ToF-SIMS Depth Profiling of Oral Drug Delivery Films for 3D Visualization and Potential Quantification of Active Pharmaceutical Particles

Published

July 30, 2019

Author(s)

Shinichiro N. Muramoto, J Greg Gillen, Cynthia J. Zeissler, Edward Garboczi

Abstract

The size, shape, and spatial distribution of active pharmaceutical ingredient (API) particles are important physical characteristics of drug delivery systems that can affect the performance, stability, appearance, and even bulk properties of the end product. This study explores the feasibility of using Time-of-Fight Secondary Ion Mass Spectrometry (ToF-SIMS) for the 3D characterization and quantification of API particles in two commercially available oral dissolvable drug delivery films. It was found that the use of an argon cluster sputter source allowed quantification of the APIs, namely buprenorphine and naloxone, at pharmacologically relevant concentration inside an organic matrix that was hundreds of micrometers thick. In addition, the 3D chemical maps could be utilized to obtain size distributions of buprenorphine particles whose effective diameters ranged from approximately 6 µm to 41 µm, with shapes that were generally spherical with a few non-spherical structures. The particles were heterogeneously distributed both laterally and as a function of depth in the film. In addition, ToF-SIMS was able to differentiate between different oral drug delivery films based on differences in the spatial distribution of buprenorphine; in one case, the particles were distributed throughout the depth of the film whereas the particles in the other case were localized close to the surface. The combination of quantification of the API along with characterization of the particle characteristics and 3D spatial distribution is potentially used for film validations and optimization.

Citation

Surface and Interface Analysis

Pub Type

Journals

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Keywords

tof-sims, argon cluster, gas cluster sources, thick films, depth profiling

Citation

Muramoto, S. , Gillen, J. , Zeissler, C. and Garboczi, E. (2019), ToF-SIMS Depth Profiling of Oral Drug Delivery Films for 3D Visualization and Potential Quantification of Active Pharmaceutical Particles, Surface and Interface Analysis, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=927842 (Accessed April 24, 2026)

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