Topical cyclosporine-containing formulations and uses thereof
AssigneeSun Pharmaceutical Industries Limited
InventorsSidney L. WEISS, Ashim K. MITRA, Eugene J. MCNALLY
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Abstract
Provided herein are formulations for topical ophthalmic formulations containing 0.087-0.093 wt % of cyclosporine, and methods of making and using such formulations. In some aspects and embodiments the formulations may include a polyoxyl lipid or fatty acid, and/or a polyalkoxylated alcohol and may include nanomicelles. Also included herein are methods of treating or preventing diseases or conditions, such as ocular diseases or conditions.
Claims31
An ophthalmic topical formulation comprising cyclosporine and one or more additional formulation ingredients, wherein cyclosporine is present in an amount of about 0.087-0.093% of the formulation.
An ophthalmic topical formulation comprising:
- 0.087-0.093 wt % cyclosporine, about 0.1-6 wt % hydrogenated 40 polyoxyl castor oil, and about 0.002-4 wt % octoxynol-40.
An ophthalmic topical formulation comprising:
- 0.087-0.093 wt % cyclosporine, about 1.0 wt % hydrogenated 40 polyoxyl castor oil, and about 0.05 wt % octoxynol-40.
An ophthalmic topical formulation comprising:
- 0.087-0.093 wt % cyclosporine,
- about 1.0 wt % hydrogenated 40 polyoxyl castor oil, and
- about 0.05 wt % octoxynol-40, and optionally
- about 0.20-0.405 wt % sodium phosphate monobasic,
- about 0.23-0.465 wt % sodium phosphate dibasic,
- about 0.05 wt % sodium chloride,
- about 0.3 wt % povidone,
- sodium hydroxide/hydrochloric acid, and
- water for injection.
An ophthalmic topical formulation comprising 0.087-0.093 wt % cyclosporine, wherein the said formulation demonstrates a clinically significant improvement as compared to the vehicle in tear production with >10 mm increase in Schimer test score from baseline.
A process of preparing the ophthalmic topical formulation of cyclosporine, said method comprising the steps of:
- (1) melting the required amount of polyoxyl lipid,
- (2) slowly adding cyclosporine to step (1) and substantially homogenizing the mixture,
- (3) adding polyalkoxylated alcohol to step (2) and continue stirring until a uniform homogeneous solution is obtained,
- (4) adding buffer system and tonicity agent to the solution obtained from step (3) and continue stirring to achieve a good dissolution,
- (5) adding required amount of bioadhesive polymer to the solution of above step,
- (6) adjusting the pH of the solution if required, and making up the final volume with water for injection;
- and
- (7) aseptically filtering and filling the solution into unit dose vials.
A process of preparing the ophthalmic topical formulation of cyclosporine, said method comprising the steps of:
- (1) melting the required amount of hydrogenated 40 polyoxyl castor oil,
- (2) slowly adding cyclosporine to step (1) and substantially homogenizing the mixture,
- (3) adding octoxynol-40 alcohol to step (2) and continue stirring until a uniform homogeneous solution is obtained,
- (4) adding phosphate buffer and sodium chloride to the solution obtained from step (3) and continue stirring to achieve a good dissolution,
- (5) adding required amount of povidone to the solution of above step,
- (6) adjusting the pH of the solution if required, and making up the final volume with water for injection;
- and
- (7) aseptically filtering and filling the solution into unit dose vials.
A process of preparing the ophthalmic topical formulation of cyclosporine, said method comprising the steps of:
- (1) dissolving the required amounts of cyclosporine, polyalkoxylated alcohol and polyoxyl lipid in a suitable solvent,
- (2) charging the solution obtained from step (1) to a suitable sized round bottom flask,
- (3) removing the solvent by rotary evaporation until a thin film is obtained,
- (4) adding and mixing required amount of water for injection to the flask containing film of step (3);
- (5) adding buffer system and tonicity agent to the solution of step (4);
- (6) adding required amount of bioadhesive polymer to the solution of above step,
- (7) adjusting the pH of the solution if required, and making up the final volume with water for injection;
- and
- (8) aseptically filtering and filling the solution into unit dose vials.
A process of preparing the ophthalmic topical formulation of cyclosporine, said method comprising the steps of:
- (1) dissolving the required amounts of cyclosporine, octoxynol-40 and hydrogenated 40 polyoxyl castor oil in a suitable solvent,
- (2) charging the solution obtained from step (1) to a suitable sized round bottom flask,
- (3) removing the solvent by rotary evaporation until a thin film is obtained,
- (4) adding and mixing required amount of water for injection to the flask containing film of step (3);
- (5) adding phosphate buffer and sodium chloride to the solution of step (4);
- (6) adding required amount of povidone to the solution of above step,
- (7) adjusting the pH of the solution if required, and making up the final volume with water for injection;
- and
- (8) aseptically filtering and filling the solution into unit dose vials.
Dependencies are inferred from the claim text.