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

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 (D50), 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.