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 a polymer matrix and a semi-crystalline or crystalline pharmaceutically active agent, wherein the active agent is dispersed in the polymer matrix. 
     
     
         2 . The composition of  claim 1 , wherein the pharmaceutically active agent is bimatoprost. 
     
     
         3 . The composition of  claim 2 , wherein the composition comprises about 2% or less impurities. 
     
     
         4 . (canceled) 
     
     
         5 . The composition of claim [[4]]3, wherein the composition comprises about 1% or less 15-keto bimatoprost. 
     
     
         6 .- 7 . (canceled) 
     
     
         8 . The composition of  claim 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 . The composition of  claim 9 , wherein the composition comprises about 0.1% 5-trans bimatoprost and about 1% 15-keto bimatoprost. 
     
     
         11 . (canceled) 
     
     
         12 . The composition of  claim 2 , wherein the semi-crystalline or crystalline bimatoprost is chemically stable in the composition for 760 days. 
     
     
         13 . The composition of  claim 1 , wherein the matrix comprises a thermosetting polymer or a thermoplastic polymer. 
     
     
         14 . The composition of  claim 13 , wherein the thermosetting polymer is silicone. 
     
     
         15 . The composition of  claim 14 , wherein the silicone is MED-4810, MED-4820, MED-4830, MED-4840, MED-4842, MED1-4855, MED-4860, MED-4870, MED-4880, or equivalents thereof. 
     
     
         16 . The composition of  claim 1 , wherein the composition is configured as an ocular insert. 
     
     
         17 . The composition of  claim 16 , wherein the ocular insert is a ring shaped ocular insert. 
     
     
         18 . The composition of  claim 17 , wherein the ring has a diameter of about 10 mm to about 40 mm and a cross-sectional thickness of about 0.1 mm to about 1.5 mm. 
     
     
         19 . (canceled) 
     
     
         20 . The composition of  claim 1 , wherein the active agent is about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, or about 22% by weight of the composition. 
     
     
         21 .- 61 . (canceled) 
     
     
         62 . A method of treating a disease or disorder of an eye of a subject in need thereof comprising placing an ocular insert in an eye of the subject, wherein the ocular insert comprises a polymer matrix and a semi-crystalline or crystalline pharmaceutically active agent dispersed in the polymer matrix. 
     
     
         63 . The method of  claim 62 , wherein the pharmaceutically active agent is bimatoprost. 
     
     
         64 . The method of  claim 62 , wherein the ocular insert comprises about 2% or less impurities. 
     
     
         65 . The method of  claim 64 , wherein the ocular insert comprises about 1% or less 15-keto bimatoprost. 
     
     
         66 . The method of  claim 64 , wherein the impurities comprise 5-trans bimatoprost. 
     
     
         67 . The method of  claim 66 , wherein the ocular insert comprises about 0.1% 5-trans bimatoprost to about 1% 5-trans bimatoprost. 
     
     
         68 . The method of  claim 62 , wherein the semi-crystalline or crystalline bimatoprost is chemically stable in the composition for 760 days. 
     
     
         69 . The method of  claim 62 , wherein the matrix comprises a thermosetting polymer or a thermoplastic polymer. 
     
     
         70 . The method of  claim 69 , wherein the thermosetting polymer is silicone. 
     
     
         71 . The method of  claim 70 , wherein the silicone is MED-4810, MED-4820, MED-4830, MED-4840, MED-4842, MED1-4855, MED-4860, MED-4870, MED-4880, or equivalents thereof. 
     
     
         72 . The method of  claim 62 , wherein the ocular insert is a ring shaped ocular insert. 
     
     
         73 . The method of  claim 72 , wherein the ring has a diameter of about 10 mm to about 40 mm and a cross-sectional thickness of about 0.1 mm to about 1.5 mm. 
     
     
         74 . The method of  claim 62 , wherein the active agent is about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, or about 22% by weight of the composition. 
     
     
         75 . The method of  claim 62 , wherein the method lowers intraocular pressure. 
     
     
         76 . The method of  claim 62 , wherein the disease or disorder is Glaucoma or dry eye syndrome.