# US 11,077,058 B2 · Dry powder compositions with magnesium stearate

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- Number: US 11,077,058 B2
- Document ID: US11077058B2
- Status: Granted
- Kind: B2
- Application number: 16/266,042
- Filed: 2019-02-02
- Published: 2019-11-07
- Granted: 2021-08-03
- Earliest claimed: 2017-09-22
- Assignees: Otitopic Inc.
- Applicants: Otitopic Inc.
- Inventors: Kambiz Yadidi
- Web page: https://patentgrep.com/patent/US11077058B2

## CPC

- A61K 9/145: {with organic compounds}
- A61K 9/0075: {for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles}
- A61K 9/008: {comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]}
- A61K 31/4365: the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
- A61K 31/616: by carboxylic acids, e.g. acetylsalicylic acid
- A61M 15/0021: {Mouthpieces therefor}
- A61M 15/003: {using capsules, e.g. to be perforated or broken-up}
- A61M 15/0035: {Piercing means}
- A61M 15/0041: {with movable piercing or cutting means}
- A61M 15/0086: {Inhalation chambers}
- A61M 16/14: by mixing different fluids, one of them being in a liquid phase
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61M 11/003: {by passing the aerosol trough sieves or filters}
- A61M 15/0023: {retractable}
- A61M 2202/064: Powder
- A61M 2205/582: by tactile feedback
- A61M 2206/16: Rotating swirling helical flow, e.g. by tangential inflows
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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

### Claim 1

A drug delivery system for administering a formulation to a person in need thereof via the respiratory tract, said system comprising:
(a) a dry powder composition 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, and ASA stability maintains about 95% or above after exposure to a condition selected from the group consisting of 15-20° C./35-45% relative humidity (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; and
(b) a dry powder inhaler.

### Claim 2 (depends on 1)

The drug delivery system of claim 1, wherein the dry powder composition further comprises clopidogrel.

### Claim 3 (depends on 1)

The drug delivery system of claim 1, wherein the magnesium 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 thy powder composition.

### Claim 4 (depends on 1)

The drug delivery system of claim 1, substantially free of carrier particles.

### Claim 5 (depends on 1)

The drug delivery system of claim 1, wherein the dry particles have a median mass aerodynamic diameter (MMAD) within a range of about 1 μm to about 5 μm.

### Claim 6 (depends on 5)

The drug delivery system of claim 5, wherein the dry particles have a MMAD within a range of about 2 μm to about 3 μm.

### Claim 7 (depends on 1)

The drug delivery system 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.

### Claim 8 (depends on 1)

The drug delivery system of claim 1, wherein the aerodynamic particle size distribution (APSD) of the dry powder composition as measured by mass deposition at stage 1 to stage 8 of a Next Generation Impactor varies by less than about 10% after the dry powder composition has been stored at 50° C./75% relative humidity for about 30 days when compared with the APSD at time, t, equals zero.

### Claim 9 (depends on 5)

The drug delivery system of claim 5, 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.

### Claim 10 (depends on 5)

The drug delivery system of claim 5, wherein the dry particles have an MMAD size distribution with a DV90 less than about 6 μm, a DV50 less than about 3 μm, and a DV10 less than about 1 μm.

### Claim 11 (depends on 10)

The drug delivery system of claim 10, wherein the DV90, DV50 and/or DV10 vary less than about 10% after the composition is stored at 50° 075% relative humidity for about 15 days.

### Claim 12 (depends on 1)

The drug delivery system of claim 1, wherein the dry powder inhaler comprises:
a housing defining a chamber having one or more air inlets, and one or more air outlets;
the chamber sized to receive a capsule which contains the dry powder composition;
a puncturing mechanism in the housing for creating one or more openings in the capsule;
an optional shield covering at least two but not all of the air inlets, wherein the optional shield comprises one or two or more covering portions, each covering portion covering at least one inlet, whereby the optional shield prevents blockage of at least two air inlets by a user grasping the apparatus; and
an end section associated with the housing, the end section sized and shaped to be received in a user's mouth or nose so that the user may inhale through the end section to aerosolize the dry powder composition and to inhale aerosolized dry powder composition that has exited the capsule.

### Claim 13 (depends on 1)

A method of treating inflammation or treating or reducing a risk of a thrombotic event, comprising administering to a subject in need thereof via the respiratory tract a dry powder composition 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, and ASA stability maintains about 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,
wherein said dry powder composition is administered using a drug delivery system of claim 1.

### Claim 14 (depends on 13)

The method of claim 13, wherein the thrombotic event comprises a myocardial infraction.

### Claim 15 (depends on 13)

The method of claim 13, wherein the thrombotic event comprises a transient ischemic event.

### Claim 16 (depends on 13)

The method of claim 13, wherein the thrombotic event comprises a stroke.

### Claim 17 (depends on 13)

The method of claim 13, wherein the thrombotic event is treated within about 5 minutes of onset of the thrombotic event.