Pharmaceutical composition and pharmaceutical dosage form comprising (E)-4-(2-(aminomethyl)-3-fluoroallyloxy)-N-tert-butylbenzamide, process for their preparation, methods for treating and uses thereof

Abstract

or a pharmaceutically acceptable salt thereof as active pharmaceutical ingredient, particularly to pharmaceutical compositions comprising (E)-4-(2-(aminomethyl)-3-fluoroallyloxy)-N-tert-butylbenzamide hydrochloride, to pharmaceutical dosage forms, to their preparation, their use and methods for therapeutic treatment.

1 - 14 . (canceled) 
     
     
         15 . A method for preventing, slowing the progression of, delaying or treating of one or more fibrotic diseases, metabolic diseases, inflammatory diseases, ocular diseases, neuroinflammatory diseases or cancers in a patient in need thereof characterized in that a pharmaceutical composition comprising a pharmaceutically acceptable salt of (E)-4-(2-(aminomethyl)-3-fluoroallyloxy)-N-tert-butylbenzamide having the following chemical structure 
       
         
           
           
               
               
           
         
       
       as active pharmaceutical ingredient, and one or more stabilizers is administered to the patient. 
     
     
         16 . The method according to  claim 15 , wherein said fibrotic or metabolic disease is selected from the group consisting of liver fibrosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), non-proliferative diabetic retinopathy and proliferative diabetic retinopathy. 
     
     
         17 . A direct compression process for making a pharmaceutical composition comprising (E)-4-(2-(aminomethyl)-3-fluoroallyloxy)-N-tert-butylbenzamide having the following chemical structure 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof as active pharmaceutical ingredient, and one or more excipients, 
       wherein said process comprises the steps of:
 (1) Premixing said active pharmaceutical ingredient and the main portion of the excipients and one or more stabilizer(s) in a mixer to obtain a pre-mixture; 
 (2) optionally dry screening the pre-mixture through a screen in order to segregate cohesive particles and to improve content uniformity; 
 (3) mixing the pre-mixture of step (1) or (2) in a mixer, optionally by adding remaining excipients to the mixture and continuing mixing; 
 (4) tableting the final mixture of step (3) by compressing it on a suitable tablet press to produce the tablet cores; 
 (5) optionally film-coating of the tablet cores of step (4) with a film coat. 
 
     
     
         18 . A pharmaceutical composition obtainable by the process of  claim 17 . 
     
     
         19 . A dry granulation process for making a pharmaceutical composition comprising (E)-4-(2-(aminomethyl)-3-fluoroallyloxy)-N-tert-butylbenzamide having the following chemical structure 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof as active pharmaceutical ingredient, and one or more excipients, 
       wherein said process comprises the steps of:
 (1) mixing said active pharmaceutical ingredient with either all or a portion of the excipients and one or more stabilizer(s) in a mixer; 
 (2) compaction of the mixture of step (1) on a suitable roller compactor; 
 (3) reducing the ribbons obtained during step (2) to granules by suitable milling or sieving steps; 
 (4) optionally mixing the granules of step (3) with the remaining excipients in a mixer to obtain the final mixture; 
 (5) tabletting the granules of step (3) or the final mixture of step (4) by compressing it on a suitable tablet press to produce the tablet cores; 
 (6) optionally film-coating of the tablet cores of step (5) with a film coat. 
 
     
     
         20 . A pharmaceutical composition obtainable by the process of  claim 19 . 
     
     
         21 . A method for treating diabetic retinopathy in a patient in need thereof characterized in that a pharmaceutical composition comprising (E)-4-(2-(aminomethyl)-3-fluoroallyloxy)-N-tert-butylbenzamide or a pharmaceutically acceptable salt thereof is administered to the patient.