EP3612186A1 — Sustained release injectable neurosteroid formulations

USPTO Abstract

The disclosure provides a sustained release injectable neurosteroid formulation comprising neurosteroid particles having a D50 of less than 10 microns, the neurosteroid particles comprising a neurosteroid of Formula I: Formula I or a pharmaceutically acceptable salt thereof, wherein: is a double or single bond and the variables, e.g., R1,R2, R3, R4, R4a, R5, R6, R7, R8, R9, R10, and R10a are described herein. The formulation comprises neurosteroid particles comprising the neurosteroid and a polymeric surface stabilizer and provides an effective plasma concentration of the neurosteroid at steady state for at least 48 hours, and in some embodiments for at least 4 weeks. The sustained release injectable neurosteroid formulation can formulated for intramuscular or subcutaneous administration. The disclosure provides a method of treating a patient having seizures, anxiety, agitation, depression (including post-partum depression), schizophrenia, post-traumatic stress disorder, or tremors by administering the sustained release neurosteroid formulation to the patient. In certain embodiments the neurosteroid is ganaxolone.