Patent ID: 9139558
Filing Date: 2015-09-22
Classification: A61K,A61P,C07C,C07D

Abstract:
1. A method of increasing oral absorption of neratinib in a patient in need thereof, comprising: administering to the patient neratinib formulated as a maleate salt, wherein the neratinib maleate salt is prepared according to a method comprising: i) mixing (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and maleic acid in a water-alcohol solution at a temperature in the range of between about 50° C. to about 60° C.; ii) cooling said solution to a temperature of about 40° C. and maintaining the cooled solution at about 40° C. for about 12 hours to precipitate the maleate salt; iii) further cooling the cooled solution to room temperature (about 25° C.) over a minimum of 4 hours and maintaining the further cooled solution at room temperature (about 25° C.) for at least 2 hours; and iv) filtering the maintained, further cooled solution to obtain crystalline (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide maleate; wherein the neratinib maleate salt formulation produces at least a two-fold greater AUC (area under concentration), relative to neratinib in a free base formulation.