title: Raman imaging of pharmaceutical materials: refractive index effects on contrast at buried interfaces.
abstract: Resolution targets composed of bilayer polydimethylsiloxane (PDMS) devices with buried polyethylene glycol (PEG) channels have been fabricated using traditional photolithographic and micromolding techniques to develop resolution targets that mimic pharmaceutical materials. Raman chemical images of the resulting PEG-in-PDMS devices composed of varying parallel line widths were investigated by imaging the PEG lines through a thin overlayer of PDMS. Additionally, a scattering agent, Al2O3, was introduced at varying concentrations to each layer of the device to explore the effects of scattering materials on Raman images. Features in the resulting chemical images of the PEG lines suggest that reflection at the PEG/PDMS interface contributes to the Raman signal. A model based on geometric optics was developed to simulate the observed image functions of the targets. The results emphasize the influence of refractive index discontinuities at the PEG/PDMS interface on the apparent size and shape of the PEG features. Such findings have an impact on interpretation of Raman images of nonabsorbing, opaque pharmaceutical samples.
authors.affiliation: Center for Drug Evaluation and Research, Division of Pharmaceutical Analysis, Food and Drug Administration, 645 S. Newstead Ave, St. Louis, MO 63110 USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Mecker-Pogue
authors.affiliation: Center for Drug Evaluation and Research, Division of Pharmaceutical Analysis, Food and Drug Administration, 645 S. Newstead Ave, St. Louis, MO 63110 USA. Electronic address: john.kauffman@fda.hhs.gov.
authors.forename: John F
authors.initials: JF
authors.lastname: Kauffman
mesh_terms: D000537:Aluminum Oxide / Q000737:chemistry; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D013059:Spectrum Analysis, Raman / Q000295:instrumentation / Q000379:methods; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods
chemical_list: D004129:Dimethylpolysiloxanes; D004364:Pharmaceutical Preparations; D011092:Polyethylene Glycols; C013830:baysilon; D000537:Aluminum Oxide
keywords: Chemical imaging; Image Resolution; Microfabrication; Pharmaceuticals; Raman