process for controlled crystallization of an active pharmaceutical ingredient from hot melt extrusion supercooled liquid state

摘要

A process for controlling crystallization of an active pharmaceutical ingredient from the supercooled liquid state by hot melt extrusion is described. A process for controlling the crystallization of certain hydrophobic active pharmaceutical ingredients (apis) from a supercooled liquid state by hot melt extrusion processing. Also provided is a pharmaceutical composition comprising a crystalline solid dispersion of a cholesterol ester transfer protein inhibitor in a hydrophilic excipient matrix. by the claimed process, the api is fed to an extrusion system in a crystalline state simultaneously with excipient vehicles, where it is first converted to a non-crystalline state by heat application and then subsequently recrystallized in situ by heat removal and shear application. recrystallization of api is controlled by vehicle formulation preset and hot melt extrusion process parameters; ie drum temperature profile, feed rate, and other. The resulting product is a dispersion of crystalline solid api in the excipient matrix where the particle diameter of api after processing is reduced compared to api in the feed process. the resulting product exhibits a faster dissolution rate compared to crystalline api formulated by conventional means; for example, micronization or co-micronization. The carrier system is comprised of at least one hydrophilic, thermoplastic polymer and may also contain various functional excipients such as antioxidants, surfactants, wetting agents, disintegrating agents, stabilizing agents, acidifying agents, or functional excipients. similar.