CN108853025B - Tilmicosin solid dispersion and preparation method thereof - Google Patents
Tilmicosin solid dispersion and preparation method thereof Download PDFInfo
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- CN108853025B CN108853025B CN201810854880.7A CN201810854880A CN108853025B CN 108853025 B CN108853025 B CN 108853025B CN 201810854880 A CN201810854880 A CN 201810854880A CN 108853025 B CN108853025 B CN 108853025B
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- A61K9/00—Medicinal preparations characterised by special physical form
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- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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Abstract
The invention discloses a tilmicosin solid dispersion which is composed of tilmicosin and a composite carrier according to the raw material weight part ratio of 1:3, wherein the composite carrier is composed of PEG6000 and poloxamer 188 according to the raw material weight part ratio of 20: 1. The invention accurately limits the raw material composition and the proportion of the composite carrier, avoids various defects of the solid dispersion prepared by a single carrier, and can be quickly dissolved in water and be convenient for storage. The tilmicosin solid dispersion prepared by the invention has important clinical application value for improving the bioavailability, stability and drinking water administration convenience and treating diseases in time. The preparation method has simple process and strong operation controllability, and is beneficial to large-scale industrial production.
Description
Technical Field
The invention relates to the field of veterinary medicines, and in particular relates to a medicinal solid dispersion.
Background
Tilmicosin is a novel macrolide antibiotic semisynthesized by tylosin and specially used for livestock, has good inhibition effect on gram-positive bacteria, partial gram-negative bacteria, mycoplasma, spirochetes and the like, has stronger antibacterial activity than tylosin on actinomycetes pleuropneumoniae and pasteurella, and has no cross resistance with clinically common antibiotics. The traditional Chinese medicine composition is mainly used for treating animal respiratory diseases and mastitis of lactating animals in clinic, and particularly shows remarkable superiority in treating porcine respiratory disease syndrome and porcine reproductive and respiratory syndrome. However, tilmicosin has certain irritation, and the tilmicosin is mainly administrated in an oral administration mode and a subcutaneous injection mode, and is particularly administrated by injection with caution to pigs, so that the clinical popularization and application of the tilmicosin in veterinarians are limited.
Tilmicosin is insoluble in water, has bitter taste and is alkaline, oral administration can stimulate gastric mucosa and sometimes cause anaphylactic reaction, the target organ of toxic action is heart, and negative heart effect can be caused when tilmicosin is injected intravenously or intramuscularly at too fast and large dose, so that animals die. The phosphate is mainly phosphate in the market, is easy to be damaged by gastric acid after being taken orally, is incompletely absorbed, and has low bioavailability and short half-life in vivo. Clinically, the medicine is mainly taken by mixing materials, but sick animals are easy to lose appetite and cannot play a role in timely treatment. The method improves the water solubility, bioavailability and targeting property of the tilmicosin, prolongs the half-life period of the tilmicosin in vivo and enhances the curative effect, and becomes one of the important subjects of the research on the high-efficiency utilization of the tilmicosin at present. In recent years, new technologies such as micro-capsules, micro-spheres, micro-pills, nano-emulsions, enteric-coated particles, inclusion compounds, liposomes, solid dispersions and the like are applied to the research of tilmicosin preparations, so that the solubility of the medicament is improved to a certain extent, the bitter taste of tilmicosin is covered, and the tilmicosin preparation has the functions of slow release and targeting. However, tilmicosin targets on alveolar macrophages, so that the tilmicosin has a targeted treatment effect, and the sustained-release preparation cannot play a role in timely treatment of some acute diseases. Most of the techniques need to add organic reagents, have large dosage and high cost, are sometimes difficult to remove and pollute the environment, and at present, the new techniques of the preparations are not applied to actual production.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a tilmicosin solid dispersion which is soluble powder capable of covering bitter taste and dissolving in water and can effectively improve bioavailability. Also provided is a method for producing the solid dispersion.
The technical scheme adopted by the invention is as follows: the tilmicosin solid dispersion comprises tilmicosin and a composite carrier according to the raw material weight part ratio of 1:3, wherein the composite carrier comprises PEG6000 and poloxamer 188 according to the raw material weight part ratio of 20: 1.
According to the research, the tilmicosin solid dispersion prepared by singly adopting the PEG6000 carrier is not easy to bond and has a slow dissolving speed, and the tilmicosin solid dispersion prepared by singly adopting the poloxamer 188 as the carrier is high in viscosity and easy to bond, but has a fast dissolving speed. Namely, the single adoption of the two carriers has the defect of non-negligible defect in the actual production and application processes. The invention takes synergistic consideration from multiple aspects of solid dispersion viscosity, dissolution speed and maximum dissolution rate, and accurately limits that the composite carrier is composed of PEG6000 and poloxamer 188 according to the weight part ratio of 20:1, so that the composite carrier has moderate viscosity and good dissolution rate, the dissolution rate reaches over 71.8% at 2min, is 22.4 times of tilmicosin original drug, and is basically and completely dissolved at 15min, thereby effectively improving the bioavailability of tilmicosin.
A preparation method of the tilmicosin solid dispersion comprises the following process steps:
1) taking PEG6000 and poloxamer 188 according to the weight parts of the raw materials, putting the raw materials into a container together, heating and melting the raw materials in a water bath, adding tilmicosin while stirring, and continuously stirring until the tilmicosin is completely melted in a medium to obtain a semi-finished product;
2) taking out the container, pouring the semi-finished product into a precooled metal tray, then transferring to a temperature of-20 ℃ for solidification, drying at a temperature of 35 ℃, and grinding and sieving to obtain the tilmicosin solid dispersion finished product.
As a further improvement of the above scheme, the temperature of the water bath heating in step 1) is controlled at 57 ℃.
As a further improvement of the above scheme, the stirring time of the stirring in the step 1) is 1 h.
As a further improvement of the above solution, the curing time of the curing in step 2) is 12 h.
As a further improvement of the scheme, the drying time of the drying in the step 2) is 24 h.
As a further improvement of the scheme, the sieving in the step 2) is 80-mesh sieving.
The invention has the beneficial effects that:
the invention accurately limits the raw material composition and the proportion of the composite carrier, avoids various defects of the solid dispersion prepared by a single carrier, and can be quickly dissolved in water and be convenient for storage. The tilmicosin solid dispersion prepared by the invention has important clinical application value for improving the bioavailability, stability and drinking water administration convenience and treating diseases in time.
The preparation method has simple process and strong operation controllability, and is beneficial to large-scale industrial production.
Detailed Description
The present invention is specifically described below with reference to examples in order to facilitate understanding of the present invention by those skilled in the art. It should be particularly noted that the examples are given solely for the purpose of illustration and are not to be construed as limitations on the scope of the invention, as non-essential improvements and modifications to the invention may occur to those skilled in the art, which fall within the scope of the invention as defined by the appended claims. Meanwhile, the raw materials mentioned below are not specified in detail and are all commercial products; the process steps or preparation methods not mentioned in detail are all process steps or preparation methods known to the person skilled in the art.
Example 1
The tilmicosin solid dispersion comprises tilmicosin and a composite carrier according to the raw material weight part ratio of 1:3, wherein the composite carrier comprises PEG6000 and poloxamer 188 according to the raw material weight part ratio of 20: 1.
The preparation method comprises the following steps:
1) taking 20 parts of PEG6000 and 1 part of poloxamer 188 according to the weight parts of the raw materials, putting the raw materials into a container together, heating and melting the raw materials in a water bath at 57 ℃, adding 7 parts of tilmicosin while stirring for 1 hour until the tilmicosin is completely dissolved in a medium, and obtaining a semi-finished product;
2) and taking out the container, pouring the semi-finished product into a precooled metal tray, then transferring the semi-finished product to a temperature of minus 20 ℃ for curing for 12 hours, then drying the semi-finished product at a temperature of 35 ℃ for 24 hours, and grinding and sieving the semi-finished product with a 80-mesh sieve to obtain a finished product of the tilmicosin solid dispersion in the embodiment 1.
The finished product obtained in example 1 is tested for dissolution by in vitro dissolution test according to the second method (paddle method) of appendix 160 of the first part of the 2015 edition of pharmacopoeia of the people's republic of China, and the test result shows that the maximum dissolution rate is 72.02% within 2min and the finished product is completely dissolved within 15 min.
Example 2
The tilmicosin solid dispersion comprises tilmicosin and a composite carrier according to the raw material weight part ratio of 1:3, wherein the composite carrier comprises PEG6000 and poloxamer 188 according to the raw material weight part ratio of 20: 1.
The preparation method comprises the following steps:
1) taking 10 parts of PEG6000 and 0.5 part of poloxamer 188 according to the weight parts of the raw materials, putting the raw materials into a container together, heating and melting the raw materials in a water bath at 57 ℃, adding 3.5 parts of tilmicosin while stirring for 1 hour until the tilmicosin is completely dissolved in a medium, and obtaining a semi-finished product;
2) and taking out the container, pouring the semi-finished product into a precooled metal tray, then transferring the semi-finished product to a temperature of minus 20 ℃ for curing for 12 hours, then drying the semi-finished product at a temperature of 35 ℃ for 24 hours, and grinding and sieving the semi-finished product with a 80-mesh sieve to obtain a finished product of the tilmicosin solid dispersion of the embodiment 2.
The dissolution of the finished product obtained in example 2 is measured in vitro, and the drug dissolution is measured according to the second method (paddle method) of appendix 160 of the first edition of the pharmacopoeia of the people's republic of China 2015, and the measurement result shows that the maximum dissolution rate is 71.85% within 2min and the finished product is completely dissolved within 15 min.
Example 3
The tilmicosin solid dispersion comprises tilmicosin and a composite carrier according to the raw material weight part ratio of 1:3, wherein the composite carrier comprises PEG6000 and poloxamer 188 according to the raw material weight part ratio of 20: 1.
The preparation method comprises the following steps:
1) taking 40 parts of PEG6000 and 2 parts of poloxamer 188 according to the weight parts of the raw materials, putting the raw materials into a container together, heating and melting the raw materials in a water bath at 57 ℃, adding 14 parts of tilmicosin while stirring for 1 hour until the tilmicosin is completely dissolved in a medium, and obtaining a semi-finished product;
2) and taking out the container, pouring the semi-finished product into a precooled metal tray, then transferring the semi-finished product to a temperature of minus 20 ℃ for curing for 12 hours, then drying the semi-finished product at a temperature of 35 ℃ for 24 hours, and grinding and sieving the semi-finished product with a 80-mesh sieve to obtain a finished product of the tilmicosin solid dispersion in the embodiment 3.
The dissolution rate of the finished product obtained in example 3 is measured in vitro according to the second method (paddle method) in appendix 160 of the first edition of the pharmacopoeia of the people's republic of China 2015, and the measurement result shows that the maximum dissolution rate is 72.36% within 2min and the finished product is completely dissolved within 15 min.
The above embodiments are preferred embodiments of the present invention, and all similar processes and equivalent variations to those of the present invention should fall within the scope of the present invention.
Claims (8)
1. A tilmicosin solid dispersion, which is characterized in that: the tilmicosin and the composite carrier are mixed according to the weight ratio of 1:3, and the composite carrier is mixed according to the weight ratio of 20:1 of PEG6000 and poloxamer 188.
2. The tilmicosin solid dispersion according to claim 1, wherein: the solid dispersion has dissolution rate of above 71.8% in 2min and substantially complete dissolution in 15 min.
3. A process for the preparation of the tilmicosin solid dispersion of claim 1 or 2, characterized by comprising the process steps of:
1) taking PEG6000 and poloxamer 188 according to the weight parts of the raw materials, putting the raw materials into a container together, heating and melting the raw materials in a water bath, adding tilmicosin while stirring, and continuously stirring until the tilmicosin is completely melted in a medium to obtain a semi-finished product;
2) taking out the container, pouring the semi-finished product into a precooled metal tray, then transferring to a temperature of-20 ℃ for solidification, drying at a temperature of 35 ℃, and grinding and sieving to obtain the tilmicosin solid dispersion finished product.
4. The method for preparing a tilmicosin solid dispersion according to claim 3, wherein: the temperature of the water bath heating in step 1) was controlled at 57 ℃.
5. The method for preparing a tilmicosin solid dispersion according to claim 3, wherein: the stirring time of the stirring in the step 1) is 1 h.
6. The method for preparing a tilmicosin solid dispersion according to claim 3, wherein: the curing time of the curing in the step 2) is 12 h.
7. The method for preparing a tilmicosin solid dispersion according to claim 3, wherein: the drying time for the drying in the step 2) is 24 h.
8. The method for preparing a tilmicosin solid dispersion according to claim 3, wherein: the sieving in the step 2) is 80-mesh sieving.
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| CN109953997B (en) * | 2019-04-22 | 2021-06-29 | 佛山科学技术学院 | Preparation method of tilmicosin preparation |
| CN111407728B (en) * | 2020-04-16 | 2022-02-22 | 重庆市畜牧科学院 | Tilmicosin enteric solid dispersion and preparation method and application thereof |
| CN115645376B (en) * | 2022-10-26 | 2023-10-31 | 山东德州神牛药业有限公司 | Efficient double-layer coated tilmicosin pellets and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670516A (en) * | 2012-05-29 | 2012-09-19 | 广东大华农动物保健品股份有限公司 | Tilmicosin soluble powder and preparation method thereof |
| CN104721826A (en) * | 2015-04-14 | 2015-06-24 | 四川美嘉龙生物科技有限公司 | Tilmicosin preparation and preparation method thereof |
| CN105582019A (en) * | 2014-10-27 | 2016-05-18 | 河南惠通天下生物工程有限公司 | Tilmicosin solid dispersing agent and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670516A (en) * | 2012-05-29 | 2012-09-19 | 广东大华农动物保健品股份有限公司 | Tilmicosin soluble powder and preparation method thereof |
| CN105582019A (en) * | 2014-10-27 | 2016-05-18 | 河南惠通天下生物工程有限公司 | Tilmicosin solid dispersing agent and preparation method thereof |
| CN104721826A (en) * | 2015-04-14 | 2015-06-24 | 四川美嘉龙生物科技有限公司 | Tilmicosin preparation and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 不同工艺制备替米考星固体分散体及溶出特性研究;吕彪，等;《中国动物保健》;20141231;第16卷(第12期);第11-15页 * |
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Effective date of registration: 20210423 Address after: 528000 Guangdong Province, Foshan city Shunde District Daliang Honggang Industrial Zone Patentee after: GUANGDONG YANGBLE BIOPHARMACEUTICALS Co.,Ltd. Address before: 528000 Foshan University, Guangdong Province, Nanhai District, Nanhai District, Xian Xi reservoir West Road, Foshan University Patentee before: FOSHAN University |