Chemical Imaging of Drug Delivery Systems with Structured Surfaces–a Combined Analytical Approach of Confocal Raman Microscopy and Optical Profilometry

Abstract

Confocal Raman microscopy is an analytical technique with a steadily increasing impact in the field of pharmaceutics as the instrumental setup allows for nondestructive visualization of component distribution within drug delivery systems. Here, the attention is mainly focused on classic solid carrier systems like tablets, pellets, or extrudates. Due to the opacity of these systems, Raman analysis is restricted either to exterior surfaces or cross sections. As Raman spectra are only recorded from one focal plane at a time, the sample is usually altered to create a smooth and even surface. However, this manipulation can lead to misinterpretation of the analytical results. Here, we present a trendsetting approach to overcome these analytical pitfalls with a combination of confocal Raman microscopy and optical profilometry. By acquiring a topography profile of the sample area of interest prior to Raman spectroscopy, the profile height information allowed to level the focal plane to the sample surface for each spectrum acquisition. We first demonstrated the basic principle of this complementary approach in a case study using a tilted silica wafer. In a second step, we successfully adapted the two techniques to investigate an extrudate and a lyophilisate as two exemplary solid drug carrier systems. Component distribution analysis with the novel analytical approach was neither hampered by the curvature of the cylindrical extrudate nor the highly structured surface of the lyophilisate. Therefore, the combined analytical approach bears a great potential to be implemented in diversified fields of pharmaceutical sciences.

Submicron polymeric particles prepared by vibrational spray-drying: Semisolid formulation and skin penetration/permeation studies

“…Figure 3A depicts the single Raman spectra of the three components DEX, PCL and deoxycholate contained in the spray-dried particles. As the rough surface of the particle powder hinders accurate spectra acquisition with the confocal microscope, the surface was virtually corrected by recording topography profiles of the respective sample areas prior to Raman analysis [37]. Subsequently, the topography profile could be overlaid with the false color Raman image for a combined three dimensional visualization.…”

Large area sub-micron chemical imaging of magnesium in sea urchin teeth

“…For Raman chemical imaging and True Surface Ò microscopy, two confocal Raman systems were used (Franzen et al, 2013;Kann and Windbergs, 2013). For traditional Raman imaging, a confocal Raman microscope (alpha300R, WITec, Ulm, Germany) equipped with a frequency doubled Nd:YAG laser (532 nm) and a piezoscanner (P-527, Physik Instrumente, Karlsruhe, Germany) was employed.…”

Novel insights into controlled drug release from coated pellets by confocal Raman microscopy

“…However, samples with highly structured surfaces are challenging for analysis with confocal microscopy techniques, as only one focal plane can be analyzed at a time. As a complementary analytical approach, the combination of CRM and optical topography has already been described as a strategy to overcome this drawback . Optical topography prior to Raman spectroscopy analysis allows three‐dimensional mapping of the topographic height differences (topography profile), thus enabling to level the focal plane to the sample surface for acquisition of Raman spectra.…”