CN105267981A - Method for preparing enrofloxacin solid dispersion - Google Patents
Method for preparing enrofloxacin solid dispersion Download PDFInfo
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- CN105267981A CN105267981A CN201510809944.8A CN201510809944A CN105267981A CN 105267981 A CN105267981 A CN 105267981A CN 201510809944 A CN201510809944 A CN 201510809944A CN 105267981 A CN105267981 A CN 105267981A
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Abstract
The invention discloses a method for preparing enrofloxacin solid dispersion, and belongs to the technical field of veterinary medicinal preparations. The technical scheme mainly includes that the method comprises adding water into cyclodextrin to prepare suspension, adding enrofloxacin monomers into the suspension, sufficiently uniformly mixing the cyclodextrin and the suspension with each other by the aid of a colloid grinder under the condition of temperatures of 50-60 DEG C and grinding the cyclodextrin and the suspension to obtain paste; adding carbohydrate carriers into the paste, continuously sufficiently grinding the paste and the carbohydrate carriers for 1-3 h to obtain mixtures, drying the mixtures at low temperatures of 60 DEG C, washing the mixtures by the aid of solvent detergents by 1-3 times to obtain precipitates and drying the precipitates at low temperatures of 60 DEG C to obtain the enrofloxacin solid dispersion. The method has the advantages that the water solubility of enrofloxacin can be improved by the enrofloxacin solid dispersion prepared by the aid of the method, the bitterness of the enrofloxacin can be effectively hidden, and the method is a novel process for preparing enrofloxacin preparations.
Description
Technical field
The invention belongs to pharmaceutic preparation for livestock technical field, be specifically related to a kind of preparation method of Enrofloxacin solid dispersion.
Background technology
Enrofloxacin (Enrofloxacin), also known as ENR or enrofloxacin, belongs to the quinolones of chemosynthesis.This medicine is the broad-spectrum sterilization medicine of animal specific, has specially good effect to mycoplasma, is mainly used in an infection that the respiratory tract such as poultry and house pet, digestive tract, genitourinary system etc. are caused by antibacterial or mycoplasma.
This product is micro-yellow or greenish orange yellow crystalline powder, bitter in the mouth, and slightly soluble in methanol is atomic molten in water, easily molten in acetic acid, hydrochloric acid or sodium hydroxide.Enrofloxacin is medicine the most frequently used on veterinary clinic, is also animal specific medicine, but atomic molten in water due to it, and taste is bitter, have impact on its application on veterinary clinic.So, improve the water solublity of enrofloxacin and reduce the key that its bitterness is development and application enrofloxacin.
Summary of the invention
The present invention is the preparation method that the defect overcoming enrofloxacin poorly water-soluble and taste hardship provides a kind of Enrofloxacin solid dispersion, the method adopts beta-cyclodextrin inclusion compound technology and solid dispersions technique, first for enrofloxacin enclose is become clathrate, and then carry out solid dispersal, thus solve the defect of enrofloxacin poorly water-soluble and taste hardship.
The present invention adopts following technical scheme for solving the problems of the technologies described above, a kind of preparation method of Enrofloxacin solid dispersion, it is characterized in that concrete steps are: add water in the cyclodextrin of 30-45 weight portion and make suspension, add the enrofloxacin monomer of 10-20 weight portion, fully mix with colloid mill, grind to form pasty state under the condition of 50-60 DEG C; Then add the carbohydrate carrier of 20-50 weight portion, continue fully to grind 1-3h, mixture is through 60 DEG C of cold drying, and add solvent detergent washing 1-3 time, taking precipitate, obtains Enrofloxacin solid dispersion through 60 DEG C of cold drying.
Further restriction, described cyclodextrin is beta-schardinger dextrin-, HP-β-CD or sulfobutyl ether-beta-cyclodextrin.
Further restriction, in described suspension, amount of water is 2-5 times of enrofloxacin monomer mass.
Further restriction, described carbohydrate carrier is galactose, sucrose or dextran.
Further restriction, described solvent detergent is chloroform or ethanol.
Further restriction, described Enrofloxacin solid dispersion is for the preparation of one-tenth oral formulations or ejection preparation.
Present invention employs enrofloxacin/beta-cyclodextrin inclusion compound technology and Enrofloxacin solid dispersion technology of preparing, first enrofloxacin and beta-schardinger dextrin-are carried out enclose and form clathrate, then the enrofloxacin of non-enclose and clathrate are scattered in solid carrier and prepare Enrofloxacin solid dispersion.Enrofloxacin is after beta-cyclodextrin inclusion compound and dispersion, its physical property creates change, increase dissolubility and the bioavailability of medicine on the one hand, cover bad smell on the other hand, reduce zest and toxic and side effects, thus solving the defect of enrofloxacin poorly water-soluble and bitter in the mouth, the exploitation for enrofloxacin novel formulation provides a kind of new technique.
The present invention has following advantage: (1) preparation technology is simple, and enclose is effective, suitability for scale production; (2) improve the water solublity of enrofloxacin; (3) bitterness of enrofloxacin is masked.
Detailed description of the invention
Be described in further details foregoing of the present invention by the following examples, but this should be interpreted as that the scope of the above-mentioned theme of the present invention is only limitted to following embodiment, all technology realized based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1
Beta-schardinger dextrin-30g is added water in 60mL, prepares suspension, under 60 DEG C of conditions, add enrofloxacin monomer 10g, fully mix with colloid mill, grind to form pasty state; Add galactose 20g, continue grinding 2h, 60 DEG C of cold drying, add chloroform three times, and precipitate, through 60 DEG C of oven dry, obtains stable Enrofloxacin solid dispersion.
Embodiment 2
HP-β-CD 45g is added water in 60mL, prepare suspension, under 50 DEG C of conditions, add enrofloxacin monomer 15g, fully grind mixing with colloid mill, grind to form pasty state; Add sucrose 30g, continue grinding 3h, 60 DEG C of cold drying, add chloroform three times, and precipitate 60 DEG C oven dry, obtains stable Enrofloxacin solid dispersion.
Embodiment 3
Sulfobutyl ether-beta-cyclodextrin 30g is added water in 60mL, prepares suspension, under 50 DEG C of conditions, add enrofloxacin monomer 20g, fully grind mixing with colloid mill, grind to form pasty state; Add galactose 50g, continue grinding 1h, 60 DEG C of cold drying, add washing with alcohol three times, and precipitate, through 60 DEG C of oven dry, obtains stable Enrofloxacin solid dispersion.
Wherein, optimum preparation method is example 1, and the Enrofloxacin solid dispersion of following test all refers to that example 1 prepares medicine.
Solid dispersion quality evaluation
1. materials and methods
1.1 test material
1.1.1 for reagent thing
The former powder of enrofloxacin, enrofloxacin/Benexate Hydrochloride (with reference to clathrate preparation method, obtaining after washing drying), Enrofloxacin solid dispersion.
1.1.2 instrument
Ultraviolet spectrophotometer
1.2 test method
1.2.1 the preparation of standard solution
The former powder 25mg of accurately weighed enrofloxacin, puts in 250mL measuring bottle, and add 0.1mol/L sodium hydroxide solution 10mL, jolting makes dissolving, is diluted with water to scale, shakes up, and precision measures 5mL, puts in 100mL measuring bottle, is diluted with water to scale, shake up.
1.2.2 the preparation of test solution
Accurately weighed enrofloxacin/Benexate Hydrochloride 100mg(is about equivalent to enrofloxacin 25mg), enrofloxacin dispersion 150mg(is about equivalent to enrofloxacin 25mg), put in 250mL measuring bottle respectively, add 0.1mol/L sodium hydroxide solution 10mL, jolting makes dissolving, is diluted with water to scale, shake up, precision measures 5mL respectively, puts in 100mL measuring bottle, is diluted with water to scale, shake up, be labeled as test sample 1 and test sample 2 respectively.
1.2.3 assay
By preparation standard solution and need testing solution respectively according to ultraviolet spectrophotometry, 271nm place mensuration its light absorption value, calculate the content of its dispersion according to following formula.
2. results and analysis
2.1 the content of test sample
The light absorption value that upper machine measures the former powder of enrofloxacin, test sample 1 and test sample 2 is respectively 0.509,0.382 and 0.458, substitute into the content that computing formula obtains test sample 1 and test sample 2 and be respectively 75.0% and 90.0%, namely in enrofloxacin/Benexate Hydrochloride and Enrofloxacin solid dispersion, the content of enrofloxacin is respectively 75.0% and 90.0%.
3 discussion and analysis
Can be found out by the content measuring enrofloxacin in enrofloxacin/Benexate Hydrochloride and Enrofloxacin solid dispersion respectively, the content of the enrofloxacin in Enrofloxacin solid dispersion improves 15.0% than the content in clathrate, this shows not defined solid dispersion by the enrofloxacin monomer of cyclodextrin inclusion compound and galactose with hydrogen bonded, thus causes determining enrofloxacin content to be improved.
Enrofloxacin, after cyclodextrin inclusion compound, can cover the bitterness of enrofloxacin, reduces zest and toxic and side effects; After enrofloxacin and water-solubility carrier are prepared into solid dispersion, water solublity and the bioavailability of enrofloxacin can be improved.Cyclodextrin inclusion technique and water-solubility carrier dispersion technology combine by this method, not only mask the bitterness of enrofloxacin, also improve water solublity and the bioavailability of enrofloxacin.And this preparation method is simple to operate, suitable plant layout preparation.
Dissolubility test
1, test material
Nessler colorimetric tube, distilled water, sodium bicarbonate
2, for reagent thing
For sample 1: Enrofloxacin solid dispersion.
For sample 2: the former powder of enrofloxacin.
3, test method
Precision measures the former powder 500mg of above-mentioned enrofloxacin and is equivalent to the Enrofloxacin solid dispersion of enrofloxacin 500mg in 100mL beaker, and add water 100mL, stirs, and observes solution character situation.As solution clarification, then continue to increase test sample amount, increase 0.5g at every turn, to muddy to solution.Record the consumption that each test sample adds respectively.
4, result of the test
Dissolubility test result is as table 1:
5, discussion and analysis
Can be found out by drug solubility test, the former powder 0.5g of enrofloxacin is insoluble in 100mL water, and phenomenon in 100mL water appears being insoluble in Enrofloxacin solid dispersion after 2g, as can be seen here, the water solublity of the enrofloxacin prepared by clathrate process is improved greatly, is about original 3 times.
Palatability testing
1, for reagent thing
10% enrofloxacin and 10% Enrofloxacin solid dispersion, mix the ratio interpolation medicine of medicine 1kg respectively in 1000kg feedstuff before experiment.
2, laboratory animal
30 health pig, average weight, at about 40kg, is divided into three groups at random, divides into groups 10, arranges matched group, for examination group 1 with for examination group 2.Fasting 12h before experiment.
3. method
Control group fed does not add the daily feedstuff 20kg of medicine.
Feed for examination group 1 the daily feedstuff 20kg of enrofloxacin spice.
Feed for examination group 2 the daily feedstuff 20kg of Enrofloxacin solid dispersion spice.
The same time starts feeding, observes each group of situation of searching for food, and weighs each group of remaining feed relative, calculates feed intake.
4, results and analysis
The laboratory animal situation of searching for food adds following table
| Test grouping | To search for food situation | Feed intake |
| Matched group | Normally | 16kg |
| For examination group 1 | Be reluctant to search for food | 10kg |
| For examination group 2 | Normally | 20kg |
As seen from the above table, for examination group 1(10% enrofloxacin) to search for food in poor shape, feed intake also declines.Matched group feed intake is normal, and feed intake is 16kg, and for examination group 2(10% Enrofloxacin solid dispersion) situation of searching for food normal, feed intake is 2 times for examination group 1.As can be seen here Enrofloxacin solid dispersion is obviously masked the bitterness of enrofloxacin, do not affect animal and search for food normally, feed intake slightly increases, and palatability is better.
More than show and describe ultimate principle of the present invention, principal character and advantage, without departing from the spirit and scope of the present invention, the present invention also has various changes and modifications, and these changes and improvements all fall into claimed scope of the present invention.
Claims (6)
1. the preparation method of an Enrofloxacin solid dispersion, it is characterized in that concrete steps are: add water in the cyclodextrin of 30-45 weight portion and make suspension, add the enrofloxacin monomer of 10-20 weight portion again, fully mix with colloid mill, grind to form pasty state under the condition of 50-60 DEG C; Then add the carbohydrate carrier of 20-50 weight portion, continue fully to grind 1-3h, mixture is through 60 DEG C of cold drying, and add solvent detergent washing 1-3 time, taking precipitate, obtains Enrofloxacin solid dispersion through 60 DEG C of cold drying.
2. the preparation method of Enrofloxacin solid dispersion according to claim 1, is characterized in that: described cyclodextrin is beta-schardinger dextrin-, HP-β-CD or sulfobutyl ether-beta-cyclodextrin.
3. the preparation method of Enrofloxacin solid dispersion according to claim 1, is characterized in that: in described suspension, amount of water is 2-5 times of enrofloxacin monomer mass.
4. the preparation method of Enrofloxacin solid dispersion according to claim 1, is characterized in that: described carbohydrate carrier is galactose, sucrose or dextran.
5. the preparation method of Enrofloxacin solid dispersion according to claim 1, is characterized in that: described solvent detergent is chloroform or ethanol.
6. the preparation method of Enrofloxacin solid dispersion according to claim 1, is characterized in that: described Enrofloxacin solid dispersion is for the preparation of one-tenth oral formulations or ejection preparation.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109453390A (en) * | 2018-11-30 | 2019-03-12 | 佛山科学技术学院 | A kind of Enrofloxacin hydroxypropyl cyclodextrin inclusion and its preparation method and application |
| CN112569370A (en) * | 2020-12-30 | 2021-03-30 | 广东三水正大康畜牧发展有限公司 | Water-soluble enrofloxacin clathrate compound, simple molecular coating method thereof and prepared solid preparation |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109453390A (en) * | 2018-11-30 | 2019-03-12 | 佛山科学技术学院 | A kind of Enrofloxacin hydroxypropyl cyclodextrin inclusion and its preparation method and application |
| CN109453390B (en) * | 2018-11-30 | 2021-11-30 | 佛山科学技术学院 | Enrofloxacin hydroxypropyl cyclodextrin inclusion compound and preparation method and application thereof |
| CN112569370A (en) * | 2020-12-30 | 2021-03-30 | 广东三水正大康畜牧发展有限公司 | Water-soluble enrofloxacin clathrate compound, simple molecular coating method thereof and prepared solid preparation |
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