Relationship between the cohesion of guest particles on the flow behaviour of interactive mixtures.

In this study, we aimed to investigate the effects cohesion of small surface-engineered guest binder particles on the flow behaviour of interactive mixtures. Polyvinylpyrrolidone (PVP) - a model pharmaceutical binder - was spray-dried with varying l-leucine feed concentrations to create small surface-engineered binder particles with varying cohesion. These spray-dried formulations were characterised by their particle size distribution, morphology and cohesion. Interactive mixtures were produced by blending these spray-dried formulations with paracetamol. The resultant blends were visualised under scanning electron microscope to confirm formation of interactive mixtures. Surface coverage of paracetamol by guest particles as well as the flow behaviour of these mixtures were examined. The flow performance of interactive mixtures was evaluated using measurements of conditioned bulk density, basic flowability energy, aeration energy and compressibility. With higher feed l-leucine concentrations, the surface roughness of small binder particles increased, while their cohesion decreased. Visual inspection of the SEM images of the blends indicated that the guest particles adhered to the surface of paracetamol resulting in effective formation of interactive mixtures. These images also showed that the low-cohesion guest particles were better de-agglomerated that consequently formed a more homogeneous interactive mixture with paracetamol compared with high-cohesion formulations. The flow performance of interactive mixtures changed as a function of the cohesion of the guest particles. Interactive mixtures with low-cohesion guest binder particles showed notably improved bulk flow performance compared with those containing high-cohesion guest binder particles. Thus, our study suggests that the cohesion of guest particles dictates the flow performance of interactive mixtures.

Process Analytical Technology for High Shear Wet Granulation: Wet Mass Consistency Reported by In-Line Drag Flow Force Sensor Is Consistent With Powder Rheology Measured by At-Line FT4 Powder Rheometer.

Drag flow force (DFF) sensor that measures the force exerted by wet mass in a granulator on a thin cylindrical probe was shown as a promising process analytical technology for real-time in-line high-resolution monitoring of wet mass consistency during high shear wet granulation. Our previous studies indicated that this process analytical technology tool could be correlated to granulation end point established independently through drug product critical quality attributes. In this study, the measurements of flow force by a DFF sensor, taken during wet granulation of 3 placebo formulations with different binder content, are compared with concurrent at line FT4 Powder Rheometer characterization of wet granules collected at different time points of the processing. The wet mass consistency measured by the DFF sensor correlated well with the granulation's resistance to flow and interparticulate interactions as measured by FT4 Powder Rheometer. This indicated that the force pulse magnitude measured by the DFF sensor was indicative of fundamental material properties (e.g., shear viscosity and granule size/density), as they were changing during the granulation process. These studies indicate that DFF sensor can be a valuable tool for wet granulation formulation and process development and scale up, as well as for routine monitoring and control during manufacturing.