Continuous Feeding and Blending Demonstration with Co-Processed Drug Substance

Abstract

Continuous direct compression (CDC) of solid oral dosage forms requires materials exhibiting acceptable flow and compression properties. The desired active pharmaceutical ingredient (API) powder properties can be 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 powder properties to overcome these difficulties. In this manuscript, performance of a co-processed API was evaluated in a continuous feeding and blending process using GEA ConsiGma® Continuous Dosing and Blending Unit (CDB1). The co-processed theophylline was generated via a methodology in which polymer was precipitated and coated the crystalline theophylline particles resulting in nearly spherical agglomerates. A range of drug loads (1-25% w/w), flow rates (15-40 kg/h) and blender speeds (220-400 rpm) were studied. The results demonstrated that the co-processed API can be successfully fed through a loss-in-weight feeder and blended with other excipients in a high shear blender to generate tablets with acceptable content uniformity at 1-25% w/w drug loads. This study supports that using co-processed API with enhanced powder properties is a promising approach to enable continuous manufacturing for APIs with challenging properties.