Dry powder formulation for pulmonary delivery and methods of use
Pharmaceutical compositions are provided for pulmonary administration of a JAK inhibitor, and, for example, dry powder formulations that include a JAK inhibitor and an agglomerated lactose carrier. Methods of making and using the pharmaceutical composition, as well as kits and dosage forms are also provided.
1 . A pharmaceutical composition for pulmonary administration comprising: a dry powder formulation comprising from about 10 weight % (wt %) of a JAK inhibitor or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable agglomerated lactose carrier, the carrier having a d50 from about 100 μm to about 350 μm and a d90 from about 250 μm to about 450 μm.
2 . The pharmaceutical composition according to claim 1 , wherein the JAK inhibitor or a pharmaceutically acceptable salt thereof, comprises from about 10 wt % to about 50% wt % of the dry powder formulation.
3 . The pharmaceutical composition according to claim 1 , wherein the JAK inhibitor or a pharmaceutically acceptable salt thereof, is micronized.
4 . The pharmaceutical composition according to claim 3 , wherein the micronized JAK inhibitor or a pharmaceutically acceptable salt thereof, has a d90 from about 1 μm to about 10 μm.
5 . The pharmaceutical composition according to claim 3 , wherein the micronized JAK inhibitor or a pharmaceutically acceptable salt thereof, has a d90 of less than about 5 μm.
6 . The pharmaceutical composition according to claim 1 , comprising a fine particle fraction from about 10% to about 70%.
7 . The pharmaceutical composition according to claim 1 , comprising a sieved agglomerated lactose carrier, wherein the sieved lactose carrier comprises α-monohydrate lactose with a d50 from about 130 μm to about 310 μm, or from about 170 μm to about 270 μm.
8 . The pharmaceutical composition according to claim 7 , wherein the sieved lactose carrier comprises α-monohydrate lactose with a d90 from about 290 μm to about 400 μm.
9 . The pharmaceutical composition according to claim 7 , wherein the crystallized agglomerated lactose carrier is not sieved.
10 . The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is stable at 30° C. at 75% relative humidity for at least 3 months.
11 . A unit dosage of the pharmaceutical composition according to claim 1 , comprising from about 1 mg to about 5 mg JAK inhibitor or a pharmaceutically acceptable salt thereof.
12 . A dry powder inhaler comprising the pharmaceutical composition according to claim 1 .
13 . The dry powder inhaler of claim 12 , wherein the dry powder inhaler comprises a multi-dose inhaler.
14 . A method of treating a JAK-related disease in a subject comprising pulmonary administration of a therapeutically effective amount of a pharmaceutical composition according to claim 1 .
15 . The method according to claim 14 , wherein the JAK-related disease is selected from inflammation, allergies, asthma, transplant rejection, T-cell mediated autoimmune diseases, Type II inflammatory diseases, diseases of the central nervous system, pulmonary diseases, delayed Type IV hypersensitivity reactions, and ocular disorders.