Vilazodone pharmaceutical composition, preparation method therefor and use thereof

1 . A vilazodone pharmaceutical composition, which is a liquid injection, comprising: based on a percentage of a mass of an ingredient in grams to the volume of the liquid injection in milliliters, 1.00-50.00% of solid particles of an active ingredient, greater than 0 and not exceeding 5.00% of a wetting agent, 0-5.00% of a stabilizer, 0-5.00% of an osmotic pressure regulator, greater than 0 and not exceeding 5.00% of a buffer, and a solvent,

wherein the active ingredient is selected from vilazodone, vilazodone hydrochloride, a solvate thereof, and mixtures thereof,

wherein the solid particles of the active ingredient have the following particle size distribution: a Dv(10) of no more than 20 micrometers, a Dv(50) of no more than 50 micrometers, and a Dv(90) of no more than 100 micrometers;

the wetting agent is a polysorbate;

the stabilizer is one or more selected from polyvinylpyrrolidone, sodium deoxycholate, and sodium carboxymethylcellulose;

the osmotic pressure regulator is mannitol;

the buffer is one or more selected from phosphoric acid and phosphate; and

the solvent is water.

2 . The vilazodone pharmaceutical composition according to claim 1 , having a pH value of 6.5-8.0.

3 . The vilazodone pharmaceutical composition according to claim 1 , wherein the liquid injection further comprises one or more selected from a suspending agent, a buffer, a surfactant, a polymer, an electrolyte, and a non-electrolyte.

4 . The vilazodone pharmaceutical composition according to claim 3 , wherein

the suspending agent comprises one or more selected from sodium carboxymethylcellulose, polyethylene glycol, and povidone;

and/or,

the buffer comprises one or more selected from phosphoric acid, phosphate, citric acid, sodium citrate, hydrochloric acid, sodium hydroxide, tris(hydroxymethyl)aminomethane, sodium hydroxide, hydrochloric acid, and a mixture thereof.

5 . The vilazodone pharmaceutical composition according to claim 4 , wherein:

the antioxidant comprises one or more selected from citric acid, vitamin C, and vitamin E;

and/or,

the metal ion chelating agent comprises ethylenediaminetetraacetic acid;

and/or,

the poloxamer comprises one or more selected from poloxamer 188, poloxamer 124 and poloxamer 407;

and/or,

the polysorbate comprises one or more selected from polysorbate 80 and polysorbate 20;

and/or,

the povidone comprises one or more selected from polyvidone K12, polyvidone K17, PLASDONETM C-12 polyvidone, PLASDONETM C-17 polyvidone, and PLASDONETM C-30 polyvidone;

and/or,

the polyethylene glycol includes comprises polyethylene glycol 3350;

and/or,

the cross-linked polymer comprises sodium carboxymethylcellulose;

and/or,

the phosphate comprises one or more selected from sodium dihydrogen phosphate, disodium hydrogen phosphate, anhydrates or hydrates of sodium dihydrogen phosphate, and anhydrates or hydrates of disodium hydrogen phosphate.

6 . A preparation method for the vilazodone pharmaceutical composition according to claim 1 , comprising the following steps:

step 1: mixing the solid particles of the active ingredient and auxiliaries comprising the wetting agent, the stabilizer, the osmotic pressure regulator, the buffer, and the solvent to obtain a premix; and

step 2: grinding the premix obtained in step 1 together with zirconium beads to obtain the vilazodone pharmaceutical composition.

7 . A pharmaceutical formulation comprising the vilazodone pharmaceutical composition according to claim 1 , wherein the liquid injection is an aqueous suspension.

8 . A method for treating depression, comprising administering the vilazodone pharmaceutical composition according to claim 1 to a patient in need thereof.

9 . A method of partially agonizing 5-hydroxytryptamine 1A (5-HT 1A ) and/or selectively inhibiting reuptake of 5-hydroxytryptamine (5-HT), comprising administering the vilazodone pharmaceutical composition according to claim 1 to a patient in need thereof.

10 . The vilazodone pharmaceutical composition according to claim 1 , wherein: the particle size Dv(10) of the solid particles of the active ingredient is not greater than 10 micrometers; the particle size Dv(50) comprising the solid particles of the active ingredient is not greater than 40 micrometers; the particle size Dv(90) of the solid particles of the active ingredient is not greater than 80 micrometers;

or,

the particle size Dv(10) of the solid particles of the active ingredient is not greater than 8 micrometers; the particle size Dv(50) of the active ingredient is not greater than 30 micrometers; the particle size Dv(90) of the solid particles of the active ingredient is not greater than 50 micrometers.

11 . The vilazodone pharmaceutical composition according to claim 1 , wherein:

the solid particles of the active ingredient is of 5.00-30.00%;

and/or, the wetting is of greater than 0 and not exceeding 2.00%;

and/or, the osmotic pressure regulator is of 1.00%-5.00%;

and/or, the stabilizer is of 0-1.00%;

and/or, the buffer in is of greater than 0 and not exceeding 1.00%;

and/or, the wetting agent is one or more selected from polysorbate 20 and polysorbate 80;

and/or, the buffer is one or more selected from sodium dihydrogen phosphate, disodium hydrogen phosphate, anhydrates or hydrates of sodium dihydrogen phosphate, and anhydrates or hydrates of disodium hydrogen phosphate;

and/or, the polyvinylpyrrolidone is PVP K12.

12 . The vilazodone pharmaceutical composition according to claim 1 ,

selected from one of the following formulas:

formula av: 30% vilazodone hydrochloride, 1% polysorbate 20, 2.15% mannitol, 0.08% anhydrous sodium dihydrogen phosphate, and 0.4% anhydrous disodium hydrogen phosphate, with the balance being water;

formula bv: 5% vilazodone hydrochloride, 1% polysorbate 20, 0.3% PVP K12, and 0.3% sodium deoxycholate, with the balance being water;

formula cv: 20% vilazodone hydrochloride, 1% polysorbate 20, 0.3% PVP K12, 0.3% sodium deoxycholate, 0.45% disodium hydrogen phosphate, 0.09% sodium dihydrogen phosphate, 2.5% mannitol, and 0.18% sodium carboxymethylcellulose, with the balance being water;

formula dv: 36.3% vilazodone hydrochloride, 0.91% polysorbate 20, 0.34% disodium hydrogen phosphate, 0.07% sodium dihydrogen phosphate, 2.0% mannitol, and 0.21% sodium carboxymethylcellulose, with the balance being water;

formula ev: 30% vilazodone hydrochloride, 1% polysorbate 20, 0.38% disodium hydrogen phosphate, 0.08% sodium dihydrogen phosphate, 2.20% mannitol, and 0.23% sodium carboxymethylcellulose, with the balance being water;

and

formula fv: 30-40% vilazodone hydrochloride, 1% polysorbate 20, 0-0.3% PVP K12, 0.33-0.39% disodium hydrogen phosphate, 0.07-0.08% sodium dihydrogen phosphate, 1.6-2.2% mannitol, and 0-1.0% sodium carboxymethylcellulose, with the balance being water.