Prediction of in-vitro dissolution and tablet hardness from optical porosity measurements

Advanced manufacturing technologies such as continuous processing require fast information on the quality of intermediates and products. Process analytical technologies (PAT) to monitor many critical quality attributes (CQAs) have been developed and successfully implemented in pharmaceutical industry. However, there are some CQAs, which still have to be measured off-line with significant effort due to the lack of suitable PAT sensors. Two prominent examples are the in-vitro dissolution and the tablet hardness. Both are obtained via destructive measurement, and the dissolution is tedious and time-consuming to determine. In this study, these two CQAs were predicted via correlation with the optical porosity of tablets. The optical porosity was measured via a novel combination of gas in scattering media absorption spectroscopy (GASMAS) and photon time of flight spectroscopy (pTOFS) with a SpectraPore instrument. The approach was tested in a continuous tableting line and showed promising results in predicting the amount of drug released after specific dissolution times as well as the tablet hardness. This indicates that the measurement of optical porosity can support control strategies within the real-time release testing (RTRT) concept.