MICROSPHERE FORMULATIONS COMPRISING KETAMINE AND METHODS FORMAKING AND USING THE SAME

1 . A microsphere formulation, comprising:

polymer microspheres, each polymer microsphere comprising:

(1) esketamine; and

(2) a biodegradable poly(lactide) polymer having an inherent viscosity of about 0.6 dL/g to about 0.72 dL/g,

wherein each polymer microsphere has a ketamine drug load of about 12 wt/wt % to about 17 wt/wt %;

wherein the polymer microspheres have a particle size of about 80 μm (D 50 ) to about 110 μm (D 50 ); and

wherein the polymer microspheres are characterized in that each of the polymer microspheres comprises a plurality of internal macrovoids.

2 . The microsphere formulation of claim 1 , wherein the microsphere formulation is characterized in that about 75% to 100% of the ketamine is released over a period of between about 25 to about 35 days of injection into a human subject, but not more than about 10% of the ketamine has been released within 24 hours of injection into the human subject.

3 . The microsphere formulation of claim 1 , wherein the biodegradable poly(lactide) polymer has an inherent viscosity between about 0.67 dL/g and about 0.72 dL/g.

4 . The microsphere formulation of claim 1 , wherein each polymer microsphere has a ketamine drug load of about 13 wt/wt % to about 16 wt/wt %.

5 . The microsphere formulation of claim 1 , wherein the polymer microspheres have a particle size of about 90 (D 50 ).

6 . A pharmaceutical composition comprising the microsphere formulation of claim 1 .

7 . A method for treating depression, the method comprising intramuscularly or subcutaneously injecting a patient in need thereof with a therapeutically effective amount of a microsphere formulation as claimed in claim 1 .

8 . A microsphere formulation, comprising:

polymer microspheres, each polymer microsphere comprising:

(i) ketamine; and

(ii) a biodegradable poly(lactide) polymer;

wherein each polymer microsphere has a ketamine drug load of about 10 wt/wt % to about 30 wt/wt %, and

wherein the polymer microspheres have a particle size greater than 60 um (D 50 ).

9 . The microsphere formulation of claim 8 , wherein the polymer microspheres have a particle size of about 80 μm (D 50 ) to about 110 μm (D 50 ).

10 . The microsphere formulation of claim 8 , wherein the ketamine comprises a free base form of esketamine.

11 . The microsphere formulation of claim 8 , wherein each polymer microsphere has a ketamine drug load of between about 12 wt/wt % to about 17 wt/wt %.

12 . The microsphere formulation of claim 8 , wherein the biodegradable poly(lactide) polymer has an inherent viscosity from about 0.6 dL/g to about 0.72 dL/g.

13 . The microsphere formulation of claim 8 , wherein the microsphere formulation is characterized in that about 75% to 100% of the ketamine is released over a period of between about 25 to about 35 days of injection into a human subject, but not more than about 10% of the ketamine has been released within 24 hours of injection into the human subject.

14 . The microsphere formulation of claim 8 , characterized in that each of the polymer microspheres comprises a plurality of internal emulsions comprising water and a surfactant.

15 . The microsphere formulation of claim 8 , characterized in that each of the polymer microspheres comprises a plurality of internal macrovoids.

16 . A pharmaceutical composition comprising the microsphere formulation of claim 8 .

17 . A method for treating depression, the method comprising intramuscularly or subcutaneously injecting a patient in need thereof with a therapeutically effective amount of a microsphere formulation as claimed in claim 8 .

18 . A kit, comprising:

(A) a microsphere formulation, the microsphere formulation comprising:

polymer microspheres, each polymer microsphere comprising:

(1) esketamine; and

(2) an ester-terminated biodegradable poly(lactide) polymer having an inherent viscosity of about 0.67 dL/g,

wherein each polymer microsphere has a ketamine drug load of about 14 wt/wt % to about 15 wt/wt %;

wherein the polymer microspheres have a particle size of about 90 μm (D 50 ); and

wherein the polymer microspheres are characterized in that each of the polymer microspheres comprises a plurality of internal macrovoids; and

wherein the microsphere formulation is characterized in that about 75% to 100% of the ketamine is released over a period of between about 25 to about 35 days of injection into a human subject, but not more than about 10% of the ketamine has been released within 24 hours of injection into the human subject.

19 . The kit of claim 18 , further comprising a diluent.

20 . The kit of claim 18 , further comprising a syringe.