Confocal Raman microscopy for mapping phase segregation in individually dried particles composed of lactose and macromolecules

Abstract

The quality of powder is determined by its functionality such as dissolution, encapsulation and flowability. The functionality of powder is in turn determined by their primary properties such as morphology and composition which need to be studied. Hence morphology and surface composition has been largely investigated in spray dried powders and individually dried particles. On the contrary, there is only scarce information regarding the internal structure. With the aim of acquiring a better understanding of the localization of different ingredients in spray dried powders we have used confocal Raman microscopy to investigate the internal microstructure of individually dried particles. In this study three different macromolecules have been investigated: bovine serum albumin, hydroxypropyl methyl cellulose, and triblock co-polymer poloxamer in a lactose matrix are compared at various macromolecule to lactose ratios. The surface and internal component distribution in response to the macromolecule concentration has been established. For the first time phase segregation in particles during a short drying time range is shown. Macromolecules were enriched at the surface of the dried particles and a macromolecule depleted layer was observed below the surface. Macromolecule enriched domains were found segregated from the amorphous lactose matrix in the internal part of the particles. Confocal Raman microscopy was found to be a powerful tool for internal mapping in individually dried particles.