CN102258462A - Method for improving stability of ambroxolhydrochloride - Google Patents
Method for improving stability of ambroxolhydrochloride Download PDFInfo
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- CN102258462A CN102258462A CN2011101968355A CN201110196835A CN102258462A CN 102258462 A CN102258462 A CN 102258462A CN 2011101968355 A CN2011101968355 A CN 2011101968355A CN 201110196835 A CN201110196835 A CN 201110196835A CN 102258462 A CN102258462 A CN 102258462A
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Abstract
The invention relates to a method for improving the stability of ambroxolhydrochloride. For the characteristics such as microsolubility and unstability of ambroxolhydrochloride as the main ingredient, glycerine and propylene glycol can effectively solubilize the ambroxolhydrochloride, the formula and the preparation method of the glycerine have larger influence on the stability of the main medicine, while the product obtained by the formula and the preparation method of the propylene glycol has good stability; and proved by the acceleration stability and long-term stability test, the formula and the preparation method have better stability than the stability test of the similar products on the market.
Description
Technical field
The present invention relates to the preparation method of ambroxol hydrochloride.
Background technology
Ambroxol hydrochloride (ambroxol hydrochloride) has another name called the hydrochloric acid NA-872, it is phlegm dissolving agent of new generation, can promote bronchus cilium emptying campaign, helping airway secretions discharges, be mainly used in the treatment of eliminating the phlegm of acute and chronic respiratory tract disease, particularly chronic bronchitis clinically.The less stable of existing ambroxol hydrochloride in the relevant dosage form that with water is solution.
Summary of the invention
The object of the invention is to overcome ambroxol hydrochloride deliquescent defective and a kind of prescription and preparation method that can improve ambroxol hydrochloride stability is provided in water.
The concrete technical scheme of the present invention is, and to be adjuvant with the propylene glycol improve a lot to the stability of ambroxol hydrochloride, and consumption is for containing propylene glycol 5～40%, and optimum amount is for containing propylene glycol 10～40%.
A kind of method that improves ambroxol hydrochloride stability of the present invention, whenever make 1000ml, the weight portion of its main constituent is as follows: ambroxol hydrochloride 6g, propylene glycol 100～400g, surplus is; get propylene glycol and add 100ml～500ml boiled water mixing, add ambroxol hydrochloride and make dissolving, add in the above-mentioned adjuvant solution; add water to 1000ml; mixing, fill, promptly.
Above-mentioned a kind of method that improves ambroxol hydrochloride stability, its adjuvant also has sorbitol, sodium benzoate, citric acid, sucralose, essence, and above-mentioned material is got sorbitol, sodium benzoate, citric acid, sucralose and is added water boil, puts cold; Other gets propylene glycol and adds the boiled water mixing, adds ambroxol hydrochloride and makes dissolving, adds in the above-mentioned adjuvant solution, add essence, add water to mixing, fill promptly, is whenever made 1000ml, the weight portion of its main constituent is as follows: ambroxol hydrochloride 6g, propylene glycol 20～400g, sorbitol 20～300g, sodium benzoate 2～3.5g, citric acid 0.2～6g, sucralose 0.2～1.5g, essence 0.2～2ml, surplus is a purified water.
Further, a kind of method that improves ambroxol hydrochloride stability of the present invention is: get sorbitol, sodium benzoate, citric acid, sucralose and added water boil 10～30 minutes, put and be chilled to 40～80 ℃; Other gets propylene glycol and adds 100ml～500ml boiled water mixing, adds ambroxol hydrochloride and makes dissolving, adds in the above-mentioned adjuvant solution, adds essence, adds water to 1000ml, mixing, and fill, promptly.
Further, a kind of method that improves ambroxol hydrochloride stability of the present invention, whenever make 1000ml, the weight portion of its main constituent is as follows: ambroxol hydrochloride 6g, propylene glycol 100～250g, sorbitol 50～250g, sodium benzoate 2～3.5g, citric acid 0.2～3g, sucralose 0.2～1g, essence 0.2～2ml, surplus is a purified water.
Further, a kind of method that improves ambroxol hydrochloride stability of the present invention is: get sorbitol, sodium benzoate, citric acid, sucralose and added water boil 10～30 minutes, put and be chilled to 40～80 ℃; Other gets propylene glycol and adds 100ml～500ml boiled water mixing, adds ambroxol hydrochloride and makes dissolving, adds in the above-mentioned adjuvant solution, adds essence, adds purified water to 1000ml, mixing, and fill, promptly.
A kind of method that improves ambroxol hydrochloride stability of the present invention, the prepared medicine of this method is syrup, oral administration solution or oral liquid.In order to reduce the adjuvant kind as far as possible, adopt different auxiliary material to test respectively, be evaluation index with character, mouthfeel, dissolubility.With reference to commercially available ambroxol hydrochloride oral solution, relatively lack glycerol, sorbitol respectively, the difference of the character when propylene glycol, Mentholum, saccharin sodium, sucralose, mouthfeel, dissolubility, content, related substance, it is effective that the glycerinated prescription of result contains the sample taste masking of propylene glycol prescription, and obviously improving drug main, the propylene glycol prescription wants ingredient stability, so determine that main adjuvant is a propylene glycol, be aided with sorbitol, sodium benzoate, citric acid, sucralose, essence.
Stability test is the result show: 9 batch samples are through 6 months accelerated tests, no significant changes such as character, discriminating and microbial limit.090901 ~ 090,906 6 batch contains glycerol prescription sample pH value and has increased by 0.06～0.19 respectively, and the trend of rising is arranged, and citric acid content height, the prescription pH value that glycerol content is low rise little, otherwise it is big to rise; Its related substances obviously increases, and value added is also relevant with prescription, citric acid content height, the prescription that glycerol content is low, and related substance increases less; Single impurity content also has trend of rising gradually simultaneously, wherein more obvious with the content increase of impurity A, content also descends to some extent, illustrate that glycerinated sample is 40 ℃ ± 2 ℃ of temperature, relative humidity is that principal agent is degraded under 75% ± 5% the accelerated stability test condition, and the higher relatively reason of this product impurity A, impurity B content is relevant with adjuvant glycerol.
20100401 ~ 20100403 batch samples are the sample that contains the propylene glycol prescription, accelerated test result shows that character, discriminating, pH value and the microbial limit of above-mentioned sample and commercially available sample do not have significant change, and its related substances increases by 0.08%, 0.03%, 0.01% respectively; And commercially available with the kind sample under the same conditions the related substance impurity content increased by 0.59%, content descends to some extent.Show that the sample that contains the propylene glycol prescription has good stability under the accelerated test condition, and the stability that obviously is better than commercially available product, show that the present invention has the stability more superior than the product that goes on the market to ambroxol hydrochloride in the relevant dosage form that with water is solution, provide a kind of ideal prescription and preparation method for improving the stability of ambroxol hydrochloride in the relevant dosage form that with water is solution.
The specific embodiment
Embodiment one:
A kind of method that improves ambroxol hydrochloride stability, whenever make 1000ml, the weight portion of its main constituent is as follows: ambroxol hydrochloride 6g, propylene glycol 100～400g, surplus is; get propylene glycol and add 100ml～500ml boiled water mixing, add ambroxol hydrochloride and make dissolving, add in the above-mentioned adjuvant solution; add water to 1000ml; mixing, fill, promptly.
Embodiment two:
The present invention further specifies as follows in conjunction with specific embodiments: above-mentioned material, and get sorbitol, sodium benzoate, citric acid, sucralose and added water boil 10～30 minutes, put and be chilled to 40～80 ℃; Other gets propylene glycol and adds 100ml～500ml boiled water mixing, adds ambroxol hydrochloride and makes dissolving, adds in the above-mentioned adjuvant solution, adds essence, adds water to 1000ml, mixing, and fill, promptly.
Claims (6)
1. method that improves ambroxol hydrochloride stability, it is characterized in that: whenever make 1000ml, the weight portion of its main constituent is as follows: ambroxol hydrochloride 6g, propylene glycol 100～400g, surplus is; get propylene glycol and add 100ml～500ml boiled water mixing, add ambroxol hydrochloride and make dissolving, add in the above-mentioned adjuvant solution; add water to 1000ml; mixing, fill, promptly.
2. a kind of according to claim 1 method that improves ambroxol hydrochloride stability, it is characterized in that: adjuvant also has sorbitol, sodium benzoate, citric acid, sucralose, essence, above-mentioned material is got sorbitol, sodium benzoate, citric acid, sucralose and is added water boil, puts cold; Other gets propylene glycol and adds the boiled water mixing, adds ambroxol hydrochloride and makes dissolving, adds in the above-mentioned adjuvant solution, add essence, add water to mixing, fill promptly, is whenever made 1000ml, the weight portion of its main constituent is as follows: ambroxol hydrochloride 6g, propylene glycol 20～400g, sorbitol 20～300g, sodium benzoate 2～3.5g, citric acid 0.2～6g, sucralose 0.2～1.5g, essence 0.2～2ml, surplus is a purified water.
3. as a kind of method that improves ambroxol hydrochloride stability as described in the claim 2, it is characterized in that: get sorbitol, sodium benzoate, citric acid, sucralose and added water boil 10～30 minutes, put and be chilled to 40～80 ℃; Other gets propylene glycol and adds 100ml～500ml boiled water mixing, adds ambroxol hydrochloride and makes dissolving, adds in the above-mentioned adjuvant solution, adds essence, adds water to 1000ml, mixing, and fill, promptly.
4. as a kind of method that improves ambroxol hydrochloride stability as described in the claim 2, it is characterized in that: whenever make 1000ml, the weight portion of its main constituent is as follows: ambroxol hydrochloride 6g, propylene glycol 100～250g, sorbitol 50～250g, sodium benzoate 2～3.5g, citric acid 0.2～3g, sucralose 0.2～1g, essence 0.2～2ml, surplus is a purified water.
5. as a kind of method that improves ambroxol hydrochloride stability as described in the claim 2, it is characterized in that: get sorbitol, sodium benzoate, citric acid, sucralose and added water boil 10～30 minutes, put and be chilled to 40～80 ℃; Other gets propylene glycol and adds 100ml～500ml boiled water mixing, adds ambroxol hydrochloride and makes dissolving, adds in the above-mentioned adjuvant solution, adds essence, adds purified water to 1000ml, mixing, and fill, promptly.
6. as the described a kind of method that improves ambroxol hydrochloride stability of claim 1～5, it is characterized in that the prepared medicine of this method is syrup, oral administration solution or oral liquid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2011101968355A CN102258462A (en) | 2011-07-14 | 2011-07-14 | Method for improving stability of ambroxolhydrochloride |
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| CN2011101968355A CN102258462A (en) | 2011-07-14 | 2011-07-14 | Method for improving stability of ambroxolhydrochloride |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015177147A1 (en) * | 2014-05-23 | 2015-11-26 | Boehringer Ingelheim International Gmbh | Cough medicine containing ambroxol hydrochloride |
| CN105193707A (en) * | 2014-06-30 | 2015-12-30 | 南京瑞尔医药有限公司 | Ambroxol hydrochloride oral solution and preparation method thereof |
| CN105287367A (en) * | 2015-10-13 | 2016-02-03 | 华润三九（南昌）药业有限公司 | Oral liquid preparation of ambroxol hydrochloride as well as preparation method and application of oral liquid preparation |
| CN107362134A (en) * | 2017-07-23 | 2017-11-21 | 南京正宽医药科技有限公司 | A kind of ambroxol hydrochloride oral solution and preparation method thereof |
| CN108057121A (en) * | 2017-12-28 | 2018-05-22 | 广东伊茗药业有限公司 | One kind makes the stability-enhanced pharmaceutical composition of ambroxol hydrochloride |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101103968A (en) * | 2006-07-14 | 2008-01-16 | 海南盛科生命科学研究院 | Ambroxol oral liquid with good taste |
| CN101627967A (en) * | 2009-08-03 | 2010-01-20 | 上海华源药业（宁夏）沙赛制药有限公司 | Ambroxol hydrochloride liquid preparation and preparation method thereof |
-
2011
- 2011-07-14 CN CN2011101968355A patent/CN102258462A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101103968A (en) * | 2006-07-14 | 2008-01-16 | 海南盛科生命科学研究院 | Ambroxol oral liquid with good taste |
| CN101627967A (en) * | 2009-08-03 | 2010-01-20 | 上海华源药业（宁夏）沙赛制药有限公司 | Ambroxol hydrochloride liquid preparation and preparation method thereof |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015177147A1 (en) * | 2014-05-23 | 2015-11-26 | Boehringer Ingelheim International Gmbh | Cough medicine containing ambroxol hydrochloride |
| CN106413688A (en) * | 2014-05-23 | 2017-02-15 | 勃林格殷格翰国际有限公司 | Cough medicine containing ambroxol hydrochloride |
| EA036554B1 (en) * | 2014-05-23 | 2020-11-23 | Бёрингер Ингельхайм Интернациональ Гмбх | Cough syrup containing ambroxol hydrochloride |
| CN105193707A (en) * | 2014-06-30 | 2015-12-30 | 南京瑞尔医药有限公司 | Ambroxol hydrochloride oral solution and preparation method thereof |
| CN105287367A (en) * | 2015-10-13 | 2016-02-03 | 华润三九（南昌）药业有限公司 | Oral liquid preparation of ambroxol hydrochloride as well as preparation method and application of oral liquid preparation |
| CN105287367B (en) * | 2015-10-13 | 2018-07-10 | 华润三九（南昌）药业有限公司 | A kind of oral liquid of ambroxol hydrochloride and preparation method and application |
| CN107362134A (en) * | 2017-07-23 | 2017-11-21 | 南京正宽医药科技有限公司 | A kind of ambroxol hydrochloride oral solution and preparation method thereof |
| CN108057121A (en) * | 2017-12-28 | 2018-05-22 | 广东伊茗药业有限公司 | One kind makes the stability-enhanced pharmaceutical composition of ambroxol hydrochloride |
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Application publication date: 20111130 |