Ambroxol orally disintegrating film composition, its preparation method and use

Abstract

The present invention provides an orally disintegrating ambroxol film composition, its preparation method, and use. The orally disintegrating ambroxol film composition comprises an active drug, a film-forming material, and a flavoring agent, where the active drug is 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl)benzylamine and / or its pharmacologically acceptable salt, such as ambroxol hydrochloride. The orally disintegrating ambroxol film composition according to the present invention has the advantages of being thin, pleasant to the taste, stable, instantly dissolving in the oral cavity without the need for water, and having a fast oral absorption rate. Furthermore, the orally disintegrating ambroxol film composition is simple to process, has a high drug loading, and has good drug content uniformity, making it a promising market.

Description

Detailed Description of the Invention

[0001] [Technical field] This application claims priority from a prior patent application bearing patent application number 202211420255.4 and entitled "Ambroxol Hydrochloride Orally Disintegrating Film Composition, Its Preparation Method, and Use," filed with the State Intellectual Property Administration of China on November 14, 2022, the entire text of which is incorporated herein by reference.

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

[0003] [Background technology] Ambroxol hydrochloride is the active metabolite of the expectorant bromhexine. It is less toxic than bromhexine but more active than bromhexine. Ambroxol hydrochloride is a mucolytic agent developed by Boehringer Ingelheim, Germany. This drug was first launched in Germany in the early 1980s and has since been sold in many countries, including France, Italy, Japan, and Spain. It is a new-generation mucolytic agent that improves phlegm clearance and promotes pulmonary surfactant, airway secretions, and ciliary movement. Clinically, it can regulate the secretion of mucus and viscous slurry, activate ciliary movement, easily dilute phlegm, enhance the transport of mucus out of the body and facilitate its excretion, promote the synthesis of pulmonary surfactant, maintain alveolar tension, ensure pulmonary function index, promote the penetration of antibiotics into tissues to increase their concentration, enhance bactericidal effect, antioxidant, reduce the release of inflammatory mediators to alleviate inflammatory reactions, and synergize with bronchial antispasmodics to enhance the therapeutic effect of antispasmodics. Therefore, this drug is widely used in the expectoration treatment of acute and chronic respiratory diseases accompanied by abnormal respiratory secretions, especially chronic bronchitis, and in the adjunctive treatment of neonatal respiratory distress syndrome and pulmonary surgery. It has the advantages of low toxicity, clear therapeutic effect, and synergistic effect when combined with antibiotics, making it one of the most commonly used expectorants.

[0004] Currently, Yuanken's dosage forms available in the Chinese market include injections, tablets, sustained-release capsules, and oral solution. The drug has undergone national approval procedures and has been approved in 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, generic medicines such as injections, oral solutions, syrups, granules, regular tablets, capsules, sustained-release tablets, extended-release capsules, orally disintegrating tablets, dispersible tablets, and chewable tablets are also available in China.

[0006] Ambroxol is extremely popular among clinicians due to its highly pronounced expectorant effect, and its injections are widely used (off-label) for the nebulization treatment of patients with respiratory diseases. However, the weakly acidic ambroxol injection itself can irritate the airways even after nebulization, causing airway spasms and respiratory distress, a problem that is particularly pronounced in COPD patients. Furthermore, injections prepared with saline may pose a risk of pulmonary infection or asthma exacerbation after nebulization, regardless of the particle size or additives (including preservatives). However, in 2019, Hanmei submitted a Category 5.2 new drug, ambroxol hydrochloride solution (JXHS1700033) (which was granted priority review as a "pediatric drug"), and its marketing application was approved by the National Medical Products Administration. This drug also addresses the problem of pediatric patients needing large doses of ambroxol, which cannot be met clinically with existing dosage forms.

[0007] In China, all ambroxol oral formulations are over-the-counter (OTC) drugs, are among the best-selling respiratory medications, and are used by a wide range of populations, primarily infants and children. The instructions for use for ambroxol hydrochloride oral solution also clearly state that it can be administered to infants. However, there is considerable international controversy regarding the use of such products in infants. Many organizations are concerned about the appropriateness of using ambroxol as an expectorant in children under 6 years of age, and believe that the benefits of such medications do not outweigh the risks in this patient population.

[0008] Ambroxol tablets and sustained-release capsules require swallowing with water to complete the dosage. This dosage form has low compliance among some elderly, children, and patients with swallowing disorders, and its use is limited or ineffective in special circumstances (such as lack of drinking water). Meanwhile, injectable formulations pose safety risks and low patient compliance. Oral solutions, while tasty, have drawbacks such as large dosages, difficulty in quantification, and poor stability. They also require high production and packaging requirements and are inconvenient to carry, resulting in numerous inconveniences and risks for patients during administration, transportation, and transportation.

[0009] Ambroxol hydrochloride is slightly soluble in water. This drug has a bitter taste and a numbing sensation, which lasts for a long time and cannot be masked by adding conventional solubilizers or flavoring agents. As a result, patient compliance is poor, which is particularly undesirable for children. Patent document CN102846581A discloses an orally disintegrating film of ambroxol hydrochloride. However, experiments have shown that the orally disintegrating film of ambroxol hydrochloride prepared using this formulation has weak mechanical strength, poor stability, slow disintegration, and a complicated preparation process, making it unsuitable for industrial production.

[0010] Therefore, there is an urgent need to develop a pharmaceutical formulation of ambroxol hydrochloride that is stable, has good taste, and provides good patient compliance.

[0011] [Summary of the Invention] [Problem to be solved by the invention] The present invention provides an orally disintegrating film composition of ambroxol hydrochloride, a preparation method thereof, and use thereof, in order to overcome the drawbacks of the orally disintegrating films of ambroxol hydrochloride in the prior art, such as poor taste, poor stability, and / or poor patient compliance. The orally disintegrating film composition of ambroxol hydrochloride according to the present invention has the advantages of being thin, having good taste, stable properties, stable mechanical properties, dissolving immediately in the oral cavity without drinking water, and having a fast oral absorption rate. In addition, it is easy to process, has a high drug loading, and has good drug content uniformity, and has a promising future market.

[0012] [Means for solving the problem] The present invention provides an orally disintegrating ambroxol film composition comprising an active drug, a film-forming material, and a flavoring agent, wherein the active drug is 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl)benzylamine (also known as ambroxol) or a pharmacologically acceptable salt thereof, such as 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl)benzylamine hydrochloride (also known as ambroxol hydrochloride) represented by Formula I:

[0013] [ka] According to an embodiment of the present invention, the orally disintegrating film composition of ambroxol according to the present invention may be an orally disintegrating film composition of ambroxol hydrochloride.

[0014] According to an embodiment of the present invention, the orally disintegrating film composition of ambroxol (for example, the orally disintegrating film composition of ambroxol hydrochloride) according to the present invention preferably does not contain a pH adjuster.

[0015] According to an embodiment of the present invention, the orally disintegrating film composition of ambroxol (e.g., the orally disintegrating film composition of ambroxol hydrochloride) preferably does not contain a pH adjuster present in a free state. The pH adjuster present in a free state refers to a pH adjuster that does not form a salt with an active drug.

[0016] According to an embodiment of the present invention, the pH adjuster includes, but is not limited to, pharmaceutically acceptable acids (e.g., organic acids, inorganic acids, organic bases, and inorganic bases) known in the art for adjusting pH. Examples of inorganic acids include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of organic acids include acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, sulfosalicylic acid, formic acid, and trifluoroacetic acid.

[0017] According to an embodiment of the present invention, the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition) according to the present invention does not contain a basic pH adjuster, such as a pharmaceutically acceptable base known in the art for adjusting the pH value.

[0018] According to an embodiment of the present invention, the mass content of the active drug is 1.00% to 40.00%, preferably 5.00% to 30.00%, for example, 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%, where the mass content refers to the proportion of the mass of the active drug to the total mass of the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition).

[0019] According to an embodiment of the present invention, the flavoring agent is a substance that masks unpleasant tastes such as bitterness and numbness, and may be selected from cation exchange resins, and the cation exchange resins are one, two, or three selected from sodium polystyrene sulfonate, polacrilin potassium, and polacrilin resin.

[0020] Preferably, the particle size D90 of the cation exchange resin is less than 200 μm.

[0021] Preferably, the mass content of the odorant is 10.00% to 70.00%, more preferably 15.00% to 60.00%, for example, 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%, and the mass content refers to the proportion of the mass of the odorant to the total mass of the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition).

[0022] According to an embodiment of the present invention, the film-forming material is a drug carrier and is one or more selected from xanthan gum, guar gum, pectin, gelatin, shellac, gum arabic, starch, dextrin, agar, sodium alginate, zein, hypromellose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, polyvinyl alcohol, pullulan, polyvinylpyrrolidone, polyethylene glycol, polyoxyethylene, acrylic acid copolymer, polylactic acid, and silicone rubber.

[0023] Preferably, the mass content of the film-forming material is 10.00% to 70.00%, preferably 15.00% to 60.00%, for example, 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%, and the mass content refers to the proportion of the mass of the film-forming material to the total mass of the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition).

[0024] According to an embodiment of the present invention, the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition) described in the present invention may further comprise one or more of a plasticizer, a flavoring agent, a coloring agent, and a filler. For example, the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition) may or may not comprise a flavoring agent.

[0025] According to an embodiment of the present invention, the plasticizer is a substance that lowers the glass transition temperature of the film, improves the plasticity and toughness, and increases the elongation ratio, and may be one or more selected from polyethylene glycol, glycerol, propylene glycol, silicone oil, polypropylene glycol, and hexanediol.

[0026] Preferably, the mass content of the plasticizer is 0 to 30.00%, preferably 0 to 25.00%, for example, 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%, and the mass content refers to the proportion of the mass of the plasticizer to the total mass of the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition).

[0027] According to an embodiment of the present invention, the flavoring agent is a substance that plays a role in masking flavor, and may be one or more selected from aspartame, sucralose, fructose, sucrose, stevioside, neotame, glycyrrhizin, flavors, fragrances, saccharin, and saccharin sodium.

[0028] Preferably, the mass content of the flavoring agent is 0 to 50.00%, preferably 0 to 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%, and the mass content refers to the proportion of the mass of the flavoring agent to the total mass of the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition).

[0029] According to an embodiment of the present invention, the coloring agent is a substance that can be used to improve the appearance color of the formulation, identify the concentration of the formulation, distinguish the application method, and reduce patients' aversion to taking the medication, and is one or more selected from titanium dioxide, pigments, and lakes.

[0030] Preferably, the mass content of the colorant is 0 to 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%, and the mass content refers to the proportion of the mass of the colorant to the total mass of the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition).

[0031] According to an embodiment of the present invention, the filler is a solid substance that can be added to a material to improve the material's properties, or to achieve solubilization or weight gain, and reduce material costs, and may be one or more selected from sucrose, glucose, maltose, lactose, sorbitol, xylitol, maltitol, galactitol, erythritol, dextrin, and trehalose.

[0032] Preferably, the mass content of the filler is 0 to 20.00%, for example, 0%, 1.00%, 5.00%, 10.00%, 15.00%, or 20.00%, and the mass content refers to the proportion of the mass of the filler to the total mass of the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition).

[0033] According to an embodiment of the present invention, the orally disintegrating film composition of ambroxol (for example, an orally disintegrating film composition of ambroxol hydrochloride) is selected from the following formulations 1-1 to 1-5, in terms of mass content.

[0034] Formulation 1-1: Contains 15-22% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 18-52% polacrilin potassium, 18-35% film-forming material, 8-12% plasticizer, and 0.3-7% flavoring agent and / or coloring agent.

[0035] Formulation 1-2: Contains 15-22% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 18-46% polacrilin potassium, 18-60% film-forming material, 2-22% plasticizer, and 0-0.05% flavoring agent and / or coloring agent.

[0036] Formulations 1-3: Contains 17-21% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 35-40% polacrilin potassium, 34-41% film-forming material, and 2-6% flavoring agent and / or coloring agent.

[0037] Formulations 1-4: Contains 9-13% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 22-48% sodium polystyrene sulfonate, 30-40% film-forming material, 5-25% plasticizer, and 0.2-10% flavoring agent and / or coloring agent.

[0038] Formulations 1-5: Contains 18-24% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 20-24% sodium polystyrene sulfonate, 13-15% film-forming material, and 40-45% flavoring agent.

[0039] According to an embodiment of the present invention, in the above-mentioned formulations 1-1 to 1-5, the film-forming material is one or more of xanthan gum, polyvinyl alcohol, hypromellose, pullulan, and sodium alginate.

[0040] According to an embodiment of the present invention, in Blends 1-1 to 1-5, the plasticizer is glycerol.

[0041] According to an embodiment of the present invention, in Formulations 1-1 to 1-5, the colorant is a lake.

[0042] The orally disintegrating film composition of ambroxol hydrochloride according to the present invention may have any of the following formulations:

[0043] Formulation 2-1: 18-22% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 48-52% polacrilin potassium, 14-32% film-forming material, 6-10% plasticizer, and 1-3% flavoring agent and / or colorant, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0044] Formulation 2-2: Contains 14-18% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 39-43% polacrilin potassium, 25-29% film-forming material, 9-13% plasticizer, and 1.5-6% flavoring agent and / or colorant, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0045] Formulation 2-3: 13-17% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 36-40% polacrilin potassium, 28-32% film-forming material, 8-12% plasticizer, 1-11% flavoring agent and / or colorant, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0046] Formulation 2-4: 17-21% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 17-21% polacrilin potassium, 58-52% film-forming material, and 0.5-4% plasticizer, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0047] Formulation 2-5: 17-21% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 36-40% polacrilin potassium, 34-41% film-forming material, and 2-6% flavoring agent and / or coloring agent, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0048] Formulation 2-6: 14-18% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 38-42% polacrilin potassium, 30-34% film-forming material, 9-13% plasticizer, 0-0.02% flavoring agent and / or colorant, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0049] Formulation 2-7: 14-18% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 37-41% polacrilin potassium, 29-33% film-forming material, 8-12% plasticizer, 0-6% flavoring agent and / or colorant, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0050] Formulation 2-8: 14-18% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 38-42% polacrilin potassium, 30-34% film-forming material, 9-13% plasticizer, 0-0.5% flavoring agent and / or colorant, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0051] Formulation 2-9: 13-17% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 43-47% polacrilin potassium, 18-22% film-forming material, and 18-22% plasticizer, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0052] Formulation 2-10: 7-11% ambroxol or a pharmacologically 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 colorant, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0053] Formulation 2-11: 10-14% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 21-25% sodium polystyrene sulfonate, 35-39% film-forming material, 23-27% plasticizer, 0-0.5% flavoring agent and / or colorant, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0054] Formulation 2-12: 20-22% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 20-22% sodium polystyrene sulfonate, 12-16% film-forming material, and 30-50% flavoring agent and / or colorant, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0055] According to an embodiment of the present invention, in Formulations 2-1 to 2-12, the film-forming material is one or more of xanthan gum, polyvinyl alcohol, hypromellose, pullulan, and sodium alginate.

[0056] According to an embodiment of the present invention, in Blends 2-1 to 2-12, the plasticizer is glycerol.

[0057] According to an embodiment of the present invention, in Formulations 2-1 to 2-12, the colorant is a lake.

[0058] The orally disintegrating ambroxol film composition according to the present invention may have any of the following formulations:

[0059] Formulation 3-1: Contains 18-22% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 48-52% polacrilin potassium, 11-15% xanthan gum, 4-8% polyvinyl alcohol, 6-10% glycerol, and 1-3% aspartame, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0060] Formulation 3-2: 14-18% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 39-43% polacrilin potassium, 25-29% polyvinyl alcohol, 9-13% glycerol, 0.5-1.5% stevioside, 0.5-1.5% flavor, and 0.5-3% lake, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0061] Formulation 3-3: 13-17% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 36-40% polacrilin potassium, 28-32% polyvinyl alcohol, 8-12% glycerol, 1-5% sucralose, 1-5% flavor, and 0-0.05% lake, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0062] Formulation 3-4: Contains 17-21% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 17-21% polacrilin potassium, 58-52% hypromellose, and 0.5-4% glycerol, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0063] Formulation 3-5: 17-21% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 36-40% polacrilin potassium, 23-27% polyvinyl alcohol, 11-14% pullulan, and 2-6% sucralose, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0064] Formulations 3-6: 14-18% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 38-42% polacrilin potassium, 30-34% polyvinyl alcohol, 9-13% glycerol, and 0-0.02% lake, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0065] Formulations 3-7: 14-18% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 37-41% polacrilin potassium, 29-33% polyvinyl alcohol, 8-12% glycerol, 1-5% sucralose, and 0-0.05% lake, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0066] Formulations 3-8: 14-18% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 38-42% polacrilin potassium, 30-34% polyvinyl alcohol, 9-13% glycerol, 0-0.1% neotame, and 0-0.05% lake, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0067] Formulation 3-9: 13-17% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 43-47% polacrilin potassium, 18-22% xanthan gum, and 18-22% glycerol, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0068] Formulation 3-10: 7-11% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 44-48% sodium polystyrene sulfonate, 16-20% sodium alginate, 10-14% polyvinyl alcohol, 4-8% glycerol, 1-5% sucralose, 1-5% stevioside, and 1-5% flavor, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0069] Formulation 3-11: 10-14% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 21-25% sodium polystyrene sulfonate, 35-39% hypromellose, 23-27% glycerol, and 0-0.5% lake, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0070] Formulation 3-12: 20-22% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 20-22% sodium polystyrene sulfonate, 12-16% xanthan gum, 12-16% sucralose, 12-16% stevioside, and 12-16% flavor, where the percentages refer to the proportion of the mass of each component to the total mass of the composition.

[0071] The orally disintegrating film composition of ambroxol hydrochloride according to the present invention may have any of the following formulations:

[0072] Formulation 1: Ambroxol hydrochloride 20.00%, polacrilin potassium 50.00%, xanthan gum 13.33%, polyvinyl alcohol 6.67%, glycerol 8.67%, and aspartame 1.33%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0073] Formulation 2: Ambroxol hydrochloride 16.48%, polacrilin potassium 41.21%, polyvinyl alcohol 27.47%, glycerol 10.99%, stevioside 1.10%, flavor 1.10%, and lake 1.65%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0074] Formulation 3: Ambroxol hydrochloride 15.23%, polacrilin potassium 38.06%, polyvinyl alcohol 30.45%, glycerol 10.15%, sucralose 3.05%, flavor 3.05%, and lake 0.02%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0075] Formulation 4: Ambroxol hydrochloride 19.48%, polacrilin potassium 19.48%, hypromellose 58.44%, and glycerol 2.60%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0076] Formulation 5: Ambroxol hydrochloride 19.23%, polacrilin potassium 38.46%, polyvinyl alcohol 25.64%, pullulan 12.82%, and sucralose 3.85%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0077] Formulation 6: Ambroxol hydrochloride 16.21%, polacrilin potassium 40.53%, polyvinyl alcohol 32.43%, glycerol 10.81%, and lake 0.02%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0078] Formulation 7: Ambroxol hydrochloride 15.70%, polacrilin potassium 39.26%, polyvinyl alcohol 31.41%, glycerol 10.47%, sucralose 3.14%, and lake 0.02%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0079] Formulation 8: Ambroxol hydrochloride 16.16%, polacrilin potassium 40.40%, polyvinyl alcohol 32.32%, glycerol 10.77%, neotame 0.32%, and lake 0.02%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0080] Formulation 9: Ambroxol hydrochloride 15.00%, polacrilin potassium 45.00%, xanthan gum 20.00%, and glycerol 20.00%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0081] Formulation 10: Ambroxol hydrochloride 9.09%, sodium polystyrene sulfonate 45.45%, sodium alginate 18.18%, polyvinyl alcohol 12.12%, glycerol 6.06%, sucralose 3.03%, stevioside 3.03%, and flavor 3.03%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0082] Formulation 11: Ambroxol hydrochloride 12.45%, sodium polystyrene sulfonate 24.90%, hypromellose 37.34%, glycerol 24.90%, and lake 0.41%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0083] Formulation 12: Ambroxol hydrochloride 21.43%, sodium polystyrene sulfonate 21.43%, xanthan gum 14.29%, sucralose 14.29%, stevioside 14.29%, and flavor 14.29%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0084] Formulation 13: Ambroxol hydrochloride 15.22%, polacrilin potassium 38.06%, polyvinyl alcohol 30.45%, glycerol 10.15%, sucralose 3.05%, flavor 3.05%, and lake 0.02%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0085] Formulation 14: Ambroxol hydrochloride 16.17%, polacrilin potassium 40.40%, polyvinyl alcohol 32.32%, glycerol 10.77%, neotame 0.32%, and lake 0.02%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0086] Formulation 15: Ambroxol hydrochloride 9.10%, sodium polystyrene sulfonate 45.45%, sodium alginate 18.18%, polyvinyl alcohol 12.12%, glycerol 6.06%, sucralose 3.03%, stevioside 3.03%, and flavor 3.03%, where the percentages refer to the proportion of the weight of each component to the total weight of the composition.

[0087] Formulation 16: Ambroxol hydrochloride 21.43%, sodium polystyrene sulfonate 21.43%, xanthan gum 14.29%, sucralose 14.29%, stevioside 14.29%, and flavor 14.27%, where the percentages refer to the weight of each component relative to the total weight of the composition.

[0088] According to an embodiment of the present invention, the mass content of each component in the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition) is 100%, although there may be a rounding error of ±0.2% due to rounding of values.

[0089] The present invention also provides a method for preparing the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition), comprising the following steps:

[0090] Step 1: Prepare an aqueous solution of the active drug.

[0091] Step 2: Add the odorant to the aqueous solution obtained in Step 1 and stir to obtain a sample.

[0092] Step 3: Centrifuge the sample obtained in step 2 and discard a portion of the supernatant so that the mass of the remaining lower layer material is 10–15 times the mass of the active drug to obtain the drug-loaded resin.

[0093] Step 4: The film-forming material is dissolved in water, mixed with one or more of the flavoring agent, plasticizer, colorant, and filler (if any), and stirred uniformly to obtain a paste liquid.

[0094] Step 5: The drug-loaded resin obtained in Step 3 is transferred to the paste obtained in Step 4 and thoroughly stirred to obtain a uniform paste. After stirring is completed, air bubbles are removed from the paste under vacuum, and the orally disintegrating film formulation of ambroxol hydrochloride is obtained through coating, drying, and cutting.

[0095] According to an embodiment of the present invention, in step 1, the active drug solution is prepared, preferably under light-protected conditions.

[0096] According to an embodiment of the present invention, in step 1, the water is preferably purified water.

[0097] According to an embodiment of the present invention, in step 2, the stirring is preferably performed in the dark.

[0098] According to an embodiment of the present invention, in step 2, the stirring time is preferably 8 hours or more.

[0099] According to an embodiment of the present invention, in step 3, the centrifugation is preferably carried out in a centrifuge, which may be a tabletop centrifuge or a low-speed centrifuge.

[0100] According to an embodiment of the present invention, the thickness of the film in the ambroxol orally disintegrating film composition (for example, ambroxol hydrochloride orally disintegrating film composition) is 10 μm to 300 μm, for example, 20 μm to 100 μm.

[0101] According to an embodiment of the present invention, the orally disintegrating film composition of ambroxol (e.g., orally disintegrating film composition of ambroxol hydrochloride) can be completely disintegrated in 900 ml of simulated saliva at 37±1°C within 120 seconds, for example, within 80 seconds.

[0102] The present invention also provides use of the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition) in the preparation of a medicament for treating and / or preventing an indication for which ambroxol or a pharmacologically acceptable salt thereof is used, such as an allergy.

[0103] According to an embodiment of the present invention, the drug is an expectorant or mucolytic agent.

[0104] According to an embodiment of the present invention, the drug is used for expectorant treatment of acute or chronic respiratory diseases accompanied by abnormal respiratory secretions, especially chronic bronchitis, and for adjunctive treatment of neonatal respiratory distress syndrome and pulmonary surgery.

[0105] The present invention also provides a method for preventing and / or treating a disease or disorder, comprising administering the ambroxol orally disintegrating film composition (e.g., ambroxol hydrochloride orally disintegrating film composition) to a patient (e.g., a human or other mammal) in need thereof.

[0106] According to an embodiment of the present invention, the disease or disorder is selected from acute or chronic respiratory diseases accompanied by allergies, excessive sputum, abnormal respiratory secretions, in particular chronic bronchitis, neonatal respiratory distress syndrome and symptoms after lung surgery.

[0107] The orally disintegrating film composition of ambroxol of the present invention, particularly the orally disintegrating film composition of ambroxol hydrochloride, has a good dissolution rate, disintegrates quickly in the oral cavity, does not leave a rough feeling after dissolution, improves the taste of the drug, and can improve patient compliance. Furthermore, the orally disintegrating film composition of ambroxol of the present invention, particularly the orally disintegrating film composition of ambroxol hydrochloride, has a uniform appearance and excellent flexibility. No sedimentation occurs during the preparation of the film solution, and the content uniformity meets the requirements.

[0108] All reagents and raw materials used in the present invention are commercially available.

[0109] [Effects of the invention] The orally disintegrating film composition of ambroxol according to the present invention (e.g., an orally disintegrating film composition of ambroxol hydrochloride) has advantages such as thin thickness, good taste, further improved stability, dissolution in the oral cavity without drinking water, and rapid oral absorption, and has a promising future market potential.

[0110] Furthermore, the orally disintegrating film composition of ambroxol of the present invention (e.g., the orally disintegrating film composition of ambroxol hydrochloride) has easy availability of raw materials, a simple process, easy operation, a high drug loading, and good drug content uniformity, making it suitable for industrial production.

[0111] [Mode for Carrying Out the Invention] The present invention will be further described below with reference to examples, but the present invention is not limited to these examples. In the following examples, experimental methods without specific conditions are carried out according to conventional methods and conditions or selected according to the product instructions.

[0112] Examples 1 to 12 The content of each component in Examples 1 to 12 in Table 1 below is the mass content of each component in the blend after drying (excluding water) calculated based on the mass of each component.

[0113] [Table 1] JPEG2025539954000003.jpg255168JPEG2025539954000004.jpg51169

[0114] "*" indicates that the substance is removed during the process, and " / " indicates that it is not included.

[0115] The method for preparing each of the example formulations above includes the following:

[0116] 1) Weighing of ingredients The raw materials and auxiliary materials were weighed according to the formulation amounts and prepared for use.

[0117] 2) Drug loading onto resin A: Under light-protected conditions, the active drug was added to a certain amount of purified water and completely dissolved.

[0118] B: An odorant was added to the above solution, and stirring was continued for 8 hours or more in the dark.

[0119] C: The above sample was centrifuged in a low-speed tabletop large-capacity centrifuge, and after centrifugation, a portion of the supernatant was discarded so that the mass of the remaining underlying material was 10–15 times the mass of the active drug.

[0120] 3) Preparation of paste D: The film-forming material was dissolved in a certain amount of purified water, and flavoring agents, plasticizers, and colorants (if any) were added and stirred uniformly.

[0121] E: The lower layer material from step 2) was transferred to the solution prepared in step 3) and thoroughly stirred to obtain a uniform paste solution. After stirring was completed, air bubbles were removed from the paste solution in a vacuum environment.

[0122] 4) Coating, drying, and cutting G: The above paste liquid was applied using a coating machine, dried, and then cut into an appropriate size to obtain an orally disintegrating film formulation of ambroxol hydrochloride.

[0123] Comparative Examples 1 to 3 Comparative Examples 1-3 were prepared in the same manner as Examples 3-5 disclosed in CN 102846581 A.

[0124] [Table 2] An "*" indicates that the material is removed during the process.

[0125] Testing Characteristics The orally disintegrating films of ambroxol hydrochloride prepared according to the above Comparative Examples 1 to 3 and Examples 3 to 8 were examined for mechanical strength, disintegration time and related substances.

[0126] Test example 1 Test method for mechanical strength of disintegrating film The ambroxol hydrochloride orally disintegrating films were tested with a texture analyzer to calculate their tensile strength, elongation, and folding endurance, and the results are shown in Table 3 below (six samples were tested for each example).

[0127] [Table 3] JPEG2025539954000007.jpg253169JPEG2025539954000008.jpg141169

[0128] Note: "Cross-sectional area" in the above table refers to the surface area of ​​the orally disintegrating film.

[0129] The maximum force (gf) is the maximum force that the oral disintegrating film can resist after the yielding stage. Tensile strength (MPa) = Maximum force (gf) ÷ 102 ÷ Cross-sectional area (mm 2 ), elongation rate = maximum force distance (mm) ÷ sample height (mm) × 100%.

[0130] The average tensile strength is the average of six sets of data.

[0131] The maximum force distance is the distance the orally disintegrating film stretches when subjected to the maximum force.

[0132] The average elongation rate is the average of six sets of data.

[0133] Folding resistance refers to the ability of an orally disintegrating film to withstand folding at 180°C.

[0134] The above results indicate that the orally disintegrating films of ambroxol hydrochloride prepared according to Examples 3 to 8 have higher tensile strength and folding endurance than those of Comparative Examples 1 to 3, and are more suitable for commercial production, transportation, storage, and administration to patients.

[0135] Test example 2 Six orally disintegrating films were prepared for each of Examples 1 to 12 and Comparative Examples 1 to 3, and the disintegration time of the orally disintegrating films was measured. The test method was as follows: 900 ml of pH 6.8 phosphate buffer medium was added to a 1000 ml beaker (see the preparation method described in the section on buffers in Chinese Pharmacopoeia 2020, 8004) and heated to 37 ± 0.5 ° C. Six orally disintegrating films were simultaneously placed in the beaker of a disintegrating device, and the time until all six orally disintegrating films of each Example and Comparative Example were completely disintegrated was recorded. These results are summarized in Table 4 below.

[0136] [Table 4] The results showed that the orally disintegrating films of ambroxol hydrochloride prepared according to Examples 1 to 12 could be completely disintegrated within 120 seconds.

[0137] Test example 3 Testing of related substances in orally disintegrating films In Comparative Examples 1 to 3, the compatibility experiments of raw materials and auxiliary materials were designed according to the mass ratio of ambroxol hydrochloride and citric acid. The raw materials and auxiliary materials were left at a high temperature of 60°C for 30 days to detect the compatibility of the raw materials and auxiliary materials and the levels of related substances in Comparative Examples 1 to 3 and Examples 3 to 8.

[0138] The detection of related substances was measured according to high-performance liquid chromatography (Chinese Pharmacopoeia, 2020 edition, Four Parts General Rule 0512).

[0139] Solvent: Methanol Test sample solution: Two pieces (7.5 mg standard) or one piece (15 mg standard) of this product (samples prepared in the above Examples or Comparative Examples) were taken and placed in a 20 mL volumetric flask, an appropriate amount of methanol was added, and the mixture was sonicated for 15 minutes to dissolve the ambroxol hydrochloride. After cooling, a solution containing approximately 0.75 mg of ambroxol hydrochloride per mL was prepared using methanol, and the supernatant was used as the test sample solution.

[0140] Control solution: An appropriate amount of the test product solution was accurately measured and diluted with methanol to prepare a solution containing approximately 1.5 μg per mL.

[0141] Chromatography conditions: The packing material used was octylsilane-bonded silica gel (Agient ZORBAX SB-C8 4.6 mm * 150 mm, 3.5 μm). The mobile phase was 10 mmol / L diammonium hydrogen phosphate solution (adjusted to pH 7.0 with phosphoric acid) - acetonitrile (50:50). The detection wavelength was 248 nm. The flow rate was 0.8 mL per minute. The column temperature was 30 °C. The injection plate temperature was 4 °C, the injection volume was 10 μL, and the run time was 30 min.

[0142] System suitability requirements: In the chromatogram of the test article solution, the resolution between the main peak and adjacent chromatographic peaks must meet requirements.

[0143] Measurement method: The test solution and the control solution were accurately measured and injected into the liquid chromatograph, and the chromatograms were recorded for 30 minutes.

[0144] [Table 5]

[0145] [Table 6] JPEG2025539954000012.jpg167169Note: * indicates that the ratio was based on the guidelines and does not include other supplementary materials.

[0146] The results show that the orally disintegrating films prepared in Examples 3 to 6 of the present invention have good stability, but the contents of unknown impurities are relatively high in Comparative Examples 1 to 3. The stability of the orally disintegrating films of the present application is superior to that of Comparative Examples 1 to 3.

[0147] Test example 4 Testing the dissolution curve of oral disintegrating films The orally disintegrating films of ambroxol hydrochloride prepared in Examples 1, 3, and 6 to 8 were tested for dissolution curves under the following conditions: Method 4 (paddle-over-disk method) of "Chinese Pharmacopoeia", 2020 edition, Part 4, 0931, Methods for Determination of Dissolution and Release Rates; The orally disintegrating films of ambroxol hydrochloride were placed on a stainless steel mesh dish using a stirring paddle according to Method 1 and a dissolution cup according to Method 2.

[0148] Test equipment: Dissolution equipment manufactured by Tendai Tenhatsu Co., Ltd.

[0149] Test media: pH 1.2 hydrochloric acid solution, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer.

[0150] Experimental conditions: medium volume 900 ml, temperature 37 ± 0.5 °C, stirring speed 50 rpm, sampling times 5 min, 10 min, 15 min, 30 min.

[0151] The dissolution results and dissolution curves of two batches of ambroxol hydrochloride orally disintegrating film are shown in the following table.

[0152] [Table 7] JPEG2025539954000014.jpg22169The results showed that the cumulative dissolution rates of the orally disintegrating films of ambroxol hydrochloride of the present invention after 15 minutes in pH 1.2 hydrochloric acid solution and pH 6.8 phosphate buffer solution were all 85% or more, and in pH 4.5 acetate buffer solution, the cumulative dissolution rates of the preparations of Examples 3 and batches 6 to 8 after 15 minutes were 85% or more, and the cumulative dissolution rates of the preparation of Example 1 batch after 30 minutes were all 85% or more.

[0153] Test example 4 Evaluation of palatability of orally disintegrating films A batch of ambroxol hydrochloride orally disintegrating film was prepared according to Example 3. Referring to the "Technical Guideline Principles for the Design and Evaluation of the Taste of Pediatric Drugs (Public Comment Draft)" and the literature "Li Pan et al. Application and Development Research of Volunteer Sensory Testing in Drug Taste Evaluation [J], Chinese Journal of Pharmacopoeia, 2017, 52(22):1971-1975," six volunteers were randomly selected to evaluate the palatability of this batch of ambroxol hydrochloride orally disintegrating film using a combination of bitterness value rating method and multifactorial survey evaluation method.

[0154] Depending on the quality characteristics of the orally disintegrating films, palatability was evaluated in terms of appearance, bitterness, sweetness, numbness, and foreign body sensation in the mouth. Of these, bitterness, numbness, and foreign body sensation in the mouth were the main scoring items, and appearance and sweetness were secondary evaluation items. The grades and scoring rules are as follows:

[0155] [Table 8] The results showed that the final palatability scores of the six volunteers were all in the range of 24 to 30, indicating that the orally disintegrating film of ambroxol hydrochloride prepared according to the present invention had a good taste and was well accepted.

[0156] According to the above experimental data, the orally disintegrating film of ambroxol hydrochloride according to the present invention has the advantages of being thin, having good taste, stable properties, instantly dissolving in the oral cavity without drinking water, and being rapidly absorbed orally.

[0157] The above is an illustrative description of the embodiments of the technical solutions of the present invention. It should be understood that the protection scope of the present invention is not limited to the above embodiments. Any modifications, equivalent replacements, improvements, etc. made by those skilled in the art within the spirit and principle of the present invention should be included in the protection scope of the claims of this application.

Claims

1. 1. An orally disintegrating film composition of ambroxol, comprising: The present invention relates to a composition comprising an active drug, a film-forming material, and an odor masking agent, wherein the active drug comprises 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl)benzylamine or a pharmacologically acceptable salt thereof, for example, the hydrochloride salt of 2-amino-3,5-dibromo-N-(trans-4-hydroxycyclohexyl)benzylamine represented by the following formula I: 【Chemistry 1】 Preferably, the orally disintegrating film composition of ambroxol is an orally disintegrating film composition of ambroxol hydrochloride, Preferably, the orally disintegrating film of ambroxol The composition (e.g., ambroxol hydrochloride orally disintegrating film composition) is characterized in that it does not contain a pH adjuster, for example, the pH adjuster includes, but is not limited to, a pharmaceutically acceptable acid for adjusting the pH value.

2. The composition according to claim 1, characterized in that the mass content of the active drug is 1.00% to 40.00%, preferably 5.00% to 30.00%, and the mass content refers to the proportion of the mass of the active drug to the total mass of the composition.

3. the odor masking agent is a cation exchange resin, and the cation exchange resin is preferably one, two or three selected from sodium polystyrene sulfonate, polacrilin potassium, and polacrilin resin, and the particle size D90 of the cation exchange resin is preferably less than 200 μm; and / or The composition according to claim 1 or 2, characterized in that the mass content of the odorant is 10.00% to 70.00%, preferably 15.00% to 60.00%, and the mass content refers to the proportion of the mass of the odorant to the total mass of the composition.

4. the film-forming material is one or more selected from xanthan gum, guar gum, pectin, gelatin, shellac, gum arabic, starch, dextrin, agar, sodium alginate, zein, hypromellose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, polyvinyl alcohol, pullulan, polyvinylpyrrolidone, sodium alginate, polyethylene glycol, polyoxyethylene, acrylic acid copolymer, polylactic acid, and silicone rubber; and / or The composition according to any one of claims 1 to 3, characterized in that the mass content of the film-forming material is 10.00% to 70.00%, preferably 15.00% to 60.00%, and the mass content refers to the proportion of the mass of the film-forming material to the total mass of the composition.

5. The composition of any one of claims 1 to 4, further comprising one or more of a plasticizer, a flavoring agent, a colorant, and a filler.

6. the plasticizer is one or more selected from polyethylene glycol, glycerol, propylene glycol, silicone oil, polypropylene glycol, and hexanediol; and / or the flavoring agent is one or more selected from aspartame, sucralose, fructose, sucrose, stevioside, neotame, glycyrrhizin, flavors, fragrances, saccharin, and saccharin sodium; and / or the colorant is one or more selected from titanium dioxide, pigments, and lakes; and / or 6. The composition of claim 5, wherein the filler is one or more selected from sucrose, glucose, maltose, lactose, sorbitol, xylitol, maltitol, galactitol, erythritol, dextrin, and trehalose.

7. the mass content of the plasticizer is 0 to 30.00%, preferably 0 to 25.00%, and the mass content refers to the proportion of the mass of the plasticizer to the total mass of the composition; and / or the mass content of the flavoring agent is 0 to 50.00%, preferably 0 to 45.00%, and the mass content refers to the ratio of the mass of the flavoring agent to the total mass of the composition; and / or the mass content of the colorant is 0 to 2.00%, and the mass content refers to the ratio of the mass of the colorant to the total mass of the composition; and / or The composition according to claim 6, wherein the mass content of the filler is 0 to 20.00%, the mass content referring to the proportion of the mass of the filler to the total mass of the composition.

8. The composition comprises: Formulation 1-1 comprising 15-22% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 18-52% polacrilin potassium, 18-35% film-forming material, 8-12% plasticizer, and 0.3-7% flavoring agent and / or coloring agent; Formulation 1-2 comprising 15-22% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 18-46% polacrilin potassium, 18-60% film-forming material, 2-22% plasticizer, and 0-0.05% flavoring agent and / or coloring agent; Formulations 1-3 comprising 17-21% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 35-40% polacrilin potassium, 34-41% film-forming material, and 2-6% flavoring and / or coloring agent; Formulations 1-4 comprising 9-13% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 22-48% sodium polystyrene sulfonate, 30-40% film-forming material, 5-25% plasticizer, and 0.2-10% flavoring agent and / or coloring agent; The composition according to any one of claims 1 to 7, which is any one of formulations selected from formulations 1 to 5, comprising 18 to 24% ambroxol or a pharmacologically acceptable salt thereof (e.g., ambroxol hydrochloride), 20 to 24% sodium polystyrene sulfonate, 13 to 15% film-forming material, and 40 to 45% flavoring agent.

9. the thickness of the composition is 10 μm to 300 μm; and / or The composition according to any one of claims 1 to 8, characterized in that the composition is completely disintegrated in 900 ml of simulated saliva at 37±0.5°C within 120 seconds.

10. Use of a composition according to any one of claims 1 to 9 in the preparation of a medicament for treating and / or preventing allergies, comprising: Preferably, the drug is an expectorant or mucolytic agent; Preferably, the drug is used in the expectorant treatment of acute or chronic respiratory diseases accompanied by abnormal respiratory secretions, especially chronic bronchitis, and in the adjunctive treatment of neonatal respiratory distress syndrome and pulmonary surgery.

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