Ophthalmic preparations
The present invention provides ophthalmic formulations containing cyclosporine, methods for preparing the formulation, and methods for using the formulation.
1. An ophthalmic nanoemulsion formulation comprising:
(a) a cyclosporine selected from the group consisting of cyclosporines A, B, C, D and G,
(b) ethanol,
(c) at least one oil, wherein the oil comprises medium chain triglycerides,
(d) at least one surfactant, wherein the surfactant is a polysorbate,
(e) at least one cationic preservative, and
(f) water or phosphate buffered saline,
wherein (i) the cyclosporine is in a solid particulate state and in a soluble state, (ii) the cyclosporine in the solid particulate state is present in the water or the phosphate buffered saline, (iii) the formulation is phospholipid-free, and (iv) the formulation comprises globules of oil comprising dissolved cyclosporine, wherein the globules have a mean diameter between 100 and 250 nm,
wherein the at least one cationic preservative is selected from the group consisting of cetyltrimethylammonium bromide, cetylpyridinium chloride, benzethonium chloride, and benzalkonium chloride.
2. The ophthalmic formulation of claim 1 , wherein the cyclosporine is cyclosporine A.
3. The ophthalmic formulation of claim 1 , wherein the formulation is a mixture of dissolved cyclosporine in the oil globules and the cyclosporine in the solid particulate state is present in the water or the phosphate buffered saline.
4. The formulation of claim 1 , wherein the at least one surfactant is Polysorbate 80.
5. The formulation of claim 1 , further comprising a viscosity modifier.
6. The formulation of claim 5 , wherein the viscosity modifier is selected from the group consisting of a cellulose derivative, a polysaccharide and a synthetic polymer.
7. An ophthalmic nanoemulsion formulation comprising:
(a) a cyclosporine selected from the group consisting of cyclosporines A, B, C, D and G,
(b) ethanol,
(c) at least one oil, wherein the oil comprises medium chain triglycerides,
(d) at least one surfactant, wherein the surfactant is a polysorbate,
(e) at least one cationic preservative, and
(f) water or phosphate buffered saline,
wherein (i) the cyclosporine is in a solid particulate state and in a soluble state, (ii) the cyclosporine in the solid particulate state is present in the water or phosphate buffered saline, (iii) the formulation is phospholipid-free, and (iv) the formulation comprises globules of oil comprising dissolved cyclosporine, wherein the globules have a mean diameter between 100 and 250 nm,
wherein the at least one cationic preservative is benzalkonium chloride.