Introduction

This course is an introduction to solid state characterization of organic molecules. Techniques include x-ray powder diffraction (XRPD), thermal methods spectroscopic methods, and water uptake.

For each technique, basic theory is presented along with its application to organic molecules. Information on instrumentation, sample preparation, and data analysis is included in the modules. Use of the technique to differentiate and quantitate solid forms (polymorphs) is discussed and case studies are presented to show how the measurements were used in real life situations.

  • XRPD theory and best practices
  • Thermal analysis methods and how they are used together
  • Spectrometric methods overview and when to use them
  • Water sorption measurements and how to determine when water may be an issue
  • Case studies to show how the techniques were used to solve real world problems

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Module 1. X-Ray Powder Diffraction (XRPD) 

  • Diffraction basics
  • Instrumentation (geometry, detectors, data collection modes)
  • Sampling issues (preferred orientation, particle size)
  • Variable temperature XRPD
  • Data Analysis
  • Quantitation
  • Case study


Module 2. Thermal Methods

  • Differential scanning calorimetry (DSC)
    • Overview
    • Calibration
    • Sample preparation
    • Measurements and data analysis (enthalpy of fusion, glass transition temperature)
  • Hot stage microscopy
    • Instrumentation
    • Use
  • Thermogravimetry (TG)
    • Instrumentation
    • Use
    • Thermogravimetry-infrared (TG-IR) measurements
  • Determination of thermodynamic stability
  • Monotropic vs enantiotropic systems
    • Energy temperature diagrams
    • Quantitation
    • Case study


Module 3. Infrared (IR) Spectroscopy

  • Theory
  • Instrumentation
  • Sampling Techniques (DRIFTS, ATR, imaging)
  • Variable temperature IR
  • Near- IR (NIR)
  • Data Analysis
  • Quantitation
  • Case Study


Module 4. Raman Spectroscopy

  • Theory
  • Instrumentation
  • Sample preparation
  • In-situ measurements (crystallization studies, RH, hot and cold stage microscopy)
  • Applications (form identification, form conversion, interactions, processing, stability, screening)
  • Imaging
  • Quantitation
  • Case Study


Module 5. NMR Spectroscopy

  • Theory
  • Solid state NMR
  • Solution NMR
  • Applications (solvent identification, interactions, salts/cocrystal identification, mixture analysis, suspensions, reactions)
  • Quantitation
  • Case Study


Module 6. Water Sorption

  • Water-solid interactions (absorption, adsorption, deliquescence)
  • Automated instrumentation
  • Data collection, analysis, and interpretation
  • Relative humidity chambers
  • Hygroscopicity flow chart, how to determine if water will be an issue, strategies to deal with problematic materials
  • Case studies included in the various sections