Crystallization touches every aspect of our lives from the foods we eat and the medicines we take, to the fuels we use to power our communities. The majority of pharmaceutical products go through at least one crystallization step during their manufacture. Salt and sugar are delivered to our dinner tables as crystals. The unwanted crystallization of gas hydrates played a role in the recent Deepwater Horizon oil spill. Continue reading
At the 2010 American Institute of Chemical Engineers (AIChE) Annual Meeting in Salt Lake City, there were a number of well-attended sessions dealing with the related topics of Quality by Design (QbD) and Process Analytical Technologies (PAT). Continue reading
I recently had the pleasure of collaborating with a group of very talented scientists at EMS and International Institute of Pharmaceutical Research (IIPF). EMS and IIPF are two pharmaceutical companies based in Hortolândia, a city roughly 100 miles northwest of Sao Paulo, Brazil. We worked on an interesting project where FBRM was used to track Active Pharmaceutical Ingredient (API) particle size reduction during wet milling. Traditionally, offline laser diffraction had been used to track this process; however this approach proved to be time consuming, prone to inaccuracy and potentially hazardous. Continue reading
On Tuesday, November 2, METTLER TOLEDO held its 1st Symposium in Cambridge, MA, hosted by Novartis Institutes for BioMedical Research (NIBR). The success of the Symposium went beyond expectations: 65 scientists representing a large variety of small companies (CoNCERT, Cubist, Tetraphase), larger companies (Pfizer, Dow, Amgen), and research institutions (Massachusetts Institute of Technology) attended the event. The main themes of the Symposium were crystallization and process safety. Des O’Grady and I started by giving an overview of the technologies later covered by the industry speakers: Focused Beam Reflectance Measurement (FBRM®), Particle Video Microscope (PVM®), EasyMax™, RC1, and ReactIR™. Continue reading
In July, I announced that I would be chairing next week’s In Process Particle Forum being held in Iselin, NJ. Today, I want to highlight one of the papers that will be presented at In Process Particle Forum. Steve Mehrman of Johnson & Johnson will present on using FBRM C35 during fluid bed granulation development and scale-up.
A paper by Jose Quevedo and Robert Pfeffer titled In Situ Measurements of Gas Fluidized Nanoagglomerates was just published on the web and will also be published in an upcoming issue of Industrial & Engineering Chemical Research.
The paper explores the in-process measurement of nanoparticle aggregates in a fluidized bed. Real-time, in-process particle system measurement with FBRM (Focused Beam Reflectance Measurement) and PVM (Particle Video Microscopy) show significant differences in the density and mean size of the aggregates formed in conventional fluid beds and microjet assisted fluid bed.
The authors report:
“Nanoparticles cannot be fluidized as individual particles but instead fluidize in the form of large (mean size about 100-400 μm), highly porous (internal porosity greater than 98%), hierarchical fractal structured agglomerates. Many nanopowders are very difficult to fluidize because of the large cohesive forces between the particles due to their very small size and high surface area…
In situ agglomerate size measurements and imaging of fluidized nanoagglomerates were achieved by reducing the electrostatic charge in the bed and using the FBRM and PVM probes from Lasentec.”
Electrostatic charges were reduced by bubbling the fluidizing gas through an alcohol-water mixture. This dramatically reduced adhesion of particles to surfaces and greatly improved the quality of the on-line measurements in this dry fluidized bed.
In Situ Measurements of Gas Fluidized Nanoagglomerates
Jose A. Quevedo† and Robert Pfeffer*‡
Otto York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, New Jersey 07102
Ind. Eng. Chem. Res., Article ASAP
Publication Date (Web): March 2, 2010
† Current address: Shell Global Solutions, P.O. Box 38000, 1030BN Amsterdam, The Netherlands.
‡ Current address: Department of Chemical Engineering, Arizona State University, Tempe, AZ 85287.
In case you missed the live webinar, Calibration Free Supersaturation Assessment and Control for the Development and Optimization of Crystallization Processes, presented today by Mark Barrett, Ph.D., Senior Research and Development Engineer, Solid State Pharmaceutical Cluster (SSPC) – Ireland, the on-demand version of Calibration Free Supersaturation Assessment and Control for the Development and Optimization of Crystallization Processes is now available.
If you are interested in discussing Crystallization topics with Mark Barrett and over 300 others who work in Crystallization, I invite you to join the LinkedIn Crystallization Community.
I am excited to be chairing the upcoming In Process Particle Forum focused on Liquid and Solid Dosage Formulations on September 15 in Woodbridge, NJ. This will be the third year in a row that METTLER TOLEDO has brought together expert users of FBRM and PVM to present their cutting edge research to a group of their peers. This year, we have the best agenda yet with four industry papers from:
- Bristol-Myers Squibb
- Johnson and Johnson
I’m currently traveling in Brazil, specifically around an area called Minas Gerais (General Mines). As the name suggests, mining is the main industry in Minas Gerais; they extract almost every ore you can imagine to make metals from aluminum to zinc. Continue reading
Wiley InterScience highlighted a paper that was just published in MacroMolecular Reaction Engineering by Professor Rolf Mülhaupt and his student Rainer Xalter of Albert-Ludwigs University in Freiburg, Germany.
This paper discusses the use of METTLER TOLEDO FBRM® and PVM® for real-time in-process monitoring of polymer and catalyst particles. During the polymerization of high-density polyethylene (HDPE), FBRM® and PVM® are used to determine polymer growth kinetics and to measure the effects of catalyst breakage and attrition within standard commercial-scale reactors.
“Unprecedented insight into the particle growth processes during ethylene slurry polymerizations catalyzed by supported single-site and Ziegler catalysts was gained by online monitoring using two different probes inserted directly into the reactor. FBRM online monitoring complemented by PVM online visualization of polymer particles allowed for the distinction of different types of particle growth processes depending on catalyst type and productivity.”
Citation: “On-line Monitoring of Polyolefin Particle Growth in Catalytic Olefin Slurry Polymerization by means of LasentecTM Focused Beam Reflectance Measurement (FBRM) and Video Microscopy (PVM) Probes”, R. Xalter and R. Mülhaupt, Macromol. React. Eng. 2010, 4, 25. http://doi.wiley.com/10.1002/mren.200900048?crel=US_AC_eAdv_Blog