Oxymetazoline compositions
The present disclosure is directed to compositions comprising oxymetazoline and methods of stabilizing oxymetazoline compositions for long term storage.
1. A child-resistant packaging having a single use container enclosed therein, wherein the single use container comprises an aqueous ophthalmic, sterile, preservative-free formulation comprising:
a) about 0.1 wt % oxymetazoline or a pharmaceutically acceptable salt thereof;
b) sodium chloride, potassium chloride, calcium chloride, and magnesium chloride;
c) about 0.5 wt % hypromellose;
d) sodium acetate and sodium citrate;
e) hydrochloric acid; and
f) water,
wherein the formulation has a pH range from about 5.8 to about 6.8;
wherein the container delivers about 0.035 mg of oxymetazoline or a pharmaceutically acceptable salt thereof per drop; and
wherein the formulation has a viscosity of about 15 cPs to about 35 cPs.
2. The child-resistant packaging of claim 1 , wherein the packaging is a foil pouch.
3. The child-resistant packaging of claim 2 , wherein the foil pouch is a foil laminate pouch.
4. The child-resistant packaging of claim 1 , wherein the formulation has an osmolality of from about 290 to about 365 mOsm/kg.
5. The child-resistant packaging of claim 1 , wherein the container is formed by a blow/fill/seal process.
6. The child-resistant packaging of claim 1 , wherein the container is a low density polyethylene container.
7. The child-resistant packaging of claim 1 , wherein the pharmaceutically acceptable salt is oxymetazoline hydrochloride.
8. The child-resistant packaging of claim 1 , wherein the formulation comprises about 0.64 wt % of sodium chloride, about 0.075 wt % of potassium chloride, about 0.048 wt % of calcium chloride, and about 0.03 wt % of magnesium chloride.
9. The child-resistant packaging of claim 8 , wherein the calcium chloride is calcium chloride dihydrate and the magnesium chloride is magnesium chloride hexahydrate.
10. The child-resistant packaging of claim 1 , wherein the sodium acetate is sodium acetate trihydrate and the sodium citrate is sodium citrate dihydrate.
11. The child-resistant packaging of claim 1 , wherein the formulation comprises about 0.39 wt % sodium acetate and about 0.17 wt % sodium citrate.
12. The child-resistant packaging of claim 1 , wherein the formulation has a pH range from about 6.3 to about 6.5.
13. The child-resistant packaging of claim 1 , wherein the formulation maintains a pH range from about 5.8 to about 6.8, a viscosity from about 15 cPs to about 35 cPs, and an osmolality from about 290 to about 365 mOsm/kg for a period of 6 months.
14. The child-resistant packaging of claim 1 , wherein the formulation is aseptically prepared.
15. A child-resistant foil pouch having a single use low density polyethylene container enclosed therein, wherein the single use container comprises an aqueous ophthalmic, sterile, preservative-free formulation comprising:
a) about 0.1 wt % oxymetazoline hydrochloride;
b) sodium chloride, potassium chloride, calcium chloride, and magnesium chloride;
c) about 0.5 wt % hypromellose;
d) sodium acetate and sodium citrate;
e) hydrochloric acid; and
f) water,
wherein the formulation has a pH range from about 5.8 to about 6.8,
wherein the formulation has a viscosity of from about 15 cPs to about 35 cPs,
wherein the formulation has an osmolality of from about 290 to about 365 mOsm/kg, and
wherein the container delivers about 0.035 mg of oxymetazoline or a pharmaceutically acceptable salt thereof per drop.
16. The child-resistant foil pouch of claim 15 , wherein the foil pouch is a foil laminate pouch.
17. The child-resistant foil pouch of claim 15 , wherein the fill of the container is about 0.3 mL.
18. The child-resistant foil pouch of claim 15 , wherein volume of the container is about 0.5 mL.
19. The child-resistant foil pouch of claim 15 , wherein the container is formed by a blow/fill/seal process.
20. The child-resistant foil pouch of claim 15 , wherein the formulation comprises about 0.64 wt % of sodium chloride, about 0.075 wt % of potassium chloride, about 0.048 wt % of calcium chloride or calcium chloride dihydrate, and about 0.03 wt % of magnesium chloride or magnesium chloride hexahydrate.
21. The child-resistant foil pouch of claim 15 , wherein the sodium acetate is sodium acetate trihydrate and the sodium citrate is sodium citrate dihydrate.
22. The child-resistant foil pouch of claim 15 , wherein the formulation comprises about 0.39 wt % sodium acetate and about 0.17 wt % sodium citrate.
23. The child-resistant foil pouch of claim 15 , wherein the formulation maintains a pH range from about 5.8 to about 6.8, a viscosity from about 15 cPs to about 35 cPs, and an osmolality from about 290 to about 365 mOsm/kg for a period of 6 months.
24. The child-resistant packaging of claim 13 , wherein the formulation maintains the pH range, the viscosity range and the osmolality range for a period of 12 months.
25. The child-resistant packaging of claim 13 , wherein the formulation maintains the pH range, the viscosity range and the osmolality range for a period of 18 months.
26. The child-resistant packaging of claim 13 , wherein the formulation maintains the pH range, the viscosity range and the osmolality range at a temperature of about 25° C. and about 60% relative humidity.
27. The child-resistant foil pouch of claim 23 , wherein the formulation maintains the pH range, the viscosity range and the osmolality range for a period of 12 months.
28. The child-resistant foil pouch of claim 23 , wherein the formulation maintains the pH range, the viscosity range and the osmolality range for a period of 18 months.
29. The child-resistant foil pouch of claim 23 , wherein the formulation maintains the pH range, the viscosity range and the osmolality range at a temperature of about 25° C. and about 60% relative humidity.