Garnet E. Peck Symposium - 2006 Abstracts, Bios and Presentations

• Garnet E. Peck - Monitoring of Roller Compacted Powders by Full Spectrum NIR and Tensile Strength - Abstract/Bio | Presentation
• Gregory E. Amidon - Data-driven Formulation Development Using Material Sparing Methods - Abstract/Bio | Presentation
• Keith J. Bowman - Fracture and Mechanical Properties of Porous Body Compacts - Abstract/Bio | Presentation
• Alberto Cuitiño - Multiscale Modeling of Compaction - Abstract/Bio | Presentation
• Stephen W. Hoag - Evaluation of the Deformation Behavior of Methacrylic Acid Copolymers Using a Compaction Simulator - Abstract/Bio | Presentation
• Matthew P. Mullarney - Anisotropy in pharmaceutical compacts - Abstract/Bio | Presentation

The two major challenges in the use of dry granulation by roller compaction are the compact and granule characteristics. A method for real-time in-line near- infrared (NIR) monitoring of roller compaction has been studied. Multivariate analysis using partial least square projections to latent structures was used to relate the spectral data with key compact attributes: content uniformity, moisture content, relative density, tensile strength, and Young's modulus. NIR calibration curves were generated using the spectral data collected on simulated ribbons. Tablets prepared under uni-axial compression and tested on the data from another set of simulated ribbons by monitoring the ribbons exited the roller compactor were studied. For all compact attributes, the NIR predicted values agreed well with the values measured using a reference method.

Biosketch: Dr. Garnet E. Peck, Professor Emeritus, Purdue University continues to conduct research and mentor graduate students at Purdue University. He received his B.S. (1957) degree in Pharmacy from Ohio Northern University and the M.S. (1959) and Ph.D. degrees in industrial pharmacy from Purdue University. From 1962 to 1967 Dr. Peck was employed by the Mead Johnson Research Center, and in 1967 he returned to Purdue University to join the Department of Industrial and Physical Pharmacy. He was associate department head from 1989 to 1996 and director of the industrial pharmacy laboratory until he retired in 2003.

Dr. Peck's research interests include optimization of drug product design and process design, in particular those systems involving tablets: topical drug adsorption, flow of solid systems, dispersed systems design and evaluation, new tablet coating materials and procedures, and excipient-drug interaction. His research has resulted in over 150 scientific publications. Dr. Peck is a member of the APhA, the PT Section of the American Association of Pharmaceutical Scientists, ACS, AACP, New York Academy of Science, Sigma Xi, Rho Chi, Phi Lambda Upsilon, Phi Kappa Phi and is a Fellow of the AAAS, APRS, AAPS and the American Institute of Chemists. Dr. Peck was Chairman of the IPT Section of the Academy of Pharmaceutical Sciences for 1983-84. He was elected to the 1985-90 United States Pharmacopeia Committee of Revision and then re-elected to the committee for 1990-95 and 1995-2000. He was elected to the Committee of Experts, Excipients for 2000-05 and has been re-elected for the 2006-2010 term. He is currently a member of the Food and Drug Administration Advisory Committee, and is an expert witness for the FDA. Dr. Peck is a founding member of the Catholic Academy of Science in the United States which was established in 1987. On March 20, 1994, the American Pharmaceutical Association awarded him the Sidney L. Riegelman Research Achievement Award in Pharmaceutics, and he received the Pharmaceutical Technology Publishers' Award in September, 1994.

Traditional formulation development is often conducted with laboratory scale batches that can consume kilograms of drug. However, the desire to reduce resource costs and decrease development time has required the development of material sparing methods for formulation development. In this presentation, particle (size, shape, distribution), powder (density, flow, cohesivity), compact (mechanical properties), and tablet (hardness, disintegration, friability, stability) characterization using material sparing methods will be discussed. This data-driven, material-sparing formulation development approach has been successfully used to predict the performance of tablets on scale-up.

Biosketch:Dr. Amidon received his Bachelor of Science degree in Medicinal Chemistry (1974) and his Ph.D. in Pharmaceutical Chemistry (1979) from the University of Michigan at Ann Arbor, MI. He is currently a Research Fellow at Pfizer, Inc in the Enabled Solid Dosage Forms group in Ann Arbor. He leads the Materials Assessment laboratory in Ann Arbor that is responsible for physical and mechanical property characterization of compounds, excipients and formulations in early development. Dr. Amidon is recognized for his expertise in the physical and mechanical property characterization of active pharmaceutical ingredients, excipients, products, and manufacturing processes as well as the development of scientific strategies for oral solid dosage form development. Dr. Amidon is a member of the USP Council of Experts and Chair of the USP Expert Committee on Excipient General Chapters. Dr. Amidon holds the title of Adjunct Associate Professor of Pharmaceutics at the University of Michigan, Ann Arbor, MI. He is a Fellow of the American Association of Pharmaceutical Scientists and a past recipient of the Ebert Prize from the American Pharmaceutical Association.

A materials science and engineering approach to understanding the fracture and mechanical properties of pharmaceutical compacts is vital during solid dosage manufacturing. Current techniques of measuring the tensile strength of pharmaceutical compacts, including transverse compression, diametral compression, and bend tests are being investigated to determine their viability in measuring a true tensile strength. Fracture toughness and Young's modulus are also common materials science mechanical properties of interest and techniques to measure these properties are being under evaluation. A mechanics approach to evaluating fracture modes and characteristics are also of interest. At this time experimental methods have been applied to evaluating the transverse compression test as defined by Hiestand and we have been investigating the effects of different experimental parameters on the validity of test data. In this presentation we will discuss the approaches used to evaluate the mechanical properties of pharmaceutical compacts in the context of materials science and engineering approaches applied to a broader range of materials.

Biosketch: Keith Bowman joined the faculty as Assistant Professor at Purdue University in 1988 after receiving his degrees from Case Western Reserve University (CWRU), (B.S. 1981, M.S. 1983) and the University of Michigan (Ph.D. 1987). He was promoted to Associate Professor in 1992, and then promoted to Professor in 1996. Keith Bowman also served as a visiting professor and received Alexander von Humboldt Research Awards at the Technical University of Darmstadt, Germany in 1996 and again in 2002. He served as a visiting professor at the University of New South Wales in Sydney, Australia in 2003. In 2005 he began a one year appointment as Interim Head of the Purdue School of Materials Engineering. He was named a Fellow of the American Ceramic Society in 2000 and has held several division and society-wide positions. Awards at Purdue University include receiving the Purdue Materials Engineering Best Teaching Award in 1992 and 1995 and Purdue's highest teaching award, the Charles Murphy Undergraduate Teaching Award in 1995. In 2003 Professor Bowman's name was added to the Purdue Book of Great Teachers. Professor Bowman has served as advisor or co-advisor to twenty master's and twenty doctoral students. His research group has lead efforts to quantify and model preferred orientation and property anisotropy in metals, ceramics and composites. Ceramics research has included elastic and fracture properties of structural materials as well as functional properties of electronic materials. This research has included the use of several different neutron and synchrotron sources to complement x-ray texture research using area detector diffraction. Professor Bowman has given plenary, invited and contributed research presentations in fifteen countries and has ongoing international collaborations with colleagues in Germany and Australia. Current research includes correlating crystallographic texture with domain orientation in poled, depoled and cyclically poled piezoelectric materials and evaluation of the mechanical behavior of compacts used to produce pharmaceutical products. Professor Bowman has over one hundred publications in print and is the author of a textbook An Introduction to Mechanical Behavior of Materials (Wiley, 2004).

In this talk we discuss several aspects the mechanics of densification pf powders. First we concentrate on the theoretical aspect of the early stages of densification, which are controlled by particle rearrangement. Our studies are motivated by experimental evidence that shows that during densification by particle rearrangement the domain of the compact is shared between a high-density region (where rearrangement has taken place already) and a low-density region (where the initial particle configuration remains essentially unchanged). In other words, the density is spatially heterogeneous, and densification proceeds in a discontinuous fashion, by growth of the high-density region at the expense of the low-density region. Our interpretation of this evidence is that particle rearrangement occurs in the form of a phase transformation. We substantiate our interpretation by studying the energetics of powder densification by particle rearrangement. Then, we present an array of numerical techniques to study the evolution of powder beds under confined conditions. In particular, we describe a mixed discrete/continuum or granular quasicontinuum (GQC) approach, which retains most of the advantages of discrete approaches, while circumventing some of their drawbacks. Quasi-continuum formulations have been recently proposed in the context of processes involving atomistic scale such as crystal defects, plastic deformation and fracture. In here, however, we focus on a formulation, which is tailored to describe granular systems to include heterogeneous powder beds.

Biosketch: Dr. Alberto M. Cuitiño is a Professor of Mechanical and Aerospace Engineering at Rutgers University. He is a member of the Rutgers Pharmaceutical Engineering Program (since 1995). Professor Cuitiño obtained a Civil Engineering Diploma from the University of Buenos Aires, Argentina, in 1986, and a MS degree in Applied Mathematics and a Ph.D. degree in Solid Mechanics from Brown University in 1992 and 1994 respectively. His research interests include multi-scale modeling, dislocation mechanics, consolidation of granular materials, modeling of solid foams, digital image correlation, folding patterns in thin films and modeling of ferroelectric polymers and ceramics. He is the author of several peer reviewed scientific articles and lectures at technical conferences, companies, and universities. Professor Cuitiño is currently the editor of Mechanics (a publication of the American Academy of Mechanics) and also the applied mechanics subject editor for the Latin American Applied Research. He has been a consultant to a number of drug and ingredient manufacturers on issues of ingredient properties and their effects on finished products.

Using a specially instrumented compaction simulator, the purpose of this study was to dynamically determine the mechanical properties of methacrylic acid copolymers (Eudragit) based upon a three-dimensional analysis. Materials studied included Eudragit L100-55, Eudragit L100 and hydroxypropyl methylcellulose (HPMC) K4M. These excipients were compressed into tablets using a compaction simulator. An instrumented die was used for the measurement of radial die-wall force. Tablets were compressed using a saw tooth displacement profile at two compression speeds-1 mm/sec and 100 mm/sec and three different compression pressures- 90, 125 and 250 MPa. Using three-dimensional analysis the mechanical parameters were determined from stress strain data. HPMC, methacrylate polymers (L100 & L100-55) exhibited plastic deformation and significant speed sensitivity. The yield pressure values of the binary mixes of the polymers were linearly related to the weight fractions of the neat polymers. The residual die-wall forces and net work of compaction followed ideal mixing rules and could be predicted from the neat materials based on the weight fraction of the polymers. The presence of methacrylate polymers in the binary mixes increased the residual die-wall forces, possibly indicating a change in elasticity.

Biosketch: Stephen W. Hoag, Ph.D., is an associate professor of Pharmaceutical Sciences at the University of Maryland; he received his Ph.D. in Pharmaceutics for the University of Minnesota-Twin Cities and a B.S. in Biochemistry for the University of Wisconsin-Madison. He has been a visiting professor at 3M Pharmaceuticals and Abbott Laboratories. In addition, Dr. Hoag serves on the USP's Counsel of experts and is on the editorial advisor board for the Handbook of Pharmaceutical Excipients. His primary research interests are in the areas of tablet press instrumentation and tablet compaction modeling, particle size measurement, the formulation of controlled release tablets, capsule filling and process analytical technology (PAT).

The mechanical property anisotropy of compacts made from six commercially available pharmaceutical excipient powders was evaluated. Uni-axially compressed cubic compacts of each excipient were subjected to pendulum impact testing and transverse tensile testing in several orientations. The pendulum impact test was used to measure the dynamic indentation hardness of each compact face (side, top, and bottom). Transverse tensile testing was utilized to determine the compact axial and radial tensile strength values. The indentation hardness (top ≈ bottom > side) and tensile strength tests (radial > axial) revealed mechanical property anisotropy in all the compacts. The extent of mechanical property anisotropy was quantified by using dimensionless ratios and was found to be significantly different for each material. In general, compacts with a higher degree of compact mechanical anisotropy also exhibited a higher brittle fracture index (BFI). This suggests that the macroscopic flaws intentionally made in the compact for the BFI measurement were similar to the flaws induced in highly anisotropic materials during uni-axial compaction. These results are consistent with the practical observation that brittle materials are more likely to exhibit failure in a plane normal to the compaction axis, i.e. experience tablet capping and lamination phenomena.

Biosketch: Matthew Mullarney graduated from the University of Connecticut in 1998 with a Bachelor of Science degree in Chemical Engineering. In 1999, he joined Pfizer Global Research Development as a scientist in the Pharmaceutical R&D Materials Assessment Laboratory. In 2004, he earned his Master of Science degree in Chemical Engineering from the University of Connecticut while studying the diffusion behavior of drugs in thermoprocessible hydrogels. Over his seven years at Pfizer, Matthew's primary research has focused on developing and implementing methods for studying the powder flow and compact mechanical properties of pharmaceutical powders. He has published scientific research papers in journals such as the International Journal of Pharmaceutics, Pharmaceutical Technology, Journal of Pharmaceutical Sciences, and Polymer.