Predicting optimal wet granulation parameters for extrusion-spheronisation of pharmaceutical pellets using a mixer...

Mixer torque rheometry (MTR) was evaluated as a pre-production (pre-formulation and optimization) tool for predicting ideal liquid-to-solid ratios (L/S) for extrusion-spheronisation of a wide range of APIs using 10g formulations. APIs of low, medium and high solubility were formulated at low and high loadings (15 and 40% w/w, respectively) with PVP as binder (5%) and MCC as the major excipient. L/S corresponding to the maximum torque produced during wet massing in the MTR, L/S_(maxT), was 0.8 for the low solubility APIs, which decreased to 0.6 for some of the more soluble APIs, especially at high loadings. Formulations extruded-spheronised at L/S_maxT) produced pellets of acceptable size (between 900 and 1400um) for all formulations, but mostly of unacceptable shape (dumb-bells of aspect ratio 1.2). Increasing L/S by 25% successfully produced spherical or near-spherical (aspect ratio 1.1) pellets for all formulations except one of the highly soluble APIs (piracetam) at high loading. Overall, MTR was demonstrated to be a useful pre-formulation and optimization tool in extrusion-spheronisation.