Ophthalmic formulations

Abstract

The present invention relates to an ophthalmic formulation which comprises a fine particle of Compound A in an aqueous suspension and a manufacturing process thereof. More specifically, the present invention relates to a topically applied ophthalmic aqueous suspension which is obtainable by suspending fine particles of Compound A in an aqueous vehicle containing a surfactant and boric acid. The invention also provides processes for making the ophthalmic formulations and to methods of use thereof.

1 . A method of reducing intraocular pressure comprising the step of: topically applying an effective amount of an ophthalmic formulation to an affected eye of a patient, wherein the formulation comprises:
 (a) an aqueous suspension of micronized Compound A from 0.1 to 5.0% (w/v) in the formulation;   (b) a surfactant;   (c) boric acid from about 0.05 to about 2.0% (w/v); and   (d) a buffering agent that maintains the pH from about 6.0 to about 7.0.   
     
     
         2 . The method according to  claim 1 , wherein the ophthalmic formulation is administered to the affected eye of the subject in about 30 to about 50 μl drops. 
     
     
         3 . The method according to  claim 1 , wherein the ophthalmic formulation is administered in about 1 to about 2 drops once or twice daily. 
     
     
         4 . The method according to  claim 1 , wherein the subject has normal-tension glaucoma, OHT, or POAG. 
     
     
         5 . A method of treating retinal ganglion cell damage comprising the step of: applying an effective amount of an ophthalmic formulation to an affected eye of a patient, wherein the formulation comprises:
 (a) an aqueous suspension of micronized Compound A from 0.1 to 5.0% (w/v) in the formulation;   (b) a surfactant;   (c) boric acid from about 0.05 to about 2.0% (w/v); and   (d) a buffering agent that maintains the pH from about 6.0 to about 7.0.   
     
     
         6 . The method of  claim 5 , wherein the ophthalmic formulation is administered to the affected eye of the subject in about 30 to about 50 μl drops. 
     
     
         7 . The method of  claim 6 , wherein the ophthalmic formulation is administered in 1 to 2 drops once or twice daily. 
     
     
         8 . A method of preventing retinal ganglion cell damage comprising the step of: applying an effective amount of an ophthalmic formulation to an affected eye of a patient, wherein the formulation comprises:
 (a) an aqueous suspension of micronized Compound A from 0.1 to 5.0% (w/v) in the formulation;   (b) a surfactant;   (c) boric acid from about 0.05 to about 2.0% (w/v); and   (d) a buffering agent that maintains the pH from about 6.0 to about 7.0.   
     
     
         9 . The method as claimed in  claim 8  wherein the ophthalmic formulation is administered to the affected eye of the subject in about 30 to about 50 μl drops. 
     
     
         10 . The method as claimed in  claim 9  wherein the ophthalmic formulation is administered in 1 to 2 drops once or twice daily. 
     
     
         11 . A process for preparing an ophthalmic formulation comprising:
 (a) an aqueous suspension of micronized Compound A from 0.1 to 5.0% (w/v) in the formulation;   (b) a surfactant;   (c) boric acid from about 0.05 to about 2.0% (w/v); and   (d) a buffering agent that maintains the pH from about 6.0 to about 7.0;   
       wherein the process comprises the steps of:
 (i) micronizing Compound A into particle sizes of less than about 50 microns; 
 (ii) suspending the particles of Compound A in an aqueous suspension with a surfactant and a buffering agent; 
 (iii) curing the product from step (b) at about 40° Celsius for between about 24 to about 96 hours; and 
 (iv) adding boric acid from about 0.05 to about 2.0% (w/v). 
 
     
     
         12 . The process of  claim 11 , wherein steps (a)-(c) are performed with a volume of less than about 20% of the final volume of the ophthalmic formulation. 
     
     
         13 . The process of  claim 11 , further comprising filtering the cured product of step (c) as a concentrated slurry. 
     
     
         14 . The process of  claim 11 , further comprising adding a second ophthalmic agent. 
     
     
         15 . The process of  claim 14 , wherein the second ophthalmic agent is selected from the group comprising prostaglandin analogs, β-blockers, carbonic anhydrase inhibitors, rho-kinase inhibitors, α 2  agonists, miotics, neuroprotectants, A 3  antagonists, A 2 A agonists, ion channel modulators and combinations thereof. 
     
     
         16 . The process of  claim 15 , wherein the second ophthalmic agent is a prostaglandin analog. 
     
     
         17 . The process of  claim 16 , wherein the prostaglandin analog is latanoprost.