Webinar Review: New Technologies to Streamline Chemical Imaging and Quantification of Active Pharmaceutical Ingredient (API) Forms in Drug Development

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  • Published: Jun 13, 2019
  • Categories: X-ray Spectrometry / Infrared Spectroscopy / Raman / NMR Knowledge Base
thumbnail image: Webinar Review: New Technologies to Streamline Chemical Imaging and Quantification of Active Pharmaceutical Ingredient (API) Forms in Drug Development

Webinar Review

New Technologies to Streamline Chemical Imaging and Quantification of API Forms in Drug Development


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This webinar describes the application and advantages of Raman and IR Spectroscopy for the analysis of oral solid dose pharmaceutical drugs.

In the first part of the webinar, the viewer is introduced to crystallinity analysis using three different methods: Transmission Raman Spectroscopy, X-Ray Powder Diffraction and solid-state NMR Spectroscopy. The second part of the presentation explores Infrared Imaging for the analysis of (multi-layered) tablets including presentation of several examples.

During drug development, a frequent problem is that development compounds may have low water solubility in their stable crystalline forms. This can be remedied by transforming the compound into a metastable, amorphous form. Metastable forms of compounds are, however, likely to revert to their thermodynamically stable states, therefore determining the crystallinity of the compound is an important attribute.


Transmission Raman Spectroscopy of crystallinity in drug formulations

Achieving adequate exposure of drug substances can be challenging when low water-soluble compounds are used in drug product development. Bioavailability can be optimized using prodrugs and drug conjugates, lead optimization through chemistry, and formulation design.  Formulation design for low water-soluble substances can be achieved via dispersion and stabilization through spray drying of the drug in a polymeric matrix (e.g. HPMCAS) as an amorphous solid dispersion (ASD), which displays higher bioavailability.  Since amorphous forms absorb water and tend to crystallize over time, a sensitive quantification of the crystallinity is key to maintaining bioavailability of the drug.  In Archana Kumar’s presentation, the proof of concept and sensitivity of a transmission Raman spectroscopy (TRS) approach to the detection of low levels of crystalline drugs in an ASD is presented and compared to existing X-ray powder diffraction (XRPD) and solid state nuclear magnetic resonance spectroscopy (ssNMR) methods. It is shown that XRPD and ssNMR are suitable for analysing the active pharmaceutical ingredient (API) at high concentration but may not be suitable for the final drug product. Commonly the API in an amorphous SD contributes about 20% of the mass, dissolved in 80% polymer. XRPD can reliably detect crystalline API at concentrations higher than 18% (relative crystallinity). In ssNMR the peaks produced by amorphous state API are broad and overlay the peaks produced by crystalline API, leading to reliable detection at concentrations higher than 4.5% relative crystalline API after deconvolution; however, this method is time consuming.

After an introduction to TRS, Archana explains how this technique can be used for the analysis of low concentrations of crystalline API in amorphous API, technical considerations, instrument settings, data acquisition and analysis. She shows that the TRS method can produce measurements with comparable sensitivity and accuracy as ssNMR (~24h) in about 1 to 5 minutes per sample without needing destructive sample preparation methods.


API measurements in tablets

The second part of the on-demand webinar presents the Agilent 8700 LDIR Chemical Imaging System that employs quantum cascade laser technology, and its application for  the analysis of drug tablets, biological tissues, laminates, microplastic and polymorphs.  A system and technical  overview is given by Lester Taylor followed by a presentation  demonstrating how to use the instrument for the analysis of a tablet, resulting in an image showing the distribution of the components on the surface of a tablet. Next, a demonstration of the technology applied to microscope slide mounted tissue sections allowing for visualization of the distribution of lipids even in a very large field of view, such as a complete section of a mouse brain.  Finally, Lester Taylor talks about the usage of the system of API analysis in drugs. Compared to TRS, IR provides additional information, for example substances which are Raman inactive.


For the full contents of the webinar, register to view the on-demand presentation here.

Your Presenters

Archana Kumar, Ph.D.

Archana Kumar, Ph.D. 

Scientist, Small Molecule Analytical Chemistry and Quality Control

Genentech Inc.

Cristian Cojocariu

Lester Taylor, Ph.D.

Pharma Marketing,
Agilent Technologies

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