DRY POWDER ESKETAMINE COMPOSITION FOR USE IN THE TREATMENT OF BIPOLAR DEPRESSION BY PULMONARY ADMINISTRATION
A dry powder inhalable pharmaceutical composition comprising ketamine or its pharmaceutically acceptable salt for use in a method of treatment of depression by administration via pulmonary route. The composition is especially useful for the treatment of treatment-resistant or treatment-refractory depression.
1 - 31 . (canceled)
32 . A method of treating bipolar depression comprising administering to a patient in need thereof a dosage form comprising a dry powder composition formulated for administration to the lungs via oral inhalation, wherein the dry powder composition comprises:
a nominal unit dose of esketamine, or a pharmaceutically acceptable salt thereof, and wherein the nominal unit dose is 4 mg, calculated as free base;
30-95% by weight of a carbohydrate bulking agent; and
0.2-3% by weight of a stabilizing agent.
33 . The method of claim 32 , wherein the esketamine, or pharmaceutically acceptable salt thereof, is esketamine hydrochloride.
34 . The method of claim 32 , wherein the dry powder composition has a particle diameter d50 of 1-10 μM, as measured by laser diffraction.
35 . The method of claim 34 , wherein the dry powder has a particle diameter d90 of 3-35 μm, as measured by laser diffraction.
36 . The dosage form of claim 32 , wherein the carbohydrate bulking agent is lactose monohydrate.
37 . The dosage form of claim 32 , wherein the stabilizing agent is magnesium stearate.
38 . The dosage form of claim 36 , wherein the stabilizing agent is magnesium stearate.
39 . The method of claim 32 , wherein administering the dosage form provides an emitted dose of at least 1.0 mg of esketamine calculated as a free base.
40 . The method of claim 39 , wherein the fraction of the emitted dose delivered to the lungs is at least 40%.
41 . The method of 32 , wherein the dosage form is self-administered by a patient by inhalation in at least 3 sequences of administrations, said sequences being separated from each other by a break period without any administrations.
42 . The method of claim 41 , wherein each sequence of administrations takes place in a period of about 30 minutes.
43 . The method of claim 41 , wherein the break period is about 15 minutes.
44 . The method of claim 32 , wherein the dosage form comprises lactose monohydrate, magnesium stearate and 4.6 mg of esketamine hydrochloride.
45 . The method of claim 32 , wherein the dosage form comprises lactose monohydrate, magnesium stearate and 4.6 mg of esketamine hydrochloride, wherein the dry powder comprises about 20% by weight esketamine hydrochloride.
46 . The method of claim 32 , wherein the dosage form comprises lactose monohydrate, magnesium stearate and esketamine hydrochloride, wherein the dry powder comprises about 1.6% by weight magnesium stearate.
47 . A method of treating bipolar depression comprising administering to a patient in need thereof a dosage form comprising a dry powder composition formulated for administration to the lungs via oral inhalation, wherein:
the dry powder composition comprises:
a nominal unit dose of 4.6 mg of esketamine hydrochloride, wherein the dry powder comprises about 20% by weight esketamine hydrochloride;
a carbohydrate bulking agent; and
0.2-3% by weight of a stabilizing agent.
48 . The method of claim 47 , wherein the dry powder composition has a particle diameter d50 of 1-10 μM, as measured by laser diffraction.
49 . The method of claim 48 , wherein the dry powder has a particle diameter d90 of 3-35 μm, as measured by laser diffraction.
50 . The dosage form of claim 47 , wherein the carbohydrate bulking agent is lactose monohydrate.
51 . The dosage form of claim 47 , wherein the stabilizing agent is magnesium stearate.
52 . The dosage form of claim 50 , wherein the stabilizing agent is magnesium stearate.
53 . The method of claim 47 , wherein administering the dosage form provides an emitted dose of at least 1.0 mg of esketamine calculated as a free base.
54 . The method of claim 53 , wherein the fraction of the emitted dose delivered to the lungs is at least 40%.
55 . The method of 47 , wherein the dosage form is self-administered by a patient by inhalation in at least 3 sequences of administrations, said sequences being separated from each other by a break period without any administrations.
56 . The method of claim 55 , wherein each sequence of administrations takes place in a period of about 30 minutes.
57 . The method of claim 55 , wherein the break period is about 15 minutes.