COMPOSITIONS AND METHODS FOR DEEP DERMAL DRUG DELIVERY
Pharmaceutical compositions for the topical administration of a drug to the pilosebaceous unit and methods for administering the same. As disclosed herein, the inventors of the present invention have made the surprising discovery that pharmaceutical compositions comprising small particles of an active pharmaceutical ingredient and a silicone, such as dimethicone or cyclomethicone, can be administered to the pilosebaceous unit. The pharmaceutical composition can comprise SHR0302 or spironolactone as an active pharmaceutical ingredient.
1 . A pharmaceutical composition comprising:
a therapeutically effective amount of SHR0302 or a pharmaceutically acceptable salt thereof, wherein a primary particle size distribution of the SHR0302 is characterized by a D90 value of less than about 20 μm; and
a silicone selected from the group consisting of dimethicone and cyclomethicone.
2 . The pharmaceutical composition of claim 1 , wherein the composition is a suspension.
3 . The pharmaceutical composition of claim 1 , wherein the composition comprises about 0.10% w/w to about 5% w/w of SHR0302 or a salt thereof.
4 . The pharmaceutical composition of claim 1 , wherein a primary particle size distribution of the SHR0302 is characterized by a D90 value of less than about 10 μm.
5 . The pharmaceutical composition of claim 1 , wherein a primary particle size distribution of the SHR0302 is characterized by a D90 value of less than about 5 μm.
6 . The pharmaceutical composition of claim 1 , wherein a primary particle size distribution of the SHR0302 is characterized by a D50 value of less than about 1.0 μm.
7 . The pharmaceutical composition of claim 1 , wherein a primary particle size distribution of the SHR0302 is characterized by a D10 value of less than about 0.50 μm.
8 . A method of treating alopecia areata in a subject in need thereof comprising:
topically administering to the subject a pharmaceutical composition comprising: (a) a therapeutically effective amount of SHR0302 or a pharmaceutically acceptable salt thereof, wherein a primary particle size distribution of the SHR0302 is characterized by a D90 value of less than about 20 μm; and (b) a silicone selected from the group consisting of dimethicone and cyclomethicone.
9 . The method of claim 8 , wherein the SHR0302 is delivered to the pilosebaceous unit.
10 . The method of claim 8 , wherein the SHR0302 achieves dermal penetration of at least 1 mm in the subject.
11 . The method of claim 8 , wherein the pharmaceutical composition is a suspension.
12 . The method of claim 8 , wherein the composition comprises about 0.10% w/w to about 5% w/w of SHR0302 or a salt thereof.
13 . The method of claim 8 , wherein a primary particle size distribution of the SHR0302 is characterized by a D90 value of less than about 10 μm.
14 . The method of claim 8 , wherein a primary particle size distribution of the SHR0302 is characterized by a D90 value of less than about 5 μm.
15 . The method of claim 8 , wherein a primary particle size distribution of the SHR0302 is characterized by a D50 value of less than about 1.0 μm.
16 . The method of claim 8 , wherein a primary particle size distribution of the SHR0302 is characterized by a D10 value of less than about 0.50 μm.
17 . A pharmaceutical composition comprising:
a therapeutically effective amount of an active pharmaceutical ingredient, wherein a primary particle size distribution of the active pharmaceutical ingredient is characterized by a D90 value of less than about 20 μm; and
a silicone selected from the group consisting of dimethicone and cyclomethicone.
18 . The pharmaceutical composition of claim 17 , wherein the composition comprises about 0.10% w/w to about 5% w/w of the active pharmaceutical ingredient.
19 . The pharmaceutical composition of claim 17 , wherein a primary particle size distribution of the active pharmaceutical ingredient is characterized by a D90 value of less than about 10 μm.
20 . The pharmaceutical composition of claim 17 , wherein a primary particle size distribution of the active pharmaceutical ingredient is characterized by a D90 value of less than about 5 μm.
21 . The pharmaceutical composition of claim 17 , wherein the active pharmaceutical ingredient is delivered to the pilosebaceous unit.
22 . The pharmaceutical composition of claim 17 , wherein the active pharmaceutical ingredient is capable of achieving dermal penetration of at least 1 mm in the subject.