# US 10,946,029 B2 · Dry powder formulation comprising a corticosteroid and a beta-adrenergic for administration by inhalation

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- Number: US 10,946,029 B2
- Document ID: US10946029B2
- Status: Granted
- Kind: B2
- Application number: 16/015,666
- Filed: 2018-06-22
- Published: 2018-10-18
- Granted: 2021-03-16
- Earliest claimed: 2012-01-25
- Assignees: Chiesi Farmaceutici S.p.A.
- Applicants: CHIESI FARMACEUTICI S.p.A.
- Inventors: Elisa Monari; Anna Maria Cantarelli; Daniela Cocconi; Irene Pasquali
- Web page: https://patentgrep.com/patent/US10946029B2

## CPC

- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 9/0075: {for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles}
- A61K 9/14: Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)}
- A61K 9/145: {with organic compounds}
- A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
- A61K 31/20: having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61M 15/003: {using capsules, e.g. to be perforated or broken-up}
- A61M 15/009: {using medicine packages with incorporated spraying means, e.g. aerosol cans (pocket atomiser of the injector type A61M11/08)}
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61M 2202/064: Powder
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- 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

Compositions comprising a corticosteroid and a beta-adrenergic are useful for treating inflammatory or obstructive airways diseases.

## Claims

### Claim 1

A dry powder formulation, comprising:
a) a fraction of fine particles having a mass median diameter lower than 10 micron comprising particles of alpha-lactose monohydrate;
b) a fraction of coarse particles constituted of alpha-lactose monohydrate having a mass diameter comprised between 60 and 500 micron and the ratio between the fine particles and the coarse particles being comprised between 1:99 and 30:70 percent by weight; and
c) formoterol fumarate dihydrate in combination with beclometasone dipropionate (BDP) as active ingredient both in form of micronized particles; wherein i) no more than 10% of said BDP particles have a volume diameter lower than 0.6 micron, ii) no more than 50% of said particles have a volume diameter comprised between 1.5 micron and 2.0 micron; and iii) at least 90% of said particles have a volume diameter lower than 4.7 micron,
wherein said formulation is contained in a dry powder inhaler and
wherein said dry powder inhaler delivers formoterol fumarate dihydrate in a therapeutical dose of 6 or 12 μg, and BDP in a therapeutical dose of 100 or 200 μg per actuation of the inhaler; and whereby said formulation is therapeutically equivalent a formulation for pressurized metered dose inhalers (pMDIs) comprising the same amounts of BDP and formoterol fumarate dihydrate dissolved in a mixture of ethanol and HFA134a propellant.

### Claim 2 (depends on 1)

The formulation, according to claim 1 wherein the d(v,0.1) of the BDP particles is comprised between 0.8 and 1.0 micron, the d(v0.5) is comprised between 1.5 and 2.0 micron, the d(v,0.9) is comprised between 2.5 and 4.7 micron and the particle size span, defined as [d(v,0.9)−d(v,0.1)]/d(v,0.5) is comprised between 1.2 and 2.2.

### Claim 3 (depends on 2)

The formulation according to claim 2, wherein the BDP particles have a particle size span comprised between 1.3 and 2.1.

### Claim 4 (depends on 1)

The formulation according to claim 1, wherein the BDP particles are further characterized by a specific surface area comprised between 5.5 and 7.0 m2/g.

### Claim 5 (depends on 4)

The formulation according to claim 4, wherein the specific surface area of the BDP particles is comprised between 5.9 and 6.8 m2/g.

### Claim 6 (depends on 1)

The formulation according to claim 1, wherein the ratio of fine particles a) and coarse particles b) is comprised between 2:98 and 20:80 percent by weight.

### Claim 7 (depends on 6)

The formulation according to claim 6, wherein the ratio of fine particles a) and coarse particles b) is 10:90 percent by weight.

### Claim 8 (depends on 1)

The formulation according to claim 1, wherein the coarse particles b) have a mass median diameter is comprised between 150 micron and 500 microns.

### Claim 9 (depends on 8)

The formulation according to claim 8, wherein the mass diameter is comprised between 212 and 355 micron.

### Claim 10 (depends on 1)

The formulation according to claim 1 constituted of:
a) a fraction of fine particles made of a mixture composed of 98 percent by weight of particles of alpha-lactose monohydrate and 2 percent by weight of magnesium stearate, said mixture having a mass median diameter equal to or lower than 6 micron;
b) a fraction of coarse particles constituted of alpha-lactose monohydrate having a mass diameter comprised between 212 and 355 micron and the ratio between the fine particles and the coarse particles being 10:90 percent by weight; and
c) formoterol fumarate dihydrate in combination with beclometasone dipropionate (BDP) as active ingredient both in form of micronized particles; wherein i) no more than 10% of said BDP particles have a volume diameter lower than 0.7 micron, ii) no more than 50% of said particles have a volume diameter comprised between 1.6 micron and 1.9 micron; and iii) at least 90% of said particles have a volume diameter lower than 4.0 micron.

### Claim 11 (depends on 1)

The formulation according to claim 1 for treatment of an inflammatory or obstructive airways disease.

### Claim 12 (depends on 11)

The formulation according to claim 11, wherein the disease is asthma or chronic obstructive pulmonary disease (COPD).