Surface-Sensitive Characterization of ALD Films on Drug Particles: How PiFM Outperforms Conventional Techniques

Introduction

Coating the surface of acetaminophen particles with Al₂O₃ and ZnO via atomic layer deposition (ALD) has been shown to effectively modulate drug release rates [1]. The success of these approaches fundamentally depends on the uniform and conformal application of ALD coatings [2]. This, in turn, raises a critical question: how can we rigorously confirm the successful formation of an ultrathin layer? Addressing this question necessitates a technique capable of providing surface-sensitive chemical information with high spatial resolution.

Current methods

While surface-sensitive techniques such as TOF-SIMS can detect the presence of Al₂O₃, they are limited to identifying its existence rather than providing comprehensive information on its distribution or coverage across the particle surface. Merely establishing the presence of Al₂O₃ at isolated locations is insufficient for validating uniform ALD deposition, thereby excluding TOF-SIMS and similar methods from consideration for this application.

Techniques such as SEM/EDS and TEM-EDS may also be considered; however, the integration of their signals over significant sample thicknesses results in a lack of true surface sensitivity, especially for characterizing ultrathin or single-molecule layers. In practice, SEM/EDS and TEM-EDS are far more likely to yield dominant drug substrate and elemental signals, with little to no sensitivity to the ALD overlayer.

ATR-FTIR is another candidate technique, utilizing an evanescent wave generated at the interface of a high-refractive-index crystal to probe the sample. Figure 1 demonstrates the application of ATR-FTIR to Al₂O₃ ALD on acetaminophen. However, as evident from the spectra, ATR-FTIR lacks the required surface sensitivity for this application. The spectra of untreated acetaminophen and that of acetaminophen after 50 ALD cycles are essentially indistinguishable.

Learn More?

Please click on ‘Request Application Note’  and we will send you the full application note: ‘Surface-Sensitive Characterization of ALD Films on Drug Particles: How PiFM Outperforms Conventional Techniques’.