Compound emblic leafflower fruit sore-throat relieving lozenge film-coated tablet for treating throat diseases and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a compound emblic leafflower fruit sore-throat relieving lozenge film-coated tablet for treating throat diseases and a preparation method thereof. The compound emblic leafflower fruit sore-throat relieving lozenge film-coated tablet for treating throat diseases comprises a tablet core and a film coating layer wrapping the tablet core, the tablet core comprises phyllanthus emblica dry paste powder, compound dry powder, menthol, borneol, corn starch, sucrose powder and hydroxypropyl methylcellulose; the compound dry powder is a water extract of a mixture of radix scrophulariae, platycodon grandiflorum and liquorice; the weight ratio of the corn starch to the sucrose powder to the hydroxypropyl methylcellulose is (0.5-15): (45-60): (0.5-8); the film coating layer comprises gelatin; the weight ratio of the gelatin to the hydroxypropyl methylcellulose is (0.5-8): (0.3-3). The compound emblic leafflower fruit sore-throat relieving lozenge film-coated tablet for treating throat diseases has good storage stability, and the appearance and palatability are improved.

Description

Technical Field

[0001] This application relates to the field of traditional Chinese medicine preparation technology, and in particular to compound Phyllanthus emblica throat lozenges with film coating for the treatment of throat diseases and their preparation method. Background Technology

[0002] Compound Phyllanthus emblica lozenges (National Drug Approval Number B20020422) utilize pharmacological effects such as clearing heat and detoxifying, reducing swelling and relieving pain to specifically alleviate throat symptoms such as dryness, itching, pain, burning discomfort, foreign body sensation, and dry cough with little phlegm. It has clinical advantages in the adjunctive treatment of throat diseases. However, the active components of Compound Phyllanthus emblica lozenges may leach out during storage. Therefore, it is necessary to improve the dosage form of Compound Phyllanthus emblica lozenges to enhance its storage stability.

[0003] Film coating technology is a technique that uses polymer materials to form a thin film on the surface of a drug to encapsulate it. Compared to traditional sugar coating, it reduces coating weight gain, shortens drying time, and improves moisture resistance and dissolution. It is currently widely used in the production of tablets and pills. However, no film-coated tablets of Compound Phyllanthus emblica lozenges have been reported. Furthermore, Compound Phyllanthus emblica lozenges contain borneol, menthol, and other volatile components. Film coating technology has limited effectiveness in blocking these volatile components, and they may precipitate on the surface after a period of storage, affecting the quality of the drug. Summary of the Invention

[0004] Based on this, one or more embodiments of this application provide a compound Phyllanthus emblica throat lozenge film-coated tablet for treating throat diseases and a method for preparing the same. The compound Phyllanthus emblica throat lozenge film-coated tablet for treating throat diseases has good storage stability, can avoid the release of volatile active ingredients, and improves appearance and palatability.

[0005] The compound Phyllanthus emblica throat lozenges of this application for the treatment of throat diseases are film-coated tablets, which include a tablet core and a film coating layer that wraps the tablet core.

[0006] The tablet core comprises Phyllanthus emblica extract powder, compound powder, menthol, borneol, corn starch, sucrose powder, and hydroxypropyl methylcellulose; the compound powder is an aqueous extract of a mixture of Scrophularia ningpoensis, Platycodon grandiflorus, and Glycyrrhiza uralensis; the weight ratio of corn starch, sucrose powder, and hydroxypropyl methylcellulose is (0.5-15):(45-60):(0.5-8);

[0007] The film coating layer comprises gelatin; the weight ratio of the gelatin to the hydroxypropyl methylcellulose is (0.5-8):(0.3-3).

[0008] Furthermore, based on the weight of the compound Phyllanthus emblica throat lozenges for treating throat diseases, it comprises: 0.5%~2% of the Phyllanthus emblica dry extract powder; 3%~15% of the compound dry powder; 0.1%~0.5% of the menthol; 0.05%~0.5% of the borneol; 0.5%~15% of the corn starch; 45%~60% of the sucrose powder; 0.5%~8% of the hydroxypropyl methylcellulose; and 0.3%~3% of the gelatin.

[0009] In some embodiments, the core also includes at least one of dextrin, talc, and magnesium stearate.

[0010] Further, based on the weight of the compound Phyllanthus emblica throat lozenges for treating throat diseases, it comprises: 0.5%~2% of the Phyllanthus emblica dry extract powder; 3%~15% of the compound dry powder; 0.1%~0.5% of the menthol; 0.05%~0.5% of the borneol; 0.5%~15% of the corn starch; 45%~60% of the sucrose powder; 0.5%~8% of the hydroxypropyl methylcellulose; 10%~30% of the dextrin; 0.5%~5% of the talc; and 0.5%~5% of the magnesium stearate; and 0.3%~3% of the gelatin.

[0011] In some embodiments, the preparation method of the amla extract powder includes the following steps: washing fresh amla fruits, removing the pits, juicing, filtering to obtain the filtrate, concentrating the filtrate, and drying to obtain the amla extract powder; and / or,

[0012] The preparation method of the compound dry powder includes the following steps: mixing Scrophularia, Platycodon, and Glycyrrhiza in a mass ratio of 3:3:1; decocting the mixture with water, concentrating, and drying to obtain the compound dry powder; and / or,

[0013] The weight ratio of the dried amla extract powder, the compound powder, the menthol, and the borneol is (0.5-2):(3-15):(0.1-0.5):(0.05-0.5), and the total accounts for 3.65%-18% of the weight of the film-coated compound amla throat lozenges used to treat throat diseases.

[0014] This application also provides a method for preparing the compound Phyllanthus emblica throat lozenges film-coated tablets for treating throat diseases as described above, comprising the following steps:

[0015] The tablet core is spray-coated with a coating solution; the coating solution comprises gelatin and a first alcohol solvent, wherein the mass concentration of the gelatin is 1% to 5%; the first alcohol solvent comprises ethanol and water.

[0016] The weight ratio of the coating solution to the tablet core is (0.5-2):100;

[0017] Optionally, the volume concentration of ethanol in the first alcohol solvent is 40%-80%.

[0018] In some embodiments, the preparation method of the coating solution includes the following steps:

[0019] The gelatin was added to the first alcohol solvent and mixed. After standing for 2-24 hours, it was dissolved by heating in a water bath to obtain a solution.

[0020] The solution is filtered through an 80-100 mesh sieve to obtain the coating solution.

[0021] In some embodiments, the method for preparing the wafer core includes the following steps:

[0022] The amla extract powder, the compound powder, the corn starch, the sucrose powder, and the hydroxypropyl methylcellulose are mixed and then added to a second alcohol solution to form a soft material; the second alcohol solvent comprises ethanol and water.

[0023] The soft material is granulated, dried, and sieved to obtain granules;

[0024] The borneol and menthol are dissolved in a tertiary alcohol solution, sprayed into the granules and mixed, and then the magnesium stearate and talc are added and mixed to obtain mixed granules; the tertiary alcohol solvent consists of ethanol and water.

[0025] The mixed granules are compressed into tablets to obtain tablet cores;

[0026] Optionally, the volume concentration of ethanol in the second alcohol solution is 60%-90%;

[0027] Optionally, the volume concentration of ethanol in the third alcohol solution is 40%-95%.

[0028] Furthermore, granulation includes dispersion using a 10-14 mesh sieve; and / or,

[0029] The drying temperature is 50℃-75℃; and / or,

[0030] Screening includes screening using a 15-17 mesh sieve.

[0031] In some embodiments, the step of spray coating the wafer core with a coating solution includes:

[0032] The wafer core is loaded into the coating cylinder, and the rotation speed of the coating cylinder is set to 3-8 revolutions / min;

[0033] The coating solution is atomized and sprayed onto the tablet core to form a coating.

[0034] The outlet air temperature of the coating cylinder is 45℃-65℃, and the inlet air temperature is ≤100℃.

[0035] The compound amla throat lozenge film-coated tablet of this application for treating throat diseases contains a suitable proportion of corn starch, sucrose powder, and hydroxypropyl methylcellulose in its core. This core, together with the gelatin in the film coating layer, forms a synergistic barrier system. The corn starch and sucrose form a dense, porous structure on the surface of the core material, adsorbing volatile components and reducing their migration to the coating layer. During granulation, hydroxypropyl methylcellulose cross-links with gelatin molecules through hydrogen bonds, enhancing the mechanical strength of the coating layer and effectively preventing the gelatin from becoming brittle. Through this synergistic barrier system, the compound amla throat lozenge film-coated tablet for treating throat diseases can maintain a stable glassy state under temperature and humidity changes, significantly improving barrier efficiency and effectively preventing the precipitation of volatile components, thus exhibiting excellent storage stability.

[0036] The compound Phyllanthus emblica throat lozenge film-coated tablets of this application for the treatment of throat diseases also have excellent optical transparency, fully presenting the inherent color of the tablet core, and its slightly sweet properties can effectively neutralize the bitterness of borneol; sensory evaluation tests show that the palatability score is greatly improved.

[0037] The compound Phyllanthus emblica throat lozenges of this application for the treatment of throat diseases have low raw material costs. In some embodiments, the raw material cost can be reduced by about 30% to 40% compared with commercially available premixed coating agents. The formulation process has the advantages of simple operation, high production efficiency, low energy consumption, easy control of process parameters, and good batch-to-batch stability. It meets GMP requirements and is suitable for large-scale continuous production.

[0038] In some preferred embodiments, the compound Phyllanthus emblica throat lozenge film-coated tablets for treating throat diseases have been verified by long-term stability studies and variable temperature environment test data. Under 12-month accelerated test conditions, no volatile active ingredients were released, and the appearance remained stable, thus extending the effective period to 36 months, demonstrating good market application prospects. Detailed Implementation

[0039] The present application is further described below with reference to embodiments and examples. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the application. Furthermore, it should be understood that after reading the teachings of this application, those skilled in the art can make various alterations or modifications to this application, and these equivalent forms also fall within the protection scope of the appended claims.

[0040] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0041] The term “and / or” as used in this application includes any and all combinations of one or more of the associated listed items.

[0042] The compound Phyllanthus emblica throat lozenges of this application for the treatment of throat diseases are film-coated tablets, which include a tablet core and a film coating layer that wraps the tablet core.

[0043] The tablet core consists of Phyllanthus emblica extract powder, compound powder, menthol, borneol, corn starch, sucrose powder, and hydroxypropyl methylcellulose; the compound powder is an aqueous extract of a mixture of Scrophularia ningpoensis, Platycodon grandiflorus, and Glycyrrhiza uralensis; the weight ratio of corn starch, sucrose powder, and hydroxypropyl methylcellulose is (0.5-15):(45-60):(0.5-8);

[0044] The film coating layer comprises gelatin; the weight ratio of gelatin to hydroxypropyl methylcellulose is (0.5-8):(0.3-3). Optionally, the weight ratio of corn starch, sucrose powder, and hydroxypropyl methylcellulose is selected from any value within the range of (0.5-15):(45-60):(0.5-8), for example, 1:90:1 (0.5:45:0.5), 1:90:16 (0.5:45:8), 30:90:1 (15:45:0.5), 15:45:8, 1:120:1 (0.5:60:0.5), 1:120:16 (0.5:60:8), 30:120:1 (15:60:0.5), 15:60:8, etc.

[0045] Optionally, the weight ratio of gelatin to hydroxypropyl methylcellulose is selected from any value in the range of (0.5-8):(0.3-3), such as 5:3 (0.5:0.3), 1:6 (0.5:3), 80:3 (8:0.3), 8:3, etc.

[0046] The Phyllanthus emblica dry extract powder and compound dry powder of this application refer to the relevant limitations in the implementation standard of Compound Phyllanthus emblica Throat Lozenges (National Drug Approval Number B20020422), and the proportion of each active ingredient refers to the above standard.

[0047] In some embodiments, the preparation method of Phyllanthus emblica extract powder includes the following steps: washing fresh Phyllanthus emblica, removing the pits, juicing, filtering to obtain the filtrate, concentrating the filtrate, drying to obtain Phyllanthus emblica extract powder.

[0048] In some specific embodiments, the preparation method of Phyllanthus emblica extract powder includes the following steps: Fresh Phyllanthus emblica fruits are washed, pitted, and juiced to obtain juice and pomace. The pomace is juiced again, and the two juices are combined and filtered to obtain Phyllanthus emblica juice. The Phyllanthus emblica juice and water are added to a concentrator at a ratio of 1:2 and concentrated to a Baume degree of 8-10 Be. The mixture is boiled for 3 hours, and after boiling, it is further concentrated to 18-22 Be (70-80℃) to obtain a concentrated solution. The concentrated solution is spray-dried into powder (inlet air temperature 170-180℃, outlet air temperature 70-90℃) to obtain Phyllanthus emblica extract powder.

[0049] In some embodiments, the preparation method of the compound dry powder includes the following steps: mixing Scrophularia, Platycodon and Glycyrrhiza in a mass ratio of 3:3:1, decocting the mixture with water, concentrating and drying to obtain the compound dry powder.

[0050] In some specific embodiments, the preparation method of the compound dry powder includes the following steps: Scrophularia, Platycodon, and Glycyrrhiza are mixed in a 3:3:1 mass ratio, and extracted twice with water. For the first extraction, 10-12 times the amount of water is added, and the mixture is boiled for 1-2.5 hours. For the second extraction, 8-10 times the amount of water is added, and the mixture is boiled for 1-2.5 hours. The mixture is filtered, and the two filtrates are combined. The filtrate is concentrated to a Baume degree of (18-22 Be) (75-80℃) to obtain a concentrated solution. The concentrated solution is spray-dried into powder (inlet air temperature 160-180℃, outlet air temperature 70-90℃), and the spray-dried powder is pulverized through an 80-mesh sieve for later use.

[0051] Furthermore, the weight ratio of Phyllanthus emblica dry powder, compound dry powder, menthol, and borneol is (0.5-2):(3-15):(0.1-0.5):(0.05-0.5), and the total accounts for 3.65%-18% of the weight of the film-coated tablets of the Compound Phyllanthus emblica Throat Lozenges used to treat throat diseases.

[0052] Furthermore, based on the weight of the compound Phyllanthus emblica throat lozenges used to treat throat diseases, it comprises 0.5%~2% Phyllanthus emblica dry extract powder; 3%~15% compound dry powder; 0.1%~0.5% menthol; 0.05%~0.5% borneol; 0.5%~15% corn starch; 45%~60% sucrose powder; 0.5%~8% hydroxypropyl methylcellulose; and 0.3%~3% gelatin.

[0053] In this embodiment, provided that the weight percentage of the compound Phyllanthus emblica throat lozenges used to treat throat diseases is 100%, the weight percentage of Phyllanthus emblica dry powder can be freely selected from 0.5% to 2%, for example, 0.5%, 1%, 2%, etc.; the weight percentage of the compound dry powder can be freely selected from 3% to 15%, for example, 3%, 10%, 15%, etc.; the weight percentage of menthol can be freely selected from 0.1% to 0.5%, for example, 0.1%, 0.2%, 0.5%, etc.; and the weight percentage of borneol can be freely selected from 0.05% to 0.5%, for example, 0.05%. The weight percentage of corn starch can be freely selected from 0.5% to 15%, for example, 0.5%, 1%, 2%, 5%, 10%, 15%, etc.; the weight percentage of sucrose powder can be freely selected from 45% to 60%, for example, 45%, 50%, 55%, 60%, etc.; the weight percentage of hydroxypropyl methylcellulose can be freely selected from 0.5% to 8%, for example, 0.5%, 1%, 2%, 5%, 8%, etc.; the weight percentage of gelatin can be freely selected from 0.3% to 3%, for example, 0.3%, 1%, 2%, 3%, etc. In some embodiments, the core also includes at least one of dextrin, talc, and magnesium stearate.

[0054] Furthermore, based on the weight of the compound Phyllanthus emblica throat lozenges used to treat throat diseases, it comprises 0.5%~2% Phyllanthus emblica dry extract powder; 3%~15% compound dry powder; 0.1%~0.5% menthol; 0.05%~0.5% borneol; 0.5%~15% corn starch; 45%~60% sucrose powder; 0.5%~8% hydroxypropyl methylcellulose; 10%~30% dextrin; 0.5%~5% talc; and 0.5%~5% magnesium stearate; and 0.3%~3% gelatin. In this embodiment, provided that the weight percentage of the compound amla throat lozenges used to treat throat diseases is 100%, the weight percentage of amla dry powder can be freely selected from 0.5% to 2%, for example, 0.5%, 1%, 2%, etc.; the weight percentage of the compound dry powder can be freely selected from 3% to 15%, for example, 3%, 10%, 15%, etc.; the weight percentage of menthol can be freely selected from 0.1% to 0.5%, for example, 0.1%, 0.2%, 0.5%, etc.; the weight percentage of borneol can be freely selected from 0.05% to 0.5%, for example, 0.05%, 0.1%, 0.2%, 0.5%, etc.; the weight percentage of corn starch can be freely selected from 0.5% to 15%, for example, 0.5%, 1%, 2%, 5%, 10%, 15%, etc. The weight percentage of sucrose powder can be freely selected from 45% to 60%, for example, 45%, 50%, 55%, 60%, etc.; the weight percentage of hydroxypropyl methylcellulose can be freely selected from 0.5% to 8%, for example, 0.5%, 1%, 2%, 5%, 8%, etc.; the weight percentage of dextrin can be freely selected from 10% to 30%, for example, 10%, 15%, 20%, 25%, 30%, etc.; the weight percentage of talc can be freely selected from 0.5% to 5%, for example, 0.5%, 1%, 2%, 5%, etc.; the weight percentage of magnesium stearate can be freely selected from 0.5% to 5%, for example, 0.5%, 1%, 2%, 5%, etc.; the weight percentage of gelatin can be freely selected from 0.3% to 3%, for example, 0.3%, 1%, 2%, 3%, etc.

[0055] In some embodiments, the compound powder is prepared by decoction, concentration and drying of Scrophularia, Platycodon, and Glycyrrhiza in a mass ratio of 3:3:1.

[0056] This application also provides a method for preparing the compound Phyllanthus emblica throat lozenge film-coated tablets for treating throat diseases, as described above, including the following steps:

[0057] The tablet core is spray-coated with a coating solution; the coating solution consists of gelatin and a first alcohol solvent, the mass concentration of gelatin is 1% to 5% (e.g., 1%, 2%, 3%, 4%, 5%, etc.); the first alcohol solvent consists of ethanol and water;

[0058] The weight ratio of coating solution to tablet core is (0.5-2):100 (e.g., 0.5:100, 1:100, 2:100, etc.).

[0059] Optionally, the volume concentration of ethanol in the first alcohol solvent is 40%-80% (e.g., 40%, 50%, 60%, 70%, 80%, etc.).

[0060] In some embodiments, the preparation method of the coating solution includes the following steps:

[0061] Gelatin is added to a primary alcohol solvent and mixed. After standing for 2-24 hours (e.g., 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, etc.), it is dissolved by heating in a water bath to obtain a solution.

[0062] The solution is filtered through an 80-100 mesh sieve to obtain the coating solution.

[0063] In some embodiments, the method for preparing the wafer core includes the following steps:

[0064] Phyllanthus emblica extract powder, compound powder, corn starch, sucrose powder and hydroxypropyl methylcellulose are mixed and added to a second alcohol solution to make a soft material; the second alcohol solvent consists of ethanol and water.

[0065] The soft material is granulated, dried, and sieved to obtain granules;

[0066] Borneol and menthol are dissolved in a tertiary alcohol solution, sprayed into the granules and mixed, and then magnesium stearate and talc are added and mixed to obtain mixed granules; the tertiary alcohol solvent consists of ethanol and water.

[0067] The mixed granules are compressed into tablets to obtain tablet cores;

[0068] Optionally, the volume concentration of ethanol in the second alcohol solution is 60%-90% (e.g., 60%, 70%, 80%, 90%, etc.).

[0069] Optionally, the volume concentration of ethanol in the third alcohol solution is 40%-95% (e.g., 40%, 60%, 80%, 90%, 95%, etc.).

[0070] Furthermore, granulation includes dispersion using a 10-14 mesh sieve; and / or,

[0071] The drying temperature is 50℃-75℃ (e.g., 50℃, 60℃, 70℃, 75℃, etc.); and / or,

[0072] Screening includes screening using a 15-17 mesh sieve.

[0073] In some embodiments, the step of spray coating the tablet core with a coating solution includes:

[0074] Load the film core into the coating cylinder and set the rotation speed of the coating cylinder to 3-8 revolutions per minute;

[0075] The coating solution is atomized and sprayed onto the tablet core to form a coating;

[0076] The outlet air temperature of the coating cylinder is 45℃-65℃ (e.g., 45℃, 50℃, 55℃, 60℃, 65℃, etc.), and the inlet air temperature is ≤100℃, which can be further 80℃-100℃ (e.g., 80℃, 90℃, 100℃, etc.).

[0077] The compound amla throat lozenge film-coated tablet of this application for treating throat diseases contains a suitable proportion of corn starch, sucrose powder, and hydroxypropyl methylcellulose in its core. This core, together with the gelatin in the film coating layer, forms a synergistic barrier system. The corn starch and sucrose form a dense, porous structure on the surface of the core material, adsorbing volatile components and reducing their migration to the coating layer. During granulation, hydroxypropyl methylcellulose cross-links with gelatin molecules through hydrogen bonds, enhancing the mechanical strength of the coating layer and effectively preventing the gelatin from becoming brittle. Through this synergistic barrier system, the compound amla throat lozenge film-coated tablet for treating throat diseases can maintain a stable glassy state under temperature and humidity changes, significantly improving barrier efficiency and effectively preventing the precipitation of volatile components, thus exhibiting excellent storage stability.

[0078] The following are some specific examples.

[0079] For experimental parameters not specified in the following specific embodiments, please refer to the guidelines given in this application document first, or refer to experimental manuals or other experimental methods known in the art, or refer to the experimental conditions recommended by the manufacturer.

[0080] The raw materials and reagents involved in the following specific embodiments can be obtained commercially or prepared by those skilled in the art using known methods.

[0081] The equipment and testing instruments used in the following examples are: 3100C electronic balance, BS223S electronic balance, CH-18 core removal machine, 5m 3 Multifunctional extraction tank, SJN-1000 triple-effect energy-saving concentrator, QPG-25 spray dryer unit, SP1500 laboratory spray dryer, WF-30B universal high-speed pulverizer, HZD800B automatic lifting hopper mixer, FL-200 fluidized bed dryer granulator, YK-160A swing granulator, GZPL40C high-speed rotary tablet press, BGB-150C high-efficiency coating machine, Waters 2695-2998 high-performance liquid chromatograph.

[0082] I. Preparation of Compound Phyllanthus Phyllanthus Throat Lozenges with Film Coating for the Treatment of Throat Diseases.

[0083] Example 1

[0084] The preparation method of compound Phyllanthus emblica throat lozenges for treating throat diseases provided in this embodiment includes the following steps:

[0085] S1. Scrophularia, Platycodon, and Glycyrrhiza (in a 3:3:1 mass ratio) were extracted twice with water. For the first extraction, 10-12 times the amount of water was added, and the mixture was boiled for 1-2.5 hours. For the second extraction, 8-10 times the amount of water was added, and the mixture was boiled for 1-2.5 hours. The mixture was filtered, and the two filtrates were combined. The filtrates were concentrated to a Baume degree of 18-22 Be (75-80℃) to obtain a concentrated solution. The concentrated solution was spray-dried into powder (inlet air temperature 160-180℃, outlet air temperature 70-90℃). The spray-dried powder was then pulverized through an 80-mesh sieve to obtain the compound dry powder.

[0086] S2. Phyllanthus emblica extract powder: Wash fresh Phyllanthus emblica fruits, remove the pits, and juice them to obtain juice and pulp. Juice the pulp again, combine the two juices, and filter to obtain Phyllanthus emblica juice. Add Phyllanthus emblica juice and water to a concentrator at a ratio of 1:2 and concentrate to a Baume degree of 8-10 Be. Boil for 3 hours, and after boiling, continue concentrating to 18-22 Be (70-80℃) to obtain a concentrated liquid. Spray dry the concentrated liquid into powder (inlet air temperature 170-180℃, outlet air temperature 70-90℃) to obtain Phyllanthus emblica extract powder.

[0087] S3. Mix the dried amla extract powder, compound powder, corn starch, sucrose powder, hydroxypropyl methylcellulose, and dextrin in a wet granulator, then pass the mixture through a vibrating granulator. Mix again in a wet granulator for 1-10 minutes, add an appropriate amount of 60%-90% ethanol, and mix for 2-4 minutes to form a soft mass. Disperse the soft mass through a 10-14 mesh sieve in a vibrating granulator to form wet granules. Dry the granules in a fluidized bed dryer at 50-75℃, and then sieve through a 16 mesh sieve to obtain compound amla throat lozenge granules.

[0088] S4. Dissolve borneol and menthol in 80%-95% ethanol and stir until completely dissolved. Place the above compound amla throat lozenge granules in a trough mixer, spray in the borneol and menthol mixture and mix evenly. Add magnesium stearate and talc powder and mix evenly to obtain compound amla throat lozenge granules.

[0089] S5. The above-mentioned compound amla throat lozenges were mixed and compressed to obtain tablet cores.

[0090] S6. Add gelatin to 40-80% ethanol according to the ratio and stir. After standing for 2-24 hours, heat in a water bath until completely dissolved, stir evenly, pass through an 80-100 mesh sieve, and keep sealed and warm to obtain the coating solution. Preheat the drum, pour in the tablet cores to be coated, preheat the tablet cores, adjust the spray nozzle to achieve a suitable atomization state, control the coating cylinder speed at 3-8 rpm during the coating process, the outlet air temperature should be controlled at 45-65℃, and the inlet air temperature is generally ≤100℃, mainly focusing on keeping the outlet air temperature within the control range. After spraying the prepared solution, stop the machine, turn off the hot air, and turn on the exhaust air to allow the temperature of the coated tablets to slowly drop to room temperature (during this period, the coated tablets should be rotated from time to time), and remove the film-coated tablets. The moisture content after coating is ≤7.0%; the tablet weight after coating is controlled at 1.0±4.5%, yielding the compound Phyllanthus emblica throat lozenges film-coated tablets for the treatment of throat diseases.

[0091] Comparative Example 1

[0092] This comparative example uses a conventional method for preparing compound Phyllanthus emblica throat lozenges coated with hydroxypropyl methylcellulose (HPMC). The specific operational steps are basically the same as in Example 1, with steps S1-S5 being identical. The difference is in S6: 20 times the amount of hydroxypropyl methylcellulose in 95% ethanol is added to a beaker while stirring. The hydroxypropyl methylcellulose is added rapidly and evenly at a constant stirring speed until homogeneous. Then, 10 times the amount of the prescribed hydroxypropyl methylcellulose in purified water is added and stirred until homogeneous. The mixture is allowed to soak until it swells evenly. Then, the prescribed amount of talc is added and stirred for 45 minutes. The mixture is then passed through a 100-mesh sieve and set aside. The drum is preheated, and the tablet cores to be coated are poured in. The tablet cores are preheated, and the spray nozzle is adjusted to achieve a suitable atomization state. During the coating process, the coating cylinder speed is controlled at 6 rpm. The outlet air temperature during the coating process should be controlled at 58-66℃, and the inlet air temperature ≤100℃.

[0093] Comparative Example 2

[0094] This comparative example uses a conventional Opadryl film coating agent (290F690003-CN transparent) to prepare compound Phyllanthus emblica throat lozenges. The specific operating steps are basically the same as in Example 1, with steps S1-S5 being identical. The difference is in S6: the Opadryl film coating agent (290F690003-CN transparent) is added to purified water to prepare a 20% coating suspension. The drum is preheated, and the tablet cores to be coated are poured in. The tablet cores are preheated, and the spray nozzle is adjusted to achieve a suitable atomization state. During the coating process, the coating cylinder speed is controlled at 6 rpm, and the outlet air temperature should be controlled between 58-66℃, while the inlet air temperature should be ≤100℃.

[0095] Comparative Example 3

[0096] This comparative example uses a conventional method for preparing compound Phyllanthus emblica throat lozenges coated with the standard European yellow coating agent YCM-C-050996 and sucralose. The specific operational steps are basically the same as in Example 1, with steps S1-S5 being identical. The difference is in step S6: YCM-C-050996 and sucralose are added to purified water to prepare a 15% coating suspension. The drum is preheated, and the tablet cores to be coated are poured in. The tablet cores are preheated, and the spray nozzle is adjusted to achieve a suitable atomization state. During the coating process, the coating cylinder speed is controlled at 6 rpm, and the outlet air temperature should be controlled between 58-66℃, while the inlet air temperature should be ≤100℃.

[0097] Comparative Example 4

[0098] This comparative example uses a conventional gelatin + talc coating method to prepare compound Phyllanthus emblica throat lozenges: the specific operation steps are basically the same as in Example 1, and steps S1-S5 are exactly the same as in Example 1; the difference is: S6: add 0.5% gelatin to 20-60% ethanol and stir, let stand for 14-18 hours, then heat in a water bath until completely dissolved, add 0.1% talc and stir evenly, then pass through a 100-sieve. Keep sealed and warm, for later use. Preheat the drum, pour in the tablet cores to be coated, preheat the tablet cores, adjust the spray nozzle to achieve a suitable atomization state, control the coating cylinder speed at 6 rpm during the coating process, the outlet air temperature during the coating process should be controlled at 58-66℃, and the inlet air temperature ≤100℃.

[0099] Comparative Example 5

[0100] This comparative example uses the preparation method of Compound Phyllanthus emblica Throat Lozenges: the specific operation steps are basically the same as in Example 1, steps S1-S5 are exactly the same as in Example 1, no coating, and it is a plain tablet.

[0101] Comparative Example 6

[0102] This comparative example uses the preparation method of compound Phyllanthus emblica throat lozenge film-coated tablets: the specific operation steps are basically the same as in Example 1, and steps S1-S2 and S4-S6 are exactly the same as in Example 1, except that the proportion of corn starch in S3 is 0.5%.

[0103] Comparative Example 7

[0104] This comparative example uses the preparation method of compound Phyllanthus emblica throat lozenge film-coated tablets: the specific operation steps are basically the same as in Example 1, and steps S1-S2 and S4-S6 are exactly the same as in Example 1, except that the proportion of corn starch in S3 is 20%.

[0105] Comparative Example 8

[0106] This comparative example uses the preparation method of compound Phyllanthus emblica throat lozenge film-coated tablets: the specific operation steps are basically the same as in Example 1, and steps S1-S2 and S4-S6 are exactly the same as in Example 1, except that hydroxypropyl methylcellulose is not added in S3.

[0107] Comparative Example 9

[0108] This comparative example uses the preparation method of compound Phyllanthus emblica throat lozenge film-coated tablets: the specific operation steps are basically the same as in Example 1, and steps S1 and S3-S5 are exactly the same as in Example 1, except that the proportion of hydroxypropyl methylcellulose in S2 is 10%.

[0109] Comparative Example 10

[0110] This comparative example uses the preparation method of compound Phyllanthus emblica throat lozenge film-coated tablets: the specific operation steps are basically the same as in Example 1, and steps S1-S2 and S4-S6 are exactly the same as in Example 1, except that the proportion of hydroxypropyl methylcellulose in S3 is 0.2%.

[0111] Comparative Example 11

[0112] This comparative example uses the preparation method of compound Phyllanthus emblica throat lozenge film-coated tablets: the specific operation steps are basically the same as in Example 1, and steps S1-S2 and S4-S6 are exactly the same as in Example 1, except that the proportion of sucrose powder in S3 is 70%.

[0113] Comparative Example 12

[0114] This comparative example uses the preparation method of compound Phyllanthus emblica throat lozenge film-coated tablets: the specific operation steps are basically the same as in Example 1, and steps S1-S2 and S4-S6 are exactly the same as in Example 1, except that the proportion of sucrose powder in S3 is 10%.

[0115] Comparative Example 12

[0116] This comparative example uses the preparation method of compound Phyllanthus emblica throat lozenge film-coated tablets: the specific operation steps are basically the same as in Example 1, and steps S1-S2 and S4-S6 are exactly the same as in Example 1, except that the proportion of sucrose powder in S3 is 10%.

[0117] Comparative Example 13

[0118] This comparative example uses the preparation method of compound Phyllanthus emblica throat lozenge film-coated tablets: the specific operation steps are basically the same as in Example 1, and the steps of S1-S2 and S4-S6 are exactly the same as in Example 1. The difference is that the hydroxypropyl methylcellulose in S3 is in the ratio of gelatin to hydroxypropyl methylcellulose = 0.5:5.

[0119] Comparative Example 14

[0120] This comparative example uses the preparation method of compound Phyllanthus emblica throat lozenge film-coated tablets: the specific operation steps are basically the same as in Example 1, and steps S1-S2 and S4-S6 are exactly the same as in Example 1. The difference is that the hydroxypropyl methylcellulose in S3 is in the ratio of gelatin to hydroxypropyl methylcellulose = 8:0.1.

[0121] II. Stability testing of Compound Phyllanthus emblica Throat Lozenges Film-coated Tablets in Examples and Comparative Examples.

[0122] (1) Acceleration stability

[0123] The samples from Example 1 and Comparative Examples 1-5 were placed in a stability test chamber at a temperature of 40℃±2℃ and a relative humidity of 75%±5%. The test results are shown in Table 1.

[0124] Table 1. Accelerated stability test results of Example 1 and Comparative Examples 1-5

[0125]

[0126] (2) Temperature stability comparison test (indoor)

[0127] The samples from Example 1 and Comparative Examples 1-5 were placed in a fixed process room at a temperature of 18-30℃ and a relative humidity of 40%-80%. The temperature and humidity were recorded daily, and the test results are shown in Table 2.

[0128] Table 2. Temperature stability test results (indoor) of Example 1 and Comparative Examples 1-5

[0129]

[0130] (3) Temperature stability comparison test (indoor + outdoor)

[0131] Test conditions: Simulating temperature changes during the storage and transportation of normal production samples. Simulation conditions include:

[0132] a) Temperature and humidity controlled storage (warehouse storage) conditions: Temperature 20-30℃, relative humidity 40%-65%. Operation: Record temperature and humidity data daily according to the actual temperature in the process room. Duration: 3 months;

[0133] b) Outdoor sun exposure (during transportation): 5 consecutive days of direct sunlight, 8 hours per day, actual temperature 27-45℃, relative humidity 30%-39%. Operation: Record temperature and humidity data daily.

[0134] c) Alternating placement in air-conditioned and normal temperature rooms (summer home conditions) Conditions: Air-conditioned room set to 26℃, air conditioning turned off at night. Procedure: Alternate placement for 2 months, recording environmental conditions daily;

[0135] d) Observation at room temperature (autumn and winter home conditions): Record the temperature and humidity daily according to the actual temperature of the office, with a temperature of 20-30℃ and a relative humidity of 40%-65%.

[0136] The test results are shown in Table 3.

[0137] Table 3. Temperature stability test results of Example 1 and Comparative Examples 1-5 (indoor + outdoor)

[0138]

[0139] Note: Crystallization is determined by observation with a 10× magnifying glass and a hand-held electric light. If there are ≥10 crystal points / piece, it is recorded as "obvious crystallization"; 1~5 crystals are recorded as "slight crystallization"; and 0 crystals are recorded as "none".

[0140] (4) Destructive test of core material and auxiliary material ratio

[0141] Table 4. Results of the destructive test on the core material and auxiliary material ratios of Example 1 and Comparative Examples 6-7

[0142]

[0143] Based on the destructive test results of the core material excipient ratio in Example 1 and Comparative Examples 6-14, it can be seen that the core material excipient combination used in Example 1 of this application, which includes appropriate amounts of corn starch, sucrose powder, and hydroxypropyl methylcellulose (HPMC), together with the gelatin contained in the film coating layer, constructs a synergistic barrier system. This system enhances the physical stability and barrier performance of the formulation through multiple mechanisms. Specifically, corn starch and sucrose powder form a dense and porous composite structure on the surface of the core material, which can effectively adsorb volatile components and inhibit their migration to the coating layer during storage; at the same time, hydroxypropyl methylcellulose can cross-link with the gelatin molecules in the coating layer through hydrogen bonds during wet granulation, significantly enhancing the mechanical strength of the coating film, thereby overcoming the defect of single gelatin material being prone to brittleness under temperature and humidity changes. On this basis, this synergistic system helps to maintain the tablet as a whole in a stable glassy state, avoiding quality deterioration caused by component migration or phase transition.

[0144] The system experiments of Comparative Examples 6-14 further revealed the key impact of each component and its proportion on product stability. When the corn starch content was too low (e.g., Comparative Example 6, 0.5%), the core material's adsorption capacity for volatile components was insufficient, leading to significant crystallization in the accelerated testing, with a coating cracking rate of 35%. Conversely, when the corn starch content was too high (e.g., Comparative Example 7, 20%), the core material became too dense, affecting drug release and causing slight crystallization and 20% coating cracking. The amount of hydroxypropyl methylcellulose also needed to be strictly controlled: its complete absence (Comparative Example 8) weakened the bonding force between the coating and the tablet core, resulting in a coating cracking rate of 18%. When the amount was too low (Comparative Example 10, 0.2%), it could not effectively crosslink with gelatin, resulting in slight crystallization and 15% cracking. When the amount was too high (Comparative Example 9, 10%), the increased rigidity of the system caused stress cracking, leading to slight crystallization and a 25% cracking rate. An excessively high sucrose content also negatively impacts stability: excessively high content (Comparative Example 11, 70%) leads to an overly sweet system and decreased structural stability, resulting in significant crystallization and 30% cracking; excessively low content (Comparative Example 12, 10%) makes it difficult to form an effective porous adsorption structure, also causing significant crystallization and 40% cracking. Furthermore, the ratio of gelatin to hydroxypropyl methylcellulose is crucial; too much hydroxypropyl methylcellulose (Comparative Example 13) or too little (Comparative Example 14) will cause an imbalance in the mechanical properties of the coating layer, resulting in cracking rates of 45% and 30%, respectively.

[0145] In summary, the appropriate formulation range determined in this application (0.5-15% corn starch, 45-60% sucrose powder, 0.5-8% hydroxypropyl methylcellulose, and a weight ratio of gelatin to hydroxypropyl methylcellulose of 0.5-8:0.3-3) effectively balances multiple requirements such as core material structure construction, coating layer reinforcement, and interfacial synergy. Within the aforementioned suitable range, the compound Phyllanthus emblica throat lozenge film-coated tablets of this application did not exhibit crystallization during the 12-month accelerated testing, the coating layer remained intact without cracking, and the drug release performance was good, demonstrating excellent storage stability and dosage form reliability.

[0146] (5) Temperature and humidity cycling test (to verify mechanical stability)

[0147] The samples from Example 1 and Comparative Examples 6-7 were placed under the following cycling conditions:

[0148] a) 40℃ / 75%RH × 48h;

[0149] b) 25℃ / 40% RH × 24h.

[0150] The test was performed after 5 cycles, and the results are shown in Table 5.

[0151] Table 5. Results of temperature and humidity cycling tests in Example 1 and Comparative Examples 6-7

[0152]

[0153] III. Sensory evaluation of the Compound Phyllanthus emblica Throat Lozenges Film-coated Tablets in the Examples and Comparative Examples.

[0154] Sensory evaluation of five groups of Compound Phyllanthus emblica throat lozenges (n=30) were conducted, including Example 1 (gelatin film coating), Comparative Example 1 (HPMC coating), Comparative Example 2 (commercially available Obadai coating), Comparative Example 3 (Anhui Shanhe coating + sucralose), and Comparative Example 5 (plain tablets). All samples were randomly coded, and evaluators scored them independently. Rinsing with water was performed at 5-minute intervals. A double-blind method was used. The results are shown in Table 6.

[0155] Table 6 Sensory evaluation results of Example 1 and Comparative Examples 1, 2, 3, and 5

[0156]

[0157] The results show:

[0158] Appearance / Color: Example 1 (gelatin coating) and Comparative Example 3 (colored sweet coating) scored the highest (>8.0), with the highest gelatin film transparency, completely preserving the original color of the core and without interference from the pigment modification layer; Comparative Example 5 (plain film) easily attracted dust and had a dull color, scoring the lowest.

[0159] Taste / Smoothness: The gelatin-coated group (Example 1) was significantly better than other coated groups and uncoated sheets (p<0.05). The soft texture of gelatin itself improved the smoothness in the mouth; the HPMC and Opadry coated groups had a slight plastic and astringent taste.

[0160] Bitterness suppression: The highest score was achieved in Example 1 (gelatin) group (8.1), significantly higher than all comparative examples (p<0.01). The slightly sweet properties of gelatin effectively neutralized the bitterness of borneol; the score of Comparative Example 3 (Shanhe + Sweet), supplemented with a single bitterness masking agent, was the second highest (7.5); the bitterness was particularly pronounced in the unpalatable tablet group (4.8).

[0161] Cooling sensation perception: The intensity of the cooling sensation in each group was relatively long-lasting, indicating that the coating did not hinder the release of borneol and menthol; the uncoated group (without coating) scored slightly higher but did not have an advantage in sensory acceptance.

[0162] Overall Acceptability: The gelatin-coated group (Example 1) scored significantly higher (8.3), verifying that it optimizes the overall product experience through the synergistic effect of optical transparency, slightly sweet characteristics and lubricating palatability; the other coating groups showed optimization effects in a single dimension but failed to achieve the best overall performance; the uncoated group had the worst overall experience (5.1).

[0163] The technical features of the above-described embodiments and examples can be combined in any suitable manner. For the sake of brevity, not all possible combinations of the technical features in the above-described embodiments and examples are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0164] The embodiments described above merely illustrate several implementation methods of this application and should not be construed as limiting the scope of the patent application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Furthermore, it should be understood that after reading the above teachings, those skilled in the art can make various alterations or modifications to this application, and the equivalent forms obtained also fall within the protection scope of this application. It should also be understood that technical solutions obtained by those skilled in the art based on the technical solutions provided in this application through logical analysis, reasoning, or limited experimentation are all within the protection scope of the appended claims. Therefore, the protection scope of this patent application should be determined by the appended claims, and the specification can be used to interpret the content of the claims.

Claims

1. A compound Phyllanthus emblica throat lozenge film-coated tablet for treating throat diseases, characterized in that, Includes the wafer core and a thin film coating layer that encapsulates the wafer core; The tablet core comprises Phyllanthus emblica extract powder, compound powder, menthol, borneol, corn starch, sucrose powder, and hydroxypropyl methylcellulose; the compound powder is an aqueous extract of a mixture of Scrophularia ningpoensis, Platycodon grandiflorus, and Glycyrrhiza uralensis; the weight ratio of corn starch, sucrose powder, and hydroxypropyl methylcellulose is (0.5-15):(45-60):(0.5-8); The film coating layer comprises gelatin; the weight ratio of the gelatin to the hydroxypropyl methylcellulose is (0.5-8):(0.3-3).

2. The compound Phyllanthus emblica throat lozenge film-coated tablet for treating throat diseases according to claim 1, characterized in that, Based on the weight of the compound amla throat lozenges film-coated tablets for treating throat diseases, it comprises 0.5%~2% of the amla dry extract powder, 3%~15% of the compound dry powder; 0.1%~0.5% of the menthol, 0.05%~0.5% of the borneol, 0.5%~15% of the corn starch, 45%~60% of the sucrose powder, 0.5%~8% of the hydroxypropyl methylcellulose, and 0.3%~3% of the gelatin.

3. The compound Phyllanthus emblica throat lozenge film-coated tablet for treating throat diseases according to claim 1 or 2, characterized in that, The core also includes at least one of dextrin, talc, and magnesium stearate.

4. The compound Phyllanthus emblica throat lozenge film-coated tablet for treating throat diseases according to claim 3, characterized in that, Based on the weight of the compound amla throat lozenges film-coated tablets for treating throat diseases, it comprises: 0.5%~2% amla extract powder; 3%~15% compound powder; 0.1%~0.5% menthol; 0.05%~0.5% borneol; 0.5%~15% corn starch; 45%~60% sucrose powder; 0.5%~8% hydroxypropyl methylcellulose; 10%~30% dextrin; 0.5%~5% talc; and 0.5%~5% magnesium stearate; and 0.3%~3% gelatin.

5. The compound Phyllanthus emblica throat lozenge film-coated tablet for treating throat diseases according to claim 1, characterized in that, The preparation method of the amla fruit extract powder includes the following steps: washing fresh amla fruits, removing the pits, juicing, filtering to obtain the filtrate, concentrating the filtrate, and drying to obtain the amla fruit extract powder; and / or, The preparation method of the compound dry powder includes the following steps: mixing Scrophularia, Platycodon, and Glycyrrhiza in a mass ratio of 3:3:1; decocting the mixture with water, concentrating, and drying to obtain the compound dry powder; and / or, The weight ratio of the dried amla extract powder, the compound powder, the menthol, and the borneol is (0.5-2):(3-15):(0.1-0.5):(0.05-0.5), and the total accounts for 3.65%-18% of the weight of the film-coated compound amla throat lozenges used to treat throat diseases.

6. The method for preparing compound Phyllanthus emblica throat lozenges for treating throat diseases according to any one of claims 1-5, characterized in that, Includes the following steps: The tablet core is spray-coated with a coating solution; the coating solution comprises gelatin and a first alcohol solvent, wherein the mass concentration of the gelatin is 1% to 5%; the first alcohol solvent comprises ethanol and water. The weight ratio of the coating solution to the tablet core is (0.5-2):100; Optionally, the volume concentration of ethanol in the first alcohol solvent is 40%-80%.

7. The preparation method according to claim 6, characterized in that, The preparation method of the coating solution includes the following steps: The gelatin was added to the first alcohol solvent and mixed. After standing for 2-24 hours, it was dissolved by heating in a water bath to obtain a solution. The solution is filtered through an 80-100 mesh sieve to obtain the coating solution.

8. The preparation method according to claim 6 or 7, characterized in that, The method for preparing the chip core includes the following steps: The amla extract powder, the compound powder, the corn starch, the sucrose powder, and the hydroxypropyl methylcellulose are mixed and then added to a second alcohol solution to form a soft material; the second alcohol solvent comprises ethanol and water. The soft material is granulated, dried, and sieved to obtain granules; The borneol and menthol are dissolved in a tertiary alcohol solution, sprayed into the granules and mixed, and then the magnesium stearate and talc are added and mixed to obtain mixed granules; the tertiary alcohol solvent consists of ethanol and water. The mixed granules are compressed into tablets to obtain tablet cores; Optionally, the volume concentration of ethanol in the second alcohol solution is 60%-90%; Optionally, the volume concentration of ethanol in the third alcohol solution is 40%-95%.

9. The preparation method according to claim 8, characterized in that, Granulation includes dispersion using a 10-14 mesh sieve; and / or, The drying temperature is 50℃-75℃; and / or, Screening includes screening using a 15-17 mesh sieve.

10. The preparation method according to any one of claims 6-7 and 9, characterized in that, The step of spray coating the wafer core with a coating solution includes: The wafer core is loaded into the coating cylinder, and the rotation speed of the coating cylinder is set to 3-8 revolutions / min; The coating solution is atomized and sprayed onto the tablet core to form a coating; and / or, In the step of spray coating the wafer core with coating solution, the outlet air temperature is 45℃-65℃ and the inlet air temperature is ≤100℃.

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