News

Posted On: 10/06/2006

Visualizing Dryer Problems

PharmaManufacturing.com

Operating fluid bed dryers today still involves more art than it does science. “Basically, an operator looks through a sight glass and manually controls the process, ” says Todd Pugsley, professor of chemical engineering at the University of Saskatchewan (Saskatoon).

Scale-up is even more problematic, he says, since what happens at the benchtop level is very different from what happens during full-scale production. “Patterns within the vessels change,” he says. And those changes ultimately affect product quality; larger granules can be segregated or finer granules entrained. Highly potent drugs or protein-based therapies are at greatest risk for quality problems.

Pugsley and his team have been studying the gas-particle and particle-particle interactions of fluid bed drying since 1998. They’re using new sensors, tomography and high-speed photography to capture the dynamic behavior of particles in the dryer. “Tomography’s nonintrusive, and you get a clear picture of what’s going on,” Pugsley says.

A team including Pugsley and his colleagues, as well as Merck Frosst Canada, used electrical capacitance tomography to determine the optimal flow behavior to improve drying and minimize fines. Then they used models to calibrate the sensor and confirmed results with X-ray tomography.

In a previous project, they had used a piezoelectric sensor to measure pressure fluctuation within a dryer. They replaced the product bowl’s viewing window with an acrylic insert threaded so that the transducer could be mounted within it. They then collected data for both a dry and a wet bed of granules, with the wet bed moving from 33% wt. to 4% wt. moisture.

Chaos analysis, in the form of the S-statistic method, developed by J.R. van Ommen of the Technical University of Delft (see PharmaManufacturing.com for more on this) was then used to analyze data. Hydrodynamics varied depending on the amount of moisture present. “When you take wet granules in a fluidized bed and start to dry them, the behavior of gases and the solid flow patterns change significantly,” says Pugsley. Ultimately, knowledge gained will lead to automatic control systems, he says.

Not only drug manufacturers are refining visual hydrodynamic measurement techniques. The fluidized bed equipment maker Glatt used fiber optics and high-speed photography to characterize the Wurster coating process and pinpoint problem zones, to optimize it for tablet coating. Research ultimately led to the design of a new insert (p. 19) that improves coating uniformity.

Academic research promises to raise the level of process understanding. “Manufacturers will be able to show FDA that they understand how changes in gas velocity and changes in the humidity of incoming air affect the process, as well as product quality,” says Pugsley. Research in this subject is also ongoing at the University of Calgary, the City College of New York, and Rutgers University.

Product Spotlight: Tablet Coating

Insert Improves Wurster Coating for Tablets, Particles

The Glatt Group has commercialized several improvements to the original “Wurster bottom spray” fluid bed technology invented by Dr. Dale Wurster in the 1950s.  Early versions of the Wurster were used for tablet coating, particularly when coatings were applied using volatile organic solvents.  However, the need for tablets to have very high hardness and low friability, and increased use of water-based coatings, led to greater interest in perforated pan coating equipment.  Wurster was favored for producing or coating particles and pellets.  Since Wurster offers a good distribution uniformity, interest in the technology for tablet coating re-emerged 
However, a Wurster designed for pellet coating could be problematic for controlled release formulations involving tablets, due to the potential for slow or no-flow zones, and tablet damage caused by impact with various insert components.  These problems could be especially severe in cases where the coating determined the release of active ingredient and coating uniformity was critical, explains David Jones, vice president of Glatt’s Pharmaceutical Services Division, a division of Glatt Air Tecchniques, Inc.(Ramsey, N.J.).
To optimize the Wurster process for controlled release tablet coating, it was first necessary to study the deficiencies in radial and axial mixing, and to identify “problem zones” within the equipment. Jones used fiber optics and high speed photography to visualize process dynamics.  One problem zone was traced to the base of the product container, at the perpendicular interface of the container wall and horizontal orifice plate (Diagram).  A second involved the impact of horizontally flowing tablets with the vertically disposed spray nozzle. Based on findings, Jones and his colleagues designed an insert to improve coating uniformity, and minimize machine/tablet interactions. 
Glatt’s tablet coating technologies include a patented Wurster HS (for high speed) system, which is said to provide for faster spray rates and reduced agglomeration.Glatt’s MacroWurster has been demonstrated to provide for a more uniform coating, and to reduce tablet attrition. 
For more information, visit www.glattpharmaceuticals.com/e/00_home/00.htm 

Coating System “Packages” the Tablet

BioProgress PLC’s TabWrap, a continuous coating machine, has been installed at a GMP-certified manufacturing facility in Spain. The company, Farmasierra (Madrid) will evaluate how it compares with traditional coating methods in improving release.

Developed by Bioprogress Technology Ltd. (Cambridgeshire, U.K.), as part of its NRobe platform, TabWrap wraps each compressed tablet in an edible film sheet, using animal ingredient-free XGel films developed by BioProgress. It is a dry process; the coating is applied in the film, eliminating the need for an additional drying step, thereby saving manufacturing costs.

According to BioProgress, by-passing drying eliminates the risk of chips and damage within the dryer, and the clumping, picking and sticking that can result from spray coating. The technology is said to facilitate tablet printing and, potentially, barcoding. TabWrap can process single-, two- and three-colored tablets and is said to provide a tamper-evident seal.

For more information, visit www.bioprogress.com

Brand Differentiation Expertise for Tablet Coating

Colorcon’s Brand Enhancement System for Tablets (BEST) is designed to help pharmaceutical manufacturers better distinguish their tablets through the use of color, shape, high-definition imprinting, special coatings, flavor and security identifiers.

For more information, visit www.colorcon.com/best