Explorations in Effusivity

An annual effusivity seminar draws a standing-room-only crowd. Wyeth, AstraZeneca, Patheon, and USP share their research findings.

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It was more than the free wine that brought a crowd of 80 pharma professionals and equipment makers to the fourth annual Mathis Effusivity Seminar in Baltimore last month. Thermal effusivity is gaining notoriety as a key metric for improved process control in blending and drying, and a cornerstone of the process analytical technology (PAT) movement. Those in attendance heard representatives of several industry leaders, such as Wyeth, AstraZeneca and contract manufacturer Patheon, put down their proprietary shields and share the finer points of their effusivity experiments.

The standing room only event, held during the American Association of Pharmaceutical Scientists (AAPS) annual meeting, was sponsored by Mathis Instruments, whose latest line of effusivity sensors make real-time monitoring possible. Mathis has partnered with equipment and software vendors—among them, FMC, Symex, Tote Systems, and Invensys—to create pilot versions of effusivity-monitoring systems currently being put to the test by industry.

Effusive about effusivity

Whereas last year’s seminar drew attendees curious for a little exposure to PAT, this year’s had much more purpose, says Mathis president Nancy Mathis. “This year people were very anxious to get real information about effusivity and PAT and to learn how you really do it,” she says.

Effusivity is a combination of conductivity, density and heat capacity. It is a function of, among other things, particle structure, particle size and shape, and material composition, and thus differs from material to material and changes during blending and drying processes. Measuring effusivity, therefore, can be an effective means of monitoring blend uniformity, homogenization, and concentration, or moisture content during drying. “Any time a material becomes homogenous, or separates, or changes properties by drying, that’s what effusivity tests,” Mathis told the Baltimore gathering.

Mathis began the meeting by discussing her latest sensors, which are smaller (17 mm. in diameter) than previous versions and equipped for wireless data transmission. She then gave the floor to representatives of firms beta testing the devices and entire effusivity systems.

Patheon's points

Steven Closs, senior process engineer at Patheon, discussed studies his firm conducted to correlate effusivity measurements with those of high performance liquid chromatography (HPLC). Closs and colleagues were able to establish blend endpoints based upon effusivity readings (rather than based upon time), then take samples to the lab for chromatography analysis. The two measurements correlated down to 0.5% with active ingredients, Closs noted.

Patheon is also studying effusivity’s role in measurement system analysis (MSA). Preliminary results suggest that effusivity is an effective means of determining variation due to product, repeatability and reproducibility, and thus can be integral in setting meaningful specifications, reducing error and increasing blend sensitivity.

Patheon’s next step is to duplicate these tests in a wireless environment, which will allow it to test another dynamic, the rotational speed of the blender, Closs said.

AstraZeneca's assessment

AstraZeneca is evaluating the use of effusivity sensors to monitor lubrication. Ted Larason, one of the company’s senior engineers, discussed conclusions of studies measuring the distribution of magnesium stearate during blending. Most importantly, AstraZeneca found thermal effusivity is an effective way to monitor, and possibly even to control, magnesium stearate distribution. Larason also discussed a variety of other lessons learned, such as how to optimize the position of effusivity sensors on the blender cover.

Wyeth's work-in-progress

Scientists and engineers at Wyeth Pharmaceuticals, meanwhile, are looking into how effectively effusivity sensors determine endpoints in drying processes. Jean Sebastien Semard, a Wyeth product and process development scientist, detailed his firm’s sensor system that had been custom-designed by Invensys and which incorporates Invensys’ automated sampling technology and software. The system includes a wall-mounted human machine interface (HMI), integrated boards in the control panel of the fluid bed dryer, SQL-based software on a Wonderware platform, and a sampler containing the effusivity sensor which attaches to an existing port in a dryer can.

Wyeth tested several multicomponent mixtures in attempts to correlate effusivity with loss on drying (% LOD) measurements. It was satisfied with its results, said Semard, and hopes to improve them in its wireless beta testing.

USP's understandings

Finally, Gary Ritchie, a scientific fellow with the U.S. Pharmacopeia, discussed USP’s initial studies. While Ritchie cautioned that his lab is just getting familiar with effusivity technologies, he does believe that effusivity can be a key component of multivariate analysis. By measuring effusivity over a wide array of solids, semi-solids and liquids, Ritchie and his colleagues were able to get a better sense of variability due to factors such as humidity, room temperature and particle size. “It’s safe to say that if you explore the multivariate approach with the technique, you can do much more than with just a univariate approach,” he said.

Results of the wireless beta testing of effusivity will be announced at January’s IFPAC conference, Mathis said. She also hopes to have wireless demonstrations by Mathis and several partners at April’s Interphex show in New York.

For more information on the effusivity seminar and its presentations, contact Mathis sales and marketing coordinator Nadine Chiasson, at Nadine@Mathisinstruments.com.

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