Oral formulations of Edaravone and method of manufacturing thereof

1 . A pharmaceutical composition, comprising an oral suspension, wherein the oral suspension comprises:

edaravone or a pharmaceutically acceptable salt thereof, in a concentration of at least 2% w/v; and the following pharmaceutically acceptable excipients;

a. an antioxidant, in a concentration of not more than 3.5% w/v;

b. a wetting agent, in a concentration of not more than 20% w/v;

c. a suspending or thickening agent, in a concentration of not more than 2% w/v;

d. an anti-foaming agent, in a concentration ranging from 0% w/v to 1% w/v;

e. a sweetening, coloring, or flavouring agent, in a concentration ranging from 0% w/v to 0.5% w/v; and

f. a vehicle, in a concentration of at least 65% w/v;

wherein each concentration is based on the total amount of the formulation;

wherein Edaravone is in a micronized form in the oral suspension; and

wherein the particle size D 100 of the micronized form of Edaravone is less than 8000 nm.

2 . The pharmaceutical composition as claimed in claim 1 , wherein the antioxidant is selected from the group consisting of citric acid anhydrous, sodium bisulphite, L-cysteine HCl, Butylated hydroxytoluene, butylated hydroxy anisole, ascorbic acid, and mixtures thereof.

3 . The pharmaceutical composition as claimed in claim 1 , wherein the wetting agent is selected from the group consisting of PEG 400, PEG 500, polyoxyethylene sorbitan monooleate (Tween 80/HLB15), an oleoyl polyoxyl-6 glyceride, β-cyclodextrin, alcohol, polyethylene glycol and mixtures thereof.

4 . The pharmaceutical composition as claimed in claim 1 , wherein the suspending or thickening agent is selected from the group consisting of HPMC E15 premium, Hydroxypropyl methylcellulose (3 CPS), Hydroxypropyl methylcellulose (15 CPS), Sodium alginate, Xanthan gum, fumed silica, Sodium carboxymethyl cellulose and mixtures thereof.

5 . The pharmaceutical composition as claimed in claim 1 , wherein the anti-foaming agent is selected from the group consisting of simethicone, dimethicone, and mixtures thereof.

6 . The pharmaceutical composition as claimed in claim 1 , wherein the sweetening or flavouring agent is selected from the group consisting of black pepper oleoresin, sucralose, erythrosine, piperine, and mixtures thereof.

7 . The pharmaceutical composition as claimed in claim 1 , wherein the oral suspension comprises:

Edaravone or a pharmaceutically acceptable salt thereof, in a concentration of at least 25 mg/ml;

water, in a concentration of at least 75% w/v; and

the following pharmaceutically acceptable excipients:

citric acid anhydrous in an amount of up to 0.05% w/v;

sodium bisulphite in an amount of up to 2% w/v;

L-cysteine HCl in an amount of up to 1% w/v;

simethicone in an amount of up to 0.6% w/v;

PEG 400 in an amount of up to 15% w/v;

polyoxyethylene sorbitan monooleate in an amount of up to 0.7% w/v;

oleoyl macrogol-6 glyceride in an amount of up to 1% w/v;

fumed silica in an amount of up to 0.5% w/v;

black pepper oleoresin in an amount of up to 0.3% w/v;

HPMC in an amount of up to 1% w/v;

xanthan gum in an amount of up to 0.37% w/v; and

sucralose in an amount of up to 0.2% w/v;

wherein Edaravone is in a micronized form in the oral suspension; and

the particle size D100 of the micronized form is less than 8000 nm.

8 . The pharmaceutical composition as claimed in claim 1 , wherein the oral suspension is produced by a process comprising:

mixing micronized Edaravone with the wetting agent to form a first mixture;

adding the vehicle to the first mixture to form a slurry; and

transferring the slurry to a colloid mill to make a uniform suspension.

9 . The pharmaceutical composition as claimed in claim 1 , wherein the oral suspension is produced by a process comprising:

mixing micronized Edaravone with the wetting agent to form a first mixture, wherein the wetting agent is PEG 400, polyoxyethylene sorbitan monooleate, oleoyl macrogol-6 glyceride, or a mixture thereof;

adding the water to the first mixture to form a slurry; and

transferring the slurry to a colloid mill to make a uniform suspension.