Ambroxol orally disintegrating film composition, method of preparation and use thereof

Abstract

The application provides an ambroxol oral dissolving film composition, a preparation method and application thereof. The ambroxol oral dissolving film composition comprises an active drug, a film forming material and a taste masking agent, and the active drug is 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) benzylamine and / or a pharmaceutically acceptable salt thereof, for example, ambroxol hydrochloride. The ambroxol oral dissolving film composition provided by the application has the advantages of thin thickness, good taste, stable properties, immediate dissolution in the oral cavity without drinking water, and fast oral absorption speed. Moreover, the ambroxol oral dissolving film composition has the advantages of simple process, high drug loading, good drug content uniformity, and good market prospect.

Description

[0001] This application claims priority to the prior application filed on November 14, 2022, with the China National Intellectual Property Office, and with the patent application number 202211420255.4, and with the invention name "Ambroxol Hydrochloride Orally Disintegrating Film Composition, Its Preparation Method and Application". The entire contents of this application are incorporated herein by reference. TECHNICAL FIELD

[0002] The present application relates to an ambroxol hydrochloride orally disintegrating film composition, its preparation method and application. BACKGROUND

[0003] Ambroxol Hydrochloride is the active metabolite of mucolytic drug bromhexine, with lower toxicity than bromhexine and higher activity than bromhexine. Ambroxol Hydrochloride is a mucolytic agent developed by Boehringer Ingelheim Company in Germany. The drug was first marketed in Germany in the early 1980s, and then in France, Italy, Japan, Spain and many other countries. It is a new generation of mucolytic agent that can improve sputum discharge and has the effect of promoting lung surfactant and airway secretion and ciliary movement. In clinical practice, it can regulate mucus and mucous secretion, activate ciliary oscillation, easily dilute sputum, strengthen the outward transport of mucus, and easily discharge it. It can also promote the synthesis of lung surfactant to maintain alveolar tension and ensure lung function indicators; promote the penetration of antibiotics into tissues to increase the concentration and enhance the bactericidal effect; antioxidant, reduce the release of inflammatory mediators to reduce inflammatory response; and synergize with bronchial antispasmodic substances to improve the efficacy of antispasmodic drugs. Therefore, the drug can be widely used in clinical practice for the treatment of acute and chronic respiratory diseases associated with abnormal respiratory tract secretion, especially for the treatment of chronic bronchitis, and as an adjunctive therapy for neonatal respiratory distress syndrome and lung surgery, with low toxicity, definite efficacy, and good synergistic effect with antibiotics. It is one of the most commonly used mucolytic drugs.

[0004] Currently, the original research company has marketed injection, tablet, sustained-release capsule and oral solution in China. The drug has passed the approval procedures in the following countries: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the Netherlands.

[0005] In addition, there are injection, oral solution, syrup, granules, ordinary tablets, capsules, sustained-release tablets, sustained-release capsules, orally disintegrating tablets, dispersible tablets, chewable tablets and other generic drugs on the market.

[0006] Ambroxol is very popular among clinicians due to its very significant expectorant effect, and its injection is widely used for aerosol therapy (off-label use) in patients with respiratory diseases. However, in fact, the weakly acidic ambroxol injection itself can stimulate the airway after aerosolization, leading to airway spasm and causing breathing difficulties, which is more obvious in COPD patients. In addition, the injection prepared with normal saline may have the risk of lung infection or induce asthma exacerbation after aerosol inhalation, in terms of both aerosol particle diameter and excipients (including preservatives). However, in 2019, the marketing application of ambroxol hydrochloride solution for inhalation (JXHS1700033) submitted by Korea and the United States as a new drug of Category 5.2 (the reason for "drug for children" was given priority for evaluation) was approved by the National Medical Products Administration, which is also aimed at the pain point that pediatric patients need to use ambroxol in large quantities but the existing dosage forms cannot meet the clinical needs.

[0007] In China, ambroxol oral preparations are all over-the-counter drugs (OTC), and are one of the best-selling drugs for the respiratory system, with a wide range of users, especially infants and children. However, the use of such products in infants is controversial internationally. Many institutions are concerned about whether it is appropriate for children under 6 years old to use ambroxol as an expectorant, and believe that the benefits of such drugs to this patient population are not greater than the risks.

[0008] Ambroxol ordinary tablets and sustained-release capsules need to be taken with water and by swallowing action, and the compliance of this dosage form is poor for some elderly people, children, and patients with difficulty in swallowing, and its use is restricted in some special conditions (such as lack of drinking water) or is poor in effect. The injection has safety hazards and poor patient compliance. Although the oral solution has a good taste, it has the disadvantages of large dosage, difficulty in quantification, poor stability, and high requirements for production process and packaging, which brings many inconveniences and safety factors to patients in terms of taking, carrying, and transporting.

[0009] Ambroxol hydrochloride is slightly soluble in water, and has a bitter and numb taste, with a long-lasting aftertaste and numbness, which cannot be masked by adding conventional solubilizers and flavoring agents, resulting in poor patient compliance, especially for children. Patent document CN102846581A discloses ambroxol hydrochloride oral film, but experiments have found that the ambroxol hydrochloride oral film prepared according to the prescription has poor mechanical strength, poor stability, slow disintegration, and complex preparation process, which is not conducive to commercial production.

[0010] Therefore, there is an urgent need to develop an ambroxol hydrochloride pharmaceutical preparation with good stability, good taste, and good patient compliance. SUMMARY

[0011] In order to overcome the defects of poor taste, poor stability and / or poor patient compliance of the existing technology of ambroxol hydrochloride oral dissolving film, the present application provides an ambroxol hydrochloride oral dissolving film composition, a preparation method and application thereof. The ambroxol hydrochloride oral dissolving film composition provided by the present application has the advantages of thin thickness, good taste, stable properties, stable mechanical properties, immediate dissolution in the oral cavity without the need for drinking water, fast oral absorption speed, simple process, high drug loading, good drug content uniformity and good market prospect.

[0012] The present application provides an ambroxol oral dissolving film composition, which comprises an active drug, a film-forming material and a taste masking agent, wherein the active drug comprises 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) benzylamine (also known as ambroxol) or a pharmaceutically acceptable salt thereof, such as the hydrochloride salt of 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl) benzylamine (also known as ambroxol hydrochloride), as shown in Formula I.

[0013]

[0014] According to an embodiment of the present application, the ambroxol oral dissolving film composition described in the present application can be an ambroxol hydrochloride oral dissolving film composition.

[0015] According to an embodiment of the present application, the ambroxol oral dissolving film composition (such as the ambroxol hydrochloride oral dissolving film composition) described in the present application preferably does not contain a pH adjusting agent.

[0016] According to an embodiment of the present application, the ambroxol oral dissolving film composition (such as the ambroxol hydrochloride oral dissolving film composition) described in the present application preferably does not contain a free pH adjusting agent. The free pH adjusting agent refers to a pH adjusting agent that is not in the form of a salt with the active drug.

[0017] According to an embodiment of the present application, the pH adjusting agent includes, but is not limited to, pharmaceutically acceptable acids known in the art for adjusting pH, such as organic acids, inorganic acids, organic bases and inorganic bases. The above-mentioned inorganic acids include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; the above-mentioned organic acids include, for example, acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid (citric acid), benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, sulfosalicylic acid, formic acid, trifluoroacetic acid and the like.

[0018] According to an embodiment of the present application, the ambroxol oral dissolving film composition (such as the ambroxol hydrochloride oral dissolving film composition) described in the present application does not contain a basic pH adjusting agent, such as a pharmaceutically acceptable base known in the art for adjusting pH.

[0019] According to embodiments of the present application, the active pharmaceutical agent is present in an amount of 1.00% to 40.00%, preferably 5.00% to 30.00%, such as 5.00%, 6.00%, 7.00%, 8.00%, 9.00%, 9.09%, 10.00%, 12.45%, 15.00%, 15.23%, 16.48%, 19.23%, 19.48%, 20.00%, 21.43%, 25.00%, or 30.00%, wherein the amount is the weight of the active pharmaceutical agent relative to the total weight of the ambroxol orodispersible film composition (e.g., ambroxol hydrochloride orodispersible film composition).

[0020] According to embodiments of the present application, the taste-masking agent is a substance that masks bitter and pungent tastes, and can be selected from the group consisting of cation exchange resins, such as one, two, or three of sodium polystyrene sulfonate, potassium polacrillin potassium, and polacrilin resin.

[0021] Preferably, the cation exchange resin has a particle size D90 of less than 200 μm.

[0022] Preferably, the taste-masking agent is present in an amount of 10.00% to 70.00%, further preferably 15.00% to 60.00%, such as 10.00%, 12.00%, 15.00%, 19.48%, 20.00%, 21.43%, 24.90%, 25.00%, 30.00%, 30.30%, 38.06%, 38.46%, 40.00%, 41.21%, 45.00%, 45.45%, 50.00%, 55.00%, or 60.00%, wherein the amount is the weight of the taste-masking agent relative to the total weight of the ambroxol orodispersible film composition (e.g., ambroxol hydrochloride orodispersible film composition).

[0023] According to embodiments of the present application, the film-forming material is a carrier for the pharmaceutical agent, and is selected from the group consisting of xanthan gum, guar gum, pectin, gelatin, shellac, gum arabic, starch, dextrin, agar, sodium alginate, zein, hypromellose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl alcohol, pullulan, polyvinylpyrrolidone, polyethylene glycol, polyoxyethylene, acrylic acid copolymer, polylactic acid, and silicone rubber.

[0024] Preferably, the film-forming material is present in an amount of 10.00% to 70.00%, preferably 15.00% to 60.00%, such as 10.00%, 12.00%, 14.29%, 15.00%, 20.00%, 25.00%, 27.47%, 30.00%, 30.30%, 30.45%, 35.00%, 37.34%, 38.46%, 40.00%, 45.00%, 50.00%, 55.00%, 58.44%, or 60.00%, by weight of the total composition.

[0025] According to embodiments of the present application, the ambroxol oral film composition (such as ambroxol hydrochloride oral film composition) of the present application can further comprise one or more of a plasticizer, a flavoring agent, a coloring agent, and a filler. As an example, the ambroxol oral film composition (such as ambroxol hydrochloride oral film composition) can or can not comprise a flavoring agent.

[0026] According to embodiments of the present application, the plasticizer refers to a substance used to lower the glass transition temperature of the film, increase plasticity and toughness, and improve the elongation rate, which can be selected from one or more of polyethylene glycol, glycerol, propylene glycol, silicone oil, polypropylene glycol, and hexylene glycol.

[0027] Preferably, the plasticizer is present in an amount of 0 to 30.00%, preferably 0 to 25.00%, such as 1.00%, 2.00%, 2.60%, 3.00%, 4.00%, 5.00%, 6.00%, 6.06%, 7.00%, 8.00%, 8.67%, 9.00%, 10.00%, 10.15%, 10.99%, 15.00%, 20.00%, 24.90%, 25.00%, or 30.00%, by weight of the total composition.

[0028] According to embodiments of the present application, the flavoring agent refers to a substance that has a flavoring effect, which can be selected from one, two, or more of aspartame, sucralose, fructose, sucrose, stevioside, neotame, glycyrrhizin, essence, spice, saccharin, and sodium saccharin.

[0029] Preferably, the mass percentage of the flavoring agent is 0-50.00%, preferably 0-45.00%, for example 1.00%, 1.10%, 1.20%, 1.30%, 1.33%, 1.40%, 1.50%, 1.60%, 1.70%, 1.80%, 1.90%, 2.00%, 2.10%, 2.20%, 2.30%, 2.40%, 2.50%, 2.60%, 2.70%, 2.80%, 2.90%, 3.00%, 3.05%, 3.50%, 3.85%, 4.00%, 5.00%, 6.00%, 7.00%, 8.00%, 9.00%, 9.09%, 10.00%, 12.00%, 15.00%, 20.00%, 25.00%, 30.00%, 35.00%, 40.00%, 42.87%, 45.00% or 50.00%, wherein the mass percentage refers to the mass of the flavoring agent accounting for the percentage of the total mass of the ambroxol oral film composition (such as ambroxol hydrochloride oral film composition).

[0030] According to an embodiment of the present application, the coloring agent refers to a substance capable of improving the appearance of the color of the preparation, identifying the concentration of the preparation, distinguishing the application method and reducing the aversion of patients to medication, and is selected from one, two or more of titanium dioxide, pigments and color lakes.

[0031] Preferably, the mass percentage of the coloring agent is 0-2.00%, for example 0, 0.02%, 0.10%, 0.15%, 0.20%, 0.25%, 0.30%, 0.41%, 0.50%, 0.60%, 0.70%, 0.80%, 0.90%, 1.00%, 1.10%, 1.20%, 1.30%, 1.40%, 1.50%, 1.60%, 1.65%, 1.70%, 1.80%, 1.90% or 2.00%, wherein the mass percentage refers to the mass of the coloring agent accounting for the percentage of the total mass of the ambroxol oral film composition (such as ambroxol hydrochloride oral film composition).

[0032] According to an embodiment of the present application, the filler refers to a solid substance added to the material to improve the performance of the material, or to increase the capacity and weight, and reduce the cost of the material. It can be selected from one or more of sucrose, glucose, maltose, lactose, sorbitol, xylitol, maltitol, galactitol, erythritol, dextrin and trehalose.

[0033] Preferably, the mass percentage of the filler is 0-20.00%, for example 0%, 1.00%, 5.00%, 10.00%, 15.00% or 20.00%, wherein the mass percentage refers to the mass of the filler accounting for the percentage of the total mass of the ambroxol oral film composition (such as ambroxol hydrochloride oral film composition).

[0034] According to embodiments of the present application, the ambroxol oral film composition (such as ambroxol hydrochloride oral film composition) is selected from the following Formulas 1-1 to 1-5 in mass percentage:

[0035] Formula 1-1 comprises: 15-22% ambroxol or a pharmaceutically acceptable salt thereof (such as ambroxol hydrochloride), 18-52% polacrillin potassium, 18-35% film forming material, 8-12% plasticizer, 0.3-7% flavoring agent and / or colorant;

[0036] Formula 1-2 comprises: 15-22% ambroxol or a pharmaceutically acceptable salt thereof (such as ambroxol hydrochloride), 18-46% polacrillin potassium, 18-60% film forming material, 2-22% plasticizer, and 0-0.05% flavoring agent and / or colorant;

[0037] Formula 1-3 comprises: 17-21% ambroxol or a pharmaceutically acceptable salt thereof (such as ambroxol hydrochloride), 35-40% polacrillin potassium, 34-41% film forming material, and 2-6% flavoring agent and / or colorant;

[0038] Formula 1-4 comprises: 9-13% ambroxol or a pharmaceutically acceptable salt thereof (such as ambroxol hydrochloride), 22-48% sodium polystyrene sulfonate, 30-40% film forming material, 5-25% plasticizer, and 0.2-10% flavoring agent and / or colorant;

[0039] Formula 1-5 comprises: 18-24% ambroxol or a pharmaceutically acceptable salt thereof (such as ambroxol hydrochloride), 20-24% sodium polystyrene sulfonate, 13-15% film forming material, and 40-45% flavoring agent.

[0040] According to embodiments of the present application, in the Formulas 1-1 to 1-5, the film forming material is one, two or more of xanthan gum, polyvinyl alcohol, hypromellose, pullulan, sodium alginate.

[0041] According to embodiments of the present application, in the Formulas 1-1 to 1-5, the plasticizer is glycerol.

[0042] According to embodiments of the present application, in the Formulas 1-1 to 1-5, the colorant is lake.

[0043] The ambroxol hydrochloride oral film composition according to the present application can be any of the following formulas:

[0044] Formulation 2-1 : 18-22% ambroxol or a pharmaceutically acceptable salt thereof (e.g. ambroxol hydrochloride), 48-52% glyceryl caprylate, 14-32% film forming material, 6-10% plasticizer, and 1-3% of a flavoring agent and / or a coloring agent, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0045] Formulation 2-2: 14-18% ambroxol or a pharmaceutically acceptable salt thereof (e.g. ambroxol hydrochloride), 39-43% glyceryl caprylate, 25-29% film forming material, 9-13% plasticizer, 1.5-6% of a flavoring agent and / or a coloring agent, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0046] Formulation 2-3: 13-17% ambroxol or a pharmaceutically acceptable salt thereof (e.g. ambroxol hydrochloride), 36-40% glyceryl caprylate, 28-32% film forming material, 8-12% plasticizer, 1-11% of a flavoring agent and / or a coloring agent, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0047] Formulation 2-4: 17-21% ambroxol or a pharmaceutically acceptable salt thereof (e.g. ambroxol hydrochloride), 17-21% glyceryl caprylate, 58-52% film forming material, and 0.5-4% plasticizer, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0048] Formulation 2-5: 17-21% ambroxol or a pharmaceutically acceptable salt thereof (e.g. ambroxol hydrochloride), 36-40% glyceryl caprylate, 34-41% film forming material, and 2-6% of a flavoring agent and / or a coloring agent, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0049] Formulation 2-6: 14-18% ambroxol or a pharmaceutically acceptable salt thereof (e.g. ambroxol hydrochloride), 38-42% glyceryl caprylate, 30-34% film forming material, 9-13% plasticizer, and 0-0.02% of a flavoring agent and / or a coloring agent, the percentages referring to the mass of each component as a percentage of the total mass of the composition.

[0050] Formulation 2-7: 14-18% ambroxol or a pharmaceutically acceptable salt thereof (e.g. ambroxol hydrochloride), 37-41% glyceryl caprylate, 29-33% film forming material, 8-12% plasticizer, 0-6% of a flavoring agent and / or a coloring agent, the percentages referring to the mass of each component as a percentage of the total mass of the composition.

[0051] Formulation 2-8: 14-18% ambroxol or a pharmaceutically acceptable salt thereof (e.g. ambroxol hydrochloride), 38-42% polacrillin potassium, 30-34% film forming material, 9-13% plasticizer, 0-0.5% flavoring agent and / or coloring agent, the percentages referring to the mass of each component as a percentage of the total mass of the composition.

[0052] Formulation 2-9: 13-17% ambroxol or a pharmaceutically acceptable salt thereof (e.g. ambroxol hydrochloride), 43-47% polacrillin potassium, 18-22% film forming material and 18-22% plasticizer, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0053] Formulation 2-10: 7-11% ambroxol or a pharmaceutically acceptable salt thereof (e.g. ambroxol hydrochloride), 44-48% sodium polystyrene sulfonate, 26-34% film forming material, 4-8% plasticizer, 1-15% flavoring agent and / or coloring agent, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0054] Formulation 2-11: 10-14% ambroxol or a pharmaceutically acceptable salt thereof (e.g. ambroxol hydrochloride), 21-25% sodium polystyrene sulfonate, 35-39% film forming material, 23-27% plasticizer and 0-0.5% flavoring agent and / or coloring agent, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0055] Formulation 2-12: 20-22% ambroxol or a pharmaceutically acceptable salt thereof (e.g. ambroxol hydrochloride), 20-22% sodium polystyrene sulfonate, 12-16% film forming material, 30-50% flavoring agent and / or coloring agent, the percentages referring to the mass of each component as a percentage of the total mass of the composition.

[0056] According to an embodiment of the present application, in Formulation 2-1 to Formulation 2-12, the film forming material is one, two or more of xanthan gum, polyvinyl alcohol, hypromellose, pullulan, sodium alginate.

[0057] According to an embodiment of the present application, in Formulation 2-1 to Formulation 2-12, the plasticizer is glycerol.

[0058] According to an embodiment of the present application, in Formulation 2-1 to Formulation 2-12, the coloring agent is a lake.

[0059] The ambroxol orally dissolving film composition according to the present application can be any of the following formulations:

[0060] Formulation 3-1: 18-22% ambroxol or a pharmaceutically acceptable salt thereof (e.g., ambroxol hydrochloride), 48-52% polacrillin potassium, 11-15% xanthan gum, 4-8% polyvinyl alcohol, 6-10% glycerol, and 1-3% aspartame, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0061] Formulation 3-2: 14-18% ambroxol or a pharmaceutically acceptable salt thereof (e.g., ambroxol hydrochloride), 39-43% polacrillin potassium, 25-29% polyvinyl alcohol, 9-13% glycerol, 0.5-1.5% stevioside, 0.5-1.5% flavoring, and 0.5-3% lake, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0062] Formulation 3-3: 13-17% ambroxol or a pharmaceutically acceptable salt thereof (e.g., ambroxol hydrochloride), 36-40% polacrillin potassium, 28-32% polyvinyl alcohol, 8-12% glycerol, 1-5% sucralose, 1-5% flavoring, and 0-0.05% lake, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0063] Formulation 3-4: 17-21% ambroxol or a pharmaceutically acceptable salt thereof (e.g., ambroxol hydrochloride), 17-21% polacrillin potassium, 58-52% hypromellose, and 0.5-4% glycerol, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0064] Formulation 3-5: 17-21% ambroxol or a pharmaceutically acceptable salt thereof (e.g., ambroxol hydrochloride), 36-40% polacrillin potassium, 23-27% polyvinyl alcohol, 11-14% pullulan, and 2-6% sucralose, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0065] Formulation 3-6: 14-18% ambroxol or a pharmaceutically acceptable salt thereof (e.g., ambroxol hydrochloride), 38-42% polacrillin potassium, 30-34% polyvinyl alcohol, 9-13% glycerol, and 0-0.02% lake, the percentages referring to the mass of each component as a percentage of the total mass of the composition.

[0066] Formulation 3-7: 14-18% ambroxol or a pharmaceutically acceptable salt thereof (e.g., ambroxol hydrochloride), 37-41% polacrillin potassium, 29-33% polyvinyl alcohol, 8-12% glycerol, 1-5% sucralose, and 0-0.05% lake, the percentages referring to the mass of each component as a percentage of the total mass of the composition.

[0067] Formulation 3-8: 14-18% ambroxol or pharmaceutically acceptable salt thereof (such as ambroxol hydrochloride), 38-42% polacrilin potassium, 30-34% polyvinyl alcohol, 9-13% glycerol, 0-0.1% neotame and 0-0.05% lake, the percentages referring to the mass of each component as a percentage of the total mass of the composition.

[0068] Formulation 3-9: 13-17% ambroxol or pharmaceutically acceptable salt thereof (such as ambroxol hydrochloride), 43-47% polacrilin potassium, 18-22% xanthan gum and 18-22% glycerol, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0069] Formulation 3-10: 7-11% ambroxol or pharmaceutically acceptable salt thereof (such as ambroxol hydrochloride), 44-48% sodium polystyrene sulfonate, 16-20% sodium alginate, 10-14% polyvinyl alcohol, 4-8% glycerol, 1-5% chloro sucrose, 1-5% stevioside and 1-5% flavouring, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0070] Formulation 3-11: 10-14% ambroxol or pharmaceutically acceptable salt thereof (such as ambroxol hydrochloride), 21-25% sodium polystyrene sulfonate, 35-39% hypromellose, 23-27% glycerol and 0-0.5% lake, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0071] Formulation 3-12: 20-22% ambroxol or pharmaceutically acceptable salt thereof (such as ambroxol hydrochloride), 20-22% sodium polystyrene sulfonate, 12-16% xanthan gum, 12-16% chloro sucrose, 12-16% stevioside and 12-16% flavouring, the percentages referring to the mass of each component as a percentage of the total mass of the composition.

[0072] The ambroxol hydrochloride orally dissolving film composition according to the present application can be any of the following formulations:

[0073] Formulation one: 20.00% ambroxol hydrochloride, 50.00% polacrilin potassium, 13.33% xanthan gum, 6.67% polyvinyl alcohol, 8.67% glycerol and 1.33% aspartame, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0074] Formulation two: 16.48% ambroxol hydrochloride, 41.21% polacrilin potassium, 27.47% polyvinyl alcohol, 10.99% glycerol, 1.10% stevioside, 1.10% flavouring and 1.65% lake, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0075] Formula Three: 15.23% ambroxol hydrochloride, 38.06% polacrillin potassium, 30.45% polyvinyl alcohol, 10.15% glycerol, 3.05% sucralose, 3.05% flavor and 0.02% lake, the percentage referring to the mass of each component in the total mass of the composition;

[0076] Formula Four: 19.48% ambroxol hydrochloride, 19.48% polacrillin potassium, 58.44% hypromellose and 2.60% glycerol, the percentage referring to the mass of each component in the total mass of the composition;

[0077] Formula Five: 19.23% ambroxol hydrochloride, 38.46% polacrillin potassium, 25.64% polyvinyl alcohol, 12.82% pullulan and 3.85% sucralose, the percentage referring to the mass of each component in the total mass of the composition;

[0078] Formula Six: 16.21% ambroxol hydrochloride, 40.53% polacrillin potassium, 32.43% polyvinyl alcohol, 10.81% glycerol and 0.02% lake, the percentage referring to the mass of each component in the total mass of the composition.

[0079] Formula Seven: 15.70% ambroxol hydrochloride, 39.26% polacrillin potassium, 31.41% polyvinyl alcohol, 10.47% glycerol, 3.14% sucralose and 0.02% lake, the percentage referring to the mass of each component in the total mass of the composition.

[0080] Formula Eight: 16.16% ambroxol hydrochloride, 40.40% polacrillin potassium, 32.32% polyvinyl alcohol, 10.77% glycerol, 0.32% neotame and 0.02% lake, the percentage referring to the mass of each component in the total mass of the composition.

[0081] Formula Nine: 15.00% ambroxol hydrochloride, 45.00% polacrillin potassium, 20.00% xanthan gum and 20.00% glycerol, the percentage referring to the mass of each component in the total mass of the composition;

[0082] Formula Ten: 9.09% ambroxol hydrochloride, 45.45% sodium polystyrene sulfonate, 18.18% sodium alginate, 12.12% polyvinyl alcohol, 6.06% glycerol, 3.03% sucralose, 3.03% stevioside and 3.03% flavor, the percentage referring to the mass of each component in the total mass of the composition;

[0083] Formulation Eleven: 12.45% ambroxol hydrochloride, 24.90% sodium polystyrene sulfonate, 37.34% hydroxypropyl methylcellulose, 24.90% glycerol and 0.41% lake, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0084] Formulation Twelve: 21.43% ambroxol hydrochloride, 21.43% sodium polystyrene sulfonate, 14.29% xanthan gum, 14.29% sucralose, 14.29% stevioside and 14.29% flavour, the percentages referring to the mass of each component as a percentage of the total mass of the composition.

[0085] Formulation Thirteen: 15.22% ambroxol hydrochloride, 38.06% potassium polyclitol glycoside, 30.45% polyvinyl alcohol, 10.15% glycerol, 3.05% sucralose, 3.05% flavour and 0.02% lake, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0086] Formulation Fourteen: 16.17% ambroxol hydrochloride, 40.40% potassium polyclitol glycoside, 32.32% polyvinyl alcohol, 10.77% glycerol, 0.32% neotame and 0.02% lake, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0087] Formulation Fifteen: 9.10% ambroxol hydrochloride, 45.45% sodium polystyrene sulfonate, 18.18% sodium alginate, 12.12% polyvinyl alcohol, 6.06% glycerol, 3.03% sucralose, 3.03% stevioside and 3.03% flavour, the percentages referring to the mass of each component as a percentage of the total mass of the composition;

[0088] Formulation Sixteen: 21.43% ambroxol hydrochloride, 21.43% sodium polystyrene sulfonate, 14.29% xanthan gum, 14.29% sucralose, 14.29% stevioside and 14.27% flavour, the percentages referring to the mass of each component as a percentage of the total mass of the composition.

[0089] According to an embodiment of the present application, the mass percentage content of each component in the ambroxol oral film composition (such as ambroxol hydrochloride oral film composition) is 100%. However, it should be understood that there can be a rounding error of ±0.2% due to rounding of numerical values.

[0090] The present application also provides a method for preparing the ambroxol oral film composition (such as ambroxol hydrochloride oral film composition) described above, which comprises the following steps:

[0091] Step 1: preparing an aqueous solution of the active drug;

[0092] Step 2: taste masking agent is added to the aqueous solution obtained in step 1, and stirred to obtain a sample;

[0093] Step 3: the sample obtained in step 2 is centrifuged, and part of the supernatant is discarded, and the remaining lower layer is weighed to be 10-15 times the weight of the active drug to obtain a drug-loaded resin;

[0094] Step 4: the film-forming material is dissolved in water, and then mixed with one or more of the flavoring agent, plasticizer, colorant and filler (if present), and stirred uniformly to obtain a glue solution;

[0095] Step 5: the drug-loaded resin obtained in step 3 is transferred to the glue solution obtained in step 4, and stirred thoroughly to obtain a uniform glue solution. After stirring, the glue solution is vacuumed to remove bubbles, coated, dried, and cut to obtain the ambroxol hydrochloride oral film preparation.

[0096] According to an embodiment of the present application, in step 1, the active drug solution is preferably prepared in the dark.

[0097] According to an embodiment of the present application, in step 1, the water is preferably purified water.

[0098] According to an embodiment of the present application, in step 2, the stirring is preferably carried out in the dark.

[0099] According to an embodiment of the present application, in step 2, the stirring time is preferably more than 8 hours.

[0100] According to an embodiment of the present application, in step 3, the centrifugation is preferably carried out in a centrifuge; the centrifuge can be a table centrifuge, and the centrifuge can be a low-speed centrifuge.

[0101] According to an embodiment of the present application, in the ambroxol oral film composition (such as ambroxol hydrochloride oral film composition), the thickness of the film is 10-300 μm, for example, 20-100 μm.

[0102] According to an embodiment of the present application, the ambroxol oral film composition (such as ambroxol hydrochloride oral film composition) can be completely disintegrated in 900 ml of simulated saliva at 37±1°C within 120 seconds, for example, within 80 seconds.

[0103] The present application also provides the use of the ambroxol oral film composition (such as ambroxol hydrochloride oral film composition) in the preparation of a medicament for treating and / or preventing indications for which ambroxol or a pharmaceutically acceptable salt thereof is indicated, for example, allergy.

[0104] According to an embodiment of the present application, the medicament is a expectorant or mucolytic agent.

[0105] According to embodiments of the present invention, the drug is used for the expectorant treatment of acute or chronic respiratory diseases accompanied by abnormal respiratory secretions, particularly chronic bronchitis, neonatal respiratory distress syndrome, and as an adjunct to lung surgery.

[0106] The present invention also provides a method for preventing and / or treating diseases or conditions, comprising administering the ambroxol oral solution composition (such as ambroxol hydrochloride oral solution composition) to a patient in need (e.g., a human or other mammal).

[0107] According to an embodiment of the present invention, the disease or symptom is selected from acute or chronic respiratory diseases such as allergies, excessive phlegm, and abnormal respiratory secretions, especially chronic bronchitis, neonatal respiratory distress syndrome, and symptoms after lung surgery.

[0108] The ambroxol oral dissolving film composition of the present invention, particularly the ambroxol hydrochloride oral dissolving film composition, exhibits a good dissolution rate, rapidly disintegrates in the oral cavity, and dissolves without a gritty sensation, improving the taste of the medication and increasing patient compliance. Furthermore, the ambroxol oral dissolving film composition of the present invention, particularly the ambroxol hydrochloride oral dissolving film composition, produces a film with uniform appearance and good flexibility. No sedimentation occurs during film solution preparation, and the content uniformity meets requirements.

[0109] The reagents and raw materials used in this invention are all commercially available.

[0110] Beneficial effects

[0111] The ambroxol oral dissolving film composition (such as ambroxol hydrochloride oral dissolving film composition) provided by the present invention has the advantages of thin thickness, good taste, improved stability, and can be dissolved in the mouth without drinking water and has a fast oral absorption rate, and has good market prospects.

[0112] Furthermore, the ambroxol oral soluble film composition of the present invention (such as ambroxol hydrochloride oral soluble film composition) has readily available raw materials, simple process, easy operation, high drug loading capacity, and good drug content uniformity, making it suitable for industrial production. Detailed Implementation

[0113] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0114] Examples 1-12

[0115] The percentage content of each component in Examples 1-12 in Table 1 below is the mass percentage of the component in the dried (water-free) formulation, calculated based on the mass of each component:

[0116] Table 1

[0117]

[0118]

[0119] " " indicates that the substance is removed during the process; " / " indicates that it is not contained.

[0120] The preparation method of each of the above examples includes:

[0121] 1) Weigh the ingredients

[0122] Weigh the raw and auxiliary materials according to the prescription amount for standby use.

[0123] 2) Resin drug loading

[0124] A: Under light-proof conditions, add the active drug to a certain amount of purified water and completely dissolve it.

[0125] B: Add a taste masking agent to the above solution and continue to stir in the dark for more than 8 hours.

[0126] C: Centrifuge the above sample in a low-speed benchtop high-capacity centrifuge. After centrifugation, discard part of the supernatant, and make the remaining lower layer material have a mass of 10-15 times that of the active drug.

[0127] 3) Preparation of glue solution

[0128] D: Dissolve the film-forming material in a certain amount of purified water, add the flavoring agent, plasticizer and coloring agent (if any), and stir uniformly.

[0129] E: Transfer the lower layer material in step 2) to the solution prepared in step 3) and stir thoroughly to obtain a uniform glue solution. After stirring, remove the air bubbles in the glue solution in a vacuum environment.

[0130] 4) Coating, drying and cutting

[0131] G: Coat the above glue solution on a coating machine, cut it into the appropriate size after drying, and obtain the ambroxol hydrochloride oral film preparation.

[0132] Comparative Examples 1-3

[0133] Comparative Examples 1-3 were prepared according to the manner of Examples 3-5 disclosed in CN 102846581 A:

[0134] Table 2

[0135]

[0136] " " indicates that the substance is removed during the process.

[0137] Performance test

[0138] The above Comparative Examples 1-3 and the ambroxol hydrochloride oral dissolving films prepared according to Examples 3-8 were subjected to mechanical strength, disintegration time and related substance tests, respectively.

[0139] Test Example 1

[0140] Mechanical strength test method of oral dissolving film

[0141] The ambroxol hydrochloride oral dissolving films were tested using a texture analyzer, and the tensile strength, percentage elongation and folding endurance thereof were calculated, with the results shown in Table 3 below (6 samples were tested for each example):

[0142] Table 3

[0143]

[0144]

[0145]

[0146] Note: The "cross-sectional area" in the above table is the surface area of the oral dissolving film.

[0147] The maximum force (gf) is the maximum force that the oral dissolving film can resist after the yield stage.

[0148] Tensile strength (MPa) = maximum force (gf) ÷ 102 ÷ cross-sectional area (mm 2 ), percentage elongation = maximum force distance (mm) ÷ sample height (mm) x 100%.

[0149] The average tensile strength is the average of 6 sets of data.

[0150] The maximum force distance is the distance of the elongation of the oral dissolving film under the maximum force.

[0151] The average percentage elongation is the average of 6 sets of data.

[0152] The folding endurance is the force that the oral dissolving film can withstand when folded 180°.

[0153] The above results show that the tensile strength and folding endurance of the ambroxol hydrochloride oral dissolving films prepared according to Examples 3-8 are higher than those of Comparative Examples 1-3, and are more suitable for commercial production, transportation, storage and patient use.

[0154] Test Example 2

[0155] Respectively, 6 pieces of the orally dissolving films prepared in Examples 1-12 and Comparative Examples 1-3 were taken to determine the disintegration time of the orally dissolving films. The test method was as follows: 900 ml of pH 6.8 phosphate buffer medium (the preparation method refers to the 8004 buffer under the Chinese Pharmacopoeia 2020 edition) was added to a 1000 ml beaker and heated to 37±0.5℃. 6 pieces of the orally dissolving films were placed in the beaker of the disintegration tester at the same time, and the time for all 6 pieces of the orally dissolving films of each example and comparative example to completely disintegrate was recorded. The results are summarized in Table 4 below.

[0156] Table 4

[0157]

[0158]

[0159] The results show that the ambroxol hydrochloride orally dissolving films prepared in Examples 1-12 can completely disintegrate within 120 s.

[0160] Test Example 3

[0161] Orally dissolving film related substance test

[0162] According to the mass ratio of ambroxol hydrochloride to citric acid in Comparative Examples 1-3, the raw material compatibility experiment was designed, and the raw material compatibility, the related substance level of Comparative Examples 1-3 and Examples 3-8 were detected after being placed at high temperature 60℃ for 30 days.

[0163] The related substance detection method was determined by high performance liquid chromatography (Chinese Pharmacopoeia 2020 edition four general 0512).

[0164] Solvent methanol

[0165] The test sample solution was prepared by taking two pieces (7.5 mg specification) or one piece (15 mg specification) of the product (sample prepared in the above examples or comparative examples), placing them in a 20 mL volumetric flask, adding an appropriate amount of methanol, and ultrasonicating for 15 minutes to dissolve the ambroxol hydrochloride. After cooling, a solution containing about 0.75 mg of ambroxol hydrochloride per 1 mL was prepared with methanol. The supernatant was taken as the test sample solution.

[0166] The control solution was prepared by accurately measuring an appropriate amount of the test sample solution and diluting it with methanol to prepare a solution containing about 1.5 μg per 1 mL.

[0167] The chromatographic conditions were as follows: octylsilane bonded silica gel as the filler (Agient ZORBAX SB-C8 4.6 mm*150 mm, 3.5 μm; 10 mmol / L diammonium hydrogen phosphate solution (pH adjusted to 7.0 with phosphoric acid)-acetonitrile (50:50) as the mobile phase; detection wavelength was 248 nm; flow rate was 0.8 mL per minute; column temperature was 30℃; sample injection plate temperature was 4℃, sample injection volume was 10 μL, and running time was 30 minutes.

[0168] System suitability The resolution between the main peak and the adjacent peak in the chromatogram of the test solution shall meet the requirements.

[0169] The test solution and the control solution were precisely measured, injected into the liquid chromatograph, and the chromatogram was recorded for 30 minutes.

[0170] Table 5 Impurity correction factor and limit

[0171] Impurity Name Relative Retention Time correction factor * ]] Limit AXS-IM-A 0.75 1.0 0.2％ AXS-IM-B 0.82 1.0 0.5％ AXS-IM-C 2.14 1.0 0.2％ AXS-IM-E 1.46 1.0 0.2％ AXS-IM-I 0.64 1.0 0.5％ Other Individual Impurities / 1.0 0.2％ Total Impurities / / 1.0％

[0172] Table 6 Related substance test results

[0173]

[0174]

[0175] Note: * represents the ratio in the reference guidance principle, and no other adjuvants.

[0176] The results show that the oral dissolving film prepared in Examples 3-6 has good stability, and the unknown impurity content in Comparative Examples 1-3 is higher. The oral dissolving film of the present application has better stability than Comparative Examples 1-3.

[0177] Test Example 4

[0178] Dissolution curve test of oral dissolving film

[0179] The oral dissolving films of ambroxol hydrochloride prepared in Examples 1, 3, 6-8 were placed in a stainless steel mesh disc according to the fourth method (paddle method) of dissolution and release determination method in Chinese Pharmacopoeia 2020 edition 0931, using method 1 stirring paddle, dissolution cup according to the second method, and the dissolution curve of ambroxol hydrochloride oral dissolving film was detected. The test conditions are as follows:

[0180] Test device: Tianfa dissolution tester.

[0181] Test medium: pH 1.2 hydrochloric acid solution, pH 4.5 acetate buffer and pH 6.8 phosphate buffer.

[0182] Experimental conditions: The volume of the medium is 900ml, the temperature is 37±0.5℃, the stirring speed is 50rpm, and the sampling time is 5min, 10min, 15min and 30min.

[0183] The dissolution results and dissolution curve test results of two batches of ambroxol hydrochloride oral dissolving films are shown in the following table:

[0184] Table 7

[0185]

[0186]

[0187] The results show that the cumulative dissolution of the ambroxol hydrochloride oral dissolving film of the application in pH 1.2 hydrochloric acid solution and pH 6.8 phosphate buffer solution is more than 85% at 15 min; in pH 4.5 acetate buffer solution, the cumulative dissolution of the preparations of batches 3, 6-8 is more than 85% at 15 min, and the cumulative dissolution of the preparation of batch 1 is more than 85% at 30 min.

[0188] Test Example 4

[0189] Palatability evaluation of the oral dissolving film

[0190] The ambroxol hydrochloride oral dissolving film of batch 3 was prepared according to Example 3, and 6 volunteers were randomly selected to evaluate the palatability of the ambroxol hydrochloride oral dissolving film of the batch by comprehensively using the bitterness value grade evaluation method and the multi-factor investigation evaluation method according to the Technical Guidelines for the Design and Evaluation of the Taste of Medicines for Children (Open Draft) and the literature “Li Pan, et al. Application and development of sensory test in drug taste evaluation [J]. Chinese Pharmaceutical Journal, 2017, 52(22): 1971-1975”.

[0191] According to the quality attributes of the oral dissolving film, the palatability was evaluated from the aspects of appearance, bitterness, sweetness, numbness, and foreign body sensation in the mouth, among which bitterness, numbness, and foreign body sensation in the mouth were the main scoring items, and appearance and sweetness were the bonus items. The grade and scoring rules were as follows:

[0192] Table 8 Palatability evaluation table of the oral dissolving film

[0193]

[0194] The results show that the final palatability scores of the 6 volunteers are all in the range of 24-30, and the ambroxol hydrochloride oral dissolving film prepared by the application has good taste and good acceptance.

[0195] As can be seen from the above experimental data, the ambroxol hydrochloride oral dissolving film provided by the application has the advantages of thin thickness, good taste, stable properties, immediate dissolution in the oral cavity without the need for drinking water, and fast oral absorption speed.

[0196] The above has exemplarily described the implementation manners of the technical scheme of the application. It should be understood that the protection scope of the application is not limited to the above implementation manners. Any modification, equivalent replacement, improvement, etc. made by those skilled in the art within the spirit and principle of the application shall be included in the protection scope of the claims of the application.

Claims

1. An oral dissolving film composition, characterized in that: The composition is selected from any of the following compositions: Composition 1-1 comprises: 15-22% ambroxol hydrochloride, 18-52% polykrylene potassium, 18-35% film-forming material, 8-12% plasticizer, 0.3-7% flavoring agent and / or colorant, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 1-2 comprise: 15-22% ambroxol hydrochloride, 18-46% polykrylene potassium, 18-60% film-forming material, 2-22% plasticizer, and 0-0.05% flavoring agent and / or coloring agent, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 1-3 comprise: 17-21% ambroxol hydrochloride, 35-40% polycrylene potassium, 34-41% film-forming material, and 2-6% flavoring agent and / or coloring agent, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 1-5 comprise: 18-24% ambroxol hydrochloride, 20-24% sodium polystyrene sulfonate, 13-15% film-forming material, and 40-45% flavoring agent, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; The film-forming material is selected from one or more of xanthan gum, hydroxypropyl methylcellulose, polyvinyl alcohol, and pullulan. The plasticizer is selected from one or more of polyethylene glycol, glycerin, propylene glycol, silicone oil, polypropylene glycol, and hexanediol; The flavoring agent is selected from one or more of aspartame, sucralose, fructose, sucrose, steviol glycoside, neotame, glycyrrhizin, flavoring, fragrance, saccharin and sodium saccharin; The colorant is selected from one or more of titanium dioxide, pigments, and lakes; The composition does not contain any free pH adjusters.

2. An oral dissolving film composition, characterized in that: The composition is selected from any of the following compositions: Composition 2-1: 18-22% ambroxol hydrochloride, 48-52% polycrylene potassium, 14-32% film-forming material, 6-10% plasticizer and 1-3% flavoring agent and / or coloring agent, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Composition 2-2: 15-18% ambroxol hydrochloride, 39-43% polycrylene potassium, 25-29% film-forming material, 9-13% plasticizer, 1.5-6% flavoring agent and / or colorant, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 2-3: 15-17% ambroxol hydrochloride, 36-40% polykrylene potassium, 28-32% film-forming material, 8-12% plasticizer, 1-11% flavoring agent and / or colorant, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 2-4: 17-21% ambroxol hydrochloride, 17-21% polykrylene potassium, 58-52% film-forming material and 0.5-4% plasticizer, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 2-5: 17-21% ambroxol hydrochloride, 36-40% polycrylene potassium, 34-41% film-forming material and 2-6% flavoring agent and / or coloring agent, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 2-6: 15-18% ambroxol hydrochloride, 38-42% polycrylene potassium, 30-34% film-forming material, 9-13% plasticizer and 0-0.02% flavoring agent and / or coloring agent, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 2-7: 15-18% ambroxol hydrochloride, 37-41% polycrylene potassium, 29-33% film-forming material, 8-12% plasticizer, 0-6% flavoring agent and / or colorant, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 2-8: 15-18% ambroxol hydrochloride, 38-42% polycrylene potassium, 30-34% film-forming material, 9-13% plasticizer, 0-0.5% flavoring agent and / or colorant, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 2-9: 15-17% ambroxol hydrochloride, 43-47% polykrylene potassium, 18-22% film-forming material and 18-22% plasticizer, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Composition 2-12: 20-22% ambroxol hydrochloride, 20-22% sodium polystyrene sulfonate, 12-16% film-forming material, 30-50% flavoring agent and / or coloring agent, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; The film-forming material is selected from one or more of xanthan gum, hydroxypropyl methylcellulose, polyvinyl alcohol, and pullulan. The plasticizer is selected from one or more of polyethylene glycol, glycerin, propylene glycol, silicone oil, polypropylene glycol, and hexanediol; The flavoring agent is selected from one or more of aspartame, sucralose, fructose, sucrose, steviol glycoside, neotame, glycyrrhizin, flavoring, fragrance, saccharin and sodium saccharin; The colorant is selected from one or more of titanium dioxide, pigments, and lakes.

3. An oral dissolving film composition, characterized in that: The composition is selected from any of the following compositions: Composition 3-1: 18-22% ambroxol hydrochloride, 48-52% polycrylene potassium, 11-15% xanthan gum, 4-8% polyvinyl alcohol, 6-10% glycerol and 1-3% aspartame, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Composition 3-2: 15-18% ambroxol hydrochloride, 39-43% polykrylamide potassium, 25-29% polyvinyl alcohol, 9-13% glycerin, 0.5-1.5% steviol glycoside, 0.5-1.5% fragrance and 0.5-3% lake, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Composition 3-3: 15-17% ambroxol hydrochloride, 36-40% potassium polykrylamide, 28-32% polyvinyl alcohol, 8-12% glycerol, 1-5% sucralose, 1-5% flavoring and 0-0.05% lake, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 3-4: 17-21% ambroxol hydrochloride, 17-21% polykrylamide potassium, 58-52% hydroxypropyl methylcellulose and 0.5-4% glycerol, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 3-5: 17-21% ambroxol hydrochloride, 36-40% potassium polykrylamide, 23-27% polyvinyl alcohol, 11-14% pullulan and 2-6% sucralose, where the percentages refer to the mass of each component as a percentage of the total mass of the composition; Compositions 3-6: 15-18% ambroxol hydrochloride, 38-42% polycrylene potassium, 30-34% polyvinyl alcohol, 9-13% glycerol and 0-0.02% lake, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 3-7: 15-18% ambroxol hydrochloride, 37-41% potassium polycrylene, 29-33% polyvinyl alcohol, 8-12% glycerol, 1-5% sucralose and 0-0.05% lake, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 3-8: 15-18% ambroxol hydrochloride, 38-42% polycrylene potassium, 30-34% polyvinyl alcohol, 9-13% glycerol, 0-0.1% neotame and 0-0.05% lake, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Compositions 3-9: 15-17% ambroxol hydrochloride, 43-47% polykrylene potassium, 18-22% xanthan gum and 18-22% glycerin, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Composition 3-12: 20-22% ambroxol hydrochloride, 20-22% sodium polystyrene sulfonate, 12-16% xanthan gum, 12-16% sucralose, 12-16% steviol glycoside and 12-16% fragrance, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition.

4. An oral dissolving film composition, characterized in that: The composition is selected from any of the following compositions: Composition 1: 20.00% ambroxol hydrochloride, 50.00% polycrylene potassium, 13.33% xanthan gum, 6.67% polyvinyl alcohol, 8.67% glycerin and 1.33% aspartame, where the percentages refer to the mass of each component as a percentage of the total mass of the composition; Composition 2: 16.48% ambroxol hydrochloride, 41.21% potassium polycrylene, 27.47% polyvinyl alcohol, 10.99% glycerin, 1.10% steviol glycoside, 1.10% fragrance and 1.65% lake, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Composition 3: 15.23% ambroxol hydrochloride, 38.06% potassium polycrylene, 30.45% polyvinyl alcohol, 10.15% glycerin, 3.05% sucralose, 3.05% flavoring and 0.02% lake, where the percentages refer to the mass percentage of each component to the total mass of the composition; Composition 4: 19.48% ambroxol hydrochloride, 19.48% polycrylene potassium, 58.44% hydroxypropyl methylcellulose and 2.60% glycerol, where the percentages refer to the mass percentage of each component to the total mass of the composition; Composition 5: 19.23% ambroxol hydrochloride, 38.46% potassium polykrylamide, 25.64% polyvinyl alcohol, 12.82% pullulan and 3.85% sucralose, where the percentages refer to the mass of each component as a percentage of the total mass of the composition; Composition 6: 16.21% ambroxol hydrochloride, 40.53% polycrylene potassium, 32.43% polyvinyl alcohol, 10.81% glycerol and 0.02% lake, where the percentages refer to the mass percentage of each component to the total mass of the composition; Composition 7: 15.70% ambroxol hydrochloride, 39.26% potassium polycrylene, 31.41% polyvinyl alcohol, 10.47% glycerol, 3.14% sucralose and 0.02% lake, where the percentages refer to the mass percentage of each component to the total mass of the composition; Composition 8: 16.16% ambroxol hydrochloride, 40.40% polycrylene potassium, 32.32% polyvinyl alcohol, 10.77% glycerol, 0.32% neotame and 0.02% lake, where the percentages refer to the mass percentage of each component to the total mass of the composition; Composition Nine: 15.00% ambroxol hydrochloride, 45.00% polycrylene potassium, 20.00% xanthan gum and 20.00% glycerin, where the percentages refer to the mass percentage of each component to the total mass of the composition; Composition Twelve: 21.43% ambroxol hydrochloride, 21.43% sodium polystyrene sulfonate, 14.29% xanthan gum, 14.29% sucralose, 14.29% steviol glycoside and 14.29% fragrance, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Composition 13: 15.22% ambroxol hydrochloride, 38.06% polycrylene potassium, 30.45% polyvinyl alcohol, 10.15% glycerin, 3.05% sucralose, 3.05% flavoring and 0.02% lake, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Composition Fourteen: 16.17% ambroxol hydrochloride, 40.40% polycrylene potassium, 32.32% polyvinyl alcohol, 10.77% glycerol, 0.32% neotame and 0.02% lake, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition; Composition Sixteen: 21.43% ambroxol hydrochloride, 21.43% sodium polystyrene sulfonate, 14.29% xanthan gum, 14.29% sucralose, 14.29% steviol glycoside and 14.27% fragrance, wherein the percentages refer to the percentage of the mass of each component to the total mass of the composition.

5. The composition according to any one of claims 1-4, characterized in that: The composition completely disintegrated within 120 seconds in 900 ml of simulated saliva at 37±0.5°C.

6. The composition according to any one of claims 1-4, characterized in that: The thickness of the composition is 10 μm-300 μm; and / or, The particle size D90 of the cation exchange resin is less than 200 μm.

7. Use of the composition according to any one of claims 1-6 in the preparation of a medicament for treating and / or preventing allergies.

8. The application as described in claim 7, characterized in that, The drug is an expectorant or a mucolytic.

9. The application as described in claim 7, characterized in that, The drug is used for acute or chronic respiratory diseases accompanied by abnormal respiratory secretions.

10. The application as described in claim 7, characterized in that, The drug is used for expectorant treatment of chronic bronchitis, as well as as an adjunct therapy for neonatal respiratory distress and lung surgery.

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