DRY POWDER FORMULATIONS FOR INHALATION
A respirable dry powder can include acetylsalicylic acid in particles having a mass median aerodynamic diameter (MMAD) within a range of about 0.5 μm to about 10 μm. The respirable dry powder may contain a pharmaceutically acceptable excipient, such as an amino acid (e.g., Leucine), in an amount ranging from about 0.1% (w/w) to about 40% (w/w) of the particles.
1 . A dry powder composition for delivery by inhalation, said dry powder composition comprising dry particles that comprise acetylsalicylic acid or a pharmaceutically acceptable salt thereof, wherein the dry particles have a mass median aerodynamic diameter (MMAD) within a range of about 0.5 μm to about 10 μm, wherein the composition further comprises leucine in an amount ranging from about 5% (w/w) to about 15% (w/w) of the composition.
2 . The dry powder composition of claim 1 , wherein the leucineis in an amount ranging from about 6% (w/w) to about 15% (w/w) of the composition.
3 . The dry powder composition of claim 1 , wherein the leucineis in an amount ranging from about 6% (w/w) to about 14% (w/w) of the composition.
4 . The dry powder composition of claim 1 , wherein the leucineis in an amount ranging from about 7% (w/w) to about 13% (w/w) of the composition.
5 . The dry powder composition of claim 1 , wherein the leucineis in an amount of about 5% (w/w) of the composition.
6 . The dry powder composition of claim 1 , wherein the leucineis in an amount of about 15% (w/w) of the composition.
7 . The dry powder composition of claim 1 , wherein the acetylsalicylic acid or pharmaceutically acceptable salt thereof is in an amount greater than 40% (w/w) of the composition.
8 . The dry powder composition of claim 1 , wherein acetylsalicylic acid or a pharmaceutically acceptable salt thereof is in an amount greater than 50% (w/w) of the composition.
9 . The dry powder composition of claim 1 , wherein the MMAD ranges from about 2.0 to about 5.0 μm.
10 . The dry powder composition of claim 1 , wherein the MMAD ranges from about 3.0 to about 4.0 μm.
11 . The dry powder composition of claim 1 , wherein the dry powder composition maintains a purity of acetylsalicylic acid or the pharmaceutically acceptable salt thereof of about 98.5% or higher, about 99% or higher, or about 99.5% of higher after storage at 4° C., 25° C./60% RH, 30° C./65% RH, or 40° C./75% RH for one or two months.
12 . The dry powder composition of claim 1 , wherein the dry powder composition maintains a purity of acetylsalicylic acid or the pharmaceutically acceptable salt thereof of about 95.0% or higher, about 96.5% or higher, about 97.0% of higher, about 97.5% or higher, about 98% or higher, about 98.5% or higher, or about 98.8% or higher, after storage at 4° C., 25° C./60% RH, 30° C./65% RH, or 40° C./75% RH for six months.
13 . The dry powder composition of claim 1 , wherein the dry powder composition comprises sialic acid (SA) in an amount of about 5.0% or lower, about 4.0% or lower, about 3.0% or lower, about 2.0% or lower, about 1.0% or lower, about 0.05% or lower, after storage at 4° C., 25° C./60% RH, 30° C./65% RH, or 40° C./75% RH for one month, two months, or six months.
14 . The dry powder composition of claim 1 , wherein the morphology of the dry particles remains consistent after storage at 4° C., 25° C./60% RH, 30° C./65% RH, or 40° C./75% RH for one month, two months, or six months.
15 . The dry powder composition of claim 15 , wherein the particles comprise crystals.
16 . The dry powder composition of claim 1 , wherein a particle size distribution of the dry particles remains consistent after storage at 4° C., 25° C./60% RH, 30° C./65% RH, or 40° C./75% RH for one month, two months, or six months.
17 . The dry powder composition of claim 16 , wherein one or more parameters selected from the group consisting of MMAD, D (v 0.1), D (v0.5), D(v0.9), D[3,2], D[4,3] and span of the dry particles have a change of about 10% or lower, about 5% or lower, or about 2.5% or lower, after storage at 4° C., 25° C./60% RH, 30° C./65% RH, or 40° C./75% RH for one month, two months, or six months.
18 . A drug delivery system effective to reduce the risk of a thrombotic event or treat thrombosis, wherein the system comprises the dry powder composition of claim 1 , and wherein acetylsalicylic acid is present at a dose ranging from about 5 mg to about 40 mg.
19 . The drug delivery system of claim 18 , further comprising clopidogrel.
20 . The drug delivery system of claim 18 , further comprising another excipient.