1. Academic Validation
  2. Predicting optimal wet granulation parameters for extrusion-spheronisation of pharmaceutical pellets using a mixer torque rheometer

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

  • Int J Pharm. 2017 Jan 30;517(1-2):19-24. doi: 10.1016/j.ijpharm.2016.11.057.
Manuel Kuhs 1 John Moore 1 Gayathri Kollamaram 1 Gavin Walker 1 Denise Croker 2
Affiliations

Affiliations

  • 1 Bernal Institute, University of Limerick, Ireland.
  • 2 Bernal Institute, University of Limerick, Ireland. Electronic address: [email protected].
Abstract

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/SmaxT) 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.

Keywords

Extrusionspheronisation; Liquid-solid ratio; Mixer torque rheometry; Pre-formulation; Wet granulation.

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