	US 12,233,165 B2
	Microsphere formulations comprising ketamine and methods for making and using the same
Rachel Minrovic, Chardon, OH (US); Kelsey Kaht, Cleveland, OH (US); and Tracy Richey, Kent, OH (US)
Assigned to Oakwood Laboratories, LLC, Oakwood Village, OH (US)
Filed by Oakwood Laboratories, LLC, Oakwood Village, OH (US)
Filed on Aug. 17, 2021, as Appl. No. 17/404,128.
Claims priority of provisional application 63/149,911, filed on Feb. 16, 2021.
Claims priority of provisional application 63/067,068, filed on Aug. 18, 2020.
Prior Publication US 2022/0054420 A1, Feb. 24, 2022
Int. Cl. A61K 9/16 (2006.01); A61K 31/135 (2006.01)

CPC A61K 9/1647 (2013.01) [A61K 9/1682 (2013.01); A61K 31/135 (2013.01)]

6 Claims

1. A microsphere formulation, comprising:

polymer microspheres, each polymer microsphere comprising:

esketamine in a concentration of about 10 wt/wt % to about 30 wt/wt %; and

a biodegradable poly(lactide) polymer in a concentration of about 70 wt/wt % to about 90 wt/wt %, wherein the biodegradable poly(lactide) polymer has an inherent viscosity from about 0.6 dL/g to about 0.7 dL/g;

wherein the polymer microspheres have a particle size greater than 60 μm (D₅₀);

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

wherein the polymer microspheres are prepared by a method that does not include the use of a porogen, the method comprising:

(i) contacting the esketamine with the biodegradable poly(lactide) polymer in the presence of a solvent to form an organic component;

(ii) emulsifying an inner aqueous component comprising water with the organic component to form a primary emulsion;

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

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

(v) subjecting the polymer microspheres to dehydration.