Three-Dimensional Time-of-Flight Secondary Ion Mass Spectrometry Imaging of a Pharmaceutical in a Coronary Stent Coating as a Function of Elution Time

Abstract

Three-dimensional (3D) chemical images reveal the surface and subsurface distribution of pharmaceutical molecules in a coronary stent coating and are used to visualize the drug distribution as a function of elution time. The coronary stent coating consists of 25% (w/w) sirolimus in a poly(lactic-co-glycolic acid) (PLGA) matrix and is spray-coated onto metal coupons. Information regarding the 3D distribution of sirolimus in PLGA as a function of elution time was obtained by time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging using a Au(+) ion beam for analysis in conjunction with a C(60)(+) ion beam for sputter depth profiling. The examined formulation is shown to have large areas of the surface as well as subsurface channels that are composed primarily of the drug, followed by a drug-depleted region, and finally, a relatively homogeneous dispersion of the drug in the polymer matrix. Elution is shown to occur from the drug-enriched surface region on a relatively short time scale and more gradually from the subsurface regions of homogeneously dispersed drug. Bulk composition was also probed by X-ray photoelectron spectroscopy (XPS) depth profiling and confocal Raman imaging, the results of which substantiate the TOF-SIMS 3D images. Finally, the effectiveness of a C(60)(+) ion beam for use in 3D characterization of organic systems is demonstrated against another polyatomic ion source (e.g., SF(5)(+)).