Dry powder formulations for inhalation

• US 9,993,488 B2
• Filed: 02/20/2015
• Issued: 06/12/2018
• Est. Priority Date: 02/20/2014
• Status: Active Grant

• Current Assignee: Vectura, Inc. (Vectura Group Ltd.)
• Original Assignee: Otitopic Inc.
• Inventors: Yadidi, Kambiz
• Primary Examiner(s): LOVE, TREVOR M
• Application Number:
  US14/628,148
• Publication Number:
  US 20160022705A1
• Time in Patent Office: 1,208 Days
• 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 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

A respirable dry powder including 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 a phospholipid, in an amount ranging from about 0.1% (w/w) to about 10% (w/w) of the particles.

Claims

1. A dry powder composition for delivery to a subjects lungs by a dry powder inhaler, the composition comprising dry particles that comprise acetylsalicylic acid, or a pharmaceutically acceptable salt thereof;

wherein said dry particles have a mass median aerodynamic diameter (MMAD) within a range of 0.5 μ

m to 5 μ

m, wherein said dry particles have a DV50 in a range of 3-6.7 μ

m and a DV10 in a range of 0.9-3.3 μ

m wherein the dry particles further comprise a pharmaceutically acceptable excipient, wherein the pharmaceutically acceptable excipient comprises one or more phospholipids in an amount ranging from 0.1% (w/w) to 10% (w/w) of the composition, wherein acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, is in an amount of 50% (w/w) or more of the composition, and wherein the dry powder composition is free of carrier particles.

2. The dry powder composition of claim 1, wherein the dry particles have an MMAD size distribution such that said particles exhibit a DV90 less than 20 μ

m a DV 50 less than 4 μ

m, and a DV10 less than 2 μ

m.

3. The dry powder composition of claim 1, wherein the composition comprises particles have an MMAD size distribution such that said particles exhibit a DV90 less than 10 μ

m, a DV50 less than 4 μ

m, and a DV10 less than 1 μ

m.

4. The dry powder composition of claim 1, wherein the particles have an MMAD size distribution such that said particles exhibit a DV90 less than 6 μ

m.

5. The dry powder composition of claim 1, wherein the phospholipid is dipalmitoyl phosphotidylcholine (DPPC), distearoyl phosphotidylcholine (DSPC), lecithin, or a combination thereof.

6. The dry powder composition of claim 1, wherein the phospholipid is in an amount ranging from 1% to 5% w/w of the composition.

7. The dry powder composition of claim 1, further comprising clopidogrel.

8. 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, and wherein the acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, is present at a dose of 40 mg or less.

9. A method of treating thrombosis or reducing the risk of a thromboembolic event, comprising administering to a subject in need thereof the dry powder composition of claim 1 by a dry powder inhaler, wherein the dose of the acetylsalicylic acid administered to said subject is 40 mg or less.

10. The method of claim 9, wherein the dry powder composition comprises acetylsalicylic acid and clopidogrel, and wherein the dose of the clopidogrel administered to the subject is 75 mg or less.

11. The dry powder composition of claim 1, wherein acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, is in an amount of 60% (w/w) or more of the composition.

12. The dry powder composition of claim 1, wherein acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, is in an amount of 70% (w/w) or more of the composition.

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

14. The dry powder composition of claim 1, wherein acetylsalicylic acid, or a pharmaceutically acceptable salt thereof, is in an amount of 90% (w/w) or more of the composition.