(346b) Fundamental Concepts and Practical Experimentation on Multi-Layer Tablets

Multi-layer tablets present unique technical challenges in developing robust compositions and processes that meet the marketed drug product quality attributes. These challenges result from the increased engineering complexity and sensitivity in merging multiple formulations into a single dosage form such that the resulting mechanical performance is able to sustain subsequent handling, processing, and environmental conditioning. The aim of this talk is to highlight the fundamental variables that drive this interfacial mechanical performance through the exploration of model material systems that cover a range of material performance including plastically deforming to brittle materials and hygroscopic to non-hygroscopic materials. In short, the interfacial strength of multi-layered tablets is derived from a combination of the interface architecture and material mismatch during compaction and unloading, the stresses invoked during ejection, and the mechanically and environmentally induced post compaction differential expansion. With this fundamental understanding in mind, experimental measurements are made that aim to predict multi-layer tablet performance at full-scale production through the use of hydraulic compaction simulators. Using this tool, the initial design space of a range of materials for multi-layer product is mapped out in terms of not only interfacial strength after compression but also under accelerated environmental conditions.