Dry powder compositions with magnesium stearate

• US 10,195,147 B1
• Filed: 09/26/2017
• Issued: 02/05/2019
• Est. Priority Date: 09/22/2017
• Status: Active Grant

• Current Assignee: Vectura, Inc. (Vectura Group Ltd.)
• Original Assignee: Otitopic Inc. (Philip Morris Limited)
• Inventors: Yadidi, Kambiz
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Singh, Randeep
• Application Number:
  US15/716,492
• Time in Patent Office: 497 Days
• Field of Search: None
• CPC Class Codes: A61K 31/4365 the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
• CPC Class Codes: A61K 31/616 by carboxylic acids, e.g. acetylsalicylic acid
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61M 11/003 by passing the aerosol trough sieves or filters
• CPC Class Codes: A61M 15/0021 Mouthpieces therefor
• CPC Class Codes: A61M 15/0023 retractable
• CPC Class Codes: A61M 15/003 using capsules, e.g. to be perforated or broken-up
• CPC Class Codes: A61M 15/0035 Piercing means
• CPC Class Codes: A61M 15/0041 with movable piercing or cutting means
• CPC Class Codes: A61M 15/0086 Inhalation chambers
• CPC Class Codes: A61M 16/14 by mixing different fluids, one of them being in a liquid phase
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: A61M 2205/582 by tactile feedback
• CPC Class Codes: A61M 2206/16 Rotating swirling helical flow, e.g. by tangential inflows
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

A stable dry powder composition for inhalation includes acetylsalicylic acid in particles having a mass median aerodynamic diameter (MMAD) in a range of about 1 μm to about 5 μm. The dry powder composition may contain a pharmaceutically acceptable excipient, such as a stearate, in an amount ranging from about 0.04% (w/w) to about 0.06% (w/w), or from about 0.4% (w/w) to about 0.6% (w/w), of the composition.

Claims

1. A dry powder composition for delivery to a subject by inhalation, comprising dry particles comprising acetylsalicylic acid (ASA), or a pharmaceutically acceptable salt thereof, co-micronized with magnesium stearate, wherein the magnesium stearate is in an amount of about 0.05% (w/w) to about 0.5% (w/w) of the dry powder composition, wherein ASA stability maintains 95% or above after exposure to a condition selected from the group consisting of 15-20°

C./35-45% RH, 20°

C./40% RH, 30°

C./60% RH, 40°

C./75% RH, and 50°

C./75% RH, for two weeks, four weeks, 30 days, a month, six weeks, eight weeks, or 12 months.

2. The dry powder composition of claim 1, wherein the stearate is in an amount ranging from about 0.04% (w/w) to about 0.06% (w/w), or from about 0.4% (w/w) to about 0.6% (w/w), of the dry powder composition, wherein acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, is in an amount of about 50% (w/w) or more of the dry powder composition.

3. The dry powder composition of claim 1, substantially free of carrier particles.

4. The dry powder composition of claim 1, wherein the dry particles have a MMAD within a range of about 1 μ

m to about 5 μ

m.

5. The dry powder composition of claim 4, wherein the dry particles have a MMAD within a range of about 2 μ

m to about 3 μ

m.

6. The dry powder composition of claim 1, wherein acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, is in an amount of about 80% (w/w) or more of the dry powder composition.

7. The dry powder composition of claim 1, wherein the APSD of the dry powder composition as measured by mass deposition at stage 1 to stage 8 of a NGI varies by less than about 10% after the dry powder composition have been stored at 50°

C./75% relative humidity for about 30 days when compared with the APSD at time, t, equals zero.

8. The dry powder composition of claim 4, wherein the MMAD of the dry particles varies by less than about 10% after the dry powder composition have been stored at 50°

C./75% relative humidity for about 5 days when compared with the MMAD at time, t, equals zero.

9. The dry powder composition of claim 4, wherein the dry particles have an MMAD size distribution with a DV90 less than about 6 μ

m, a DV50 less than about 3 μ

m, and a DV10 less than about 1 μ

m.

10. The dry powder composition of claim 9, wherein the DV90, DV50 and/or DV10 vary less than about 10% after the composition is stored at 50°

C./75% relative humidity for about 15 days.

11. A drug delivery system effective to reduce the risk of a thromboembolic event or treat thrombosis, wherein the system comprises the dry powder composition of claim 1.

12. The drug delivery system of claim 11, further comprising clopidogrel.

13. A drug delivery system comprising a dry powder inhaler and the dry powder composition of claim 1.

14. A method of treating or reducing a risk of a thromboembolic event, comprising administering to a subject in need thereof the dry powder composition of claim 1.

15. The method of claim 14, wherein the thromboembolic event comprises a myocardial infraction.

16. The method of claim 14, wherein the thromboembolic event comprises a transient ischemic event.