Preparation of solid cyclodextrin complexes for ophthalmic active pharmaceutical ingredient delivery

Abstract

The present disclosure relates to ophthalmic compositions containing solid complexes of active pharmaceutical ingredient and cyclodextrin, to their method of preparation and their uses. The compositions can include an active agent drug/cyclodextrin complex substantially dissolved in an aqueous eye drop vehicle. The ophthalmic composition is generally in the form of a microsuspension including an active agent complex having a diameter of less than about 100 μm.

1 .- 109 . (canceled) 
     
     
         110 . A sterile ophthalmic microsuspension comprising, in an ophthalmically acceptable medium:
 a solid complex comprising dexamethasone and γ-cyclodextrin, wherein said solid complex has a diameter D50 from about 1 μm to about 25 μm; and   wherein the microsuspension comprises less than 1% by weight of degradation products or degradation products, based on weight of the dexamethasone.   
     
     
         111 . The sterile ophthalmic microsuspension according to  claim 110 , wherein the amount of γ-cyclodextrin is from 5% to 20% by weight based on the volume of the microsuspension. 
     
     
         112 . The sterile ophthalmic microsuspension according to  claim 110 , wherein the amount of γ-cyclodextrin is from 12% to 16% by weight based on the volume of the microsuspension. 
     
     
         113 . The sterile ophthalmic microsuspension according to  claim 110 , wherein the microsuspension comprises less than 0.5% by weight of 16,17-unsaturated dexamethasone or a mixture of dexamethasone enol aldehydes based on the weight of the dexamethasone. 
     
     
         114 . The sterile ophthalmic microsuspension according to  claim 110 , wherein the microsuspension comprises less than 0.5% by weight of dexamethasone enol aldehydes based on the weight of dexamethasone. 
     
     
         115 . The sterile ophthalmic microsuspension according to  claim 110 , wherein the dexamethasone is present in the composition at a concentration of about 10 mg/mL to about 20 mg/mL. 
     
     
         116 . The sterile ophthalmic microsuspension according to  claim 110 , wherein 60 to 95% by weight of the dexamethasone in the microsuspension is in the form of a solid complex. 
     
     
         117 . The sterile ophthalmic microsuspension according to  claim 110 , wherein the microsuspension further comprises a polymer. 
     
     
         118 . The sterile ophthalmic microsuspension according to  claim 110 , wherein the microsuspension further comprises a polymer and the amount of polymer is 1 to 4%, by weight of polymer based on the volume of the microsuspension. 
     
     
         119 . The sterile ophthalmic microsuspension according to  claim 117 , wherein the polymer is poloxamer. 
     
     
         120 . The sterile ophthalmic microsuspension according to  claim 110 , wherein the microsuspension comprises:
 1% to 2% of dexamethasone;   12% to 16% of γ-cyclodextrin;   2.2% to 2.8% of a polymer;   0% to 0.2% of a stabilizing agent;   0% to 1% of an electrolyte; and   water;   
       wherein the % are % by weight based on the weight of the microsuspension. 
     
     
         121 . The sterile ophthalmic composition according to  claim 110 , wherein the microsuspension comprises:
 about 1.5% of dexamethasone;   about 14% of γ-cyclodextrin;   about 2.5% of a poloxamer;   about 0.1% of disodium edetate;   about 0.57% of sodium chloride; and   water;   
       wherein the % are % by weight based on the weight of the composition. 
     
     
         122 . The sterile ophthalmic composition according to claim  1 , wherein the microsuspension has a pH between about 5.0 and about 6.0.