Design and Scale-up of a Co-processing Technology to Improve Powder Properties of Drug Substances

Abstract

Many active pharmaceutical ingredients (APIs) display poor powder properties and cannot be directly compressed into tablets with sufficient strength. The desired powder properties are often difficult to achieve through conventional particle engineering approaches, such as particle size and habit modification during crystallization. Co-processing of API with excipients can significantly improve the functional properties to overcome these difficulties. Herein, a co-processing technology was developed to improve powder properties in which the polymer is precipitated and coats the crystalline API particles resulting in discrete, nearly spherical agglomerates. Critical process parameters were identified and scalability up to 50 kg scale was demonstrated in the pilot plant. The co-processed APIs generated under various process conditions were formulated into blends at 50–90 wt % loading and successfully processed by direct compression.