Characterization of heterogeneity and spatial distribution of phases in complex solid dispersions by thermal analysis by structural characterization and X-ray micro computed tomography

Purpose: This study investigated the effect of drug-excipient miscibility on the heterogeneity and spatial distribution of phase separation in pharmaceutical solid dispersions at a micron-scale using two novel and complementary characterization techniques, thermal analysis by structural characterization (TASC) and X-ray micro-computed tomography (XCT) in conjunction with conventional characterization methods. Method: Complex dispersions containing felodipine, TPGS, PEG and PEO were prepared using hot melt extrusion-injection moulding. The phase separation behavior of the samples was characterized using TASC and XCT in conjunction with conventional thermal, microscopic and spectroscopic techniques. The in vitro drug release study was performed to demonstrate the impact of phase separation on dissolution of the dispersions. Results: The conventional characterization results indicated the phase separating nature of the carrier materials in the patches and the presence of crystalline drug in the patches with the highest drug loading (30% w/w). TASC and XCT where used to provide insight into the spatial configuration of the separate phases. TASC enabled assessment of the increased heterogeneity of the dispersions with increasing the drug loading. XCT allowed the visualization of the accumulation of phase separated (crystalline) drug clusters at the interface of air pockets in the patches with highest drug loading which led to poor dissolution performance. Semi-quantitative assessment of the phase separated drug clusters in the patches were attempted using XCT. Conclusion: TASC and XμCT can provide unique information regarding the phase separation behavior of solid dispersions which can be closely associated with important product quality indicators such as heterogeneity and microstructure

Thank You to Our 2020 Peer Reviewers

Thank you to the reviewers of AGU Advances. In 2020, we all faced the enormous and unexpected challenges of the Covid‐19 pandemic, with its host of new and competing demands on our time. Thus, we are especially grateful to the 154 people who provided reviews for AGU Advances and helped our fledgling journal complete its first year. Peer‐review is essential to the process of doing and publishing science, and our reviewers have helped define our new journal by indicating papers expected to have broad impact that advance a discipline, have broad impact across disciplines, or have policy relevance. All papers submitted to AGU Advances first go through an editorial consultation. We are committed to respecting reviewers’ time and only send papers for review that the consulting editors agree meet our criteria. Sometimes this means we send papers back to the authors with suggestions how to improve the fit to our journal. Another way we try to streamline the review process is by giving the authors the option to transfer reviews if after review we decide the paper is better suited to another AGU journal. As a relatively new journal, we still have few enough reviewers that we do not want to identify them by name. Nonetheless, you know who you are. Please accept our sincere thanks for generously sharing your expertise and working to improve AGU Advances

Confronting Racism to Advance Our Science

As individuals serving on the AGU Advances editorial board, we condemn racism, affirm that Black Lives Matter, and recognize that inequality is built into the systems that have allowed us to prosper. We aim to persistently foster discussion about racism, inequity, and the need to make our community more diverse and inclusive. This will help AGU Advances do a better job in publishing important science that inclusively reflects the ideas and contributions of all in our community

Instability of the southern Canadian Shield during the late Proterozoic

Cratons are generally considered to comprise lithosphere that has remained tectonically quiescent for billions of years. Direct evidence for stability is mainly founded in the Phanerozoic sedimentary record and low-temperature thermochronology, but for extensive parts of Canada, earlier stability has been inferred due to the lack of an extensive rock record in both time and space. We used 40Ar/39Ar multi-diffusion domain (MDD) analysis of K-feldspar to constrain cratonic thermal histories across an intermediate (~150-350°C) temperature range in an attempt to link published high-temperature geochronology that resolves the timing of orogenesis and metamorphism with lower-temperature data suited for upper-crustal burial and unroofing histories. This work is focused on understanding the transition from Archean-Paleoproterozoic crustal growth to later intervals of stability, and how uninterrupted that record is throughout Earth’s Proterozoic “Middle Age.” Intermediate-temperature thermal histories of cratonic rocks at well-constrained localities within the southern Canadian Shield of North America challenge the stability worldview because our data indicate that these rocks were at elevated temperatures in the Proterozoic. Feldspars from granitic rocks collected at the surface cooled at rates of <0.5°C/Ma subsequent to orogenesis, seemingly characteristic of cratonic lithosphere, but modeled thermal histories suggest that at ca. 1.1-1.0 Ga these rocks were still near ~200°C – signaling either reheating, or prolonged residence at mid-crustal depths assuming a normal cratonic geothermal gradient. After 1.0 Ga, the regions we sampled then underwent further cooling such that they were at or near the surface (<< 60°C) in the early Paleozoic. Explaining mid-crustal residence at 1.0 Ga is challenging. A widespread, prolonged reheating history via burial is not supported by stratigraphic information, however assuming a purely monotonic cooling history requires at the very least 5 km of exhumation beginning at ca. 1.0 Ga. A possible explanation may be found in evidence of magmatic underplating that thickened the crust, driving uplift and erosion. The timing of this underplating coincides with Mid-Continent extension, Grenville orogenesis, and assembly of the supercontinent Rodinia. 40Ar/39Ar MDD data demonstrate that this technique can be successfully applied to older rocks and fill in a large observational gap. These data also raise questions about the evolution of cratons during the Proterozoic and the nature of cratonic stability across deep time

Relict topography within the Hangay Mountains in central Mongolia: Quantifying long-term exhumation and relief change in an old landscape

The Hangay Mountains are a high-elevation, low-relief landscape within the greater Mongolian Plateau of central Asia. New bedrock apatite (U-Th)/He single-grain ages from the Hangay span ~70 to 200 Ma, with a mean of 122.7 ± 24.0 Ma (2σ). Detrital apatite samples from the Selenga and Orkhon Rivers, north of the mountains, yield dominant (U-Th)/He age populations of ~115 to 130 Ma, as well as an older population not seen in the Hangay granitic bedrock data. These low-temperature data record regional exhumation of central Mongolia in the Mesozoic followed by limited erosion of <1-2 km since the Jurassic-Cretaceous, ruling out rapid exhumation of this magnitude associated with any late Cenozoic uplift. Apatite (U-Th)/He age-elevation patterns suggest long-term thermal stability of the upper crust, and thermal model inversions require late Mesozoic uplift and spatially variable exhumation driven by isostasy in concert with relief evolution to produce the observed cooling ages in the Hangay region. Alpine cirques and intact moraines are indicative of more recent, climate-driven erosion in the higher peaks of the western Hangay. Regionally, modeling suggests topographic "planation" in the Jurassic followed by rapid relief growth that was completed by the mid-Cretaceous. These results support Mesozoic topograhic evolution and relative stability of the landscape enduring throughout the Cenozoic with very little subsequent exhumation. These data support the notion that in the absence of strong tectonic or climate forcing, erosion is limited and remnant landscapes can persist over 10s-100s of millions of years in a state of disequilibrium