K-5a2 solid dispersion and its preparation method and application in preparation

Abstract

The present invention belongs to the technical field of preparation of pharmaceutical preparations, and specifically relates to K-5a2 solid dispersions and preparation methods thereof and their applications in preparations. The K-5a2 solid dispersion of the present invention comprises the following raw materials: K-5a2, a carrier, 4.5 to 9 parts of a diluent, an antioxidant, and an organic solvent. The preparation comprises the following steps: dissolving K-5a2 and an antioxidant in an organic solvent, first adding a carrier, then adding a diluent, and drying twice to obtain a K-5a2 solid dispersion. The K-5a2 solid dispersion is applied in preparations, and the K-5a2 solid dispersion is prepared into one of K-5a2 tablets, K-5a2 capsules, and K-5a2 dry suspensions. The K-5a2 solid dispersion provided by the present invention is used to prepare tablets, capsules, and dry suspensions, has good water solubility, and has high bioavailability. The present invention also provides a method for preparing a K-5a2 solid dispersion.

Description

Technical Field

[0001] The present invention belongs to the technical field of preparation of pharmaceutical preparations, and in particular relates to a K-5a2 solid dispersion and a preparation method thereof and application in preparations. Background Art

[0002] K-5a2 has the chemical name: 4-((4-((4-(4-cyano-2,6-dimethylphenoxy)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-1-yl)methyl)benzenesulfonamide. It is a white or off-white powder at room temperature. It is easily soluble in the organic solvent N,N-dimethylformamide (DMF), slightly soluble in dimethyl sulfoxide (DMSO), slightly soluble in ethyl acetate (EA), and almost insoluble in water. The chemical properties are relatively stable, and the molecular formula is C 27 H 28 N 6 O 3 S 2 , molecular weight is 548.68. K-5a2 has achieved good results in the treatment of adult patients infected with HIV-1.

[0003] Solid dispersion (SD) refers to a dispersed system in solid form formed by uniformly dispersing drugs in a carrier in highly dispersed states such as molecular, amorphous, and microcrystalline states. As an intermediate for pharmaceutical preparations, solid dispersions can increase the solubility of poorly soluble drugs, improve bioavailability, delay drug release, increase drug stability, and solidify liquid drugs. As a new type of drug, K-5a2 has significant pharmacological activity, but its poor solubility limits its wide clinical application. Traditional formulation methods are difficult to effectively solve the problems of low solubility and slow dissolution rate of K-5a2, resulting in poor drug efficacy and reduced patient compliance. Summary of the invention

[0004] The technical problem to be solved by the present invention is to overcome the above-mentioned defects of the prior art and provide a K-5a2 solid dispersion with good dispersibility. The K-5a2 tablets, K-5a2 capsules and K-5a2 dry suspension prepared by the present invention have good water solubility and high bioavailability. The present invention also provides a method for preparing the K-5a2 solid dispersion.

[0005] The K-5a2 solid dispersion of the present invention comprises the following raw materials in parts by weight: 5 to 20 parts of K-5a2, 45 to 100 parts of a carrier, 4.5 to 9 parts of a diluent, 0.5 to 5 parts of an antioxidant, and 400 to 600 parts of an organic solvent.

[0006] The carrier is one of hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), and hydroxyethyl cellulose (HEC); the diluent is mannitol (MAN) or lactose (LAC); the antioxidant is one of 2,6-di-tert-butyl-p-cresol (BHT), butylated hydroxyanisole (BHA), and propyl gallate (PG); and the organic solvent is a mixture of ethyl acetate (EA) and acetone (ACE).

[0007] The preparation method of the K-5a2 solid dispersion comprises the following steps:

[0008] 1) dissolving K-5a2 and an antioxidant in an organic solvent to prepare a first solution;

[0009] 2) first adding a carrier to the first solution, then adding a diluent, stirring and swelling, to obtain a second solution;

[0010] 3) drying the second solution until the loss on drying is ≤3.0% to obtain a solid material;

[0011] 4) Crush and screen the solid materials;

[0012] 5) Continue drying until the loss on drying is ≤1.0% to obtain K-5a2 solid dispersion.

[0013] In step 2), the carrier addition time is not less than 60 minutes, the diluent addition time is not less than 30 minutes, and the speed is 450±150rpm (adjusted according to the stirring state of the solution). In step 3), the drying is one of rotary evaporation, spray drying, and freeze drying. The pulverization method is one of mechanical pulverization and air flow pulverization.

[0014] The K-5a2 solid dispersion is used in preparation: the K-5a2 solid dispersion is prepared into one of K-5a2 tablets, K-5a2 capsules and K-5a2 dry suspensions.

[0015] The K-5a2 tablets are prepared from K-5a2 solid dispersion and auxiliary material a according to a tableting process, wherein the auxiliary material a includes a diluent, a disintegrant, and a lubricant. The preparation method of the K-5a2 tablets comprises the following steps: mixing the K-5a2 solid dispersion and the auxiliary material a to obtain a mixture, and tableting the mixture to obtain the K-5a2 tablets.

[0016] The K-5a2 capsule is a capsule content composed of K-5a2 solid dispersion and auxiliary material a, and a capsule shell is made according to a filling process, the auxiliary material a includes a diluent, a disintegrant, and a lubricant, and the capsule shell is gelatin or hydroxypropyl methylcellulose. The preparation method of the K-5a2 capsule comprises the following steps: mixing the K-5a2 solid dispersion and the auxiliary material a to obtain a mixture, and filling the mixture into capsules to obtain the K-5a2 capsule.

[0017] The diluent is at least one of mannitol, lactose, microcrystalline cellulose, calcium phosphate and calcium hydrogen phosphate; the disintegrant is one of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose and sodium carboxymethyl starch; and the lubricant is one of magnesium stearate and sodium stearyl fumarate.

[0018] The K-5a2 dry suspension is prepared by mixing the K-5a2 solid dispersion and the auxiliary material b. The preparation method of the K-5a2 dry suspension comprises the following steps: mixing the K-5a2 solid dispersion and the auxiliary material b to obtain a mixture, packaging the mixture in an aluminum bag to obtain the K-5a2 dry suspension, and controlling the ambient humidity to be lower than 50% during the filling process.

[0019] The auxiliary material b includes a thickener, a pH regulator, and a flavoring agent; the thickener is one or more of silicon dioxide, hydroxypropyl methylcellulose, cross-linked sodium carboxymethyl cellulose, gum arabic, and xanthan gum; the pH regulator is one or both of citric acid and succinic acid; the flavoring agent is one or more of pineapple flavor, raspberry flavor, aspartame, and stevioside.

[0020] Specifically, the preparation method of the K-5a2 solid dispersion comprises the following steps:

[0021] 1) Weigh ethyl acetate and acetone in a beaker and stir to mix evenly. Weigh K-5a2 API and antioxidant and add them to the mixed solution. Stir to dissolve to obtain the first solution.

[0022] 2) Slowly add the carrier to the first solution. The addition time shall not be less than 60 minutes. After all the carrier is added, stir at 450±150rpm (adjusted according to the stirring state of the solution) for 30 minutes to fully disperse and swell the carrier. Then slowly add the diluent. The addition time shall not be less than 30 minutes. After all the diluent is added, stir for 30 minutes to fully mix the solution to obtain the second solution.

[0023] 3) Transfer the second solution to a rotary evaporator for the first drying step. Set the vacuum degree to -95±5KPa, set the water bath heating temperature to 50±5℃, set the rotation speed to 60±5rpm, and perform rotary evaporation for 6 hours. Stop the machine to detect the drying loss. If it is ≤3.0%, discharge the material. Otherwise, continue the rotary evaporation with the same parameters as above, and take samples every 2 hours to detect the drying loss. Discharge the material when it is ≤3.0%.

[0024] 4) The material obtained in step 3) is crushed using a FW-100 high-speed universal crusher, with a single crushing time of 60 seconds. The crushed material is sieved using a 60-mesh standard sieve, and the crusher is effectively cooled. The material on the sieve is continued to be crushed, and the material under the sieve is collected for later use.

[0025] 5) The fine powder collected in step 4) is dried in the second step, the vacuum is set to -95±5KPa, the water bath is turned on and the temperature is set to 50±5℃, the rotation is turned on and the speed is set to 60±5rpm, and after rotary evaporation for 6 hours, the machine is stopped to detect the drying loss. If it is ≤1.0%, the material is discharged. Otherwise, the rotary evaporation parameters are the same as above, and samples are taken every 2 hours to detect the drying loss. If it is ≤1.0%, the material is discharged. The dried fine powder is sieved with a 60-mesh sieve, and the material under the sieve is the K-5a2 solid dispersion.

[0026] The K-5a2 solid dispersion of the present invention uses hydroxypropyl methylcellulose as a carrier. Hydroxypropyl methylcellulose is a commonly used auxiliary material in oral solid preparations, usually used as an adhesive or a sustained-release material, has good safety, and has no toxic side effects on the human body. Mannitol is a commonly used diluent in oral solid preparations, and is also often used as a freeze-drying protective agent for freeze-dried preparations, with high safety. BHT is a commonly used antioxidant in pharmaceutical preparations, has low toxicity, is generally used in small amounts, and has little harm to the human body. Ethyl acetate and acetone are both Class III solvents specified in the pharmacopoeia, and can be used in oral solid preparations, with a limit control of the finished product of ≤1.0%. Increasing its water solubility by using a solid dispersion greatly increases bioavailability, reduces the dosage, and can also correspondingly reduce the occurrence of adverse reactions.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] (1) The K-5a2 solid dispersion prepared by the present invention improves the water solubility of K-5a2, improves the bioavailability, and can reduce the dosage of the preparation specification from 100 mg / tablet to 5-20 mg / tablet.

[0029] (2) The present invention utilizes the encapsulation effect of a suitable carrier to delay the hydrolysis and oxidation of the drug, thereby maintaining the stability and effectiveness of the drug.

[0030] (3) The present invention utilizes solid dispersion technology to dissolve K-5a2 and then dilute it to a solid dispersion with a concentration of 9.09% to 14.93%. Compared with direct mixing of raw materials and excipients, the solid dispersion has better uniformity and the prepared tablets have more uniform content, which is beneficial to reducing the impact of individual tablet content differences on safety and effectiveness. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 The figure is a schematic diagram of the process for preparing the K-5a2 solid dispersion of the present invention.

[0032] Figure 2 The DSC spectra of the solid dispersions of Prescription 1 and K-5a2 in Example 4 are shown in FIG.

[0033] Figure 3 The dissolution curves of K-5a2 tablets of Prescription 1, Prescription 5, and Prescription 9 in Example 5 are shown.

[0034] Figure 4 The dissolution curves of K-5a2 capsules of Prescription 1, Prescription 5, and Prescription 9 in Example 6 are shown.

[0035] Figure 5 The dissolution curves of the K-5a2 dry suspensions of Prescription 1, Prescription 5, and Prescription 9 in Example 7 are shown. DETAILED DESCRIPTION

[0036] The present invention will be further described below in conjunction with specific embodiments.

[0037] The raw materials and additives used in the following examples and comparative examples are all commercially available products.

[0038] The parameters in the following preparation methods are set to fixed values ​​and the fluctuation range of parameters in the experiment, such as 450±150rpm, 450rpm is a fixed value, and ±150rpm is the fluctuation range during the entire experiment, and other parameters are the same. The following Examples 6 and 7 are made into capsules and dry suspensions respectively, but the dissolution tests therein are all tests of their contents and have nothing to do with the corresponding capsule shells and outer bags.

[0039] Example 1

[0040] The preparation method of the K-5a2 solid dispersion is shown in the schematic flow chart as follows: Figure 1 As shown, the specific steps include:

[0041] 1) Weigh ethyl acetate and acetone in a beaker and stir to mix evenly. Weigh K-5a2 API and antioxidant and add them to the mixed solution. Stir to dissolve to obtain the first solution.

[0042] 2) Slowly add the carrier to the first solution, the addition time shall not be less than 60 minutes. After all the materials are added, stir at 450±150rpm (adjust according to the stirring state to make all the materials flow), stir for 30 minutes to fully disperse and swell the carrier, then slowly add the diluent, the addition time shall not be less than 30 minutes. After all the materials are added, stir for 30 minutes to fully mix the solution to obtain the second solution.

[0043] 3) Transfer the second solution to a 2L rotary evaporator for the first drying step. Set the vacuum degree to -95±5KPa, set the water bath heating temperature to 50±5℃, set the rotation speed to 60±5rpm, and perform rotary evaporation for 6 hours. Stop the machine to detect the drying loss. If it is ≤3.0%, discharge the material. Otherwise, continue the rotary evaporation with the same parameters as above, and take samples every 2 hours to detect the drying loss. Discharge the material when it is ≤3.0%.

[0044] 4) The material obtained in step 3) is crushed using a FW-100 high-speed universal crusher, with a single crushing time of 60 seconds. The crushed material is sieved using a 60-mesh standard sieve, and the crusher is effectively cooled. The material on the sieve is continued to be crushed, and the material under the sieve is collected for later use.

[0045] 5) The fine powder collected in step 4) is dried in the second step, the vacuum is set to -95±5KPa, the water bath is set to 50±5℃, the rotation is set to 60±5rpmrpm, and after 6 hours of rotary evaporation, the machine is stopped to detect the drying loss. If it is ≤1.0%, the material is discharged. Otherwise, the rotary evaporation parameters are the same as above, and samples are taken every 2 hours to detect the drying loss. If it is ≤1.0%, the material is discharged. The dried fine powder is sieved with a 60-mesh standard sieve, and the material under the sieve is the K-5a2 solid dispersion.

[0046] Example 2

[0047] The K-5a2 solid dispersion comprises the following formulation:

[0048] Prescription 1 to Prescription 14 were prepared according to the steps described in Example 1.

[0049] Prescription 1: As shown in Table 1, prepare a 9.09% K-5a2 solid dispersion (5 mg).

[0050] Table 1 Prescribing information

[0051]

[0052] Prescription 2: As shown in Table 2, prepare a K-5a2 solid dispersion with a concentration of 9.09% (5 mg).

[0053] Table 2 Prescribing information

[0054]

[0055] Prescription 3: As shown in Table 3, prepare a K-5a2 solid dispersion with a concentration of 9.09% (5 mg).

[0056] Table 3 Prescribing information

[0057]

[0058] Prescription 4: As shown in Table 4, prepare a K-5a2 solid dispersion with a concentration of 9.09% (5 mg).

[0059] Table 4 Prescribing information

[0060]

[0061] Prescription 5: As shown in Table 5, prepare a K-5a2 solid dispersion with a concentration of 9.09% (5 mg).

[0062] Table 5 Prescribing information

[0063]

[0064] Prescription 6: As shown in Table 6, prepare a K-5a2 solid dispersion with a concentration of 9.09% (5 mg).

[0065] Table 6 Prescribing information

[0066]

[0067] Prescription 7: As shown in Table 7, prepare a K-5a2 solid dispersion with a concentration of 9.09% (5 mg).

[0068] Table 7 Prescription Information

[0069]

[0070] Prescription 8: As shown in Table 8, prepare a K-5a2 solid dispersion with a concentration of 9.09% (5 mg).

[0071] Table 8 Prescription Information

[0072]

[0073] Prescription 9: As shown in Table 9, prepare a K-5a2 solid dispersion with a concentration of 9.09% (5 mg).

[0074] Table 9 Prescription Information

[0075]

[0076] Prescription 10: As shown in Table 10, prepare a K-5a2 solid dispersion (5 mg) with a concentration of 9.09%.

[0077] Table 10 Prescription Information

[0078]

[0079] Prescription 11: As shown in Table 11, prepare a K-5a2 solid dispersion (5 mg) with a concentration of 9.09%.

[0080] Table 11 Prescription Information

[0081]

[0082] Prescription 12: As shown in Table 12, prepare a K-5a2 solid dispersion (5 mg) with a concentration of 9.09%.

[0083] Table 12 Prescribing Information

[0084]

[0085] Prescription 13: As shown in Table 13, prepare a K-5a2 solid dispersion (10 mg) with a concentration of 11.24%.

[0086] Table 13 Prescription Information

[0087]

[0088] Prescription 14: As shown in Table 14, prepare a K-5a2 solid dispersion (20 mg) with a concentration of 14.93%.

[0089] Table 14 Prescribing Information

[0090]

[0091] Example 3

[0092] The above Prescription 1, Prescription 4, Prescription 5, Prescription 8, Prescription 9, Prescription 12, Prescription 13, and Prescription 14 were prepared into K-5a2 solid dispersions according to Example 1, and the solubility of K-5a2 raw materials at pH 2.0 hydrochloric acid solution, pH 4.5 acetate solution, and pH 6.8 phosphate solution at 37±2°C was tested. The results are shown in Tables 15 to 17.

[0093] Table 15 Solubility in pH 2.0 hydrochloric acid solution

[0094]

[0095] Table 16 Solubility in pH 4.5 acetate solution

[0096]

[0097] Table 17 Solubility in pH 6.8 phosphate solution

[0098]

[0099] It can be seen from Tables 15 to 17 above that the solubility (37±2°C) of the solid dispersion prepared by the present invention in pH 2.0 hydrochloric acid solution, pH 4.5 acetate solution, and pH 6.8 phosphate solution is significantly improved compared with the K-5a2 raw material.

[0100] Example 4

[0101] The K-5a2 solid dispersion prepared in recipe 1 and the K-5a2 raw material were simultaneously subjected to DSC (differential scanning calorimetry) detection. The differential scanning calorimetry analysis chart was collected on DSC1 / 500 / FAN. The chart is as follows: Figure 2 As shown by Figure 2 It can be seen that the K-5a2 raw material has two characteristic peaks at 220°C~240°C and 310°C~330°C, while the solid dispersion of Prescription 1 of the present invention has no characteristic peaks and exhibits an amorphous state.

[0102] Example 5

[0103] The preparation method of the K-5a2 tablet comprises the following steps:

[0104] The K-5a2 solid dispersion and auxiliary material a are mixed to obtain a mixture, and the mixture is tableted to obtain the K-5a2 tablet. The auxiliary material a includes a diluent, a disintegrant, and a lubricant.

[0105] The K-5a2 solid dispersion is the K-5a2 solid dispersion prepared by Prescription 1, Prescription 5, and Prescription 9 in the above-mentioned Example 2. The prescription information of the tablets prepared according to Prescription 1, Prescription 5, and Prescription 9 is shown in Table 18.

[0106] Table 18 Prescription information of K-5a2 tablets

[0107]

[0108] The specific preparation steps of the tablets of the above prescription are:

[0109] (1) Weigh the K-5a2 solid dispersion powder obtained from Prescription 1, Prescription 5, and Prescription 9 in Example 2, mix well with the above-mentioned excipients (mannitol, microcrystalline cellulose, and cross-linked polyvinylpyrrolidone), and then add the weighed magnesium stearate and mix well.

[0110] (2) Use a rotary tablet press to compress the material in step (1) into tablets with a hardness of 50N~100N and a friability that meets the requirements.

[0111] (3) The tablets compressed in step (2) are formed into solid pharmaceutical composite hard tablets using polyamide / aluminum / polyvinyl chloride cold stamping and packaged in pharmaceutical aluminum foil.

[0112] The tablets prepared above were subjected to dissolution curve testing: 0.01N hydrochloric acid solution, paddle method 50 revolutions, medium volume 900mL, sampling time 5min, 10min, 15min, 30min, N=6 tablets. The dissolution curves of the tablets of prescription 1, prescription 5, and prescription 9 are as follows: Figure 3 The dissolution rates at 5 min, 10 min, 15 min, 30 min and the RSD% of the dissolution rates of 6 tablets are shown in Table 19.

[0113] Table 19 RSD% of dissolution of K-5a2 and 6 tablets

[0114]

[0115] Example 6

[0116] The preparation method of the K-5a2 capsule comprises the following steps:

[0117] The K-5a2 capsule is a capsule content consisting of K-5a2 solid dispersion and auxiliary material a, and the capsule shell is made according to a filling process, specifically, after adding diluents microcrystalline cellulose and mannitol, disintegrant cross-linked polyvinylpyrrolidone, and lubricant magnesium stearate to the K-5a2 solid dispersion, it is filled into a No. 1 milky white capsule. The K-5a2 solid dispersion is the K-5a2 solid dispersion prepared by prescription 1, prescription 5, and prescription 9 in the above-mentioned Example 2. The capsule prescription information prepared according to prescription 1, prescription 5, and prescription 9 is shown in Table 20.

[0118] Table 20K-5a2 Capsule Prescription Information

[0119]

[0120] The K-5a2 capsules prepared above were subjected to dissolution curve testing: 0.01N hydrochloric acid solution, basket method 100 revolutions, medium volume 900mL, sampling time 5min, 10min, 15min, 30min, N=6. The dissolution curves of K-5a2 capsules of prescription 1, prescription 5, and prescription 9 are shown in Figure 4 The dissolution rates at 5min, 10min, 15min, and 30min and the RSD% of the dissolution rates of the six capsules are shown in Table 21.

[0121] Table 21 RSD% of dissolution of K-5a2 and dissolution of 6 capsules

[0122] Example 7

[0123] The preparation method of the K-5a2 dry suspension comprises the following steps:

[0124] The K-5a2 solid dispersion and the auxiliary material b (thickeners hydroxypropyl methylcellulose and xanthan gum, pH regulator citric acid, flavoring agents pineapple flavor and aspartame) are mixed to obtain a mixture, and the mixture is packaged in an aluminum bag to obtain the K-5a2 dry suspension. The ambient humidity is controlled to be lower than 50% during the filling process.

[0125] The K-5a2 solid dispersion is the K-5a2 solid dispersion prepared by Prescription 1, Prescription 5, and Prescription 9 in the above-mentioned Example 2. The prescription information of the dry suspension prepared according to Prescription 1, Prescription 5, and Prescription 9 is shown in Table 22.

[0126] Table 22K-5a2 Prescription Information for Dry Suspension

[0127]

[0128] The K-5a2 dry suspension prepared above was subjected to dissolution curve testing: 0.01N hydrochloric acid solution, paddle method 50 revolutions, medium volume 900mL, sampling time 5min, 10min, 15min, 30min, N=6 bags. The dissolution curves of the K-5a2 dry suspensions of Prescription 1, Prescription 5, and Prescription 9 are shown in FIG. Figure 5 The RSD% of the dissolution at 5min, 10min, 15min, 30min, 45min, 60min, 90min, 120min and the dissolution of 6 bags of dry suspension are shown in Table 23.

[0129] Table 23 RSD% of dissolution of K-5a2 and 6 bags of dry suspension

[0130]

[0131] From the above Tables 19, 21, 23 and Figure 3 , 4 It can be seen from Figure 5 that after the K-5a2 solid dispersion prepared by the present invention is used to make tablets, capsules, and dry suspensions, the dissolution rate is high and the dissolution is stable, thus maintaining the stability and effectiveness of the drug.

Claims

1. A method for preparing a K-5a2 solid dispersion, characterized in that: The following steps are involved: 1) dissolving K-5a2 and an antioxidant in an organic solvent to prepare a first solution; 2) first adding a carrier to the first solution, then adding a diluent, stirring and swelling, to obtain a second solution; 3) drying the second solution until the loss on drying is ≤3.0% to obtain a solid material; 4) Crush and screen the solid materials; 5) Continue drying until the loss on drying is ≤1.0% to obtain K-5a2 solid dispersion; The K-5a2 solid dispersion comprises the following raw materials in parts by weight: 5 to 20 parts of K-5a2, 45 to 100 parts of a carrier, 4.5 to 9 parts of a diluent, 0.5 to 5 parts of an antioxidant, and 400 to 600 parts of an organic solvent; The carrier is one of hydroxypropyl methylcellulose, hydroxypropyl cellulose and hydroxyethyl cellulose; the diluent is mannitol or lactose; the antioxidant is one of 2,6-di-tert-butyl-p-cresol, butylated hydroxyanisole and propyl gallate; and the organic solvent is a mixture of ethyl acetate and acetone.

2. The method for preparing the K-5a2 solid dispersion according to claim 1, characterized in that: In step 2), the carrier addition time is not less than 60 minutes, the diluent addition time is not less than 30 minutes, and the stirring speed is 450±150 rpm.

3. A K-5a2 solid dispersion prepared by the preparation method of claim 1 or 2 for use in formulations, characterized in that: The K-5a2 solid dispersion is prepared into one of K-5a2 tablets, K-5a2 capsules and K-5a2 dry suspensions.

4. The K-5a2 solid dispersion according to claim 3 is used in a preparation, characterized in that: The K-5a2 tablets are prepared from K-5a2 solid dispersion and auxiliary material a according to a tableting process, wherein the auxiliary material a includes a diluent, a disintegrant, and a lubricant.

5. The K-5a2 solid dispersion according to claim 4 is used in a preparation, characterized in that: The K-5a2 capsule is a capsule content consisting of K-5a2 solid dispersion and auxiliary material a, and a capsule shell is made according to a filling process. The auxiliary material a includes a diluent, a disintegrant, and a lubricant, and the capsule shell is gelatin or hydroxypropyl methylcellulose.

6. The K-5a2 solid dispersion according to claim 4 or 5 is used in a preparation, characterized in that: The diluent is at least one of mannitol, lactose, microcrystalline cellulose, calcium phosphate and calcium hydrogen phosphate; the disintegrant is one of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose and sodium carboxymethyl starch; and the lubricant is one of magnesium stearate and sodium stearyl fumarate.

7. The K-5a2 solid dispersion according to claim 3 is used in a preparation, characterized in that: The K-5a2 dry suspension is prepared by mixing the K-5a2 solid dispersion and auxiliary material b.

8. The K-5a2 solid dispersion according to claim 7 is used in a preparation, characterized in that: The auxiliary material b includes a thickener, a pH regulator, and a flavoring agent; the thickener is one or more of silicon dioxide, hydroxypropyl methylcellulose, cross-linked sodium carboxymethyl cellulose, gum arabic, and xanthan gum; the pH regulator is one or both of citric acid and succinic acid; the flavoring agent is one or more of pineapple flavor, raspberry flavor, aspartame, and stevioside.

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