Methods for ophthalmic delivery of roflumilast
Inventors
Chaudhuri, Bhaskar • Gukasyan, Hovhannes John
Assignees
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Publication Number
US-12102622-B2
Publication Date
2024-10-01
Expiration Date
Abstract
Methods for the ophthalmic delivery of roflumilast. The inventors have made the surprising discovery that the administration of pharmaceutical compositions comprising roflumilast to the cornea preferentially delivers the drug laterally through the ocular surface and anterior tissues of the eye. In contrast to the delivery of roflumilast to the skin, which primarily travels transversely through the various tissues of the skin, or many other topical ocular pharmaceutical compositions which travel through the cornea to the aqueous humor, the delivery of drug to the eye to the cornea travels laterally to the ocular surface and anterior tissues of the eye. Such methods can result in elevated levels of the drug in the cornea and other ocular surface and anterior tissues of the eye (e.g., iris-ciliary body, sclera, conjunctiva, and aqueous humor) relative to the interior or posterior tissues of the eye.
Core Innovation
The invention relates to methods for treating a patient having an inflammatory disorder of an ocular surface or anterior tissue of the eye by administering an ophthalmic pharmaceutical composition comprising a therapeutically effective amount of roflumilast to a cornea. The composition comprises ingredients set forth in Tables 1, 2, 3, 4, 5, or 6 and is formulated as a suspension. The composition delivers roflumilast to the cornea and subsequently travels laterally through the ocular surface and anterior tissues of the eye.
The described delivery pattern is characterized by preferential exposure of anterior compartments compared with posterior compartments. In particular, the composition delivers elevated levels of roflumilast to the ocular surface or an anterior portion of the eye relative to a posterior compartment of the eye. Elevated levels are also described for specific eye tissues including the cornea, conjunctiva, iris-ciliary body, sclera, and aqueous humor.
The invention further describes pharmacokinetic behavior including a laterally traveling pattern rather than a trans-corneal route and includes a depot effect. The depot effect is characterized by increasing roflumilast concentration over time in targeted anterior tissues, with sustained exposure after repeated dosing. This depot effect is described for the cornea and is also described for the iris-ciliary body, each indicated by increased roflumilast concentration relative to an earlier time after administration.
Claims Coverage
The partial content includes two independent claims, each directed to treating an ocular-surface or anterior-tissue inflammatory disorder using topical ophthalmic administration of roflumilast to the cornea with specified formulation ingredients and delivery distribution outcomes, and each requiring an ophthalmic suspension delivered to the cornea.
Corneal ophthalmic delivery of roflumilast for inflammatory ocular surface/anterior tissue disorder with lateral travel
Administering an ophthalmic pharmaceutical composition comprising a therapeutically effective amount of roflumilast to a cornea, where the composition comprises ingredients set forth in Tables 1, 2, 3, 4, 5, or 6, wherein the composition delivers roflumilast to the cornea and subsequently travels laterally through the ocular surface and anterior tissues of the eye, and wherein the ophthalmic pharmaceutical composition is a suspension.
Corneal ophthalmic delivery of roflumilast in suspension for elevated anterior versus posterior roflumilast levels
Administering an ophthalmic pharmaceutical composition comprising a therapeutically effective amount of roflumilast to a cornea, where the composition comprises ingredients set forth in Tables 1, 2, 3, 4, 5, or 6, wherein the composition delivers elevated levels of roflumilast to the ocular surface or an anterior portion of the eye of the patient relative to a posterior compartment of the eye of the patient, and wherein the ophthalmic pharmaceutical composition is a suspension.
Across the two independent claims, treatment is provided by administering a therapeutically effective amount of roflumilast in an ophthalmic suspension to the cornea using formulations from Tables 1–6, with the key inventive outcome being lateral travel through ocular surface and anterior tissues and/or elevated anterior (ocular surface/anterior compartment) roflumilast levels relative to a posterior compartment.
Stated Advantages
Preferentially drives roflumilast exposure to the ocular surface and anterior tissues while limiting posterior tissue exposure.
Produces a lateral traveling delivery pattern through ocular surface and anterior tissues rather than a trans-corneal route.
Provides a depot effect, with increasing roflumilast concentration over time and sustained exposure after repeated dosing.
Documented Applications
Treating a patient having an inflammatory disorder of an ocular surface or anterior tissue of the eye.
Delivery and pharmacokinetic characterization of roflumilast after topical ophthalmic administration to the cornea, including anterior-tissue elevated levels and depot effect (cornea; iris-ciliary body), as described in preclinical studies using Dutch Belted Rabbits and Balb/C mice.
Allergic conjunctivitis (ragweed model) described in the document as part of the study context.
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