Taste-masking coating preparation and preparation method thereof

Abstract

The invention belongs to the field of oral solid preparations, and particularly relates to a taste-masking coating preparation which is suitable for being taken by patients with dysphagia and has no bitter taste and a preparation method thereof. A medicine core is directly subjected to taste masking through a coating technology, and at least three layers of coatings, namely an acidic protective layer, an isolating layer and a taste masking layer, are arranged outside medicine active ingredients of the preparation, so that the medicine can be quickly released, has good taste and a good taste masking effect, cannot be released into an oral cavity in a taking process, and is free of toxic and side effects. And thus, bitter and astringent taste and other bad tastes are avoided. When the preparation enters the gastric environment, the coating film is quickly dissolved, and the medicine is released into the gastric acid environment, so that the medicine is absorbed by the organism to achieve a treatment effect.

Description

[0001] This application is a divisional application of a Chinese invention patent application with an application date of July 18, 2016, an application number of 201610565347.X, and an invention title of "A taste-masking coating preparation and its preparation method". Technical Field

[0002] The present invention belongs to the field of oral solid preparations, and particularly relates to a taste-masking coating preparation suitable for patients with dysphagia and without bitter taste, and a preparation method thereof. Background Art

[0003] Oral administration is the most commonly used administration method, and its advantages are safe and convenient medication, easy to be accepted and adopted by patients. However, the disadvantages are slow absorption, generally taking half an hour to become effective after oral administration, and being easily destroyed by the gastrointestinal tract. Drugs with strong irritation to the gastrointestinal tract, or having an unpleasant smell, or having poor absorption in the gastrointestinal tract and unable to reach the required therapeutic concentration are not suitable for preparing into oral preparations. Among them, oral preparations include dosage forms such as tablets, capsules, granules, and oral liquids. For patients with swallowing difficulties such as children and the elderly, the former two are not suitable.

[0004] Research shows that dysphagia does not only refer to populations such as children and the elderly whose self-swallowing ability has not yet developed / regressed, but also includes temporary or long-term dysphagia that may be caused by congenital developmental imperfections, diseases, physical injuries, etc. For example, in a small number of people, due to imperfect development of the diaphragm, when swallowing, the drug is likely to enter the trachea rather than the esophagus, which is also a type of dysphagia.

[0005] Compared with liquid dosage forms such as oral liquids, granules (including fine granules), dry suspensions, etc. as non-aqueous solid preparations, prepared as common alternative products such as tablets and capsules, have their unique advantages, such as low preparation cost, easy storage and carrying, etc. At present, for patients with dysphagia, taking such oral solid preparations is nothing more than two methods, that is, dissolving / dispersing them in water and then taking them, or swallowing them directly. However, no matter which method is adopted, due to the increase in the specific surface area of such preparations (compared with solid preparations such as tablets), it is easy to expose the unpleasant smell of the drug, bringing inconvenience to taking. In addition, the survey shows that compared with the former taking method, many patients are more willing to swallow such preparations directly rather than taking them after adding water for dispersion / dissolution. This may be because taking directly is more convenient and the unpleasant smell of the preparation is smaller. And it is particularly suitable for unconscious critical patients.

[0006] However, the biggest problem with directly swallowing non-aqueous solid preparations prepared by the prior art is that particles or microparticles will produce a certain astringent feeling in the mouth, resulting in an increase in the time the preparation stays in the mouth rather than quickly entering the esophagus. Unfortunately, this shortcoming is further magnified for patients with dysphagia.

[0007] In addition, since most drugs have unpleasant odors such as bitterness and irritation, the uncomfortable feeling brought to patients when taking them directly will cause psychological barriers to taking them, greatly limiting the application of such preparations. Therefore, taste masking is also one of the problems that must be solved for direct swallowing preparations.

[0008] The coating method is the most commonly used taste masking method for solid preparations. Coating refers to using coating materials such as Eudragit, ethyl cellulose (EC), hydroxypropyl methylcellulose (HPMC), etc. to coat drug powders or drug cores (pellets or granules) of a certain size and hardness to achieve the purpose of taste masking, including three types: film coating, enteric coating, and sugar coating. After coating, the contact between the drug and taste buds can be reduced, thus masking the taste. At the same time, it can also play the roles of moisture-proof, light-proof, air isolation, improving drug stability, and controlling the drug release rate and site.

[0009] The coating materials ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) film coatings are not affected by pH and are released at a certain rate in various in vivo environments. For drugs with relatively strong bitterness, the taste masking film can achieve the taste masking function but it is difficult to release the drug quickly and completely. WO1999 / 026608 provides a coated granule of granular crystalline ibuprofen, which adopts the method of directly coating the drug. A coating film composed of a water-insoluble polymer ethyl cellulose, a hydrophilic polymer hydroxypropyl methylcellulose, and silica in a certain weight ratio is coated on a drug core with a certain particle size in a water-alcohol dispersion to obtain a taste-masked and stable ibuprofen granule. However, due to the use of water-insoluble ethyl cellulose, its release is still affected.

[0010] Eudragit dissolves in acid and swells in water and neutral and alkaline environments. Although it overcomes the disadvantages of ethyl cellulose to a certain extent, it is too affected by the in vivo environment and too dependent on the gastric acid environment. When different people take drugs, the differences in the gastric acid environment will also affect the drug release.

[0011] For poorly soluble drugs with relatively serious bitterness, how to provide excellent taste masking effects while ensuring the rapid release of drugs and the effectiveness of drugs has become an urgent problem to be solved in the prior art. Summary of the Invention

[0012] The present invention provides an easily swallowable taste-masked coated preparation and its preparation method. By directly performing taste masking on the drug core through coating technology, the drug can be rapidly released while having a good taste, with good taste masking effects, and will not be released into the oral cavity during the taking process, so there will be no unpleasant tastes such as bitterness. When the preparation enters the gastric environment, the coating film dissolves rapidly, and the drug is released into the gastric acid environment, and then is absorbed by the body to play a therapeutic role.

[0013] The taste-masking coating preparation described in the present invention is characterized in that it comprises at least three coating layers outside the pharmaceutically active ingredient, namely an acidic protective layer, a barrier layer and a taste-masking layer. The taste-masking ingredient in the taste-masking layer is Eudragit, and the acidic protective layer contains an acidic pH regulator that can rapidly release the preparation ingredients.

[0014] The taste-masking coating preparation in the present invention comprises at least three coating structures: an acidic protective layer, a barrier layer and a taste-masking layer. All three coating structures can play a role in masking the peculiar smell of the pharmaceutically active ingredient, but the main structure for taste masking is the taste-masking layer. The taste-masking layer contains a coating skeleton ingredient, i.e., the taste-masking ingredient Eudragit, such as Eudragit E100. Eudragit dissolves in acid and swells in water and neutral and alkaline environments. It is greatly affected by the in vivo environment. For example, when taking medicine at different time points before and after meals, the drug release rate is different. In addition, Eudragit is too dependent on the gastric acid environment, and changes in the gastric acid environment will also affect the drug release. Based on the above points, an acidic protective layer is designed to increase the release of the taste-masking layer and the drug release rate. The acidic protective layer contains an acidic pH regulator, which can provide an acidic environment so that the taste-masking Eudragit coating film can also have an immediate release in neutral and alkaline buffer solutions, excluding the influence of the in vivo environment and its gastric acid environment during medication. In order to prevent the direct contact between the taste-masking coating layer and the acidic coating layer and improve the stability of the preparation, a barrier layer is added between the taste-masking coating layer and the acidic coating layer.

[0015] The acidic protective layer includes an acidic pH regulator selected from one or more of the following: citric acid, lactic acid, tartaric acid, malic acid, adipic acid, fumaric acid, phosphoric acid, metatartaric acid, gluconic acid, acetic acid, ascorbic acid, succinic acid, fumaric acid.

[0016] The dosage of the acidic pH regulator in the acidic protective layer is not strictly limited as long as the purpose can be achieved, that is, the taste-masking layer can have an immediate release in various environments. Its mass percentage content in the acidic protective layer can be 15% - 50%, preferably 15% - 45%, more preferably 20% - 40%, and most preferably 25% - 30%.

[0017] The acidic protective layer further includes one or more of the following components: binder, anti-adhesive, plasticizer, surfactant, filler, flavoring agent, lubricant, disintegrant. In one embodiment of the present invention, it includes a binder and an anti-adhesive.

[0018] There are no particular restrictions on the binder, anti-adhesive agent, plasticizer, surfactant, filler, flavoring agent, lubricant, and disintegrant, as long as they can form a stable acidic protective layer. For example, the binder can be selected from one or more of the following: powdered sugar, syrup, starch paste, polyvinylpyrrolidone, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, mucilage, dextrin, sodium alginate, polyvinyl alcohol, etc.; the anti-adhesive agent can be selected from one or more of the following: talc powder, colloidal silica, corn starch, magnesium stearate, glycerol monostearate, etc.; the plasticizer can be selected from one or more of the following: triethyl citrate, dibutyl sebacate, dibutyl phthalate, glyceryl triacetate, castor oil, glycerol, propylene glycol, polyethylene glycol, etc.; the surfactant can be selected from one or more of the following: Tween series, Span series, lecithin, sodium dodecyl sulfate, etc.; the filler can be selected from one or more of the following: starch, sucrose, dextrin, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, microcrystalline cellulose, mannitol, lactose, pregelatinized starch; the flavoring agent can be selected from one or more of the following: lactose, sucrose, glucose, mannitol, citric acid, peppermint oil, etc.; the lubricant can be selected from one or more of the following: magnesium stearate, calcium stearate, talc powder, sodium dodecyl sulfate, magnesium dodecyl sulfate, colloidal silica, etc.; the disintegrant can be selected from one or more of the following: starch, crystalline cellulose, calcium carbonate, CMC-Na, sodium alginate, etc.

[0019] According to the taste-masking coating preparation of the present invention, the mass percentage content of Eudragit in the taste-masking layer is 30% to 80%, preferably 35% to 75%, more preferably 40% to 65%, and most preferably 45% to 60%.

[0020] The taste-masking layer further includes one or more components selected from the following: binder, anti-adhesive agent, plasticizer, surfactant, filler, flavoring agent, lubricant, disintegrant. For example, in one embodiment of the present invention, it includes a pore-forming agent and an anti-adhesive agent.

[0021] There are no particular limitations on the adhesive, anti-adhesive, plasticizer, surfactant, filler, flavoring agent, lubricant, and disintegrant, as long as they can form a stable acidic protective layer. For example, the adhesive can be selected from one or more of the following: powdered sugar, syrup, starch paste, polyvinylpyrrolidone, methylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, mucilage, dextrin, sodium alginate, polyvinyl alcohol, etc.; the anti-adhesive can be selected from one or more of the following: talc powder, colloidal silica, corn starch, magnesium stearate, glycerol monostearate, etc.; the plasticizer can be selected from one or more of the following: triethyl citrate, dibutyl sebacate, dibutyl phthalate, glyceryl triacetate, castor oil, glycerol, propylene glycol, polyethylene glycol, etc.; the surfactant can be selected from one or more of the following: Tween series, Span series, lecithin, sodium dodecyl sulfate, etc.; the filler can be selected from one or more of the following: starch, sucrose, dextrin, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, microcrystalline cellulose, mannitol, lactose, pregelatinized starch; the flavoring agent can be selected from one or more of the following: lactose, sucrose, glucose, mannitol, citric acid, peppermint oil, etc.; the lubricant can be selected from one or more of the following: magnesium stearate, calcium stearate, talc powder, sodium dodecyl sulfate, magnesium dodecyl sulfate, colloidal silica, etc.; the disintegrant can be selected from one or more of the following: starch, crystalline cellulose, calcium carbonate, CMC-Na, sodium alginate, etc.

[0022] According to the taste masking coating preparation of the present invention, the barrier layer is sandwiched between the acidic protective layer and the taste masking layer, playing a role in enhancing the drug stability. Commonly used barrier layer coating materials include film-forming coating materials such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, polyethylene glycol, talc powder, stearic acid, etc.

[0023] There are no particular limitations on the active ingredient in the present invention, which refers to a single compound or a combination of two or more compounds selected from the following with pharmacological activity, including synthetic chemical medicines, biological drugs, active effective substances extracted from plants, active single components, etc. For example, it can be: antihypertensive drugs, anxiolytic drugs, antithrombotic drugs, anticonvulsant drugs, hypoglycemic drugs, decongestants, antihistamines, cough suppressants, anti-tumor drugs, β-blockers, anti-inflammatory drugs, antipsychotic drugs, cognitive function promoters, anti-atherosclerotic drugs, cholesterol-lowering drugs, anti-obesity drugs, autoimmune disease drugs, anti-impotence drugs, antibacterial and antifungal drugs, hypnotics, antibiotics, antidepressants, antiviral drugs, etc. In one embodiment of the present invention, the active ingredient is prednisone, and in other embodiments, the active ingredients include loratadine, cefixime, etc.

[0024] When coating an active ingredient with an acidic protective layer, an isolating layer, a taste-masking layer, etc., one can choose to directly coat the drug powder, or can also choose to prepare the active ingredient into forms such as drug-loaded pellets, drug-loaded granule agents, drug-loaded micro tablets, etc. according to conventional preparation methods in the art, and then perform coating.

[0025] The taste-masking coating preparation of the present invention may further include a fourth smooth layer, and the fourth smooth layer includes a component gelling agent. The gelling agent can be selected from: gelatin, carrageenan, xanthan gum, konjac powder, carbomer, agar, etc., preferably carbomer, such as carbomer 971. The dosage of the gelling agent can be 10% - 50%, preferably 12% - 45%, more preferably 15% - 40%. Coating the fourth smooth layer on the taste-masking coating preparation of the present invention can, on the one hand, achieve a better taste-masking effect, and on the other hand, the gelling agent can form a gel when encountering water, making the surface of the pellets very smooth, achieving a better swallowing effect, realizing swallowing without water, and greatly improving the compliance of medication.

[0026] The taste-masking coating preparation of the present invention can also be mixed with a flavoring material to prepare a taste-masking preparation with a better taste-masking effect. The flavoring material can further enhance the taste-masking effect of the taste-masking coating preparation, and increase the taste and compliance of patients, especially child patients, when taking the medicine. The composition components of the flavoring material can be any medicinal excipients or their mixtures that can cover the peculiar smell of the drug and are easily accepted by patients, especially child patients, for example, including one or more of the following components: flavoring agents, sweeteners, sour agents, diluents, gelling agents, lubricants; the components with flavoring functions can be directly mixed with the taste-masking coating preparation of the present invention and used as the flavoring material, or the flavoring components such as flavoring agents, sweeteners, sour agents, etc. can be prepared into flavoring granules by conventional methods in the art and used as the flavoring material. In one embodiment of the present invention, the flavoring material simultaneously includes a diluent, a binder, a sweetener, a sour agent, and a flavoring agent.

[0027] The flavoring agent is selected from one or more of artificial flavors or natural flavors. Natural flavors include lemon oil, anise oil, peppermint oil, etc., and artificial flavors include sweet orange essence, strawberry essence, vanilla essence, peppermint essence, lemon essence, banana essence, etc.; the sweetener is selected from one or more of aspartame, sucralose, acesulfame potassium, sodium cyclamate, mannitol, sorbitol; the sour agent is selected from one or more of citric acid, sodium citrate, potassium citrate, sodium citrate monohydrate, malic acid, tartaric acid; the diluent is selected from one or more of sorbitol, mannitol, sucrose; the binder is selected from one or more of sodium carboxymethyl cellulose, polyvinylpyrrolidone, methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose; the lubricant has no special limitation and can be a commonly used lubricant in pharmacy, for example, selected from one or two or more of talc powder, magnesium stearate, stearic acid, colloidal silica, titanium dioxide, magnesium oxide.

[0028] Among them, the contents of the sweetener, flavoring agent, and acidulant cannot be 0 simultaneously; the content of the diluent can be 50% - 95%, preferably 55% - 90%, more preferably 60% - 85%; the content of the binder can be 1% - 15%, preferably 2% - 14%, more preferably 5% - 11%; the content of the lubricant can be 0 - 10%, preferably 0.2% - 8%, more preferably 0.5% - 6%; the content of the sweetener can be 0 - 10%, preferably 0.2% - 8%, more preferably 0.5% - 6%; the content of the flavoring agent can be 0 - 10%, preferably 0.2% - 8%, more preferably 0.3% - 6%; the content of the acidulant can be 0 - 10%, preferably 0.5% - 8%, more preferably 2% - 5.5%.

[0029] The present invention also provides a method for preparing the above-mentioned taste-masking coating preparation, including:

[0030] 1. Acidic protective layer coating: Prepare a suspension of the pH regulator and other coating components with water, and perform fluidized bed coating on the active ingredient drug powder or drug-loaded pellets, granules, or microtablets carrying the active ingredient. After the coating is completed, continue drying and perform screening.

[0031] 2. Barrier layer coating: Prepare a suspension of the barrier layer coating components with water, select fluidized bed coating, and perform barrier layer coating on the product obtained in the first step. After the coating is completed, continue drying and perform screening.

[0032] 3. Taste-masking layer coating: Prepare a suspension of Eudragit and other taste-masking layer coating components, select fluidized bed

[0033] coating, and perform taste-masking coating on the product obtained in the second step. After the coating is completed, continue drying and perform screening.

[0034] The taste-masking coating preparation of the present invention can also be subjected to additional functional coating. For example, in order to obtain better taste masking and lubricating mouthfeel, it can also include a fourth smooth layer. The fourth smooth layer includes a component of a gelling agent. The gelling agent can form a gel when it encounters water, making the surface of the pellets very smooth, achieving a better swallowing effect, enabling swallowing without water, greatly improving the compliance of medication. The gelling agent can be selected from: gelatin, carrageenan, xanthan gum, konjac powder, carbomer, agar, etc., preferably carbomer, such as carbomer 971. The coating method for the smooth layer can be selected from the commonly used methods in the art, such as fluidized bed coating.

[0035] The taste masking coated preparation of the present invention can also be mixed with flavoring granules to prepare a taste masking granule with better taste masking effect. The flavoring granules can further enhance the taste masking effect of the taste masking coated preparation, improve the taste and compliance of patients, especially children, when taking medicine. The flavoring granules can be prepared by conventional granulation methods. After pressing flavoring materials and / or other components, such as flavoring agents, sweeteners, sour agents, diluents, gelling agents and / or lubricants, etc. into granules, they are mixed with the taste masking coated preparation. They can also be directly mixed evenly with the powder of flavoring materials and / or other components and then directly mixed with the taste masking coated preparation. Detailed implementation manners

[0036] The following examples are used to further explain or illustrate the content of the present invention. The described examples are only for helping to understand the content of the present invention and should not be construed as limiting the gist and protection scope of the present invention.

[0037] Example 1. Taste masking coated pellets of prednisone

[0038] The active drug prednisone is carried in the form of drug-loaded pellets. The prednisone drug-loaded pellets are sequentially coated with an acidic protective layer, a barrier layer, and a taste masking layer. The raw materials and their dosages of each layer are as follows:

[0039] Drug-loaded pellets:

[0040] Ingredient Dosage per unit preparation Sucrose core with a diameter of 0.5 - 0.6 mm 190 mg Prednisone 5 mg Hypromellose E5 LV 5 mg Tween 80 1 mg Citric acid 1 mg

[0041] Acidic protective layer:

[0042] Citric acid 5 mg Hypromellose E5 LV 1 mg Talc 15 mg

[0043] Barrier layer:

[0044] Hypromellose E5 LV 11.2 mg Talc 5 mg

[0045] Taste masking layer:

[0046] Eudragit E100 12 mg Polyethylene glycol 6000 1.2 mg Talc 6 mg

[0047] The preparation method is as follows:

[0048] 1. Preparation of drug-loaded pellets:

[0049] Dissolve prednisone, citric acid, hypromellose, and Tween 80 in water to make a solution. Select fluidized bed coating to coat the sucrose core with the drug. Control the material temperature at 35-45°C during the coating process. After the coating is completed, continue to dry for 30 minutes. Then perform screening and collect the pellets between 25 and 50 meshes.

[0050] 2. Coating of acidic protective film:

[0051] Prepare a suspension of citric acid, hypromellose, and talc powder with water, select fluidized bed coating, and perform acidic protection coating on the loaded pills. Control the material temperature at 30 - 35°C during the coating process, and continue drying for 30 minutes after the coating is completed. Then perform screening and collect the pellets between 25 - 50 mesh.

[0052] 3. Barrier layer coating:

[0053] Prepare a suspension of hypromellose and talc powder with water, select fluidized bed coating, and perform barrier layer coating on the pellets obtained in the second step. Control the material temperature at 40 - 50°C during the coating process, and continue drying for 30 minutes after the coating is completed. Then perform screening and collect the pellets between 25 - 50 mesh.

[0054] 4. Taste - masking layer coating:

[0055] Prepare a suspension of Eudragit E100, talc powder, and polyethylene glycol with ethanol, select fluidized bed coating, and perform taste - masking coating on the barrier - coated pellets. Control the material temperature at 30 - 35°C during the coating process, and continue drying for 30 minutes after the coating is completed. Then screen the pellets and collect the pellets between 25 - 50 mesh.

[0056] Micro - pellets control group of prednisone taste - masking coated preparation: The formulation raw materials, dosages, and its preparation method refer to Example 1, with the only difference being that the coating of the acidic protection layer is removed.

[0057] Evaluate the prednisone taste - masking coated micro - pellets prepared in Example 1 from two aspects: taste during administration and dissolution rate.

[0058] Taste during administration: For 10 volunteers, without informing them of the difference between Example 1 and the control group, the taste of the preparation was statistically analyzed after swallowing. All 10 people thought that there was no strange taste during the administration of the taste - masking coated micro - pellets in Example 1 and the control group, and 9 people thought that the product of Example 1 was more acceptable in taste than that of the control group.

[0059] Dissolution rate: According to the dissolution and release determination method (the second method in General Principles 0931, Volume IV of the Chinese Pharmacopoeia 2015 Edition), use 500 ml of water as the dissolution medium and the rotation speed is 50 revolutions per minute. Sampling is carried out for determination at 30 minutes, and the dissolution rate shall not be less than 80%.

[0060] Example 1 Control group 5 minutes 0.5％ 0.7％ 10 minutes 55.8％ 15.2％ 15 minutes 93.5％ 39.4％ 30 minutes 95.4％ 66.9％ 45 minutes 96.3％ 79.6％ 60 minutes 98.1％ 87.7％

[0061] Dissolution rate determination method:

[0062] Evaluating the taste - masking coated preparation of the present invention from two aspects of taste during administration and dissolution rate shows that for drugs with relatively severe bitterness, especially poorly soluble drugs, the present invention can provide excellent taste - masking effects while ensuring the rapid release of drugs and guaranteeing the effectiveness of drugs.

[0063] Example 2. Loratadine Taste-Masked Coated Granules

[0064] Direct powder coating was carried out using loratadine drug powder, and an acidic protective layer, an isolating layer, and a taste-masking layer were sequentially coated on the outer layer of the drug. The raw materials and their dosages for each layer are as follows:

[0065] Acidic protective layer:

[0066] Ingredient Dosage per unit preparation Tartaric acid 5.5 mg Hypromellose E5 LV 1.2 mg Stearic acid 13 mg

[0067] Isolating layer:

[0068] Hypromellose E5 LV 12.0 mg Magnesium stearate 5 mg

[0069] Taste-masking layer:

[0070] Eudragit E100 11.7 mg Polyethylene glycol 6000 1.4 mg Magnesium stearate 5.5 mg

[0071] The preparation method is as follows:

[0072] 1. Acidic protective film coating:

[0073] Tartaric acid, hypromellose, and stearic acid were formulated into a suspension with water, and fluidized bed coating was selected to carry out acidic protective coating on the loratadine dry powder. The material temperature was controlled at 30 - 35°C during the coating process, and drying was continued for 30 minutes after the coating was completed. Screening was carried out, and the granules between 25 - 50 meshes were collected.

[0074] 2. Isolating layer coating:

[0075] Hypromellose and magnesium stearate were formulated into a suspension with water, and fluidized bed coating was selected to carry out isolating layer coating on the granules obtained in the first step. The material temperature was controlled at 40 - 50°C during the coating process, and drying was continued for 30 minutes after the coating was completed. Screening was carried out, and the granules between 25 - 50 meshes were collected.

[0076] 3. Taste-masking layer coating:

[0077] Eudragit E100, magnesium stearate, and polyethylene glycol were formulated into a suspension with ethanol, and fluidized bed coating was selected to carry out taste-masking coating on the granules obtained in the second step. The material temperature was controlled at 30 - 35°C during the coating process, and drying was continued for 30 minutes after the coating was completed. Screening was carried out on the granules, and the granules between 25 - 50 meshes were collected.

[0078] Taste during administration: The method was the same as that in Example 1. 10 people took it, and all indicated that there was no bitter taste during the taking process and the acceptance degree was high.

[0079] Dissolution rate: The method was the same as that in Example 1. The dissolution rate at 10 minutes was 50%, at 30 minutes was 92%, and at 45 minutes was 95%. The drug was released rapidly.

[0080] Example 3. Cefixime Taste-Masked Coated Granules

[0081] Direct powder coating was carried out using cefixime drug powder, and an acidic protective layer, an isolating layer, and a taste-masking layer were sequentially coated on the outer layer of the drug. The raw materials and their dosages for each layer are as follows:

[0082] Acidic protective layer:

[0083] Ingredient Dosage per unit preparation Malic acid 6.5 mg Hypromellose E5 LV 1.2 mg Magnesium stearate 15 mg

[0084] Isolating layer:

[0085] Hypromellose E5 LV 12.5 mg Talc 5 mg

[0086] Taste-masking layer:

[0087] Eudragit E100 12.5 mg Polyethylene glycol 6000 1.1 mg Talc 5.5 mg

[0088] The preparation method is as follows:

[0089] 1. Acidic protective film coating:

[0090] Malic acid, hypromellose, and magnesium stearate were formulated into a suspension with water, and fluidized bed coating was selected to carry out acidic protective coating on the dry cefixime powder. During the coating process, the material temperature was controlled at 30 - 35°C. After the coating was completed, drying was continued for 30 minutes. Then screening was carried out, and the granules between 25 - 50 meshes were collected.

[0091] 2. Isolating layer coating:

[0092] Hypromellose and talc were formulated into a suspension with water, and fluidized bed coating was selected to carry out isolating layer coating on the granules obtained in the first step. During the coating process, the material temperature was controlled at 40 - 50°C. After the coating was completed, drying was continued for 30 minutes. Then screening was carried out, and the granules between 25 - 50 meshes were collected.

[0093] 3. Taste-masking layer coating:

[0094] Eudragit E100, talc, and polyethylene glycol were formulated into a suspension with ethanol, and fluidized bed coating was selected to carry out taste-masking coating on the granules obtained in the second step. During the coating process, the material temperature was controlled at 30 - 35°C. After the coating was completed, drying was continued for 30 minutes. Then screening was carried out on the granules, and the granules between 25 - 50 meshes were collected.

[0095] Taste during taking: The method was the same as that in Example 1. 10 people took it, and all of them indicated that there was no bitter taste during the taking process and the acceptance degree was high.

[0096] Dissolution rate: The method was the same as that in Example 1. The dissolution rate at 10 minutes was 52%, at 30 minutes was 91%, and at 45 minutes was 95%. The drug release was rapid.

[0097] Example 4. Taste-masked enteric-coated prednisone pellets

[0098] The taste-masked enteric-coated prednisone pellets obtained in Example 1 were further coated with a smoothing layer, and the prescription of the smoothing layer was as follows:

[0099] Ingredient Dosage per unit preparation Povidone K29 / 32 18 mg Carbomer 971 54 mg Talc 18 mg Stearic acid 50 9 mg Sodium bicarbonate 36 mg

[0100] Preparation method: Prepare a suspension of povidone K29 / 32, carbomer 971, talc, stearic acid 50, and sodium bicarbonate in ethanol, select fluidized bed coating, and perform smoothing coating on the taste-masked enteric-coated pellets. Control the temperature of the material at 30 - 35 °C during the coating process, and continue drying for 30 minutes after the coating is completed. Screen the pellets and collect the pellets between 25 - 50 mesh.

[0101] Taste during taking: The method was the same as in Example 1. 10 people took the product and all indicated that there was no bitter taste during the taking process, and the taste acceptance degree was higher than that in Example 1.

[0102] Dissolution rate: The method was the same as in Example 1. The dissolution rate at 10 minutes was 49%, at 30 minutes was 90%, and at 45 minutes was 95%. The drug was released rapidly, and the smoothing layer coating had almost no effect on the drug release rate.

[0103] Example 5. Flavoring materials

[0104] To further improve the taste during taking, the taste-masked enteric-coated preparation in the present invention can be mixed with flavoring materials. Weigh sorbitol, citric acid, aspartame, sodium carboxymethylcellulose, and orange essence and mix them for 5 - 10 minutes.

[0105] Ingredient Dosage per unit preparation Sorbitol 150 mg Aspartame 1 mg Sodium carboxymethyl cellulose 20 mg Citric acid 10 mg Orange essence 0.5 mg

[0106] After uniformly mixing the flavoring materials with the taste-masked enteric-coated prednisone preparations of Example 1 and Example 4, the taste during taking and dissolution rate of the prepared taste-masked preparations were measured:

[0107] Taste during taking: The method was the same as in Example 1. 10 people took the product and all indicated that there was no bitter taste during the taking process, and the taste acceptance degree was better than that in Example 1 and Example 4.

[0108] Dissolution rate: The method was the same as in Example 1. For the preparation obtained by mixing Example 1 and the flavoring materials, the dissolution rate at 10 minutes was 52%, at 30 minutes was 92%, and at 45 minutes was 96%. For the preparation obtained by mixing Example 4 and the flavoring materials, the dissolution rate at 10 minutes was 49%, at 30 minutes was 90%, and at 45 minutes was 95%. The flavoring materials had almost no effect on the drug release rate.

Claims

1. A taste-masking coating preparation, characterized in that It contains at least three layers of coatings outside the drug active ingredient, namely an acidic protective layer, a separating layer and a taste masking layer. The taste masking ingredient in the taste masking layer is Eudragit, and the acidic protective layer contains an acidic pH regulator that can rapidly release the preparation ingredients.

2. The taste-masking coating preparation according to claim 1, characterized in that, The acidic pH regulator in the acidic protective layer includes one or more selected from the following: citric acid, lactic acid, tartaric acid, malic acid, adipic acid, fumaric acid, phosphoric acid, metatartaric acid, gluconic acid, acetic acid, ascorbic acid, succinic acid, fumaric acid.

3. The taste-masking coating preparation according to any one of claims 1 to 2, characterized in that, The mass percentage content of the acidic pH regulator in the acidic protective layer is 15% - 50%, preferably 15% - 45%, more preferably 20% - 40%, and most preferably 25% - 30%.

4. The taste-masking coating preparation according to any one of claims 1 to 3, characterized in that, The acidic protective layer also includes one or more selected from the following components: binder, anti-adhesive, plasticizer, surfactant, filler, flavoring agent, lubricant, disintegrant.

5. The taste masking coating preparation according to any one of claims 1 to 4, characterized in that, The components of the acidic protective layer include a binder and an anti-adhesive in addition to the acidic pH regulator.

6. The taste-masking coating preparation according to any one of claims 1 to 5, characterized in that The mass percentage content of Eudragit in the taste masking layer is 30% - 80%, preferably 35% - 75%, more preferably 40% - 65%, and most preferably 45% - 60%.

7. The taste-masking coating preparation according to any one of claims 1 to 6, characterized in that, The taste masking layer also includes one or more selected from the following components: binder, anti-adhesive, plasticizer, surfactant, filler, flavoring agent, lubricant, disintegrant.

8. The taste-masking coating preparation according to any one of claims 1 to 7, characterized in that, The components of the taste masking layer include a pore-forming agent and an anti-adhesive in addition to Eudragit.

9. The taste-masking coating preparation according to any one of claims 1 to 8, characterized in that The separating layer separates the acidic protective layer from the taste masking layer, and it includes one or more selected from the following components: binder, anti-adhesive, plasticizer, surfactant, filler, flavoring agent, lubricant, disintegrant.

10. The taste-masking coating preparation according to any one of claims 1 to 9, characterized in that, The active ingredient refers to a single compound or a combination of two or more compounds selected from the following with pharmacological activity: antihypertensive, anxiolytic, antithrombotic, anticonvulsant, hypoglycemic, decongestant, antihistamine, antitussive, antineoplastic, β-blocker, anti-inflammatory, antipsychotic, cognitive function promoter, anti-atherosclerotic, cholesterol-lowering, anti-obesity, autoimmune disease drug, anti-impotence drug, antibacterial and antifungal drug, hypnotic, antibiotic, antidepressant, antiviral drug.

11. The taste-masking coating preparation according to any one of claims 1 to 10, characterized in that, It also includes a fourth smooth layer, and the fourth smooth layer includes a gelling agent as a component.

12. The taste-masking coating preparation according to any one of claims 1 to 11, characterized in that, A flavoring material for further enhancing the taste masking effect is also added.

13. The taste-masking coating preparation according to any one of claims 1 to 12, characterized in that, The taste masking coated preparation is a granule, pellet or tablet.

14. A method for preparing the taste masking coated preparation according to any one of claims 1 - 13, comprising: Coating of the acidic protective layer: Prepare a suspension of the pH regulator and other coating components with water, and perform fluidized bed coating on the active ingredient drug powder or drug-loaded pellets, granules, tablets carrying the active ingredient. After the coating is completed, continue drying and perform screening; Coating of the separating layer: Prepare a suspension of the separating layer coating components with water, select fluidized bed coating, and perform separating layer coating on the product obtained in the first step. After the coating is completed, continue drying and perform screening; Taste-masking layer coating: Prepare a suspension by mixing Eudragit and other components of the taste-masking layer coating. Select fluidized bed coating to perform taste-masking coating on the product obtained in the second step. After the coating is completed, continue drying and then perform screening.