Abstract: The present invention relates to high concentration ophthalmic pharmaceutical formulations of the phosphodiesterase-4 inhibitor, roflumilast, which are suitable for intravitreal or other ocular administration to injection sites internal or external to the eye and orbit. The compositions can comprise about 2% to about 5% w/v of roflumilast, a viscosity agent, a tonicity agent, a buffer agent, a surfactant, and water. The pharmaceutical compositions are stable with little to no impurities and can be injected from a 27 Gauge or 30 Gauge syringe with minimal force, resulting in therapeutic levels of pharmaceutical in relevant tissues for the ocular surface, anterior compartment, vitreous/posterior compartments, and tissues or chambers surrounding the eye.

Abstract: The disclosure provides a method of reducing the frequency of administration of an anti-VEGF agent to a subject diagnosed with wet age-related macular degeneration. The method comprises administering a CCR3 inhibitory agent to the subject; administering the anti-VEGF agent to the subject after the administering of the CCR3 inhibitory agent; and administering additional subsequent doses of the anti-VEGF agent to the subject at a frequency less than the recommended frequency. The disclosure further provides a method of treating a subject suffering from a retina-associated disease, the method comprising administering an anti-VEGF agent to a subject suffering from a retina-associated disease and previously treated with a CCR3 inhibitory agent, wherein the anti-VEGF agent is administered at a frequency less than the recommended frequency for the anti-VEGF agent.

Abstract: The present invention relates to methods of treating ocular inflammatory diseases by administering ophthalmic pharmaceutical compositions of roflumilast. Administration of ophthalmic pharmaceutical compositions of roflumilast can provide significant immunomodulatory and anti-inflammatory activity relative to existing immunomodulatory, immunosuppressant, or non-steroidal anti-inflammatory therapies, including corticosteroids and antihistamines, while also providing an improved safety and convenience profile relative to one or both agents.

Abstract: The present invention relates to stable, ophthalmic pharmaceutical formulations of the phosphodiesterase-4 inhibitor, roflumilast, and methods of making the same. Novel ophthalmic pharmaceutical formulations of roflumilast can comprise a viscosity agent, a surfactant, and a buffer. In preferred embodiments, the pH of the ophthalmic pharmaceutical composition is between 6.0 and 6.7. Methods of making stable, ophthalmic pharmaceutical formulations of roflumilast can include separate active and inactive ingredient processes. Further, the methods can include clarity filtration to mitigate particle size aggregation and to create an optimized suspension. Further, the methods can include terminal sterilization of the final drug product.