A kind of perospirone hydrochloride tablet and preparation method thereof

Abstract

The present invention relates to the field of medicine, and discloses a perospirone hydrochloride tablet and a preparation method thereof, wherein the perospirone hydrochloride tablet comprises a tablet core and a coating, and the tablet core comprises the following components in parts by weight: 4.62-12.62 parts of perospirone hydrochloride, 20-36 parts of corn starch, 44-73 parts of lactose, 2-9 parts of carboxymethylcellulose calcium, 1-5 parts of adhesive, 6.68-14.68 parts of microcrystalline cellulose, and 0.3-1.1 parts of lubricant. The perospirone hydrochloride tablet prepared by the method provided by the present invention has a similar dissolution behavior to a reference preparation, has a higher similarity factor f2 (f2 value is more than 80%), and achieves a high degree of bioequivalence with the reference preparation.

Description

Technical Field

[0001] The invention relates to the field of medicine, and in particular to a perospirone hydrochloride tablet and a preparation method thereof. Background Art

[0002] Perospirone hydrochloride is a commonly used nonsteroidal anti-inflammatory drug used to relieve mild to moderate pain and fever symptoms. It is widely used in the treatment of arthritis, rheumatism, muscle pain, chest pain, toothache, headache, dysmenorrhea and other diseases. Chinese invention application CN202210097030 discloses a perospirone hydrochloride pharmaceutical composition, a preparation method thereof and its application, which adopts a direct mixing tableting process with a 5min dissolution rate of 98-100.5% under a pH 1.0 medium, which is much faster than the reference preparation. At present, there is still room for improvement in perospirone hydrochloride tablets, so that the various parameters of perospirone hydrochloride tablets are close to the reference preparation, and perospirone hydrochloride tablets with high bioequivalence are obtained. Summary of the invention

[0003] Purpose of the invention: The technical problem to be solved by the present invention is to provide a pyrospirone hydrochloride tablet and a preparation method thereof in view of the deficiencies in the prior art.

[0004] In order to solve the above technical problems, the present invention discloses the following technical solutions:

[0005] In a first aspect, the present invention discloses a perospirone hydrochloride tablet.

[0006] Wherein, the perospirone hydrochloride tablet comprises a tablet core and a coating, and the tablet core comprises the following components in parts by weight:

[0007] Perospirone hydrochloride 4.62-12.62 parts

[0008] 20-36 parts corn starch

[0009] Lactose 44-73 parts

[0010] Calcium carboxymethylcellulose 2-9 parts

[0011] Adhesive 1-5 parts

[0012] Microcrystalline cellulose 6.68-14.68 parts

[0013] Lubricant 0.3-1.1 parts.

[0014] In the present invention, the binder is polyvinyl alcohol.

[0015] In some embodiments, the core comprises the following components in parts by weight:

[0016] Perospirone hydrochloride 6.62-10.62 parts

[0017] 24-42 parts corn starch

[0018] Lactose 48-69 parts

[0019] 3-8 parts of carboxymethylcellulose calcium

[0020] 2-4 parts of adhesive

[0021] Microcrystalline cellulose 8.68-12.68 parts

[0022] Lubricant 0.5-0.9 parts.

[0023] In some embodiments, the core comprises the following components in parts by weight:

[0024] 8.62 parts of Perospirone Hydrochloride

[0025] 28-38 parts corn starch

[0026] Lactose 52-65 parts

[0027] 4-7 parts of carboxymethylcellulose calcium

[0028] 3 parts adhesive

[0029] Microcrystalline cellulose 10.68 parts

[0030] 0.7 parts of lubricant.

[0031] In some embodiments, the coating accounts for 1%-8% of the total weight of the core, such as 2%, 4%, 6%.

[0032] In some embodiments, the prescription of the perospirone hydrochloride tablets further comprises the following components in parts by weight: 2.8-4.4 parts of film coating premix, preferably 3.2-4.0 parts, preferably 3.6 parts.

[0033] In some embodiments, the particle size D90 of the perospirone hydrochloride is 15-20 um.

[0034] In some embodiments, the lubricant comprises magnesium stearate.

[0035] In some embodiments, the perospirone hydrochloride tablet is prepared by the following method, comprising:

[0036] (1) mixing corn starch, perospirone hydrochloride, first carboxymethylcellulose calcium, and lactose to obtain a mixture;

[0037] (2) adding the obtained mixture into a fluidized bed, adding a binder, and granulating the mixture in the fluidized bed to obtain first granules;

[0038] (3) drying and granulating the obtained first granules to obtain second granules;

[0039] (4) The obtained second granules are mixed with microcrystalline cellulose, a second carboxymethyl cellulose calcium and a lubricant, compressed into tablets and coated.

[0040] The first carboxymethylcellulose calcium accounts for 57%-100% of the prescribed amount of carboxymethylcellulose calcium, and the rest is the second carboxymethylcellulose calcium.

[0041] In step (2), the binder is added in the form of an aqueous solution of the binder, and the concentration of the aqueous solution is preferably 1 wt%-3 wt%.

[0042] Step (2) comprises adding the obtained mixture into a fluidized bed, and when the temperature of the mixture rises to 35-45°C, spraying a binder to carry out granulation; preferably, the air inlet temperature of the fluidized bed during the granulation process is 65-85°C; preferably, the atomization pressure of the fluidized bed during the granulation process is 0.5-5 bar, preferably 1-3 bar; preferably, the pump speed of the fluidized bed during the granulation process is 15-25 rpm, preferably 18-22 rpm.

[0043] In step (3), the granulation is performed by a crushing and granulating machine, the aperture of the screen in the crushing and granulating machine is 0.4-0.8 mm, preferably 0.6 mm; preferably, the tableting hardness is controlled to be 5-7 kg; preferably, the tableting obtains a plain tablet, and the obtained plain tablet is coated, preferably with a coating weight gain of 2%-4%. In some embodiments, the coating is performed by a gastric soluble film coating premix; in some embodiments, it is configured to be coated with an 8-12%wt aqueous solution, such as 10%wt.

[0044] In some embodiments, the method specifically comprises:

[0045] (1) corn starch, perospirone hydrochloride with a D90 of 15-20 um, first carboxymethylcellulose calcium, and lactose are mixed using a pulverizing and granulating machine to obtain a mixture; the sieve aperture of the pulverizing and granulating machine is 0.5-0.7 mm;

[0046] (2) The obtained mixture is added to a fluidized bed, and when the temperature of the mixture rises to 35-45°C, a binder is sprayed in for granulation to obtain first granules; during the granulation process, the inlet air temperature of the fluidized bed is 65-85°C, the atomization pressure is 1-3 bar, and the pump speed is 18-22 rpm;

[0047] (3) drying the obtained first granules and arranging them by a crushing and granulating machine to obtain second granules; the aperture of the screen in the crushing and granulating machine is 0.4-0.8 mm;

[0048] (4) The obtained second granules are mixed with microcrystalline cellulose, a second carboxymethyl cellulose calcium and a lubricant, and the tableting hardness is controlled to be 5-7 kg, and the weight gain of the plain tablet coating is 2%-4%; the microcrystalline cellulose, the second carboxymethyl cellulose calcium and the lubricant need to pass through a 40-mesh sieve.

[0049] In a second aspect, the present invention discloses a method for preparing the above-mentioned perospirone hydrochloride tablets.

[0050] Wherein, the method comprises:

[0051] (1) mixing corn starch, perospirone hydrochloride, first carboxymethylcellulose calcium, and lactose to obtain a mixture;

[0052] (2) adding the obtained mixture into a fluidized bed, adding a binder, and granulating the mixture in the fluidized bed to obtain first granules;

[0053] (3) drying and granulating the obtained first granules to obtain second granules;

[0054] (4) The obtained second granules are mixed with microcrystalline cellulose, a second carboxymethyl cellulose calcium and a lubricant, compressed into tablets and coated.

[0055] The first carboxymethylcellulose calcium accounts for 57%-100% of the prescribed amount of carboxymethylcellulose calcium, and the rest is the second carboxymethylcellulose calcium.

[0056] In step (2), the binder is added in the form of an aqueous solution of the binder, and the concentration of the aqueous solution is preferably 1%-3%.

[0057] Step (2) comprises adding the obtained mixture into a fluidized bed, and when the temperature of the mixture rises to 35-45°C, spraying a binder to carry out granulation; preferably, the air inlet temperature of the fluidized bed during the granulation process is 65-85°C; preferably, the atomization pressure of the fluidized bed during the granulation process is 0.5-5 bar, preferably 1-3 bar; preferably, the pump speed of the fluidized bed during the granulation process is 15-25 rpm, preferably 18-22 rpm.

[0058] In step (3), the granulation is performed by a pulverizing and granulating machine, the aperture of the screen in the pulverizing and granulating machine is 0.4-0.8 mm, preferably 0.6 mm; preferably, the tableting hardness is controlled to be 5-7 kg, such as 6 kg; preferably, the tableting obtains plain tablets, and the obtained plain tablets are coated, preferably the coating weight gain is 2%-4%, such as 3%.

[0059] In some embodiments, the method specifically comprises:

[0060] (1) corn starch, perospirone hydrochloride with a D90 of 15-20 um, first carboxymethylcellulose calcium, and lactose are mixed using a pulverizing and granulating machine to obtain a mixture; the sieve aperture of the pulverizing and granulating machine is 0.5-0.7 mm;

[0061] (2) The obtained mixture is added to a fluidized bed, and when the temperature of the mixture rises to 35-45°C, a binder is sprayed in for granulation to obtain first granules; during the granulation process, the inlet air temperature of the fluidized bed is 65-85°C, the atomization pressure is 1-3 bar, and the pump speed is 18-22 rpm;

[0062] (3) drying the obtained first granules and arranging them by a crushing and granulating machine to obtain second granules; the aperture of the screen in the crushing and granulating machine is 0.4-0.8 mm;

[0063] (4) The obtained second granules are mixed with microcrystalline cellulose, a second carboxymethyl cellulose calcium and a lubricant, and the tableting hardness is controlled to be 5-7kg, such as 6kg, and the weight gain of the plain tablet coating is 2%-4%; the microcrystalline cellulose, the second carboxymethyl cellulose calcium and the lubricant need to pass through a 40-mesh sieve.

[0064] The perospirone hydrochloride tablets prepared by the present invention have the following release characteristics: in a medium of pH 1.2, at 30 rpm, in a basket method test, the cumulative dissolution after 5 minutes is 10%-23%, the cumulative dissolution after 10 minutes is 50%-60%, the cumulative dissolution after 15 minutes is 62%-70%, and the cumulative dissolution after 30 minutes is 72%-79%.

[0065] In some embodiments, the pheniramine hydrochloride tablets have the following release characteristics: in a medium with a pH of 1.2, at 30 rpm, in a basket test, the cumulative dissolution after 5 minutes is 11%-22%, the cumulative dissolution after 10 minutes is 51%-59%, the cumulative dissolution after 15 minutes is 63%-69%, and the cumulative dissolution after 30 minutes is 73%-78%; preferably, the pheniramine hydrochloride tablets have the following release characteristics: in a medium with a pH of 1.2, at 30 rpm, in a basket test, the cumulative dissolution after 5 minutes is 12%-21%, the cumulative dissolution after 10 minutes is 52%-58%, the cumulative dissolution after 15 minutes is 64%-68%, and the cumulative dissolution after 30 minutes is 74%-77%.

[0066] In some embodiments, the perospirone hydrochloride tablets have the following release characteristics:

[0067] In a medium of pH 1.2, at 30 rpm, in a basket method test, the cumulative dissolution after 5 minutes is 15%-17%, the cumulative dissolution after 10 minutes is 51%-53%, the cumulative dissolution after 15 minutes is 63%-65%, and the cumulative dissolution after 30 minutes is 73%-75%; preferably, the cumulative dissolution after 5 minutes is 16%, the cumulative dissolution after 10 minutes is 52%, the cumulative dissolution after 15 minutes is 64%, and the cumulative dissolution after 30 minutes is 74%;

[0068] or,

[0069] In a medium of pH 1.2, at 30 rpm, in a basket method test, the cumulative dissolution after 5 minutes is 20%-22%, the cumulative dissolution after 10 minutes is 54%-56%, the cumulative dissolution after 15 minutes is 65%-67%, and the cumulative dissolution after 30 minutes is 74%-76%; preferably, the cumulative dissolution after 5 minutes is 21%, the cumulative dissolution after 10 minutes is 55%, the cumulative dissolution after 15 minutes is 66%, and the cumulative dissolution after 30 minutes is 75%;

[0070] or,

[0071] In a medium of pH 1.2, at 30 rpm, in a basket method test, the cumulative dissolution after 5 minutes is 11%-13%, the cumulative dissolution after 10 minutes is 52%-54%, the cumulative dissolution after 15 minutes is 64%-66%, and the cumulative dissolution after 30 minutes is 74%-76%; preferably, the cumulative dissolution after 5 minutes is 12%, the cumulative dissolution after 10 minutes is 53%, the cumulative dissolution after 15 minutes is 65%, and the cumulative dissolution after 30 minutes is 75%;

[0072] or,

[0073] In a medium of pH 1.2, at 30 rpm, in the basket method test, the cumulative dissolution after 5 minutes is 20%-22%, the cumulative dissolution after 10 minutes is 57%-59%, the cumulative dissolution after 15 minutes is 67%-69%, and the cumulative dissolution after 30 minutes is 76%-78%; preferably, the cumulative dissolution after 5 minutes is 21%, the cumulative dissolution after 10 minutes is 58%, the cumulative dissolution after 15 minutes is 68%, and the cumulative dissolution after 30 minutes is 77%.

[0074] Beneficial effects:

[0075] The perospirone hydrochloride tablets prepared by the method provided by the present invention have similar dissolution behavior to the reference preparation, have a higher similarity factor f2 (the f2 value is above 80%), and achieve a high degree of bioequivalence with the reference preparation. BRIEF DESCRIPTION OF THE DRAWINGS

[0076] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments, and the above and / or other advantages of the present invention will become more clear.

[0077] Figure 1 The dissolution curves of the preparations obtained in Examples 1-3 and the reference preparation are shown in FIG.

[0078] Figure 2 The dissolution curve of the preparation of Example 2 was tested by the paddle method at pH 1.2 and 50 rpm.

[0079] Figure 3 The dissolution curve of the preparation of Example 2 was tested by the pH 4.5-basket method at 30 rpm.

[0080] Figure 4 The dissolution curve of the preparation of Example 2 was tested by the paddle method at pH 4.5 and 50 rpm.

[0081] Figure 5 The dissolution curve of the preparation of Example 2 was tested by the paddle method at pH 6.5 and 50 rpm.

[0082] Figure 6 This is an electron microscope image of the API in Example 2 after hammer crushing.

[0083] Figure 7 This is an electron microscope image of the API in Comparative Example 1 after hammer crushing.

[0084] Figure 8 The dissolution curves of the preparation obtained in Comparative Example 1, the preparation obtained in Example 2 and the reference preparation are shown in FIG.

[0085] Fig. 9 The dissolution curves of the preparation obtained in Comparative Example 3, the preparation obtained in Example 2 and the reference preparation are shown. DETAILED DESCRIPTION

[0086] The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0087] The experimental methods described in the following examples are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0088] The reference preparation used in the present invention is Lullan, source: Sumitomo Pharma Co., Ltd., Japan, with a specification of 8 mg.

[0089] Examples 1-4

[0090] A preparation method of phenoxyethanol hydrochloride, wherein the weight proportions of various raw material components are shown in Table 1.

[0091] Table 1 Prescriptions of Examples 1-4

[0092]

[0093] Note: The amount of the first carboxymethylcellulose calcium is 4 mg, and the rest is the second carboxymethylcellulose calcium.

[0094] The specific preparation process is as follows:

[0095] (1) Crush of API

[0096] Hammer mill, 15000rpm crushing frequency, D (90) = 15-20um.

[0097] (2) Weighing and pretreatment of raw and auxiliary materials

[0098] Corn starch, perospirone hydrochloride, first carboxymethylcellulose calcium, and lactose were granulated and mixed using a conical pulverizer with a mesh size of 0.6 mm at 500 rpm to obtain a mixture.

[0099] Microcrystalline cellulose, second carboxymethyl cellulose calcium, and magnesium stearate are weighed through a 40-mesh sieve for later use.

[0100] (3) Prepare adhesive

[0101] Add purified water (concentration of 2 wt%) to polyvinyl alcohol and stir until it becomes clear.

[0102] (4) Fluidized bed granulation

[0103] Add the mixture obtained in step (2) into the fluidized bed. When the material temperature rises to 40°C, start granulation and spray the binder to maintain the fluidized state. The inlet air temperature is 65-85°C, the atomization pressure is 1-3 bar, and the pump speed is 18-22 rpm. After the spraying is completed, dry the particles until the moisture content is 2-4% (105°C, 5 min).

[0104] (5) Dry whole grain

[0105] The dried particles in step (4) are granulated using a cone-shaped pulverizer with a screen size of 0.6 mm at 600-800 rpm.

[0106] (6) Total mixing

[0107] Add the prescribed amount of microcrystalline cellulose and the second amount of carboxymethyl cellulose calcium to the granules after dry granulation in step (5), mix in a mixer at a mixing parameter of 10 rpm for 30 minutes, and then add the prescribed amount of magnesium stearate and mix at 10 rpm for 3 minutes.

[0108] (7) Tableting

[0109] The tablets were compressed on a rotary tablet press using a 7.0 mm diameter round notched die and the hardness was controlled to be 5-7 kg.

[0110] (8) Coating

[0111] The gastric soluble film coating premix is ​​prepared into a 10%wt aqueous solution for coating, and the plain tablets are coated in a high-efficiency coating machine to increase their weight by 2%-4%.

[0112] Comparative Example 1

[0113] Same as Example 2, except that the step (1) of crushing the raw material drug is replaced by:

[0114] Air flow crushing, 0.4MPa crushing pressure, D(90)=9-13um.

[0115] Comparative Example 2

[0116] Same as Example 2, except that the weighing and pretreatment of raw materials and auxiliary materials in step (2) are replaced by:

[0117] Corn starch, perospirone hydrochloride, first carboxymethylcellulose calcium and lactose are granulated and mixed using an oscillating sieve with a mesh size of 0.6 mm to obtain a mixture.

[0118] Microcrystalline cellulose, second carboxymethyl cellulose calcium, and magnesium stearate are weighed through a 40-mesh sieve for later use.

[0119] Comparative Example 3

[0120] Same as Example 2, except that step (5) of dry granulation is replaced by:

[0121] The dried granules were granulated using a 1.5 mm granulator at 600-800 rpm.

[0122] Comparative Example 4

[0123] The same as Example 2, except that the concentration of the binder configured in step (3) is changed to 4 wt %, and the fluidized bed granulation in step (4) is replaced by a high shear wet granulation machine for granulation, as shown in Table 2 below.

[0124] Table 2 Wet granulation process

[0125]

[0126] Test example

[0127] 1. Testing of the Preparations Obtained in Examples 1-4

[0128] The dissolution of the reference preparation and the preparations obtained in Examples 1 to 4 was tested by the basket method at 30 rpm, 900 ml, pH 1.2 hydrochloric acid medium.

[0129] The results are shown in Table 3 and Figure 1 As shown, the dissolution behavior of the pyrospirone hydrochloride tablets prepared in Examples 1-4 is similar to that of the reference preparation, and has a high similarity factor f2 (2023C) (f2 is above 80%). Among them, the amount of the second carboxymethylcellulose calcium in Examples 1-3 mainly affects the dissolution rate in 5 minutes. After 5 minutes, the effect of the added disintegrant has ended, and the dissolution curves are similar.

[0130] Table 3 Dissolution of the reference preparation and the preparations obtained in Examples 1-4 (pH 1.2 hydrochloric acid medium-basket method 30rpm)

[0131]

[0132] 2. Detection of the preparation obtained in Example 2

[0133] (1) Dissolution test of the reference preparation and the preparation obtained in Example 2 in other media

[0134] pH 1.2 hydrochloric acid medium - paddle method 50rpm 900ml

[0135] pH4.5-acetic acid medium basket method 30rpm 900ml

[0136] pH4.5-acetic acid medium paddle method 50rpm 900ml

[0137] pH6.5-Phosphoric acid medium paddle method 50rpm 900ml

[0138] The results are shown in Tables 4-7 and Figure 2-Figure 5 shown.

[0139] Table 4 pH 1.2 - Paddle method 50 rpm

[0140]

[0141] Table 5 pH 4.5 - basket method 30 rpm

[0142]

[0143] Table 6 pH 4.5 - Paddle method 50 rpm

[0144]

[0145] Table 7 pH 6.5 - Paddle method 50 rpm

[0146]

[0147] (2) The electron microscope image of the raw material of Example 2 after hammer crushing is as follows Figure 6 shown.

[0148] (3) Content determination

[0149]

Content Determination

[0150] Test solution Take 10 tablets of this product, place in a 200ml volumetric flask, add an appropriate amount of mobile phase, sonicate and shake to dissolve the perospirone hydrochloride, dilute to the scale with mobile phase, shake well, filter, accurately measure 5ml of the filtrate, place in a 25ml volumetric flask, dilute to the scale with mobile phase, and shake well.

[0151] Reference solution Take an appropriate amount of perospirone hydrochloride reference substance, weigh accurately, add mobile phase to dissolve and quantitatively dilute to make a solution containing approximately 80 µg of perospirone hydrochloride per 1 ml.

[0152] The chromatographic conditions were as follows: octadecylsilane bonded silica gel was used as filler (GL Sciences Inertsil ODS-3 4.6×250mm, 5μm or a chromatographic column of equivalent performance); phosphate (0.02mol / L potassium dihydrogen phosphate solution, pH adjusted to 2.0 with phosphoric acid)-acetonitrile (65:35) was used as the mobile phase; the flow rate was 1.0ml per minute; the column temperature was 30°C; the detection wavelength was 230nm; and the injection volume was 20μl.

[0153] The results are shown in Table 8. The effect of forced mixing in Example 2 is that the average content of the obtained preparation is 101.0%, and the RSD is as low as 0.7%, which is more uniform.

[0154] Table 8

[0155]

[0156] (4) Equivalence test between the preparation obtained in Example 2 and the reference preparation

[0157] In the bioequivalence experiment between the preparation obtained in Example 2 and the reference preparation, the test design was two preparations, two cycles, and crossover single fasting administration. The confidence interval was calculated through data statistics. The interval was within the range of 80-125%, which can be regarded as equivalent to the preparation obtained in Example 2 and the reference preparation (see "Technical Guidelines for Human Bioequivalence Studies of Generic Chemical Drugs Using Pharmacokinetic Parameters as Endpoint Evaluation Indicators").

[0158] Table 9 Be fasting data: Statistical analysis results of bioequivalence of perospirone (fasting, N=16)

[0159]

[0160] 2. Dissolution and other tests of comparative examples 1-3

[0161] (1) Comparative Example 1 - Airflow Crushing

[0162] Electron microscope image of the raw material air flow milling Figure 7 As shown, the dissolution of the preparation obtained in Comparative Example 1 is shown in Tables 10 and Figure 8As shown, the particle size of the raw material in Comparative Example 1 is smaller after air flow grinding, and the dissolution rate is faster. The hammer grinding raw material is closer to the reference dissolution data, and the hammer grinding raw material is preferred.

[0163] Table 10 Dissolution of the preparation obtained in Comparative Example 1

[0164]

[0165] (2) Comparative Example 2 - Vibrating Screen

[0166] The RSD of the content detection of the preparation obtained in Comparative Example 2 was as high as 2.6%, and the uniformity was poor.

[0167] Table 11

[0168]

[0169] (3) Comparative Example 3

[0170] The particle sizes of the particles of comparative example 3 after being sized with a 1.5 mm sieve and the particles after dry granulation in step (5) of example 2 were measured. The sieves with different mesh sizes were arranged in the order of 40 mesh, 60 mesh, 80 mesh, 100 mesh and 150 mesh from top to bottom. The retention ratios of the sieves with different mesh sizes are shown in Table 12.

[0171] Table 12

[0172]

[0173] Dissolution test is shown in Table 13 and Fig. 9 As shown, the results show that the f2 value of the preparation obtained in Comparative Example 3 is as low as 62.2%, indicating that the size of the particles has a significant effect on the dissolution rate of the preparation.

[0174] Table 13 Dissolution of the preparation obtained in Comparative Example 3

[0175]

[0176] (4) Comparative Example 4

[0177] The dissolution data of the preparation obtained in Comparative Example 4 is shown in Table 14. The results show that the f2 value of the preparation obtained in Comparative Example 3 is as low as 62.2%.

[0178] Table 14 Dissolution of the preparation obtained in Comparative Example 4

[0179]

[0180] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A perospirone hydrochloride tablet, characterized in that: The tablet comprises a core and a coating, wherein the core comprises the following components in parts by weight: Perospirone hydrochloride 4.62-12.62 parts 20-36 parts corn starch Lactose 44-73 parts 4-7 parts of carboxymethylcellulose calcium Polyvinyl alcohol 1-5 parts Microcrystalline cellulose 6.68-14.68 parts Lubricant 0.3-1.1 parts; The particle size D90 of the perospirone hydrochloride is 15-20 um; The lubricant is magnesium stearate; The perospirone hydrochloride tablets are prepared by the following method, which comprises: (1) corn starch, perospirone hydrochloride, first carboxymethylcellulose calcium, and lactose are mixed using a pulverizing and granulating machine to obtain a mixture; (2) adding the obtained mixture into a fluidized bed, adding polyvinyl alcohol, and granulating the mixture in the fluidized bed to obtain first granules; (3) drying and granulating the obtained first granules to obtain second granules; (4) mixing the obtained second granules with microcrystalline cellulose, a second carboxymethylcellulose calcium and a lubricant; The first carboxymethylcellulose calcium is 57%-100% of the prescribed amount of carboxymethylcellulose calcium, and the remainder is the second carboxymethylcellulose calcium; In step (1), the aperture of the screen in the pulverizing and granulating machine is 0.5-0.7 mm; In step (2), the polyvinyl alcohol is added in the form of an aqueous solution of polyvinyl alcohol, and the concentration of the aqueous solution is 1wt%-3wt%; In step (3), the granulation is performed by using a crushing and granulating machine, and the aperture of the screen in the crushing and granulating machine is 0.4-0.8 mm.

2. The perospirone hydrochloride tablet according to claim 1, characterized in that The core comprises the following components in parts by weight: Perospirone hydrochloride 6.62-10.62 parts 24-42 parts corn starch Lactose 48-69 parts 4-7 parts of carboxymethylcellulose calcium 2-4 parts of polyvinyl alcohol Microcrystalline cellulose 8.68-12.68 parts Lubricant 0.5-0.9 parts.

3. The perospirone hydrochloride tablet according to claim 2, characterized in that The coating accounts for 1%-8% of the total weight of the tablet core.

4. The perospirone hydrochloride tablets according to claim 1, characterized in that Step (2) comprises adding the obtained mixture into a fluidized bed, and when the temperature of the mixture rises to 35-45°C, spraying polyvinyl alcohol into the fluidized bed for granulation; during the granulation process, the air inlet temperature of the fluidized bed is 65-85°C, the atomization pressure is 0.5-5ba, and the pump speed is 15-25rpm.

5. The perospirone hydrochloride tablet according to claim 1, characterized in that: The method further comprises tableting and coating; the tableting hardness is controlled to be 5-7kg; and the coating weight gain is controlled to be 2%-4%.

6. A perospirone hydrochloride tablet, characterized in that: The tablet comprises a core and a coating, wherein the core comprises the following components in parts by weight: 8.62 parts of Perospirone Hydrochloride 28-38 parts corn starch Lactose 52-65 parts 4-7 parts of carboxymethylcellulose calcium 3 parts of polyvinyl alcohol Microcrystalline cellulose 10.68 parts 0.7 parts of lubricant; The lubricant includes magnesium stearate; The particle size D90 of the perospirone hydrochloride is 15-20 um; The coating accounts for 2%-4% of the total weight of the tablet core; The preparation method of the perospirone hydrochloride tablets comprises: (1) corn starch, perospirone hydrochloride, first carboxymethylcellulose calcium, and lactose are mixed using a pulverizing and granulating machine to obtain a mixture; (2) The obtained mixture is added to a fluidized bed, and when the temperature of the mixture rises to 35-45°C, polyvinyl alcohol is sprayed into the fluidized bed for granulation to obtain first particles; during the granulation process, the inlet air temperature of the fluidized bed is 65-85°C, the atomization pressure is 1-3 bar, and the pump speed is 18-22 rpm; (3) drying the obtained first granules and arranging them by a crushing and granulating machine to obtain second granules; the aperture of the screen in the crushing and granulating machine is 0.4-0.8 mm; (4) The obtained second granules are mixed with microcrystalline cellulose, a second carboxymethyl cellulose calcium and a lubricant, and the tableting hardness is controlled to be 5-7 kg, and the weight of the plain tablet coating is increased by 2%-4%; the microcrystalline cellulose, the second carboxymethyl cellulose calcium and the lubricant need to be sieved through a 40-mesh sieve; in, In step (1), the first carboxymethylcellulose calcium is 57%-100% of the prescribed amount of carboxymethylcellulose calcium, and the remainder is the second carboxymethylcellulose calcium; In step (1), the aperture of the screen in the crushing and granulating machine is 0.5-0.7 mm.

7. The perospirone hydrochloride tablets according to claim 6, characterized in that: The core comprises the following components in parts by weight: 8.62 parts of Perospirone Hydrochloride 28 parts corn starch Lactose 60.5 parts 5.5 parts of carboxymethylcellulose calcium 3 parts of polyvinyl alcohol Microcrystalline cellulose 10.68 parts 0.7 parts of lubricant.

8. The perospirone hydrochloride tablets according to any one of claims 1 to 3 or 5 to 7, characterized in that: The perospirone hydrochloride tablets have the following release characteristics: in a medium of pH 1.2, at 30 rpm, in a basket method test, the cumulative dissolution after 5 minutes is 10%-23%, the cumulative dissolution after 10 minutes is 50%-60%, the cumulative dissolution after 15 minutes is 62%-70%, and the cumulative dissolution after 30 minutes is 72%-79%.

9. The method for preparing the perospirone hydrochloride tablets according to any one of claims 1 to 3, characterized in that: include: (1) corn starch, perospirone hydrochloride, first carboxymethylcellulose calcium, and lactose are mixed using a pulverizing and granulating machine to obtain a mixture; (2) adding the obtained mixture into a fluidized bed, adding polyvinyl alcohol, and granulating the mixture in the fluidized bed to obtain first granules; (3) drying and granulating the obtained first granules to obtain second granules; (4) mixing the obtained second granules with microcrystalline cellulose, a second carboxymethylcellulose calcium and a lubricant; The first carboxymethylcellulose calcium is 57%-100% of the prescribed amount of carboxymethylcellulose calcium, and the remainder is the second carboxymethylcellulose calcium; In step (1), the aperture of the screen in the pulverizing and granulating machine is 0.5-0.7 mm; In step (2), the polyvinyl alcohol is added in the form of an aqueous solution of polyvinyl alcohol, and the concentration of the aqueous solution is 1wt%-3wt%; Step (2) includes adding the obtained mixture into a fluidized bed, and when the temperature of the mixture rises to 35-45°C, spraying polyvinyl alcohol into the fluidized bed for granulation; during the granulation process, the inlet air temperature of the fluidized bed is 65-85°C, the atomization pressure is 0.5-5ba, and the pump speed is 15-25rpm; In step (3), the granulation is performed by using a crushing and granulating machine, and the aperture of the screen in the crushing and granulating machine is 0.4-0.8 mm; The method further comprises tableting and coating; the tableting hardness is controlled to be 5-7kg; and the coating weight gain is controlled to be 2%-4%.

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