Intravenous Ganaxolone Formulations and Methods of Use in Treating Status Epilepticus and Other Seizure Disorders
The disclosure provides an injectable ganaxolone formulation comprising ganaxolone, sulfobutyl ether-β-cyclodextrin; and water. The injectable ganaxolone formulation optionally includes a surfactant and a pH modifier. The ganaxolone and sulfobutyl ether-β-cyclodextrin may be in an inclusion complex. The disclosure also provides a lyophilized powder of the ganaxolone/sulfobutyl ether-β-cyclodextrin formulation that may be reconstituted in water for injection. The disclosure provides a method of treating a patient having a seizure disorder, stroke, or traumatic brain injury, comprising administering an effective amount of the injectable ganaxolone formulation comprising ganaxolone, sulfobutyl ether-β-cyclodextrin; and water. The disclosure also provides combination methods in which the injectable ganaxolone/sulfobutyl ether-β-cyclodextrin formulation is administered in combination with at least one additional active agent.
1 - 59 . (canceled)
60 . An aqueous injectable ganaxolone formulation comprising:
a) ganaxolone in an amount of about 1 mg/ml;
b) sulfobutyl ether-β-cyclodextrin; and
d) a buffer selected from
i) a phosphate; or
ii) a citrate buffer;
wherein the ganaxolone and sulfobutyl ether-β-cyclodextrin form an inclusion complex, the w/w ratio of sulfobutyl ether-β-cyclodextrin to ganaxolone is about 52:1 to about 70:1, and the aqueous injectable formulation has a pH of about 6.01-7.10.
61 . The aqueous injectable ganaxolone formulation of claim 60 , wherein the inclusion complex comprises a ratio of one ganaxolone molecule to one sulfobutyl ether-β-cyclodextrin molecule.
62 . The aqueous injectable ganaxolone formulation of claim 60 , wherein the w/w ratio of sulfobutyl ether-β-cyclodextrin to ganaxolone is about 60:1.
63 . The aqueous injectable ganaxolone formulation of claim 60 , wherein the formulation is formulated for intravenous administration.
64 . The aqueous injectable ganaxolone formulation of claim 60 , wherein the formulation further comprises a tonicity adjusting agent.
65 . The aqueous injectable ganaxolone formulation of claim 63 , wherein the formulation is isotonic with human plasma.
66 . The aqueous injectable ganaxolone formulation of claim 64 , wherein the tonicity adjusting agent is sodium chloride.
67 . The aqueous injectable ganaxolone formulation of claim 60 , wherein the formulation is contained within a glass vial.
68 . The aqueous injectable ganaxolone formulation of claim 60 , wherein the buffer is a citrate buffer.
69 . The aqueous injectable ganaxolone formulation of claim 60 , wherein the buffer is a phosphate buffer.