Imaging Cleaved Tablets to Determine API Size and Distribution Metrics from Coatings and Particles

Synopsis

When formulating and deconstructing tablets, accurately determining API particle metrics, coating thicknesses, distribution, and polymorphic form is critical. With the majority of APIs having a particle size below 30 µm, producing this information requires high spatial resolution (down to 1 µm) and high chemical specificity so different polymorphic forms are revealed. Maintaining the integrity of particle and granule domains is hugely desirable to ensure subsequent statistics from analyses are representative of the contents. Naturally cleaving the tablet surface, which is not mechanically altered, via microtoming or milling, achieves this and drastically simplifies the sample preparation process.
Here we present a series of case studies, highlighting the benefit of generating chemical images (from Raman spectral data) with topographic and morphology information. This benefits the spatial resolution and therefore accuracy of metrics derived from chemical image analysis as well as enabling correlation between physical and chemical tablet properties. Collecting Raman data over a complex surface also enables the analysis of coatings and API distribution from uncoated tablets and high spatial resolution analysis of powders.
Examples will include:
• Multi-API chemical/morphological correlation
• Small API domain size cleaved tablet analysis
• Pre-formulation granule blend analysis
• Coating thickness and uniformity