DESC:FORM 2

THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)

“TABLET COMPRISING BREXPIPRAZOLE OR A SALT OF THEREOF”

ALEMBIC PHARMACEUTICALS LIMITED
An Indian Company
Alembic Campus, Alembic Road, Vadodara-390 003, Gujarat, India

The following specification describes the invention and the manner in which it is to be performed:

TECHNICAL FIELD:
The present invention relates to a pharmaceutical composition comprising Brexpiprazole or a salt thereof as an active ingredient.

BACK GROUND:
Drug substances are usually administered as part of a formulation in combination with one or more other pharmaceutical agents that serve varied and specialized pharmaceutical functions. Dosage forms of various types may be made through selective use of pharmaceutical excipients. As pharmaceutical excipients have various functions and contribute to the pharmaceutical formulations in many different ways, e.g., disintegration time, dilution, drug release profile, stability, preservation, bioavailability, solubilisation, thickening, colouring, flavouring, etc. The properties that are commonly considered when formulating an active drug substance include bioavailability, ease of manufacture, ease of administration, and stability of the dosage form. Due to the varying properties of the active drug substance to be formulated, dosage forms typically require pharmaceutical excipients that are uniquely tailored to the active drug substance in order to achieve advantageous physical and pharmaceutical properties.

Brexpiprazole or a salt thereof is known to act as a dopamine D2 receptor partial agonist, a serotonin 5-HT2A receptor antagonist, and an a1 adrenergic receptor antagonist, as well as a serotonin uptake inhibitor (or a serotonin uptake inhibitor) disclosed in Japan patent application no JP2006316052, and to possess a wide therapeutic spectrum in the treatment of central nervous system diseases (in particular, schizophrenia).

US20140234417A1 (US’417) discloses the formulation of Brexpiprazole or a salt thereof prepared by wet granulation method and limited with use of specific binder i.e. hydroxyl propyl cellulose and hydrophobic lubricant such as magnesium stearate.

OBJECT OF THE INVENTION:
Provided herein is a tablet containing, as an active ingredient, 7-[4-(4-benzo[b] thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one (“Brexpiprazole”), or a salt thereof.

An object of present invention is to formulate a tablet comprising Brexpiprazole or a salt thereof as an active ingredient having particle size (D90) less than about 70 microns.

Another object of present invention is to provide a tablet comprising Brexpiprazole or salt thereof and hydrophilic lubricant.

Another object of present invention is to formulate a tablet comprising Brexpiprazole or salt thereof without use of Binder.

The present invention provides a tablet comprising Brexpiprazole or a salt thereof as an active ingredient and having excellent disintegration ability, storage stability.

DETAILED DESCRIPTION OF THE INVENTION:
The tablet of the present invention comprises Brexpiprazole or a salt thereof as an active ingredient.

Brexpiprazole or a salt thereof can be produced by a known method, for example, that disclosed in Japanese Unexamined Patent Publication No. 2006-316052 or a method based thereon.

Salts of Brexpiprazole are not particularly limited as long as they are pharmacologically acceptable. Preferable examples thereof include: metal salts such as alkali metal salts (e.g., sodium salts and potassium salts), alkaline earth metal salts (e.g., calcium salts and magnesium salts), salts of inorganic bases such as ammonium salts, alkali metal carbonates (e.g., lithium carbonate, potassium carbonate, sodium carbonate, and cesium carbonate), alkali metal hydrogen carbonates (e.g., lithium hydrogen carbonate, sodium hydrogen carbonate, and potassium hydrogen carbonate), and alkali metal hydroxides (e.g., lithium hydroxide, sodium hydroxide, potassium hydroxide, and cesium hydroxide); salts of organic bases such as tri(lower)alkylamines (e.g., trimethylamine, triethylamine, and N-ethyldiisopropylamine), pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, dimethylaniline, N-(lower)alkyl-morpholine (e.g., N-methylmorpholine), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO); salts of inorganic acids such as hydrochloride, hydrobromate, sulfate, nitrate, and phosphate; salts of organic acids such as formate, acetate, propionate, oxalate, malonate, succinate, fumarate, maleate, lactate, malate, citrate, tartrate, carbonate, picrate, methanesulfonate, ethanesulfonate, p-toluenesulfonate, and glutamate; and the like.

Brexpiprazole or a salt thereof comprises preferably about 0.05 to 25% by weight, and more preferably about 0.1 to 15% by weight with respect to the weight of the tablet.

The tablet of the present invention preferably comprises additives such as diluents/ fillers (a), disintegrant (b), and a hydrophilic lubricant (c) and devoid of any binders.

Examples of diluents/ fillers (a) include, for example, sugar such as fructose, white soft sugar, sucrose, powdered sucrose, lactose, powdered hydrogenated maltose starch syrup, and maltose; sugar alcohols such as D-mannitol, D-sorbitol, xylitol, erythritol, maltitol; starch such as wheat starch, corn starch, and potato starch; starch derivatives such as dextrin, beta-cyclodextrin; cellulose or a derivative thereof such as microcrystalline cellulose, powdered cellulose, ethyl cellulose; silicic acid or a salt thereof such as light anhydrous silicic acid, hydrated silicon dioxide, silicon dioxide, calcium silicate, magnesium silicate, and magnesium aluminometasilicate; kaolin; titanium oxide; magnesium oxide; talc; precipitated calcium carbonate; anhydrous dibasic calcium phosphate.

These diluents/ fillers (a) may be used singly or in a combination of two or more. Among these, sugar, a sugar alcohol, starch, and cellulose are preferable, and lactose, microcrystalline cellulose and corn starch are more preferable.

The diluents/ fillers (a) content is not particularly limited, and is preferably about 10 to 98.5% by weight with respect to the weight of the tablet, more preferably about 20 to 95%, and still more preferably about 30 to 90% by weight.

By setting the content and the amount of the diluents/ fillers (a) as described above, the productivity can be improved.

Examples of disintegrates (b) include starch or a derivative thereof such as wheat starch, corn starch, potato starch, partially pregelatinized starch, sodium carboxymethyl starch, and hydroxypropyl starch; cellulose or a derivative thereof such as microcrystalline cellulose, carboxymethyl cellulose (carmellose), calcium carboxymethyl cellulose (carmellose calcium), croscarmellose sodium, and low-substituted hydroxypropyl cellulose; crospovidone; alginic acid; and bentonite. These disintegrants (b) may be used singly or in a combination of two or more. Among these, starch or a derivative thereof, and cellulose or a derivative thereof are preferable, and sodium carboxymethyl starch, carmellose calcium, croscarmellose sodium and low-substituted hydroxypropyl cellulose are more preferable.

Here, in the present specification, “low-substituted hydroxypropyl cellulose” is a derivative of cellulose including hydroxypropoxy groups by about 5 to 16%. The amount of the hydroxypropoxy groups in the low-substituted hydroxypropyl cellulose may be measured by a method listed in, for example, the Japanese Pharmacopeia. The low-substituted hydroxypropyl cellulose may be produced by a method known in the art, or a commercially available product thereof may also be used. Examples of commercially available products of the low-substituted hydroxypropyl cellulose include, but are not limited to, “LH series” and “NBD series” manufactured by Shin-Etsu Chemical Co., Ltd.

The disintegrant (b) content is not particularly limited, and is preferably about 1 to 25% by weight with respect to the weight of the tablet, more preferably about 2 to 20% by weight, and still more preferably about 3 to 16% by weight.

Hydrophilic lubricants helps in achieving faster dissolution rate of the tablet unlike hydrophobic lubricant, magnesium stearate.

Examples of hydrophilic lubricants (c) include Boric acid, Sodium benzoate, Sodium oleate, Sodium acetate, Magnesium lauryl sulfate, Sodium stearyl fumarate, SLS and Polyethylene glycol (macrogols such as macrogol 400, macrogol 600, macrogol 1500, macrogol 4000, and macrogol 6000). These lubricants (c) may be used singly or in a combination of two or more. Among these, sodium stearyl fumarate, stearate, sucrose ester of fatty acid, and hydrogenated oil are preferable, and sodium stearyl fumarate is most preferable.

The lubricant (c) content is not particularly limited, and is preferably about 0.1 to 10% by weight with respect to the weight of the tablet more preferably about 0.2 to 8% by weight, and still more preferably about 0.3 to 7% by weight.

The tablet of the present invention may comprise other components in addition to the diluents/ fillers (a), the disintegrant (b), and the hydrophilic lubricant (c). Examples of other components include various additives applicable to tablets, such as colorants, pH adjusters, preservatives, taste enhancers, antioxidants, buffers, chelating agents, abrasives, solvents, hardening agents, surfactants, sweeteners, fluidizers, brightening agents, and flavours. Those components may be used in an amount that does not adversely affect the present invention.

The tablet of the present invention is a film-coated tablet comprises the above described components to achieve long-term storage stability and prevent degradation due to light or the like.

The coating layer may comprise pharmaceutical additives, such as a coating agent, plasticizer, dispersant, defoaming agent, and the like, usually used for coating (for providing a coat to) orally administrable pharmaceutical preparations.

Examples of additives include celluloses such as microcrystalline cellulose, methyl cellulose, ethyl cellulose, carmellose sodium, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose (hypromellose) and derivatives thereof; polyethylene glycol (macrogol); polyvinyl alcohol; titanium oxide; and talc. These additives may be used singly or in a combination of two or more.

In the present invention, for coating of the tablet opadry is more preferred.

Furthermore, by using suitable colorant in film coating, excellent photo-stability can be supplied to the tablets. Suitable grade of coloured opadry can be used for coating of the tablet.

The opadry content is preferably about 0.1 to 6% by weight with respect to the total weight of the coated tablet.

Specific preferable examples of the additives contained in the tablet of the present invention include:
as an diluents/ fillers (a), at least one member selected from the group consisting of sugars, sugar alcohols, starches, and celluloses;
as disintegrants (b), at least one member selected from the group consisting of cellulose derivatives and starch derivatives; and,
as a hydrophilic lubricant (c), sodium stearyl fumarate.

From a standpoint of productivity and disintegration ability, these additives are preferably used in a combination of: as an diluents/ fillers (a), at least one member selected from the group consisting of lactose, corn starch, and microcrystalline cellulose; as disintegrants (b), at least one member selected from the group consisting of low-substituted hydroxypropyl cellulose, croscarmellose sodium, and sodium carboxymethyl starch; and, as a hydrophilic lubricant (c), sodium stearyl fumarate.

Brexpiprazole is having low water solubility hence effect of particle size is imperative to drug product or drug product manufacturing. Particle size of powder materials has become one of the crucial aspects in drug product development and quality control of solid oral dosage forms. The particle size of the drug substance may have significant effects on final drug product performance (e.g., dissolution, bioavailability, content uniformity etc.). Method for determination of particle size is well known in art and done by laser light scattering technique.
In one embodiment, particle size (D90) is preferably of about 70 microns. In another embodiment, particle size (D90) is more preferably of about 50 microns. In another embodiment, particle size is most preferably about 5 to about 25 microns.

The tablet of the present invention preferably contains each of the components in the content and amount shown below.
Contents of each of the components in the Tablet
Brexpiprazole or a salt thereof:
Sugar and/or sugar alcohol:
Starch:
Cellulose:

0.05 to 20% by weight
20 to 80% by weight
5 to 50% by weight
1 to 35% by weight
At least one member selected from the group consisting of low-substituted hydroxypropyl cellulose, croscarmellose sodium, and starch derivatives:
Lubricant: 1 to 25% by weight

0.1 to 10% by weight

The content and amount of each of the components in a further preferable mode of the tablet of the present invention are shown below.
Contents of each of the components in the Tablet
Brexpiprazole or a salt thereof:
Lactose:
Corn Starch:
Microcrystalline cellulose:

0.1 to 15% by weight
30 to 60% by weight
10 to 30% by weight
5 to 35% by weight
At least one member selected from the group consisting of low-substituted hydroxypropyl cellulose, croscarmellose sodium, and starch derivatives:
Sodium stearyl fumarate: 2 to 15% by weight

0.1 to 10% by weight

When the tablet of the present invention is a coated tablet, preferable examples of the additives contained in the coated tablet include, as the components for an uncoated tablet before coating:
as diluents/ fillers (a), at least one member selected from the group consisting of sugars, sugar alcohols, starches, and celluloses;
as disintegrates (b), at least one member selected from the group consisting of cellulose derivatives and starch derivatives; and
as a hydrophilic lubricant (c), sodium stearyl fumarate, and
as components for the coating layer (d), opadry coating agent.

Furthermore, when the tablet of the present invention is a coated tablet, a more preferable combination is a formulation obtained by applying a coating layer on an uncoated tablet; in which, the uncoated tablet contains Brexpiprazole or a salt thereof, lactose, corn starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose and sodium stearyl fumarate, and the coating layer contains suitably selected opadry coating agent.

The preferable content and amount of each of the components, and further preferable content and amount of each of the components in a preferable mode of the coated tablet are shown below.

Content of each of the Components in the uncoated tablet
Brexpiprazole or a salt thereof:
Sugar and/or sugar alcohol:
Starch:
Cellulose: 0.05 to 20% by weight
20 to 80% by weight
5 to 50% by weight
1 to 35% by weight
At least one member selected from the group consisting of low-substituted hydroxypropyl cellulose, croscarmellose sodium, and starch derivatives:
Lubricant: 1 to 25% by weight

0.1 to 10% by weight
Content of coating layer (per entire coated tablet)
Opadry 1 to 6% by weight

The method for producing the tablet of the present invention is not particularly limited; for example, the tablet of the present invention can be produced by a step of forming into a tablet a mixture containing Brexpiprazole or a salt thereof, and components other than Brexpiprazole or a salt thereof necessary to form a tablet (i.e., diluents/ fillers (a), a disintegrant (b), a lubricant (c) and the like. Alternatively, the tablet of the present invention can be produced by the method comprising: a mixture containing Brexpiprazole or a salt thereof, diluents/ fillers (a) and a disintegrant (b), and further mixing thereto a lubricant (c); and compressing the obtained mixture into a tablet.

The method used for forming a tablet is not particularly limited. Examples thereof include direct compression, roller compaction, dry granulation methods and wet granulation methods (e.g., a fluidized-bed granulation method, and a knead-granulation method). Among these, direct compression methods are preferably used for the production, from a standpoint of being able to uniformly mix the active ingredient and other components in the tablet and being able to obtain a tablet whose components are uniformly distributed therein.

Examples of the tablet forming methods include tableting, such as direct compression tableting, dry tableting, wet tableting, and external lubrication tableting.

The coated tablet of the present invention can be produced by mixing opadry and a liquid medium. The surface of the uncoated tablet obtained by the method described above is coated using suitable coating agent and coating machine; and successively drying it.

Examples of the liquid medium (e.g., a dispersion medium) used in the above described step include: purified water; methanol, ethanol, isopropanol, and like lower alcohols; acetone, methyl ethyl ketone, and like ketones; dichloromethane, dichloroethane, chloroform, carbon tetrachloride and like halogenated hydrocarbons; and mixtures of these solvents.

The tablet of the present invention preferably comprises Brexpiprazole, which is an active ingredient, or a salt thereof in an amount of about 0.05 to 25 mg.

The dose of the tablet of the present invention is suitably selected according to the intended use; the patient's age, sex, and other conditions; the severity of the disease; and the like. The dose is preferably selected so that the amount of Brexpiprazole (i.e., the active ingredient) or a salt thereof taken is about 0.05 to 6 mg per day.

Examples
The present invention is explained in detail below with reference to Examples. However, the scope of the present invention is not limited to these Examples.

Process for Making Dosage Forms
Dosage forms provided herein can be prepared by any of the methods of pharmacy, but all methods include the step of bringing the active ingredient into association with the excipient, which constitutes one or more necessary ingredients.

In general, the composition are prepared by weighing, screening and uniformly blending the dry powder mix including active ingredient and the excipients, further mixing the lubricant with the blend, followed by direct compaction. The uncoated tablets can be subjected to coating using coating agent and suitable coating machine.

Direct compression is a process by which the tablets are compressed directly from powder blends of the active pharmaceutical ingredient (API) and suitable excipients (including diluents, disintegrants, and lubricants, etc.), which will flow uniformly into a die cavity and form into a firm compact. Even though the final powder blend meets the acceptance criteria of blend uniformity, API may segregate or agglomerate after mixing and prior to compression due to the differences of particle size among different components in the mixture.

Direct Compression is the least complex way of oral dosage production as it contains the fewest process stages, leading to a shorter process cycle, effective and faster production times. Direct compression avoids many of the problems associated with wet and dry granulations.

1. Screening
The process for making the pharmaceutical compositions of the invention preferably includes weighing of the active ingredient and the excipient(s) as per the formula, then screening of the active ingredient and the excipient(s). Sift Brexpiprazole, Lactose monohydrate, Corn Starch (5%), Low-substituted hydroxypropyl cellulose, colloidal silicon dioxide and microcrystalline cellulose through 40# sieve.

2. Blending
This mixture is then loaded in the conta blender and blended for 30min at 16 rpm to achieve uniform mixing.

3. Lubrication
Lubricant, sodium stearyl fumarate, is then sifted through 60# sieve. Then the screened lubricant and the blended mixture is loaded in the conta blender and blended for 5 min at 16 rpm to achieve uniform mixing.

4. Compression
The formulation mixture can be tableted into the desired size and shape tablet using, for example, a tablet press or other conventional tableting equipment and standard techniques.

5. Coating
The required quantity of opadry is dispersed in the purified water using mechanical stirrer for 30 min. The core tablet is then coated with the opadry coating liquid using suitable machine.

Embodiments provided herein may be more fully understood by reference to the following examples. These examples are meant to be illustrative of pharmaceutical compositions and dosage forms provided herein, but are not in any way limiting.

Example 1: Impact of particle size on dissolution of Brexpiprazole tablet.
Table 1
Comparative dissolution profile of brexpiprazole tablets 4mg in OGD media to assess impact of API PSD on dissolution
pH 4.3 acetate buffer (0.05M), 50 rpm, USP II, 900ml
API PSD D90 : 9.629 µm D90 : 102.749 µm
Time (min) Batch No: 705002251 Batch No: 963/015
%DR %RSD %DR %RSD
5 86 4.6 23 3.5
10 94 4.4 35 8.4
15 97 4.3 41 4.6
20 97 3.7 49 5.3
30 97 3.8 55 3.4
45 98 3.6 65 8.1

Comparative dissolution study was conducted of Brexpiprazole 4mg tablet in OGD media to evaluate the influence of particle size on the dissolution rate. Based on the dissolution data attained on comparison of different particle size of the Brexpiprazole in the tablet, it was observed that smaller particle size i.e. D90 about 10 microns with large surface area resulted in faster and enhanced dissolution rate compared to larger particle size i.e. D90 of about 100 microns.

Example 2:
4 mg tablets of brexpiprazole prepared by direct compression method described above by using following inactive constituents as per illustrated quantities in Table 2. Tablets prepared subjected to comparative dissolution study, results are shown in Table 3.

Table 2 Composition 4 mg tablets (B1)
Sr. No Ingredient B1
(%w/w)
1 Brexpiprazole 4.30
2 Lactose Monohydrate 47.31
3 Corn Starch (5%) 9.68
4 Low substituted hydroxypropyl cellulose 9.68
5 Colloidal Silicon Dioxide 0.97
6 Microcrystalline Cellulose 22.90
7 Sodium Stearyl Fumarate 1.94
Weight of Core Tablet 96.77
Opadry White 3.23
Purified Water q.s.
Weight of Coated Tablet 100.00

The dissolution study was conducted of the formulated Brexpiprazole tablet in comparison with the REXULTI® tablets 4mg (Marketed by Otsuka America Pharmaceutical) in OGD media at 50 rpm using USP type II Paddle apparatus. The B1 formulation was selected having 4mg strength for the dissolution study.

Table 3 Dissolution data
Comparative dissolution profile of Rexulti (Brexpiprazole) tablets 4mg Vs Test Product (B1) in OGD media
pH 4.3 acetate buffer (0.05M), 50 rpm, USP II, 900ml
Rexulti® 4mg B1
Time (min) %DR %RSD %DR %RSD
0 0 0 0 0
5 86 6.9 80 7.1
10 95 3.1 91 3.7
15 95 1.5 95 1.5
20 97 1.9 96 2.5
30 98 2.2 97 1.7
45 97 1.8 98 1.9

Results of dissolution study of inventive tablets with REXULTI® tablets (Marketed by Otsuka America Pharmaceutical) showed no significant difference.

Example 3:
2 mg tablets of Brexpiprazole prepared by direct compression method described above by using following inactive constituents as per illustrated quantities in Table 4. Tablets prepared subjected to comparative dissolution study results are shown in Table 5.

Table 4 Composition 2 mg tablets (B2)
Sr. No Ingredient B2
(%w/w)
1 Brexpiprazole 2.15
2 Lactose Monohydrate 47.31
3 Corn Starch (5%) 7.74
4 Low substituted hydroxypropyl cellulose 4.84
5 Microcrystalline Cellulose 32.80
6 Sodium Stearyl Fumarate 1.94
Weight of Core Tablet 96.78
Opadry White 3.22
Purified Water q.s.
Weight of Coated Tablet 100.00

The dissolution study was conducted of the formulated Brexpiprazole tablet in comparison with the REXULTI® tablets 2mg (Marketed by Otsuka America Pharmaceutical) in OGD media at 50 rpm using USP type II Paddle apparatus. The B2 formulation was selected having 2mg strength for the dissolution study.

Comparative dissolution profile of Rexulti (Brexpiprazole) tablets 2mg Vs Test Product (B2) in OGD media
pH 4.3 Acetate buffer, 50 rpm, USP II, 900ml
B2 Rexulti® 2mg
Time (min) %DR %RSD %DR %RSD
5 63 4.8 67 9.1
10 84 1.9 84 5.2
15 88 2.8 91 3
20 91 3.5 95 2.6
30 93 1.8 97 3.5
45 93 2.5 99 2

Results of dissolution study of inventive tablets with REXULTI® tablets (Marketed by Otsuka America Pharmaceutical) showed no significant difference.

Stability of Formulation
Stability study was conducted for both B1 and B2 formulation, according to the ICH guidelines, for 6 months at accelerated condition (40°C/75% RH) and at room temperature. Based on the parameters such as physical appearance and chemical impurity, the pharmaceutical formulation was found to be stable.
While examples of certain particular embodiments are provided herein, it will be apparent to those skilled in the art that various changes and modifications may be made. Such modifications are also intended to fall within the scope of the appended claims. ,CLAIMS:We claim:
Claim 1. A tablet comprising Brexpiprazole or a salt thereof as an active ingredient having particle size (D90) less than about 70 microns and at least a pharmaceutically acceptable inactive ingredient.
Claim 2. The tablets according to claim 1 comprises Brexpiprazole or a salt thereof as an active ingredient having particle size (D90) less than about 25 microns.
Claim 3. A tablet comprising Brexpiprazole or a salt thereof as an active ingredient is devoid of binder.
Claim 4. A tablet comprising Brexpiprazole or a salt thereof as an active ingredient is prepared by using at least one hydrophilic lubricant.
Claim 5. The tablet according to claim 4, wherein the hydrophilic lubricant according is sodium Stearyl fumarate.
Claim 6. The tablets according to any preceding claim comprising,
0.05 to 20% by weight of Brexpiprazole or a salt thereof,
20 to 65% by weight of Sugar and/or sugar alcohol,
5 to 25% by weight of Starch,
1 to 35% by weight of cellulose,
1 to 20% by weight of disintegrant,
0.1 to 6% by weight of hydrophilic lubricant,
1 to 6% by weight of coating agent.
Claim 7. A method of producing a tablet of Brexpiprazole or a salt thereof comprises direct compression method.
Claim 8. A tablet comprising Brexpiprazole or a salt thereof as an active ingredient, a diluent (a), a disintegrant (b), a hydrophilic lubricant (c), and a coating agent (d), wherein the diluent (a) is at least one or more member selected from the group consisting of lactose, corn starch, and microcrystalline cellulose; the binder; the disintegrant (b) is at least one member selected from the group consisting of low-substituted hydroxypropyl cellulose, croscarmellose sodium, and sodium carboxymethyl starch; the hydrophilic lubricant (c) is sodium Stearyl fumarate and the coating agent (d) is opadry.
Wherein tablets prepared by using Brexpiprazole having particle size (D90) less than about 25 microns.
Claim 9. A tablet comprising Brexpiprazole or a salt thereof as an active ingredient, a diluent (a), a disintegrant (b), a hydrophilic lubricant (c), and a coating agent (d), wherein the diluent (a) is at least one or more member selected from the group consisting of lactose, corn starch, and microcrystalline cellulose; the binder; the disintegrant (b) is at least one member selected from the group consisting of low-substituted hydroxypropyl cellulose, croscarmellose sodium, and sodium carboxymethyl starch; the hydrophilic lubricant (c) is sodium Stearyl fumarate and the coating agent (d) is opadry; having dissolution rate of more than 85% of Brexpiprazole released in 30 mins.