Claims for Patent: 11,596,599

Summary for Patent: 11,596,599

Title:	Compositions and methods for ophthalmic and/or other applications
Abstract:	Particles, compositions, and methods that aid particle transport in mucus are provided. The particles, compositions, and methods may be used, in some instances, for ophthalmic and/or other applications. In some embodiments, the compositions and methods may involve modifying the surface coatings of particles, such as particles of pharmaceutical agents that have a low aqueous solubility. Such compositions and methods can be used to achieve efficient transport of particles of pharmaceutical agents though mucus barriers in the body for a wide spectrum of applications, including drug delivery, imaging, and diagnostic applications. In certain embodiments, a pharmaceutical composition including such particles is well-suited for ophthalmic applications, and may be used for delivering pharmaceutical agents to the front of the eye and/or the back of the eye.
Inventor(s):	Alexey Popov, Elizabeth M. Enlow, Hongming Chen, James Bourassa
Assignee:	Alcon Inc , Johns Hopkins University
Application Number:	US17/170,701
Patent Claims:	1. A method for treating a dry eye syndrome in a patient in need thereof comprising: administering topically to an eye of the patient an ophthalmic suspension comprising: (a) a plurality of mucus-penetrating coated nanoparticles, wherein each of the coated nanoparticles comprises: (i) a core particle comprising loteprednol etabonate, wherein the loteprednol etabonate comprises at least 90 wt % of the core particle; and (ii) a poloxamer non-covalently adsorbed to the core particle, wherein the poloxamer is poloxamer 407, poloxamer 188, poloxamer 335, or poloxamer 333; and (b) water; wherein the ophthalmic suspension comprises less than 1% w/v loteprednol etabonate; wherein the ratio of the poloxamer to the loteprednol etabonate present in the ophthalmic suspension is from 1:1 to 0.1:1; and wherein the ophthalmic suspension is formulated as an eye drop. 2. The method of claim 1, wherein the ratio of the weight of the loteprednol etabonate present in the ophthalmic suspension to the weight of the poloxamer present in the ophthalmic suspension is greater than or equal to about 1:1, and less than or equal to about 3:1. 3. The method of claim 2, wherein the loteprednol etabonate is present in the ophthalmic suspension in an amount of about 0.2% w/v to about 0.4% w/v. 4. The method of claim 1, wherein the ophthalmic suspension further comprises a chelating agent, wherein the chelating agent is disodium ethylenediaminetetraacetic acid. 5. The method of claim 4, wherein the disodium ethylenediaminetetraacetic acid is present in the ophthalmic suspension in an amount of about 0.001% w/v to about 0.1% w/v. 6. The method of claim 1, wherein the ophthalmic suspension further comprises glycerin. 7. The method of claim 6, wherein the glycerin is present in the ophthalmic suspension in an amount of about 0.5% w/v to about 3% w/v. 8. The method of claim 7, wherein the ophthalmic suspension comprises less than or equal to about 0.5 wt % 17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-4-ene-17-carboxylic acid chloromethyl ester relative to the weight of the loteprednol etabonate in the ophthalmic suspension. 9. The method of claim 1, wherein the ophthalmic suspension further comprises sodium chloride. 10. The method of claim 9, wherein the sodium chloride is present in the ophthalmic suspension in an amount of about 0.1% w/v to about 1% w/v. 11. The method of claim 1, wherein the poloxamer is poloxamer 407. 12. The method of claim 3, wherein the poloxamer is poloxamer 407. 13. The method of claim 1, wherein the osmolality of the ophthalmic suspension is about 300 mOsm/kg. 14. The method of claim 1, wherein the ophthalmic suspension has an osmolarity of about 250 mOsm/L to about 310 mOsm/L. 15. The method of claim 1, wherein the core particle is a loteprednol etabonate nanoparticle. 16. A method for treating a dry eye syndrome in a patient in need thereof comprising: administering topically to an eye of the patient an ophthalmic suspension comprising: (a) a plurality of mucus-penetrating coated particles, wherein each of the coated particles comprises: (i) a core particle comprising loteprednol etabonate, wherein the loteprednol etabonate comprises at least 90 wt % of the core particle; and (ii) poloxamer 407 non-covalently adsorbed to the core particle; (b) a buffering agent; and (c) water; wherein the ophthalmic suspension comprises less than 1% w/v loteprednol etabonate; wherein the ratio of the poloxamer 407 to the loteprednol etabonate present in the ophthalmic suspension is from 1:1 to 0.1:1; wherein the ophthalmic suspension is formulated as an eye drop; and wherein the coated particles have an average particle size of about 200 nm to about 700 nm. 17. The method of claim 16, wherein the ophthalmic suspension comprises about 0.2% w/v to about 0.4% w/v of loteprednol etabonate in total. 18. The method of claim 16, wherein the ratio of the weight of the loteprednol etabonate present in the ophthalmic suspension to the weight of the poloxamer 407 present in the ophthalmic suspension is greater than or equal to about 1:1 and less than or equal to about 3:1. 19. The method of claim 18, wherein the ophthalmic suspension further comprises a chelating agent, wherein the chelating agent is disodium ethylenediaminetetraacetic acid. 20. The method of claim 16, wherein the ophthalmic suspension further comprises glycerin. 21. The method of claim 20, wherein the glycerin is present in the ophthalmic suspension in an amount of about 0.5% w/v to about 3% w/v. 22. The method of claim 16, wherein the ophthalmic suspension further comprises sodium chloride. 23. The method of claim 22, wherein the sodium chloride is present in the ophthalmic suspension in an amount of about 0.1% w/v to about 1% w/v. 24. The method of claim 21, wherein the ophthalmic suspension comprises less than or equal to about 0.5 wt % 17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-4-ene-17-carboxylic acid chloromethyl ester relative to the weight of the loteprednol etabonate in the ophthalmic suspension. 25. The method of claim 16, wherein the ophthalmic suspension further comprises benzalkonium chloride. 26. The method of claim 1, wherein the average particle size is a Z-average diameter measured by the dynamic light scattering. 27. The method of claim 26, wherein the core particle is a loteprednol etabonate nanoparticle. 28. The method of claim 16, wherein the osmolality of the ophthalmic suspension is about 300 mOsm/kg. 29. The method of claim 16, wherein the ophthalmic suspension has an osmolarity of about 250 mOsm/L to about 310 mOsm/L. 30. The method of claim 16, wherein the buffering agent comprises sodium citrate and citric acid. 31. The method of claim 1, wherein the poloxamer is adsorbed to the core particle at an average density of at least 0.01 molecules/nm2 and less than about 10 molecules/nm2. 32. The method of claim 12, wherein the ophthalmic suspension has an osmolarity of about 250 mOsm/L to about 310 mOsm/L. 33. The method of claim 12, wherein the poloxamer r407 is adsorbed to the core particle at an average density of at least 0.01 molecules/nm2 and less than about 10 molecules/nm2. 34. The method of claim 16, wherein the poloxamer 407 is adsorbed to the core particle at an average density of at least 0.01 molecules/nm2 and less than about 10 molecules/nm2. 35. The method of claim 18, wherein the ophthalmic suspension has an osmolarity of about 250 mOsm/L to about 310 mOsm/L. 36. The method of claim 18, wherein the disodium ethylenediaminetetraacetic acid is present in the ophthalmic suspension in an amount of about 0.001% w/v to about 0.1% w/v.