Garnet E. Peck Symposium - 2007 Abstracts, Bios and Presentations

• James Pazdan - Practical Statistical Considerations in the Design, Analysis, and Validation for the use of NIR for CU and Blend Uniformity in Solid Dosage Formulations - Abstract/Bio | Presentation
• M. Teresa Carvajal - Surface Energy and Functionality of Powders - Abstract/Bio | Presentation
• Lynne S. Taylor - In-line Spectroscopic Monitoring of Crystallization Processes - Abstract/Bio | Presentation
• Chetan P. Pujara - Granulation: Preparation, Evaluation, and Control - Abstract/Bio | Presentation
• James K. Drennen - Practical and Theoretical Concerns for Spectroscopic Determination of Pharmaceutical Compact Hardness and Density - Abstract/Bio | Presentation
• Rodolfo Romañach - Determination of Drug Content by Near Infrared Spectroscopy - Progress Along the Learning Curve - Abstract/Bio | Presentation

There is a wide availability of software packages that will accurately compute PLS and PCR models, often with this type of software conveniently bundled with the NIR equipment. However, in many cases, it leaves the user in the dark concerning the following topics: basic statistical concepts of bias and random variability, proper fitting of linear models, complete understanding of cross and test validation, experimental design concepts for testing robustness, the usefulness of and how to analyze replicate NIR sample measurements, how to fully validate and test robustness of the assay, ideas for setting up calibration samples, etc. This talk will explain some of these basic concepts, and provide simple formulas and approaches that can be computed in Excel or in a simple basic statistical package, that will supplement the basic PLS or PCR approach analysis provided by the packaged software.

Learning objective: Understand and properly utilize some of the basic statistical concepts for the development and validation of NIR in content uniformity and blend uniformity.

Biosketch: Dr. Pazdan received his MS in Applied Probability and Statistics from Northern Illinois University and his BS in Psychology from Illinois Institute of Technology. and is responsible for consultation and development of experimental designs (DOE) in formulation, analytical assay development, teaching of basic and applied courses in statistics, developing simple software tools to be used by scientists for a variety of statistical problems, development and maintenance of new validated stability analysis programs to be used globally throughout Novartis, and extensive statistical support for the experimental design aspects of the CRADA that Novartis has with the FDA for a full design space submission that also includes developing and validating models for the use of NIR for content uniformity and blend uniformity. His interest/expertise includes experimental design, linear models, variance component estimation and confidence intervals, density estimation, partial least squares, general nonparametric techniques, and nonlinear modeling.

Pharmaceutical unit operations are intended to alter the bulk (macroscopic) properties of the material being subjected to the process. However, when working with powders, changes in bulk properties brought about by the process inevitably alter the surface properties of the particles. If we consider that powders interact with each other at the surface level, it follows that pharmaceutical unit operations alter the interactive properties of powders in ways that are not controlled nor fully understood. The combined effects of surface energetics and surface topology are the determining factors on the functionality and processability of pharmaceutical powders. Powder functionality can be used as the strategic basis for optimizing the performance of dry powder mixtures used in formulations, especially those intended for inhalation and oral administration. This scheme requires better understanding of the behavior and stability of the pharmaceutical particulate materials when exposed to different conditions of temperature, moisture, pressure and shear. This talk will focus on the characterization of as well as on the exploitation of physical, chemical and environmental factors that influence surface energy, particle interactions and cohesion-adhesion behavior of powders during dosage form manufacturing as well as on the product shelf-life.

Learning objective: Understand how a materials surface science approach is important to developing a means to characterize, control, stabilize and optimize powder properties at every step in the manufacturing process.

Biosketch: M. Teresa Carvajal is an Assistant Professor of Industrial and Physical Pharmacy at Purdue University. She received her PhD in 2001 from the University of Bath. Her research focuses on materials surface science for understanding and controlling properties of particles at the microscopic level in order to control the macroscopic properties and behavior of powders. She focuses on the study of the properties of powders and powder technology, including solid-solid and solid-liquid interactions as strategies for formulation for inhalation and oral dosage forms. Prior to joining Purdue, Dr. Carvajal worked in the pharmaceutical industry for 13 years. First at Hoffmann-La Roche where she worked on the development of oral dosage forms, including tablets, hard and soft gelatin capsules, solid dispersions, and self-emulsifying systems. Dr. Carvajal's work on the properties and behavior of powders and powder blends extended into the development of powder-device combinations for pulmonary delivery of peptides and small organic molecules. She subsequently joined Bayer Pharmaceuticals, where she was responsible for pre-formulation and early formulation work for lead drug discovery compounds. Her research involves the study of surface microstructures and the energetic surface properties of powders. Of special interest to Carvajal's research is the relationship between the surface properties of powders and the physical functionality of drugs and excipients.

Most pharmaceutical manufacturing processes involve batch crystallization of the active pharmaceutical ingredient (API) from solution as a process of purification, final crystal form selection, and/or particle size control. Uncontrolled crystallization can also occur during secondary manufacturing for certain susceptible compounds which can undergo process-induced form transformations. Crystallization is an extremely complex process, particularly when multiple crystal forms can be produced, as is common with pharmaceutical materials. In-line monitoring techniques can be used to better understand and control crystallization processes. In this presentation, the use of-line Raman spectroscopy to monitor crystallization processes during both primary and secondary manufacturing operations is discussed.

Learning objective: Discuss the advantages and disadvantages of Raman spectroscopy for crystallization monitoring.

Biosketch: Lynne S. Taylor is currently an Associate Professor in the Department of Industrial and Physical Pharmacy at Purdue University. Prior to moving to academia, she spent 5 years working at AstraZeneca in Sweden where she was an associate principle scientist within the Solid State Analysis group. Lynne graduated with a Bachelor of Pharmacy degree from the University of Bath and a PhD in Pharmaceutical Technology, from the University of Bradford, UK. In between her degrees, she spent some time working in pharmacy in both the UK and Zimbabwe. After her PhD, Lynne was a postdoctoral researcher with Professor Zografi at the School of Pharmacy, University of Wisconsin-Madison. Her current research interests center on the investigation of water-solid interactions, amorphous materials, amorphous molecular level solid dispersions, hydrates and polymorphs, and the application of vibrational spectroscopy to probe molecular level aspects of the solid state. She has approximately 40 peer reviewed publications related to these research areas. She was the recipient of the AAPS New Investigator Grant and the AACP New Investigator Award in 2003 and has served as a member of the Editorial Advisory Board for the Journal of Pharmaceutical Sciences since 2002.

Granulation is a particle design process whereby small particles are brought together to form physically strong agglomerates. High-shear wet granulation, fluidized-bed granulation, and roller compaction followed by milling are commonly used granulation techniques in the pharmaceutical industry. Primary granule properties of interest are granule size and size distribution, intragranular porosity and granule strength. Bulk properties of interest include bulk density, flowability, and moisture content. This presentation will focus on techniques used to monitor and control wet granulation processes. Several techniques to observe and control granulation processes are currently being used in the pharmaceutical industry e.g., impeller torque in high-shear mixers. More recently, probes have been used to monitor and control particle size or moisture content of the granulation in high-shear mixers and fluid-bed granulators. Appropriate use of these techniques can provide a more thorough understanding of a formulation and manufacturing process to establish meaningful design space, specifications, and manufacturing controls.

Learning objective: To present the fundamentals of wet granulation and the techniques for monitoring & controlling the processes.

Biosketch: Chetan Pujara is currently Director and Head of Product Formulation Development group at Allergan Inc. He received his B.S. degree in Pharmacy from BITS, Pilani, India and PhD in Pharmaceutics from Purdue University, West Lafayette, IN. Prior to joining Allergan, Chetan was employed by Abbott Laboratories for ten years in Global Pharmaceutical R&D. His work experience includes physico-chemical characterization of NMEs & excipients, development of formulations and manufacturing processes for NMEs & LCM of marketed compounds. His research interests are in the areas of powder physical properties, process scale-up and PAT. Chetan is an Adjunct Associate Professor in the Department of Industrial and Physical Pharmacy, Purdue University and is the current Chair of the Industrial Advisory Board of the Dane O. Kildsig Center for Pharmaceutical Processing Research. He is also a member of the Physical Properties Working Group of PQRI.

Pharmaceutical scientists have long had an interest in measuring tablet hardness and compact density. Practical methods for nondestructive determination of mechanical properties of pharmaceutical compacts are of interest for the pharmaceutical scientists and engineers responsible for monitoring and controlling pharmaceutical processes. Recent work regarding photon migration patterns provide a valuable understanding of the factors affecting the volume of interrogation and ultimately provide practical methods for the accurate nondestructive prediction of mechanical properties of materials during processing.

Learning objective: Explain the practical and theoretical limitations of accurate prediction of compact hardness of tablets with nondestructive spectroscopic methods.

Biosketch: Dr. Drennen received a B.S. in Pharmacy from Duquesne University in 1985 and a Ph.D. in Pharmaceutical Sciences in 1990 from the University of Kentucky. He is presently Associate Dean for Research and Graduate Programs in the Mylan School of Pharmacy and Graduate School of Pharmaceutical Sciences at Duquesne University. He is a co-founder and Director of the Duquesne University Center for Pharmaceutical Technology. He has served as the Pharmaceutical Editor and the North American Editor of the Journal of Near Infrared Spectroscopy and as the Editor of the Pharmaceutical Validation Column for NIRnews. Dr. Drennen was the recipient of the first international Buchi NIR Award, in September 2001. Dr. Drennen has consulted widely with the pharmaceutical industry and is a partner in the consulting company Strategic Process Control Technologies, LLC. He is Editor-in-Chief of the Journal of Pharmaceutical Innovation.

A number of researchers have worked for over a decade on the development of near infrared (NIR) spectroscopic methods to determine drug content in tablets. NIR methods may determine the drug content of tablets without sample preparation, and easily analyze 30 tablets per hour in transmission mode or over 100 tablets per minute through diffuse reflectance measurements. The development of NIR methods requires understanding spectroscopy, chemometrics, and at least a rough visualization of the interaction of radiation with particles. This last goal, interaction of radiation with particles, is fundamental and probably the most challenging since several theories have sought to explain this interaction for more than a century. The conference will summarize the lessons learned in developing NIR methods to determine drug content, present recent work with low drug content tablets and efforts to estimate detection limits for NIR transmission methods.

Learning objective: Discuss the advantages of using NIR spectroscopy to determine drug content in tablets and the steps needed to develop a NIR method to determine content uniformity.

Biosketch: Dr. Romañach is currently Professor of Chemistry at the University of Puerto Rico - Mayagüez Campus. He completed his Ph.D. in Chemistry in 1986 at the University of Georgia under the direction of Dr. James A. de Haseth. He has over 20 years of experience in vibrational spectroscopy, and worked in Puerto Rico's pharmaceutical industry for 12 years prior to joining the UPR-Mayagüez faculty. In the pharmaceutical industry he worked extensively in assay and cleaning validation, and in providing analytical support for API and pharmaceutical process related problems. He currently teaches Quantitative Chemical Analysis and Instrumental Analysis courses, and has developed a new course titled Pharmaceutical Analytical Chemistry (QUIM 5205). His research is focused on the development of near infrared and Raman spectroscopic methods for applications of interest to the pharmaceutical industry, teaching chemometrics to industry professionals, and strengthening industry/university interactions. His research projects have been funded by INDUNIV and the NSF Center of Pharmaceutical Process Research. He is also a researcher in the new NSF - Engineering Research Center for Structured Organic Particulate Systems.