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)(+)).

Chemical and spatial analysis of protein loaded PLGA microspheres for drug delivery applications

“…The technique of Time of Flight -Secondary Ion Mass Spectrometry (ToF-SIMS) has been extensively used to study pharmaceutical systems [14][15][16][17][18][19]. The utility of ToF-SIMS arises from the ability to provide high specificity chemical information with good depth resolution (~1-2 nm).…”

“…ToF-SIMS depth profiling has been used to analyse biomedically relevant thin films [17,19] to elucidate the spatial distribution of various constituents within such systems through the bulk of the sample. Due to the topography encountered with microsphere structure and the artefacts this can induce in ToF-SIMS data, this has not been as widely applied to the study of this type of structure.…”

“…Raman mapping has previously been applied to pharmaceutical systems including drug loaded polymeric microspheres [22,23], thin polymer films [18,19,24,25] and tablet compound identification [26], specifically using multivariate methods of analysis [27][28][29].…”

Molecular Depth Profiling with Cluster Ion Beams

“…One of the major shortcomings of SF 5 + and other smaller cluster ion beams is that they tend to accumulate damage much more rapidly than other cluster ion beam sources. 11,12,16,18,85 The reasoning behind this is most likely attributed to its small size. First, there is higher impact energy per constituent atom in the cluster when the clusters are smaller.…”

“…These increased damage accumulation affects with SF 5 + as compared to C 60 + have also been observed in PMMA samples 12,16 and PLA-based drug delivery systems. 18 A particularly surprising result from a recent interlaboratory study appears to show that atomic ion bombardment is much more effective in resolving these layers than SF 5 + . 85 When employing Ar or Cs, for example, all four layers are resolved, whereas, in Figure 5.36, there is only a very broad feature that is indicative of the second layer.…”