Microsphere formulations comprising ketamine and methods for making and using the same

1 . A microsphere formulation, comprising:

polymer microspheres, each polymer microsphere comprising:

(i) an active pharmaceutical ingredient consisting essentially of ketamine or esketamine; and

(ii) a biodegradable polymer consisting essentially of an acid end-capped poly(lactide) (PLA) polymer, having an inherent viscosity (IV) of about 0.1 to about 0.3 dL/g,

wherein each polymer microsphere has a ketamine or esketamine drug load of between about 20 wt/wt % to about 50 wt/wt %, and

wherein the polymer microspheres have a particle size of between about 30 μm to about 90 μm (D 50 ), and

wherein the polymer microspheres are characterized in that each of the polymer microspheres comprises an internal polymer phase, and a plurality of internal macrovoids dispersed within the internal polymer phase; and

wherein the polymer microspheres are prepared by a method comprising:

(1) contacting the ketamine with the PLA polymer in the presence of a solvent to form an organic component;

(2) emulsifying an inner aqueous component consisting essentially of water, polyvinyl alcohol, and NaCl with the organic component to form a primary emulsion;

(3) emulsifying the primary emulsion with a continuous phase comprising water to form a secondary emulsion;

(4) removing the solvent from the secondary emulsion to form the polymer microspheres; and

(5) subjecting the polymer microspheres to dehydration.

2 . The microsphere formulation of claim 1 , wherein the active pharmaceutical ingredient consists essentially of esketamine.

3 . The microsphere formulation of claim 1 , wherein each polymer microsphere has a ketamine or esketamine drug load of between about 20 wt/wt % to about 30 wt/wt %.

4 . The microsphere formulation of claim 1 , wherein the polymer microspheres have a particle size of between about 45 μm about 90 μm (D 50 ).

5 . The microsphere formulation of claim 1 , wherein the PLA polymer has an IV of between about 0.13 dL/g and 0.26 dL/g.

6 . The microsphere formulation of claim 1 , wherein each polymer microsphere has a ketamine or esketamine drug load of between about 25 wt/wt % to about 35 wt/wt %.

7 . The microsphere formulation of claim 1 , wherein each of the polymer microsphere has a ketamine or esketamine drug load of between about 25 wt/wt % to about 30 wt/wt %, and wherein the polymer microspheres have a particle size of between about 45 μm about 90 μm (D 50 ).

8 . A kit, the kit comprising: (i) the microsphere formulation of claim 1 ; and (ii) a diluent for administration.

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

10 . The microsphere formulation of claim 1 , wherein each of the polymer microspheres is further characterized in that the ketamine or esketamine is dispersed within the internal polymer phase.