title: Predicting optimal wet granulation parameters for extrusion-spheronisation of pharmaceutical pellets using a mixer torque rheometer.
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.
authors.affiliation: Bernal Institute, University of Limerick, Ireland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Kuhs
authors.affiliation: Bernal Institute, University of Limerick, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: Moore
authors.affiliation: Bernal Institute, University of Limerick, Ireland.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Kollamaram
authors.affiliation: Bernal Institute, University of Limerick, Ireland.
authors.forename: Gavin
authors.initials: G
authors.lastname: Walker
authors.affiliation: Bernal Institute, University of Limerick, Ireland. Electronic address: denise.croker@ul.ie.
authors.forename: Denise
authors.initials: D
authors.lastname: Croker
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000295:instrumentation* / Q000379:methods; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010992:Plethysmography, Impedance / Q000295:instrumentation / Q000379:methods; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods; D014867:Water / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations; D014867:Water
keywords: Extrusionspheronisation; Liquid-solid ratio; Mixer torque rheometry; Pre-formulation; Wet granulation