Comprehensive evaluation of layer separation tendency of novel three-layered tablets with geometric and mechanical properties

The layer separation tendency of a novel three-layered matrix tablet was investigated according to various physical properties and novel experiments. Even though layer separation did not occur during manufacturing process and storage, it was observed during a dissolution test depending on the mid-layer formulation. According to the powder properties of the mid-layer substances, Form A, which had higher porosity and lower density than Form B, displayed a tendency of layer separation. These properties correlated with the degree of absorption of the aqueous medium into the mid-layer, which was evaluated by water uptake and mass loss tests. Water uptake and mass loss profiles of the formulations were similar, but the mass loss property of Form A was about 5% higher at the time points, due to the faster dissolution rate of the mid-layer in the first 0.5 h. Using a texture analyzer, the layer separation force of the system and adhesion force between the barrier layers were evaluated to understand the correlation between the geometric property and layer separation tendency. During the first 0.5 h, the wrapping property of the swollen barrier layers significantly affected the layer separation tendency. The drug release profiles of two formulations could be divided into three stages on the basis of their geometric property as it showed a sigmoid-type. However, for the first stage (about initial 1 h in duration), the drug release of Form A was more than Form B due to the mid-layer's powder properties. The results provided valuable information for detailed understanding of issues in the development of a multi-layered system and indicated the importance of a well-designed tablet formulation and manufacturing process.