Methods and compositions for ocular application

Abstract

The present application provides compositions and methods for treatment of ocular inflammatory conditions, dry eye diseases, and abnormal corneal neovascularization, using etiprednol. In one example, a composition is provided comprising a semi-fluorinated alkane compound such as, e.g., perfluorohexyloctane; and an additive selected from paraffin, propylene glycol diacetate (PGD), a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid, phenethyl alcohol, ethanol, isopropanol, glycerol, propylene glycol, polyethylene glycol, n-butanol, or combinations thereof. Eye drops comprising the compositions are also provided. Methods of using the compositions are also provided and include methods for reducing one or more symptoms of ocular inflammatory conditions, dry eye diseases, or abnormal corneal neovascularization.

Description

[0001] METHODS AND COMPOSITIONS FOR OCULAR APPLICATION CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 737,187, filed December 20, 2024, the entire contents of which are hereby incorporated by reference.

[0002] TECHNICAL FIELD

[0003] This disclosure relates to ophthalmological compositions comprising etiprednol, for treatment of ocular inflammatory conditions, dry eye diseases, and abnormal corneal neovascularization, and methods for using the compositions.

[0004] BACKGROUND

[0005] Millions of people worldwide suffer from vision changes, discomfort, or symptoms related to ocular inflammatory conditions, dry eye diseases, and abnormal corneal neovascularization. Conventional steroids can sometimes relieve the symptoms of these diseases and may also provide effective treatment; however, conventional steroids can cause side effects, including, in some cases, systemic effects. In addition, steroids can be difficult to formulate for ocular delivery. There are limited treatments available for many of these eye diseases. Thus, there is a need for a widely available and effective treatment to help relieve these conditions and symptoms.

[0006] SUMMARY

[0007] This disclosure relates to compositions for ophthalmological use, comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, and methods using the compositions, such as methods for treating or slowing the progression of, or reducing one or more symptoms of, an ocular condition in a subject such as, e.g., ocular inflammatory condition, dry eye disease, or abnormal corneal neovascularization. This disclosure is based in part on a surprising realization that the compositions described herein, containing etiprednol, can provide similar therapeutic effectiveness as compared to conventional corticosteroids, while also limiting the side effects and systemic effects as compared to conventional corticosteroids, and the surprising realization that etiprednol can be formulated in a manner that is stable and effective for ocular delivery.

[0008] Glucocorticosteroids are potent drugs that are usually effective against inflammatory diseases of the body, due to their anti-inflammatory action. However, such conventional glucocorticosteroids bring side effects, especially when administered chronically. Locally-delivered glucocrticosteroids also bring unwanted side effects, both locally, and systemically. Attempts to avoid the unwanted side effects have brought development of so-call "soft steroids", which are more easily metabolized into inactive metabolites, thus making it possible to limit the drug effects to locally administered sites. These are delivered close to their site of action and quickly metabolized to reduce systemic exposure and limit unwanted side effects. One example of a first generation soft steroid is loteprednol, which has previously been used in ocular treatment. However, despite the soft nature of this steroid, loteprednol still presents safety concerns around systemic and unwanted side effects. For example, the FDA-approved ocular use of loteprednol is limited to 14 days due to the safety concerns.

[0009] Etiprednol, developed for asthma treatment, is a second generation soft steroid and is a softer steroid than loteprednol. However, with this very soft steroid, comes challenges, including whether the etiprednol is too soft to exhibit therapeutic activity, as well as whether etiprednol is too labile to be formulated for certain delivery routes, such as ocular delivery, and whether etiprednol is too easily metabolized in an ocular environment so as to lose efficacy in that environment. The Applicant has surprisingly found that etiprednol is safe to use in the eye, and exhibits lower side effect potential than loteprednol and other steroids. Applicant has further surprisingly found that, despite the very soft nature of etiprednol, it is indeed active and effective in treating the ocular conditions described herein. Applicant has further surprisingly found that etiprednol can be formulated in a stable composition for ocular delivery and preferentially delivered transcomeally, despite the instability and labile nature of etiprednol.

[0010] This disclosure provides compositions comprising etiprednol. In some optional instances, this disclosure provides compositions comprising etiprednol and a semifluorinated alkane (SFA) compound, and, optionally, an additive selected from paraffin, medium chain triglycerides (MCT), propylene glycol diacetate (PGD), a semi-fluorinated alkyl alcohol (SFAOH), a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid, phenethyl alcohol, ethanol, isopropanol, glycerol, propylene glycol, propylene glycol dilaurate, polyethylene glycol, n-butanol, and combinations thereof, and methods for making and using the compositions. The compositions described herein can provide efficacy with improved reduction in side effects and systemic effects as compared to conventional corticosteroid treatments. The compositions can also provide stable delivery of etiprednol, and, in some instances, selective transcorneal delivery of etiprednol. In some instances, the etiprednol in the composition can be chemically stable for at least 1 month, at least 2 months, at least 3 months, at least 6 months, at least 9 months, at least 1 year, at least 18 months, at least 2 years or longer.

[0011] In one aspect, described herein is a method for treating, slowing the progression of, or reducing one or more symptoms of an ocular inflammatory condition affecting a front of an eye in a subject in need thereof comprising administering a composition comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, to an eye of the subject.

[0012] In these and other instances, the methods and topical ophthalmological compositions described herein can optionally have the following features. The ocular condition can be selected from or related to Sjogren's syndrome, conjunctivitis, inflammation caused by surgery, injury, or other conditions, eye swelling, redness, itching, or pain, uveitis, scleritis and episcleritis, corneal transplant, corneal allograft rejection, allergic eye diseases, Stevens-Johnson Syndrome, vernal keratoconjunctivitis, peripheral ulcerative keratitis, graft vs host disease, cicatrising conjunctival disorders, and anterior uveitis. The corneal transplant can be a form of endothelial keratoplasty (EK). The EK can be selected from Descemet Stripping Endothelial Keratoplasty (DSEK), Descemet Stripping (Automated) EK (DS AEK) or ultrathin (UT)-DSAEK.

[0013] In another aspect, provided herein is a method for treating, slowing the progression of, or reducing one or more symptoms of dry eye disease, dry eye syndrome, meibomian gland disfunction, keratoconjunctivitis sicca, inflammatory dry eye disease, or combinations thereof in a subject in need thereof, the method comprising administering to an eye of the subject a composition comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, to an eye of the subject.

[0014] In another aspect, provided herein is a method for treating, slowing the progression of, or reducing one or more symptoms of abnormal corneal neovascularization in a subject in need thereof comprising administering a composition comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, to an eye of the subject.

[0015] In these and other instances, the methods can optionally have the following features. The abnormal corneal neovascularization can be, can be caused by, or can be related to a condition selected from alkali bums or injury induced neovascularization, corneal graft rejection in high-risk comeal transplant patients, neovascular glaucoma, contact lens induced redness neovascularization, ocular rosacea, ocular pemphigoid, limbal stem cell deficiency, Sjogren's syndrome, atopic conjunctivitis, graft versus host disease, Lyell's syndrome, Stevens-Johnson syndrome, or ulceration.

[0016] In these and other instances, the methods and topical ophthalmological compositions described herein can optionally have the following features. The method can further comprise delivering the etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, to a cornea of the eye of the subject. The method can further comprise delivering the etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, through selective transcorneal absorption. The composition can be a topical ophthalmological composition. The subject can be a human.

[0017] In another aspect, provided herein are topical ophthalmic compositions comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof. In another aspect, provided herein are eye drops comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof.

[0018] In these and other instances, the methods and topical ophthalmological compositions described herein can optionally have the following features. The composition or eye drop can be nonaqueous. The composition or eye drop can further comprise a semi-fluorinated alkane compound. The semi-fluorinated alkane compound can be selected from perfluorobutylheptane (F4H5), perfluorobutylhexane (F4H6), perfluorohexylbutane (F6H4), perfluorohexylhexane (F6H6), perfluorohexyloctane (F6H8), and perfluorohexyldecane (F6H10) and combinations thereof. The method composition or eye drop can further comprise an additive selected from paraffin, propylene glycol diacetate (PGD), a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid, phenethyl alcohol, ethanol, isopropanol, glycerol, propylene glycol, propylene glycol dilaurate, polyethylene glycol, n-butanol, or combinations thereof. The semi-fluorinated alkane compound can be present in a concentration of from about 50% to about 99.9% (w / w) in the topical ophthalmological composition. The additive can be present in a concentration of from about 0.1% to about 50% (w / w). The additive can be present in a concentration of from about 1% to about 30% (w / w) and the semi -fluorinated alkane compound is present in a concentration of from about 70% to about 99% (w / w). The semifluorinated alkane compound can be perfluorohexyloctane (F6H8) or perfluorobutylheptane (F4H5). The etiprednol can be present in an amount of from about 0.005% (w / w) to about 10 % (w / w).

[0019] In these and other instances, the methods and topical ophthalmological compositions described herein can optionally have the following features. The composition or eye drop can be nonaqueous. The composition or eye drop can further comprise a semi-fluorinated alkane compound. The additive can be PGD. The additive can be paraffin. The paraffin can be liquid paraffin. The additive can be a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, or an alkyl ester of a fatty acid. The additive can be a propylene glycol monocaprylate, a propylene glycol dicaprylate, propylene glycol dilaurate, or a combination thereof. The additive can comprise propylene glycol monocaprylate at a purity of at least 90%. The topical composition or eye drop can be in the form of a solution, a suspension, or an emulsion. The topical ophthalmological composition or eye drop can be a nanoemulsion.

[0020] In these and other instances, the methods and topical ophthalmological compositions described herein can optionally have the following features. The composition or eye drop can be nonaqueous. The composition or eye drop can further comprise a semi-fluorinated alkane compound.

[0021] In these and other instances, the methods and topical ophthalmological compositions described herein can optionally have the following features. The additive can be a propylene glycol monocaprylate, a propylene glycol dicaprylate, propylene glycol dilaurate, or a combination thereof, the additive can be present in an amount of from about 1% to about 20% (w / w), and the SFA can be present in an amount of from about 80% to about 99% (w / w). The additive can be PGD, the PGD can be present in an amount of from about 3% to about 10% (w / w), and the SFA can be present in an amount of from about 90% to about 97% (w / w). The additive can be paraffin, the paraffin can be present in an amount of from about 1% to about 20% (w / w), and the SFA can be present in an amount of from about 80% to about 99%. The etiprednol can be etiprednol dicloacetate.

[0022] In another aspect, provided herein are eye drops consisting essentially of etiprednol, or a derivative, analogue, or diastereomer or enantiomer thereof;

[0023] a semi-fluorinated alkane compound; and

[0024] an additive selected from paraffin, propylene glycol diacetate (PGD), a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid, phenethyl alcohol, ethanol, isopropanol, glycerol, propylene glycol, propylene glycol dilaurate, polyethylene glycol, n-butanol, or combinations thereof.

[0025] In some embodiments, the compositions and methods provided herein can provide several advantages. First, in some instances, the compositions provided herein can provide efficacy in treating, slowing the progression of, or reducing one or more symptoms of an ocular inflammatory condition, dry eye diseases, or abnormal corneal neovascularization with a very soft steroid. This can, in some instances, provide efficacy while also providing improved reduction in side effects and systemic effects as compared to conventional corticosteroid treatments.

[0026] Second, in some instances, the compositions and methods provided herein can provide selective transcorneal delivery of etiprednol. This benefit can, in some instances, maximize the effectiveness of the etiprednol in the target tissue before it breaks down chemically, while also limiting its effects on other tissues. This can also help to reduce side effects and systemic effects.

[0027] Third, in some instances, the compositions and methods provided herein can provide stable delivery of etiprednol to maintain efficacy, despite the chemical instability of etiprednol in ocular formulations and the ocular environment.

[0028] Fourth, in some instances, the compositions and methods described herein can be useful for longer term treatment, due to the reduced side effects.

[0029] Other features and advantages of the present application will be apparent from the following detailed description and from the claims.

[0030] DETAILED DESCRIPTION

[0031] Provided herein are compositions for treating, slowing the progression of, or reducing one or more symptoms of an ocular condition. The compositions can, in some instances, comprise etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof. Also provided herein are methods for using the compositions, such as for treating, slowing the progression of, or reducing one or more symptoms of an ocular inflammatory condition, e.g., an ocular inflammatory condition affecting a front of an eye in a subject in need thereof, treating, slowing the progression of, or reducing one or more symptoms of dry eye disease, dry eye syndrome, meibomian gland disfunction, keratoconjunctivitis sicca, inflammatory dry eye disease, or combinations thereof, and treating, slowing the progression of, or reducing one or more symptoms of abnormal corneal neovascularization.

[0032] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application belongs. Methods and materials are described herein for use in the present application; other suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control.

[0033] As used herein, the term “about” means “approximately” (e.g., plus or minus approximately 10% of the indicated value).

[0034] As used herein, the term “contacting” refers to the bringing together of indicated moieties in an in vitro system or an in vivo system. For example, “contacting” the eye tissue with a compound of the invention includes the administration of a compound of the present invention to an individual or patient, such as a human, having the eye tissue in need of treatment, as well as, for example, introducing a compound of the invention into a sample containing a cellular or purified preparation containing the ocular tissue.

[0035] As used herein, the term “individual”, “patient”, or “subject” used interchangeably, refers to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and most preferably humans. In some embodiment, a human subject may be of any age, for example, from 0 to 100 years old. As used herein, “pediatric subject” and “child” are used interchangeably and refer to subjects from 0 to 18 years old, for example, 1, 2, 5, 10, 12, or 14 years old.

[0036] As used herein, the phrase “effective amount” or “therapeutically effective amount” refers to the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue, system, animal, individual or human that is being sought by a researcher, veterinarian, medical doctor or other clinician.

[0037] As used herein the term “treating” or “treatment” refers to 1) inhibiting the disease; for example, inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., arresting further development of the pathology and / or symptomatology), or 2) ameliorating the disease; for example, ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and / or symptomatology). The term “alkyl,” as used herein, refers to saturated, monovalent hydrocarbon moieties having linear or branched moieties or combinations thereof and containing the specified (e.g., 1 to 26) carbon atoms.

[0038] The term “alkenyl,” as used herein, refers to aliphatic hydrocarbon moieties having linear or branched moieties or combinations thereof, containing at least one carbon-carbon double bond and having one of its hydrogen atoms replaced with a bond, and containing the specified (e.g., 1 to 26) carbon atoms.

[0039] The term “cycloalkyl,” as used herein, refers to a monovalent or divalent group of, e.g., 3 to 8 carbon atoms, derived from a saturated cyclic hydrocarbon. Cycloalkyl groups can be monocyclic or polycyclic.

[0040] The term “hydroxyalkyl,” as used herein, refers to an alkyl group as defined above, wherein one or more of the alkyl group's hydrogen atoms have been replaced with an — OH group.

[0041] The term “hydroxyalkenyl,” as used herein, refers to an alkenyl group as defined above, wherein one or more of the alkenyl group's hydrogen atoms have been replaced with an — OH group.

[0042] The formula “H”, as used herein, represents a hydrogen atom.

[0043] The formula “O”, as used herein, represents an oxygen atom.

[0044] The formula “P”, as used herein, represents a phosphorus atom.

[0045] The term “compound” as used herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted, including racemic mixtures. Compounds herein identified by name or structure as one particular tautomeric form are intended to include other tautomeric forms unless otherwise specified.

[0046] The compositions described herein comprise etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof. Etiprednol is a synthetic glucocorticoid corticosteroid having the chemical formula C22H30O5. Etiprednol is also believed to be a second generation soft steroid, with faster inactivation / metabolization than both conventional corticosteroids and first generation soft steroids (such as loteprednol). In some embodiments, the etiprednol is etiprednol dicloacetate. In some instances of the compositions described herein, the composition is nonaqueous. In some instances of the compositions described herein, the composition is a solution, a suspension, an emulsion, or an oil-in-oil emulsion.

[0047] The compositions described herein can include a semifluorinated alkane (SFA). A semifluorinated alkane is an amphiphilic liquid with two mutually immiscible moieties (hydrocarbon segment and perfluorinated segment) bound covalently. In some instances, the semifluorinated alkane can be a partially fluorinated alkane compound having a formula CF3(CF2)m(CH2)nCH3. In some instances, m is an integer from 1 to 10, and n is an integer from 1 to 10. For example, m is can be 1, 2, 3, 4, 5, or 6. In another example, n can be 1, 2, 3, 4, 5, or 6. Suitable examples of semifluorinated alkane compounds include perfluorobutylhexane (F4H6), perfluorohexylbutane (F6H4), perfluorohexylhexane (F6H6), perfluorohexyloctane (F6H8), and perfluorohexyl decane (F6H10). In some instances, the SFA is perfluorohexyloctane (F6H8).

[0048] The structure of F6H8 is shown below:

[0049]

[0050] F6H8 (CF3(CF2)5(CH2)7CH3)

[0051] In some instances, the SFA can be present in the compositions in an amount of from about 50% to about 99% (w / w), from about 60% to about 99% (w / w), from about 65% to about 99% (w / w), from about 70% to about 99% (w / w), from about 75% to about 99% (w / w), from about 80% to about 99% (w / w), from about 85% to about 99% (w / w), from about 90% to about 99% (w / w), from about 95% to about 99% (w / w), from about 50% to about 90% (w / w), from about 60% to about 90% (w / w), from about 70% to about 90% (w / w), about 99% (w / w), about 98% (w / w), about 97% (w / w), about 96% (w / w), about 95% (w / w), about 94% (w / w), about 93% (w / w), about 92% (w / w), about 91% (w / w), about 90% (w / w), about 89% (w / w), about 88% (w / w), about 87% (w / w), about 86% (w / w), about 85% (w / w), about 80% (w / w), about 75% (w / w), about 70% (w / w), about 65% (w / w), about 60% (w / w), about 55% (w / w), or about 50% (w / w). The compositions described herein can include an additive selected from paraffin, medium chain triglycerides (MCT), propylene glycol diacetate (PGD), a semi-fluorinated alkyl alcohol, a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid, phenethyl alcohol, ethanol, isopropanol, glycerol, propylene glycol, propylene glycol dilaurate, polyethylene glycol, n-butanol, or combinations thereof.

[0052] In some instances, the additive can be present in an amount of from about 1% to about 50% (w / w), from about 1% to about 45% (w / w), from about 1% to about 40% (w / w), from about 1% to about 35% (w / w), 1% to about 30% (w / w), from about 1% to about 25% (w / w), from about 1% to about 20% (w / w), from about 1% to about 15% (w / w), from about 1% to about 10% (w / w), from about 5% to about 20% (w / w), from about 5% to about 15% (w / w), from about 10% to about 15% (w / w), from about 10% to about 20% (w / w), from about 10% to about 30% (w / w), about 30% (w / w), about 25% (w / w), about 20% (w / w), about 15% (w / w), about 10% (w / w), about 9% (w / w), about 8% (w / w), about 7% (w / w), about 6% (w / w), about 5% (w / w), about 4% (w / w), about 3% (w / w), about 2% (w / w), or about 1% (w / w).

[0053] In some instances, the compositions described herein can include paraffin. In some instances, the paraffin can be liquid paraffin.

[0054] In some instances, the compositions described herein can include propylene glycol diacetate (PGD), also known as 1,2-Diacetoxypropane.

[0055] In some instances, the compositions described herein can include propylene glycol dilaurate (PG-2L).

[0056] In some instances, the compositions described herein can include medium chain triglycerides (MCT). Medium-chain triglycerides (MCTs) are triglycerides of fatty acids. The fatty acids have an aliphatic chain of 6-12 carbon atoms, and can be, for example, hexanoic acid, octanoic acid, decanoic acid, and dodecanoic acid. The MCTs can be a single triglyceride or a mixture of triglycerides. Representative chemical structures of the MCTs are shown below. '9

[0057]

[0058] In some instances, the fatty acids in the MCT can comprise hexanoic acid, octanoic acid, decanoic acid, dodecanoic acid or combinations of two or more thereof. In some instances, the fatty acids in the MCT consist essentially of hexanoic acid, octanoic acid, decanoic acid, dodecanoic acid or combinations thereof.

[0059] In some instances, the MCT can be present in the compositions in an amount of from about 1% to about 50% (w / w), from about 1% to about 45% (w / w), from about 1% to about 40% (w / w), from about 1% to about 35% (w / w), 1% to about 30% (w / w), from about 1% to about 25% (w / w), from about 1% to about 20% (w / w), from about 1% to about 15% (w / w), from about 1% to about 10% (w / w), from about 5% to about 20% (w / w), from about 5% to about 15% (w / w), from about 10% to about 15% (w / w), from about 10% to about 20% (w / w), from about 10% to about 30% (w / w), about 30% (w / w), about 25% (w / w), about 20% (w / w), about 15% (w / w), about 10% (w / w), about 9% (w / w), about 8% (w / w), about 7% (w / w), about 6% (w / w), about 5% (w / w), about 4% (w / w), about 3% (w / w), about 2% (w / w), or about 1% (w / w). In some instances, the MCT can be present in the compositions in an amount of from about 5% to about 20% (w / w) MCT.

[0060] The compositions described herein can include a semi-fluorinated alkyl alcohol compound (SFAOH).

[0061] In some instances, the semi-fluorinated alkyl alcohol can be a partially fluorinated alkyl alcohol compound having a formula F(CF2)xR1(OH)y. In some instances, R1can be a linear or branched alkyl having 1 to 8 carbon atoms. In some instances, x is an integer from 1 to 10, and y is an integer from 1 to 4. For example, x can be 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In another example, y can be 1, 2, 3, or 4, 5. Exemplary, non-limiting semifluorinated alkyl alcohols include 4,4,5,5,5-pentafluoro-l-pentanol; 4,4,4-trifluoro-l-butanol; 3,3,3-trifluoro-l-proponal; 2,2,3,3,4,4,4-heptafluoro-l-butanol; 2, 2, 3, 3, 4, 4, 5,5,5- nonafluoro- 1 -pentanol; 1H, IH-perfluorohexan-l -ol; 1H, 1 H-perfluoro- 1 -heptanol;

[0062] 1 H, 1 H-perfluoro- 1 -octanol; 1H, 1 H-perfluoro- 1 -nonanol; 3 -(perfluorohexyl)propanol- 1; and 7,7,8,8,8-pentafluorooctan-l-ol.

[0063] In some embodiments, the SFAOH can be present in the compositions in an amount of from about 0.1% to about 99% (w / w), from about 0.1% to about 80% (w / w), from about 0.1% to about 50% (w / w), from about 0.1% to about 30% (w / w), from about 0.1% to about 20% (w / w), from about 0.1% to about 15% (w / w), from about 0.1% to about 10% (w / w), from about 0.1% to about 5% (w / w), about 20% (w / w), about 15% (w / w), about 10% (w / w), about 5% (w / w), about 3% (w / w), or about 1% (w / w), from about 1% to about 30% (w / w), from about 1% to about 25% (w / w), from about 1% to about 20% (w / w), from about 5% to about 20% (w / w), from about 5% to about 15% (w / w), from about 10% to about 99.9% (w / w), from about 20% to about 99.9% (w / w), from about 30% to about 99.9% (w / w), from about 40% to about 99.9% (w / w), from about 50% to about 99.9% (w / w), from about 60% to about 99.9% (w / w), from about 65% to about 99.9% (w / w), from about 70% to about 99.9% (w / w), from about 75% to about 99.9% (w / w), from about 80% to about 99.9% (w / w), from about 85% to about 99.9% (w / w), from about 90% to about 99.9% (w / w), from about 95% to about 99.9% (w / w), from about 98% to about 99.9% (w / w), from about 20% to about 80% (w / w), from about 20% to about 70% (w / w), from about 20% to about 60% (w / w), from about 20% to about 50% (w / w), from about 20% to about 40 % (w / w), from about 20% to about 30% (w / w), from about 30% to about 80% (w / w), from about 40% to about 80% (w / w), from about 50% to about 80% (w / w), from about 60% to about 80% (w / w), from about 70% to about 80% (w / w), from about 50% to about 90% (w / w), from about 60% to about 90% (w / w), from about 70% to about 90% (w / w), about 99.9% (w / w), about 99% (w / w), about 98% (w / w), about 97% (w / w), about 96% (w / w), about 95% (w / w), about 94% (w / w), about 93% (w / w), about 92% (w / w), about 91% (w / w), about 90% (w / w), about 85% (w / w), about 80% (w / w), about 75% (w / w), about 70% (w / w), about 65% (w / w), about 60% (w / w), about 55% (w / w), about 50% (w / w), about 45% (w / w), about 40% (w / w), about 35% (w / w), about 30% (w / w), about 25% (w / w), about 20% (w / w), about 15% (w / w), about 10% (w / w), about 9% (w / w), about 8% (w / w), about 7% (w / w), about 6% (w / w), about 5% (w / w), about 4% (w / w), about 3% (w / w), about 2% (w / w), about 1% (w / w), about 0.5% (w / w), or about 0.1% (w / w), from about 1% to about 30% (w / w), from about 1% to about 25% (w / w), from about 1% to about 20% (w / w), from about 1% to about 15% (w / w), from about 1% to about 10% (w / w), from about 5% to about 20% (w / w), from about 5% to about 15% (w / w), from about 10% to about 15% (w / w), from about 10% to about 20% (w / w), from about 10% to about 30% (w / w), about 30% (w / w), about 25% (w / w), about 20% (w / w), about 15% (w / w), about 10% (w / w), about 9% (w / w), about 8% (w / w), about 7% (w / w), about 6% (w / w), about 5% (w / w), about 4% (w / w), about 3% (w / w), about 2% (w / w), or about 1% (w / w).

[0064] The compositions described herein can include one or more additive compound(s) that are oils with certain ester functionality. The one or more additive compound(s) can be selected from a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid; and combinations thereof.

[0065] In some instances, the additive can be oils with certain ester functionality and can be selected from a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid; and combinations thereof. In some instances, the additive compound(s) can comprise more than one ester group. Where more than one ester group is present in the additive compound, each acyl group in the compound can independently derive from a same or different fatty acid. In some instances, the additive compound(s) can be a mixture of two or more different additive compounds selected from hydroxyalkyl esters of an aliphatic fatty acid, hydroxyacid alkyl esters, alkyl esters of fatty acids, or combinations thereof. In some instances, at least one of the one or more additive compound(s) has a hydrophilic-lipophilic balance (HLB) value of less than or equal to 3.4 as calculated according to the formula: HLB = 20(1 -(S / A)), wherein S is number of ester saponification, and A is the acid number of the fatty acid.

[0066] In some instances, the additive compound(s) can be a hydroxyalkyl ester of an aliphatic fatty acid. In some instances, the hydroxyalkyl ester of an aliphatic fatty acid can be a propylene glycol mono or di-ester of C4-C20 fatty acid, or a glycerol of 1, 2 or 1, 3 di -ester of C4-C20 fatty acid, or a glycerol of a mono ester of a C4-20 fatty acid. The fatty acid can be saturated or unsaturated, linear or branched.

[0067] In some instances, the hydroxyalkyl ester of an aliphatic fatty acid is a compound of any one of Formulas (II)-(VIII):

[0068]

[0069] (Formula 11)

[0070]

[0071] (Formula III) O.

[0072] (••OH

[0073] R

[0074]

[0075] (Formula IV)

[0076]

[0077] (Formula V)

[0078]

[0079] (Formula VI)

[0080] O

[0081] kOH

[0082]

[0083] (Formula VII)

[0084] ; and

[0085] .—OH

[0086] ko

[0087] i

[0088] J O'

[0089]

[0090] HO" '

[0091] (Formula Vlll)

[0092] In some instances, R6and R7can each, independently, be a linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl having 3 to 19 carbon atoms. In some instances, R6and R7can each, independently, be a linear or branched alkyl having 7 to 17 carbon atoms. In some instances, R can be H or an aliphatic linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl group having 1-6 carbon atoms, optionally wherein one H atom on each carbon atom can independently be replaced with one -OH group. In some instances, R can be H or an aliphatic linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl group having 1-4 carbon atoms. In some instances, for R, one H atom on each carbon atom can independently be replaced with one -OH group. In some instances, n is an integer from 1 to 12, optionally from 2 to 3. For example, n can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12. In some instances, the additive compound(s) can be an alkyl ester of a fatty acid. In some instances, the alkyl ester of a fatty acid is a compound of Formula (IX):

[0093] 0

[0094]

[0095] (Formula IX)

[0096] In some instances, x is an integer from 2 to 3. In some instances, y is an integer from 4 to 7. For example, x can be 2 or 3. In another example, y can be 4, 5, 6, or 7.

[0097] In some instances, the additive compound(s) can be a hydroxyacid alkyl ester. In some instances, the hydroxyacid alkyl ester can be a medium-chain alkyl C12 to C15 lactate or glycolate. In some instances, the hydroxyacid alkyl ester can be a compound of any one of Formulas (X)-(XII):

[0098] O-Rg

[0099] o

[0100] OH

[0101] (Formula X)

[0102]

[0103] (Formula XI)

[0104] ; and 0,

[0105] tf

[0106] U-R

[0107] 0

[0108] 1 J

[0109]

[0110] R O'

[0111] (Formula XII)

[0112] In some instances, R6and R7can each, independently, be a linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl having 3 to 19 carbon atoms. In some instances, R6and R7can each, independently, be a linear or branched alkyl having 7 to 17 carbon atoms. In some instances, R can be H or an aliphatic linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl group having 1-6 carbon atoms, optionally wherein one H atom on each carbon atom can independently be replaced with one -OH group. In some instances, R can be H or an aliphatic linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl group having 1-4 carbon atoms. In some instances, for R, one H atom on each carbon atom can independently be replaced with one -OH group. In some instances, R8can be a linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl having 6 to 20 carbon atoms. In some instances, R8can be a linear or branched alkyl having 12 to 15 carbon atoms.

[0113] Exemplary, non-limiting additive compounds include3-hydroxypropane-1,2-diyl bis(icosanoate); 3-hydroxypropane-l,2-diyl dinonadecanoate; 3-hydroxypropane-l,2-diyl distearate; 3-hydroxypropane-l,2-diyl diheptadecanoate; 3-hydroxypropane-l,2-diyl dipalmitate; 3-hydroxypropane-l,2-diyl dipentadecanoate; 3 -hydroxypropane- 1,2-diyl ditetradecanoate; 3-hydroxypropane-l,2-diyl ditridecanoate; 3-hydroxypropane-l,2-diyl didodecanoate; 3 -hydroxy propane- 1,2-diyl diundecanoate; 3-hydroxypropane-l,2-diyl bis(decanoate); 3 -hydroxypropane- 1,2-diyl dinonanoate; 3 -hydroxypropane- 1,2-diyl dioctanoate; l-(heptanoyloxy)-3-hydroxypropan-2-yl octanoate; 3 -hydroxypropane- 1,2-diyl diheptanoate; 2-(heptanoyloxy)-3-hydroxypropyl octanoate; l-(hexanoyloxy)-3-hydroxypropan-2-yl heptanoate; 3 -hydroxypropane- 1,2-diyl dihexanoate; l-hydroxy-3-(pentanoyloxy)propan-2-yl hexanoate; l-(butyryloxy)-3-hydroxypropan-2-yl hexanoate; l-(butyryloxy)-3-hydroxypropan-2-yl pentanoate; 3 -hydroxypropane- 1,2-diyl dibutyrate; 1 -(butyryloxy)-3-hydroxypropan-2-yl octanoate; 2-(butyryloxy)-3-hydroxypropyl octanoate; 2-hydroxypropane- 1,3 -diyl bis(icosanoate); 2-hydroxypropane- 1,3 -diyl dinonadecanoate; 2-hydroxypropane- 1,3-diyl distearate; 2-hydroxypropane- 1,3 -diyl diheptadecanoate; 2-hydroxypropane- 1,3 -diyl dipalmitate; 2-hydroxypropane- 1,3 -diyl dipentadecanoate; 2-hydroxypropane- 1,3 -diyl di tetradecanoate; 2-hydroxypropane- 1,3-diyl ditridecanoate; 2-hydroxypropane- 1,3 -diyl didodecanoate; 2-hydroxypropane- 1,3-diyl bis(decanoate); 2-hydroxy-3-(octanoyloxy)propyl decanoate; 2-hydroxypropane- 1,3-diyl dioctanoate; 3 -(hexanoyloxy)-2-hydroxy propyl octanoate; 2-hydroxypropane- 1,3-diyl dihexanoate; 3-(hexanoyloxy)-2-hydroxypropyl octanoate; 3-(butyryloxy)-2-hydroxypropyl octanoate; 3-(butyryloxy)-2-hydroxypropyl hexanoate; 2-hydroxypropane- 1,3-diyl dibutyrate; 2-hydroxy octyl icosanoate; 2-hydroxyheptyl icosanoate; 2-hydroxyhexyl icosanoate; 2-hydroxypentyl icosanoate; 2-hydroxypentyl stearate; 2-hydroxypropyl stearate; 2-hydroxybutyl stearate; 2-hydroxybutyl palmitate; 2-hydroxypentyl palmitate; 2-hydroxypentyl tetradecanoate; 2-hydroxybutyl tetradecanoate; 2-hydroxypropyl tetradecanoate; 2-hydroxypentyl dodecanoate; 2-hydroxybutyl dodecanoate; 2-hydroxypropyl dodecanoate; 2-hydroxypropyl decanoate; 2-hydroxybutyl decanoate; 2-hydroxypentyl decanoate; 2-hydroxypentyl octanoate; 2-hydroxybutyl octanoate; 2-hydroxypropyl octanoate; 2-hydroxypropyl hexanoate; 2-hydroxypropyl butyrate; 2-hydroxybutyl butyrate; 1 -hydroxy octan-2-yl icosanoate; 1-hydroxyoctan-2-yl stearate; l-hydroxyhexan-2-yl stearate; 1 -hydroxypentan-2-yl stearate; 1-hydroxypentan-2-yl palmitate; 1 -hydroxypropan-2-yl stearate; 1 -hydroxypropan-2-yl palmitate; 1 -hydroxypropan -2 -yl tetradecanoate; l-hydroxypropan-2-yl dodecanoate; 1-hydroxypropan-2-yl decanoate; 1 -hydroxypropan -2-yl octanoate; l-hydroxypropan-2-yl hexanoate; l-hydroxypropan-2-yl butyrate; 1 -hydroxybutan-2-yl butyrate; 1-hydroxypentan-2-yl butyrate; 1 -hydroxy octan-2-yl butyrate; 2-hydroxy ethyl icosanoate; 2-hydroxyethyl stearate; 2-hydroxyethyl palmitate; 2-hydroxyethyl tetradecanoate; 2-hydroxyethyl dodecanoate; 2-hydroxyethyl decanoate; 2-hydroxyethyl octanoate; 2-hydroxy ethyl hexanoate; 2-hydroxyethyl butyrate; 3-hydroxypropyl butyrate; 3-hydroxypropyl hexanoate; 3-hydroxypropyl pentanoate; 3-hydroxypropyl heptanoate; 3-hydroxypropyl octanoate; 3-hydroxypropyl decanoate; 3-hydroxypropyl dodecanoate; 3-hydroxypropyl tetradecanoate; 3-hydroxypropyl palmitate; 3-hydroxypropyl stearate; 3- hydroxypropyl icosanoate; pentadecyl 2-hydroxypropanoate; pentadecyl 2-hydroxyacetate; tetradecyl 2-hydroxypropanoate; tetradecyl 2-hydroxyacetate; tridecyl 2-hydroxyacetate; tridecyl 2-hydroxypropanoate; dodecyl 2-hydroxypropanoate; dodecyl 2-hydroxyacetate; decyl 2-hydroxyacetate; decyl 2-hydroxypropanoate; octyl 2-hydroxypropanoate; 2,3-dihydroxypropyl icosanoate; 2,3-dihydroxypropyl stearate; 2,3-dihydroxypropyl palmitate; 2,3-dihydroxypropyl tetradecanoate; 2,3-dihydroxypropyl dodecanoate; 2,3-dihydroxypropyl decanoate; 2,3-dihydroxypropyl octanoate; 2,3-dihydroxypropyl hexanoate; 2,3-dihydroxypropyl butyrate; l,3-dihydroxypropan-2-yl butyrate; l,3-dihydroxypropan-2-yl pentanoate; l,3-dihydroxypropan-2-yl hexanoate; 1.3-dihydroxypropan-2-yl heptanoate; l,3-dihydroxypropan-2-yl octanoate; 1,3-dihydroxypropan-2-yl nonanoate; l,3-dihydroxypropan-2-yl decanoate; 1,3-dihydroxypropan-2-yl dodecanoate; 1, 3 -dihydroxypropan-2-yl tetradecanoate; 1,3-dihydroxypropan-2-yl palmitate; l,3-dihydroxypropan-2-yl stearate; 1,3-dihydroxypropan-2-yl icosanoate; 2,3-dihydroxypropyl nonanoate; 2,3-dihydroxypropyl heptanoate; 2,3-dihydroxypropyl pentanoate; dodecyl octanoate; tetradecyl octanoate; hexadecyl octanoate; octadecyl octanoate; octadecyl decanoate; hexadecyl decanoate; tetradecyl decanoate; and dodecyl decanoate; propane- 1,2-diyl dibutyrate; 2-(butyryloxy)propyl pentanoate; propane- 1,2-diyl dipentanoate; 2-(pentanoyloxy)propyl hexanoate; propane- 1,2-diyl dihexanoate; 2-(hexanoyloxy)propyl heptanoate; 2-(heptanoyloxy)propyl octanoate; 2-(heptanoyloxy)propyl nonanoate; 2-(octanoyloxy)propyl nonanoate; propane- 1,2-diyl dinonanoate; 2-(nonanoyloxy)propyl decanoate; propane- 1,2-diyl bis(decanoate); 2-(decanoyloxy)propyl dodecanoate; propane- 1,2-diyl didodecanoate; 2-(dodecanoyloxy)propyl tetradecanoate; propane- 1,2-diyl di tetradecanoate; 1 -(tetradecanoyloxy)propan-2-yl palmitate; propane- 1,2-diyl dipalmitate; l-(palmitoyloxy)propan-2-yl stearate; propane- 1,2-diyl distearate; 2-(stearoyloxy)propyl icosanoate; propane- 1,2-diyl bis(icosanoate); 2-m ethylpropane- 1,3-diyl bis(icosanoate); 2-methyl-3-(stearoyloxy)propyl icosanoate; 2-methylpropane- 1,3-diyl distearate; 2-methyl-3 -(palmitoyloxy )propyl stearate; 2-methylpropane- 1,3 -diyl dipalmitate; 2-methyl-3-(tetradecanoyloxy)propyl palmitate; 2-methylpropane- 1,3 -diyl di tetradecanoate; 3-(dodecanoyloxy)-2-methylpropyl tetradecanoate; 2-methylpropane- 1.3 -diyl didodecanoate; 3-(decanoyloxy)-2-methylpropyl dodecanoate; 2-methylpropane- 1,3-diyl bis(decanoate); 2-methyl-3-(nonanoyloxy)propyl decanoate; 2-methylpropane-1,3-diyl dinonanoate; 2-methyl-3-(octanoyloxy)propyl nonanoate; 2-methylpropane-l,3-diyl dioctanoate; 3-(heptanoyloxy)-2-methylpropyl octanoate; 3-(hexanoyloxy)-2-methylpropyl octanoate; 3 -(hexanoyloxy)-2-m ethylpropyl heptanoate; 2-methyl-3-(pentanoyloxy)propyl hexanoate; 3-(butyryloxy)-2-methylpropyl pentanoate; 2-methylpropane- 1,3 -diyl dibutyrate; a cetostearyl alcohol; a cetyl alcohol; docosanol; ethylhexyl hydroxystearate; glyceryl 1 -stearate; glyceryl dibehenate; glyceryl distearate; glycerylricinoleate; lauryl lactate; a lauroyl polyoxylglyceride; a myristyl alcohol; octyldodecanol; polyoxyl 35 castor oil; polyoxyl 40 hydrogented castor oil; polyoxyl 40 stearate; sorbitan monolaurate; sorbitan monooleate; sorbitan monopalmitate; sorbitan monostearate; sorbitan sesquioleate; sorbitan trioleate; sorbitan tristearate; trihydroxy stearin; and combinations of two or more thereof.

[0114] The compositions described herein can include one or more excipient compound(s) that are oils with certain ester functionality. The one or more excipient compound(s) can be selected from a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid; and combinations thereof.

[0115] Applicant has surprisingly found that the addition of these excipient compounds (or combinations thereof) can result in solubility of APIs in the composition, e.g., in SFAs. Without being bound by theory, it is believed that the ester functionality of the excipient compound(s) allows good solubility, miscibility, and / or emulsifying capability in the SFA of the compositions. Applicant has surprisingly found that the inclusion of the excipient compound(s) in the compositions described herein can create a suitable delivery system for APIs, including both water soluble and water insoluble APIs. The compositions described herein can thus provide suitable delivery compositions for water insoluble APIs for which there were, prior to the present invention disclosed herein, very limited ways to formulate, or APIs that have low solubility in aqueous formulations. Nonlimiting examples of APIs that have limited or no solubility in aqueous formulations that can be suitably formulated in compositions described herein include, APIs such as steroids, tyrosine kinase inhibitor class compounds, and compounds containing one or more aromatic heterocyclic functionalities. In some instances, the excipient compound(s) are oils with certain ester functionality and can be selected from a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid; and combinations thereof. In some instances, the excipient compound(s) can comprise more than one ester group. Where more than one ester group is present in the excipient compound, each acyl group in the compound can independently derive from a same or different fatty acid. In some instances, the excipient compound(s) can be a mixture of two or more different excipient compounds selected from hydroxyalkyl esters of an aliphatic fatty acid, hydroxyacid alkyl esters, alkyl esters of fatty acids, or combinations thereof. In some instances, at least one of the one or more excipient compound(s) has a hydrophilic-lipophilic balance (HLB) value of less than or equal to 3.4 as calculated according to the formula: HLB = 20(l-(S / A)), wherein S is number of ester saponification, and A is the acid number of the fatty acid.

[0116] In some instances, the excipient compound(s) can be a hydroxyalkyl ester of an aliphatic fatty acid. In some instances, the hydroxyalkyl ester of an aliphatic fatty acid can be a propylene glycol mono or di-ester of C4-C20 fatty acid, or a glycerol of 1, 2 or 1, 3 di -ester of C4-C20 fatty acid, or a glycerol of a mono ester of a C4-20 fatty acid. The fatty acid can be saturated or unsaturated, linear or branched.

[0117] In some instances, the hydroxyalkyl ester of an aliphatic fatty acid is a compound of any one of Formulas (II)-(VIII):

[0118] O,

[0119] rd

[0120] i-o

[0121] i

[0122]

[0123] (Formula II)

[0124]

[0125] (Formula III) p y-R1r-o

[0126]

[0127] R (Formula IV)

[0128]

[0129] (Formula V)

[0130]

[0131] HO

[0132] (Formul a VI) Q

[0133] W

[0134] ■d

[0135]

[0136] (Formula VII)

[0137] ; and

[0138]

[0139] (Formula VIII)

[0140] In some instances, R6and R7can each, independently, be a linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl having 3 to 19 carbon atoms. In some instances, R6and R7can each, independently, be a linear or branched alkyl having 7 to 17 carbon atoms. In some instances, R can be H or an aliphatic linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl group having 1-6 carbon atoms, optionally wherein one H atom on each carbon atom can independently be replaced with one -OH group. In some instances, R can be H or an aliphatic linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxy alkenyl group having 1-4 carbon atoms. In some instances, for R, one H atom on each carbon atom can independently be replaced with one -OH group. In some instances, n is an integer from 1 to 12, optionally from 2 to 3. For example, n can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12.

[0141] In some instances, the excipient compound(s) can be an alkyl ester of a fatty acid. In some instances, the alkyl ester of a fatty acid is a compound of Formula (IX):

[0142] y

[0143] (Formula IX)

[0144]

[0145] In some instances, x is an integer from 2 to 3. In some instances, y is an integer from 4 to 7. For example, x can be 2 or 3. In another example, y can be 4, 5, 6, or 7.

[0146] In some instances, the excipient compound(s) can be a hydroxyacid alkyl ester. In some instances, the hydroxyacid alkyl ester can be a medium-chain alkyl C12 to C15 lactate or glycolate. In some instances, the hydroxyacid alkyl ester can be a compound of any one of Formulas (X)-(XII):

[0147] O-Rg

[0148] o

[0149] on

[0150] R

[0151] (Formula X)

[0152] 0

[0153]

[0154] (Formula XI)

[0155] ; and

[0156] 0

[0157] 'W

[0158] R

[0159]

[0160] (Formula XII)

[0161] In some instances, R6and R7can each, independently, be a linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl having 3 to 19 carbon atoms. In some instances, R6and R7can each, independently, be a linear or branched alkyl having 7 to 17 carbon atoms. In some instances, R can be H or an aliphatic linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl group having 1-6 carbon atoms, optionally wherein one H atom on each carbon atom can independently be replaced with one -OH group. In some instances, R can be H or an aliphatic linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl group having 1-4 carbon atoms. In some instances, for R, one H atom on each carbon atom can independently be replaced with one -OH group. In some instances, R8can be a linear or branched alkyl, alkenyl, hydroxyalkyl, or hydroxyalkenyl having 6 to 20 carbon atoms. In some instances, R8can be a linear or branched alkyl having 12 to 15 carbon atoms.

[0162] Exemplary, non-limiting excipient compounds include3-hydroxypropane-1,2-diyl bis(icosanoate); 3 -hydroxypropane- 1,2-diyl dinonadecanoate; 3 -hydroxypropane- 1,2-diyl distearate; 3 -hydroxypropane- 1,2-diyl diheptadecanoate; 3-hydroxypropane- 1,2-diyl dipalmitate; 3 -hydroxypropane- 1,2-diyl dipentadecanoate; 3 -hydroxypropane- 1,2-diyl di tetradecanoate; 3 -hydroxypropane- 1,2-diyl ditridecanoate; 3-hydroxypropane- 1,2-diyl didodecanoate; 3-hydroxypropane- 1,2-diyl diundecanoate; 3-hydroxypropane- 1,2-diyl bis(decanoate); 3-hydroxypropane- 1,2-diyl dinonanoate; 3 -hydroxypropane- 1,2-diyl dioctanoate; l-(heptanoyloxy)-3-hydroxypropan-2-yl octanoate; 3-hydroxypropane- 1,2-diyl diheptanoate; 2-(heptanoyloxy)-3 -hydroxypropyl octanoate; l-(hexanoyloxy)-3-hydroxypropan-2-yl heptanoate; 3 -hydroxypropane- 1,2-diyl dihexanoate; 1 -hydroxy-3 -(pentanoyloxy)propan-2-yl hexanoate; l-(butyryloxy)-3-hydroxypropan-2-yl hexanoate; l-(butyryloxy)-3-hydroxypropan-2-yl pentanoate; 3 -hydroxypropane- 1,2-diyl dibutyrate; 1 -(butyryloxy)-3-hydroxypropan-2-yl octanoate; 2-(butyryloxy)-3-hydroxypropyl octanoate; 2-hydroxypropane- 1,3 -diyl bis(icosanoate); 2-hydroxypropane- 1,3 -diyl dinonadecanoate; 2-hydroxypropane- 1,3-diyl distearate; 2-hydroxypropane- 1,3 -diyl diheptadecanoate; 2-hydroxypropane- 1,3 -diyl dipalmitate; 2-hydroxypropane- 1,3 -diyl dipentadecanoate; 2-hydroxypropane- 1,3 -diyl ditetradecanoate; 2-hydroxypropane- 1,3-diyl ditridecanoate; 2-hydroxypropane- 1,3 -diyl didodecanoate; 2-hydroxypropane- 1,3-diyl bis(decanoate); 2-hydroxy-3-(octanoyloxy)propyl decanoate; 2-hydroxypropane- 1,3-diyl dioctanoate; 3-(hexanoyloxy)-2-hydroxypropyl octanoate; 2-hydroxypropane- 1,3-diyl dihexanoate; 3-(hexanoyloxy)-2-hydroxypropyl octanoate; 3-(butyryloxy)-2-hydroxypropyl octanoate; 3-(butyryloxy)-2-hydroxypropyl hexanoate; 2-hydroxypropane- 1,3-diyl dibutyrate; 2-hydroxyoctyl icosanoate; 2-hydroxyheptyl icosanoate; 2-hydroxyhexyl icosanoate; 2-hydroxypentyl icosanoate; 2-hydroxypentyl stearate; 2-hydroxypropyl stearate; 2-hydroxybutyl stearate; 2-hydroxybutyl palmitate; 2-hydroxypentyl palmitate; 2-hydroxypentyl tetradecanoate; 2-hydroxybutyl tetradecanoate; 2-hydroxypropyl tetradecanoate; 2-hydroxypentyl dodecanoate; 2-hydroxybutyl dodecanoate; 2-hydroxypropyl dodecanoate; 2-hydroxypropyl decanoate; 2-hydroxybutyl decanoate; 2-hydroxypentyl decanoate; 2-hydroxypentyl octanoate; 2-hydroxybutyl octanoate; 2-hydroxypropyl octanoate; 2-hydroxypropyl hexanoate; 2-hydroxypropyl butyrate; 2-hydroxybutyl butyrate; 1 -hydroxy octan-2-yl icosanoate; 1-hydroxyoctan-2-yl stearate; l-hydroxyhexan-2-yl stearate; 1 -hydroxypentan-2-yl stearate; 1-hydroxypentan-2-yl palmitate; 1 -hydroxypropan-2-yl stearate; 1 -hydroxypropan-2-yl palmitate; 1 -hydroxypropan -2 -yl tetradecanoate; l-hydroxypropan-2-yl dodecanoate; 1-hydroxypropan-2-yl decanoate; 1 -hydroxypropan-2-yl octanoate; l-hydroxypropan-2-yl hexanoate; l-hydroxypropan-2-yl butyrate; 1 -hydroxybutan-2-yl butyrate; 1-hydroxypentan-2-yl butyrate; 1 -hydroxy octan-2-yl butyrate; 2-hydroxy ethyl icosanoate; 2-hydroxyethyl stearate; 2-hydroxyethyl palmitate; 2-hydroxyethyl tetradecanoate; 2-hydroxyethyl dodecanoate; 2-hydroxyethyl decanoate; 2-hydroxyethyl octanoate; 2-hydroxy ethyl hexanoate; 2-hydroxyethyl butyrate; 3-hydroxypropyl butyrate; 3-hydroxypropyl hexanoate; 3-hydroxypropyl pentanoate; 3-hydroxypropyl heptanoate; 3-hydroxypropyl octanoate; 3-hydroxypropyl decanoate; 3-hydroxypropyl dodecanoate; 3-hydroxypropyl tetradecanoate; 3-hydroxypropyl palmitate; 3-hydroxypropyl stearate; 3-hydroxypropyl icosanoate; pentadecyl 2-hydroxypropanoate; pentadecyl 2-hydroxyacetate; tetradecyl 2-hydroxypropanoate; tetradecyl 2-hydroxyacetate; tridecyl 2-hydroxyacetate; tridecyl 2-hydroxypropanoate; dodecyl 2-hydroxypropanoate; dodecyl 2-hydroxyacetate; decyl 2-hydroxyacetate; decyl 2-hydroxypropanoate; octyl 2-hydroxypropanoate; 2, 3 -dihydroxy propyl icosanoate; 2,3-dihydroxypropyl stearate; 2,3-dihydroxypropyl palmitate; 2,3-dihydroxypropyl tetradecanoate; 2,3-dihydroxypropyl dodecanoate; 2,3-dihydroxypropyl decanoate; 2,3-dihydroxypropyl octanoate; 2,3-dihydroxypropyl hexanoate; 2,3-dihydroxypropyl butyrate; l,3-dihydroxypropan-2-yl butyrate; l,3-dihydroxypropan-2-yl pentanoate; l,3-dihydroxypropan-2-yl hexanoate; l,3-dihydroxypropan-2-yl heptanoate; l,3-dihydroxypropan-2-yl octanoate; 1,3-dihydroxypropan-2-yl nonanoate; l,3-dihydroxypropan-2-yl decanoate; 1,3- dihydroxypropan-2-yl dodecanoate; l,3-dihydroxypropan-2-yl tetradecanoate; 1,3-dihydroxypropan-2-yl palmitate; l,3-dihydroxypropan-2-yl stearate; 1,3-dihydroxypropan-2-yl icosanoate; 2,3 -dihydroxypropyl nonanoate; 2,3-dihydroxypropyl heptanoate; 2,3-dihydroxypropyl pentanoate; dodecyl octanoate; tetradecyl octanoate; hexadecyl octanoate; octadecyl octanoate; octadecyl decanoate; hexadecyl decanoate; tetradecyl decanoate; and dodecyl decanoate; propane- 1,2-diyl dibutyrate; 2-(butyryloxy)propyl pentanoate; propane- 1,2-diyl dipentanoate; 2-(pentanoyloxy)propyl hexanoate; propane- 1,2-diyl dihexanoate; 2-(hexanoyloxy)propyl heptanoate; 2-(heptanoyloxy)propyl octanoate; 2-(heptanoyloxy)propyl nonanoate; 2-(octanoyloxy)propyl nonanoate; propane- 1,2-diyl dinonanoate; 2-(nonanoyloxy)propyl decanoate; propane- 1,2-diyl bis(decanoate); 2-(decanoyloxy)propyl dodecanoate; propane- 1,2-diyl didodecanoate; 2-(dodecanoyloxy)propyl tetradecanoate; propane- 1,2-diyl ditetradecanoate; 1 -(tetradecanoyloxy)propan-2-yl palmitate; propane- 1,2-diyl dipalmitate; l-(palmitoyloxy)propan-2-yl stearate; propane- 1,2-diyl distearate; 2-(stearoyloxy)propyl icosanoate; propane- 1,2-diyl bis(icosanoate); 2-methylpropane-1,3-diyl bis(icosanoate); 2-methyl-3-(stearoyloxy)propyl icosanoate; 2-methylpropane- 1,3-diyl distearate; 2-methyl-3-(palmitoyloxy)propyl stearate; 2-methylpropane- 1,3 -diyl dipalmitate; 2-methyl-3-(tetradecanoyloxy)propyl palmitate; 2-methylpropane- 1,3 -diyl di tetradecanoate; 3-(dodecanoyloxy)-2-methylpropyl tetradecanoate; 2-methylpropane- 1,3 -diyl didodecanoate; 3-(decanoyloxy)-2-methylpropyl dodecanoate; 2-methylpropane- 1,3 -diyl bis(decanoate); 2-methyl-3-(nonanoyloxy)propyl decanoate; 2-methylpropane- 1,3 -diyl dinonanoate; 2-methyl-3-(octanoyloxy)propyl nonanoate; 2-methylpropane- 1,3-diyl dioctanoate; 3-(heptanoyloxy)-2-methylpropyl octanoate; 3-(hexanoyloxy)-2-m ethylpropyl octanoate; 3 -(hexanoy loxy)-2-m ethylpropyl heptanoate; 2-methyl-3-(pentanoyloxy)propyl hexanoate; 3-(butyryloxy)-2-methylpropyl pentanoate; 2-m ethylpropane- 1,3 -diyl dibutyrate; a cetostearyl alcohol; a cetyl alcohol; docosanol; ethylhexyl hydroxystearate; glyceryl 1 -stearate; glyceryl dibehenate; glyceryl distearate; glycerylricinoleate; lauryl lactate; a lauroyl polyoxylglyceride; a myristyl alcohol; octyldodecanol; polyoxyl 35 castor oil; polyoxyl 40 hydrogented castor oil; polyoxyl 40 stearate; sorbitan monolaurate; sorbitan monooleate; sorbitan monopalmitate; sorbitan monostearate; sorbitan sesquioleate; sorbitan trioleate; sorbitan tristearate; trihydroxy stearin; and combinations of two or more thereof.

[0163] In some instances, the additive can be a propylene glycol monocaprylate, a propylene glycol dicaprylate, or a combination thereof. In some instances, the additive can be a purified form of propylene glycol monocaprylate. For example, the propylene glycol monocaprylate can have at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, or at least 97% or greater purity. In some instances, the additive can contain at least 90% propylene glycol monocaprylate and no more than 10% propylene glycol dicaprylate, at least 91% propylene glycol monocaprylate and no more than 9% propylene glycol dicaprylate, at least 92% propylene glycol monocaprylate and no more than 8% propylene glycol dicaprylate, at least 93% propylene glycol monocaprylate and no more than 7% propylene glycol dicaprylate, at least 94% propylene glycol monocaprylate and no more than 6% propylene glycol dicaprylate, at least 95% propylene glycol monocaprylate and no more than 5% propylene glycol dicaprylate, at least 96% propylene glycol monocaprylate and no more than 4% propylene glycol dicaprylate, or at least 97% propylene glycol monocaprylate and no more than 3% propylene glycol dicaprylate.

[0164] The compositions described herein can, in some instances, include as additive an alcohol selected from phenethyl alcohol, ethanol, isopropanol, glycerol, propylene glycol, polyethylene glycol, n-butanol, and combinations thereof.

[0165] The compositions of the present application can include those suitable for any acceptable route of administration. Suitable examples of acceptable routes of administration include ocular, topical ocular, ocular injection, and the like. In some embodiments, the topical composition is an ophthalmic composition, e.g., for intraocular administration. Suitable examples of ophthalmic compositions include eye drops, emulsions, nanoemulsions, and oils. Any one of these ophthalmic compositions can be administered directly to the cornea or surface of the eye, using, for example, a plastic or latex applicator (e.g., a single-use applicator), an eye dropper, a glass pipette, or a rubber bulb.

[0166] In some instances, the compositions described herein are absorbed transcorneally or are selectively absorbed transcorneally. The phrases “absorbed via the transcorneal route,” “absorbed via transcorneal pathway,” and “absorbed transcorneally” are used interchangeably and relate to transcorneal absorption. In transcorneal absorption, a drug typically penetrates the eye through cornea to the aqueous humor to the iris. In the periorbital absorption, drug typically penetrates the eye through the conjunctival to the scleral to the ciliary body. In some instances, a composition described herein is absorbed transcorneally (e.g., at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, or at least 70% of the composition is absorbed transcorneally, e.g., as determined by an assay known in the art or described in the working examples herein). In some instances, a composition described herein is selectively absorbed transcorneally (e.g., at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, or at least 70% more of the composition is absorbed transcorneally as compared to the amount absorbed periorbitally, e.g., as determined by an assay known in the art or described in the working examples herein, or at least 1.5-fold, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 10-fold, or at least 20-fold more of the composition is absorbed transcorneally as compared to the amount absorbed periorbitally, e.g., as determined by an assay known in the art or described in the working examples herein). In some instances, the amount of the composition that is absorbed transcorneally is at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, or at least 70% greater than the amount that is absorbed periorbitally.

[0167] In some instances, the etiprednol of a composition of the present application is absorbed transcorneally or is selectively absorbed transcorneally. In some instances, etiprednol described herein is absorbed transcorneally (e.g., at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, or at least 70% of the etiprednol is absorbed transcorneally, e.g., as determined by an assay known in the art or described in the working examples herein). In some instances, etiprednol described herein is selectively absorbed transcorneally (e.g., at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, or at least 70% more of the etiprednol is absorbed transcorneally as compared to the amount absorbed periorbitally, e.g., as determined by an assay known in the art or described in the working examples herein, or at least 1.5-fold, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 10-fold, or at least 20-fold more of the etiprednol is absorbed transcomeally as compared to the amount absorbed periorbitally, e.g., as determined by an assay known in the art or described in the working examples herein). In some instances, the amount of the etiprednol that is absorbed transcomeally is at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, or at least 70% greater than the amount that is absorbed periorbitally.

[0168] In some instances, the composition has a pH of about 6 to about 8.

[0169] In some instances, the compositions can be in the form of an organic composition without aqueous components.

[0170] In some instances, the compositions can be in the form of a solution or suspension. In some instances, the compositions can be in the form of an emulsion. In some instances, the compositions can be in the form of a nano / emulsion. In some instances, the nano-emulsions can be oil-in-oil emulsions. In some instances, the nanoemulsions can have a droplet size D90 of less than 100 nm.

[0171] “Droplet size” of an emulsion refers to the peak droplet size or the mean droplet size, of the dispersed phase. “Droplet size D90” refers to the case that 90% of the particles have a size smaller than the indicated size. Droplet size can be measured by methods known in the art, e.g., by light scattering after dilution in water using a High-Performance Particle Sizer.

[0172] In some instances, the nano-emulsions can have a droplet size D90 of less than about 50 nm, less than about 50 nm, less than about 50 nm, less than about 50 nm, less than about 50 nm, less than about 50 nm, less than about 50 nm, or less than about 50 nm, or from about 1 to 20 nm, from about 1 to 10 nm, from about 1 to 5 nm, or from about 2 to 3 nm.

[0173] In some instances, the methods for making the nano emulsions can comprise combining an additive with a semi-fluorinated alkane compound to form a mixture, wherein said mixture comprises from about 1% to about 50% (w / w) said additive and from about 50% to about 99% (w / w) of said semi-fluorinated alkane compound; and emulsifying said mixture and reducing droplet particle size D90 within said mixture to less than 100 nm by physical agitation selected from high speed stirring, vortexing, sonicating, heating and stirring, or homogenizing the mixture until the droplet size reaches droplet particle size D90 of less than 100 nm, less than about 50 nm, less than about 50 nm, less than about 50 nm, less than about 50 nm, less than about 50 nm, less than about 50 nm, less than about 50 nm, or less than about 50 nm, or from about 1 to 20 nm, from about 1 to 10 nm, from about 1 to 5 nm, or from about 2 to 3 nm. In some instances, the methods for making the nano emulsions can comprise uniformly and intimately bringing into association the additive and SFAas disclosed herein, and emulsifying said mixture and reducing droplet particle size D90 within said mixture to less than 100 nm by physical agitation as described herein.

[0174] In some instances, the methods can further comprise measuring the droplet particle size of the mixture during or following said physical agitation.

[0175] This disclosure also includes pharmaceutical kits useful, for example, in the treatment of disorders, diseases and conditions referred to herein, which include one or more containers containing a pharmaceutical composition comprising a therapeutically effective amount of a compound of the present disclosure. Such kits can further include, if desired, one or more of various conventional pharmaceutical kit components, such as, for example, containers with one or more pharmaceutically acceptable carriers, additional containers, etc. Instructions, either as inserts or as labels, indicating quantities of the components to be administered, guidelines for administration, and / or guidelines for mixing the components, can also be included in the kit. The kit may optionally include an additional therapeutic agent as described herein.

[0176] In some embodiments, a kit can comprise a dispensing device preloaded with a composition as described herein.

[0177] Also provided herein are methods for treating ocular diseases or conditions using the compositions described herein. In some instances, the ocular diseases or conditions can be an ocular inflammatory condition affecting a front of an eye.

[0178] Exemplary, non-limiting an ocular inflammatory conditions affecting a front of an eye that can be treated with the compositions and methods described herein can include Sjogren's syndrome, conjunctivitis, inflammation caused by surgery, injury, or other conditions, eye swelling, redness, itching, or pain, uveitis, scleritis and episcleritis, corneal transplant, corneal allograft rejection, allergic eye diseases, Stevens-Johnson Syndrome, vernal keratoconjunctivitis, peripheral ulcerative keratitis, graft vs host disease, cicatrising conjunctival disorders, anterior uveitis, and others. In some instances, the corneal transplant can be a form of endothelial keratoplasty (EK). In some instances, the EK can be Descemet Stripping Endothelial Keratoplasty (DSEK), Descemet Stripping (Automated) EK (DS AEK) or ultrathin (UT)-DSAEK.

[0179] In some instances, the ocular diseases or conditions can be a dry eye disease of dry eye related disease.

[0180] Exemplary, nonlimiting dry eye diseases or related conditions that can be treated with the compositions and methods described herein include inflammatory dry eye disease; dry eye syndrome, dysfunctional tear syndrome, keratoconjunctivitis sicca, Sjbgrens syndrome, lacrimal gland insufficiency, meibomian gland disease, dry eye disease (DED), including, aqueous deficient DED and evaporative DED, as well as other related ocular diseases.

[0181] In some instances, the ocular diseases or conditions can be a form of abnormal corneal neovascularization.

[0182] Exemplary, non-limiting abnormal corneal neovascularization that can be treated with the compositions and methods described herein can include or can be caused by or related to a condition such as alkali burns or injury induced neovascularization, corneal graft rejection in high-risk corneal transplant patients, neovascular glaucoma, contact lens induced redness neovascularization, ocular rosacea, ocular pemphigoid, limbal stem cell deficiency, Sjogren's syndrome, atopic conjunctivitis, graft versus host disease, Lyell's syndrome, Stevens Johnson syndrome, and ulceration.

[0183] In some instances, the methods can include a method for treating, slowing the progression of, or reducing one or more symptoms of an ocular condition in a subject comprising administering the topical ophthalmological compositions described herein to the eye of a subject. Administering can in some instances include contacting the eye with the composition.

[0184] In some instances, the compositions can be administered on a daily basis (e.g., as a single dose or as two or more divided doses, e.g., once daily, two times daily, three times daily, or four times daily) or non-daily basis (e.g., every other day, every two days, every three days, once weekly, twice weekly, once every two weeks, once a month), or sporadically, e.g., on an as / needed basis. In some instances, the compositions can be administered once every about 2 to about 8 hours. In some instances, the compositions can be administered three times a day. In some instances, the compositions can be administered once a day.

[0185] In some instances of the compositions and methods described herein, the compositions described herein can include etiprednol. Etiprednol, and its analogs are included within the scope of the present invention. Such solvates include for example hydrates, alcoholates (e.g., ethanol solvate), and the like. Etiprednol can exist in different polymorphic forms. Such forms are intended to be included within the scope of the present disclosure.

[0186] In some instances, the etiprednol or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, can be present in an amount of from about 0.001% to about 5% (w / w), from about 0.01% to about 5% (w / w), from about 0.1% to about 5% (w / w), from about 0.2% to about 5% (w / w), from about 0.5% to about 5% (w / w), from about 1% to about 5% (w / w), from about 2% to about 5% (w / w), from about 3% to about 5% (w / w), from about 4% to about 5% (w / w), from about 0.001% to about 2% (w / w), from about 0.001% to about 1% (w / w), from about 0.001% to about 0.9% (w / w), from about 0.001% to about 0.8% (w / w), from about 0.001% to about 0.7% (w / w), from about 0.001% to about 0.6% (w / w), from about 0.001% to about 0.5% (w / w), from about 0.001% to about 0.4% (w / w), from about 0.001% to about 0.3% (w / w), from about 0.001% to about 0.2% (w / w), from about 0.001% to about 0.1% (w / w), from about 0.01% to about 2% (w / w), from about 0.01% to about 1% (w / w), from about 0.01% to about 0.9% (w / w), from about 0.01% to about 0.8% (w / w), from about 0.01% to about 0.7% (w / w), from about 0.01% to about 0.6% (w / w), from about 0.01% to about 0.5% (w / w), from about 0.01% to about 0.4% (w / w), from about 0.01% to about 0.3% (w / w), from about 0.01% to about 0.2% (w / w), from about 0.01% to about 0.1% (w / w), from about 0.001% to about 2% (w / w), from about 0.001% to about 1% (w / w), from about 0.1% to about 0.9% (w / w), from about 0.1% to about 0.8% (w / w), from about 0.1% to about 0.7% (w / w), from about 0.1% to about 0.6% (w / w), from about 0.1% to about 0.5% (w / w), from about 0.1% to about 0.4% (w / w), from about 0.1% to about 0.3% (w / w), and from about 0.1% to about 0.2% (w / w). In some instances, the etiprednol can be present in the compositions or nano-emulsions described herein in an amount of about 0.02% (w / w). In some instances, the etiprednol can be present in the compositions or nanoemulsions described herein in an amount of about 0.04% (w / w). In some instances, the etiprednol can be present in the compositions or nano-emulsions described herein in an amount of about 0.05% (w / w). In some instances, the etiprednol can be present in the compositions or nano-emulsions described herein in an amount of about 0.06% (w / w). In some instances, the etiprednol can be present in the compositions or nano-emulsions described herein in an amount of about 1% (w / w).

[0187] In some instances, the etiprednol or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, can be present in an amount of from about 0.0001% to about 5% (w / w), from about 0.1% to about 2.5% (w / w), from about 0.1% to about 2% (w / w), from about 0.1% to about 1.5% (w / w), from about 0.1% to about 1% (w / w), from about 0.001% to about 0.01% (w / w), from about 0.001% to about 0.009% (w / w), from about 0.001% to about 0.008% (w / w), from about 0.001% to about 0.007% (w / w), from about 0.001% to about 0.006% (w / w), from about 0.001% to about 0.005% (w / w), from about 0.001% to about 0.004% (w / w), from about 0.001% to about 0.003% (w / w), from about 0.001% to about 0.002% (w / w), from about 0.0001% to about 0.001% (w / w), from about 0.0001% to about 0.0009% (w / w), from about 0.0001% to about 0.0008% (w / w), from about 0.0001% to about 0.0007% (w / w), from about 0.0001% to about 0.0006% (w / w), from about 0.0001% to about 0.0005% (w / w), from about 0.0001% to about 0.0004% (w / w), from about 0.0001% to about 0.0003% (w / w), from about 0.0001% to about 0.0002% (w / w), from about 0.15% to about 0.5% (w / w), from about 0.15% to about 0.45% (w / w), from about 0.15% to about 0.4% (w / w), from about 0.15% to about 0.35% (w / w), from about 0.15% to about 0.3% (w / w), from about 0.15% to about 0.25% (w / w), from about 0.15% to about 0.2% (w / w), from about 0.1% to about 1.7% (w / w), from about 0.1% to about 1.3% (w / w), from about 0.1% to about 0.5% (w / w), from about 0.1% to about 0.45% (w / w), from about 0.1% to about 0.4% (w / w), from about 0.1% to about 0.35% (w / w), from about 0.1% to about 0.3% (w / w), from about 0.1% to about 0.25% (w / w), from about 0.1% to about 0.2% (w / w), from about 0.15% to about 0.5% (w / w), from about 0.15% to about 0.45% (w / w), from about 0.15% to about 0.4% (w / w), from about 0.15% to about 0.35% (w / w), from about 0.15% to about 0.3% (w / w), from about 0.15% to about 0.25% (w / w), from about 0.15% to about 0.2% (w / w), from about 0.1 % to about 1.7% (w / w), from about 0.1 % to about 1.3% (w / w), from about 0.1 % to about 0.7% (w / w), from about 0.1% to about 2% (w / w), from about 0.3% to about 2% (w / w), from about 0.5% to about 2% (w / w), from about 0.7% to about 2% (w / w), from about 1% to about 2% (w / w), from about 1.3% to about 2% (w / w), from about 1.5% to about 2% (w / w), from about 1.7% to about 2% (w / w), from about 0.3% to about 1% (w / w), from about 0.3% to about 1.3% (w / w), from about 0.3% to about 1% (w / w), from about 0.5% to about 1% (w / w), from about 0.5% to about 0.7% (w / w), from about 0.5% to about 1% (w / w), from about 0.5 to about 1.5% (w / w), from about 0.5% to about 2% (w / w), from about 0.5% to about 0.7% (w / w), from about 0.7% to about 1% (w / w), from about 1% to about 1.3 % (w / w), from about 1.3% to about 1.5% (w / w), from about 1.5% to about 2% (w / w), about 0.1% (w / w), about 0.2% (w / w), about 0.3% (w / w), about 0.4% (w / w), about 0.5% (w / w), about 0.6% (w / w), about 0.7% (w / w), about 0.8% (w / w), about 0.9% (w / w), about 1% (w / w), about 1.3% (w / w), about 1.5% (w / w), about 1.7% (w / w), about 2% (w / w), about 2.5% (w / w), about 3% (w / w), about 3.5% (w / w), about 4% (w / w), about 4.5% (w / w), about 5% (w / w), about 5.5% (w / w), about 0.001%(w / w), about 0.002% (w / w), about 0.003%(w / w), about 0.004% (w / w), about 0.005%(w / w), about 0.0011% (w / w), about 0.0012% (w / w), about 0.0013% (w / w), about 0.0014% (w / w), about 0.0015% (w / w), about 0.0016% (w / w), about 0.0017% (w / w), about 0.0018% (w / w), about 0.0019% (w / w), about 0.002% (w / w), about 0.0021% (w / w), about 0.0022% (w / w), about 0.0023% (w / w), about 0.0024% (w / w), about 0.0025% (w / w), about 0.0026% (w / w), about 0.0027% (w / w), about 0.0028% (w / w), about 0.0029% (w / w), about 0.0030% (w / w), about 0.0031% (w / w), about 0.0032% (w / w), about 0.0033% (w / w), about 0.0034% (w / w), about 0.0035% (w / w), about 0.0036% (w / w), about 0.0037% (w / w), about 0.0038% (w / w), about 0.0039% (w / w), about 0.0001% (w / w), about 0.0002% (w / w), about 0.0003% (w / w), about 0.0004% (w / w), about 0.0005% (w / w), about 0.0006% (w / w), about 0.0007% (w / w), about 0.0008% (w / w), or about 0.0009% (w / w).

[0188] The compositions disclosed herein may, in some instances, also comprise one or more additional therapeutic agents, excipients, or diluents including, but not limited to, absorbents, anti -irritants, preservatives, antioxidants, coloring agents / pigments, emollients (moisturizers), emulsifiers, film-forming / holding agents, prescription drugs, surfactants / detergent cleansing agents, penetration enhancers, viscosity enhancers, and thickeners.

[0189] The invention will be further described in the following examples, which do not limit the scope of the invention.

[0190] It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

[0191] EXAMPLES

[0192] Example 1: Solubility of Etiprednol in Exemplary Compositions

[0193] 1.1 Method

[0194] Chromatographic column: SHIMADAU Shim-pack GIST C18 5um, 4.6 mm (ID) x 250 mm (L), 5 μm

[0195] Mobile phase A: 0.05% Trifluoroacetic acid-Water

[0196] Mobile phase B: 0.05% Trifluoroacetic acid- Acetonitrile

[0197] Flow rate: 1.0 mL / min Detector / wavelength: UV / 242nm

[0198] Injection volume: 10 μL Column temperature: 45°C

[0199] Running time: 35min

[0200] Time (min) % Mobile phase A % Mobile phase B

[0201] 0.01 60 40

[0202] 25 0 100

[0203] 25.01 60 40

[0204] 35 60 40

[0205]

[0206] 1.2 Experiment Various formulations of Etiprednol were prepared as in Table 1 below. As a specific example of preparation of one exemplary formulation, 10%PG-8 (purified) / 90%F6H8, PG-8 (purified) was added to Etiprednol dicloacetate and mixed evenly; after complete dissolution, F6H8 was added to achieve the noted concentration of PG-8 in Table 1.

[0207] 1.3 Results

[0208] Results of solubility observations are shown in Table 1 below.

[0209] Table 1. Solubility of Etiprednol in Exemplary Compositions

[0210] Solubility(mg / g)

[0211] Etiprednol

[0212] Name

[0213] dicloacetate

[0214] 100%F4H5 0.0043

[0215] 100%F6H8 0.0023

[0216] 100%MCT 5.43

[0217] 10%MCT / 90%F6H8 0.40

[0218] 10%MCT / 90%F4H5 0.36

[0219] 5%F4H 1 OH / 95%F6H8 0.88

[0220] 10%F4Hl OH / 90%F6H8 2.24

[0221] 20%F4Hl OH / 80%F6H8 3.69

[0222] 10%F4H10H / 90%F4H5 3.87

[0223] 5%F4H10H / 10%PG- 1.63

[0224] 8 / 85%F6H8

[0225] 100%F4H20H 8.62

[0226] 10%F4H20H / 90%F6H8 0.91

[0227] 100%F6H10H 15.32

[0228] 10%F6Hl OH / 90%F6H8 1.69

[0229] 20%F6Hl OH / 80%F6H8 3.51

[0230] 100%F6H20H 3.5

[0231] 10%F6H20H / 90%F6H8 0.39

[0232] 100%PG-8 (purified) 30.81

[0233] 10%PG-8

[0234] 1.12

[0235] (purified) / 90%F6H8

[0236] 3%PGD / 97%F6H8 0.14

[0237]

[0238] 10%PG-2L / 90%F6H8 0.15

[0239] 100%F3H10H 24.16

[0240] 10%F3H 1 OH / 90%F6H8 2.64

[0241] 20%F3H10H / 80%F6H8 4.94

[0242]

[0243] 100% light liquid paraffin 0

[0244] Example 2: Etiprednol in a dry eye disease (DED) model

[0245] Etiprednol dicloacetate is tested in a murine DED model as described in De Paiva 2006 to determine its ability to improve DED.

[0246] Model establishment:

[0247] Dry eye is induced in C57BL / 6 mice, aged 6 to 8 weeks, by subcutaneous injection of 0.5 mg / 0.2 mL scopolamine hydrobromide (Sigma- Aldrich, St. Louis, MO) in alternating hindquarters administered four times a day (8 AM, 11 AM, 2 PM, and 5 PM) and by exposure to an air draft and less than 40% ambient humidity for 18 hours per day, as previously reported.

[0248] Treatments:

[0249] • Normal untreated control (no dry eye induction and no topical treatment);

[0250] • DED control (dry eye induced and received no eye drops);

[0251] • Saline control (dry eye induced and received saline eye drops, 1 pl / eye bilaterally, 4 time / day);

[0252] • Etiprednol dicloacetate (dry eye induced and received saline eye drops, 1 pl / eye bilaterally, 4 time / day)

[0253] Measurements:

[0254] After two weeks of treatment, the corneal permeability and smoothness scores are assessed as described by De Paiva 2006 and Pflugfelder 2005.

[0255] Example 3: Etiprednol dicloacetate in a corneal neovascularization model Etiprednol dicloacetate is tested in a rabbit corneal neovascularization model as described in Ribeiro 2012 to determine its ability to suppress corneal neovascularization.

[0256] Model establishment:

[0257] The inflammatory corneal angiogenesis model is induced by punctual alkaline cauterization as described (Ribeiro 2012). After the animals are anesthetized, eyelids are held apart with a blepharostat, exposing almost the entire corneal surface and the upper limbal area. The rabbits are submitted to a punctual cauterization on the top periphery of the right cornea with the aid of a microscope, using a magnification of 16-X by using a circular piece of filter paper (3 mm diameter), previously soaked in a solution of sodium hydroxide (NaOH) 1 M for 30 s (excess solution is blotted away with gauze). The filter paper is left for 2 min at approximately 1 mm from the conjunctival limbal tissue in the 12-o’clock position near the insertion of the upper rectus muscle. The eye is subsequently rinsed with 5 ml sodium chloride at 0.9% solution to remove excess NaOH. The technique produced a 3.5-mm-wide, homogeneous and circular cauterization site with well-defined borders. The animals are returned to their cages only after complete emergence from anesthesia.

[0258] Treatments:

[0259] The rabbits are randomly allocated to three treatment groups: a vehicle group, consisting of 6 rabbits that are treated with 1 drop (40 μl) of the vehicle eyedrop, instilled in the conjunctival sac 3 times per day; a positive control group, consisting of 6 rabbits that are treated with topical instillation of 1 drop (40 μl) of loteprednol etabonate (LE) 0.5% eyedrop 3 times per day; a Etiprednol dicloacetate group, composed of 6 rabbits that are treated with 1 drop (40 μl) of Etiprednol dicloacetate 0.5% in the conjunctival sac 3 times per day. Treatments are initiated on the day of cauterization (day zero) and continued for 21 days.

[0260] Measurements:

[0261] On days 3, 9, 15 and 21, digital photos of the eyes are obtained, and the vascular area on cornea is measured with the ImageJ software.

[0262] Example 4: Ocular Pharmacokinetics of Etiprednol Dicloacetate

[0263] The ocular pharmacokinetics of Etiprednol Dicloacetate and Loteprednol Carbonate are evaluated via a single topical ocular dosing of 0.25% Etiprednol Dicloacetate and 0.25% Loteprednol Carbonate in rabbits.

[0264] Rabbits are randomly assigned to two treatment groups. After gentle shaking, a single 12 microliter drop of either 0.25% Etiprednol Dicloacetate or 0.25% Loteprednol Carbonate formulation is administered to both eyes of each rabbit. At each of the following time points, 0.083, 0.25, 0.5, 1, 2, 4, 8, and 24 hour post dosing, three rabbits from each treatment group are euthanized by intravenous barbiturate overdose and plasma samples are obtained. Both eyes from each rabbit are harvested, and samples are collected from aqueous humor, vitreous humor, cornea, conjunctiva, iris / ciliary body, retina / choroid and sclera. All samples are assayed using liquid chromatography-tandem mass spectrometry (LC-MS / MS). The analysis for each matrix is performed separately and tissue-specific standard curves are generated separately for both formulations.

[0265] Plasma and aqueous humor samples are diluted with control plasma or aqueous humor, respectively, and analyzed directly. Ocular tissue samples are weighted, homogenized, and diluted with methanol prior to analysis. The lower limit of quantitation is 0.4 ng / (g or mL).

[0266] Example 5: Stability of Etiprednol in Exemplary

[0267] Various formulations of Etiprednol were prepared as described in Example 1 above. Concentration of Etiprednol was determined and recorded on Day 0. The compositions were then divided and placed into storage at three different storage temperatures. The concentration of Etiprednol was determined after 1 month, 2 months, 3, months, 6 months, 9 months, and 12 months.

[0268] Results of Stability are shown in Tables 5A-5E below.

[0269] Table 5A: Stability of Etiprednol in 10%F4H1OH / 90%F6H8

[0270] Assay(mg / g)

[0271] Condition

[0272] Time

[0273] 2-8°C 25°C 40°C

[0274] Od 1.05 1.05 1.05

[0275] IM 1.08 1.07 1.07

[0276] 2M 1.07 1.07 1.08

[0277]

[0278] 3M 1.08 1.08 1.08 6M 1.07 1.08 1.09 9M 1.08 1.09 1.09

[0279]

[0280] 12M 1.07 1.08 1.08

[0281] Table 5B: Stability of Etiprednol in 10%F6H10H / 90%F6H8

[0282] Assay(mg / g)

[0283] Condition

[0284] Time

[0285] 2-8°C 25°C 40°C

[0286] Od 0.55 0.55 0.55 IM 0.55 0.55 0.55 2M 0.54 0.54 0.54 3M 0.54 0.54 0.54 6M 0.54 0.55 0.55 9M 0.54 0.55 0.56

[0287]

[0288] 12M 0.54 0.55 0.55

[0289] Table 5C: Stability of Etiprednol in 10%F4H10H / 90%F4H5

[0290] Assay(mg / g)

[0291] Condition

[0292] Time

[0293] 2-8°C 25°C 40°C

[0294] Od 0.52 0.52 0.52 IM 0.54 0.54 0.55 2M 0.54 0.54 0.56 3M 0.55 0.55 0.56

[0295]

[0296] 6M 0.54 0.54 0.61

[0297] Table 5D: Stability of Etiprednol in 10%F6H10H / 90%F4H5

[0298] Assay(mg / g)

[0299]

[0300] Time Condition 2-8°C 25°C 40°C

[0301] Od 0.52 0.52 0.52

[0302] IM 0.52 0.53 0.53

[0303] 2M 0.52 0.53 0.54

[0304] 3M 0.52 0.53 0.54

[0305]

[0306] 6M 0.52 0.53 0.58

[0307] Table 5E: Stability of Etiprednol in 10%PG-8 / 90%F6H8

[0308] Assay(mg / g)

[0309] Condition

[0310] Time

[0311] 2-8°C 25°C 40°C Od 0.52 0.52 0.52 IM 0.35 (Preci pitati on) 0.53 0.50 2M - 0.52 0.53 3M - 0.53 0.53 6M - 0.54 0.54

[0312]

[0313] EMBODIMENTS

[0314] 1. A method for treating, slowing the progression of, or reducing one or more symptoms of an ocular inflammatory condition affecting a front of an eye in a subject in need thereof comprising administering a composition comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, to an eye of the subject.

[0315] 2. The method of embodiment 1, wherein the ocular condition is selected from or related to Sjogren's syndrome, conjunctivitis, inflammation caused by surgery, injury, or other conditions, eye swelling, redness, itching, or pain, uveitis, scleritis and episcleritis, corneal transplant, corneal allograft rejection, allergic eye diseases, Stevens-Johnson Syndrome, vernal keratoconjunctivitis, peripheral ulcerative keratitis, graft vs host disease, cicatrising conjunctival disorders, and anterior uveitis.

[0316] 3. The method of embodiment 2, wherein the corneal transplant is a form of endothelial keratoplasty (EK).

[0317] 4. The method of embodiment 3, wherein the EK is selected from Descemet Stripping Endothelial Keratoplasty (DSEK), Descemet Stripping (Automated) EK (DS AEK) or ultrathin (UT)-DSAEK.

[0318] 5. A method for treating, slowing the progression of, or reducing one or more symptoms of dry eye disease, dry eye syndrome, meibomian gland disfunction, keratoconjunctivitis sicca, inflammatory dry eye disease, or combinations thereof in a subject in need thereof, the method comprising administering to an eye of the subject a composition comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, to an eye of the subject.

[0319] 6. A method for treating, slowing the progression of, or reducing one or more symptoms of abnormal corneal neovascularization in a subject in need thereof comprising administering a composition comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, to an eye of the subject.

[0320] 7. The method of embodiment 6, wherein the abnormal corneal neovascularization is, is caused by, or is related to a condition selected from alkali burns or injury induced neovascularization, corneal graft rejection in high-risk corneal transplant patients, neovascular glaucoma, contact lens induced redness neovascularization, ocular rosacea, ocular pemphigoid, limbal stem cell deficiency, Sjogren's syndrome, atopic conjunctivitis, graft versus host disease, Lyell's syndrome and Stevens-Johnson syndrome, or ulceration.

[0321] 8. The method of any one of embodiments 1-7, wherein the method further comprises delivering the etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, to a cornea of the eye of the subject.

[0322] 9. The method of any one of embodiments 1-8, wherein the method further comprises delivering the etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, through selective transcomeal absorption. 10. The method of any one of embodiments 1-9, wherein the composition is a topical ophthalmological composition.

[0323] 11. The method of any one of embodiments 1-10, wherein the subject is a human. 12. A topical ophthalmic composition comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof.

[0324] 13. Eye drops comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof.

[0325] 14. The method of any one of embodiments 1-11, or the composition of embodiment 12, or the eye drops of embodiment 13, wherein the composition or eye drop is nonaqueous.

[0326] 15. The method of any one of embodiments 1-11 or 14, or the composition of embodiments 12 or 14, or the eye drops of embodiment 13 or 14, wherein the composition or eye drop further comprises a semi-fluorinated alkane compound.

[0327] 16. The method of embodiment 15, or the composition of embodiment 15, or the eye drops of embodiment 15, wherein the semi-fluorinated alkane compound is selected from perfluorobutylheptane (F4H5), perfluorobutylhexane (F4H6), perfluorohexylbutane (F6H4), perfluorohexylhexane (F6H6), perfluorohexyloctane (F6H8), and perfluorohexyldecane (F6H10) and combinations thereof.

[0328] 17. The method of any one of embodiments 1-11 or 14-16, or the composition of embodiment 12 or 14-16, or the eye drops of embodiment 13 or 14-16, wherein the composition or the eye drop further comprises an additive selected from paraffin, propylene glycol diacetate (PGD), a semi-fluorinated alkyl alcohol, a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid, phenethyl alcohol, ethanol, isopropanol, glycerol, propylene glycol, propylene glycol dilaurate, polyethylene glycol, n-butanol, or combinations thereof.

[0329] 18. The method of any one of embodiments 15-17, or the composition of any one of embodiments 15-17, or the eye drops of any one of embodiments 15-17, wherein the semi-fluorinated alkane compound is present in a concentration of from about 50% to about 99.9% (w / w) in the topical ophthalmological composition. 19. The method of any one of embodiments 17-18, or the composition of any one of embodiments 17-18, or the eye drops of any one of embodiments 17-18, wherein the additive is present in a concentration of from about 0.1% to about 50% (w / w).

[0330] 20. The method of any one of embodiments 17-19, or the composition of any one of embodiments 17-19, or the eye drops of any one of embodiments 17-19, wherein the additive is present in a concentration of from about 1% to about 30% (w / w) and the semi-fluorinated alkane compound is present in a concentration of from about 70% to about 99% (w / w).

[0331] 21. The method of any one of embodiments 15-20, or the composition of any one of embodiments 15-20, or the eye drops of any one of embodiments 15-20, wherein the semifluorinated alkane compound is perfluorohexyloctane (F6H8) or perfluorobutylheptane (F4H5).

[0332] 22. The method of any one of embodiments 1-11 or 14-21, or the composition of any one of embodiments 12 or 14-21, or the eye drops of any one of embodiments 13 or 14-21, wherein the etiprednol is present in an amount of from about 0.005% (w / w) to about 10 % (w / w).

[0333] 23. The method of any one of embodiments 1-11 or 14-22, or the composition of any one of embodiments 12 or 14-22, or the eye drops of any one of embodiments 13 or 14-22, wherein the additive is PGD.

[0334] 24. The method of any one of embodiments 1-11 or 14-22, or the composition of any one of embodiments 12 or 14-22, or the eye drops of any one of embodiments 13 or 14-22, wherein the additive is paraffin.

[0335] 25. The method of embodiment 24, or the composition of embodiment 24, or the eye drops of embodiment 24, wherein the paraffin is liquid paraffin.

[0336] 26. The method of any one of embodiments 1-11 or 14-22, or the composition of any one of embodiments 12 or 14-22, or the eye drops of any one of embodiments 13 or 14-22, wherein the additive is a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, or an alkyl ester of a fatty acid.

[0337] 27. The method of embodiment 26, or the composition of embodiment 26, or the eye drops of embodiment 26, wherein the additive is a propylene glycol monocaprylate, a propylene glycol dicaprylate, a propylene glycol dilaurate, or a combination thereof.

[0338] 28. The method of any one of embodiments 26-27, or the composition of any one of embodiments 26-27, or the eye drops of any one of embodiments 26-27, wherein the additive comprises propylene glycol monocaprylate at a purity of at least 90%.

[0339] 29. The method of any one of embodiments 1-11 or 14-28 or 37, or the composition of any one of embodiments 12 or 14-28 or 37, or the eye drops of any one of embodiments 13 or 14-28 or 37, wherein the topical composition or eye drop is in the form of a solution, a suspension, or an emulsion.

[0340] 30. The method of any one of embodiments 1-11 or 14-29 or 37, or the composition of any one of embodiments 12 or 14-29 or 37, or the eye drops of any one of embodiments 13 or 14-29 or 37, wherein the topical ophthalmological composition or the eye drop is a nanoemulsion.

[0341] 31. The method of any one of embodiments 1-11 or 14-22 or 26-30, or the composition of any one of embodiments 12 or 14-22 or 26-30, or the eye drops of any one of embodiments 13 or 14-22 or 26-30, wherein

[0342] the additive is a propylene glycol monocaprylate, a propylene glycol dicaprylate, propylene glycol dilaurate, or a combination thereof,

[0343] the additive is present in an amount of from about 1% to about 20% (w / w), and

[0344] the SFA is present in an amount of from about 80% to about 99% (w / w).

[0345] 32. The method of any one of embodiments 1-11 or 14-23 or 28-29, or the composition of any one of embodiments 12 or 14-23 or 28-29, or the eye drops of any one of embodiments 13 or 14-23 or 28-29, wherein

[0346] the additive is PGD,

[0347] the PGD is present in an amount of from about 3% to about 10% (w / w), and

[0348] the SFA is present in an amount of from about 90% to about 97% (w / w).

[0349] 33. The method of any one of embodiments 1-11 or 14-22 or 24-25 or 28-29, or the composition of any one of embodiments 12 or 14-22 or 24-25 or 28-29, or the eye drops of any one of embodiments 13 or 14-22 or 24-25 or 28-29, wherein the additive is paraffin,

[0350] the paraffin is present in an amount of from about 1% to about 20% (w / w), and

[0351] the SFA is present in an amount of from about 80% to about 99%. 34. The method of any one of embodiments 1-11 or 14-33 or 36-37, or the composition of any one of embodiments 12 or 14-33 or 36-37, or the eye drops of any one of embodiments 13 or 14-33 or 36-37, wherein the etiprednol is etiprednol dicloacetate.

[0352] 35. A topical ophthalmological composition, consisting essentially of:

[0353] etiprednol, or a derivative, analogue, or diastereomer or enantiomer thereof;

[0354] a semi-fluorinated alkane compound; and

[0355] an additive selected from paraffin, propylene glycol diacetate (PGD), a hydroxyalkyl ester of an aliphatic fatty acid, a semi-fluorinated alkyl alcohol, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid, phenethyl alcohol, ethanol, isopropanol, glycerol, propylene glycol, propylene glycol dilaurate, polyethylene glycol, n-butanol, or combinations thereof.

[0356] 36. The method of any one of embodiments 1-11 or 14-22 or 24-25 or 28-29, or the composition of any one of embodiments 12 or 14-22 or 24-25 or 28-29, or the eye drops of any one of embodiments 13 or 14-22 or 24-25 or 28-29, wherein

[0357] the additive is a semi-fluorinated alkyl alcohol,

[0358] the semi-fluorinated alkyl alcohol is present in an amount of from about 1% to about 30% (w / w), and

[0359] the SFA is present in an amount of from about 70% to about 99%. 37. The method of any one of embodiments 1-11 or 14-22, or the composition of any one of embodiments 12 or 14-22, or the eye drops of any one of embodiments 13 or 14-22, wherein the additive is a semi-fluorinated alkyl alcohol. OTHER EMBODIMENTS

[0360] It is to be understood that while the present application has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the present application, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

[0361] REFERENCES

[0362] 1. De Paiva CS, Corrales RM, Villarreal AL, Farley W, Li DQ, Stern ME, Pflugfelder SC. Apical corneal barrier disruption in experimental murine dry eye is abrogated by methylprednisolone and doxycycline. Invest Ophthalmol Vis Sci. 2006 Jul;47(7):2847-56. doi: 10.1167 / iovs.05-1281.

[0363] 2. Pflugfelder SC, Farley W, Luo L, Chen LZ, de Paiva CS, Olmos LC, Li DQ, Fini ME. Matrix metalloproteinase-9 knockout confers resistance to corneal epithelial barrier disruption in experimental dry eye. Am J Pathol. 2005 Jan;166(1):61-71. doi: 10.1016 / S0002-9440( 10)62232-8.

[0364] 3. Ribeiro JC, Vagnaldo Fechine F, Ribeiro MZ, Barreiro EJ, Lima LM, Ricardo NM, Amaral de Moraes ME, Odorico de Moraes M. Potential inhibitory effect of LASSBio-596, a new thalidomide hybrid, on inflammatory corneal angiogenesis in rabbits. Ophthalmic Res. 2012;48(4): 177-85. doi: 10.1159 / 000337137.

Claims

WHAT IS CLAIMED IS:

1. A method for treating, slowing the progression of, or reducing one or more symptoms of an ocular inflammatory condition affecting a front of an eye in a subject in need thereof comprising administering a composition comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, to an eye of the subject.

2. The method of claim 1, wherein the ocular condition is selected from or related to Sjogren's syndrome, conjunctivitis, inflammation caused by surgery, injury, or other conditions, eye swelling, redness, itching, or pain, uveitis, scleritis and episcleritis, corneal transplant, corneal allograft rejection, allergic eye diseases, Stevens-Johnson Syndrome, vernal keratoconjunctivitis, peripheral ulcerative keratitis, graft vs host disease, cicatrising conjunctival disorders, and anterior uveitis.

3. The method of claim 2, wherein the corneal transplant is a form of endothelial keratoplasty (EK).

4. A method for treating, slowing the progression of, or reducing one or more symptoms of dry eye disease, dry eye syndrome, meibomian gland disfunction, keratoconjunctivitis sicca, inflammatory dry eye disease, or combinations thereof in a subject in need thereof, the method comprising administering to an eye of the subject a composition comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, to an eye of the subject.

5. A method for treating, slowing the progression of, or reducing one or more symptoms of abnormal corneal neovascularization in a subject in need thereof comprising administering a composition comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, to an eye of the subject.

6. The method of claim 5, wherein the abnormal corneal neovascularization is, is caused by, or is related to a condition selected from alkali bums or injury inducedneovascularization, corneal graft rejection in high-risk corneal transplant patients, neovascular glaucoma, contact lens induced redness neovascularization, ocular rosacea, ocular pemphigoid, limbal stem cell deficiency, Sjogren's syndrome, atopic conjunctivitis, graft versus host disease, Lyell's syndrome and Stevens- Johnson syndrome, or ulceration.

7. The method of any one of claims 1-6, wherein the method further comprises delivering the etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof, to a cornea of the eye of the subject.

8. A topical ophthalmic composition comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof.

9. Eye drops comprising etiprednol, or a derivative, analogue, racemic mixture, or diastereomer or enantiomer thereof.

10. The method of any one of claims 1-7, or the composition of claim 8, or the eye drops of claim 9, wherein the composition or eye drop is nonaqueous.

11. The method of any one of claims 1-7 or 10, or the composition of any one of claims 8 or 10, or the eye drops of any one of claims 9 or 10, wherein the composition or eye drop further comprises a semi-fluorinated alkane (SFA) compound.

12. The method of claim 11, or the composition of claim 11, or the eye drops of claim 11, wherein the semi-fluorinated alkane compound is selected from perfluorobutylheptane (F4H5), perfluorobutylhexane (F4H6), perfluorohexylbutane (F6H4), perfluorohexylhexane (F6H6), perfluorohexyloctane (F6H8), and perfluorohexyldecane (F6H10) and combinations thereof.

13. The method of any one of claims 1-7 or 10-12, or the composition of any one of claims 8 or 10-12, or the eye drops of any one of claims 9 or 10-12, wherein the composition or the eye drop further comprises an additive selected from paraffin, propylene glycol diacetate (PGD), a semi-fluorinated alkyl alcohol, a hydroxyalkyl ester of an aliphatic fatty acid, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid, phenethyl alcohol, ethanol, isopropanol, glycerol, propyleneglycol, propylene glycol dilaurate, polyethylene glycol, n-butanol, or combinations thereof.

14. The method of any one of claims 11-13, or the composition of any one of claims 11-13, or the eye drops of any one of claims 11-13, wherein the semi-fluorinated alkane compound is present in a concentration of from about 50% to about 99.9% (w / w) in the composition.

15. The method of any one of claims 13-14, or the composition of any one of claims 13-14, or the eye drops of any one of claims 13-14, wherein the additive is present in a concentration of from about 0.1% to about 50% (w / w).

16. The method of any one of claims 1-7 or 10-15, or the composition of any one of claims 8 or 10-15, or the eye drops of any one of claims 9 or 10-15, wherein the etiprednol is present in an amount of from about 0.005% (w / w) to about 10 % (w / w).

17. The method of any one of claims 1-7 or 10-16 or 19-20, or the composition of any one of claims 8 or 10-16 or 19-20, or the eye drops of any one of claims 9 or 10- 16 or 19-20, wherein the etiprednol is etiprednol dicloacetate.

18. A topical ophthalmological composition, consisting essentially of:etiprednol, or a derivative, analogue, or diastereomer or enantiomer thereof;a semi-fluorinated alkane compound; andan additive selected from paraffin, propylene glycol diacetate (PGD), a hydroxyalkyl ester of an aliphatic fatty acid, a semi-fluorinated alkyl alcohol, a hydroxyacid alkyl ester, an alkyl ester of a fatty acid, phenethyl alcohol, ethanol, isopropanol, glycerol, propylene glycol, propylene glycol dilaurate, polyethylene glycol, n-butanol, or combinations thereof.

19. The method of any one of claims 1-7 or 13-17, or the composition of any one of claims 8 or 13-17, or the eye drops of any one of claims 9 or 13-17, wherein the additive is a semi-fluorinated alkyl alcohol,the semi-fluorinated alkyl alcohol is present in an amount of from about 1% to about 30% (w / w), andthe SFA is present in an amount of from about 70% to about 99%.

20. The method of any one of claims 1-7 or 13-17, or the composition of any one of claims 8 or 13-17, or the eye drops of any one of claims 9 or 13-17, wherein the additive is a semi-fluorinated alkyl alcohol.

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