Cross-sectional analysis of impregnated excipient particles by energy dispersive X-ray spectroscopy

Abstract

Impregnation of active pharmaceutical ingredients (APIs) onto porous excipients has numerous benefits for solid dosage formulations. Previous work has successfully demonstrated the manufacturing of pharmaceuticals using fluidized bed (FB) impregnation of APIs onto porous carriers and discussed its advantages (such as easy to implement, improvement of blend uniformity and dissolution kinetics, and stabilization of amorphous APIs). This study aims to develop methods for analysis of the spatial distribution of the impregnated API inside the porous excipient. An understanding of the spatial distribution of the API can be important if one wants to achieve high drug loadings. In addition, the spatial distribution of the API can impact its dissolution rate. The impregnation profile is analyzed using energy dispersive X-ray spectroscopy (EDS). Two formulations are investigated using Fenofibrate and Acetaminophen (model APIs), impregnated onto Neusilin (porous excipient). Several methods are presented for particle embedding and cutting in order to produce cross-sections for analysis. Embedding with carbon-based resins/adhesives produces cross-sections with high quality but the resins contaminate the sample with carbon and reduce the detection of trace elements. Manually cutting particles immobilized on carbon tape or inorganic-based adhesives produces cross-sections with a higher degree of roughness but improves the detection of trace elements and reduces/eliminates carbon contamination in the sample, allowing for API detection by its carbon footprint. EDS analytical results showed that for both Fenofibrate and Acetaminophen formulations examined in this work, the API profile is highly uniform (detected by both carbon and characteristic trace elements).