Process for the preparation of colesevelam hydrochloride

摘要

A novel process of manufacturing colesevelam hydrochloride including the steps of alkylating polyallylamine with n-decylbromide and 6-bromohexyl trimethyl ammonium bromide, followed by cross-linking the alkylated polyallylamine with epichlorohydrin in an aqueous medium, and adding a suitable chloride ion source to obtain colesevelam hydrochloride.

主权项

1. A process for the preparation of colesevelam and/or pharmaceutically acceptable salts thereof comprising:
(a) reacting a polyallylamine solution with two alkylating agents to form an alkylated polyallylamine; and (b) crosslinking the alkylated polyallylamine from step (a) with epichlorohydrin to form colesevelam, wherein one of the two alkylating agents is selected from a group consisting of n-decyl bromide, n-decyl chloride, n-decyl tosylate, n-decyl mesylate, n-decyl triflate, n-decyl iodide, n-decyl fluoride, and a combination thereof; and wherein the other of the two alkylating agents is selected from a group consisting of 6-bromohexyl trimethyl ammonium bromide, 6-chlorohexyl trimethyl ammonium chloride, and a combination thereof; wherein the alkylation step (a) and the crosslinking step (b) are conducted in water or an aqueous solvent mixture.