(720a) Using a Focused Beam Reflectance Measurement (FBRM) Probe to Characterize Tablet Disintegration Behavior As a Function of Drug Product Processing Conditions

Standard USP disintegration testing describes only the macro scale break-up of a tablet in a basket-rack assembly through a woven mesh. The method provides no insight into micro scale behavior, such as the particle size distribution of disintegrated tablet fragments, changes in this distribution which occur concurrently with dissolution of the active ingredient, or the dissolution rate at which of the active itself. Here we present the application of FBRM (Focused Beam Reflectance Measurement) to evaluate the evolution of particle size during the disintegration process.

Immersion of an FBRM probe in the media of a modified USP dissolution vessel enables the tracking of both particle count and size as disintegration progresses. We demonstrate how differences in upstream tablet processing steps are manifest in differences in micro scale disintegration behavior, and how FBRM-based analytics can provide insights absent from the traditional USP-based disintegration assessment. Specifically, in a roller compaction QbD assessment, granule density differences are traceable in FBRM particle size data on final tablet disintegration. Process ranges for roller compaction can be tied to specific physical properties such as granule sizes during disintegration, and help set operating ranges. Infrared and Raman techniques can be employed in parallel, monitoring active as it dissolves, and interrogating the physical form of residual solid material during the process. The resulting approach offers a more detailed analysis of initial phenomena tied to tablet disintegration, providing a deeper understanding of the relationships between material properties, processing conditions, and formulation performance.