Lurasidone hydrochloride composition and preparation method thereof

Abstract

A lurasidone hydrochloride composition and a preparation method thereof, comprising a lurasidone hydrochloride granular composition and a lubricant. The lurasidone hydrochloride granular composition comprises lurasidone hydrochloride, cross-linked sodium carboxymethyl cellulose, silicon dioxide, pregelatinized starch, a filler, and a binder.

Description

[0001] This application claims priority to the Chinese patent application filed with the Patent Office of China on August 26, 2020, with application number 202010867062.8, and invention name “A Lurasidone Hydrochloride Oral Preparation and Its Preparation Method”, the entire contents of which are incorporated herein by reference. Technical Field

[0002] The present invention belongs to the technical field of medicine and relates to a lurasidone hydrochloride composition and a preparation method thereof. Background Art

[0003] Lurasidone is an atypical antipsychotic drug. Its structural formula is as follows:

[0004]

[0005] Chinese patent CN201010564784.2 discloses a lurasidone fast-dissolving tablet and a preparation method thereof, wherein the dissolution rate is improved by making the content of pregelatinized starch by weight 10-50% of the weight of the preparation.

[0006] Chinese patent CN201410602319.1 discloses the use of a mixture of low-substituted hydroxypropyl cellulose and cross-linked sodium methylcellulose, wherein the low-substituted hydroxypropyl cellulose accounts for 5-20% of the weight of the preparation, and the mixture of cross-linked sodium methylcellulose accounts for 1-5% of the weight of the preparation. The weight ratio of low-substituted hydroxypropyl cellulose to cross-linked sodium carboxymethyl cellulose is 4-6:1. The effect of improving dissolution rate is achieved by using two disintegrants.

[0007] Bioavailability is the rate at which a drug enters its target organ or tissue and the extent to which it is utilized by that organ. Lurasidone is a poorly soluble drug, presenting bioavailability challenges when administered orally. Because drug bioavailability testing is more complex than in vitro dissolution testing, in practice, in vitro dissolution measurements can generally be used to predict the in vivo bioavailability of poorly soluble drugs. However, this correlation may be poor. Summary of the Invention

[0008] The present invention provides a lurasidone hydrochloride composition and a preparation method thereof. The lurasidone hydrochloride composition can comprehensively improve the dissolution effect of lurasidone hydrochloride and simultaneously enhance the bioavailability.

[0009] In one aspect, the present invention provides a lurasidone hydrochloride granular composition, comprising the following components: lurasidone hydrochloride, croscarmellose sodium, silicon dioxide, pregelatinized starch, a filler, and a binder.

[0010] The granular composition described herein refers to a product obtained through granulation. Granulation is the process of processing a material in a powdered state, such as a powder, into granules of a defined shape and size. Granulation, as a particle processing process, is relevant to almost all solid dosage forms. The granulated product can be a final product or an intermediate. For example, in capsule production, the granules are the final product, while in tablet production, the granules are the intermediate.

[0011] Preferably, the present invention provides a lurasidone hydrochloride granule composition, which comprises the following components: 20-45 wt% of lurasidone hydrochloride, 0.5-5.0 wt% of cross-linked sodium carboxymethyl cellulose, 0.25-4.0 wt% of silicon dioxide, greater than 0 wt% and less than 10 wt% of pregelatinized starch, a filler, and a binder.

[0012] Further preferably, the lurasidone hydrochloride granular composition of the present invention comprises 0.5-3.0 wt% of cross-linked sodium carboxymethyl cellulose, particularly preferably 1.5-2.5 wt% of cross-linked sodium carboxymethyl cellulose, preferably 0.5-1.5 wt% of silicon dioxide, particularly preferably 0.5-1 wt% of silicon dioxide, and / or preferably greater than 0 wt% and less than or equal to 9.0 wt% of pregelatinized starch.

[0013] More preferably, the lurasidone hydrochloride granular composition of the present invention comprises 30-80 wt% of filler, preferably 40-70 wt% of filler, more preferably 55-60 wt% of filler, particularly preferably 56-60 wt% of filler.

[0014] More preferably, the lurasidone hydrochloride granular composition of the present invention comprises 0.5-20 wt% of a binder, preferably 0.5-8 wt% of a binder, and particularly preferably 4.0-5.0 wt% of a binder.

[0015] Fillers suitable for the lurasidone hydrochloride granular composition of the present invention include, but are not limited to, one or any combination of mannitol, lactose, microcrystalline cellulose, xylitol, silicified microcrystalline cellulose, starch, sucrose, glucose, maltitol, fructose, sorbitol, calcium hydrogen phosphate, calcium dihydrogen phosphate, calcium silicate, etc., preferably mannitol and microcrystalline cellulose, more preferably mannitol.

[0016] Binders suitable for the lurasidone hydrochloride granule composition of the present invention include, but are not limited to, hypromellose, hydroxypropyl cellulose, methyl cellulose, copovidone, povidone, polyvinyl alcohol, etc., preferably hypromellose and polyvinyl alcohol, more preferably hypromellose.

[0017] The silicon dioxide described in the present invention is colloidal silicon dioxide.

[0018] In another aspect, the present invention provides a pharmaceutical composition of lurasidone hydrochloride, comprising the above-mentioned lurasidone hydrochloride granule composition and a lubricant, wherein the pharmaceutical composition is preferably a tablet.

[0019] Lubricants suitable for the lurasidone hydrochloride pharmaceutical composition of the present invention include, but are not limited to, stearic acid, magnesium stearate, sodium stearyl fumarate, talc, etc., preferably magnesium stearate and sodium stearyl fumarate; more preferably sodium stearyl fumarate.

[0020] Furthermore, the lurasidone hydrochloride pharmaceutical composition of the present invention contains 0.1-5 wt% of lubricant, preferably 0.5%-2 wt%, more preferably 0.75-2 wt%, and particularly preferably 0.75-1 wt%.

[0021] Furthermore, the particle size of lurasidone hydrochloride in the lurasidone hydrochloride granule composition or pharmaceutical composition of the present invention is preferably D90 of 1-25 μm, more preferably D90 of 6-25 μm, and particularly preferably D90 of 6-16 μm.

[0022] Furthermore, the particle size D50 of lurasidone hydrochloride in the lurasidone hydrochloride granule composition or pharmaceutical composition of the present invention is 2-9 μm, and particularly preferably D50 is 2.5-8 μm.

[0023] On the other hand, the present invention also provides a method for preparing a lurasidone hydrochloride granule composition, the method comprising the following steps:

[0024] 1) mixing lurasidone hydrochloride, pregelatinized starch, a filler, and cross-linked sodium carboxymethyl cellulose to obtain a mixture;

[0025] 2) wet granulating the mixture obtained in 1) with a binder and silicon dioxide, and drying to obtain a lurasidone hydrochloride granular composition.

[0026] In another aspect, the present invention also provides a method for preparing a lurasidone hydrochloride pharmaceutical composition, comprising adding a lubricant to a lurasidone hydrochloride granule composition, optionally adding an external disintegrant, and further processing the composition to obtain a pharmaceutical composition, such as compressing the composition to obtain tablets or encapsulating the composition to obtain capsules.

[0027] Preferably, the lurasidone hydrochloride pharmaceutical composition obtained above may be film-coated, if necessary.

[0028] If desired, the lurasidone hydrochloride pharmaceutical composition provided herein can be further mixed with additional excipients to prepare a dosage form such as granules, tablets, or capsules. Optionally, the additional excipients include disintegrants. Such disintegrants include, but are not limited to, cross-linked polyvinylpyrrolidone, sodium carboxymethyl starch, and calcium carboxymethylcellulose, with cross-linked polyvinylpyrrolidone being preferred.

[0029] Furthermore, the percentage of the added disintegrant in the weight of the preparation is 1-4 wt%, preferably 1.5-3 wt%.

[0030] Additives may be optionally further added to the lurasidone hydrochloride pharmaceutical composition provided by the present invention. The additives include colorants, coating agents, flavoring agents, surfactants, plasticizers, fragrances, polishing agents, and the like.

[0031] The lurasidone hydrochloride composition provided by the present invention improves the solubility and / or bioavailability of lurasidone hydrochloride. In some cases, in vivo bioavailability experiments and in vitro dissolution experiments may not be completely correlated. At the same time, the preparation method of the lurasidone hydrochloride composition of the present invention is simple to operate, has good reproducibility, and is suitable for large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the embodiments of the present invention and the technical solutions of the prior art, the following briefly introduces the drawings required for use in the embodiments and the prior art. Obviously, the drawings described below are only some embodiments of the present invention, and a person skilled in the art can also obtain other drawings based on these drawings.

[0033] Figure 1 The figures show the intra-batch variation results of the cumulative dissolution rates of lurasidone hydrochloride tablets prepared according to Example 1 of the present invention and Comparative Examples 1-2;

[0034] Figure 2 The cumulative dissolution comparison results of lurasidone hydrochloride tablets prepared according to Examples 1-4 of the present invention are shown;

[0035] Figure 3 The cumulative dissolution rate comparison results of lurasidone hydrochloride tablets prepared according to Examples 1 to 5-7 of the present invention are shown. DETAILED DESCRIPTION

[0036] To make the objectives, technical solutions, and advantages of the present invention more clearly understood, the present invention is further described below with reference to the accompanying drawings and examples. It is apparent that the described examples are only some of the embodiments of the present invention, and not all of them. All other embodiments derived by those skilled in the art based on the embodiments of the present invention are intended to fall within the scope of protection of the present invention.

[0037] The specific method for preparing the lurasidone hydrochloride tablets used in the examples of the present invention is as follows:

[0038] 1) Crush the lurasidone hydrochloride API and control its particle size D90 to be 6-24 μm for later use.

[0039] 2) Preparing a binder / silicon dioxide suspension: Dissolve the binder (the amount of the binder is 0.5-20 wt %, preferably 0.5-8 wt %, and particularly preferably 4.0-5.0 wt % of the weight of the oral preparation) in pure water, and then add silicon dioxide (the amount of silicon dioxide is 0.25-4.0 wt %, preferably 0.5-1.5 wt %, and particularly preferably 1.5-2.5 wt % of the weight of the oral preparation) to prepare a binder / silicon dioxide suspension. The binder can be, for example, hydroxypropyl methylcellulose or polyvinyl alcohol, and the concentration of the binder aqueous solution is preferably 1-15 wt %, preferably 2-8 wt %, and more preferably 5 wt %.

[0040] 3) Preparation of granules containing lurasidone hydrochloride: Add lurasidone hydrochloride, mannitol, cross-linked sodium carboxymethyl cellulose, and pregelatinized starch to a fluidized bed and mix uniformly. Add the binder / silicon dioxide suspension prepared in (2) to prepare a soft material, using fluidized bed granulation or direct high shear granulation.

[0041] 4) Drying: The granules obtained above are dried in a fluidized bed. The drying standard is a loss on drying of, for example, within 3 wt%, preferably 1-2 wt%.

[0042] 5) A lubricant is added to the granules dried in step (4) above, and the mixture is mixed to obtain a mixture. A blender such as a diffusion mixer can be used. In particular, a V blender, a double cone blender, a hopper blender, or the like can be used.

[0043] 6) Tabletting and Coating: The mixture is compressed into tablets. Plain tablets are optionally coated with Opadry to produce coated tablets. The coating material is a film coating premix. The coating equipment can be a pan-coating type. The coating weight gain is selected to be approximately 1-5 wt%, preferably 2-4 wt%.

[0044] 1. Examples 1-3 and Comparative Examples 1 and 2:

[0045] The raw materials and proportions of Examples 1-3 and Comparative Examples 1 and 2 are shown in Table 1:

[0046] Table 1

[0047]

[0048]

[0049] test:

[0050] a. Dissolution test: The preparation prepared in the present invention was subjected to a dissolution test. The measurement conditions include: test solution; pH 1.2 hydrochloric acid solution; method: paddle method; rotation speed: 50 rpm; dissolution medium volume: 900 mL.

[0051] b. Similarity of dissolution characteristics

[0052] The similarity factor f2 is used herein as an indicator for evaluating the similarity of dissolution characteristics. The f2 value is calculated using the following formula. It has been determined that if the f2 calculated from the dissolution rate of each formulation is 50 ≤ f2 ≤ 100, then each formulation prepared by the present invention has similar dissolution characteristics. After the start of the test, the dissolution rate at three time points, such as 10 minutes, 15 minutes, and 20 minutes, is used to calculate the f2 value. The formula for calculating the similarity factor f2 is as follows:

[0053]

[0054] In the above formula, Ti and Ri are the percentages of dissolution at each time point, and n is the number of points to be compared. The results are shown in Tables 2 and Figure 1 .

[0055] Table 2

[0056]

[0057]

[0058] As shown in Table 2 and Figure 1 As shown, the dissolution rate of Example 1 reached more than 85% in 15 minutes, which was able to dissolve rapidly, and the dissolution rate was basically complete and reached more than 99% in 20 minutes. In Comparative Example 2, when cross-linked sodium carboxymethyl cellulose was used alone, the dissolution of the sample in a pH 1.2 hydrochloric acid solution was too slow, which was not similar to that of Example 1. Although the disintegrants of Comparative Example 1 used L-HPC and cross-linked sodium carboxymethyl cellulose in combination to improve the solubility, the dissolution characteristics were still not similar to those of Example 1. The dissolution rate of Example 1 reached more than 85% in 15 minutes, which was able to dissolve rapidly, and the dissolution rate was basically complete and reached more than 99% in 20 minutes.

[0059] 2. Examples 1-4:

[0060] (1) Examples 1-4 raw materials and proportions are shown in Table 3:

[0061] Table 3

[0062]

[0063] (1) Test:

[0064] The dissolution results of Examples 1-4 are shown in Table 4 and Figure 2 shown.

[0065] Table 4

[0066]

[0067] As shown in Table 4 and Figure 2As shown in Table 4, the f2 values ​​in Examples 2-4 show similarities to those in Example 1. Figure 2 As shown, in Examples 1-4, the f2 value representing the similarity of dissolution characteristics is in the range of 50≤f2≤100, and preparations with similar dissolution characteristics are obtained.

[0068] 3. Examples 1, 5-7:

[0069] (1) In Examples 1, 5-7, tablets containing lurasidone hydrochloride were prepared by using lurasidone hydrochloride powders having different particle size distributions (Table 5).

[0070] Table 5

[0071]

[0072] (2) Examples 1, 5-7 raw materials and proportions are shown in Table 6:

[0073] Table 6

[0074]

[0075] (3) Testing:

[0076] The dissolution results of Examples 1, 5-7 are shown in Table 7 and Figure 3 shown.

[0077] Table 7

[0078]

[0079] As shown in Table 7 and Figure 3 As shown, the f2 values ​​in Examples 5-6 showed similarities to those in Example 1. That is, the formulations prepared by using lurasidone hydrochloride powder showed similar dissolution characteristics, preferably wherein 50% of the powder

[0080] The particle size distribution D50 is 2-9 μm, and the particle size distribution D90 with 90% particle size is 24 μm or less.

[0081] IV. Examples 1, 8-10

[0082] 1) The raw materials and proportions of Examples 1, 8-10 are as shown in Table 8:

[0083] Table 8

[0084]

[0085] Examples 8-10 were tested using the same production batch of lurasidone hydrochloride raw material. The particle size distribution of the lurasidone hydrochloride is shown in Table 9 below:

[0086] Table 9

[0087]

[0088] 2) Testing:

[0089] Examples 1, 8-10, Comparative Example 3 (trade name: The dissolution results of the product (specification: 40 mg) are shown in Table 10.

[0090] Table 10

[0091]

[0092] The results show that the f2 values ​​in Examples 1, 8-10 show that Examples 1, 8-10 and Comparative Example 3 have similar solubility.

[0093] V. Pharmacokinetic Test of Example 10 and Comparative Example 3

[0094] This experiment was designed to study the pharmacokinetic characteristics of Example 10 after a single oral administration, and compared it with Comparative Example 3 (trade name: As a comparison, the pharmacokinetic parameters of the two preparations were compared to preliminarily evaluate the difference in absorption rate and extent between Example 10 and Comparative Example 3 in healthy subjects.

[0095] This study is a randomized, open, two-period crossover, single-dose, fasting administration trial. 16 healthy subjects were randomly divided into two groups. Under fasting conditions, the subjects were orally administered with comparative example 3 (R) lurasidone hydrochloride tablets (40 mg) or example 10 (T) lurasidone hydrochloride tablets (40 mg) according to the random grouping table. 3 mL of venous blood was collected before administration (0 h) and 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 h after administration. The drug concentration of lurasidone in plasma was determined using a validated analytical method. Pharmacokinetic parameters were calculated from the blood drug concentration data, and the results were determined using a two-sided t-test.

[0096] A total of 34 subjects were screened for this trial, 16 of whom were enrolled. One subject voluntarily withdrew, and 15 subjects completed the trial. No protocol deviations or violations occurred during the trial that could have impacted the safety and welfare of the subjects or the scientific evaluation of the data. Based on the measured plasma lurasidone concentration-time data, the pharmacokinetic parameters of Comparative Example 3 and Example 10 were calculated using the statistical analysis software Winnonlin 8.3.1. A comparison of the calculated fasting mean pharmacokinetic parameters is shown in Table 11.

[0097] Table 11

[0098]

[0099] The results show that: compared with Comparative Example 3, Example 10, C max The T / R is 121.89, which shows that Example 10 has better bioavailability than Comparative Example 3.

[0100] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A lurasidone hydrochloride granular composition, comprising the following components: lurasidone hydrochloride, croscarmellose sodium, silicon dioxide, pregelatinized starch, a filler, and a binder; The filler is selected from one of mannitol, lactose, microcrystalline cellulose, xylitol, silicified microcrystalline cellulose, starch, sucrose, glucose, maltitol, fructose, sorbitol, calcium hydrogen phosphate, calcium dihydrogen phosphate and calcium silicate, or any combination thereof; The binder is selected from one of hydroxypropyl methylcellulose, hydroxypropyl cellulose, methyl cellulose, copovidone, povidone and polyvinyl alcohol or any combination thereof; The preparation method of the granular composition comprises the following steps: 1) mixing lurasidone hydrochloride, pregelatinized starch, a filler, and cross-linked sodium carboxymethyl cellulose to obtain a mixture; 2) wet granulating the mixture obtained in 1) with a binder and silicon dioxide, and drying to obtain a lurasidone hydrochloride granular composition.

2. The lurasidone hydrochloride granule composition according to claim 1, characterized in that: The lurasidone hydrochloride granule composition comprises the following components: by weight, 20 wt% to 45 wt% of lurasidone hydrochloride, 0.5 wt% to 5.0 wt% of cross-linked carboxymethyl cellulose sodium, 0.25 wt% to 4.0 wt% of silicon dioxide, more than 0 wt% and less than 10 wt% of pregelatinized starch, a filler, and a binder.

3. The lurasidone hydrochloride granule composition according to claim 2, characterized in that: The lurasidone hydrochloride granule composition comprises the following components: 0.5 wt% to 3.0 wt% of cross-linked carboxymethyl cellulose sodium.

4. The lurasidone hydrochloride granule composition according to claim 2, characterized in that: The lurasidone hydrochloride granule composition comprises the following components: 1.5 wt% to 2.5 wt% of cross-linked carboxymethyl cellulose sodium.

5. The lurasidone hydrochloride granule composition according to claim 2, characterized in that: The lurasidone hydrochloride granule composition comprises the following components: 0.5 wt% to 1.5 wt% of silicon dioxide by weight.

6. The lurasidone hydrochloride granule composition according to claim 2, characterized in that: The lurasidone hydrochloride granule composition comprises the following components: 0.5 wt% to 1 wt% of silicon dioxide.

7. The lurasidone hydrochloride granule composition according to claim 1, characterized in that: The silicon dioxide is colloidal silicon dioxide.

8. The lurasidone hydrochloride granule composition according to claim 2, characterized in that: The lurasidone hydrochloride granule composition comprises: by weight, 40 wt% to 70 wt% of a filler.

9. The lurasidone hydrochloride granule composition according to claim 1, characterized in that: The filler is selected from one or a combination of mannitol and microcrystalline cellulose.

10. The lurasidone hydrochloride granule composition according to claim 1, characterized in that: The filler is selected from mannitol.

11. The lurasidone hydrochloride granule composition according to claim 2, characterized in that: The lurasidone hydrochloride granule composition comprises: by weight, 0.5wt%-20wt% of a binder.

12. The lurasidone hydrochloride granule composition according to claim 2, characterized in that: The lurasidone hydrochloride granule composition comprises: by weight, 0.5wt%-8wt% of a binder.

13. The lurasidone hydrochloride granule composition according to claim 2, characterized in that: The lurasidone hydrochloride granule composition comprises: by weight, 4.0 wt% to 5.0 wt% of a binder.

14. The lurasidone hydrochloride granule composition according to claim 1, characterized in that: The adhesive is selected from one of hydroxypropyl methylcellulose and polyvinyl alcohol or a combination thereof.

15. The lurasidone hydrochloride granule composition according to claim 1, characterized in that: The adhesive is selected from hypromellose.

16. A pharmaceutical composition of lurasidone hydrochloride, comprising the lurasidone hydrochloride granule composition according to any one of claims 1 to 15 and a lubricant.

17. The lurasidone hydrochloride pharmaceutical composition according to claim 16, characterized in that: The lubricant is selected from one of stearic acid, magnesium stearate, sodium stearyl fumarate and talc or any combination thereof.

18. The lurasidone hydrochloride pharmaceutical composition according to claim 16, characterized in that: The lubricant is selected from one of magnesium stearate, sodium stearyl fumarate or a combination thereof.

19. The lurasidone hydrochloride pharmaceutical composition according to claim 16, characterized in that: The lubricant is selected from sodium stearyl fumarate.

20. The lurasidone hydrochloride pharmaceutical composition according to claim 16, characterized in that: The percentage of the lubricant to the weight of the preparation is 0.1 wt% to 5 wt%.

21. The lurasidone hydrochloride pharmaceutical composition according to claim 16, characterized in that: The percentage of the lubricant to the weight of the preparation is 0.5% wt% to 2 wt%.

22. The lurasidone hydrochloride pharmaceutical composition according to claim 16, characterized in that: The percentage of the lubricant to the weight of the formulation is 0.75 wt% to 2 wt%.

23. The lurasidone hydrochloride pharmaceutical composition according to claim 16, characterized in that: The percentage of the lubricant to the weight of the preparation is 0.75 wt% to 1 wt%.

24. The lurasidone hydrochloride pharmaceutical composition according to claim 16, characterized in that: The pharmaceutical composition is further processed by adding an external disintegrant.

25. The lurasidone hydrochloride pharmaceutical composition according to claim 24, characterized in that: The disintegrant is selected from one of cross-linked polyvinylpyrrolidone, sodium carboxymethyl starch, and carboxymethyl cellulose calcium, or any combination thereof.

26. The lurasidone hydrochloride pharmaceutical composition according to claim 24, characterized in that: The disintegrant is selected from cross-linked polyvinylpyrrolidone.

27. The lurasidone hydrochloride pharmaceutical composition according to claim 24, characterized in that: The percentage of the added disintegrant in the weight of the preparation is 1 wt%-4 wt%.

28. The lurasidone hydrochloride pharmaceutical composition according to claim 24, characterized in that: The percentage of the added disintegrant in the weight of the preparation is 1.5wt%-3wt%.

29. The lurasidone hydrochloride pharmaceutical composition according to claim 16, characterized in that: The pharmaceutical composition is further added with additives, which include one or any combination of colorants, flavoring agents, surfactants, plasticizers or polishing agents.

30. The lurasidone hydrochloride pharmaceutical composition according to claim 16, characterized in that: The pharmaceutical composition is further added with a coating agent.

31. The lurasidone hydrochloride pharmaceutical composition according to claim 16, characterized in that: The pharmaceutical composition is further added with a fragrance.

32. The lurasidone hydrochloride pharmaceutical composition according to claim 30, characterized in that: The coating agent is a film coating premix.

33. The lurasidone hydrochloride pharmaceutical composition according to claim 30, characterized in that: The coating agent is Opadry coating.

34. The lurasidone hydrochloride pharmaceutical composition according to claim 30, characterized in that: The weight of the pharmaceutical composition increases by 1 wt% to 5 wt% after coating.

35. The lurasidone hydrochloride pharmaceutical composition according to claim 30, characterized in that: The weight of the pharmaceutical composition increases by 2wt%-4wt% after coating.

36. The lurasidone hydrochloride granule composition according to any one of claims 1 to 15 or the lurasidone hydrochloride pharmaceutical composition according to any one of claims 16 to 35, characterized in that: The particle size D90 of the lurasidone hydrochloride is 1 μm-25 μm.

37. The lurasidone hydrochloride granule composition or lurasidone hydrochloride pharmaceutical composition according to claim 36, characterized in that: The particle size D90 of the lurasidone hydrochloride is 6 μm-25 μm.

38. The lurasidone hydrochloride granule composition or lurasidone hydrochloride pharmaceutical composition according to claim 36, characterized in that: The particle size D90 of the lurasidone hydrochloride is 6 μm-16 μm.

39. The lurasidone hydrochloride granular composition according to any one of claims 1 to 15 or the lurasidone hydrochloride pharmaceutical composition according to any one of claims 16 to 35, characterized in that: The particle size D50 of the lurasidone hydrochloride is 2 μm-9 μm.

40. The lurasidone hydrochloride granule composition or lurasidone hydrochloride pharmaceutical composition according to claim 39, characterized in that: The particle size D50 of the lurasidone hydrochloride is 2.5 μm-8 μm.

41. The lurasidone hydrochloride pharmaceutical composition according to any one of claims 16 to 35, which is in the form of granules, tablets or capsules.

42. The lurasidone hydrochloride pharmaceutical composition according to claim 41, which is in the form of a tablet.

43. A method for preparing the lurasidone hydrochloride pharmaceutical composition according to any one of claims 16 to 35, comprising adding a lubricant to the lurasidone hydrochloride granule composition according to claim 1, and optionally adding an external disintegrant to further process the composition to obtain the pharmaceutical composition.

44. The method for preparing the lurasidone hydrochloride pharmaceutical composition according to claim 43, wherein: The method further comprises tableting the pharmaceutical composition.

45. The method for preparing the lurasidone hydrochloride pharmaceutical composition according to claim 43, wherein: The method further comprises a coating operation.

46. ​​The method for preparing the lurasidone hydrochloride pharmaceutical composition according to claim 43, wherein: The method further comprises selecting a film coating premix as the coating material.

47. A method for preparing lurasidone hydrochloride tablets, comprising the following steps: 1) crushing the lurasidone hydrochloride API and controlling the particle size D90 to be between 6 μm and 24 μm for later use; 2) preparing a binder / silicon dioxide suspension: dissolving a binder in pure water in an amount of 0.5 wt% to 20 wt% based on the weight of the oral formulation, and then adding silicon dioxide to prepare a binder / silicon dioxide suspension in an amount of 0.25 wt% to 4.0 wt% based on the weight of the oral formulation, wherein the binder is selected from one or any combination of hypromellose, hydroxypropyl cellulose, methylcellulose, copovidone, povidone, and polyvinyl alcohol; 3) preparing granules containing lurasidone hydrochloride: adding lurasidone hydrochloride, mannitol, cross-linked sodium carboxymethyl cellulose, and pregelatinized starch into a fluidized bed and mixing them evenly; adding the binder / silicon dioxide suspension prepared in (2) to prepare a soft material, using fluidized bed granulation or direct high shear granulation; 4) Drying: Drying the granules obtained above in a fluidized bed; 5) adding a lubricant to the granules dried in step 4) above, mixing to obtain a mixture; 6) Tableting and coating: The above mixture is tableted, and the plain tablets are optionally coated with Opadry to obtain the final coated tablets.

48. The method for preparing lurasidone hydrochloride tablets according to claim 47, wherein: The concentration of the binder aqueous solution in step 2) is 1 wt%-15 wt%.

49. The method for preparing lurasidone hydrochloride tablets according to claim 47, wherein: The concentration of the binder aqueous solution in step 2) is 2 wt%-8 wt%.

50. The method for preparing lurasidone hydrochloride tablets according to claim 47, wherein: The concentration of the binder aqueous solution in step 2) is 5 wt %.

51. The method for preparing lurasidone hydrochloride tablets according to claim 47, wherein: The drying standard is that the drying loss is within 3 wt%.

52. The method for preparing lurasidone hydrochloride tablets according to claim 47, wherein: The drying standard is a drying loss of 1 wt% to 2 wt%.

53. The method for preparing lurasidone hydrochloride tablets according to claim 47, wherein: Mixing was performed using a diffusion mixer type agitator.

54. The method for preparing lurasidone hydrochloride tablets according to claim 47, wherein: Mixing is done using a V-blender, a double cone blender or a hopper blender.

55. The method for preparing lurasidone hydrochloride tablets according to claim 47, wherein: The coating material is selected from film coating premix.

56. The method for preparing lurasidone hydrochloride tablets according to claim 47, wherein: The coating weight gain is 1 wt%-5 wt%.

57. The method for preparing lurasidone hydrochloride tablets according to claim 47, wherein: The coating weight gain is 2 wt% to 4 wt%.

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