Controlled crystallization method of active pharmaceutical ingredients from supercooled liquid state by hot melt extrusion method

摘要

A process for controlling the crystallization of certain hydrophobic active pharmaceutical ingredients (APIs) from a supercooled liquid state by hot-melt extrusion processing is described. Also described is a pharmaceutical composition comprising a solid crystalline dispersion of a cholesterol ester transfer protein inhibitor in a hydrophilic excipient matrix. In the process of the present invention, the API is fed to an extrusion system in a crystalline state contemporaneously with carrier excipients where it is first converted to a non-crystalline state by the application of heat and then subsequently recrystallized in-situ by the removal of heat and application of shear. Recrystallization of the API is controlled by carrier formulation design and the hot-melt extrusion process parameters; i.e. barrel temperature profile, feed rate, etc.