Mechanistic characterization of bilayer tablet formulations

Abstract

The interest in bilayer tablet as an oral immediate-release/controlled-release system has substantially increased in the past decade. However, during the production of such tablets, lack of sufficient bonding and adhesion at interfaces between adjacent layers is compromising the mechanical integrity and performance of the final solid dosage form. In this study, bilayer tablets of the widely used excipient microcrystalline cellulose in the form of Avicel 102 and pregelatinized starch were formed with different pre-compression (2 kN, 4 kN, 6 kN, 8 kN) and final compression (6 kN, 10 kN, 14 kN, 18 kN) forces to quantitatively characterize the strength (σ) of the interface and the compacted adjacent layers. Bilayer tablets were axially debonded (i.e., separation of adjacent layers that are subjected to axial loading) until fracture and axial tensile strength values were determined. It was observed that when the first layer was compressed to a low porosity, the bonding with the second layer became difficult and it was not possible to produce intact bilayer tablets (σlayer > σinterface). It has been 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. Different fracture patterns, namely, clear layer break, half–half break, cap-shape break, and clear interface break were observed as a function of various initial and final compression forces. X-ray micro-computed tomography (μCT) was utilized to examine the influence of localized density distribution on the delamination (layer separation) phenomena of bilayer tablets. It has been shown that once the magnitude of the applied final layer compaction stress greatly exceeds the initial layer compaction stress, the tablet catastrophically fails at the initial layer not at the interface (σlayer < σinterface). The results of this study point out that the measurement of the interfacial strength provides insight into some of the major complications of bilayer tablets.