Leveraging ToF-SIMS imaging to investigate tenofovir disoproxil fumarate degradation at excipient interfaces in oral compressed tablets.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging has been used to study the hydrolysis of tenofovir disoproxil fumarate (TDF) to tenofovir monosoproxil (TM) within an oral compressed tablet. The ToF-SIMS images displayed a heterogenous distribution of the matrix components. Evaluation of the TM distribution revealed that it was primarily co-localized with areas of higher excipient concentration pointing toward excipient driven degradation. To support these observations, a compatibility study of TDF with each tablet component was performed via liquid chromatography. The ToF-SIMS imaging and compatibility study indicated that the excipient, Avicel® PH-102, was the primary driver of TM formation in the tablet. The hydrolysis degradation mechanism within the tablet is further rationalized through discussion of chemical and physical properties of the matrix components. The sum of this work demonstrates a new analytical workflow for probing and understanding matrix driven degradation in oral compressed tablets utilizing ToF-SIMS imaging.

Measuring Compositions in Organic Depth Profiling: Results from a VAMAS Interlaboratory Study.

We report the results of a VAMAS (Versailles Project on Advanced Materials and Standards) interlaboratory study on the measurement of composition in organic depth profiling. Layered samples with known binary compositions of Irganox 1010 and either Irganox 1098 or Fmoc-pentafluoro-l-phenylalanine in each layer were manufactured in a single batch and distributed to more than 20 participating laboratories. The samples were analyzed using argon cluster ion sputtering and either X-ray photoelectron spectroscopy (XPS) or time-of-flight secondary ion mass spectrometry (ToF-SIMS) to generate depth profiles. Participants were asked to estimate the volume fractions in two of the layers and were provided with the compositions of all other layers. Participants using XPS provided volume fractions within 0.03 of the nominal values. Participants using ToF-SIMS either made no attempt, or used various methods that gave results ranging in error from 0.02 to over 0.10 in volume fraction, the latter representing a 50% relative error for a nominal volume fraction of 0.2. Error was predominantly caused by inadequacy in the ability to compensate for primary ion intensity variations and the matrix effect in SIMS. Matrix effects in these materials appear to be more pronounced as the number of atoms in both the primary analytical ion and the secondary ion increase. Using the participants' data we show that organic SIMS matrix effects can be measured and are remarkably consistent between instruments. We provide recommendations for identifying and compensating for matrix effects. Finally, we demonstrate, using a simple normalization method, that virtually all ToF-SIMS participants could have obtained estimates of volume fraction that were at least as accurate and consistent as XPS.

Low-temperature plasma for compositional depth profiling of crosslinking organic multilayers: comparison with C60 and giant argon gas cluster sources.

RATIONALE: For organic electronics, device performance can be affected by interlayer diffusion across interfaces. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) can resolve buried structures with nanometer resolution, but instrument artifacts make this difficult. Low-temperature plasma (LTP) is suggested as a way to prepare artifact-free surfaces for accurate determination of chemical diffusion. METHODS: A model organic layer system consisting of three 1 nm delta layers of 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP) separated by three 30 nm layers of tris(8-hydroxyquinolinato)aluminum (Alq3) was used to evaluate the effectiveness of LTP etching for the preparation of crater edge surfaces for subsequent compositional depth profile analysis. This was compared with depth profiles obtained using an instrument equipped with an argon cluster sputter source. RESULTS: The quality of the depth profiles was determined by comparing the depth resolutions of the BCP delta layers. The full width at half maximum gave depth resolutions of 6.9 nm and 6.0 nm using LTP, and 6.2 nm and 5.8 nm using argon clusters. In comparison, the 1/e decay length of the trailing edge gave depth resolutions of 2.0 nm and 1.8 nm using LTP, and 3.5 nm and 3.4 nm using argon clusters. CONCLUSIONS: The comparison of the 1/e decay lengths showed that LTP can determine the thickness and composition of the buried structures without instrument artifacts. Although it does suffer from contaminant deposition, LTP was shown to be a viable option for preparing crater edges for a more accurate determination of buried structures.

Time-of-flight secondary ion mass spectroscopy with bismuth primary ions of clean and air-exposed surfaces of tellurium.

The regularity of Bi(+), Bi(3+) and Bi(3++) primary ions in the time- of-flight secondary ion mass spectroscopy fragment pattern of air oxidized Te and Bi(+) direct-current scan cleaned Te is discussed. The most intensive fragments for a cleaned Te surface are positive and negative Tex and BiTex clusters. The sequence of secondary ion cluster formation is Bi-Te alloying followed by sputtering and ionization. For oxidized Te the chemical composition of the produced TexOy fragments satisfies the relation y=2x for positive fragments and y=2x+1 for negative ones. Experimental findings are in a good agreement with the results predicted by Plog's model for TeO2.

Argon cluster ion beams for organic depth profiling: results from a VAMAS interlaboratory study.

The depth profiling of organic materials with argon cluster ion sputtering has recently become widely available with several manufacturers of surface analytical instrumentation producing sources suitable for surface analysis. In this work, we assess the performance of argon cluster sources in an interlaboratory study under the auspices of VAMAS (Versailles Project on Advanced Materials and Standards). The results are compared to a previous study that focused on C(60)(q+) cluster sources using similar reference materials. Four laboratories participated using time-of-flight secondary-ion mass spectrometry for analysis, three of them using argon cluster sputtering sources and one using a C(60)(+) cluster source. The samples used for the study were organic multilayer reference materials consisting of a ∼400-nm-thick Irganox 1010 matrix with ∼1 nm marker layers of Irganox 3114 at depths of ∼50, 100, 200, and 300 nm. In accordance with a previous report, argon cluster sputtering is shown to provide effectively constant sputtering yields through these reference materials. The work additionally demonstrates that molecular secondary ions may be used to monitor the depth profile and depth resolutions approaching a full width at half maximum (fwhm) of 5 nm can be achieved. The participants employed energies of 2.5 and 5 keV for the argon clusters, and both the sputtering yields and depth resolutions are similar to those extrapolated from C(60)(+) cluster sputtering data. In contrast to C(60)(+) cluster sputtering, however, a negligible variation in sputtering yield with depth was observed and the repeatability of the sputtering yields obtained by two participants was better than 1%. We observe that, with argon cluster sputtering, the position of the marker layers may change by up to 3 nm, depending on which secondary ion is used to monitor the material in these layers, which is an effect not previously visible with C(60)(+) cluster sputtering. We also note that electron irradiation, used for charge compensation, can induce molecular damage to areas of the reference samples well beyond the analyzed region that significantly affects molecular secondary-ion intensities in the initial stages of a depth profile in these materials.