Topical cyclosporine-containing formulations and uses thereof

A unit dose vial containing about 0.25 mL or about 0.3 mL of an ophthalmic aqueous topical formulation consisting of:

• 0.087-0.093 wt % cyclosporine,
• about 1.0 wt % hydrogenated 40 polyoxyl castor oil,
• about 0.05 wt % octoxynol-40,
• about 0.3 wt % povidone,
• about 0.05 wt % sodium chloride,
• about 0.20-0.405 wt % sodium phosphate monobasic,
• about 0.23-0.465 wt % sodium phosphate dibasic,
• sodium
• hydroxide/hydrochloric acid, and
• water,
• wherein pH of the formulation is about 5 to about 8.

A process of preparing an ophthalmic aqueous topical formulation comprising 0.09 wt % cyclosporine, about 1.0 wt % hydrogenated 40 polyoxyl castor oil, about 0.05 wt % octoxynol-40, about 0.3 wt % povidone, about 0.05 wt % sodium chloride, about 0.20-0.405 wt % sodium phosphate monobasic, and about 0.23-0.465 wt % sodium phosphate dibasic, the process comprising:

• (1) melting the hydrogenated 40 polyoxyl castor oil;
• (2) slowing adding the cyclosporine to the melted hydrogenated 40 polyoxyl castor oil of step (1) to form a mixture, and substantially homogenizing the mixture;
• (3) adding the octoxynol-40 to the mixture of step (2), and continue stirring until a uniform homogenous solution is obtained;
• (4) adding the sodium phosphate monobasic, sodium phosphate dibasic, and sodium chloride to the solution of step (3), and continue stirring to achieve dissolution to form a solution of step (4);
• (5) adding the povidone to the solution of step (4) to form a solution of step (5);
• (6) adjusting pH of the solution of step (5) to about 5 to about 8, and adding water to form a solution of step (6);
• and
• (7) aseptically filtering and filling the solution of step (6) into unit dose vials.

A process of preparing an ophthalmic aqueous topical formulation comprising 0.09 wt % cyclosporine, about 1.0 wt % hydrogenated 40 polyoxyl castor oil, about 0.05 wt % octoxynol-40, about 0.3 wt % povidone, about 0.05 wt % sodium chloride, about 0.20-0.405 wt % sodium phosphate monobasic, and about 0.23-0.465 wt % sodium phosphate dibasic, the process comprising:

• (1) dissolving the cyclosporine, octoxynol-40, and hydrogenated 40 polyoxyl castor oil in a solvent to form a solution of step (1);
• (2) removing the solvent until a thin film is obtained;
• (3) adding water to the film of step (2) to form a solution of step (3);
• (4) adding the sodium phosphate monobasic, sodium phosphate dibasic, and sodium chloride to the solution of step (3) to form a solution of step (4);
• (5) adding povidone to the solution of step (4) to form a solution of step (5);
• (6) adjusting pH of the solution of step (4) to about 5 to about 8, and adding water to form a solution of step (6);
• and
• (7) aseptically filtering and filling the solution of step (6) into unit dose vials.