Advances in PAT
What are recent advances in instrumentation to apply PAT in solid-dosage manufacturing?
Strother (NIR spectroscopy):
In addition to the development of Fourier transform NIR, the more significant advances in the industry probably relate specifically
to blending applications. There are several companies that have instruments designed to attach to blenders to monitor a mixture
of powders to ensure they are properly mixed without becoming 'overblended.'
There is also ongoing work to improve integrating NIR as part of a total analysis system. We've worked with organizations
that would like to run a battery of tests on solid-dosage forms ranging from weight, hardness, and other physical properties
to more in-depth chemical analysis from NIR. We also have found that NIR can also be used to accurately predict some physical
properties such as particle size, crystalline polymorphs, hardness, and density.
Mattes (NIR spectroscopy):
The latest technology is digital dispersive NIR. These instruments are fast and accurate and are not sensitive to vibration
as Fourier-transform (FT) instruments can be. Due to higher noise levels, FT instruments require more co-added scans for a
complete spectrum. FT instruments claim higher resolution but this is not an advantage in the NIR spectral region, where absorbance
bands are broad and where using the higher resolution only makes the FT instrument signal-to-noise poorer. New applications
are developed all the time. For example, digital dispersive diffuse transmission methods have been applied to prolonged release
tablets for the prediction of dissolution profile, which can greatly reduce analysis time. The FOSS MasterLab has proven to
be robust in harsh manufacturing environments and delivers extremely accurate and reliable results providing manufacturing
with real-time feedback on content uniformity, moisture and other quality attributes.
Automation of data acquisition and processing has allowed the rugged solid-state SyNIRgi (a Malvern NIRCI analyzer) to be
brought to the process line for data acquisition at various sample thieving points. Minimally-trained personnel can now collect
data enabling thorough process understanding.
Vaisman (particle-size analysis):
Recent advances in integration and control software have significantly simplified embedding on-line size analyzers into manufacturing
equipment. An embedded on-line analyzer, with fully integrated controls, serves to convert a traditional batch-manufacturing
unit into a continuous operation with higher throughput, less waste, and better product quality. Availability of streaming
on-line data reduces or removes the need for off-line sampling saving time and resources.
Freeman (powder-flow techniques):
As mentioned above, the measurement of powder flow and other behavioral characteristics, in a process relevant way, is relatively
new. As a result, advances in powder and process understanding are continuing at a rapid rate. Most leading global pharmaceutical
manufacturers are employing this technology in process, development, and quality-assurance environments.
1. FDA, Guidance for Industry: PAT-A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance (Rockville, MD, Sept. 2004).