Dual Automated Approach for Sizing and Characterizing Budesonide In Suspension

Angela Flowers1, Emily Landsperger1 & David Exline1

1Gateway Analytical, 2009 Kramer Road, Gibsonia, PA / 15044, USA

Summary

Budesonide suspension is a corticosteroid that is often administered by means of a nebulizer.  Like all inhalable products, the particle sizing of the active pharmaceutical ingredient (API) is important as it relates to bioavailability and rates of absorption.  Agglomerates can artificially skew particle size data when not properly accounted for.  However, it is also important to gain a full understanding of the API’s potential to agglomerate in final formulation, as agglomerate particle size can affect the API’s efficacy.  The United States Federal Drug Administration has issued draft guidance related to bioequivalence studies for budesonide suspension.  Part of the requirements for in vitro bioequivalence testing is particle size distribution and agglomerate analysis.  Automated optical sizing with Raman characterization performed by the rap.ID Single Particle Explorer (SPE) instrument and automated SEM-EDS analysis were used in the present study to obtain the size and agglomerate information of budesonide suspension.  While SEM-EDS analysis proved to be a more efficient analysis, capable of collecting data in the submicron size range, this technique exhibited limitations with identifying agglomerated particles. The SPE provided sizing results, although more time-intensive than SEM-EDS, while being able to distinguish single particles from agglomerates. The SPE also has the ability to perform sizing and agglomerate analysis on the budesonide particles while still in liquid suspension, as well as perform full chemical characterization of the API particles.  A combined approach using both of the automated methods provided the most comprehensive data on the budesonide API particle size distribution (PSD) and agglomerates.