Solid-state form of amg 706 and pharmaceutical compositions thereof

Abstract

The anti-angiogenic drug AMG 706 is provided in amorphous form. Also provided is AMG 706 drug substance wherein the AMG 706 is present, in at least a detectable amount, as amorphous AMG 706. Also provided is an AMG 706-crystallization inhibitor composite comprising particles of amorphous AMG 706 or a AMG 706 drug substance of the invention in intimate association with one or more crystallization inhibitors, for example polymers. Also provided is a pharmaceutical composition comprising such an AMG 706-crystallization inhibitor composite and one or more excipients. Also provided are processes for preparing amorphous AMG 706, AMG 706 drug substance of the invention, an AMG 706-crystallization inhibitor composite of the invention, and a pharmaceutical composition of the invention. Also provided is a method of treating a medical condition or disorder in a subject where treatment with an anti-angiogenic is indicated, comprising administering, for example orally, a composition of the invention in a therapeutically effective amount.

1 . A process for preparing amorphous form of N-(2,3-dihydro-3,3-dimethyl-1H-indol-6-yl)-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide, diphosphate salt, wherein the amorphous form has a DSC thermogram that lacks a melting point above about 200° C., comprising the steps of:
 preparing a solution of N-(2,3-dihydro-3,3-dimethyl-1H-indol-6-yl)-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide, diphosphate salt and water; and 
 removing the water. 
 
     
     
         2 . The process of  claim 1  wherein removing the water is accomplished by spray drying. 
     
     
         3 . The process of  claim 1  wherein removing the water is accomplished by lyophilization.