# US 9,750,754 B2 · Stable fixed dose pharmaceutical composition comprising mometasone and olopatadine

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- Number: US 9,750,754 B2
- Document ID: US9750754B2
- Status: Granted
- Kind: B2
- Application number: 15/183,534
- Filed: 2016-06-15
- Published: 2016-10-06
- Granted: 2017-09-05
- Earliest claimed: 2013-09-13
- Assignees: Glenmark Specialty S.A.
- Applicants: Glenmark Specialty S.A.
- Inventors: Ulhas R. Dhuppad; Ashok Katkurwar; Yashwant Gupta; Rajesh Ankam; Chandrakant Dhatrak
- Web page: https://patentgrep.com/patent/US9750754B2

## CPC

- A61K 31/58: containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048})
- A61K 9/0043: {Nose}
- A61K 9/10: Dispersions; Emulsions
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 31/335: having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 47/38: Cellulose; Derivatives thereof
- 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)

## Abstract

The present invention relates to a stable fixed dose aqueous pharmaceutical composition (e.g., contained in a container) for nasal administration to a human, comprising mometasone or its salt, olopatadine or its salt. The composition may further include a hydrocolloid. The invention also relates to a process for preparing the pharmaceutical composition, and the use of the pharmaceutical composition in the treatment of rhinitis in a subject.

## Claims

### Claim 1

A method of treating allergic rhinitis comprising intranasal administration of a fixed dose aqueous pharmaceutical composition comprising (a) 0.001% w/w to 0.075% w/w mometasone or its salt in particulate form; (b) 0.5% w/w to 0.8% w/w olopatadine or its salt in dissolved form; and (c) a hydrocolloid, wherein the composition is stable for at least 24 hours when stored at about 25° C. and about 60% relative humidity.

### Claim 2 (depends on 1)

The method of claim 1, wherein the mometasone or its salt and the olopatadine or its salt are present in a weight ratio of 1:3 to 1:106.

### Claim 3 (depends on 1)

The method of claim 1, wherein the mometasone salt is mometasone furoate and the olopatadine salt is olopatadine hydrochloride.

### Claim 4 (depends on 1)

The method of claim 1, wherein the mometasone or its salt has a mean particle size in the range of 1 μm to 20 μm.

### Claim 5 (depends on 1)

The method of claim 1, wherein the composition has a pH of 3.3 to 4.1.

### Claim 6 (depends on 1)

The method of claim 1, wherein the composition has a pH of 3.3-4.1, and an osmolality in the range of 200 mOsm/kg to 400 mOsm/kg.

### Claim 7 (depends on 1)

The method of claim 1, wherein the composition has a viscosity in the range of 10 cps to 150 cps.

### Claim 8 (depends on 1)

The method of claim 1, wherein the hydrocolloid is at least 0.1% w/w of the composition.

### Claim 9

A method of treating seasonal allergic rhinitis comprising intranasal administration of a fixed dose aqueous pharmaceutical composition comprising (a) 0.001% w/w to 0.075% w/w mometasone or its salt in particulate form; (b) 0.5% w/w to 0.8% w/w olopatadine or its salt in dissolved form; and (c) a hydrocolloid, wherein the composition is stable for at least 24 hours when stored at about 25° C. and about 60% relative humidity.

### Claim 10 (depends on 9)

The method of claim 9, wherein the mometasone or its salt and the olopatadine or its salt are present in a weight ratio of 1:3 to 1:106.

### Claim 11 (depends on 9)

The method of claim 9, wherein the mometasone salt is mometasone furoate and the olopatadine salt is olopatadine hydrochloride.

### Claim 12 (depends on 9)

The method of claim 9, wherein the mometasone or its salt has a mean particle size in the range of 1 μm to 20 μm.

### Claim 13 (depends on 9)

The method of claim 9, wherein the composition has a pH of 3.3 to 4.1.

### Claim 14 (depends on 9)

The method of claim 9, wherein the composition has a pH of 3.3-4.1, and an osmolality in the range of 200 mOsm/kg to 400 mOsm/kg.

### Claim 15 (depends on 9)

The method of claim 9, wherein the composition has a viscosity in the range of 10 cps to 150 cps.

### Claim 16 (depends on 9)

The method of claim 9, wherein the hydrocolloid is at least 0.1% w/w of the composition.

### Claim 17

A method of treating perennial allergic rhinitis comprising intranasal administration of a fixed dose aqueous pharmaceutical composition comprising (a) 0.001% w/w to 0.075% w/w mometasone or its salt in particulate form; (b) 0.5% w/w to 0.8% w/w olopatadine or its salt in dissolved form; and (c) a hydrocolloid, wherein the composition is stable for at least 24 hours when stored at about 25° C. and 60% relative humidity.

### Claim 18 (depends on 17)

The method of claim 17, wherein the mometasone or its salt and the olopatadine or its salt are present in a weight ratio of 1:3 to 1:106.

### Claim 19 (depends on 17)

The method of claim 17, wherein the mometasone salt is mometasone furoate and the olopatadine salt is olopatadine hydrochloride.

### Claim 20 (depends on 17)

The method of claim 17, wherein the mometasone or its salt has a mean particle size in the range of 1 μm to 20 μm.

### Claim 21 (depends on 17)

The method of claim 17, wherein the composition has a pH of 3.3 to 4.1.

### Claim 22 (depends on 17)

The method of claim 17, wherein the composition has a pH of 3.3-4.1, and an osmolality in the range of 200 mOsm/kg to 400 mOsm/kg.

### Claim 23 (depends on 17)

The method of claim 17, wherein the composition has a viscosity in the range of 10 cps to 150 cps.

### Claim 24 (depends on 17)

The method of claim 17, wherein the hydrocolloid is at least 0.1% w/w of the composition.

### Claim 25

A method of treating allergic rhinitis comprising intranasal administration of a stable fixed dose aqueous pharmaceutical composition comprising 0.025% or 0.05% w/w mometasone furoate monohydrate; 0.665% w/w olopatadine hydrochloride; 0.5% w/w carboxymethyl cellulose sodium; 1.2% w/w of a mixture of microcrystalline cellulose and carboxymethyl cellulose sodium; 0.02% w/w benzalkonium chloride; 0.41% w/w sodium chloride; 0.01% w/w di-sodium edetate; and 0.01% w/w polysorbate 80, wherein the composition has a pH of 3.3 to 4.1.

### Claim 26 (depends on 25)

The method of claim 25, wherein the mometasone furoate monohydrate has a mean particle size in the range of 1 μm to 20 μm.

### Claim 27 (depends on 25)

The method of claim 25, wherein the composition has an osmolality in the range of 200 mOsm/kg to 400 mOsm/kg.

### Claim 28 (depends on 25)

The method of claim 25, wherein the composition has a viscosity in the range of 10 cps to 150 cps.

### Claim 29

A stable fixed dose aqueous pharmaceutical composition for nasal administration to a human, the composition comprises (a) 0.001% w/w to 0.075% w/w mometasone or its salt; (b) 0.5% w/w to 0.8% w/w olopatadine or its salt; (c) one or more cellulose derivatives, and (d) one or more additional excipients.

### Claim 30 (depends on 29)

The pharmaceutical composition of claim 29, wherein the one or more cellulose derivatives suppress phase separation.

### Claim 31 (depends on 29)

The pharmaceutical composition of claim 29, wherein the one or more cellulose derivatives suppress phase separation for at least 24 hours when stored at about 25° C. and about 60% relative humidity.

### Claim 32 (depends on 29)

The pharmaceutical composition of claim 29, wherein the cellulose derivatives include carboxymethyl cellulose sodium.

### Claim 33 (depends on 29)

The pharmaceutical composition of claim 29, wherein the mometasone or its salt and the olopatadine or its salt are present in a weight ratio of 1:3 to 1:106.

### Claim 34 (depends on 29)

The pharmaceutical composition of claim 29, wherein the mometasone salt is mometasone furoate and the olopatadine salt is olopatadine hydrochloride.

### Claim 35 (depends on 29)

The pharmaceutical composition of claim 29, wherein the mometasone or its salt has a mean particle size in the range of 1 μm to 20 μm.

### Claim 36 (depends on 29)

The pharmaceutical composition of claim 29, wherein the composition has a pH of 3.3 to 4.1.

### Claim 37 (depends on 29)

The pharmaceutical composition of claim 29, wherein the composition has a pH of 3.3-4.1, and an osmolality in the range of 200 mOsm/kg to 400 mOsm/kg.

### Claim 38 (depends on 29)

The pharmaceutical composition of claim 29, wherein the composition has a viscosity in the range of 10 cps to 150 cps.

### Claim 39

An aqueous pharmaceutical composition for nasal administration to a human, the composition comprises (a) 0.001% w/w to 0.075% w/w mometasone or its salt; (b) 0.5% w/w to 0.8% w/w olopatadine hydrochloride, wherein the composition is substantially free of crystals of olopatadine hydrochloride.

### Claim 40 (depends on 39)

The pharmaceutical composition of claim 39, wherein the mometasone or its salt and the olopatadine hydrochloride are present in a weight ratio of 1:3 to 1:106.

### Claim 41 (depends on 39)

The pharmaceutical composition of claim 39, wherein the mometasone salt is mometasone furoate.

### Claim 42 (depends on 39)

The pharmaceutical composition of claim 39, wherein the mometasone or its salt has a mean particle size in the range of 1 μm to 20 μm.

### Claim 43 (depends on 39)

The pharmaceutical composition of claim 39, wherein the composition has a pH of 3.3 to 4.1.

### Claim 44 (depends on 39)

The pharmaceutical composition of claim 39, wherein the composition has a pH of 3.3-4.1, and an osmolality in the range of 200 mOsm/kg to 400 mOsm/kg.

### Claim 45 (depends on 39)

The pharmaceutical composition of claim 39, wherein the composition has a viscosity in the range of 10 cps to 150 cps.

### Claim 46 (depends on 39)

The pharmaceutical composition of claim 39, wherein the composition contains less than 2% of crystalline olopatadine hydrochloride, based upon 100% total weight of olopatadine hydrochloride in the composition.

### Claim 47

A stable fixed dose aqueous pharmaceutical composition for nasal administration to a human, the composition comprises (a) 0.001% w/w to 0.075% w/w mometasone or its salt; (b) 0.5% w/w to 0.8% w/w olopatadine or its salt; (c) 0.1% w/w to 3% w/w of sodium carboxymethyl cellulose, and (d) one or more additional excipients, wherein the composition has a pH of 3.3 to 4.1.

### Claim 48 (depends on 47)

The pharmaceutical composition of claim 47, wherein the carboxymethyl cellulose is present in the range of 0.15% w/w to 0.75% w/w.

### Claim 49 (depends on 47)

The pharmaceutical composition of claim 47, wherein the composition has a viscosity in the range of 10 cps to 150 cps.

### Claim 50 (depends on 47)

The pharmaceutical composition of claim 47, wherein the sodium carboxymethyl cellulose suppresses phase separation for at least 24 hours when stored at 25±2° C. and 60%±5% relative humidity.

### Claim 51 (depends on 47)

The pharmaceutical composition of claim 47, wherein the one or more additional excipients are selected from chelating agents, preservatives, buffers, surfactants, isotonicity agents, taste masking agents, antioxidants, humectants, pH adjusting agents, and mixtures thereof.