424033 Prediction of Lubrication-Based Tensile Strength Reduction Using a Discrete Element Method Approach

Monday, November 9, 2015: 9:45 AM
254B (Salt Palace Convention Center)
William R. Ketterhagen, Drug Product Design, Process Modeling & Engineering Technology, Pfizer Worldwide Research and Development, Groton, CT

In the production of pharmaceutical tablets and capsules, a lubricant such as magnesium stearate is frequently added to the powder blend or granulation to reduce friction between the powder and the tablet press or encapsulator components.  While the presence of the lubricant is generally necessary to improve manufacturability of the dosage form, if the lubricated blend is exposed to excessive shear strain during processing and handling prior to tableting or encapsulation, adverse effects on quality attributes of the final dosage form may be observed.  These effects can include an increase in wetting contact angle, a slowdown in disintegration and/or dissolution, and a reduction in tensile strength.

In this work, the extent of lubrication in a powder feed system is studied experimentally and with discrete element method (DEM) simulations.  Since a placebo blend is used to study this phenomenon, the tensile strength is the quality attribute used to quantify the extent of lubrication.  A framework for the prediction of lubrication-based tensile strength reduction using the discrete element method is proposed.  This approach utilizes a companion study in a lab-scale, high-shear mixer to map the extent of lubrication predicted in the DEM model to an experimentally relevant tensile strength prediction.  The tensile strength predictions from this approach are compared to experimental tensile strength data as well as predictions from a separate compartment modeling approach.

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