Anhydrous Amantadine Hydrochloride Oral Granules and Their Preparation Method

Abstract

This invention relates to the field of pharmaceutical preparations, specifically providing anhydrous rimantadine hydrochloride granules and a method for preparing the same. The anhydrous rimantadine hydrochloride granules are a mixture of drug-containing taste-masked granules and flavor-correcting granules. The drug-containing taste-masked granules comprise rimantadine hydrochloride and a taste-masking material, wherein the taste-masking material is a lipid or waxy material. This invention, by selecting a lipid or waxy material as the taste-masking material and mixing it with rimantadine hydrochloride to prepare drug-containing taste-masked granules, and then mixing them with flavor-correcting granules, effectively masks the taste and allows for direct swallowing without water, greatly improving medication adherence, especially suitable for children, the elderly, and other individuals with swallowing difficulties. Furthermore, the preparation method of this invention is simple, requires minimal equipment, is low-cost, and suitable for large-scale production.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparation technology, and in particular to anhydrous amantadine hydrochloride granules and their preparation method. Background Technology

[0002] Amantadine hydrochloride, CAS number 1501-84-4, chemical name: α-methyl-1-adamantanemethylamine hydrochloride; Amantadine hydrochloride works in the early stage of the viral replication cycle by inhibiting the uncoating of viral particles in host cells. It is a first-line drug for the treatment and prevention of viral colds and has significant effects on the prevention and early treatment of influenza.

[0003] Influenza is a common illness in modern clinical practice, occurring frequently in daily life. It causes symptoms such as sore throat, headache, runny nose, and fever. Anti-influenza drugs play a crucial role in treating influenza, making their development significant. Currently, many anti-influenza drugs are available on the market, such as aspirin, cold medicine granules, ribavirin, and rimantadine hydrochloride. Compared to similar drugs that have been on the market for many years, rimantadine hydrochloride has advantages such as better efficacy, longer duration of action, fewer side effects, and greater safety for human use. Furthermore, studies have shown that rimantadine hydrochloride can effectively relieve influenza symptoms in children, greatly reducing their suffering.

[0004] However, the currently available amantadine hydrochloride preparations include tablets, granules, and oral solutions. Amantadine hydrochloride has a bitter taste that is difficult to tolerate, and these dosage forms cannot easily mask the bitterness of the drug itself, resulting in a significant decrease in patient compliance and even affecting the efficacy. In particular, it limits the use of the drug by children, the elderly, and other people with difficulty swallowing.

[0005] To address the aforementioned issues, Beijing Kexin Bicheng has published related patents for anhydrous swallowable granules, such as CN106267220B and CN105982861B. These patents utilize acrylic resin coating to mask the taste, such as with Eutrich E100. Eutrich E100 is a pH-dependent excipient; due to its alkaline nature and poor compatibility with the active ingredient, an isolation coating layer is added during preparation to separate it from the active ingredient and improve stability. Simultaneously, the coating film formed by Eutrich E100 is soluble in acidic solutions with a pH below 5, thus it does not dissolve in the oral cavity (pH above 5). However, this characteristic makes it susceptible to the effects of food or stomach acid, leading to incomplete disintegration in the gastrointestinal tract. Furthermore, all of the above patents employ a micro-pellet lamination process, which is relatively complex and requires sophisticated equipment. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides anhydrous ramantadine hydrochloride granules and a method for preparing the same, thereby solving the problem of compliance with ramantadine hydrochloride medication, and is particularly suitable for children, the elderly, and other people with swallowing difficulties.

[0007] This invention provides anhydrous granules of rimantadine hydrochloride, which are a mixture of drug-containing taste-masked granules and flavor-correcting granules. The drug-containing taste-masked granules include rimantadine hydrochloride and a taste-masking material, wherein the taste-masking material is a lipid or wax material.

[0008] This invention utilizes lipid or waxy materials for taste masking. These materials encapsulate the drug, creating a physical barrier that blocks contact between the drug and taste buds, thus masking the taste. Besides taste masking, the lipid or waxy taste-masking materials of this invention offer the following advantages compared to acrylic resin coating: Lipid / waxy materials are pH-independent, unaffected by the pH of the digestive tract, have high bioavailability, and good drug compatibility, eliminating the need for other excipients to isolate the drug from the masking material; lipid / waxy materials have low melting points, requiring only melting and encapsulating the drug during preparation. The hot-melt coating process, controlled by temperature control, allows the lipid / waxy material to melt and coat the drug surface, achieving a taste masking effect. During preparation, the active pharmaceutical ingredient does not come into contact with water or other organic solvents, further improving drug stability, especially suitable for water-sensitive drugs; particles prepared using lipid / waxy materials have irregular shapes, easily mix evenly with the taste-enhancing particles, are less prone to stratification, and possess a certain smoothing effect, aiding swallowing without the need for additional lubricants.

[0009] In some embodiments of the present invention, the odor-masking material is selected from one or more of glyceryl monostearate and glyceryl behenate, beeswax, and carnauba wax.

[0010] Glyceryl monostearate and glyceryl distearate are mixed glyceryl esters of monostearate, distearate, tristearate and palmitic acid. They are generally used as emulsifiers. In this invention, they are used as a taste masking material, which can mask the bitterness of drugs, and also has a smoothing effect, increasing the ease of swallowing and improving drug compliance.

[0011] Glyceryl behenate is mainly used as a lubricant, sustained-release agent, and taste masking agent in tablets and capsules. This invention utilizes it as a taste masking material, which masks the bitterness of drugs, provides a smoothing effect, increases swallowability, and improves medication compliance.

[0012] In some embodiments of the present invention, the mass of the odor-masking material is 0.5-3 times the mass of rimantadine hydrochloride.

[0013] By controlling the amount of odor-masking material within the above range, the coating thickness of the odor-masking material can be controlled, thereby effectively masking the odor while controlling its dissolution time.

[0014] In some embodiments of the present invention, the medicated masking granules further include binders, fillers and other optional pharmaceutical excipients.

[0015] Pharmaceutical excipients refer to all other materials added to enable the formulation of a drug into a suitable dosage form. They are substances added during the formulation process to maintain stability, safety, or homogeneity, or to adapt to the characteristics of the formulation by promoting dissolution, sustained release, etc. Pharmaceutical excipients should have no physiological activity, be stable and not react with the drug, and should not affect the determination of drug content.

[0016] Adhesives are one of the main pharmaceutical excipients. They are viscous substances that bind two separate materials together. Common adhesives include starch paste, cellulose derivatives, povidone, gelatin, and polyethylene glycol. Cellulose derivatives specifically include methylcellulose (MC), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), sodium carboxymethyl cellulose (CMC-Na), and ethylcellulose (EC).

[0017] In some embodiments of the present invention, the adhesive is polyvinyl acetate K30.

[0018] Fillers are also a major pharmaceutical excipient, primarily serving to shape the mixture and improve its flowability. Commonly used fillers include lactose, microcrystalline cellulose, starch, and mannitol. Mannitol, in particular, can be used as both a filler and a sweetener.

[0019] Other optional pharmaceutical excipients include disintegrants, lubricants, release modifiers, colorants, and flavoring agents. These may be added as needed in specific embodiments.

[0020] In some embodiments of the present invention, the drug-containing masking granules consist only of rimantadine hydrochloride, a masking material, a binder, and a filler.

[0021] More preferably, the mass of the filler is 0.5-3 times the mass of rimantadine hydrochloride, and the mass of the adhesive is 0.1-1 times the mass of rimantadine hydrochloride.

[0022] In a preferred embodiment of the present invention, the medicated masking granules, by weight, consist of 50 parts of amantadine hydrochloride, 25-150 parts of masking material, 10 parts of binder, and 100 parts of filler.

[0023] In some embodiments of the invention, the flavoring particles include sweeteners, acidulants, and binders, as well as optional flavorings.

[0024] In some embodiments of the present invention, the sweetener is selected from one or more of aspartame, xylitol, maltitol, mannitol, erythritol, sucralose, acesulfame potassium, and cyclamate.

[0025] The acidulant is 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, and fumaric acid.

[0026] The adhesive used is a commonly used adhesive in the art, and may be the same as or different from the adhesive in the medicated flavor-masking granules. In some embodiments of the present invention, the adhesive in the flavor-masking granules is also povidone K30.

[0027] In some embodiments of the present invention, the flavoring granules, by weight, consist of 0.1-2 parts of sweetener, 2-20 parts of acidulant, 40-70 parts of filler and 1-10 parts of binder.

[0028] In some embodiments of the present invention, the mass ratio of the drug-containing flavor-masking granules to the flavor-correcting granules is 2:1-10:1; and the mass percentage of rimantadine hydrochloride in the drug-containing flavor-masking granules is 10%-50%.

[0029] In some embodiments of the present invention, the D90 of the drug-containing masking granules is 200μm-350μm, and the D90 of the flavor-correcting granules is 200μm-350μm.

[0030] The present invention also provides a method for preparing the above-mentioned anhydrous granules of amantadine hydrochloride, comprising the step of preparing drug-containing taste-masked granules and taste-correcting granules separately and then mixing the two.

[0031] In some embodiments of the present invention, the preparation method includes the following steps:

[0032] (1) Mix rimantadine hydrochloride, flavor masking material, binder and filler evenly, and prepare drug-containing flavor masking granules by hot melt granulation;

[0033] (2) Mix sweetener, acidulant and binder, wet granulate, dry in fluidized bed and then granulate to obtain flavored granules;

[0034] (3) Mix the drug-containing flavor-masking granules with the flavor-correcting granules to obtain anhydrous tamantadine hydrochloride oral granules.

[0035] In the hot melt granulation process, the temperature control requirement is to be higher than the melting point of the flavor-masking material, so that the flavor-masking material melts and then coats the surface of rimantadine hydrochloride.

[0036] The preparation method of the present invention is simpler than the existing micro-pellet layering drug loading process. Moreover, the hot melt granulation method is used to prepare drug-containing flavor-masked granules. During the preparation process, the raw drug does not come into contact with water or other organic solvents, which further improves the stability of the drug. At the same time, the prepared drug-containing flavor-masked granules have irregular shapes, which makes them easy to mix evenly with flavor-correcting granules and less prone to stratification, reducing the risk of uneven dosage unit content.

[0037] This invention provides anhydrous ramantadine hydrochloride granules and their preparation method. By selecting lipid or waxy materials as taste-masking materials and mixing them with ramantadine hydrochloride to form drug-containing taste-masked granules, and then mixing them with flavor-correcting granules, the taste can be effectively masked, and the granules can be swallowed directly without water, greatly improving medication compliance. This method is especially suitable for children, the elderly, and other people with swallowing difficulties. Moreover, the preparation method of this invention is simple, requires low equipment, and is low in cost, making it suitable for large-scale production.

[0038] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., refer to specific features, structures, materials, or characteristics described in connection with that embodiment or example, which are included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples. Detailed Implementation

[0039] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0040] Unless otherwise specified, all raw materials involved in the embodiments of this invention can be obtained commercially.

[0041] Examples 1-3

[0042] Examples 1-3 provide anhydrous granules of amantadine hydrochloride, the composition of which is shown in Table 1 (by weight), and the preparation method is as follows:

[0043] (1) Preparation of taste-masking granules

[0044] Take the prescribed amounts of amantadine hydrochloride, glyceryl behenate, lactose, and povidone K30, and place them in a hot melt granulator. Mix the materials evenly by stirring and shearing. Heat the mixture to 60-80℃ while stirring, granulate for 3-5 minutes, cool to 35-45℃, and granulate using a granulator to prepare flavor-masked granules with a D90 of 200μm-350μm.

[0045] (2) Preparation of flavoring granules

[0046] Take the prescribed amounts of citric acid, mannitol, povidone K30, and aspartame, place them in a wet granulator, and turn on the stirring and shearing functions to mix the materials evenly. Add an appropriate amount of water while stirring and granulate for 3-5 minutes. Then, granulate the granules using a granulator to prepare flavored granules with a D90 of 200μm-350μm.

[0047] (3) Total Mixing

[0048] Take the prescribed amounts of flavor-masking granules and flavor-correcting granules separately and mix them evenly to obtain anhydrous tamantadine hydrochloride granules.

[0049] Table 1

[0050]

[0051] Example 4

[0052] This embodiment provides anhydrous granules of rimantadine hydrochloride, which differs from Example 1 in that the amount of behenicol glyceride is 4 times that of rimantadine hydrochloride, i.e., 200 parts, as shown in Table 2.

[0053] Table 2

[0054]

[0055] The preparation process is the same as in Examples 1-3.

[0056] Example 5

[0057] This embodiment provides anhydrous granules of amantadine hydrochloride, the composition of which is shown in Table 3, and the preparation process is the same as in Examples 1-3.

[0058] Table 3

[0059]

[0060] Example 6

[0061] This embodiment provides anhydrous granules of amantadine hydrochloride, the composition of which is shown in Table 4, and the preparation process is the same as that in Examples 1-3.

[0062] Table 4

[0063]

[0064]

[0065] Example 7

[0066] This embodiment provides anhydrous granules of amantadine hydrochloride, the composition of which is shown in Table 5, and the preparation process is the same as that in Examples 1-3.

[0067] Table 5

[0068]

[0069] Comparative Example 1

[0070] This comparative example provides anhydrous granules of amantadine hydrochloride, the composition of which is shown in Table 6, and the preparation method is as follows:

[0071] (1) Preparation of micro-pellets of the above-mentioned medicine

[0072] Preparation of the upper drug layer solution: Take a certain amount of purified water and slowly add povidone K30 while stirring. Stir until completely dissolved. Add the prescribed amount of amantadine hydrochloride and stir until completely dissolved. Add talc powder and stir evenly to prepare an upper drug layer coating solution with a solid content of about 20%.

[0073] Coating with the drug layer: The drug solution is coated onto the microcrystalline cellulose pellet core (particle size 200μm) using a fluidized bed, and the material temperature is maintained between 40 and 45℃ during the spraying process.

[0074] (2) Preparation of isolation layer microspheres

[0075] Preparation of the isolation layer solution: Prepare a 5% aqueous solution of hydroxypropyl cellulose, add polyethylene glycol 5000 and talc, and stir until homogeneous.

[0076] Isolation layer coating: The drug pellets are placed in a fluidized bed, and the isolation layer drug solution is coated onto the drug pellets. During the spraying process, the material temperature is maintained between 40 and 45°C.

[0077] (3) Preparation of flavor-masking layer microspheres

[0078] Preparation of the masking layer solution: Dissolve sodium dodecyl sulfate in water, add EPO and talc, and disperse for 30 minutes using a high-shear emulsifying disperser to prepare a suspension with a solid content of about 30%.

[0079] Odor-masking coating: The isolation pellets are placed in a fluidized bed, and the odor-masking liquid is coated onto the isolation pellets. During the spraying process, the material temperature is maintained between 25 and 30°C.

[0080] (4) Preparation of smooth layer microspheres

[0081] Preparation of the lubricating layer solution: Take a certain amount of purified water, add the lubricant and stir until completely dissolved.

[0082] Smoothing coating: The taste-masked microspheres are placed in a fluidized bed, and the smoothing liquid is coated onto the isolated microspheres. During the spraying process, the material temperature is maintained between 25 and 30°C. Anhydrous oral granules with a particle size of approximately 350 μm are obtained.

[0083] (5) Preparation of flavoring granules

[0084] Take the prescribed amounts of citric acid, mannitol, povidone K30, and aspartame and mix them in a wet granulator. Turn on the stirring and shearing functions to mix the materials evenly. Add an appropriate amount of water while stirring and granulate for 3-5 minutes. Then granulate the granules using a granulator to prepare flavored granules.

[0085] (6) Total Mixing

[0086] Take the prescribed amounts of flavor-masked granules and flavor-correcting granules separately and mix them evenly to obtain anhydrous tamantadine hydrochloride granules.

[0087] Comparative Example 2

[0088] This comparative example provides anhydrous granules of amantadine hydrochloride, the composition of which is shown in Table 6. The difference between its preparation method and that of comparative example 1 is that step (2) preparation of the isolation layer micro-pellets is omitted, that is, after the preparation of the drug micro-pellets, the taste-masking layer coating is directly applied.

[0089] Table 6

[0090]

[0091] Comparative Example 3

[0092] This comparative example provides amantadine hydrochloride granules, which differ from Example 1 in that they do not contain a taste-masking material (glyceryl behenate).

[0093] Comparative Example 4

[0094] This comparative example provides amantadine hydrochloride granules, in which all the components of Example 1 are mixed and granulated in one step (i.e., flavor-masking granules and flavor-correcting granules are not prepared separately).

[0095] As a result, the flavor-masking material partially encapsulates the flavor-correcting substances, preventing them from fulfilling their flavor-correcting function. In addition, the flavor-correcting particles are easily soluble, and once dissolved, they can cause the flavor-masking layer to break down, thus failing to effectively mask the flavor.

[0096] Performance testing

[0097] The performance of the anhydrous granules of amantadine hydrochloride obtained in each embodiment and comparative example was tested, and the results are as follows:

[0098] 1. Palatability (texture) and ease of swallowing

[0099] Without informing volunteers about the product, oral tests were conducted on 20 volunteers, who were rated on palatability and ease of swallowing. The results are shown in Table 7.

[0100] Table 7

[0101] sample taste Easy to swallow Example 1 9.0 9.8 Example 2 9.1 9.8 Example 3 9.2 9.7 Example 4 9.1 9.7 Example 5 9.1 9.6 Example 6 9.2 9.7 Example 7 9.1 9.6 Comparative Example 1 9.1 9.7 Comparative Example 2 9.1 9.6 Comparative Example 3 5.0 5.5 Comparative Example 4 6.0 7.2

[0102] Note: The taste evaluation index is out of 10 points. It is evaluated based on whether the taste is good and whether there is any odor. The average score is calculated. The swallowability evaluation index is out of 10 points. It is evaluated based on whether the swallowability is completely swallowed within 2 minutes and whether the swallowing is smooth and without any gritty feeling. The average score is calculated.

[0103] The results show that when waxy materials such as behenicol glyceryl ester are used as taste-masking materials, the taste and swallowability are good, which is consistent with the existing technology (micro-pellet layer coating process). However, the method of the present invention is significantly simpler than the existing technology.

[0104] 2. Dissolution curve

[0105] Samples from each group were taken and their dissolution and release were determined according to the method for determining dissolution and release (General Chapter 0931, Method II, Chinese Pharmacopoeia 2020 Edition). Samples were taken at 5 min, 10 min, 15 min, 20 min, and 30 min using 900 ml of pH 1.0 hydrochloric acid solution as the dissolution medium and at a rotation speed of 50 rpm. The cumulative dissolution was measured and compared with that of commercially available amantadine hydrochloride tablets. The results are shown in Table 8.

[0106] Table 8

[0107]

[0108] The results showed that in Examples 1-7 and the comparative example, the dissolution rate in hydrochloric acid medium was >85% within 15 minutes, indicating rapid dissolution, consistent with the dissolution behavior of commercially available tablets. This demonstrates that the formulation prepared with the masking material provided by this invention at a dosage range of 0.5-3 times the API dosage satisfies the need for masking while being rapidly released in gastric acid, exhibiting release behavior consistent with commercially available formulations and not affecting in vivo absorption. In Example 4, the masking material was 4 times the API dosage, resulting in slower dissolution than commercially available formulations, with a dissolution rate of <85% within 15 minutes.

[0109] 3. Stability test

[0110] The examples and comparative formulations were placed at 40°C and 65% RH for 3 months. Samples were taken at 1 month, 2 months and 3 months to determine related substances (using HPLC method). The results are shown in Table 9.

[0111] Table 9

[0112]

[0113] The results showed that in Examples 1-7, no significant changes in related substances were observed after 3 months of storage at 40°C and 65% RH. In Comparative Example 2 (without the isolation layer), a significant increase in related substances was observed after 3 months of storage at 40°C and 65% RH, indicating that the existing technology, without an isolation layer, resulted in poor product stability, while the sample containing an isolation layer (Comparative Example 1) exhibited good stability. The present invention, using waxy materials such as behenicol glyceryl ester as a taste-masking material, without an isolation layer, exhibits good stability, and its formulation process is significantly simpler than that of the existing technology. The lack of significant changes in the content of related substances also indicates that the waxy materials of the present invention have good compatibility with the drug, and no impurities are generated through reactions between the compounds.

[0114] 4. Mixing uniformity

[0115] The flavor-masking granules obtained in step (1) and the flavor-correcting granules obtained in step (2) of Example 1 were taken and mixed in a mixer for 10 minutes to simulate the production process. Samples were taken at different positions in the mixing hopper to determine the mixing uniformity. The mixing uniformity of Examples 2-3 and Comparative Examples 1-2 was determined using the same method, and the results are shown in Table 10.

[0116] Table 10

[0117] sample RSD value (should be <5%) Example 1 2.4 Example 2 2.6 Example 3 2.8 Comparative Example 1 6.7 Comparative Example 2 7.2

[0118] The results show that the flavor-masking microspheres and flavor-correcting granules provided by the prior art are difficult to mix evenly because one is a round microsphere and the other is an irregular granule. Therefore, a dual-channel granule filling machine should be used for production. However, the flavor-masking granules and flavor-correcting granules provided by the present invention have qualified mixing uniformity and can be filled using a conventional single-channel filling machine.

[0119] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. Anhydrous, swallowable granules of mefamidine hydrochloride, characterized in that, It is a mixture of drug-containing flavor-masking granules and flavor-correcting granules; the drug-containing flavor-masking granules include rimantadine hydrochloride, flavor-masking material, binder and filler; the flavor-masking material is a lipid or wax material, and the flavor-masking material is selected from one or more of glyceryl monostearate and glyceryl behenate, beeswax, and carnauba wax; the filler is lactose, and the binder is povidone K30; The mass of the odor-masking material is 0.5-3 times the mass of rimantadine hydrochloride; The mass of the filler is 0.5-3 times the mass of rimantadine hydrochloride, and the mass of the adhesive is 0.1-1 times the mass of rimantadine hydrochloride.

2. The inorganic anhydrous oseltamivir pharmacon of claim 1, wherein, The flavoring particles include sweeteners, acidulants, and binders.

3. The inorganic anhydrous oseltamivir pharmacon of claim 2, wherein, The flavoring granules also include flavorings.

4. The anhydrous granules of amantadine hydrochloride according to claim 2, characterized in that, By weight, the flavoring granules consist of 0.1-2 parts sweetener, 2-20 parts acidulant, 40-70 parts filler and 1-10 parts binder.

5. The anhydrous granules of amantadine hydrochloride according to any one of claims 1-4, characterized in that, The mass ratio of the drug-containing flavor-masking granules to the flavor-correcting granules is 2:1-10:1; the mass percentage of rimantadine hydrochloride in the drug-containing flavor-masking granules is 10%-50%.

6. The anhydrous granules of amantadine hydrochloride according to claim 5, characterized in that, The D90 of the drug-containing masking granules is 200μm-350μm, and the D90 of the flavor-correcting granules is 200μm-350μm.

7. The method for preparing anhydrous ramantadine hydrochloride granules according to any one of claims 1-6, characterized in that, This includes the steps of preparing drug-containing flavor-masked granules and flavor-correcting granules separately and then mixing the two.

8. The method for preparing anhydrous ramantadine hydrochloride granules according to claim 7, characterized in that, The preparation method includes the following steps: (1) Mix ammonium hydrochloride, flavor masking material, binder and filler evenly, and prepare drug-containing flavor masking granules by hot melt granulation; (2) Mix sweetener, acidulant and binder, wet granulate, dry in fluidized bed and then granulate to obtain flavored granules; (3) Mix the drug-containing masking granules with the flavoring granules to obtain anhydrous tamantadine hydrochloride granules.

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