Preparation method of pitavastatin calcium orally disintegrating tablet for masking taste

Abstract

The invention provides a preparation method of a pitavastatin calcium orally disintegrating tablet for masking taste. The preparation method comprises the following steps: granulating soluble auxiliary materials and crude drugs in a high-speed shearing granulator for many times; mixing the finally obtained particles with an additional material to obtain a total mixed material; tabletting the total mixed material; wherein the granulation time of the first granulation is more than or equal to 15 minutes, the last granulation is that wet granules and dry soluble auxiliary materials are granulated, the particle size D10 of the raw material medicine is more than 5 microns, and the particle size D90 of the raw material medicine is less than 50 microns. According to the technical scheme, the purpose of covering the bitter taste of the medicine can be achieved through a granulation process, and the medicine does not need to be subjected to coating treatment; different from common shearing and mixing granulation, the soluble auxiliary materials are granulated with the raw material medicines in a certain sequence for multiple times, so that the process time is remarkably shortened, the medicines are prevented from being in a humid and hot environment for a long time, and the stability of the product is favorably improved.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical preparations, and in particular to a method for preparing a pitavastatin calcium orally disintegrating tablet for taste masking. Background Art

[0002] Pitavastatin calcium, English name is pitavastatin, chemical name is (+)-bis{(3R, 5S, 6E)-7-[2- Cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptanoic acid monocalcium salt is a new type of statin lipid-lowering drug jointly developed by Nissan Chemical Industries, Ltd. and Kowa Corporation of Japan. It was first launched in Japan in the form of ordinary tablets in July 2003 and orally disintegrating tablets on February 15, 2013.

[0003] Compared with ordinary tablets, orodisintegrating tablets can disintegrate in saliva within a few seconds, and do not need to be taken with water, which can improve the compliance of special medication groups, such as the elderly, children and patients with dysphagia, and people who use them under special conditions such as going out or lack of drinking water. Because orodisintegrating tablets disintegrate in the mouth, the drug will be perceptibly exposed to the taste buds. When the drug has an unpleasant taste or bitter taste, taste masking becomes a key technical issue for orodisintegrating tablets.

[0004] Pitavastatin calcium has a strong bitter taste. Patent JP2013144717A dissolves or suspends flavoring agents in a polymer material water / alcohol solution that can form a film, and then coats or sprays the drug to achieve the effect of physical isolation, thereby achieving the purpose of covering up the bitter taste. However, the problem with this process is that the drug is in the coating process, and the process time is relatively long. In the process of coating the drug, the drug needs to be exposed to a damp heat or organic reagent environment for a long time, and pitavastatin calcium is unstable to damp heat, and in contact with an organic reagent, the risk of transcrystallization will be increased, thereby increasing the potential stability risk of the product. However, when the drug is not coated, only one or more flavoring agents or sweeteners are used to mix with the drug or conventional granulation, and an acceptable taste masking effect is not achieved. Summary of the invention

[0005] The main purpose of the present invention is to provide a method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet, aiming to solve the technical problems of the existing pitavastatin calcium drug having an unsatisfactory taste-masking effect and poor stability.

[0006] To achieve the above object, the present invention provides a method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet, which comprises the following steps: The soluble excipients are granulated with the API in a high-speed shear granulator in multiple times; The finally obtained particles are mixed with the added materials to obtain a total mixed material; tableting the total mixed material; The soluble excipients are granulated with the API in a high-speed shear granulator for multiple times, including: First granulation: The API and some soluble excipients are shear-mixed and granulated using water as a wetting agent to obtain the first granules; Second granulation: adding another portion of soluble excipients to the first granules for shear mixing and granulation to obtain second granules; The third granulation: adding the last part of the soluble excipients to the second granules for shear mixing and granulation to obtain the third granules; The granulation time of the first granulation is ≥15 minutes, and the last granulation is granulation of wet granules and dry soluble excipients. The particle size of the API is D10>5μm and D90<50μm. D10 in the particle size distribution represents the particle size corresponding to 10% of the cumulative particle size distribution, and D90 in the particle size distribution represents the particle size corresponding to 90% of the cumulative particle size distribution.

[0007] Optionally, the soluble auxiliary material includes one or more of a filler, a binder, and a flavoring agent.

[0008] Optionally, the filler is lactose, the binder is hydroxypropyl cellulose, and the flavoring agent is menthol and orange flavor.

[0009] Optionally, the step of granulating the soluble excipient with the API in a high-speed shear granulator in multiple times comprises: First granulation: the API and part of lactose are shear-mixed and granulated using water as a wetting agent to obtain the first granules; Second granulation: adding hydroxypropyl cellulose to the first granules for shear mixing and granulation to obtain second granules; The third granulation: add another part of lactose to the second granules for shear mixing and granulation to obtain the third granules.

[0010] Optionally, in the second granulation step, hydroxypropyl cellulose is added in the form of dry powder or in the form of an aqueous solution.

[0011] Optionally, in the first granulation of the step, the weight ratio of the amount of the raw material to the lactose is 1:(10-20); in the second granulation of the step, the weight ratio of the amount of hydroxypropyl cellulose to the raw material is (0.5-1.5):1; in the third granulation of the step, the weight ratio of the amount of lactose to the raw material is (20-40):1.

[0012] Optionally, in the first granulation of the step, the weight ratio of the API to lactose is 1:15; in the second granulation of the step, the weight ratio of hydroxypropyl cellulose to the API is 1:1; in the third granulation of the step, the weight ratio of lactose to the API is 30:1.

[0013] Optionally, the step of granulating the soluble excipient with the API in a high-speed shear granulator in multiple times comprises: First granulation: the API and part of lactose are shear-mixed and granulated using water as a wetting agent to obtain the first granules; Second granulation: adding hydroxypropyl cellulose to the first granules for shear mixing and granulation to obtain second granules; Third granulation: Add another portion of lactose, menthol and orange flavor to the second granules for shear mixing and granulation to obtain third granules.

[0014] Optionally, in the third granulation step, the weight ratio of the total amount of menthol and orange flavor to the raw material drug is (0~1):1.

[0015] Optionally, the particle size of the raw material drug is D10>5μm and D90<20μm.

[0016] In the technical solution of the present invention, the purpose of masking the bitter taste of the drug can be achieved through the granulation process, and there is no need to coat the drug; different from the general shear mixing granulation, the present invention granulates the soluble excipients with the raw material in multiple times and in a certain order, which significantly shortens the process time, avoids the drug being in a humid and hot environment for a long time, and helps to improve product stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0018] Figure 1 The present invention is a schematic flow chart of an embodiment of a method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet.

[0019] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0020] To make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them.

[0021] It should be noted that, in the embodiments, those without specifying specific conditions are carried out according to normal conditions or conditions recommended by the manufacturer. Those without specifying the manufacturer of reagents or instruments used are conventional products that can be purchased commercially. In addition, the meaning of "and / or" appearing in the full text includes three parallel schemes, and "A and / or B" is taken as an example, including schemes A, B, or A and B that meet the same time. In addition, the technical schemes between the various embodiments can be combined with each other, but must be based on the ability of ordinary technicians in the field to achieve. When the combination of the technical schemes is contradictory or cannot be achieved, it should be considered that the combination of such technical schemes does not exist, and is not within the scope of protection required by the present invention. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in the field without making creative work, all belong to the scope of protection of the present invention.

[0022] The current drug coating process takes a long time. During the drug coating process, the drug needs to be exposed to moisture, heat or organic reagents for a long time. Pitavastatin calcium is unstable to moisture and heat, and contact with organic reagents will increase the risk of crystal transformation, thereby increasing the potential stability risk of the product. However, when the drug is not coated and only one or more flavoring agents or sweeteners are used to mix with the drug or conventional granulation is performed, an acceptable taste masking effect cannot be achieved.

[0023] In view of this, the present invention proposes a method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet, Figure 1 A schematic flow chart of an embodiment of a method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet is provided, which comprises the following steps: Step S10, granulating the soluble excipients with the raw material in a high-speed shear granulator for multiple times.

[0024] Soluble excipients include one or more of fillers, binders, and flavoring agents. The granulation time for the first granulation is ≥15 minutes, and the last granulation is to granulate the wet granules with dry soluble excipients. The particle size of the API is D10>5μm and D90<50μm. It should be noted that D10 in the particle size distribution represents the particle size corresponding to 10% of the cumulative particle size distribution, and D90 in the particle size distribution represents the particle size corresponding to 90% of the cumulative particle size distribution.

[0025] In this embodiment, the API is pitavastatin calcium, the filler is lactose, the binder is hydroxypropyl cellulose, and the flavoring agents are menthol and orange flavor. Of course, other substances that can achieve the same effect can also be used as fillers, binders, and flavoring agents, which will not be described in detail here. Preferably, the particle size of the API is D10>5μm and D90<20μm.

[0026] Among them, granulation is carried out three times with the raw material in a high-speed shear granulator. In one embodiment of the present invention, the following steps are included: Step 1 granulation: The API and part of lactose are shear-mixed and granulated with water as a wetting agent to obtain the first granules.

[0027] In a specific implementation, the API and part of lactose are added to a wet granulator, mixed at a stirring speed of 60 rpm for 10 minutes, and then purified water is added to a high-speed shear granulator in the form of a spray to perform shear mixing and granulation, and the granulation time is at least 15 minutes.

[0028] Step 2: Second granulation: Hydroxypropyl cellulose is added to perform shear mixing and granulation to obtain second granules.

[0029] In specific implementation, hydroxypropyl cellulose is added in the form of dry powder or in the form of aqueous solution. In this embodiment, hydroxypropyl cellulose and water are mixed into an aqueous solution with a weight proportion of 2-4%, which is added to a high-speed shear granulator in the form of a spray, and after shear mixing, wet granules are formed. It should be understood that even if hydroxypropyl cellulose is added in the form of dry powder, when the first granules contain water, the second granulation still obtains wet granules.

[0030] Step 3rd granulation: adding another portion of lactose therein to carry out shear mixing and granulation to obtain third granules.

[0031] In the specific implementation, the wet granules obtained by the second granulation are shear-mixed with dry lactose to form granules. The preparation process also includes the following steps: the mixed wet materials are transferred to a fluidized bed, dried until the moisture content is less than 2%, and the granules are sieved through a 1.0 mm to 2 mm sieve to obtain the third granules, i.e., the drug-containing granules.

[0032] Among them, in the first granulation step, the weight ratio of the amount of the raw material to the lactose is 1: (10-20), preferably 1:15; in the second granulation step, the weight ratio of the amount of hydroxypropyl cellulose to the raw material is (0.5-1.5): 1, preferably 1: 1; in the third granulation step, the weight ratio of the amount of lactose to the raw material is (20-40): 1, preferably 30: 1.

[0033] In other embodiments of the present invention, the third granulation step can be performed by mixing lactose and flavoring agents together for granulation, that is, in the third granulation step, another portion of lactose, orange flavor and menthol are added thereto for shear mixing and granulation. The total amount of menthol and orange flavor is in a weight ratio of (0-1):1 to the bulk drug, preferably 0.15:1.

[0034] Step S20: Mix the final particles with the added materials to obtain a total mixed material.

[0035] In a specific implementation, the external materials microcrystalline cellulose, lactose, cross-linked polyvinylpyrrolidone, yellow iron oxide, and magnesium stearate are added to the drug-containing granules obtained by the third granulation step, and mixed at a speed of 15 rpm for 5 to 15 minutes, and magnesium stearate is added and mixed for 3 to 5 minutes to obtain a total mixed material. It should be understood that the microcrystalline cellulose in the external materials is a binder, the cross-linked polyvinylpyrrolidone is a disintegrant, the yellow iron oxide is a sunscreen, and the magnesium stearate is a lubricant.

[0036] Step S30, tableting the total mixed material.

[0037] In a specific implementation, the total mixed material obtained in step S20 is tableted to control the tablet hardness to be 2-6 kg.

[0038] The technical solution of the present invention is further described in detail below in conjunction with specific embodiments and drawings. It should be understood that the following embodiments are only used to explain the present invention, and are not used to limit the present invention. Example 1

[0039] 1.1 Prescription

[0040] 1.2 Preparation method Add pitavastatin calcium and lactose with a particle size of D10>5μm and D90<20μm into a wet granulator, mix at a stirring speed of 60rpm for 10min, then add purified water in the form of spray for shear mixing and granulation, and the granulation time is 25min; prepare hydroxypropyl cellulose into an aqueous solution with a mass concentration of 3%, spray it into the above materials for a second shear mixing and granulation, and the granulation time is 2min; add lactose to the above materials, and perform a third shear mixing and granulation, and the granulation time is 3min; transfer the wet material to a fluidized bed, and dry it until the moisture content is less than 2% to collect the material. Pass the granules through a 1.0mm~2mm sieve to obtain drug-containing granules; add additional microcrystalline cellulose, lactose, cross-linked polyvinylpyrrolidone, yellow iron oxide, magnesium oxide, and magnesium stearate to the drug-containing granules and mix at a speed of 10rpm for 5min, add magnesium stearate, and mix for 4min; obtain a total mixed material; tablet the total mixed material to control the tablet hardness within 2~6kg. Example 2

[0041] 2.1 Prescription

[0042] 2.2 Preparation method Add pitavastatin calcium and lactose with particle size D10>5μm and D90<20μm into a wet granulator, mix at a stirring speed of 60rpm for 10min, then add purified water in the form of spray for shear mixing and granulation, the granulation time is 20min; prepare hydroxypropyl cellulose into an aqueous solution with a mass concentration of 3%, spray it into the above materials for a second shear mixing and granulation, the granulation time is 2min; add lactose, menthol and orange flavor to the above materials, and carry out a third shear mixing and granulation, the granulation time is 3min; transfer the wet material to a fluidized bed, dry it until the moisture content is less than 2%, and collect the material. Pass the granules through a 1.0mm~2mm sieve to obtain drug-containing granules; add microcrystalline cellulose, lactose, cross-linked polyvinylpyrrolidone, yellow iron oxide, magnesium oxide, and magnesium stearate to the drug-containing granules and mix at a speed of 15rpm for 10min, add magnesium stearate and mix for 3min; obtain a total mixed material; tablet the total mixed material to control the tablet hardness within 2~6kg. Example 3

[0043] 3.1 Prescription

[0044] 3.2 Preparation method Add pitavastatin calcium and lactose with a particle size of D10>5μm and D90<50μm into a wet granulator, mix at a stirring speed of 60rpm for 10min, add purified water in the form of spray for shear mixing and granulation, and the granulation time is 15min; prepare hydroxypropyl cellulose into an aqueous solution with a mass concentration of 3%, spray it into the above materials for a second shear mixing and granulation, and the granulation time is 2min; add lactose to the above materials, and perform a third shear mixing and granulation, and the granulation time is 3min; transfer the wet material to a fluidized bed, and dry it until the moisture content is less than 2% to collect the material. Pass the granules through a 1.0mm~2mm sieve to obtain drug-containing granules; add menthol, orange flavor, microcrystalline cellulose, lactose, cross-linked polyvinylpyrrolidone, yellow iron oxide, magnesium oxide, and magnesium stearate to the obtained drug-containing granules and mix at a speed of 15rpm for 15min, add magnesium stearate, and mix for 5min; obtain a total mixed material; tablet the obtained total mixed material, and control the tablet hardness within 2~6kg. Comparative Example 1

[0045] 4.1 Prescription

[0046] 4.2 Preparation method Add pitavastatin calcium and lactose to a wet granulator, mix at a stirring speed of 60rpm for 10min, then add hydroxypropyl cellulose in a 3% aqueous solution in the form of spray for shear mixing and granulation, and the granulation time is 2min; transfer the wet material to a fluidized bed and dry it until the moisture content is less than 2% to collect the material. Pass the granules through a 1.0mm~2mm sieve to obtain drug-containing granules; add additional materials menthol, orange flavor, microcrystalline cellulose, lactose, cross-linked polyvinylpyrrolidone, yellow iron oxide, magnesium oxide, and magnesium stearate to the drug-containing granules and mix at a speed of 15rpm for 10min, add magnesium stearate, mix for 4min, and obtain a total mixed material; press the total mixed material into tablets, and control the tablet hardness within 2~6kg. Comparative Example 2

[0047] 5.1 Prescription

[0048] 5.2 Preparation method Preparation of coating solution: dissolve or suspend hydroxypropyl methylcellulose, aminoalkyl methacrylate copolymer E, menthol, orange flavor, magnesium oxide, yellow iron oxide, and titanium dioxide in 70% ethanol in sequence; coating: put pitavastatin calcium, lactose, and cross-linked polyvinylpyrrolidone into a fluidized bed, spray the coating solution into the fluidized bed for granulation and coating, continue to dry the granules after coating until the moisture content is less than 2%, and pass the granules through a 1.0mm~2mm sieve to obtain drug-containing granules. Add lactose, cross-linked polyvinylpyrrolidone, yellow iron oxide, and magnesium stearate to the obtained drug-containing granules and mix at a speed of 15rpm for 10min, add magnesium stearate, and mix for 4min to obtain a total mixed material. The total mixed material is tableted to control the tablet hardness within 2~6kg.

[0049] The finished products prepared in the above embodiments and comparative examples were experimentally verified: 1. Disintegration test The disintegration time of the tablets was tested according to the orodisintegrating tablet test method in the general chapters of the disintegration time limit test method in the 2020 edition of the Chinese Pharmacopoeia.

[0050]

[0051] The disintegration time of Examples 1-3 and Comparative Examples 1-2 are both qualified.

[0052] 2. Palatability evaluation Six volunteers were recruited to taste the tablets of the examples and evaluate the tablets' mouthfeel, dissolution / disintegration time, and grittiness in the oral cavity. The results were summarized.

[0053]

[0054] Example 1 shows that by granulating the soluble excipients with the raw materials in batches, the purpose of masking the bitter taste can be achieved even without adding a flavoring agent; compared with Example 1 and Example 2, part of the lactose added by the third granulation is replaced with the flavoring agents menthol and orange flavor, and the dissolution time is significantly shortened. It can be seen that the flavoring agents menthol and orange flavor added in the third granulation can not only improve the taste, but also accelerate the dissolution; Examples 2 and 3 show that adding a flavoring agent can increase the palatability and have a more refreshing feeling. Compared with Example 2 and Example 3, the flavoring agent menthol , orange flavor as an additional material will affect the dissolution time of the orally disintegrating tablet, while by adding menthol and orange flavor in the third granulation, the dissolution time is significantly shortened; compared with Example 1 and Example 3, adding the flavoring agents menthol and orange flavor in the form of additional materials does not improve the dissolution time; Comparative Example 1 shows that conventional granulation cannot cover up the bitterness even with the addition of flavoring agents; Comparative Example 2 shows that the bitterness of the drug can be covered up by coating, but the dissolution time and disintegration time are both prolonged, which shows that the coating affects the disintegration of the drug.

[0055] 3. Tablet content uniformity inspection The content uniformity of the tablets of each example was tested.

[0056]

[0057] Comparison of Comparative Example 2 with other examples shows that the coating process of Comparative Example 2 increases the difference in the powder properties between the drug-containing particles and the added materials. Although both are qualified, the RSD is significantly higher than that of other examples.

[0058] 4. Stability test

[0059] Comparative Example 2 and other examples show that as the preparation time of the process increases significantly, the total impurity level increases significantly.

[0060] In summary, the orodisintegrating tablets of pitavastatin calcium prepared by the present invention have no bitter taste, the process preparation time is significantly shortened, and the tablets have more stability advantages. The purpose of masking the bitter taste of the drug can be achieved through the granulation process, and there is no need to coat the drug; different from the general shear mixing granulation, the present invention is to granulate the soluble excipients with the raw materials in multiple times and in a certain order, which significantly shortens the process time, avoids the drug from being in a hot and humid environment for a long time, and helps to improve the stability of the product.

[0061] The technical features of the above embodiments may be combined arbitrarily. To make the description concise, not all possible combinations of the technical features in the above embodiments 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.

[0062] The above embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application shall be subject to the attached claims.

Claims

1. A method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet, characterized in that: The following steps are involved: The soluble excipients are granulated with the API in a high-speed shear granulator in multiple times; The finally obtained particles are mixed with the added materials to obtain a total mixed material; tableting the total mixed material; The soluble excipients are granulated with the API in a high-speed shear granulator for multiple times, including: First granulation: The API and some soluble excipients are shear-mixed and granulated using water as a wetting agent to obtain the first granules; Second granulation: adding another portion of soluble excipients to the first granules for shear mixing and granulation to obtain second granules; The third granulation: adding the last part of soluble excipients to the second granules for shear mixing and granulation to obtain the third granules; The first granulation has a granulation time of ≥15 minutes, the third granulation is performed by granulating the wet second granules with dry soluble excipients, and the particle size of the raw material drug D10>5μm, D90<50μm.

2. The method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet according to claim 1, characterized in that: The soluble auxiliary materials include one or more of fillers, binders and flavoring agents.

3. The method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet according to claim 2, characterized in that: The filler is lactose, the binder is hydroxypropyl cellulose, and the flavoring agent is menthol and orange flavor.

4. The method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet according to claim 3, characterized in that: The steps of granulating the soluble excipients with the API in a high-speed shear granulator in multiple times include: First granulation: the API and part of lactose are shear-mixed and granulated using water as a wetting agent to obtain the first granules; Second granulation: adding hydroxypropyl cellulose to the first granules for shear mixing and granulation to obtain second granules; The third granulation: add another part of lactose to the second granules for shear mixing and granulation to obtain the third granules.

5. The method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet according to claim 4, characterized in that: In the second granulation step, hydroxypropyl cellulose is added in the form of dry powder or in the form of aqueous solution.

6. The method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet according to claim 4, characterized in that: In the first granulation of the step, the weight ratio of the amount of the raw material to the lactose is 1: (10-20); in the second granulation of the step, the weight ratio of the amount of hydroxypropyl cellulose to the raw material is (0.5-1.5): 1; in the third granulation of the step, the weight ratio of the amount of lactose to the raw material is (20-40):

1.

7. The method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet according to claim 6, characterized in that: In the first granulation of the step, the weight ratio of the API to lactose is 1:15; in the second granulation of the step, the weight ratio of hydroxypropyl cellulose to the API is 1:1; in the third granulation of the step, the weight ratio of lactose to the API is 30:

1.

8. The method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet according to claim 3, characterized in that: The steps of granulating the soluble excipients with the API in a high-speed shear granulator in multiple times include: First granulation: the API and part of lactose are shear-mixed and granulated using water as a wetting agent to obtain the first granules; Second granulation: adding hydroxypropyl cellulose to the first granules for shear mixing and granulation to obtain second granules; Third granulation: Add another portion of lactose, menthol and orange flavor to the second granules for shear mixing and granulation to obtain third granules.

9. The method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet according to claim 8, characterized in that: In the third granulation step, the weight ratio of the total amount of menthol and orange flavor to the raw material drug is (0-1):

1.

10. The method for preparing a taste-masked pitavastatin calcium orally disintegrating tablet according to claim 1, characterized in that: The particle size of the raw material drug is D10>5μm and D90<20μm.

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