Compositions and methods for treating ocular disorders
The present disclosure is directed to compositions comprising oxymetazoline and methods of treating various eye disorders related to drooping eyelids, such as ptosis, in a subject comprising administering to the subject compositions comprising oxymetazoline.
1. A method of treating acquired blepharoptosis in an adult, comprising administering to at least one ptotic eye of the adult a therapeutically effective amount of an aqueous ophthalmic, sterile, preservative-free formulation consisting of:
a) about 0.1 wt % oxymetazoline hydrochloride;
b) tonicity modifiers comprising sodium chloride, potassium chloride, calcium chloride, and magnesium chloride;
c) about 0.5 wt % to about 1.0 wt % of hypromellose or sodium carboxymethyl cellulose;
d) sodium acetate and sodium citrate;
e) hydrochloric acid; and
f) water QS,
wherein the aqueous ophthalmic formulation has a pH range from about 5.8 to about 6.8,
wherein the aqueous ophthalmic formulation has a viscosity of from about 15 cPs to about 35 cPs,
wherein the aqueous ophthalmic formulation has an osmolality of from about 290 to about 365 mOsm/kg, and
wherein the aqueous ophthalmic formulation is stable at a temperature of about 25° C. at about 40% or about 60% relative humidity for a period of 24 months.
2. The method of claim 1 , wherein the tonicity modifiers comprise 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.
3. The method of claim 1 , wherein the sodium acetate and sodium citrate comprises about 0.39 wt % sodium acetate or sodium acetate trihydrate and about 0.17 wt % sodium citrate or sodium citrate dihydrate.
4. The method of claim 1 , wherein the hypromellose comprises about 0.5 wt % hypromellose.
5. The method of claim 1 , wherein the sodium carboxymethyl cellulose comprises about 1.0 wt % sodium carboxymethyl cellulose.
6. The method of claim 1 , wherein the formulation has a pH range from about 6.3 to about 6.5.
7. The method of claim 1 , wherein the aqueous ophthalmic formulation has an osmolality of from about 290 mOsm/kg to about 330 mOsm/kg.
8. The method of claim 1 , wherein the 0.1 wt % oxymetazoline hydrochloride is equivalent to about 0.09 wt % of oxymetazoline free base.
9. The method of claim 1 , wherein the formulation is aseptically prepared.
10. The method of claim 1 , wherein the formulation has a viscosity of about 26 cPs.
11. The method of claim 1 , wherein the formulation is administered once daily to one ptotic eye or to both ptotic eyes.
12. The method of claim 1 , wherein the formulation is administered to the adult on one or more consecutive days at a dose of one drop in a single eye for a total daily dose of about 0.035 mg oxymetazoline hydrochloride.
13. The method of claim 1 , wherein the formulation is administered to the adult on one or more consecutive days at a dose of one drop in each eye for a total daily dose of about 0.07 mg oxymetazoline hydrochloride.
14. The method of claim 13 , wherein a Tmax of oxymetazoline concentration after a single-dose administration is from about 0.5 hours to about 12 hours.
15. The method of claim 13 , wherein a median Tmax of oxymetazoline concentration is about 2 hours.
16. The method of claim 13 , wherein an oxymetazoline mean and standard deviation (SD) of Cmax is about 30.5±12.7 pg/mL.
17. The method of claim 13 , wherein an oxymetazoline mean and standard deviation (SD) of area under the concentration-time curve (AUC inf ) is about 468±214 pg*hr/mL.
18. The method of claim 13 , wherein a mean oxymetazoline t 1/2 after administration is about 8.3 hours.
19. The method of claim 1 , wherein treatment efficacy is assessed with photographic measurement of Marginal reflex distance 1 (MRD1) or with the Leicester Peripheral Field Test (LPFT).
20. The method of claim 19 , wherein a MRD 1 increase of the adult continues through about 8 hours after administration.
21. The method of claim 19 , wherein the maximum increase in MRD 1 is observed about 2 hours after administration.
22. The method of claim 19 , wherein the LPFT mean score is increased from baseline by about 5-10 points after about 2 hours or about 6 hours after administration.
23. The method of claim 22 , wherein the increase from baseline is after about 14 days after administration.