Quantitative analysis of the layer separation risk in bilayer tablets using terahertz pulsed imaging.

Layer separation is a critical defect in many bilayer tablets. Despite its importance for product quality, few studies have investigated its root cause. We evaluated bilayer tablets with varying layer separation tendencies using terahertz pulsed imaging (TPI) in comparison with other analytical methods such as tensile strength measurements, friability testing, scanning electron microscopy (SEM), and X-ray computed tomography (XRCT). The layer separation risk was determined by friability testing and shown to be correlated with the final compression pressure used for bilayer tablet fabrication. TPI could nondestructively detect cracks between the component layers that lead to layer separation. The adhesion integrity of the interface was quantified by the interface index, a unique value derived from the time-domain terahertz waveform. The interface index showed good correlation to the layer separation tendency and could distinguish interface quality among seven batches of bilayer tablets. In contrast, SEM and XRCT detected structural defects but could not distinguish batches with high or low layer separation risk. TPI revealed the relationship between compression pressure and interface quality. Thus, TPI can aid in quality control by providing a precise estimate of the layer separation risk and robust quality of bilayer tablet development with better understanding of layer separation.

Analysis and prediction of absorption behavior of colon-targeted prodrug in rats by GI-transit-absorption model.

The gastrointestinal-transit-absorption (GITA) model is useful for the analysis and the prediction of the absorption behavior of drugs orally administered as solutions. In the present study, we tried to predict the plasma concentration-time profile of a colon-targeted prodrug, salicylazosulfanilic acid (SASA), and its parent drug, 5-aminosalicylic acid (5-ASA) which is regenerated after dosing. Prediction of plasma concentration-time profiles for SASA and 5-ASA was performed based on the GITA model using parameters describing GI-transit kinetics, the absorption in each GI segment, and the regeneration of 5-ASA in cecum. Plasma concentration-time profiles of both SASA and 5-ASA after oral administration of SASA were predicted very well by introducing a factor for the first-pass elimination of 5-ASA into the GITA model. The simulation study using the parameters obtained in the present study showed that about 94.7% of SASA reaches the cecum, where 5-ASA is regenerated very rapidly and 76.0% of 5-ASA is absorbed. Furthermore, the bioavailability of 5-ASA was estimated to be 0.330 because of the first-pass elimination through both cecum and liver. In conclusion, the absorption behaviors of a prodrug and its regenerated parent drug can be predicted very well and be clarified successfully using the GITA model.