Ocular insert composition of a semi-crystalline or crystalline pharmaceutically active agent

Abstract

The present disclosure includes compositions of a semi-crystalline or crystalline pharmaceutically active agent dispersed in a polymer matrix, in which the active agent is less degraded and, therefore, has lower level of impurities. The present disclosure further includes a method of reducing or preventing physical and chemical degradation of a semi-crystalline or crystalline active agent pharmaceutically active agent dispersed in a polymer matrix. A method of preparation of the composition is also included in this disclosure.

1 . An ocular composition comprising bimatoprost dispersed in a polymer matrix, wherein the polymer matrix comprises a thermosetting polymer, and wherein the composition comprises about 2% or less impurities. 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The composition of  claim 1 , wherein the impurities comprise 15-keto bimatoprost. 
     
     
         5 . The composition of  claim 4 , wherein the composition comprises about 1% or less 15-keto bimatoprost. 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . The composition of  claim 1 ,  3 , wherein the impurities comprise 5-trans bimatoprost. 
     
     
         9 . The composition of  claim 8 , wherein the composition comprises about 0.1% to about 1% 5-trans bimatoprost. 
     
     
         10 - 13 . (canceled) 
     
     
         14 . The composition of  claim 1 , wherein the thermosetting polymer is silicone. 
     
     
         15 - 60 . (canceled) 
     
     
         61 . A method of lowering intraocular pressure in an eye of a subject in need thereof, the method comprising placing the composition of  claim 1  in the eye of the subject. 
     
     
         62 . (canceled) 
     
     
         63 . A method of producing an ocular insert for an eye of a subject, the method comprising:
 (i) mixing a therapeutic agent with a silicone polymer, thereby forming a silicone polymer matrix comprising the therapeutic agent;   (ii) curing the silicone polymer matrix into a cured silicone polymer matrix comprising the therapeutic agent; and   (iii) washing the cured silicone polymer matrix with acetonitrile at room temperature; thereby removing the therapeutic agent from the outer layer of the cured silicone polymer matrix;   thereby producing the ocular insert.   
     
     
         64 . The method of  claim 63 , further comprising cooling the cured silicone polymer matrix prior to washing the cured silicone polymer matrix with acetonitrile. 
     
     
         65 . The method of  claim 63 , wherein step (i) comprises dissolving the therapeutic agent in an organic solvent to form a solution; mixing the solution with the silicone polymer, thereby forming the silicone polymer matrix comprising the therapeutic agent; and removing the organic solvent before curing the silicone polymer matrix. 
     
     
         66 . The method of  claim 63 , further comprising sterilizing the cured silicone polymer matrix. 
     
     
         67 . The method of  claim 63 , wherein the silicone polymer comprises silica and poly(dimethylsiloxane-co-methylhydrosiloxane). 
     
     
         68 . The method of  claim 63  wherein the silicone polymer comprises a first component comprising silica and a second component comprising silica and poly(dimethylsiloxane-co-methylhydrosiloxane), wherein the ratio of the first component to the second component is 1:1. 
     
     
         69 . The method of  claim 63 , comprising washing the cured silicone polymer matrix with acetonitrile for 6 hours or less. 
     
     
         70 . The method of  claim 63 , comprising washing the cured silicone polymer matrix with acetonitrile for 4 hours or less. 
     
     
         71 . The method of  claim 63 , wherein room temperature is from about 15° C. to about 30° C. 
     
     
         72 . The method of  claim 63 , comprising washing the cured silicone polymer matrix with acetonitrile for 6 hours or less and wherein room temperature is from about 15° C. to about 30° C. 
     
     
         73 . The method of  claim 63 , comprising washing the cured silicone polymer matrix with acetonitrile for 4 hours or less and wherein room temperature is from about 15° C. to about 30° C. 
     
     
         74 . The method of  claim 63 , wherein the therapeutic agent is a prostaglandin, a prostamide, a steroid, or an antibiotic. 
     
     
         75 . The method of  claim 63 , wherein the therapeutic agent is bimatoprost, latanoprost, travoprost, or tafluprost.