Investigation of transient temperature of pharmaceutical tablets during compaction with infrared thermography and computational modeling

Manufacturing of a pharmaceutical tablet from powder is always accompanied by the conversion of irreversible mechanical work of compaction into heat. The heat is generated due to friction between powder particles, particles and the die wall, plastic deformation of particles, bonding, and other irreversible processes. The resulting temperature increase potentially might have significant effects on a tablet’s mechanical properties, disintegration time, and drug release. The purpose of this research is to utilize infrared thermography (IRT) as a non-destructive, non-contact in-line process analytical technology (PAT) tool to measure pharmaceutical powders thermomechanical behavior during tablet compaction process. With instantaneous visual results from infrared measurement and in contrast to just monitoring tablet’s temperature evolution, the tablet’s rate of cooling at regular regime can be a measurable critical quality attribute (CQA) for pharmaceutical tablet quality control. For this novel approach, results show there is an enormous potential to use infrared (IR) measurement as an in-line PAT tool to discriminate tablets between same formulation but experienced different total process shear of a continuous powder flow stream in continuous pharmaceutical tablet manufacturing operations. For the first time, a novel correlation model with respect to different total process shear of model granulation is developed toward predicting tablet tensile strength that only needs (i) the tablet’s rate of cooling at regular regime obtained from IR measurement and (ii) relative density of tablet. Temperature rise can also affect physiochemical properties of the medicinal substances, including chemical stability, crystallinity and polymorphous state. The temperature increase in the powder during compaction is detrimental to heat sensitive active pharmaceutical ingredients (APIs) with low heat conductivity, such as most organic materials used in pharmaceutical formulations. Therefore, it is important to understand the thermomechanical behavior of powders during compaction. Infrared thermography (IRT) provides a useful tool to trace the temperature distribution evolution of the tablet surface after ejection from the tablet press in laboratory experiments but also during manufacturing, in particular as in-line PAT tool for quality control. We show that utilizing infrared thermography as a non-destructive and non-contact PAT tool that allows accurate tablet surface temperature fields acquisition in real time to accuracy of ± 0.1 °C during tablet compaction. Heat transfer of particulate systems in pharmaceutical tablet manufacturing is important element to be considered, yet is not fully understood. We utilize computational tools based on particle-mechanics to describe the formation of networks during the consolidation process. These heterogeneous networks are subsequently used to simulate the heat transfer process after ejection. We demonstrate the computational modeling match well with experimental results from infrared measurement, which have not been previously reported.Ph.D.Includes bibliographical reference