Bromfenac ophthalmic formulations and methods of use

Abstract

The present invention discloses a stability enhanced aqueous liquid preparation containing 2-amino-3-(4-bromobenzoyl)phenylacetic acid or its pharmacologically acceptable salt or a hydrate thereof, an alkyl aryl polyether alcohol type polymer such as tyloxapol, or a polyethylene glycol fatty acid ester such as polyethylene glycol monostearate. The present invention further discloses new bromfenac ophthalmic compositions which can potentially treat a broader patient population, and have greater stability properties, and may require a lower concentration or less doses of bromfenac then previously known bromfenac compositions. The present invention further comprises a method for treating inflammation and/or pain of the eye in a patient which method comprises topical application to the eye of a patient in need thereof of a therapeutically effective amount of a topical ophthalmic composition comprising bromfenac at a concentration of about 0.05% w/v to about 0.24% w/v.

1 . A method of treating pain and/or inflammation associated with an ocular disease, injury or disorder comprising administering to a patient, in need of such treatment, an aqueous liquid preparation comprising 2-amino-3-(4-bromobenzoyl)phenylacetic acid or a pharmaceutically acceptable salt thereof or a hydrate thereof, and an alkyl aryl polyether alcohol type polymer or a polyethylene glycol fatty acid ester.  
   
   
       2 . The method of  claim 1 , wherein the alkyl aryl polyether alcohol type polymer is tyloxapol.  
   
   
       3 . The method of  claim 2 , wherein the concentration of tyloxapol is selected from a range of about 0.01% w/v to about 0.5% w/v.  
   
   
       4 . The method of  claim 3 , wherein the concentration of tyloxapol is about 0.02 to about 0.3% w/v.  
   
   
       5 . The method of  claim 4 , wherein the pharmacologically acceptable salt of the 2-amino-3-(4-bromobenzoyl)phenylacetic acid is a sodium salt.  
   
   
       6 . The method of  claim 5 , wherein the concentration of the salt is about 0.05 to about 0.2% w/v.  
   
   
       7 . The method of  claim 6 , wherein the concentration of the salt is about 0.09 to about 0.21% w/v.  
   
   
       8 . The method of  claim 7 , wherein the pH of the aqueous liquid preparation is from about 7 to about 9.  
   
   
       9 . The method of  claim 8 , wherein the pH is from about 7.5 to about 8.5.  
   
   
       10 . The method of  claim 9 , wherein said formulation is administered once per day.  
   
   
       11 . The method of  claim 10 , wherein the ocular disease, injury, or disorder is caused by surgery, physical damage to the eye, glaucoma, diabetic retinopathy, and/or macular degeneration.  
   
   
       12 . The method of  claim 11 , wherein the ocular disease, injury, or disorder is one which results in vascular leakage in the eye or inflammation in the eye.  
   
   
       13 . The method of  claim 12 , wherein the inflammation in the eye is caused by surgical trauma; dry eye; allergic, viral, or bacterial conjunctivitis; injury from a chemical, radiation, or thermal burn; and/or penetration of a foreign body.  
   
   
       14 . The method of  claim 13 , wherein said inflammation in the eye is caused by allergic, viral, or bacterial conjunctivitis.  
   
   
       15 . The method of  claim 13 , wherein said inflammation in the eye is caused by surgical trauma.  
   
   
       16 . The method of  claim 15 , wherein said surgical trauma is the result of cataract surgery.  
   
   
       17 . The method of  claim 15 , wherein said surgical trauma is the result of a refractive eye surgery.  
   
   
       18 . The method of  claim 17 , wherein said refractive eye surgery is photorefractive keratectomy (PRK) or laser epithelial keratomileusis (LASEK) refractive eye surgery.  
   
   
       19 . A method of treating an eye wherein its normal condition has been disrupted or changed comprising: 
 administering the formulation of  claim 1  to said eye one time daily.    
   
   
       20 . The method of  claim 19 , wherein the disruption or change is due to blepharitis, conjunctivitis, scleritis, or postoperative inflammation.  
   
   
       21 . The method of  claim 19 , wherein said formulation is administered to treat or alleviate pain and/or inflammation associated with said disrupted or changed condition of the eye.  
   
   
       22 . A method for treating a patient for pain and/or inflammation associated with eye surgery comprising: 
 pre-dosing the patient for up to 48 hours before the eye surgery with the formulation of  claim 1;     wherein the formulation is applied once daily; and    applying said formulation once daily post surgery for about 14 days or until condition has been alleviated.    
   
   
       23 . The method of  claim 22 , wherein said eye surgery is cataract surgery.  
   
   
       24 . The method of  claim 22 , wherein said eye surgery is any refractive eye surgery.  
   
   
       25 . The method of  claim 24 , wherein said refractive surgery is photorefractive keratectomy (PRK) surgery or laser epithelial keratomileusis (LASEK) refractive eye surgery.  
   
   
       26 . The method of  claim 22 , wherein the pain and/or inflammation is due to postoperative eye surgery.  
   
   
       27 . The method of  claim 9 , wherein said formulation is administered twice per day.  
   
   
       28 . The method of  claim 27 , wherein the ocular disease, injury, or disorder is caused by surgery, physical damage to the eye, glaucoma, diabetic retinopathy, and/or macular degeneration.  
   
   
       29 . The method of  claim 27 , wherein the ocular disease, injury, or disorder is one which results in vascular leakage in the eye or inflammation in the eye.  
   
   
       30 . The method of  claim 29 , wherein the inflammation in the eye is caused by surgical trauma; dry eye; allergic, viral, or bacterial conjunctivitis; injury from a chemical, radiation, or thermal burn; and/or penetration of a foreign body.  
   
   
       31 . The method of  claim 30 , wherein the inflammation in the eye is caused by allergic, viral, or bacterial conjunctivitis.  
   
   
       32 . The method of  claim 30 , wherein the inflammation in the eye is caused by surgical trauma.  
   
   
       33 . The method of  claim 32 , wherein said surgical trauma is the result of cataract surgery.  
   
   
       34 . The method of  claim 32 , wherein said surgical trauma is the result of refractive eye surgery.  
   
   
       35 . The method of  claim 34 , wherein said refractive eye surgery is photorefractive keratectomy (PRK) or laser epithelial keratomileusis (LASEK) refractive eye surgery.  
   
   
       36 . A method of treating an eye wherein its normal condition has been disrupted or changed comprising: 
 administering the formulation of  claim 1  to said eye two times daily.    
   
   
       37 . The method of  claim 36 , wherein the disruption or change is due to blepharitis, conjunctivitis, schleritis, or postoperative inflammation.  
   
   
       38 . The method of  claim 36 , wherein said formulation is administered to treat or alleviate pain and/or inflammation associated with said disrupted or changed condition of the eye.  
   
   
       39 . A method for treating a patient for pain and/or inflammation associated with eye surgery comprising: 
 pre-dosing the patient for up to 48 hours before the eye surgery with the formulation of  claim 1;     wherein the formulation is applied two times daily; and    applying said formulation two times daily post surgery for about 14 days or until condition has been alleviated.    
   
   
       40 . The method of  claim 39 , wherein said eye surgery is cataract surgery.  
   
   
       41 . The method of  claim 39 , wherein said eye surgery is any refractive eye surgery.  
   
   
       42 . The method of  claim 41 , wherein said refractive eye surgery is photorefractive keratectomy (PRK) surgery or laser epithelial keratomileusis (LASEK) refractive eye surgery.  
   
   
       43 . The method of  claim 39 , wherein the pain and/or inflammation is due to postoperative eye surgery.