Phenyl pyrrole aminoguanidine salts and formulations

Abstract

The disclosure relates to oral formulations for gastric delivery of a pharmaceutically acceptable salt of a phenyl pyrrole aminoguanidine compound.

1 . An immediate-release, solid, oral dosage form comprising a salt of (E)-N-[1-(2-nitrophenyl)-1-H-pyrrole-2-yl-allylideneamino]-guanidine) (AP1189) that is an acetate salt of AP1189 or a succinate salt of AP1189, in an amount that is about 25 mg to about 250 mg (calculated as the free base);
 wherein not less than about 80% of the salt is dissolved into aqueous solution in about 15 minutes at a pH of about 1 to 3, using a USP 2 paddle equipment at 37° C. at a rotation speed of 50 rpm.   
     
     
         2 . The immediate-release, solid, oral dosage form of  claim 1 , comprising about 25 mg to about 150 mg of the salt of AP1189 (calculated as the free base). 
     
     
         3 . The immediate-release, solid, oral dosage form of  claim 1 , comprising about 50 mg to about 100 mg of the salt of AP1189 (calculated as the free base). 
     
     
         4 . The immediate-release, solid, oral dosage form of  claim 1 , comprising about 50 mg of the salt of AP1189. 
     
     
         5 . The immediate-release, solid, oral dosage form of  claim 1 , comprising about 100 mg of the salt of AP1189. 
     
     
         6 . The immediate-release, solid, oral dosage form of  claim 1 , comprising the acetate salt of AP1189. 
     
     
         7 . The immediate-release, solid, oral dosage form of  claim 1 , comprising the succinate salt of AP1189. 
     
     
         8 . The immediate-release, solid, oral dosage form of  claim 1 , wherein not less than about 80% of the salt is dissolved into aqueous solution in about 15 minutes at a pH of about 1.2, using a USP 2 paddle equipment at 37° C. at a rotation speed of 50 rpm. 
     
     
         9 . A method of treating a disorder that is rheumatoid arthritis, idiopathic membranous nephropathy (iMN) or a viral disorder with pulmonary insufficiency in a human in need thereof comprising administering a single dose of an immediate-release, solid, oral dosage form of  claim 1  to the human;
 wherein the administration results in an AP1189 T max  that is about 1 to 3 hours post-administration in fasting conditions; and/or 
 wherein the administration results in an AP1189 AUC 0-24  of not less than about 4000 hr*ng/mL; and/or 
 wherein the administration results in an AP1189 C max  of not less than 250 mg/mL; and 
 wherein one or more symptoms of the human's disorder are treated by the administration. 
 
     
     
         10 . The method of  claim 9 , wherein the immediate-release, solid, oral dosage form is administered once a day. 
     
     
         11 . The method of  claim 9 , wherein the immediate-release, solid, oral dosage form is administered twice a day. 
     
     
         12 . The method of  claim 9 , wherein the immediate-release, solid, oral dosage form is administered three times a day. 
     
     
         13 . The method of  claim 9 , wherein the disorder is rheumatoid arthritis. 
     
     
         14 . The method of  claim 9 , wherein the disorder is rheumatoid arthritis with an inappropriate response to methotrexate (MTX). 
     
     
         15 . The method according to  claim 14 , wherein said method further comprises one or more steps of co-administering MTX. 
     
     
         16 . The method of  claim 9 , wherein the disorder is idiopathic membranous nephropathy (iMN). 
     
     
         17 . The method of  claim 9 , wherein the viral diseases with pulmonary insufficiency is acute respiratory distress syndrome. 
     
     
         18 . The method of  claim 9 , wherein the viral disease is symptomatic COVID-19 with acute respiratory distress syndrome.