Characterization of pharmaceutical bilayer tablets: a fracture mechanics approach

Bilayer tablets are generating great interest recently in the pharmaceutical industry as they offer several advantages over conventional single layer tablets. However, the production of bilayer tablets has been facing great difficulties as the layered tablets are prone to delaminate at the interface and fracture in the individual layers due to insufficient bonding strength. Poor product performance is a cause of great concern as it will incur financial loses and regulatory liabilities. In the pharmaceutical industry the process of bilayer design has been heavily dependent on the trial-and-error approach during the formulation and process development stages. To overcome this hurdle it is critical to understand the mechanical properties of the materials and to develop a methodology for the characterization of bilayer tablets. The work presented in this dissertation will focus on gaining the mechanistic understanding on the factors that impact the performance of the bilayer tablets. A methodology has been developed based on the principles of fracture mechanics for the characterization of bilayer tablets. As part of this endeavor, interfacial stress intensity was estimated. To understand the impact of manufacturing process parameters and environmental conditions on the bonding strength of bilayer tablets a comprehensive DOE has been executed to obtain statistical trends. Results indicated that material properties, compaction forces of the layers and interfacial topography have a strong influence on the strength of bilayer tablets. Strength of bilayer tablets increased with the increase of interfacial roughness and curvature. Physico-mechanical properties of the powders, deformation histories of the layers, and compression process parameters greatly influenced the interfacial stress intensity factor of the bilayer tablets. For the bilayer tablets made with plastic material in the first layer, the stress intensity factor is more dependent on interfacial radius of curvature than on interfacial roughness and vice versa in the case of bilayer tablets made with brittle material in the first layer. The mechanistic understanding and the methodology developed for the characterization of the bilayer tablets in this dissertation will enable to move away from the existing “trial-and-error” approach during the design and development of bilayer tablets. The new paradigm of bilayer tablet development will incorporate the principles of the quality by design by leveraging the prior knowledge.Ph. D.Includes bibliographical referencesIncludes vitaby Niranjan K. Kottal