Ambroxol hydrochloride oral solution and preparation method thereof

Abstract

The invention relates to an ambroxol hydrochloride oral solution which is prepared from the following raw and auxiliary materials in parts by weight: 0.3-0.6 part of ambroxol hydrochloride; 0.04 to 0.06 part by weight of benzoic acid; 0.3 to 0.6 part by weight of hydroxyethyl cellulose; 0.08 to 0.2 part by weight of sucralose; 0.15 to 0.4 part by weight of essence; and the balance of purified water. The preparation method comprises the following steps: S1, adding a base solution; S2, adding ingredients; and S3, filtering. The preparation method comprises the following steps: S1, hydroxyethyl cellulose pretreatment; S2, mixing; S3, seasoning; and S4, packaging. The invention provides an ambroxol hydrochloride oral solution and a preparation method thereof. The ambroxol hydrochloride oral solution is good in taste, high in stability and high in patient compliance. And the production process is simple, stable, controllable and easy to industrialize.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to an ambroxol hydrochloride oral solution and a preparation method thereof. Background Art

[0002] The active ingredient of ambroxol hydrochloride oral solution, "ambroxol hydrochloride", its predecessor bromhexine is extracted from cyperine. Cyperine comes from an Asian plant and has been proven to be very effective in expectoration. It can loosen and thin the sputum accumulated in the respiratory tract, prevent the production of new mucus, and thus improve the cleansing function of the respiratory tract. More specifically, it can increase the secretion of serous glands in the respiratory mucosa and reduce the secretion of mucous glands, thereby reducing sputum viscosity, promoting the secretion of alveolar surfactant, and increasing bronchial ciliary movement, making sputum easier to cough up, achieving the effect of relieving cough symptoms.

[0003] The dosage forms of ambroxol hydrochloride currently available in China include injection, sterile powder for injection, spray, tablets, capsules, pills, drops, granules, syrup and oral solution. Among them, the oral solution is favored by doctors and patients because the drug is dispersed in the medium in molecular form, with a large dispersion, rapid absorption, easy to take, and can quickly exert therapeutic effects. Summary of the invention

[0004] In view of the deficiencies of the prior art, an ambroxol hydrochloride oral solution is provided, which has good taste, high stability and strong patient compliance; and the production process is simple, stable and controllable, and easy to industrialize.

[0005] The present invention is achieved through the following technical solutions:

[0006] An ambroxol hydrochloride oral solution is composed of the following raw materials and auxiliary materials in parts by weight:

[0007] Ambroxol hydrochloride: 0.3-0.6 weight part; benzoic acid: 0.04-0.06 weight part; hydroxyethyl cellulose: 0.3-0.6 weight part; sucralose: 0.08-0.2 weight part; flavor: 0.15-0.4 weight part; the balance is purified water.

[0008] Preferably, it is composed of the following raw materials by weight:

[0009] Ambroxol hydrochloride: 0.6 parts by weight; benzoic acid: 0.05 parts by weight; hydroxyethyl cellulose: 0.4 parts by weight; sucralose: 0.126 parts by weight; flavor: 0.2 parts by weight; the balance is purified water.

[0010] Preferably, it is composed of the following raw materials by weight:

[0011] Ambroxol hydrochloride: 0.3 parts by weight; benzoic acid: 0.05 parts by weight; hydroxyethyl cellulose: 0.4 parts by weight; sucralose: 0.1 parts by weight; essence: 0.2 parts by weight; the balance is purified water.

[0012] Preferably, the benzoic acid is a preservative, hydroxyethyl cellulose is a thickener, sucralose is a sweetener, and the flavor is a flavoring agent.

[0013] A preparation method of ambroxol hydrochloride oral solution comprises the following steps:

[0014] S1: pretreatment of hydroxyethyl cellulose: take purified water, slowly add hydroxyethyl cellulose under stirring, and then stir and disperse, heat and self-circulate through a colloid mill, and stir in a tank to obtain a hydroxyethyl cellulose pretreatment solution;

[0015] S2: Mixing, taking purified water, heating it, adding benzoic acid, ambroxol hydrochloride, and sucralose, stirring to dissolve, and then adding the hydroxyethyl cellulose pretreatment solution obtained in step S1, and stirring to mix;

[0016] S3: seasoning, stop heating, cool to below 30°C, add the prescribed amount of essence, stir evenly, and obtain ambroxol hydrochloride solution;

[0017] S4: packaging, filtering, filling, and capping the ambroxol hydrochloride solution obtained in step S3, and sealing the bottle using an electromagnetic induction sealing machine.

[0018] In order to further realize the present invention, the following technical solutions may be preferably selected:

[0019] Preferably, the amount of purified water in step S1 is 30% to 50% of the total amount of purified water, the addition time of hydroxyethyl cellulose is controlled within 10 to 30 minutes, the heating temperature is 50° C. to 60° C., and the colloid mill is stirred for 50 to 100 minutes after self-circulation for 20 to 30 minutes.

[0020] Preferably, after the hydroxyethyl cellulose pretreatment solution is added in step S2, the storage tank in step S1 is rinsed with purified water, and the rinse water is pumped through a colloid mill into the preparation tank in step S2 for stirring and mixing.

[0021] Preferably, in step S2, the amount of purified water used is 20% to 40% of the total amount of purified water, and the heating temperature is 50° C. to 60° C.

[0022] Preferably, in step S4, a 50 μm titanium rod and a 30 μm polypropylene filter element are used for filtration.

[0023] Through the above technical solution, the beneficial effects of the present invention are:

[0024] The ambroxol hydrochloride oral solution provided by the invention has good taste, high stability and strong patient compliance; and the preparation method thereof has simple production process, is stable and controllable and is easy to industrialize. DETAILED DESCRIPTION

[0025] In the description of the present invention, it is also necessary to explain that, unless otherwise clearly specified and limited, the terms "set", "install", "connect", and "connect" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0026] The following will be combined with the embodiments of the invention to clearly and completely describe the technical solutions in the embodiments of the invention. Obviously, the described embodiments are only part of the embodiments of the invention, not all of the embodiments. Based on the embodiments of the invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the invention.

[0027] Embodiment 1:

[0028] An ambroxol hydrochloride oral solution is composed of the following raw materials and auxiliary materials:

[0029] 0.6g of ambroxol hydrochloride, 0.05g of benzoic acid, 0.4g of hydroxyethyl cellulose, 0.126g of sucralose, 0.1g of strawberry flavor, 0.1g of vanilla flavor, and 1000ml of purified water.

[0030] Among them, benzoic acid is a preservative, hydroxyethyl cellulose is a thickener, sucralose is a sweetener, and flavor is a flavoring agent.

[0031] The following preparation method is adopted, and the specific steps are as follows:

[0032] 1) Pretreatment of hydroxyethyl cellulose: 40% purified water was taken, and 0.4 g of hydroxyethyl cellulose was slowly added under stirring and dispersed for 30 minutes. The mixture was heated to 60° C. and passed through a colloid mill for self-circulation for 20 minutes, and then stirred for 70 minutes for use.

[0033] 2) Take another 30% purified water, heat it to 60°C, add 0.05g benzoic acid, 0.3g ambroxol hydrochloride, and 0.1g sucralose, stir and dissolve, then pump the solution obtained in step 1) into the preparation tank of step 2) through a colloid mill, rinse the storage tank of step 1) with 8% purified water, and pump the rinse water into the preparation tank of step 2) through a colloid mill and stir to mix.

[0034] 3) Stop heating, cool to below 30°C, add the prescribed amount of flavor and stir evenly.

[0035] 4) The solution obtained in step 3) is filtered through a 50 μm titanium rod and a 30 μm polypropylene filter element, filled with a specified filling volume of 102 to 106 ml per bottle, capped, and sealed using an electromagnetic induction sealing machine.

[0036] Embodiment 2:

[0037] The difference from Example 1 is that the dosage of the raw material and sucralose is different. An ambroxol hydrochloride oral solution is specifically composed of the following raw materials and auxiliary materials: 0.3g ambroxol hydrochloride, 0.05g benzoic acid, 0.4g hydroxyethyl cellulose, 0.1g sucralose, 0.1g strawberry flavor, 0.1g vanilla flavor, and 1000ml purified water.

[0038] Embodiment 3:

[0039] The difference from Example 1 is that the amount of flavor is different. An ambroxol hydrochloride oral solution is specifically composed of the following raw materials and auxiliary materials: 0.6g ambroxol hydrochloride, 0.05g benzoic acid, 0.4g hydroxyethyl cellulose, 0.126g sucralose, 0.15g strawberry flavor, 0.1g vanilla flavor, and 1000ml purified water.

[0040] Embodiment 4:

[0041] The difference from Example 1 is that the amount of flavor is different. An ambroxol hydrochloride oral solution is specifically composed of the following raw materials and auxiliary materials: 0.6g ambroxol hydrochloride, 0.05g benzoic acid, 0.4g hydroxyethyl cellulose, 0.126g sucralose, 0.15g strawberry flavor, 0.05g vanilla flavor, and 1000ml purified water.

[0042] Embodiment 5:

[0043] The difference from Example 1 is that the amount of flavor is different. An ambroxol hydrochloride oral solution is specifically composed of the following raw materials and auxiliary materials: 0.6g ambroxol hydrochloride, 0.05g benzoic acid, 0.4g hydroxyethyl cellulose, 0.126g sucralose, 0.1g strawberry flavor, 0.05g vanilla flavor, and 1000ml purified water.

[0044] Embodiment 6:

[0045] The difference from Example 1 is that the amount of flavor is different. An ambroxol hydrochloride oral solution is specifically composed of the following raw materials and auxiliary materials: 0.6g ambroxol hydrochloride, 0.05g benzoic acid, 0.4g hydroxyethyl cellulose, 0.126g sucralose, 0.1g strawberry flavor, 0.15g vanilla flavor, and 1000ml purified water.

[0046] Embodiment 7:

[0047] The difference from Example 1 is that the amount of flavor is different. An ambroxol hydrochloride oral solution is specifically composed of the following raw materials and auxiliary materials: 0.6g ambroxol hydrochloride, 0.05g benzoic acid, 0.4g hydroxyethyl cellulose, 0.126g sucralose, 0.05g strawberry flavor, 0.1g vanilla flavor, and 1000ml purified water.

[0048] Embodiment 8:

[0049] The difference from Example 1 is that the amount of flavor is different. An ambroxol hydrochloride oral solution is specifically composed of the following raw materials and auxiliary materials: 0.6g ambroxol hydrochloride, 0.05g benzoic acid, 0.4g hydroxyethyl cellulose, 0.126g sucralose, 0.05g strawberry flavor, 0.15g vanilla flavor, and 1000ml purified water.

[0050] Example 9: Taste Evaluation

[0051] Evaluation method:

[0052] Table 1 Evaluation criteria:

[0053]

[0054]

[0055] Table 2 Evaluation results:

[0056] Example Strawberry flavor g / L Vanilla essence g / L Smell score Taste score Example 1 0.1 0.1 2.9 2.6 Example 3 0.15 0.1 1.9 2.3 Example 4 0.15 0.05 1.8 1.7 Example 5 0.1 0.05 1.7 1.9 Example 6 0.1 0.15 2.3 2.3 Example 7 0.05 0.1 2.5 2.4 Example 8 0.05 0.15 1.9 2.0

[0057] Example 10: Stability Evaluation

[0058] In order to further confirm the quality of the oral solution product of the present invention, the inventors studied the stability of Example 1 and Example 2 of the present invention, including the stability study of the oral solution under light, high temperature, low temperature freeze-thaw and accelerated conditions.

[0059] Table 3 Preparation quality test results of Example 1

[0060]

[0061]

[0062]

[0063]

[0064] Table 4 Preparation quality test results of Example 2

[0065]

[0066]

[0067]

[0068] The test results and taste evaluations of the above examples indicate that the formulation of the present invention has a good taste and high stability, indicating that the quality of the product can be effectively guaranteed under the formulation and process conditions and can meet the requirements of large-scale production.

[0069] Finally, it should be noted that the above are only preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, it is still possible for those skilled in the art to modify the technical solutions described in the aforementioned embodiments, or to make equivalent substitutions for some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An ambroxol hydrochloride oral solution, characterized in that, It is composed of the following raw materials by weight: Ambroxol hydrochloride: 0.3-0.6 weight part; benzoic acid: 0.04-0.06 weight part; hydroxyethyl cellulose: 0.3-0.6 weight part; sucralose: 0.08-0.2 weight part; flavor: 0.15-0.4 weight part; the balance is purified water.

2. A kind of ambroxol hydrochloride oral solution according to claim 1, characterized in that, It is composed of the following raw materials by weight: Ambroxol hydrochloride: 0.6 parts by weight; benzoic acid: 0.05 parts by weight; hydroxyethyl cellulose: 0.4 parts by weight; sucralose: 0.126 parts by weight; flavor: 0.2 parts by weight; the balance is purified water.

3. A kind of ambroxol hydrochloride oral solution according to claim 1, characterized in that, It is composed of the following raw materials by weight: Ambroxol hydrochloride: 0.3 parts by weight; benzoic acid: 0.05 parts by weight; hydroxyethyl cellulose: 0.4 parts by weight; sucralose: 0.1 parts by weight; essence: 0.2 parts by weight; the balance is purified water.

4. An ambroxol hydrochloride oral solution according to any one of claims 1 to 3, characterized in that: The benzoic acid is a preservative, the hydroxyethyl cellulose is a thickener, the sucralose is a sweetener, and the essence is a flavoring agent.

5. A method for preparing an ambroxol hydrochloride oral solution, characterized in that: The following steps are involved: S1: pretreatment of hydroxyethyl cellulose: take purified water, slowly add hydroxyethyl cellulose under stirring, and then stir and disperse, heat and self-circulate through a colloid mill, and stir in a tank to obtain a hydroxyethyl cellulose pretreatment solution; S2: Mixing, taking purified water, heating it, adding benzoic acid, ambroxol hydrochloride, and sucralose, stirring to dissolve, and then adding the hydroxyethyl cellulose pretreatment solution obtained in step S1, and stirring to mix; S3: seasoning, stop heating, cool to below 30°C, add the prescribed amount of essence, stir evenly, and obtain ambroxol hydrochloride solution; S4: packaging, filtering, filling, and capping the ambroxol hydrochloride solution obtained in step S3, and sealing the bottle using an electromagnetic induction sealing machine.

6. The method for preparing an ambroxol hydrochloride oral solution according to claim 5, wherein: In step S1, the amount of purified water used is 30% to 50% of the total amount of purified water, the addition time of hydroxyethyl cellulose is controlled within 10 to 30 minutes, the heating temperature is 50° C. to 60° C., and the colloid mill is self-circulated for 20 to 30 minutes and then stirred for 50 to 100 minutes.

7. The method for preparing an ambroxol hydrochloride oral solution according to claim 6, wherein: After the hydroxyethyl cellulose pretreatment solution is added in step S2, the storage tank in step S1 is rinsed with purified water, and the rinse water is pumped through a colloid mill into the preparation tank in step S2 for stirring and mixing.

8. The method for preparing an ambroxol hydrochloride oral solution according to claim 7, wherein: In step S2, the amount of purified water used is 20% to 40% of the total amount of purified water, and the heating temperature is 50° C. to 60° C.

9. The method for preparing an ambroxol hydrochloride oral solution according to claim 5, wherein: In the step S4, a 50 μm titanium rod and a 30 μm polypropylene filter element are used for filtration.

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