John and Brad will be speaking about using laser diffraction to correlate the in-situ (batch mode) bead diameter of chromatography media to bed stability of a packed chromatography column.  An empirical method was developed to predict the performance of a packed chromatography bed during extended use.  For a selected Hydrophobic Charge Induction Chromatography (HCIC) medium (pKa 4.8), the median bead diameter was measured in buffer under a variety of conditions of pH and conductivity.  Particle size analysis indicated a significant increase in bead diameter after equilibration in a low pH (<4) buffer.  An increased pressure drop across a packed bed at production scale (45 cm diameter) was also observed under this low pH condition. To further investigate this observation, a scale down column (3.2 cm diameter), using a constant diameter-to-height aspect ratio instead of a conventional fixed bed height, was employed to characterize bed stability over multiple cycles. In-situ bead size data was correlated to a measure of breakthrough volume and calculated HETP values when the medium was exposed to repeated cycles of swelling and compression in a packed bed.  The analysis indicated that the low pH buffer accelerated bed deterioration.  This trend was further supported by qualitative overlays of rate of change of conductivity versus totalized volume.  When the low pH buffer was ommitted from the process, increased bed stability was observed over multiple cycles.  Thus, the trends determined by particle size analysis, that the bead diameter should not change significantly if buffer pH remains above a threshold level (pKa 4.8) throughout the process step, were confirmed.  This suggests that changes in bead size could be attributed to induced electrostatic repulsion at low pH and could be modulated to increase usable column lifetime.  When correlated with packed-bed performance, particle size analysis can be a valuable tool to better characterize column lifetime at increased scale.  This technique can also be used as a predictive tool for screening new chromatgraphy media and developing robust process operations.

Dr. Lee is Vice President of Pharmaceutical Development at Particle Sciences Inc.  He is responsible for product development at Particle Sciences as well as providing support to clinical manufacturing operations and business development.  His responsibilities include oversight of preformulation, formulation development, drug delivery, analytical services, quality control, and quality assurance.

Before joining Particle Sciences, Rob held senior management positions at Novavax, Inc., Lyotropic Therapeutics, Inc., and Imcor Pharmaceutical Co.  He holds B.S.’s in Biology and Chemistry from the University of Washington and a Ph.D. in Physical Bioorganic Chemistry from the University of California, Santa Barbara.

Rob has published articles in numerous peer-reviewed journals and three book chapters plus holds 11 issued patents and 14 provisional or PCT patent applications. 

He has 20 years of experience in pharmaceutical research and development of both therapeutic drugs and diagnostic imaging agents.  Rob maintains strong academic ties, including an appointment as Adjunct Associate Professor of Pharmaceutical Chemistry at the University of Kansas in 1992, and serving as a reviewer for both the International Journal of Pharmaceutics and Journal of Pharmaceutical Sciences.

His talk will focus on nanoparticulate suspensions and emulsions.  Particle Sciences, Inc. has the infrastructure to develop and characterize formulations and drug-device combinations, prepare and characterize APIs of a desired particle size distribution, scale-up processes and develop robust analytical methodology for pharmaceutical applications of these materials.  During the course of a Client development program for  a semi-solid vaginal dosage form (gel) containing a micronized, crystalline API, PSI was requested to develop, evaluate, and ultimately validate analytical methods to measure the particle size of the API in the gel.  Methods were developed using both a HORIBA LA-950V2 laser scattering particle size analyzer and a light microscopy system coupled to Clemex imaging software.  The evaluation of these methods showed that either method could be used  for the analysis of particle size and both were amenable to validation.  Also, the results indicated a strong agreement between the two characterization methods. This agreement is very satisfying especially when considering the fundamental differences in measurement principles.  This presentation will describe the evaluation of the two methods and present some of the data generated during this work.

Bob will be speaking on VLP’s consisting of the major viral structural proteins can be produced in both mammalian and insect cells, and while they may assume similar morphologies to the native virus, they are often extensively pleomorphic. This may present problems for large-scale production and purification.  Since VLP’s are composed of lipid bilayer structures and have the potential to reform after disruption, Microfluidization using high shear pressures could reduce the size variability of VLP’s and ease purification.  In the present work, VLP supernatant produced using insect cells was analyzed for size variability by dynamic light scattering (HORIBA LB-550 DLS) and laser diffraction (HORIBA LA-950 Laser Diffraction Analyzer) both prior to and after processing with the M-110Y high shear Microfluidizer.

Dr. Panagiotou is the CTO of Microfluidics International Corporation.  Microfluidics develops high shear fluid processors for processing multiphase fluids and nanomaterial formulations. Applications of the technology include drug delivery, electrode materials for batteries and fuel cells, nanoceramics for optical coatings and carbon nanotube dispersion. Dr. Panagiotou has responsibility for the overall direction of Microfluidics’ technology and leads the development of Microfluidics Reaction Technology (MRT), an award winning process intensification technology to manufacture nanosuspensions “bottom up”. Prior to Microfluidics, Dr. Panagiotou was a Manager at Arthur D. Little and a Principal Scientist at Physical Sciences. In her previous positions, Dr. Panagiotou was involved in the development of drug eluting, polymer coatings for stents, insulin inhalation devices and spectroscopy based sensors. Dr. Panagiotou holds a MS and Ph.D. in Mechanical Engineering from Northeastern University. She co-authored over 60 papers for journals and conference proceedings and is a co-inventor of two patents.

Mark Bumiller is the Vice President of Particle Products at HORIBA Instruments.  Mark graduated from Carnegie Mellon University in chemical engineering.  He has worked in the particle characterization field for more than 20 years in product design, technical support and management roles.  He has served on the executive board of the International Fine Particle Research Institute and the Particle Technology Forum within the American Institute of Chemical Engineers.

Mark will be presenting two talks, the first on Particle Characterization Applications in the Pharmaceutical Industry, which focuses on how image analysis is being used in the pharmaceutical industry in general and for solid oral dosage forms in specific.  The second on "Nanoparticles, Nanotechnology and Nanononsence."  While the term "nanotechnology” has evolved in recent years, a major branch of this research is centered on particles in the range of 1 -100 nm where particles exhibit novel properties due to their size.  He will discuss defining the size scales involved, characterization techniques, sample preparation and nanoparticle applications.