CN115737552A - Ambroxol hydrochloride oral solution and preparation method thereof - Google Patents
Ambroxol hydrochloride oral solution and preparation method thereof Download PDFInfo
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- CN115737552A CN115737552A CN202211555639.7A CN202211555639A CN115737552A CN 115737552 A CN115737552 A CN 115737552A CN 202211555639 A CN202211555639 A CN 202211555639A CN 115737552 A CN115737552 A CN 115737552A
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Abstract
The invention discloses an ambroxol hydrochloride oral solution and a preparation method thereof, and relates to the technical field of phlegm-eliminating medicines. The technical key points are as follows: an ambroxol hydrochloride oral solution comprises the following components: ambroxol hydrochloride: 0.2-0.4 weight part; xanthan gum: 0.3-0.5 weight parts; benzoic acid: 0.04-0.06 parts by weight; sucralose: 0.08 to 0.12 part by weight; essence: 0.02-0.04 weight portion; purifying water: adding to 100 parts by volume; when the unit of the weight part is g, the unit of the volume part is mL, and the ambroxol hydrochloride oral solution prepared by the formula has the advantages of high safety, good stability and suitability for industrial production, and the quality is superior to that of the original research. The invention can effectively overcome the defects of the original ground product only by slightly changing the original ground formula, has little formula change degree and is suitable for industrialized mass production.
Description
Technical Field
The invention relates to the technical field of phlegm eliminating medicines, in particular to an ambroxol hydrochloride oral solution and a preparation method thereof.
Background
The product is a mucolytic agent, and has effects of increasing secretion of respiratory mucosa serous gland, reducing secretion of mucous gland, reducing sputum viscosity, promoting secretion of lung surfactant, increasing bronchial ciliary movement, and facilitating expectoration of sputum. Ambroxol hydrochloride is a sputum-dissolving agent developed by the company Boehringer Ingelheim, germany, and first marketed in 1978 in Germany under the trade name
And then, the oral solution is successively marketed in japan, italy, austria, france, spain, portugal, etc., in the form of inhalation solution, injection solution, oral solution, etc., which have been marketed in the european union, japan and china.
Through the related information query of the original preparation and the experimental research of the product, the following problems are found:
the original preparation contains hydroxyethyl cellulose as adjuvant, and the hydroxyethyl cellulose is loaded into FDA inactive ingredient guide (for ophthalmic preparation, oral syrup and tablet; ear and topical pharmaceutical preparation). Use in non-injectable formulations has been approved in the uk. Currently, hydroxyethyl cellulose is not approved for food use in europe and the us, although it can be used without direct contact (e.g., as packaging material). This is limited primarily by the high concentration of ethylene glycol that remains during the production of hydroxyethylcellulose. Meanwhile, the hydroxyethyl cellulose has poor water solubility, a dispersing medium such as water needs to be heated during configuration, and cooling treatment is carried out after configuration, so that the product is time-consuming and labor-consuming during industrial production.
The liquid medicine is filtered before filling to remove foreign matters and ensure the product quality. Because the product has certain viscosity, if the aperture of the filter element is too small, the filter speed is extremely slow and is not suitable for production requirements; if the aperture of the filter element is too large, the foreign matter removing effect can not be achieved. Therefore, the filter with the proper pore diameter is selected to meet the requirements of ensuring the product quality and being suitable for the industrial production target.
The Chinese patent application with the publication number of CN101152181A discloses a liquid composition containing loratadine and ambroxol hydrochloride, wherein the active ingredients of the liquid composition are loratadine and ambroxol hydrochloride, the liquid composition further contains a pharmaceutically acceptable stabilizer, a pH regulator, a preservative, a flavoring agent and a metal ion complexing agent, the flavoring agent adopts sodium chloride, an aromatic and a sweetening agent, and the sweetening agent adopts saccharin sodium. Compared with the original preparation, the saccharin sodium is an organic chemical synthesis product, has no nutritive value to human body except that the saccharin sodium causes sweet feeling in taste, influences the normal secretion of digestive enzymes in intestines and stomach and reduces the absorption capacity of small intestines when being eaten more, and the safety of the saccharin sodium is widely controversial all the time.
The Chinese patent application with the publication number of CN111494314A discloses an ambroxol hydrochloride-containing oral solution which contains pharmaceutically acceptable sorbitol, benzoic acid, AK sugar, sucralose, calcium sodium edetate, lemon essence, peppermint water and the like. Compared with the original product of the ambroxol hydrochloride oral solution, the types of the auxiliary materials are increased, and the safety of the types of the added auxiliary materials is unknown.
Therefore, a new solution is needed to solve the above problems.
Aiming at the defects in the prior art, the invention aims to provide an ambroxol hydrochloride oral solution which has the advantages of high safety and good stability.
The second purpose of the invention is to provide a preparation method of ambroxol hydrochloride oral solution, which has the advantages of simplicity, feasibility and suitability for commercial production.
In order to achieve the first purpose, the invention provides the following technical scheme:
ambroxol hydrochloride: 0.2-0.4 weight part;
xanthan gum: 0.3-0.5 weight parts;
benzoic acid: 0.04-0.06 parts by weight;
sucralose: 0.08-0.12 weight part;
essence: 0.02-0.04 weight portion;
purifying water: adding to 100 parts by volume;
when the unit of the parts by weight is g, the unit of the parts by volume is mL.
The xanthan gum is a biological gum which integrates thickening, suspending, emulsifying and stabilizing at home and abroad and has excellent performance. Compared with hydroxyethyl cellulose in the original preparation, the xanthan gum has better safety, stability, water solubility and thickening property. By adopting the technical scheme, the xanthan gum can improve the stability of the oral solution, meanwhile, the xanthan gum has good water solubility, and the dispersion medium can be quickly swelled and dissolved without high temperature, so that the xanthan gum is suitable for industrial production.
Further preferably, the composition comprises the following components:
ambroxol hydrochloride: 0.3 part by weight;
xanthan gum: 0.4 part by weight;
benzoic acid: 0.05 part by weight;
sucralose: 0.10 part by weight;
essence: 0.03 part by weight;
purifying water: adding to 100 parts by volume;
when the unit of the parts by weight is g, the unit of the parts by volume is mL.
By adopting the technical scheme, the ambroxol hydrochloride oral solution prepared from the components in the ratio has the best stability and the optimal effect.
More preferably, the ambroxol hydrochloride is prepared by the following preparation method:
(1) Dissolving benzoic acid: purified water (water temperature: 30-40 ℃) is added into the liquid preparation tank, and the benzoic acid with the prescription amount is stirred and dissolved.
(2) Dissolving xanthan gum: purified water (normal temperature) is used for stirring and dissolving xanthan gum with the prescription amount, and after complete dissolution, the xanthan gum solution is added into a liquid preparation tank.
(3) Preparation: when the temperature of the materials in the liquid preparation tank is less than or equal to 45 ℃, adding ambroxol hydrochloride with the prescription amount for complete dissolution, then adding sucralose with the prescription amount for complete dissolution, finally adding the essence for strawberry-flavored food and the essence for vanilla-flavored food, and stopping stirring after adding.
(4) And (3) volume fixing and mixing: adding purified water to a constant volume. Stirring and mixing evenly to obtain an intermediate product.
(5) Sampling and inspecting the intermediate product.
(6) Filtering and filling: filtering the medicinal liquid with polytetrafluoroethylene filter element, and filling into oral liquid medicinal polyester bottle.
(7) Packaging: labeling, boxing and boxing.
(8) And (5) inspecting and warehousing a finished product.
By adopting the technical scheme, the method has the advantages of simple and feasible process, less high-temperature condition, no high-pressure condition, energy conservation and controllable key factors, and the ambroxol hydrochloride oral solution prepared by the preparation method has high stability and long storage time.
More preferably, in the step (6), the pore size of the polytetrafluoroethylene filter element is 10 μm.
By adopting the technical scheme, the product quality can be guaranteed, the industrial production target can be met, and the obtained oral solution finished product has good properties and meets the requirements.
In summary, compared with the prior art, the invention has the following beneficial effects:
(1) The xanthan gum is adopted to replace the original grinding agent hydroxyethyl cellulose and is combined with other components in the formula, so that the safety and the stability of the oral solution are greatly improved;
(2) The xanthan gum has good water solubility, is convenient to prepare, does not need a high-temperature dispersion medium, improves the production efficiency, reduces the production cost and has high production safety;
(3) The liquid medicine is filtered by the polytetrafluoroethylene filter element, so that the product quality can be guaranteed, the industrial production target can be met, and the obtained oral solution finished product has good properties and meets the requirements. .
Detailed Description
The technical solutions of the present invention will be described clearly and completely below, and it should be apparent that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
The ambroxol hydrochloride oral solution comprises the following components: ambroxol hydrochloride: 3g of the total weight of the mixture; xanthan gum: 4g of the total weight of the mixture; benzoic acid: g; sucralose: 1g of a compound; essence: 0.3g; purifying water: adding to 1000g;
the preparation method of the ambroxol hydrochloride oral solution comprises the following steps:
(1) Dissolving benzoic acid: purified water (water temperature: 30-40 ℃) is added into the liquid preparation tank, and the benzoic acid with the prescription amount is stirred and dissolved.
(2) Dissolving xanthan gum: purified water (normal temperature) is used for stirring and dissolving xanthan gum with the prescription amount, and after complete dissolution, the xanthan gum solution is added into a liquid preparation tank.
(3) Preparation: when the temperature of the materials in the liquid preparation tank is less than or equal to 45 ℃, adding ambroxol hydrochloride with the prescription amount for complete dissolution, then adding sucralose with the prescription amount for complete dissolution, finally adding the essence for strawberry-flavored food and the essence for vanilla-flavored food, and stopping stirring after adding.
(4) And (3) volume fixing and mixing: adding purified water to a constant volume. Stirring and mixing evenly to obtain an intermediate product.
(5) Sampling and inspecting the intermediate product.
(6) Filtering and filling: filtering the medicinal liquid with polytetrafluoroethylene filter element, and filling into oral liquid medicinal polyester bottle.
(7) Packaging: labeling, boxing and boxing.
(8) And (5) inspecting and warehousing a finished product.
Example 2
The oral liquid preparation of ambroxol hydrochloride of the embodiment is prepared from the following raw materials in part by weight: the xanthan gum was replaced from 4g to 3g, and the remaining components and their weights were the same as in example 1.
The preparation method of the ambroxol hydrochloride oral solution in the embodiment is the same as that of the embodiment 1.
Example 3
The oral liquid preparation of ambroxol hydrochloride of the embodiment is prepared from the following raw materials in part by weight: the xanthan gum was replaced from 4g to 5g, and the remaining components and their weights were the same as in example 1.
The preparation method of the ambroxol hydrochloride oral solution in the embodiment is the same as that of the embodiment 1.
Comparative example 1
The comparative example is the original product of an ambroxol hydrochloride oral liquid preparation, and only the xanthan gum in the example 1 is replaced by hydroxyethyl cellulose, and the specific positions are as follows: ambroxol hydrochloride: 3g of the total weight of the mixture; hydroxyethyl cellulose: 4g of the total weight of the mixture; benzoic acid: 0.5g; sucralose: 1g of a compound; essence: 0.3g; purifying water: adding to 1000g;
the preparation method of the ambroxol hydrochloride oral solution of the embodiment is different from the embodiment 1 in that: (2) dissolving hydroxyethyl cellulose: and (3) stirring and dissolving the hydroxyethyl cellulose in the prescription amount by using purified water (more than 80 ℃), and adding the hydroxyethyl cellulose solution into a liquid preparation tank after complete dissolution. (6) filtering and filling: filtering the liquid medicine with stainless steel screen mesh, and filling into oral liquid medicinal polyester bottle. The other operation steps are the same as in example 1.
Experimental example 1
The parameters of (2) and (6) in the operation steps of example 1, example 2, example 3 and comparative example 1 were measured, and the experimental results are shown in tables 1 and 2.
TABLE 1
TABLE 2
As can be seen from table 1, compared with comparative example 1, the oral liquid formulations of ambroxol hydrochloride prepared in examples 1 to 3 only require normal temperature for dissolving xanthan gum, have shorter dissolving time, and have more obvious advantages in scale-up production. As can be seen from table 2, the comparative example 1 and examples 1 to 3 were consistent in quality after filtration for 0 day.
Experimental example 2
The oral liquid formulations of ambroxol hydrochloride prepared in example 1, example 2, example 3 and comparative example 1 were used as test samples, and the mass conditions under accelerated conditions (temperature 40 ℃, relative humidity 75%) were measured, and the experimental results are shown in tables 3 and 4.
TABLE 3
TABLE 4
As can be seen from tables 3 and 4, compared with comparative example 1, the oral liquid formulations of ambroxol hydrochloride prepared in examples 1 to 3 had stable product quality after accelerated 6-month examination, and each index had no significant change tendency compared with 0 day. The comparative example 1 is examined in 6 months, and each product has a more obvious change trend.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications derived therefrom are intended to be within the scope of the invention.
Claims (5)
1. The ambroxol hydrochloride oral solution is characterized by comprising the following components in parts by weight:
ambroxol hydrochloride: 0.2-0.4 weight parts;
xanthan gum: 0.3-0.5 weight part;
benzoic acid: 0.04-0.06 parts by weight;
sucralose: 0.08-0.12 weight part;
essence: 0.02-0.04 weight portion;
purifying water: add to 100 parts by volume.
2. The ambroxol hydrochloride oral solution according to claim 1, which is characterized in that the formulation comprises the following components in parts by weight:
ambroxol hydrochloride: 0.3 part by weight;
xanthan gum: 0.4 part by weight;
benzoic acid: 0.05 part by weight;
sucralose: 0.10 part by weight;
essence: 0.03 part by weight;
purifying water: add to 100 parts by volume.
3. Ambroxol hydrochloride oral solution according to any of claims 1-2, characterized in that the xanthan gum is 75 μm in size; when the unit of the weight part is g, the unit of the volume part is mL.
4. The ambroxol hydrochloride oral solution of claim 1, characterized in that in step (6), the polytetrafluoroethylene filter element is 5-30 μm.
5. The preparation method of the ambroxol hydrochloride oral solution is characterized by comprising the following steps: the preparation method comprises the following preparation processes:
1) Dissolving benzoic acid: adding purified water into the liquid preparation tank, wherein the water temperature is 30-40 ℃, and stirring to dissolve the benzoic acid according to the prescription amount;
2) Dissolving xanthan gum: stirring and dissolving the xanthan gum in the prescription amount by using normal-temperature purified water, and adding the xanthan gum solution into a liquid preparation tank after complete dissolution;
3) Preparation: when the temperature of the materials in the liquid preparation tank is less than or equal to 45 ℃, adding ambroxol hydrochloride with the prescription amount for complete dissolution, then adding sucralose with the prescription amount for complete dissolution, finally adding the essence for strawberry-flavored food and the essence for vanilla-flavored food, and stopping stirring after adding;
4) Volume fixing and mixing: adding purified water to a constant volume. Stirring and mixing evenly to obtain an intermediate product;
5) Sampling and inspecting the intermediate product;
6) Filtering and filling: filtering the medicinal liquid with a polytetrafluoroethylene filter element, and filling into a polyester bottle for oral liquid medicine;
7) Packaging: labeling, boxing and boxing;
8) And (5) inspecting and warehousing a finished product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN202211555639.7A CN115737552A (en) | 2022-12-06 | 2022-12-06 | Ambroxol hydrochloride oral solution and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202211555639.7A CN115737552A (en) | 2022-12-06 | 2022-12-06 | Ambroxol hydrochloride oral solution and preparation method thereof |
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| CN115737552A true CN115737552A (en) | 2023-03-07 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116350581A (en) * | 2023-03-16 | 2023-06-30 | 石家庄四药有限公司 | Acetylcysteine injection and preparation method thereof |
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- 2022-12-06 CN CN202211555639.7A patent/CN115737552A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116350581A (en) * | 2023-03-16 | 2023-06-30 | 石家庄四药有限公司 | Acetylcysteine injection and preparation method thereof |
| CN116350581B (en) * | 2023-03-16 | 2023-11-21 | 石家庄四药有限公司 | Preparation method of acetylcysteine injection |
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