Stabilized oxymetazoline formulations and their uses
The present invention provides stabilized cream formulations of oxymetazoline and uses thereof. The present invention also provides a method of treating facial erythema associated with rosacea in a patient in need of such treatment, comprising topically administering once or twice daily to the site of erythema on the face of the patient a pharmaceutical composition comprising 0.5%, 1.0% or 1.5% oxymetazoline or a pharmaceutically acceptable salt thereof as the sole active ingredient.
1. A method of treating facial erythema associated with rosacea in a patient in need of such treatment, comprising topically administering once daily to the site of erythema on the face of the patient a pharmaceutical composition comprising 1.0% w/w oxymetazoline hydrochloride thereof as the sole active ingredient, wherein the patient experiences no rebound or worsening of facial erythema post-treatment.
2. The method of claim 1 , wherein the pharmaceutical composition is in a form selected from the group consisting of solutions, gels, lotions, creams, ointments, foams, emulsions, microemulsions, milks, serums, aerosols, sprays, dispersions, microcapsules, vesicles and microparticles thereof.
3. The method of claim 2 , wherein the pharmaceutical composition is in the form of a cream.
4. The method of claim 3 , wherein the topical administration is well tolerated by the patient and results in limited systemic exposure of the oxymetazoline hydrochloride.
5. The method of claim 3 , wherein the pharmaceutical formulation further comprises methylparaben, propylparaben, phenoxyethanol, sodium citrate, citric acid, disodium edetate, butylated hydroxytoluene, lanolin, medium chain triglycerides, diisopropyl adipate, oleyl alcohol, polyethylene glycol PEG-300, polyethylene glycol PEG-6, polyethylene glycol PEG-32, glycol stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, ceteareth-25, and purified water.
6. The method of claim 3 , wherein the pharmaceutical formulation comprises about 1.0% w/w oxymetazoline HCl, about 0.2% w/w methylparaben, about 0.05% w/w propylparaben, about 0 8% w/w phenoxyethanol, about 0.3% w/w sodium citrate dihydrate, about 0.219% w/w anhydrous citric acid, about 0.01% w/w disodium edetate, about 0.05% w/w butylated hydroxytoluene, about 2% w/w anhydrous lanolin, about 7% w/w medium chain triglycerides, about 7% w/w diisopropyl adipate, about 7% w/w oleyl alcohol, about 4% w/w polyethylene glycol PEG-300, about 8% w/w polyethylene glycol PEG-6/polyethylene glycol PEG-32/glycol stearate (Tefose-63), about 8% w/w cetostearyl alcohol, about 2% w/w ceteareth-6/stearyl alcohol (Cremophor A6), about 2% w/w ceteareth-25, and purified water (q.s.).
7. The method of claim 6 , wherein the topical administration is well tolerated by the patient and results in limited systemic exposure of the oxymetazoline hydrochloride.
8. The method of claim 1 , wherein the treatment results in an at least 2-grade improvement from baseline on Clinician's Erythema Assessment (CEA) scale, Subject Self-Assessment of Erythema (SSA), or both.
9. The method of claim 1 , wherein the treatment results in an at least 1-grade improvement from baseline on Clinician's Erythema Assessment (CEA) scale, Subject Self-Assessment of Erythema (SSA), or both.
10. The method of claim 1 , wherein a median T max after 28 days of topical administration is about 10 hours to about 12 hours.
11. The method of claim 1 , wherein a mean C max after 28 days of topical administration is less than about 133.5 pg/mL.
12. The method of claim 1 , wherein the patient has a mean C max after 28 days of topical administration is less than about 66 pg/mL.
13. The method of claim 1 , wherein the patient has an AUC 0-24 post administration of less than about 2042 pg·hr/mL.
14. The method of claim 1 , wherein the patient has an AUC 0-24 post administration of less than about 1050 pg·hr/mL.
15. The method of claim 1 , wherein the facial erythema is persistent facial erythema.
16. The method of claim 1 , wherein the patient is an adult.
17. The method of claim 1 , wherein the once daily administration is a pea sized amount of the pharmaceutical composition.
18. A method of treating facial erythema associated with rosacea in a patient in need of such treatment, comprising topically administering once daily on the face of the patient a pharmaceutical composition comprising 1.0% w/w oxymetazoline hydrochloride thereof as the sole active ingredient, wherein the patient experiences no rebound or worsening of facial erythema post-treatment.
19. The method of claim 18 , wherein the pharmaceutical composition is topically administered in a thin layer to cover the entire face avoiding the eyes and lips.
20. The method of claim 18 , wherein the pharmaceutical composition is a cream further comprising methylparaben, propylparaben, phenoxyethanol, sodium citrate, citric acid, disodium edetate, butylated hydroxytoluene, lanolin, medium chain triglycerides, diisopropyl adipate, oleyl alcohol, polyethylene glycol PEG-300, polyethylene glycol PEG-6, polyethylene glycol PEG-32, glycol stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, ceteareth-25, and purified water.
21. The method of claim 20 , wherein the cream comprises about 1.0% w/w oxymetazoline HCl, about 0.2% w/w methylparaben, about 0.05% w/w propylparaben, about 0 8% w/w phenoxyethanol, about 0.3% w/w sodium citrate dihydrate, about 0.219% w/w anhydrous citric acid, about 0.01% w/w disodium edetate, about 0.05% w/w butylated hydroxytoluene, about 2% w/w anhydrous lanolin, about 7% w/w medium chain triglycerides, about 7% w/w diisopropyl adipate, about 7% w/w oleyl alcohol, about 4% w/w polyethylene glycol PEG-300, about 8% w/w polyethylene glycol PEG-6/polyethylene glycol PEG-32/glycol stearate (Tefose-63), about 8% w/w cetostearyl alcohol, about 2% w/w ceteareth-6/stearyl alcohol (Cremophor A6), about 2% w/w ceteareth-25, and purified water (q.s.).
22. The method of claim 18 , wherein the treatment results in an at least 2-grade improvement from baseline on Clinician's Erythema Assessment (CEA) scale, Subject Self-Assessment of Erythema (SSA), or both.
23. The method of claim 18 , wherein a median T max after 28 days of topical administration is about 10 hours to about 12 hours.
24. The method of claim 18 , wherein a mean C max after 28 days of topical administration is less than about 133.5 pg/mL.
25. The method of claim 18 , wherein the patient has an AUC 0-24 post administration of less than about 2042 pg·hr/mL.
26. The method of claim 18 , wherein the facial erythema is persistent facial erythema.
27. The method of claim 18 , wherein the patient is an adult.
28. A method of treating facial erythema associated with rosacea in a patient in need of such treatment, comprising topically administering once daily on the face of the patient a pharmaceutical composition comprising 1.0% w/w oxymetazoline hydrochloride thereof as the sole active ingredient.
29. The method of claim 28 , wherein the pharmaceutical composition is topically administered in a thin layer to cover the entire face avoiding the eyes and lips.
30. The method of claim 28 , wherein the pharmaceutical composition is a cream further comprising methylparaben, propylparaben, phenoxyethanol, sodium citrate, citric acid, disodium edetate, butylated hydroxytoluene, lanolin, medium chain triglycerides, diisopropyl adipate, oleyl alcohol, polyethylene glycol PEG-300, polyethylene glycol PEG-6, polyethylene glycol PEG-32, glycol stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, ceteareth-25, and purified water.
31. The method of claim 30 , wherein the cream comprises about 1.0% w/w oxymetazoline HCl, about 0.2% w/w methylparaben, about 0.05% w/w propylparaben, about 0 8% w/w phenoxyethanol, about 0.3% w/w sodium citrate dihydrate, about 0.219% w/w anhydrous citric acid, about 0.01% w/w disodium edetate, about 0.05% w/w butylated hydroxytoluene, about 2% w/w anhydrous lanolin, about 7% w/w medium chain triglycerides, about 7% w/w diisopropyl adipate, about 7% w/w oleyl alcohol, about 4% w/w polyethylene glycol PEG-300, about 8% w/w polyethylene glycol PEG-6/polyethylene glycol PEG-32/glycol stearate (Tefose-63), about 8% w/w cetostearyl alcohol, about 2% w/w ceteareth-6/stearyl alcohol (Cremophor A6), about 2% w/w ceteareth-25, and purified water (q.s.).
32. The method of claim 28 , wherein the treatment results in an at least 2-grade improvement from baseline on Clinician's Erythema Assessment (CEA) scale, Subject Self-Assessment of Erythema (SSA), or both.
33. The method of claim 28 , wherein a median T max after 28 days of topical administration is about 10 hours to about 12 hours.
34. The method of claim 28 , wherein a mean C max after 28 days of topical administration is less than about 133.5 pg/mL.
35. The method of claim 28 , wherein the patient has an AUC 0-24 post administration of less than about 2042 pg·hr/mL.
36. The method of claim 28 , wherein the facial erythema is persistent facial erythema.
37. The method of claim 28 , wherein the patient is an adult.