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. An aqueous pharmaceutical composition for nasal administration to a human in the form of a suspension comprising mometasone furoate, olopatadine hydrochloride, and a hydrocolloid in an amount sufficient for the suspension to remain in a single phase after 3 months of storage at 25±2° C. and 60%±5% relative humidity.
2. The aqueous pharmaceutical composition of claim 1 , wherein the composition has a pH of between 3.3 and 4.1.
3. The aqueous pharmaceutical composition of claim 1 , wherein the composition has an osmolality of 200 mOsm/kg to 400 mOsm/kg.
4. The aqueous pharmaceutical composition of claim 1 , wherein the composition has an osmolality of 250 mOsm/kg to 350 mOsm/kg.
5. The aqueous pharmaceutical composition of claim 1 , wherein the composition has a viscosity of 20 to 150 cps.
6. An aqueous pharmaceutical composition for nasal administration to a human in the form of a suspension comprising 0.025% w/w mometasone furoate, 0.665% w/w olopatadine hydrochloride, and a hydrocolloid in an amount sufficient for the suspension to remain in a single phase after 3 months of storage at 25±2° C. and 60%±5% relative humidity.
7. The aqueous pharmaceutical composition of claim 6 , wherein the pharmaceutical composition further comprising a hydrocolloid.
8. The aqueous pharmaceutical composition of claim 7 , wherein the hydrocolloid comprises carboxymethylcellulose sodium.
9. The aqueous pharmaceutical composition of claim 6 , wherein the pharmaceutical composition has a viscosity of 20 cps to 150 cps.
10. The aqueous pharmaceutical composition of claim 6 , wherein the mometasone furoate has a mean particle size in the range of 1 μm to 20 μm.
11. The aqueous pharmaceutical composition of claim 6 , wherein the composition has a pH of 3.3 to 4.1.
12. The aqueous pharmaceutical composition of claim 6 , wherein the composition has a pH of 3.5 to 3.9.
13. The aqueous pharmaceutical composition of claim 6 , wherein the composition has an osmolality in the range of 250 mOsm/kg to 350 mOsm/kg.
14. The aqueous pharmaceutical composition of claim 6 , wherein the composition is a single phase aqueous suspension comprising:
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 sodium phosphate heptahydrate; and
0.01% w/w polysorbate 80,
wherein the composition has a pH of 3.3 to 4.1.
15. The aqueous pharmaceutical composition of claim 6 , wherein the composition is substantially free of crystals of olopatadine hydrochloride after 3 months of storage at 25±2° C. and 60%±5% relative humidity.
16. The aqueous composition of claim 15 , wherein the composition is substantially free of crystals of olopatadine hydrochloride after 6 months of storage at 25±2° C. and 60%±5% relative humidity.
17. The aqueous composition of claim 15 , wherein the composition contains less than 0.2% by weight of crystalline olopatadine hydrochloride, based on the 100% total weight of olopatadine hydrochloride in the composition, after 3 months of storage at 25±2° C. and 60%±5% relative humidity.
18. The aqueous composition of claim 17 , wherein the composition contains less than 0.1% by weight of crystalline olopatadine hydrochloride, based on the 100% total weight of olopatadine hydrochloride in the composition, after 3 months of storage at 25±2° C. and 60%±5% relative humidity.
19. The aqueous composition of claim 16 , wherein the composition contains less than 0.2% by weight of crystalline olopatadine hydrochloride, based on the 100% total weight of olopatadine hydrochloride in the composition, after 6 months of storage at 25±2° C. and 60%±5% relative humidity.
20. The aqueous composition of claim 16 , wherein the composition contains less than 0.1% by weight of crystalline olopatadine hydrochloride, based on the 100% total weight of olopatadine hydrochloride in the composition, after 6 months of storage at 25±2° C. and 60%±5% RH.
21. The aqueous composition of claim 15 , wherein the composition has a pH of 3.3 to 4.1.
22. The aqueous composition of claim 15 , wherein the composition has a pH of 3.5 to 3.9.
23. The aqueous composition of claim 15 , wherein the composition further comprises a hydrocolloid.
24. The aqueous composition of claim 23 , wherein the hydrocolloid comprises carboxymethylcellulose sodium.
25. The aqueous composition of claim 15 , wherein the composition has a viscosity of 20 cps to 150 cps.
26. The aqueous composition of claim 15 , wherein the composition has an osmolality in the range of 250 mOsm/kg to 350 mOsm/kg.
27. The aqueous composition of claim 15 , wherein the composition comprises 0.025% by weight of mometasone furoate monohydrate and 0.665% by weight of olopatadine hydrochloride.
28. The aqueous pharmaceutical composition of claim 1 , wherein the composition has a pH of between 3.5 and 3.9.
29. The aqueous pharmaceutical composition of claim 1 , wherein the composition further comprises a buffer.
30. The aqueous pharmaceutical composition of claim 29 , wherein the buffer comprises dibasic sodium phosphate.
31. The aqueous pharmaceutical composition of claim 15 , wherein the composition further comprises a buffer.
32. The aqueous pharmaceutical composition of claim 31 , wherein the buffer comprises dibasic sodium phosphate.