Microscopy is a useful tool for form discovery and understanding. Different forms have different optical crystallographic, thermal, and infrared properties. These differences can be used help understand the relationships of different forms and, most importantly, aid in selecting the optimum form for development. The following examples illustrate how microscopy aids with solid state analysis.
Example 1 Ammonium Nitrate Thermal Microscopy
Ammonium nitrate has 5 forms and phase transitions are easily observed using thermal and polarized light microscopy. This example illustrates the power of microscopy in both solid-state form discovery and understanding.
Example 2 Triamcinolone Acetonide Optical Crystallography
Triamcinolone acetonide (TAA) known as anhydrate.
Thermal tests showed a new form which only appeared at high temperatures.
Optical crystallography demonstrated distinct differences between the two forms.
Polarized light and thermal microscopy crucial to the discovery and understanding of the two forms of TAA.
RG12525 Stable Form
A key element in the choice of solid-state form for pharmaceutical development is the determination of the stable form at ambient conditions. Microscopy is a useful tool for this determination. Particles of both forms can be introduced into a saturated solution. Over time the stable form will grow at the expense of the unstable one. In this example, Form 1 of RG12525 was determined to be the stable form at ambient conditions.
Summary
These are just a few brief examples of the ways that polarized light microscopy can aid in the development and understanding of solid state forms.