7/5/2019 Analytical Instrumentation | Thermo Fisher Scientific - US

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Analytical Instrumentation
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Spectroscopic analytical instrumentation uses molecular vibrations to provide feedback in the form of a
spectrum that identifies a material, or flags an unknown compound such as a contaminant or inclusion.
Near-infrared spectroscopy can be used for inline monitoring of the extrusion process.

Near-infrared spectroscopy offers several additional benefits to pharmaceutical production. Raman

spectroscopy offers the additional benefit of microscopic sampling and imaging, and can map whole
areas of a sample such as a tablet to screen for component distribution or contaminations. Rheology
offers critical information about the flow properties of the extrusion process, including feedback
regarding polymer melt and flow, the effect of additives and the analysis of extrudates.

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Featured analytical instruments

Antaris MX FT-NIR Process Analyzer DXR2xi Raman Imaging Microscope DXR2 Raman Microscope

Near-infrared spectroscopy for PAT monitoring

In drug manufacturing with extruders, specific characteristics such as a precise shear rate and a precise
temperature govern the formulation of a wide range of drug molecules. For bioavailability enhancement,
where inside the extruder the drug is converted into its amorphous form and molecular level dispersion
into a glassy solution, precise control of temperature and shear stress allows for precise conversion of
drug molecules from one crystalline modification into another crystalline modification. Residence time
distribution of the material processed must also be well controlled.

The process is operated normally in a continuous mode allowing high flexibility in targeted product size. By implementation of near-infrared spectroscopy
(NIRS) as process analytical tool (PAT), product quality attributes can be monitored in real-time, ensuring a constant desired product quality.
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To7/5/2019 Analytical
guarantee product quality, the quality by design (QBD) concept Instrumentation
of operating | Thermo
the process in aFisher Scientific - US
pre-determined parameter window can be applied and
replace the traditional process operation. Features include:

Near-infrared monitoring for PAT

Online monitoring of blend uniformity
Online monitoring of moisture content
Online monitoring and control of compounding process
Final product compliance
Scalable from lab experiment to production

NIRS extruder probes

In order to adopt continuous process monitoring with NIRS, fiber optic probes connect the spectrometer
to the extruder die. Rugged jacketed fiber lines use an industry-standard SMA905 connector. The
stainless steel probe body is designed for easy cleaning. Several interfaces are available for NIRS
measures using diffuse reflection or transmission modes.

NIRS extruder probes enable easy implementation of continuous monitoring, eliminating offline
sampling, the use of reagents or disposables. Chemical and physical information is available in real-
time from a single NIR spectrum.

Raman spectroscopy
Raman micro-spectroscopy provides a detailed evaluation of component distributions in compounded
drug formulations. It can identify and verify the presence of different components and contaminants in
various formulations and also provides detailed information on molecular structure and chemical
environment. This data can reveal subtle differences in the structure and orientation of molecules.
Polymorphs and solvates can be differentiated as well as the physical properties of materials such as
stress or degree of crystalline.

Chemical imaging with Raman spectroscopy

Single point Raman analysis is a powerful tool for examining materials but Raman imaging opens up a
new way of looking at samples. Imaging provides views of the spatial distributions of components and
the variation of physical properties throughout the sample.

Pharmaceutical formulations are typically complex mixtures involving multiple components. The
components go through different processing steps from raw material to the finished product.

Raman imaging enables users to identify and verify known components within the product, and identify impurities and contaminants. In some case it is also
necessary to be able to monitor the molecular state of the components to make sure that nothing unforeseen has changed during the processing steps.

Raman imaging is able to look at the spatial distribution of components and determine things like particle size and homogeneity.

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Analytical Instrumentation | Thermo Fisher Scientific - US

Optimizing process conditions in polymer-based drug delivery systems such as melt temperature and
flow behavior typically requires the investigation of additives in both lab and pilot scales. The flow
behavior during extrusion can be monitored using a lab scale extruder with rheological devices. The
effect of different modifiers and their concentration on the characteristics of the melt can be measured
quantitatively. After the extrusion process, the polymer material may be collected for further rheological
characterization.

Simultaneous rheometry and polarization microscopy using a hot stage microscope with heating/cooling capability allows studying the melting behavior of
crystals in the heating run, to investigate whether a re-crystallization occurs in the cooling run and derive suitable processing parameters for compounding
and extrusion.

This combined method allows investigating pure polymers, pure APIs and mixtures of those with plasticizers and additives and reveals whether an
amorphous solid dispersion or a crystalline solid dispersion is obtained during heating and whether it is stable during cooling or storage. Rheometry married
together with microscopy, provides well defined heating and cooling rates. It is a highly efficient screening tool delivering parameters which are traditionally
collected with several methods parallel to each other using different equipment.

Resources
Application Note: Advantages of Fourier-Transform Near-Infrared Application Note: Transfer of Near-Infrared Methods for the
Spectroscopy Analysis of Pharmaceutical Solid Dosage Forms

Application Note: Density and Copolymer Content in Polyethylene Presentation: Unlocking Solid Dosage Form Evaluation with Raman
Samples with FT-NIR Spectroscopy Imaging

Application Note: Diffuse Reflectance Fourier Transform Near-Infrared Presentation: Visualizing, Characterizing, and Analyzing
Spectroscopy to Confirm Blend Uniformity Pharmaceutical Constituents with Raman Imaging

Application Note: Evaluating Active Ingredients in Pharmaceutical Hot Scientific poster: Inline monitoring of a Hot Melt Extrusion Process
Melt Extrusion Products with Raman Imaging by Near-Infrared Spectroscopy

Application Note: Microscope Mapping on Formulated Pharmaceutical Scientific poster: Product Quality Control of a HME Co-Extrudate
Samples Using the Dispersive Raman Technique Using a Raman Imaging Microscope

Application Note: Quantification of the Active Ingredient in a
Pharmaceutical Topical Gel Formulation
Flyer: Ensure Safer and Effective Pharmaceutical Formulations by XRD
Brochure: Pharmacuetical Extrusion and Analytical Solutions
Brochure: Twin-Screw Extrusion Solutions
Product Specifications: HAAKE RheoWin software 21 CFR part 11
tools

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