Stable fixed dose pharmaceutical composition comprising mometasone and olopatadine
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.
1. A method of delivering a nasal spray comprising:
nasally delivering an aqueous pharmaceutical composition in the form of a single phase suspension, said composition comprising (a) mometasone furoate in particulate form; (b) olopatadine hydrochloride in dissolved form, and (c) a hydrocolloid in an amount sufficient to inhibit phase separation for at least 24 hours when stored at 25±2° C. and 60±5% relative humidity, wherein
the mometasone furoate and olopatadine hydrochloride are the sole active ingredients in the composition, and
the spray provides a droplet size distribution having a D10 of 5-25 μm, a D50 of 20-50 μm, a D90 of 40-120 μm, and a SPAN of not more than 4.
2. A method of claim 1 , wherein the spray provides a droplet size distribution having a D10 of 10-22 μm, D50 of 35-45 μm, and D90 of 75-115 μm, and SPAN is not more than 3.
3. A method of claim 1 , wherein the composition comprises 25 μg mometasone furoate.
4. A method of claim 1 , wherein the composition comprises 665 μg olopatadine hydrochloride.
5. A method of claim 1 , wherein the composition has a pH between 3.3 to 4.1.
6. A method of delivering a nasal spray comprising:
nasally delivering an aqueous pharmaceutical composition in the form of a single phase suspension, said composition comprising (a) mometasone furoate in particulate form; (b) olopatadine hydrochloride in dissolved form; and (c) a hydrocolloid in an amount sufficient to inhibit phase separation for at least 24 hours when stored at 25±2° C. and 60±5% relative humidity, wherein
the mometasone furoate and olopatadine hydrochloride are the sole active ingredients in the composition, and
the spray provides a droplet size distribution having a D10 of 5-25 μm, a D50 of 20-50 μm, a D90 of 40-120 μm, and a SPAN of not more than 4,
the composition has a viscosity of 10 to 200 cps, and
the pH of the composition is 3.5 to 3.9.
7. A method of claim 1 , wherein the pH of the composition is 3.5 to 3.7.
8. A method of claim 1 , wherein the mean particle size of the mometasone furoate is from 1 μm to 20 μm.
9. A method of claim 1 , wherein the composition has an osmolality of 250 mOsm/kg to 350 mOsm/kg.
10. A method of claim 1 , wherein the composition has a viscosity of 10 to 200 cps.
11. A method of claim 1 , wherein the composition remains in a single phase after at least 3 months of storage at 25±2° C. and 60%±5% relative humidity.
12. A method of claim 6 , wherein the composition results in a spray pattern having a longest axis of 15-75 mm, a shortest axis of 10-65 mm, and an ellipticity of 1-2.
13. A method of claim 1 , wherein the hydrocolloid comprises carboxymethylcellulose sodium.
14. A method of claim 1 , wherein the composition comprises:
0.025% 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;
0.94% w/w dibasic sodium phosphate heptahydrate; and
0.01% w/w polysorbate 80,
wherein the pH is from 3.5 to 3.9.