CN104688681A - Ribavirin oral liquid and preparation method thereof - Google Patents
Ribavirin oral liquid and preparation method thereof Download PDFInfo
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- CN104688681A CN104688681A CN201510118237.4A CN201510118237A CN104688681A CN 104688681 A CN104688681 A CN 104688681A CN 201510118237 A CN201510118237 A CN 201510118237A CN 104688681 A CN104688681 A CN 104688681A
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- ribavirin
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Abstract
The invention belongs to the field of medicines, in particular relates to ribavirin oral liquid, and aims at overcoming the shortages of low stability and inconvenient long-term storage of ribavirin oral liquid preparations in the prior art. According to the technical scheme, every 1000 ribavirin oral liquid reaches 5000ml and contains 0.15kg of ribavirin, 0.15 to 0.2kg of xylitol, 13.35 to 40g of sodium hydrogen phosphate, 25 to 50g of menthol, 2.5 to 10g of activated carbon, 25 to 50ml of propylene glycol, and the balance of water for injection. The ribavirin oral liquid has the beneficial effects that the pH and related materials (impurities) in the storage period are not increased, and the product safety is ensured.
Description
Technical field
The invention belongs to drug world, particularly relate to ribavirin oral solution.
Background technology
Ribavirin has another name called virazole, trifluoro azoles nucleoside, broad-spectrum antiviral drug.There is multiple virus functions such as suppressing respiratory syncytial virus, influenza virus, adenovirus.Be applicable to viral pneumonia that respiratory syncytial virus causes and bronchitis, skin bleb viral infection etc.
Ribavirin medicine can be made into several formulations form, as injection, tablet, oral liquid etc.Time wherein as oral liquid formulations, often because its stability is lower, be unfavorable for preserving, drug degradation active substance decomposition failure can be caused after long-time placement, cause drug effect to lose efficacy, thus lose therapeutic effect.There is no the means effectively solving its stability in prior art.
Summary of the invention
It is low that the present invention overcomes ribavirin oral solution preparation stability in prior art, is unfavorable for long-term deficiency of preserving, provides a kind of ribavirin oral solution and preparation method thereof.
For solving the problems of the technologies described above, the technical solution adopted in the present invention is: a kind of ribavirin oral solution, its each thousand oral liquids are 5000ml, containing ribavirin 0.15kg, xylitol 0.15 ~ 0.2kg, sodium hydrogen phosphate 13.35 ~ 40g, menthol 25g ~ 50g, active carbon 2.5 ~ 10g, propylene glycol 25 ~ 50ml, surplus is water for injection.
This product is oral solution, mainly consists of the following components:
(1) principal agent: ribavirin is white or off-white color crystalline powder, and odorless is tasteless; Easily molten in water, slightly soluble in ethanol, insoluble in ether or dichloromethane; Attention is kept in Dark Place.
(2) adjuvant: comprise xylitol, sodium hydrogen phosphate, water for injection, wherein, xylitol is sugariness regulator and suitably increases the viscosity of solution, and sodium dihydrogen phosphate is pH adjusting agent, be stabilized in by the pH value of solution in 5.5 ~ 6.0 scopes, water for injection and propylene glycol are solvent.
As preferably, for the stability making oral liquid have good mouthfeel, pH stability and composition, its each thousand oral liquids are 5000ml, containing ribavirin 0.15kg, xylitol 0.15kg, sodium hydrogen phosphate 26.7g, menthol 25g, active carbon 5g, propylene glycol 40ml, surplus is water for injection.
The preparation method of above-mentioned ribavirin oral solution, step is as follows: the water for injection adding preparation total amount 80% in preparing tank, adds xylitol, propylene glycol, ribavirin, sodium hydrogen phosphate, menthol successively, stir 20 minutes, make dissolving; Add active carbon again, be heated to 55 ± 5 DEG C of insulations 15 minutes, add to the full amount of water for injection, stir and make abundant mixing in 15 minutes; First after the titanium rod decarburization of 1 μm, then use the filter element filtering of 0.45 μm, measure the pH value of solution, guarantee that pH value is in 5.5 ~ 6.0 scopes, and measure intermediates content, content range controls 93.0% ~ 107.0%; Intermediate after the assay was approved, fill, gland; Sterilizing 15 ~ 30 minutes under 115 ~ 121 DEG C of conditions; Hunt leak qualified after, packaging.
As preferably, for ensureing that in product, microorganism is qualified, described sterilising conditions is sterilizing 15min at 121 DEG C.
Beneficial effect of the present invention is, ribavirin oral solution of the present invention has good mouthfeel, and pH content, storage life related substance (impurity) do not increase, and guarantee Product Safety; Propylene glycol solubilizing agent, plays solubilization, increases the dissolubility of ribavirin.Be that in 4.8 ~ 5.3 scopes, ribavirin dissolubility is better at ph, and adopt propylene glycol as solubilizing agent in the application, can relax the impact of Ph on its dissolubility, be in 5.5 ~ 6.0 scopes at ph, and ribavirin still has good dissolubility; And in the application, adopt xylitol as sugariness regulator, and can not only sugariness be increased, and not sugary, and go for diabetics, the scope of application is wider; Adopt menthol to be natural pastil, adjustment mouthfeel can not only be reached, and there is the effect of profit throat.
Accompanying drawing explanation
Fig. 1 is present invention process flow chart.
Detailed description of the invention
Embodiment
Table 1 component and content
| Supplementary material | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 |
| Ribavirin (g) | 3.00 | 3.00 | 3.00 | 3.00 | 3.00 |
| Xylitol (g) | 3 | 3 | 3.5 | 3 | 4 |
| Sodium hydrogen phosphate (g) | 0.267 | 0.8 | 0.4 | 0.534 | 0.6 |
| Menthol (g) | 1 | 0.5 | 0.7 | 0.5 | 0.80 |
| Active carbon (g) | 0.2 | 0.1 | 0.05 | 0.1 | 0.2 |
| Propylene glycol (ml) | 1 | 0.5 | 0.7 | 0.8 | 0.8 |
| Water for injection (ml) | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml | Add to 100ml |
| Mouthfeel (sugariness) | Sweet taste | Sweet taste | Taste is sweet | Taste is sweet | Taste is sweet |
| PH value | 5.5 | 6.0 | 5.7 | 5.6 | 5.8 |
As shown in Figure 1, the preparation method of above-mentioned ribavirin oral solution, step is as follows: the water for injection adding preparation total amount 80% in preparing tank, adds xylitol, propylene glycol, ribavirin, sodium hydrogen phosphate, menthol successively, stir 20 minutes, make dissolving; Add active carbon again, be heated to 55 ± 5 DEG C of insulations 15 minutes, add to the full amount of water for injection, stir and make abundant mixing in 15 minutes; First after the titanium rod decarburization of 1 μm, then use the filter element filtering of 0.45 μm, measure the pH value of solution, guarantee that pH value is in 5.5 ~ 6.0 scopes, and measure intermediates content, content range controls 93.0% ~ 107.0%; Intermediate after the assay was approved, fill, gland; Sterilizing 15 ~ 30 minutes under 115 ~ 121 DEG C of conditions; Hunt leak qualified after, packaging.
Placed 10 days under high temperature (60 DEG C) condition by the sample of above-mentioned preparation, after placement, sampling in the 5th day, 10 days, detects character, content and related substance, and compares with 0 day data, the results are shown in Table 2.
Table 2 adjuvant compatibility test result
Result shows: ribavirin and adjuvant certain proportion mixing sample place after 10 days under high temperature (60 DEG C) condition, not there is significant change in every quality index, illustrate principal agent and the above adjuvant compatibility good.
The sample solution of above-mentioned each prescription is placed 10 days under being placed in high temperature (60 DEG C) condition after packing, and after placement, the 10th day sampling pH value, the results are shown in Table 3.
Table 3pH change
| Time | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 | Embodiment 5 | |
| PH value | 0 | 5.5 | 6.0 | 5.7 | 5.6 | 5.8 |
| High temperature 10 | 5.45 | 5.88 | 5.65 | 5.58 | 5.73 |
Have data in above-mentioned table 3 known, the application's oral liquid is placed pH after 10 days and be there is no significant change under high temperature (60 DEG C) condition, more stable.
Claims (4)
1. a ribavirin oral solution, it is characterized in that: its each thousand oral liquids are 5000ml, containing ribavirin 0.15kg, xylitol 0.15 ~ 0.2kg, sodium hydrogen phosphate 13.35 ~ 40g, menthol 25g ~ 50g, active carbon 2.5 ~ 10g, propylene glycol 25 ~ 50ml, surplus is water for injection.
2. ribavirin oral solution according to claim 1, it is characterized in that: its each thousand oral liquids are 5000ml, containing ribavirin 0.15kg, xylitol 0.15kg, sodium hydrogen phosphate 26.7g, menthol 25g, active carbon 5g, propylene glycol 40ml, surplus is water for injection.
3. the preparation method of ribavirin oral solution according to claim 1 and 2, it is characterized in that: the water for injection adding preparation total amount 80% in preparing tank, add xylitol, propylene glycol, ribavirin, sodium hydrogen phosphate, menthol successively, stir 20 minutes, make dissolving; Add active carbon again, be heated to 55 ± 5 DEG C of insulations 15 minutes, add to the full amount of water for injection, stir and make abundant mixing in 15 minutes; First after the titanium rod decarburization of 1 μm, then use the filter element filtering of 0.45 μm, measure the pH value of solution, guarantee that pH value is within the scope of 4.5-5.5, and measure intermediates content, content range controls 93.0% ~ 107.0%; Intermediate after the assay was approved, fill, gland; Sterilizing 15 ~ 30 minutes under 115 ~ 121 DEG C of conditions; Hunt leak qualified after, packaging.
4. the preparation method of ribavirin oral solution according to claim 3, is characterized in that: described sterilising conditions is sterilizing 15min at 121 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510118237.4A CN104688681B (en) | 2015-03-17 | 2015-03-17 | Ribavirin oral solution and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510118237.4A CN104688681B (en) | 2015-03-17 | 2015-03-17 | Ribavirin oral solution and preparation method thereof |
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| CN104688681A true CN104688681A (en) | 2015-06-10 |
| CN104688681B CN104688681B (en) | 2018-01-02 |
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| CN201510118237.4A Active CN104688681B (en) | 2015-03-17 | 2015-03-17 | Ribavirin oral solution and preparation method thereof |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101632632A (en) * | 2008-07-21 | 2010-01-27 | 北京迈劲医药科技有限公司 | Sertraline oral aqueous solution and preparation method |
| JP2010132616A (en) * | 2008-12-05 | 2010-06-17 | Takada Seiyaku Kk | Ribavirin peroral tablet |
| CN104095838A (en) * | 2006-07-21 | 2014-10-15 | 莱因实验室公司 | Liquid compositions of calcium acetate |
-
2015
- 2015-03-17 CN CN201510118237.4A patent/CN104688681B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104095838A (en) * | 2006-07-21 | 2014-10-15 | 莱因实验室公司 | Liquid compositions of calcium acetate |
| CN101632632A (en) * | 2008-07-21 | 2010-01-27 | 北京迈劲医药科技有限公司 | Sertraline oral aqueous solution and preparation method |
| JP2010132616A (en) * | 2008-12-05 | 2010-06-17 | Takada Seiyaku Kk | Ribavirin peroral tablet |
Non-Patent Citations (2)
| Title |
|---|
| 徐荣周等主编: "《药物制剂生产工艺与注解》", 30 April 2008, 化学工业出版社 * |
| 温东妹等: "利巴韦林口服溶液中抑菌剂的筛选", 《中国药房》 * |
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