Measuring and Modeling Density Distributions in Pharmaceutical Tablets Katherine Doyle Advisor: Dr. Zavaliangos Mentor: Wenhai Wang

Agenda Introduction Die Compaction Tablet Formation Current Work Future Work Background  Die compaction: loose powder pressed in a die by upper and lower punch  Wide range of tablet densities possible by varying compressive force and die shape  Physical analysis coupled with FEA modeling How do we describe the mechanics of die compaction? Schematic of a die/ punch assembly 4

Agenda Introduction Die Compaction Tablet Formation Current Work Future Work Background Hydrostatic and Mises Equivalent Stresses (First and Second Invariants) Principle Stresses on a Differential Element

Background Agenda Introduction Die Compaction Tablet Formation Current Work Future Work Simple Tension: Shear: Diametrical Compression: Simple Compression: Simple tests for strength properties 3 Mohr-Coulomb Shear Failure line from simple tension, shear, diametrical compression, and simple compression:

Die Compaction Agenda Introduction Die Compaction Tablet Formation Current Work Future Work Drucker-Prager/cap Model for powder die compaction  Widely used model because accounts for:  Stronger compact in compression than tension  Cohesion, internal friction angle, and their dependence on relative density (RD)  Shear failure and cap surfaces Drucker-Prager/cap model showing two failure surfaces and various RD values on P-Q plane 1

Tablet Formation Agenda Introduction Die Compaction Tablet Formation Current Work Future Work Method for tablet formation  Equipment:  Carbide steel die and punches (flat and convex circular, convex oval)  INSTRON mechanical testing machine  Materials:  Microcrystalline cellulose  Magnesium stearate (die/punch lubricant)  Specimen preparation:  Compacted to MPa  Clean or lubricated die/punch  Sliced to show cross section INSTRON model 1127 General testing machine 5

Current Work Agenda Introduction Die Compaction Tablet Formation Current Work Future Work Experiments:  Calibration curves: compaction pressure versus RD and RD versus hardness  Microhardness testing and x-ray computerized tomography to map density distribution in tablet slices  Diametrical compression tests Clean and lubricated tablets after diametrical compression 2 Clean and lubricated tablets after diametrical compression. Experiments by K. Doyle.

Current Work Agenda Introduction Die Compaction Tablet Formation Current Work Future Work Modeling:  Learning ABAQUS FEA software  Graphical interface, coded input files, setting up problem, analysis  Gurson model (simple), Drucker-Prager/cap model  Previous results:  Physical experiment, clean die  ABAQUS simulation, clean die Density distributions on 4mm slice of convex tablet 2

Future Work Agenda Introduction Die Compaction Tablet Formation Current Work Future Work Future Experiments and Modeling:  Map density distributions of circular and oval convex tablets (verify previous experiments)  Compare manual results to x-ray tomography and simulation  Repeat and continue diametrical compression testing for wide range of RD  Continue to learn how to model with ABAQUS  Complete die compaction model of 3D oval convex tablet

References 1. Cunningham, J.C, Sinka, I.C., Zavaliangos, A Analysis of Tablet Compaction. I. Characterization of Mechanical Behavior of Powder and Powder/Tooling Friction. Journal of Pharmaceutical Science, Vol. 93, No. 8, August 2004: Cunningham, J.C, Sinka, I.C., Zavaliangos, A Analysis of Tablet Compaction. II. Finite Element Analysis of Density Distributions in Convex Tablets. Journal of Pharmaceutical Science, Vol. 93, No. 8, August 2004: A.T. Procopio, J.C. Cunningham, A. Zavaliangos Analysis of the Diametrical Compression Test and the Applicability to Plastically Deforming Materials. Journal of Materials Science. 38, pp – 3639, “Powder Forming Research.” Department of Mechanical Engineering at University of Wales Swansea “Tensile and Compression Testing.” ETS, North Tower Technologies. &sid=6

Drucker-Prager/cap Model for powder die compaction Cap Surface: Shear Surface: cohesion internal friction angle no physical meaning determined from experiments Die Compaction Agenda Introduction Die Compaction Tablet Formation Current Work Future Work