Claims for Patent: 4,782,047

Summary for Patent: 4,782,047

Title:	Aqueous steroid formulations for nasal administration
Abstract:	A non-stinging aqueous anti-inflammatory steroid formulation suitable for intranasal administration comprises: an anti-inflammatory steroid in an amount between about 0.01% and about 0.05% (w/v); propylene glycol in an amount between about 2% and about 10% (w/v); PEG 400 in an amount between about 10% and about 25% (w/v); polysorbate 20 in an amount between about 1% and about 4% (w/v); an effective amount of a preservative; an effective amount of a stabilizer; an effective amount of an antioxidant; water; and pH buffering agent sufficient to adjust the pH of the resulting solution to between about 3.5 and about 7.
Inventor(s):	Benjamin; Eric (Sunnyvale, CA), Anik; Shabbir (Mountain View, CA), Lin; Ya-Yun T. (Cupertino, CA)
Assignee:	Syntex Pharmaceuticals International Ltd. (Hamilton, BM)
Application Number:	06/866,171
Patent Claims:	1. A stable, effectively preservable, substantially non-stinging aqueous anti-inflammatory steroid formulation suitable for intranasal administration, which formulation comprises: an anti-inflammatory steroid in an amount between about 0.01% and about 0.05% (w/v); propylene glycol in an amount between about 2% and about 10% (w/v); PEG 400 in an amount between about 10% and about 25% (w/v); polysorbate 20 in an amount between about 1% and about 4% (w/v); an effective amount of preservative; an effective amount of antioxidant; an effective amount of stabilizer; water; and pH buffering agent sufficient to adjust the pH of the resulting solution to between about 3.5 and about 7. 2. The formulation of claim 1 which comprises: 3. The formulation of claim 1 which comprises: preservative in an amount between about 0.02% and about 0.08% (w/v); antioxidant in an amount between about 0.001% and about 0.05% (w/v); and stabilizer in an amount between about 0.005% and about 0.05% (w/v). 4. The formulation of claim 3 wherein said anti-inflammatory steroid is flunisolide in an amount of about 0.025% (w/v). 5. The formulation of claim 4 wherein: said preservative is benzalkonium chloride; said stabilizer is disodium EDTA; and said antioxidant is BHT. 6. The formulation of claim 5 which further comprises sorbitol in an amount between about 0.001% and about 5% (w/v). 7. The formulation of claim 6 wherein said pH buffering agent comprises: citric acid in an amount between about 0.001% and about 0.05% (w/v); and sodium citrate dihydrate in an amount between about 0.001% and about 0.05% (w/v). 8. A stable, effectively preservable, substantially non-stinging aqueous anti-inflammatory steroid formulation suitable for intranasal administration, which formulation comprises: flunisolide hemihydrate in an amount of about 0.025% (w/v); propylene glycol in an amount of about 5% (w/v); PEG 400 in an amount of about 20% (w/v); polysorbate 20 in an amount of about 2.50% (w/v); benzalkonium chloride in an amount of about 0.035% (w/v); disodium EDTA in an amount of about 0.01% (w/v); BHT in an amount of about 0.01% (w/v); citric acid in an amount of about 0.005% (w/v); sodium citrate dihydrate in an amount of about 0.00765% (w/v); sorbitol in an amount of about 2.00% (w/v); and water, wherein the pH of the resulting solution is adjusted to about 5.2. 9. A method of treating inflammation of the nasal mucosa without inducing stinging, which method comprises intranasally administering to a subject in need thereof a substantially non-stinging aqueous anti-inflammatory steroid formulation comprising an anti-inflammatory steroid in an amount between about 0.01% and about 0.05% (w/v); propylene glycol in an amount between about 2% and about 10% (w/v); PEG 400 in an amount between about 10% and about 25% (w/v); polysorbate 20 in an amount between about 1% and about 4% (w/v); an effective amount of preservative; an effective amount of antioxidant; an effective amount of stabilizer; water; and pH buffering agent sufficient to adjust the pH of the resulting solution to between about 3.5 and about 7. 10. The method of claim 9 wherein said formulation comprises: preservative in an amount between about 0.02% and about 0.08% (w/v); antioxidant in an amount between about 0.001% and about 0.05% (w/v); and stabilizer in an amount between about 0.005% and about 0.05% (w/v). 11. The method of claim 10 wherein said anti-inflammatory steroid is flunisolide in an amount of about 0.025% (w/v). 12. The method of claim 11 wherein: said preservative comprises benzalkonium chloride; said stabilizer comprises disodium EDTA; and said antioxidant comprises BHT. 13. The method of claim 12 which further comprises sorbitol in an amount between about 0.001% and about 5% (w/v). 14. The method of claim 13 wherein said pH buffering agent comprises: citric acid in an amount between about 0.001% and about 0.05% (w/v); and sodium citrate dihydrate in an amount between about 0.001% and about 0.05% (w/v). 15. A method of treating inflammation of the nasal mucosa without inducing stinging, which method comprises intranasally administering to a subject in need thereof a substantially non-stinging aqueous anti-inflammatory steroid formulation comprising flunisolide hemihydrate in an amount of about 0.025% (w/v); propylene glycol in an amount of about 5% (w/v); PEG 400 in an amount of about 20% (w/v); polysorbate 20 in an amount of about 2.50% (w/v); benzalkonium chloride in an amount of about 0.035% (w/v); disodium EDTA in an amount of about 0.01% (w/v); BHT in an amount of about 0.01% (w/v); citric acid in an amount of about 0.005% (w/v); sodium citrate dihydrate in an amount of about 0.00765% (w/v); sorbitol in an amount of about 2.00% (w/v); and water, wherein the pH of the resulting solution is adjusted to about 5.2.