Instrumentation of tableting machines : high speed compaction investigation through simulation and radial die-wall pressure monitoring

Background: The complexity of the compaction process specially with using high-speed tablet presses necessitates the use of robust monitoring tools during the process. The use of an instrumented compaction simulator in the early stage of development has a significant benefit for product development and scaling-up. Up to now, in tableting research rare attention has been paid to the measurement of die-wall pressure. Die-wall instrumentation would be essential to understand the deformation of particles under axial pressure during the compaction cycle. It would be also of great help to investigate particle–die-wall shear stresses or friction, which is the cause of many tableting problems such as capping, lamination, and sticking. Purpose: To investigate the effect of compaction process variables ((pre) compression pressure, speed, ejection angle, tooling shape), formulation variables (filler, lubricant, binder, drug loading), powder physico-chemical properties (particle size and shape, water activity) on the compaction process through radial die-wall monitoring. Common tableting problems such as capping, lamination, and sticking were also investigated. Materials and Methods: Using a fully instrumented compaction simulator, the Presster™ guided by mathematical modeling and experimental design. Materials with different compaction behaviors: viscoelastic, plastic, brittle, plastic/brittle. Results and Discussion: Regarding tablet press parameters, by increasing compaction pressure radial die-wall pressure was increased for all materials (RDP and MDP), while with increasing pre-compaction residual die-wall pressure (RDP) was decreased for plastic materials, whereas by increasing speed maximum die-wall pressure (MDP) was decreased for all materials. Plastic and brittle materials showed increased tendencies for friction because of high radial relaxation. An increasing RDP value during compaction would indicate higher tendency for friction, whereas a high constant value of MDP would provide an evidence for plastic behavior. High compaction force combined with high speed should be avoided to prevent capping. Increasing ejection angle increased friction tendencies and ejection force for powders. Effective Fall Time (EFT) derived from decompression time was a reliable tool for sticking prediction. Moreover, radial die-wall monitoring was a more sensitive tool to detect sticking in comparison to take-off force. Flat shape tooling increased radial die-wall pressure while it was reduced by concave tooling due to more homogeneity in density distribution as well as greater area of contact. However, concave tooling showed higher friction and capping in comparison to flat tooling due to more radial movement for the powder, which resulted in higher densification at the edges in comparison to flat tooling. Concerning formulation variables, additives enhancing the elasticity or weakening the bonds such as lubricants or increasing drug loading promoted the occurrence of capping, while additives improving the mechanical strength such as binders reduced capping. The RDP/MDP ratio was not suitable as a sensitive parameter for the evaluation of lubricants, since it was only changed for plastic and/or brittle materials. Also, MDP was a good predictor for axial pressure transmission to the die-wall. External lubrication reduced the die-wall-compact friction without affecting the deformation behavior of the formulation. High RDP values were not always responsible for capping, because MCC exhibited low RDP values and still showed capping, therefore, other parameters such ER0 and tensile strength should also be considered. Regarding physico-chemical properties of powders, small / irregular particles acted more plastically at high compression, showed better axial pressure transmission, more porous and stronger compacts, and had higher tendency for friction and sticking than bigger particles. On the other hand, high water activity resulted in a low RDP and friction for all materials, and a high MDP for plastic materials. This was due to the lubricating and plasticizing effects of water, respectively. Conclusion: Radial die-wall pressure monitoring is recommended as a valuable tool to assess the deformation behavior of materials and detect friction and adhesion at early stages of development and during production as well, which would be of great help to predict common scaling-up tableting problems such as capping, lamination, and sticking.