed on baking again
55~60 DEG C of dryings about 3~4 hours in case, drying course will stir back and forth, be heated evenly it, avoid showing for overdrying or overly moist
As making moisture control 5%.The particle dried is crossed into 24 mesh sieves again, carries out whole grain, particle is made.
6) magnesium stearate is added in particle, and knocks down two-dimensional motion mixer and always mix, then by total mixed particle
It is transferred between tabletting and carries out tabletting, produces ivermectin tablet 4.Wherein, the hardness of the ivermectin tablet is 3.5kgf-
7.0kgf。
Embodiment 5
Count in parts by weight, 0.32 part of ivermectin, 7 parts of PVPP, 60 parts of anhydrous Icing Sugar, microcrystalline cellulose 10
Part, 5 parts of maltodextrin, 1 part of beef flavor, 1 part of magnesium stearate, 2 parts of sodium carboxymethylcellulose, 0.02 part of butylated hydroxy anisole
And 4.9 parts of absolute ethyl alcohol.
The preparation method of the ivermectin tablet 5 is same as Example 4.
Embodiment 6
Count in parts by weight, 0.5 part of ivermectin, 7 parts of PVPP, 50 parts of anhydrous Icing Sugar, 5 parts of microcrystalline cellulose,
4 parts of maltodextrin, 4 parts of beef flavor, 3 parts of magnesium stearate, 5 parts of sodium carboxymethylcellulose, 0.02 part of butylated hydroxy anisole with
And 19.5 parts of absolute ethyl alcohol.
The preparation method of the ivermectin tablet 6 is same as Example 4.
Embodiment 7
Each raw material is weighed with following percentage by weight：0.1 part of ivermectin, 3 parts of PVPP, 80 parts of anhydrous Icing Sugar,
10 parts of microcrystalline cellulose, 10 parts of maltodextrin, 1 part of beef flavor, 1 part of magnesium stearate, 0.01 part of sodium carboxymethylcellulose, butyl
3 parts of 1 part of BHA and absolute ethyl alcohol.
The preparation method of the ivermectin tablet 7 is same as Example 4.
Comparative example 1
Each raw material is weighed with following percentage by weight：0.32 part of ivermectin, 65 parts of starch, 20 parts of mannitol, methyl are fine
Dimension plain 13 parts and 1.68 parts of magnesium stearate.
Ivermectin, starch, mannitol and methylcellulose are well mixed, softwood is made, the softwood is subjected to powder
It is broken and handled through sieving, particle is made；
Magnesium stearate is well mixed with the particle, and through compressing tablet process, produces tablet 1；
The dissolution rate test of effete test embodiment 1
Test specimen：The Yi Wei bacterium prepared respectively by 6 in the ivermectin tablet 1 of the preparation of embodiment 1, embodiment 4
6 in tablet 1 prepared by 6 in plain piece agent 4 and comparative example 1 carry out dissolution rate test
Method for testing and detecting：According to《The Ministry of Agriculture of the People's Republic of China, MOA announces No. 2548》Ivermectin chews tablet quality
Substandard dissolution detection method is carried out.Test result is as shown in table 1.
The dissolution rate test result of table 1
Conclusion：It can be seen from the data of table 1, the Yi Wei of ivermectin tablet 1 and embodiment 4 preparation prepared by embodiment 1
The equal conspicuousness of dissolution rate for the tablet 1 that rhzomorph tablet 4 is prepared relative to comparative example 1 improves, and is all higher than 90%, meets dissolution rate
It is required that.And the dissolution rate of tablet 1 prepared by comparative example 1 is unqualified.
The uniformity of dosage units of effete test embodiment 2 is tested
Test specimen：The Yi Wei bacterium prepared respectively by 10 in the ivermectin tablet 1 of the preparation of embodiment 1, embodiment 4
10 in tablet 1 prepared by 10 in plain piece agent 4 and comparative example 1 carry out uniformity of dosage units test
Method for testing and detecting：According to《The Ministry of Agriculture of the People's Republic of China, MOA announces No. 2548》Ivermectin chews tablet quality
Substandard uniformity of dosage units detection method is carried out.Test result is as shown in table 2.
The uniformity test result of table 2
Conclusion：It can be seen from the data of table 1, the Yi Wei of ivermectin tablet 1 and embodiment 4 preparation prepared by embodiment 1
The uniformity of dosage units of rhzomorph tablet 4 is very good, and its uniformity (A+2.2S) is respectively less than 15, meets uniformity requirements, and relative to right
The ivermectin uniformity of tablet 1 prepared by ratio 1 has conspicuousness raising.And the ivermectin uniformity of dosage units (A+ of comparative example 1
2.2S) it is more than 15, does not meet uniformity requirements.
The influence factor of embodiment 3 is tested
In order to verify stability of the ivermectin tablet under extraordinary environment in the present invention, Yi Wei prepared by Example 1
Ivermectin tablet 4 prepared by rhzomorph tablet 1 and embodiment 4, hot test, intense light irradiation experiment and high wet test etc. are carried out respectively
Influence factor is tested, test method reference《Republic of China Veterinary Pharmacopoeia (version in 2015)》Annex 302：Material medicine and system
Pharmaceutical preparation influence factor test method under agent stability test guideline item, specific test method are as follows：
3.1 hot test
The good sample of bubble-cap is placed 10 days at a temperature of 60 DEG C, in the 5th day and the 10th day sampling analysis.
3.2 intense light irradiations are tested
The good sample of bubble-cap is placed in the stable case of sample, placed 10 days under the conditions of 4500 ± 500lx of illumination, the 5th
It and the 10th day sampling analysis.
3.3 high wet tests
The good sample of bubble-cap is placed under 90% damp condition and places the decentralization of 10 days conditions and puts 10 days, at the 5th day and the 10th
Its sampling analysis.
Character, ivermectin content, dissolution rate to samples taken etc. carry out observation detection, and are carried out with the result of 0 day
Compare, wherein ivermectin content and the detection method of dissolution rate respectively according to《The Ministry of Agriculture of the People's Republic of China, MOA's bulletin the
No. 2548》Ivermectin content and dissolution detection method under ivermectin chewable tablets quality standard are carried out.Table 3 is Yi Wei bacterium
Plain piece agent influence factor result of the test.
The influence factor result of the test of table 3
Conclusion：It can be seen from table 3 detects data, ivermectin tablet prepared by embodiment 1 and embodiment 4 is in 60 DEG C of height
Every Testing index has no significant change under temperature, 4500 ± 500lx intense light irradiation and 90% ± 5% high humidity environment, quality compared with
For stabilization, meet stability requirement.
The accelerated stability of effete test embodiment 4 is tested
In order to verify the stability of ivermectin tablet in the present invention, ivermectin tablet 1 and reality prepared by Example 1
It is appropriate to apply the ivermectin tablet 4 of the preparation of example 4, reference《Republic of China Veterinary Pharmacopoeia (version in 2015)》Annex 302：Raw material
Pharmaceutical preparation accelerated test method under medicine and preparation stability test direction principle item is carried out, respectively 40 ± 2 DEG C of temperature,
Placed under conditions of relative humidity 75% ± 5% 6 months carry out accelerated stability test, 1st month during experiment, 2 months,
3 months, the 6 months the end of month it is separately sampled once, character, ivermectin content, dissolution rate to samples taken etc. carry out observation inspection
Survey, and compared with the result of 0 day, wherein ivermectin content and the detection method of dissolution rate respectively according to《The Chinese people
The Ministry of Agriculture of republic announces No. 2548》Ivermectin content and dissolution rate detection side under ivermectin chewable tablets quality standard
Method is carried out.Table 4 is ivermectin tablet accelerated stability test result.
The accelerated stability test result of table 4
Conclusion：It can be seen from table 4 detects data, ivermectin tablet prepared by embodiment 1 and embodiment 4 is in temperature 40
± 2 DEG C, every Testing index has no significant change under conditions of relative humidity 75% ± 5%, quality is relatively stable, meets stabilization
Property require.
The efficacy test of effete test embodiment 5
Example 1 prepares prepared by ivermectin tablet 1, ivermectin tablet 4 prepared by embodiment 4 and comparative example 1
Tablet 1 carries out anti parasitic efficacy test.
It is visible in dog plant of Huadu of Guangdong Province, selection itch, local skin dothienesis, hair follicle inflammation, hair of leafing through
The dog of black parasite excreta or parasite polypide only 40, is judged as parasitic disease dog, and every 10 are included into one group, are respectively
A, B, C and D group.A groups press the oral ivermectin tablets 1 of 0.2mg/kg, and B groups press the oral ivermectin tablets 4 of 0.2mg/kg, C groups
The tablet 1 prepared by 0.2mg/kg oral contrasts example 1, D groups are not administered, as blank control group.A groups, B groups, C groups and D components
Field stable breeding avoids cross infection.The 5th day after administration, each group fecal specimens are gathered respectively and carry out microscopy within the 10th day, the 15th day.Detection
As a result it is as shown in table 5.
The excrement testing result of table 5
Redution of eggs (%)={ worm's ovum number before [worm's ovum number after worm's ovum number-administration before administration]/administration } * 100%
Worm's ovum is with respect to slip (%)={ [not administration group nematode worm's ovum number-administration group nematode worm's ovum number]/not administration group line
Worm worm's ovum number } * 100%
Nematode Negative rate on the egg (%)=[nematode worm's ovum checks negative animal number/animal subject number] * 100%
Conclusion：The embodiment 1 prepares the ivermectin tablet 4 of ivermectin tablet 1 and the preparation of embodiment 4 relative to contrast
The anthelminthic effect of tablet 1 prepared by example 1 is significantly increased, and especially the purge ratio of hookworm, roundworm, whipworm is showed well.
In addition, during ivermectin tablet 1 and ivermectin tablet 4 is used, animal does not occur obvious uncomfortable reaction.Cause
This, ivermectin tablet of the invention also has preferably anti parasitic effect.
Each technical characteristic of embodiment described above can be combined arbitrarily, to make description succinct, not to above-mentioned reality
Apply all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not deposited
In contradiction, the scope that this specification is recorded all is considered to be.
Embodiment described above only expresses the several embodiments of the present invention, and its description is more specific and detailed, but simultaneously
Can not therefore it be construed as limiting the scope of the patent.It should be pointed out that come for one of ordinary skill in the art
Say, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the protection of the present invention
Scope.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (10)
1. a kind of ivermectin tablet, it is characterised in that be mainly prepared by each raw material of following parts by weight：Ivermectin
0.1 part -0.5 part, 3 parts -10 parts of disintegrant, 61 parts -91 parts of filler, 1 part -3 parts of lubricant, 0.1 part -5 parts of adhesive and
2 parts -20 parts of absolute ethyl alcohol.
2. ivermectin tablet according to claim 1, it is characterised in that also including parts by weight be 1 part -4 parts of seasoning
Agent and the preservative that parts by weight are 0.01 part -0.04 part.
3. ivermectin tablet according to claim 2, it is characterised in that by each raw material preparation of following parts by weight
Into：0.3 part -0.4 part of ivermectin, 5 parts -8 parts of disintegrant, 70 parts -85 parts of filler, 1 part -2 parts of lubricant, 1 part of adhesive -
0.01 part -0.03 part of 3 parts, absolute ethyl alcohol 6-16 parts, 1 part -2 parts of flavor enhancement and preservative.
4. according to the ivermectin tablet described in claim any one of 1-3, it is characterised in that the disintegrant forms sediment for carboxymethyl
Powder sodium, PVPP, Ac-Di-Sol, ethyl cellulose, methylcellulose, lauryl sodium sulfate and poly- second
One or more in alkene pyrrolidone.
5. according to the ivermectin tablet described in claim any one of 1-3, it is characterised in that the filler is without molasses sugar
One or more in powder, lactose, sucrose, starch, microcrystalline cellulose and maltodextrin.
6. ivermectin tablet according to claim 5, it is characterised in that the filler is anhydrous Icing Sugar, crystallite fibre
Dimension element and maltodextrin, wherein, the anhydrous Icing Sugar, the mass ratio of the microcrystalline cellulose and the maltodextrin are (50-
80)：(5-10)：(1-10).
7. ivermectin tablet according to claim 6, it is characterised in that the anhydrous Icing Sugar, the microcrystalline cellulose
Mass ratio with the maltodextrin is 60：10：5.
8. according to the ivermectin tablet described in claim any one of 2-3, it is characterised in that the flavor enhancement is beef flavor
And/or chicken essence；The lubricant is the one or more in magnesium stearate, talcum powder and superfine silica gel powder；Described adhesive
For the one or more in sodium carboxymethylcellulose liquid, starch slurry or hydroxypropyl methylcellulose；The preservative is para hydroxybenzene first
One or more in esters of gallic acid, butylated hydroxy anisole or dibutyl hydroxy toluene.
9. a kind of preparation method of ivermectin tablet, it is characterised in that comprise the following steps：
Ivermectin, disintegrant, filler, lubricant, bonding are weighed respectively by any one of the claim 1-8 parts by weight
Agent and absolute ethyl alcohol；
The ivermectin, absolute ethyl alcohol and filler are well mixed, drying and processing, through the intermediate that crushes, sieves and to obtain；
Binder solution is prepared, and binder solution is well mixed with the intermediate, softwood is made；
The softwood is pelletized, dry and whole grain, particle is made；
The lubricant is well mixed with the whole grain, through compressing tablet process, produces ivermectin tablet.
10. the preparation method of compound ivermectin tablet according to claim 9, it is characterised in that the ivermectin
Mass ratio with the absolute ethyl alcohol is 1：(20-40).
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP4062907A1 (en) | 2021-03-23 | 2022-09-28 | Substipharm | Formulation for oral administration of ivermectin and uses thereof |
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| CN103083344A (en) * | 2011-11-03 | 2013-05-08 | 青岛康地恩药业股份有限公司 | Compound praziquantel parasite repellent tablet for pets and preparation method thereof |
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| CN104324012A (en) * | 2014-11-04 | 2015-02-04 | 成都乾坤动物药业有限公司 | Pet active feed intake anthelmintic tablet |
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| EP4062907A1 (en) | 2021-03-23 | 2022-09-28 | Substipharm | Formulation for oral administration of ivermectin and uses thereof |
| WO2022200402A1 (en) | 2021-03-23 | 2022-09-29 | Substipharm | Oral formulation of ivermectin and uses thereof |
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