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

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• 作者：Manuel Kuhs ; John Moore ; Gayathri Kollamaram ; Gavin Walker ; Denise Croker ; ^{denise.croker@ul.ie}
• 关键词：Pre-formulation ; Mixer torque rheometry ; Extrusionspheronisation ; Wet granulation ; Liquid-solid ratio
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：30 January 2017
• 年：2017
• 卷：517
• 期：1-2
• 页码：19-24
• 全文大小：760 K
• 卷排序：517

文摘

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 10 g 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 1400 um) 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.