Emulsion formulations of multikinase inhibitors

Abstract

Compositions comprising a therapeutically effective amount of a multikinase inhibitor, such as nintedanib or axitinib or pazopanib, are provided, wherein the composition is an emulsion, such as a nanoemulsion, with lipophilic carrier (e.g., castor oil), a polyoxyl oil (e.g., polyolyl-35 castor oil), optionally with a surfactant (e.g., polysorbate 80), optionally with a cyclic oligosaccharide, such as a cyclodextrin (e.g., 2-hydroxypropyl-beta-cyclodextrin), as a solubilizer. Methods for treating ocular conditions with the compositions are also provided.

1 - 26 . (canceled) 
     
     
         27 . An emulsion comprising:
 about 0.01% to about 1% w/w of nintedanib;   about 0.3% to about 0.7% w/w of polyoxyl-35 castor oil;   about 0.1% to about 0.5% w/w of castor oil;   about 8% to about 12% w/w of 2-hydroxypropyl-beta-cyclodextrin;   about 0.1% to about 1% w/w of polysorbate 80; and   water.   
     
     
         28 . The emulsion of  claim 27 , wherein the polyoxyl-35 castor oil is present in an amount of about 0.5% w/w. 
     
     
         29 . The emulsion of  claim 27 , wherein the castor oil is present in an amount of about 0.25% w/w. 
     
     
         30 . The emulsion of  claim 27 , wherein the 2-hydroxypropyl-beta-cyclodextrin is present in an amount of about 10% w/w. 
     
     
         31 . The emulsion of  claim 27 , wherein the polysorbate 80 is present in an amount of about 0.5% w/w. 
     
     
         32 . The emulsion of  claim 27 , further comprising an additional constituent selected from a thickener, a buffering agent, an antioxidant, a tonicity agent, or a combination thereof. 
     
     
         33 . The emulsion of  claim 32 , wherein the emulsion comprises a thickener, and wherein the thickener is present in an amount of about 0.05% to about 0.5% w/w. 
     
     
         34 . The emulsion of  claim 33 , wherein the thickener comprises hydroxypropyl methylcellulose, sodium carboxymethylcellulose, or a combination thereof. 
     
     
         35 . The emulsion of  claim 32 , wherein the emulsion comprises a buffering agent, and wherein the buffering agent is present in an amount of about 0.01% to about 1.0% w/w. 
     
     
         36 . The emulsion of  claim 35 , wherein the buffering agent comprises sodium citrate, citric acid, or a combination thereof. 
     
     
         37 . The emulsion of  claim 32 , wherein the emulsion comprises an antioxidant, and wherein the antioxidant comprises edetate disodium present at an amount of about 0.01% to about 1.0% w/w. 
     
     
         38 . The emulsion of  claim 32 , wherein the emulsion comprises a tonicity agent, and wherein the tonicity agent is present in an amount of about 0.01% to about 1.0% w/w. 
     
     
         39 . The emulsion of  claim 38 , wherein the tonicity agent comprises glycerin. 
     
     
         40 . A method of treating an ocular indication, comprising administering the emulsion of  claim 27  to an eye of a subject. 
     
     
         41 . The method of  claim 40 , wherein the ocular condition is associated with angiogenesis. 
     
     
         42 . The method of  claim 40 , wherein the ocular condition is hyperemia, neovascularization, pterygium, pinguecula, glaucoma filtration surgery, minimally invasive glaucoma surgery (MIGS), cornea transplant surgery with graft rejection, graft versus host disease, dry eye disease, atopic conjunctivitis, rosacea, ocular pemphigoid, Lyell's syndrome, Steven Johnson syndrome, viral infection, bacterial infection, fungal infection, parasitic infection, contact lens induced neovascularization, ulceration, alkali burns, or stem cell deficiency.