Analysis of Particle Agglomeration and Content Uniformity by Raman Imaging

Presented at: The 39^th Annual Meeting & Exposition of the Controlled Release Society (CRS 2012)
Authors: Oksana Olkhovyk and Ryan Priore – Gateway Analytical, 5316 William Flynn Highway, Gibsonia, PA 15044
Release Date: July 16, 2012

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Figure 1. Brightfield image of the Rhinocort Aqua® droplet and Fields of View (FOV) in red used to illustrate ISPS analysis and Agglomerate Identification and Sizing analysis.

Introduction:
Examination of drug particle size distributions (PSD), the extent of drug particle aggregates and content/blending uniformity is an important part in characterization of pharmaceutical products as it directly correlates with the dissolution rate of the Active Pharmaceutical Ingredient (API). Such characterization is also necessary for measuring product quality as well as establishing bioequivalence (BE), evaluating out of specification issues and addressing pharmaceutical anti-counterfeiting. This task is particularly critical for controlled release products with multiple actives and excipients since traditional analytical methods are not suitable for in-depth characterization of these complex formulations. Drug-specific PSD reporting is a challenging task for multiple ingredient formulations, including controlled-release capsules, beads, bi-layered tablets, stents and other advanced delivery systems.

We analyzed a pharmaceutical product with one active ingredient and numerous excipients to demonstrate that Raman imaging provides more objective measurement for ingredient-specific PSD. Morphology-driven confocal Raman spectroscopy and wide-field Raman Chemical Imaging (RCI) have shown promise for drug-only sizing by distinguishing particles by chemical makeup [1]; however, for drug particles agglomerate and aggregate assessment diffraction-limited imaging resolution is needed for accurate assessment of agglomerates, especially in suspension-like formulations.

In this work, confocal Raman spectroscopy and hyperspectral Raman imaging were employed to measure and compare populations of API-specific particles as well as size and number the drug aggregates in the dosage form of a nasal spray formulation.