(346d) Mechanistic Characterization of Bilayer Tablets .I: The Role of Pre-Compaction and Compaction Forces

Solid oral dosage forms are the preferred route for many drugs and are still the most widely used formulations for new and existing complex-configuration tablets (e.g., bilayer tablets). Over the past decade or so, interest in bilayer tablets as an oral immediate-release/controlled-release system has increased substantially. However, during the production of such tablets, lack of sufficient bonding and adhesion at interfaces between the adjacent layers can compromise the mechanical integrity and performance of the final solid dosage form. A path forward to reduce the incidence of these issues in the production of bilayer tablets is to establish a rational strategy for the selection of compatible product formulations and manufacturing processes. This approach requires proper characterization of the interface of the bilayer tablets in representative pharmaceutical formulations.

In the reported study, bilayer tablets of the widely used excipient microcrystalline cellulose (MCC) in the form of Avicel 102 were formed with different pre-compaction (2kN, 4kN, 6kN, 8kN) and compaction (6kN, 10kN, 14kN, 18kN) forces to quantitatively characterize the strength (σ) of the interface and the adjacent compacted layers. In the reported experiments, using a developed tensile stress method, bilayer tablets of the same material were debonded to determine the fracture and axial tensile strength values. It was observed that when the first layer was compressed to a high density, the bonding with the second layer became difficult and it was not possible to produce intact bilayer tablets (Cases; 4kN vs. 2kN, 6kN vs. 2kN, and 8kN vs. 2kN) (σ_layer > σ_interface). It was demonstrated that the material response of the constrained MCC particles to an applied initial compression force within the initial compacted layer have a detrimental effect on the resistance to fracture of a bilayer tablet. The mechanism of failure at the interface or at the individual layers was also studied. It was shown that once the magnitude of the applied final layer compaction stress greatly exceeds the initial layer compaction stress (Cases; 2kN vs. 18kN and 4kN vs. 18kN), the tablet catastrophically fails at the first layer and not at the interface (σ_layer