Claims for Patent: 10,940,108

Summary for Patent: 10,940,108

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):	Popov; Alexey (Waltham, MA), Enlow; Elizabeth M. (Waltham, MA), Chen; Hongming (Belmont, MA), Bourassa; James (Somerville, MA)
Assignee:	The Johns Hopkins University (Baltimore, MD)
Application Number:	16/888,371
Patent Claims:	1. A method for treating a dry eye condition, comprising: administering topically to an eye of a patient in need thereof a pharmaceutical composition comprising: (a) a plurality of coated nanoparticles, each of the coated nanoparticles comprising: (i) a core particle comprising loteprednol etabonate, and wherein the loteprednol etabonate comprises at least 90 wt % of the core particle; and (ii) a coating on the core particle, the coating comprising poloxamer 407 non-covalently adsorbed to the core particle; (b) about 0.5% w/v to about 3% w/v glycerin; and (c) about 0.1% w/v to about 1% w/v sodium chloride; wherein the pharmaceutical composition is a topical suspension; wherein the pharmaceutical composition comprises about 0.1% to 2% w/v loteprednol etabonate; wherein the ratio of the total weight of the loteprednol etabonate to the total weight of the poloxamer 407 comprised in the pharmaceutical composition is about 2:1; and wherein the coated nanoparticles are mucus-penetrating. 2. The method of claim 1, wherein the core particle is substantially free of a polymeric component. 3. The method of claim 1, wherein the loteprednol etabonate is present in the pharmaceutical composition in an amount between about 0.1% and about 1% w/v. 4. The method of claim 3, wherein the loteprednol etabonate is present in the pharmaceutical composition in an amount between about 0.2% and about 0.4% w/v. 5. The method of claim 4, wherein the pharmaceutical composition further comprises about 0.001% w/v to about 0.1% w/v disodium ethylenediaminetetraacetic acid. 6. The method of claim 5, wherein the pharmaceutical composition further comprises about 0.001% w/v to about 0.05% w/v benzalkonium chloride. 7. The method of claim 1, wherein the pharmaceutical composition further comprises about 0.01% w/v to about 0.1% w/v disodium ethylenediaminetetraacetic acid. 8. The method of claim 1, wherein the poloxamer 407 coating on the particles of loteprednol etabonate is at an average density of at least 0.05 molecules/nm.sup.2 and less than 10 molecule/nm.sup.2. 9. The method of claim 8, wherein the average density is at least 0.1 molecules/nm.sup.2 and less than 10 molecule/nm.sup.2. 10. The method of claim 1, wherein the coated nanoparticles have an average size of about 200 nm to about 700 nm. 11. The method of claim 10, wherein the average size of the coated nanoparticles is as measured in Z-average diameter by dynamic light scattering. 12. The method of claim 11, wherein the polydispersity index of the coated nanoparticles is less than or equal to about 0.3 as measured by dynamic light scattering. 13. The method of claim 1, wherein the pharmaceutical composition comprises less than or equal to about 0.5 wt % 17.alpha.-[(ethoxycarbonyl)oxy]-11.beta.-hydroxy-3-oxoandrosta-4-ene-17-c- arboxylic acid chloromethyl ester relative to the weight of the loteprednol etabonate in the pharmaceutical composition. 14. The method of claim 11, wherein the pharmaceutical composition is made sterile via a sterilization process comprising gamma irradiation, and wherein the 17.alpha.-[(ethoxycarbonyl)oxy]-11.beta.-hydroxy-3-oxoandrosta-4-ene-17-c- arboxylic acid chloromethyl ester is at less than or equal to about 0.5 wt % relative to the weight of the loteprednol etabonate in the pharmaceutical composition after the gamma irradiation. 15. A method of making a pharmaceutical composition comprising: (a) a plurality of coated nanoparticles, each of the coated nanoparticles comprising: (i) a core particle comprising loteprednol etabonate, and wherein the loteprednol etabonate comprises at least 90 wt % of the core particle; and (ii) a coating on the core particle, the coating comprising poloxamer 407 non-covalently adsorbed to the core particle; and (b) about 0.5% w/v to about 3% w/v glycerin; and (c) about 0.1% w/v to about 1% w/v sodium chloride; wherein the pharmaceutical composition is a topical suspension; wherein the pharmaceutical composition comprises about 0.1% to 2% w/v loteprednol etabonate in total; wherein the ratio of the total weight of the loteprednol etabonate to the total weight of the poloxamer 407 comprised in the pharmaceutical composition is about 2:1, and wherein the coated nanoparticles are mucus-penetrating; the method comprising: milling a coarse aqueous suspension containing about 2-20% loteprednol etabonate in the form of coarse or micronized crystals, about 0.2-20% of poloxamer 407, about 0.5-3% glycerin, and about 0.1-1% sodium chloride, in the presence of milling media to produce a nanosuspension comprising coated nanoparticles of loteprednol etabonate with poloxamer 407 and sized in the range of about 200 nm to about 500 nm; and separating the nanosuspension of coated loteprednol etabonate particles from the milling media. 16. The method of claim 6, wherein the pharmaceutical composition further comprises a sodium citrate and citric acid buffer. 17. The method of claim 1, wherein the administering occurs four times daily.