(505d) Material Properties Characterization and Ingredient Agglomerate Behavior in Continuous Direct Compaction Process

In the modern pharmaceutical process, the appropriate material characterization and process setting are required to achieve robustness of product. we are proposing a decision tree methodology for rapid screening of the direct compression formulations, which enable us based on the API characteristics to define the appropriate formulation and target process setting for direct compression continuous process. The first step is to identify the failure modes. Based on our experience, direct compression continuous processes my present issues, the most important failure modes can be captured by several questions, such as Can we feed each ingredient at the required flow rate? Do material properties change during process? Do the ingredients stick and agglomerate? Can we achieve blend homogeneity? In this study, we develop characterization method focusing on the questions of material properties, ingredient sticking on equipment and agglomerate.

This work consists of two sessions. In the first session, we investigate the properties of post-feeder material. We have recently observed some material sticks on the feeder surface and some material properties might have change during feeding process. Our process cases are high and low feeding speed. More than twelve materials were studied and characterized before and post feeding on compressibility, shear cell flowability, density and electrostatic charge density. Our experimental results supported that materials with both very small particle size and high electrostatic charge potential represent increasing of compressibility and electrostatic net charge density and decreasing on density. This phenomenon is driven by the electrostatic charge accumulating when material is discharged by feeder. In the second session, we study the ingredient agglomerate potential in continuous process. A method was developed that can quantify the post-feeder agglomerate size based on the image analysis. When analyzing agglomeration of more than 25 material, we would map the material agglomerate potential based on the particle size and compressibility characterization. Moreover, a case study of semi-fine APAP was performed to determine the agglomerate characterization on the blends and tablets, and the agglomerate elimination/mitigation will also be discussed.