Ambroxol hydrochloride oral solution and preparation process thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an ambroxol hydrochloride oral solution and a preparation process thereof, and the preparation process comprises the following steps: heating purified water to 60-80 DEG C, adding sorbitol and L-cysteine into the purified water, stirring and dissolving for 10-30 minutes, adding hydroxyethyl cellulose, uniformly dispersing, and cooling to 48-52 DEG C to obtain a first mixed solution; adding ambroxol hydrochloride, benzoic acid and glycerol into the first mixed solution, stirring until the ambroxol hydrochloride, benzoic acid and glycerol are completely dissolved, finally adding essence, and uniformly mixing; and finally, fixing the volume to a set volume by adopting purified water. According to the preparation method disclosed by the invention, through collaborative optimization of dual effects of L-cysteine and a specific feeding sequence, even if the content of sorbitol reducing sugar is greater than 0.3%, the content of an impurity B can still be controlled to be less than or equal to 0.3%, the content of an impurity F can still be controlled to be less than or equal to 0.2%, the deviation between the content of related substances and a reference preparation is less than or equal to + / -0.3%, and the stability is excellent.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of pharmaceutical preparations, and particularly relates to an ambroxol hydrochloride oral solution and a preparation process thereof. BACKGROUND

[0002] The statements herein are provided only to aid in the understanding of the present application, and do not necessarily constitute prior art.

[0003] Ambroxol hydrochloride, the chemical name of which is trans-4-[(2-amino-3,5-dibromobenzyl)amino]cyclohexanol hydrochloride (C 13 H 18 Br2N2O HCl, the molecular weight of which is 414.57, is an active metabolite of bromhexine, has a direct and rapid effect of expectorant; the structural formula is as follows: .

[0004] The prescription composition of the ambroxol hydrochloride oral solution reference preparation is benzoic acid, hydroxyethyl cellulose, sorbitol (containing 1225 mg of sorbitol in 5 ml of the oral solution), glycerol, acetylsulfamethoxazole potassium, essence and purified water. As a functional excipient that has an effect on drug absorption, if the content of the excipient in the prescription of the generic drug is similar to that of the reference preparation, the bioequivalence test can be exempted. However, sorbitol is prepared from starch or sucrose-derived glucose as raw material, and after hydrogenation reduction, there is inevitably residual reducing sugar (mainly glucose). However, sorbitol is prepared from starch or sucrose-derived glucose as raw material, and after hydrogenation reduction, there is inevitably residual reducing sugar (mainly glucose); on the one hand, the reducing sugar is easy to react with ambroxol hydrochloride to generate degradation impurity B which has definite toxicity, and on the other hand, the reducing sugar itself will undergo oxidative degradation to generate ambroxol cyclic imine (impurity F) which has potential cytotoxicity and organ toxicity, and long-term intake may cause damage to liver and kidney functions. Therefore, the compliance control of the related impurities is not only a prerequisite for the marketing of drugs, but also an important guarantee for reducing the risk of adverse reactions after the marketing of drugs.

[0005] The degradation pathways of impurity B and impurity F are as follows: .

[0006] In the prior art, in order to reduce the generation of the above impurities, a method of strictly controlling the reducing sugar content of sorbitol is generally adopted (for example, the Chinese Pharmacopoeia stipulates that the reducing sugar is ≤0.3%), but this method has significant disadvantages: first, the procurement cost of sorbitol raw materials with low reducing sugar content is relatively high, and the supply stability is insufficient, which seriously limits the flexibility of industrial production; second, even if the reducing sugar content in sorbitol is strictly controlled, it is still difficult to completely inhibit the generation of impurities B and F, resulting in significant differences in the content of related substances of the marketed product, and poor quality consistency with the reference preparation. SUMMARY

[0007] In view of the deficiencies in the prior art, the purpose of the present application is to provide a kind of ambroxol hydrochloride oral solution and its preparation process. The present application cooperatively inhibits the generation of impurities B and F by adding a specific antioxidant and optimizing the feeding sequence, so that the content of related substances of the product reaches the level comparable to the reference preparation, while improving the industrial feasibility of the process.

[0008] In order to achieve the above-mentioned purpose, the present application is realized by the following technical scheme: In a first aspect, the present application provides a kind of ambroxol hydrochloride oral solution, which comprises purified water, ambroxol hydrochloride, benzoic acid, hydroxyethyl cellulose, sorbitol, glycerol, essence and L-cysteine, wherein the mass percentage of L-cysteine is 0.1%-0.3%.

[0009] In a second aspect, the present application provides a preparation method of the ambroxol hydrochloride oral solution, comprising the following steps: Heat the purified water to 60-80℃, add sorbitol and L-cysteine to it, stir and dissolve for 10-30min, then add hydroxyethyl cellulose, disperse uniformly, and then cool to 48-52℃ to obtain a first mixture; Add ambroxol hydrochloride, benzoic acid and glycerol to the first mixture, stir until completely dissolved, then add essence, and mix evenly; finally, add purified water to the set volume, and the preparation is completed.

[0010] The beneficial effects achieved by one or more embodiments of the present application are as follows: The preparation method of the present application cooperatively optimizes the dual action of L-cysteine and the specific feeding sequence, so that even if the reducing sugar content of sorbitol is >0.3%, the content of impurity B can be controlled to ≤0.3%, the content of impurity F can be controlled to ≤0.2%, the deviation of related substances from the reference preparation is ≤±0.3%, and the stability is excellent (total impurities increase ≤0.3% in 6 months of accelerated testing); the generation of toxic impurities B and F is effectively controlled, the risk of clinical medication is reduced, the product quality is highly consistent with the reference preparation, and the effectiveness and safety of clinical medication are ensured.

[0011] The preparation method of this invention eliminates the need to control the sorbitol reducing sugar content (which can be >0.3%), significantly expanding the range of raw material selection, solving the problem of unstable supply of low-reducing-sugar sorbitol, greatly reducing raw material procurement costs, and improving the flexibility of industrial production. The optimized process does not require additional special equipment and can be achieved simply by selecting specific antioxidants and adjusting the feeding sequence. It is simple to operate, controllable, and suitable for large-scale industrial production. Attached Figure Description

[0012] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0013] Figure 1 This is a typical chromatogram of a solution suitable for a substance specificity test system. The elution order is as follows: 1. Impurity F; 2. Impurity B; 3. Ambroxol; 4. Impurity D; 5. Impurity E; 6. Impurity C.

[0014] Figure 2 This is a typical chromatogram of blank excipients for substance specificity tests. Detailed Implementation

[0015] It should be noted that the following detailed description is illustrative and intended to provide further explanation of the invention. Unless otherwise specified, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0016] In response to the technical problems mentioned in the background art, the present invention provides an ambroxol hydrochloride oral solution, comprising purified water, ambroxol hydrochloride, benzoic acid, hydroxyethyl cellulose, sorbitol, glycerin, flavoring and L-cysteine, wherein the mass percentage of L-cysteine ​​(as a percentage of the total weight of the prescription, with a relative density calculated at 1.000) is 0.1%-0.3%.

[0017] L-cysteine, a reducing antioxidant with an amphoteric structure, is selected. It inhibits impurity formation through a dual mechanism of action. It utilizes the nucleophilic addition of the aldehyde group (-CHO) of glucose to the amino group (-NH2) of L-cysteine ​​to form an unstable Schiff base, which then rapidly cyclizes to form non-toxic N-glucosylcysteine ​​(an imine intermediate). This blocks the reaction between reducing sugars and ambroxol hydrochloride at the source, reducing the formation of impurities B and F. In addition, L-cysteine ​​contains a unique thiol group (-SH, a strong nucleophilic group), which can further inhibit the self-reduction of sorbitol to produce new reducing sugars, while also preventing the levels of already formed impurities B and F. Through this dual synergistic effect, the levels of related substances in the product are stabilized, and even if the sorbitol reducing sugar content is >0.3%, impurities can still be effectively controlled.

[0018] When the L-cysteine ​​content is too low, it cannot react sufficiently with reducing sugars (e.g., the glucuronidation group is not completely blocked), leading to an increase in the formation of impurities B and F (ambroxolium imine).

[0019] Excessive L-cysteine ​​content may alter the pH of the solution and affect the stability of ambroxol hydrochloride. The sulfhydryl group (-SH) in L-cysteine ​​has a distinctive off-flavor, and excessive amounts can mask the flavor of fragrances (such as vanilla) and reduce the palatability of the product.

[0020] In some embodiments, the mass percentage of L-cysteine ​​in ambroxol hydrochloride oral solution is 0.15%-0.25%.

[0021] Preferably, the mass percentage of L-cysteine ​​in the ambroxol hydrochloride oral solution is 0.17%-0.22%.

[0022] More preferably, the mass percentage of L-cysteine ​​in the ambroxol hydrochloride oral solution is 0.19%-0.21%, specifically 0.2%.

[0023] In some embodiments, the flavoring is vanilla.

[0024] In some embodiments, the reducing sugar content in the sorbitol is >0.3%.

[0025] The reducing sugar content was determined using a modified gravimetric method: 10.0 g of sorbitol was dissolved in 35 ml of water, 50 ml of alkaline copper tartrate solution was added, a glass dish was covered, and the mixture was boiled for 4-6 minutes and maintained for 2 minutes. Immediately 100 ml of freshly boiled and cooled water was added, and the mixture was filtered through a sintered glass crucible at 105°C to constant weight. The precipitate was washed several times with 30 ml of hot water, and then washed with 10 ml each of ethanol and ether. The precipitate was dried at 105°C to constant weight. The weights of cuprous oxide were not more than 67 mg, 90 mg, and 112 mg, respectively (corresponding to reducing sugar contents of 0.3%, 0.4%, and ≤0.5%, respectively).

[0026] Secondly, the present invention provides a method for preparing the ambroxol hydrochloride oral solution, comprising the following steps: Heat purified water to 60-80℃, add sorbitol and L-cysteine, stir to dissolve for 10-30 minutes, then add hydroxyethyl cellulose, disperse evenly, and cool to 48-52℃ to obtain the first mixture; Add ambroxol hydrochloride, benzoic acid and glycerin to the first mixture, stir until completely dissolved, then add the fragrance and mix well; finally, use purified water to bring the volume to the set level to obtain the final product.

[0027] First, heat purified water to 60-80℃, then add sorbitol and L-cysteine ​​and stir for 15-25 minutes until completely dissolved. This temperature range significantly increases the nucleophilic addition rate between the amino group (-NH2) of L-cysteine ​​and the aldehyde group (-CHO) of residual reducing sugars (such as glucose) from sorbitol, rapidly generating a non-toxic Schiff base and subsequent cyclization products. This ensures that the reducing sugar is fully converted before contacting ambroxol hydrochloride, blocking the formation pathways of impurity B (the product of the reaction between reducing sugar and ambroxol) and impurity F (ambroxol cyclic imine) at the source. This order cannot be adjusted and is crucial for effectively controlling impurities even when the sorbitol reducing sugar content is >0.3%.

[0028] Temperatures of 60-80℃ can promote the rapid dissolution and uniform dispersion of sorbitol (solid excipient) and L-cysteine, avoiding incomplete reaction caused by insufficient local concentrations, and laying the foundation for the stability of subsequent process steps.

[0029] A temperature of 60-80℃ is conducive to the uniform dispersion of hydroxyethyl cellulose (a polymer), avoiding clumping caused by low temperature and ensuring the homogeneity of the subsequent solution system. First, allow sorbitol and L-cysteine ​​to react fully (10-30 min) to complete the blocking of reducing sugars (generating Schiff bases and other products), and then add hydroxyethyl cellulose to prevent its thickening effect from interfering with the mixing and reaction efficiency of the first two.

[0030] After dispersing hydroxyethyl cellulose, cooling it to 48-52℃ can prevent degradation caused by high temperature when adding active pharmaceutical ingredients such as ambroxol hydrochloride, thus ensuring the stability of the active pharmaceutical ingredient.

[0031] Flavorings are volatile, and if added in advance, they will lose their aroma during the initial high-temperature or long-term stirring process. Adding them at the end can preserve their flavor to the greatest extent.

[0032] In some embodiments, ambroxol hydrochloride, benzoic acid and glycerol are added to the first mixture and stirred for 20-40 minutes until completely dissolved.

[0033] In some embodiments, purified water is used to bring the volume to a set level, then the solution is cooled to room temperature and filled.

[0034] The present invention will be further described below with reference to the embodiments.

[0035] The impurities in ambroxol hydrochloride oral solution are shown in Table 1.

[0036] Table 1. Impurities in Ambroxol Hydrochloride Oral Solution

[0037] Information on the source of raw materials in the examples and comparative examples is shown in Table 2.

[0038] Table 2 Sources of raw and auxiliary materials

[0039] Note: (1) A indicates that the NMPA has approved the use of raw materials / excipients / packaging materials in marketed formulations; (2) *: Fragrances are excipients that are exempt from registration.

[0040] Example 1 Preparation of ambroxol hydrochloride oral solution (30mg / 5ml): 1. The prescription composition (2000ml) is shown in Table 3 and is filled into 100ml soda-lime glass molded medicine bottles.

[0041] Table 3 Prescription Composition

[0042] 2. A method for preparing ambroxol hydrochloride oral solution, comprising the following steps: (1) Take 1500ml of purified water, heat it to 70℃, add 490g of sorbitol (reducing sugar content 0.5%) and 4.0g of L-cysteine ​​and stir to dissolve. Stir for 20 minutes until completely dissolved. (2) Add 6.8g of hydroxyethyl cellulose, disperse evenly and continue stirring for 20 minutes, then turn on the cooling water to cool down to 50℃±2℃; (3) Add 12g ambroxol hydrochloride, 1.92g benzoic acid, and 255g glycerin (the order of adding the three materials is not restricted), stir for 30 minutes until completely dissolved, then add vanilla flavoring, stir for 5 minutes to mix evenly, add purified water to make up to 2000ml, cool to room temperature, and fill into 100ml bottles to obtain the product.

[0043] Example 2 Preparation of ambroxol hydrochloride oral solution (30mg / 5ml): 1. The prescription composition (2000ml) is shown in Table 4 and is filled into 100ml soda-lime glass molded medicine bottles.

[0044] Table 4 Prescription Composition

[0045] 2. A method for preparing ambroxol hydrochloride oral solution, comprising the following steps: (1) Take 1500ml of purified water, heat it to 60℃, add 490g of sorbitol (reducing sugar content 0.5%) and 3.0g of L-cysteine ​​and stir to dissolve. Stir for 20 minutes until completely dissolved. (2) Add 6.8g of hydroxyethyl cellulose, disperse evenly and continue stirring for 20 minutes, then turn on the cooling water to cool down to 50℃±2℃; (3) Add 12g ambroxol hydrochloride, 1.92g benzoic acid, and 255g glycerin (the order of adding the three materials is not restricted), stir for 30 minutes until completely dissolved, then add vanilla flavoring, stir for 5 minutes to mix evenly, add purified water to make up to 2000ml, cool to room temperature, and fill into 100ml bottles to obtain the product.

[0046] Example 3 Preparation of ambroxol hydrochloride oral solution (30mg / 5ml): 1. The prescription composition (2000ml) is shown in Table 5 and is filled into 100ml soda-lime glass molded medicine bottles.

[0047] Table 5 Prescription Composition

[0048] 2. A method for preparing ambroxol hydrochloride oral solution, comprising the following steps: (1) Take 1500ml of purified water, heat it to 80℃, add 490g of sorbitol (reducing sugar content 0.5%) and 5.0g of L-cysteine ​​and stir to dissolve. Stir for 20 minutes until completely dissolved. (2) Add 6.8g of hydroxyethyl cellulose, disperse evenly and continue stirring for 20 minutes, then turn on the cooling water to cool down to 50℃±2℃; (3) Add 12g ambroxol hydrochloride, 1.92g benzoic acid, and 255g glycerin (the order of adding the three materials is not restricted), stir for 30 minutes until completely dissolved, then add vanilla flavoring, stir for 5 minutes to mix evenly, add purified water to make up to 2000ml, cool to room temperature, and fill into 100ml bottles to obtain the product.

[0049] Example 4 The difference from Example 1 is that the reducing sugar content in sorbitol is 0.4%, while all other aspects are the same as in Example 1.

[0050] Example 5 The difference from Example 1 is that the reducing sugar content in sorbitol is 0.3%, while all other aspects are the same as in Example 1.

[0051] Comparative Example 1 Preparation of ambroxol hydrochloride oral solution (30mg / 5ml): Sorbitol with a reducing sugar content of 0.5% was selected, and L-cysteine ​​was not added. Other formulations and preparation steps were the same as in Example 1.

[0052] Comparative Example 2 Preparation of ambroxol hydrochloride oral solution (30mg / 5ml): The sorbitol reducing sugar content is 0.5%, L-cysteine ​​is added but the order of feeding is adjusted, and other formulations are the same as in Example 1.

[0053] The specific preparation method is as follows: (1) Take 1500ml of purified water, heat it to 70℃, add 490g of sorbitol (reducing sugar content 0.5%), and stir for 20 minutes until completely dissolved; (2) Add 6.8g of hydroxyethyl cellulose, disperse evenly and continue stirring for 20 minutes, then add 4.0g of L-cysteine ​​and stir to dissolve. Turn on the cooling water to cool down to 50℃±2℃; Step (3) is the same as in Example 1.

[0054] Comparative Example 3 Preparation of ambroxol hydrochloride oral solution (30mg / 5ml): The sorbitol reducing sugar content is 0.5%, L-cysteine ​​is added but the order of feeding is adjusted, and other formulations are the same as in Example 1.

[0055] The specific preparation method is as follows: (1) Take 1500ml of purified water, heat it to 70℃, add 6.8g of hydroxyethyl cellulose, disperse it evenly and continue stirring for 20 minutes; (2) Then add 490g of sorbitol and 4.0g of L-cysteine ​​and stir to dissolve. Stir for 20 minutes until completely dissolved, then turn on the cooling water to cool down to 50℃±2℃. Step (3) is the same as in Example 1.

[0056] Comparative Example 4 Preparation of ambroxol hydrochloride oral solution (30mg / 5ml): The sorbitol reducing sugar content is 0.3%, and L-cysteine ​​is not added. Other formulations and preparation steps are the same as in Example 1.

[0057] Comparative Example 5 Preparation of ambroxol hydrochloride oral solution (30mg / 5ml): The sorbitol reducing sugar content is 0.5%, and sodium bisulfite is used to replace L-cysteine. Other formulations and preparation steps are the same as in Example 1.

[0058] Comparative Example 6 Preparation of ambroxol hydrochloride oral solution (30mg / 5ml): The sorbitol reducing sugar content is 0.5%, and vitamin C is used to replace L-cysteine. Other formulations and preparation steps are the same as in Example 1.

[0059] Comparative Example 7 Preparation of ambroxol hydrochloride oral solution (30mg / 5ml): The sorbitol reducing sugar content is 0.5%, and sodium metabisulfite is used to replace L-cysteine. Other formulations and preparation steps are the same as in Example 1.

[0060] Comparative Example 8 Preparation of ambroxol hydrochloride oral solution (30mg / 5ml): The sorbitol reducing sugar content is 0.5%, and sodium thiosulfate is used to replace L-cysteine. Other formulations and preparation steps are the same as in Example 1.

[0061] Comparative Example 9 Preparation of ambroxol hydrochloride oral solution (30mg / 5ml): Simultaneous comparison of related substances in batch B94833 of the reference formulation of ambroxol produced by the certified manufacturer Sanofi-Aventis Deutschland GmbH.

[0062] Performance tests: The accelerated testing involved placing the filled samples in an experimental chamber at a temperature of 40℃±2℃ and a relative humidity of 75%±5%, and then taking samples for testing after 6 months.

[0063] Methods for detecting reducing sugars: Dissolve 10.0 g of sorbitol in 35 ml of water, add 50 ml of alkaline copper tartrate solution, cover with a glass dish, boil for 4-6 minutes and maintain for 2 minutes, immediately add 100 ml of freshly boiled and cooled water, filter through a sintered glass crucible at 105 °C to constant weight, wash with 30 ml of hot water in portions, then wash the precipitate with 10 ml each of ethanol and ether, and dry at 105 °C to constant weight. The weights of cuprous oxide 67 mg, 90 mg, and 112 mg correspond to reducing sugar contents of 0.3%, 0.4%, and ≤0.5%, respectively.

[0064] Related substances detection methods: Solvent: Take an appropriate amount of 0.01 mol / L diammonium hydrogen phosphate solution (adjust the pH value to 7.0 with phosphoric acid) and acetonitrile (60:40).

[0065] System suitability solution: Take appropriate amounts of impurity A, impurity B, impurity C, impurity D, impurity E, impurity F reference standards and ambroxol hydrochloride reference standard, dissolve and dilute with solvent to prepare a mixed solution containing 2.4 μg of each impurity and about 1.2 mg of ambroxol hydrochloride per 1 ml, and shake well.

[0066] Blank excipient solution: Accurately measure 5 ml of blank excipient, place it in a 25 ml volumetric flask, dilute to the mark with solvent, shake well, filter, and collect the filtrate.

[0067] The assay was performed using high-performance liquid chromatography (HPLC) under the following chromatographic conditions: Chromatographic column: C8 column (Agilent ZORBAX SB-C8, 4.6 mm × 250 mm, 5 μm) with octylsilane-bonded silica gel as the packing material. Mobile phases: Phase A is acetonitrile-0.01 mol / L diammonium hydrogen phosphate solution (pH adjusted to 8.0 with ammonia or phosphoric acid) (20:80), and Phase B is acetonitrile-0.01 mol / L diammonium hydrogen phosphate solution (pH adjusted to 8.0 with ammonia or phosphoric acid) (80:20).

[0068] The gradient elution procedure is shown in Table 4.

[0069] Table 6 Gradient elution program

[0070] Detection wavelength: 248nm; Flow rate: 1.0 ml / min; Column temperature: 30℃; Injection volume: 10 μl.

[0071] Typical chromatograms of solutions for the suitability of the substance specificity testing system are shown below. Figure 1 As shown, the elution order is impurity F, impurity B, ambroxol, impurity D, impurity E, and impurity C.

[0072] Typical chromatograms of blank excipients in the specificity test of related substances, such as Figure 2 As shown.

[0073] Under these conditions, impurity F (retention time approximately 8.6 min) and the main components of the excipients (retention time approximately 6.8 min) achieve baseline separation with a resolution ≥1.5, enabling precise quantification of impurity F.

[0074] Product quality evaluation indicators: Using the content of related substances as the core evaluation indicator, the product must meet the following requirements: impurity B content ≤ 0.3%, impurity F content ≤ 0.2%, the deviation of the content of related substances (including impurities A, B, D, E, F, other single impurities and total impurities) from the reference preparation (Mucosolvan) ≤ ±0.2%, and the total impurity growth ≤ 0.3% after 6 months of accelerated testing. The above-mentioned related substance content can be evaluated by conventional high-performance liquid chromatography (HPLC).

[0075] Table 7 Measurement Results - Day 0

[0076] Table 8. Measurement Results - Accelerated June

[0077] Results analysis: Example 1 uses sorbitol with a reducing sugar content of 0.5% (>0.3%). By adding L-cysteine ​​and optimizing the feeding sequence, the content of related substances at day 0 and accelerated 6 months deviates from the reference preparation (Comparative Example 9) by ≤±0.3%. Impurities B and F are both controlled within the limits, and the total impurity growth meets the requirements.

[0078] The related substance content of Comparative Example 1 (without L-cysteine), Comparative Example 2 (incorrect feeding sequence), and Comparative Example 4 (other antioxidants substituted) significantly exceeded the standard and deviated greatly from the reference formulation. This proves that the core innovation of this invention - the addition of a specific antioxidant (L-cysteine) and the optimization of the feeding sequence - is the key to achieving unlimited sorbitol reducing sugar content (>0.3%) and product quality comparable to the reference formulation.

[0079] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. An oral solution of ambroxol hydrochloride, characterized in that: These include purified water, ambroxol hydrochloride, benzoic acid, hydroxyethyl cellulose, sorbitol, glycerin, flavoring, and L-cysteine, wherein the mass percentage of L-cysteine ​​is 0.1%-0.3%.

2. The ambroxol hydrochloride oral solution according to claim 1, characterized in that: In ambroxol hydrochloride oral solution, the mass percentage of L-cysteine ​​is 0.15%-0.25%.

3. The ambroxol hydrochloride oral solution according to claim 2, characterized in that: In ambroxol hydrochloride oral solution, the mass percentage of L-cysteine ​​is 0.17%-0.22%.

4. The ambroxol hydrochloride oral solution according to claim 3, characterized in that: In ambroxol hydrochloride oral solution, the mass percentage of L-cysteine ​​is 0.19%-0.21%.

5. The ambroxol hydrochloride oral solution according to claim 4, characterized in that: The mass percentage of L-cysteine ​​in ambroxol hydrochloride oral solution is 0.2%.

6. The ambroxol hydrochloride oral solution according to claim 1, characterized in that: The flavoring is vanilla.

7. The ambroxol hydrochloride oral solution according to claim 1, characterized in that: The reducing sugar content in the sorbitol is >0.3%.

8. The method for preparing the ambroxol hydrochloride oral solution according to any one of claims 1-7, characterized in that: Includes the following steps: Heat purified water to 60-80℃, add sorbitol and L-cysteine, stir to dissolve for 10-30 minutes, then add hydroxyethyl cellulose, disperse evenly, and cool to 48-52℃ to obtain the first mixture; Add ambroxol hydrochloride, benzoic acid and glycerin to the first mixture, stir until completely dissolved, then add the fragrance and mix well; finally, use purified water to bring the volume to the set level to obtain the final product.

9. The method for preparing ambroxol hydrochloride oral solution according to claim 8, characterized in that: Add ambroxol hydrochloride, benzoic acid and glycerin to the first mixture and stir for 20-40 minutes until completely dissolved.

10. The method for preparing ambroxol hydrochloride oral solution according to claim 8, characterized in that: After bringing the volume to the set level with purified water, cool to room temperature and fill.

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