Control of the Physical Form of Salmeterol Xinafoate

Two approaches to the generation of particles of the phenethanolamine, salmeterol xinafoate, are discussed. To produce particles with good flow properties a fast cooling crystallisation process was developed which delivered salmeterol xinafoate as spherical agglomerates of microcrystals which had good powder flow characteristics and could be micronised efficiently in a fluid energy mill. In a radically different approach, salmeterol xinafoate was crystallised using supercritical carbon dioxide in the SEDS (solution enhanced dispersion by supercritical fluids) process. By means of this technique the solid state form, crystal habit, and particle size of salmeterol xinafoate could be effectively controlled.