A metastable pentagonal 2D material synthesized by symmetry-driven epitaxy.

Most two-dimensional (2D) materials experimentally studied so far have hexagons as their building blocks. Only a few exceptions, such as PdSe2, are lower in energy in pentagonal phases and exhibit pentagons as building blocks. Although theory has predicted a large number of pentagonal 2D materials, many of these are metastable and their experimental realization is difficult. Here we report the successful synthesis of a metastable pentagonal 2D material, monolayer pentagonal PdTe2, by symmetry-driven epitaxy. Scanning tunnelling microscopy and complementary spectroscopy measurements are used to characterize this material, which demonstrates well-ordered low-symmetry atomic arrangements and is stabilized by lattice matching with the underlying Pd(100) substrate. Theoretical calculations, along with angle-resolved photoemission spectroscopy, reveal monolayer pentagonal PdTe2 to be a semiconductor with an indirect bandgap of 1.05 eV. Our work opens an avenue for the synthesis of pentagon-based 2D materials and gives opportunities to explore their applications such as multifunctional nanoelectronics.

Drug Release from Surfactant-Containing Amorphous Solid Dispersions: Mechanism and Role of Surfactant in Release Enhancement.

PURPOSE: To understand how surfactants affect drug release from ternary amorphous solid dispersions (ASDs), and to investigate different mechanisms of release enhancement. METHODS: Ternary ASDs containing ritonavir (RTV), polyvinylpyrrolidone/vinyl acetate (PVPVA) and a surfactant (sodium dodecyl sulfate (SDS), Tween 80, Span 20 or Span 85) were prepared with rotary evaporation. Release profiles of ternary ASDs were measured with surface normalized dissolution. Phase separation morphologies of ASD compacts during hydration/dissolution were examined in real-time with a newly developed confocal fluorescence microscopy method. The water ingress rate of different formulations was measured with dynamic vapor sorption. Microscopy was employed to check for matrix crystallization during release studies. RESULTS: All surfactants improved drug release at 30% DL, while only SDS and Tween 80 improved drug release at higher DLs, although SDS promoted matrix crystallization. The dissolution rate of neat polymer increased when SDS and Tween 80 were present. The water ingress rate also increased in the presence of all surfactants. Surfactant-incorporation affected both the kinetic and thermodynamics factors governing phase separation of RTV-PVPVA-water system, modifying the phase morphology during ASD dissolution. Importantly, SDS increased the miscibility of RTV-PVPVA-water system, whereas other surfactants mainly affected the phase separation kinetics/drug-rich barrier persistence. CONCLUSION: Incorporation of surfactants enhanced drug release from RTV-PVPVA ASDs compared to the binary system. Increased drug-polymer-water miscibility and disruption of the drug-rich barrier at the gel-solvent interface via plasticization are highlighted as two key mechanisms underlying surfactant impacts based on direct visualization of the phase separation process upon hydration and release.

Balancing Solid-State Stability and Dissolution Performance of Lumefantrine Amorphous Solid Dispersions: The Role of Polymer Choice and Drug-Polymer Interactions.

Amorphous solid dispersions (ASDs) are of great interest due to their ability to enhance the delivery of poorly soluble drugs. Recent studies have shown that, in addition to acting as a crystallization inhibitor, the polymer in an ASD plays a role in controlling the rate of drug release, notably in congruently releasing formulations, where both the drug and polymer have similar normalized release rates. The aim of this study was to compare the solid-state stability and release performance of ASDs when formulated with neutral and enteric polymers. One neutral (polyvinylpyrrolidone-vinyl acetate copolymer, PVPVA) and four enteric polymers (hypromellose acetate succinate; hypromellose phthalate; cellulose acetate phthalate, CAP; methacrylic acid-methyl methacrylate copolymer, Eudragit L 100) were used to formulate binary ASDs with lumefantrine, a hydrophobic and weakly basic antimalarial drug. The normalized drug and polymer release rates of lumefantrine-PVPVA ASDs up to 35% drug loading (DL) were similar and rapid. No drug release from PVPVA systems was detected when the DL was increased to 40%. In contrast, ASDs formulated with enteric polymers showed a DL-dependent decrease in the release rates of both the drug and polymer, whereby release was slower than for PVPVA ASDs for DLs < 40% DL. Drug release from CAP and Eudragit L 100 systems was the slowest and drug amorphous solubility was not achieved even at 5% DL. Although lumefantrine-PVPVA ASDs showed fast release, they also showed rapid drug crystallization under accelerated stability conditions, while the ASDs with enteric polymers showed much greater resistance to crystallization. This study highlights the importance of polymer selection in the formulation of ASDs, where a balance between physical stability and dissolution release must be achieved.

Impact of Drug-Polymer Intermolecular Interactions on Dissolution Performance of Copovidone-Based Amorphous Solid Dispersions.

For poorly soluble drugs formulated as amorphous solid dispersions (ASDs), fast and complete release with the generation of drug-rich colloidal particles is beneficial for optimizing drug absorption. However, this ideal dissolution profile can only be achieved when the drug releases at the same normalized rate as the polymer, also known as congruent release. This phenomenon only occurs when the drug loading (DL) is below a certain value. The maximal DL at which congruent release occurs is defined as the limit of congruency (LoC). The purpose of this study was to investigate the relationship between drug chemical structure and LoC for PVPVA-based ASDs. The compounds investigated shared a common scaffold substituted with different functional groups, capable of forming hydrogen bonds only, halogen bonds only, both hydrogen and halogen bonds, or nonspecific interactions only with the polymer. Intermolecular interactions were studied and confirmed by X-ray photoelectron spectroscopy and infrared spectroscopy. The release rates of ASDs with different DLs were investigated using surface area normalized dissolution. ASDs with hydrogen bond formation between the drug and polymer had lower LoCs, while compounds that were only able to form halogen bonds or nonspecific interactions with the polymer achieved considerably higher LoCs. This study highlights the impact of different types of drug-polymer interactions on ASD dissolution performance, providing insights into the role of drug and polymer chemical structures on the LoC and ASD performance in general.

Electric-field induced structural transition in vertical MoTe2- and Mo1-xWxTe2-based resistive memories.

Transition metal dichalcogenides have attracted attention as potential building blocks for various electronic applications due to their atomically thin nature and polymorphism. Here, we report an electric-field-induced structural transition from a 2H semiconducting to a distorted transient structure (2Hd) and orthorhombic Td conducting phase in vertical 2H-MoTe2- and Mo1-xWxTe2-based resistive random access memory (RRAM) devices. RRAM programming voltages are tunable by the transition metal dichalcogenide thickness and show a distinctive trend of requiring lower electric fields for Mo1-xWxTe2 alloys versus MoTe2 compounds. Devices showed reproducible resistive switching within 10 ns between a high resistive state and a low resistive state. Moreover, using an Al2O3/MoTe2 stack, On/off current ratios of 106 with programming currents lower than 1 µA were achieved in a selectorless RRAM architecture. The sum of these findings demonstrates that controlled electrical state switching in two-dimensional materials is achievable and highlights the potential of transition metal dichalcogenides for memory applications.

Comparison of Drug Release and Adsorption under Supersaturating Conditions for Ordered Mesoporous Silica with Indomethacin or Indomethacin Methyl Ester.

Incomplete drug release from mesoporous silica systems has been observed in several studies. This work aims to increase the understanding of this phenomenon by investigating the mechanism of drug-silica interactions and adsorption behavior from supersaturated aqueous solutions of two similar drug molecules with different hydrogen bonding capabilities. Drug-silica interactions between indomethacin or its methyl ester and SBA-15 were investigated using spectroscopic techniques (infrared, fluorescence and X-ray photoelectron) and adsorption experiments. The results demonstrate that the predominant mechanism of interaction of both drugs with silica is hydrogen bonding between drug acceptor carbonyl groups with donor groups on the silica surface. The presence of a drug hydrogen bond donor group did not enhance drug adsorption. No evidence was obtained for drug adsorption through nonspecific hydrophobic interactions. Drug adsorption onto the silica surface was investigated under supersaturating conditions through the generation of adsorption isotherms. Similar adsorption isotherms were observed for each compound when the concentration scale was normalized to the drug amorphous solubility. In other words, the equilibrium between the drug adsorbed on the silica surface and free drug in solution was related to the drug activity in solution. The high tendency of the drug to adsorb when the solution is supersaturated was, in turn, found to limit the extent of drug release during dissolution under nonsink conditions. Thus, adsorption provides an explanation for incomplete drug release.

Water-Induced Phase Separation of Spray-Dried Amorphous Solid Dispersions.

Spray drying is widely used in the manufacturing of amorphous solid dispersion (ASD) systems due to its fast drying rate, enabling kinetic trapping of the drug in amorphous form. Spray-drying conditions, such as solvent composition, can have a profound impact on the properties of spray-dried dispersions. In this study, the phase behavior of spray-dried dispersions from methanol and methanol-water mixtures was assessed using ritonavir and copovidone [poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA)] as dispersion components. The resultant ASDs were characterized using differential scanning calorimetry (DSC), fluorescence spectroscopy, X-ray photoelectron spectroscopy (XPS), as well as surface-normalized dissolution rate (SNDR) measurements. Quaternary phase diagrams were calculated using a four-component Flory-Huggins model. It was found that the addition of water to the solvent system can lead to phase separation during the spray-drying process. A 10:90 H2O/MeOH solvent system caused a minor extent of phase separation. Phase heterogeneity in the 50 and 75% drug loading ASDs prepared from this spray solvent can be detected using DSC but not with other techniques used. The 25% drug loading system did not show phase heterogeneity in solid-state characterization but exhibited a compromised dissolution rate compared to that of the miscible ASD prepared from H2O-free solvent. This is possibly due to the formation of slow-releasing drug-rich phases upon phase separation. ASDs prepared with a 60:40 H2O/MeOH solvent mixture showed phase heterogeneity with all analytical methods used. The surface composition of dispersion particles as measured by fluorescence spectroscopy and XPS showed good agreement, suggesting surface drug enrichment of the spray-dried ASD particles prepared from this solvent system. Calculated phase diagrams and drying trajectories were consistent with experimental observations, suggesting that small variations in solvent composition may cause significant changes in ASD phase behavior during drying. These findings should aid in spray-drying process development for ASD manufacturing and can be applied broadly to assess the risk of phase separation for spray-drying systems using mixed organic solvents or other solvent-based processes.

Insights into the Dissolution Behavior of Ledipasvir-Copovidone Amorphous Solid Dispersions: Role of Drug Loading and Intermolecular Interactions.

The generation of a colloidal drug-rich phase by dissolving an amorphous solid dispersion (ASD) is thought to have a positive impact on oral absorption and bioavailability. Thus, understanding which formulations generate these species is important. In this study, ledipasvir-copovidone ASDs, with and without surfactants, were prepared, and their release performance was examined at different drug loadings. An intrinsic dissolution rate assembly was used to limit potential surface area variations among formulations, and the release of both polymer and drug was monitored as a function of time. Drug-rich colloids only formed when the drug loading (DL) was at or below 5%; at a DL of 7.5% or above, drug release became negligible. The drug and polymer released congruently at and below 5% DL and incongruently at higher DLs. Thus, the limit of congruency (LoC) is between 5 and 7.5% DL. X-ray photoelectron spectroscopy (XPS) of partially dissolved tablet surfaces revealed that a drug-rich layer formed on the surface of the tablet. This was most evident for the higher DL ASDs and led to amorphous drug-controlled dissolution. Consequently, the surface drug-enriched layer physically hindered the polymer from further release. Evidence is provided that the extent of drug-polymer interactions as a function of DL plays a central role in dictating the observed release behavior. Some surfactants were found to promote the formation of drug-rich colloids at considerably higher DLs, providing a formulation strategy to increase the LoC.

Surface Composition and Formulation Heterogeneity of Protein Solids Produced by Spray Drying.

PURPOSE: The aim of this study is to determine the effects of saccharide-containing excipients on the surface composition of spray-dried protein formulations and their matrix heterogeneity. METHODS: Spray-dried formulations of myoglobin or bovine serum albumin (BSA) were prepared without excipient or with sucrose, trehalose, or dextrans. Samples were characterized by solid-state Fourier-transform infrared spectroscopy (ssFTIR), differential scanning calorimetry (DSC), size exclusion chromatography (SEC) and scanning electron microscopy (SEM). Protein surface coverage was determined by X-ray photoelectron spectroscopy (XPS), while conformational differences were determined by solid-state hydrogen/deuterium exchange with mass spectrometry (ssHDX-MS). RESULTS: Structural differences were exhibited with the inclusion of different excipients, with dextran formulations indicating perturbation of secondary structure. XPS indicated sucrose and trehalose reduced protein surface concentration better than dextran-containing formulations. Using ssHDX-MS, the amount of deuterium incorporation and populations present were the largest in the samples processed with dextrans. Linear correlation was found between protein surface coverage and ssHDX-MS peak area (R2 = 0.853) for all formulations with saccharide-containing excipients. CONCLUSIONS: Lower molecular weight species of saccharides tend to enrich the particle surface and reduce protein concentration at the air-liquid interface, resulting in reduced population heterogeneity and improved physical stability, as identified by ssHDX-MS.

Qualitative and Quantitative Characterization of Composition Heterogeneity on the Surface of Spray Dried Amorphous Solid Dispersion Particles by an Advanced Surface Analysis Platform with High Surface Sensitivity and Superior Spatial Resolution.

Surface composition critically impacts stability (e.g., crystallization) and performance (e.g., dissolution) of spray dried amorphous solid dispersion (ASD) formulations; however, traditional characterization techniques such as Raman and infrared spectroscopies may not provide useful information on surface composition on the spray dried ASD particles due to low spatial resolution, high probing depth, and lack of quantitative information. This study presents an advanced surface characterization platform consisting of two complementary techniques: X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Such a platform enables qualitative and quantitative measurements of surface composition for the fine spray dried ASD particles with ultrasurface-sensitivity (less than 10 nm from the surface) and superior spatial resolution (approximately 250 nm for ToF-SIMS). Both XPS and ToF-SIMS demonstrated that the polymer (PVPVA) was dominantly enriched on the surface of our spray dried naproxen-PVPVA ASD particles. Of a particular note was that XPS could differentiate two batches of spray dried ASD particles with a subtle difference in surface composition produced by varying feed solution solvents. This advanced surface characterization platform will provide essential surface information to understand the mechanisms underlying the impact of surface composition on stability (e.g., crystallization) and functionality (e.g., dissolution) in future studies.

Versatile technique for assessing thickness of 2D layered materials by XPS.

X-ray photoelectron spectroscopy (XPS) has been utilized as a versatile method for thickness characterization of various two-dimensional (2D) films. Accurate thickness can be measured simultaneously while acquiring XPS data for chemical characterization of 2D films having thickness up to approximately 10 nm. For validating the developed technique, thicknesses of few-layer graphene (FLG), MoS2 and amorphous boron nitride (a-BN) layer, produced by microwave plasma chemical vapor deposition (MPCVD), plasma enhanced chemical vapor deposition (PECVD), and pulsed laser deposition (PLD) respectively, were accurately measured. The intensity ratio between photoemission peaks recorded for the films (C 1s, Mo 3d, B 1s) and the substrates (Cu 2p, Al 2p, Si 2p) is the primary input parameter for thickness calculation, in addition to the atomic densities of the substrate and the film, and the corresponding electron attenuation length (EAL). The XPS data was used with a proposed model for thickness calculations, which was verified by cross-sectional transmission electron microscope (TEM) measurement of thickness for all the films. The XPS method determines thickness values averaged over an analysis area which is orders of magnitude larger than the typical area in cross-sectional TEM imaging, hence provides an advanced approach for thickness measurement over large areas of 2D materials. The study confirms that the versatile XPS method allows rapid and reliable assessment of the 2D material thickness and this method can facilitate in tailoring growth conditions for producing very thin 2D materials effectively over a large area. Furthermore, the XPS measurement for a typical 2D material is non-destructive and does not require special sample preparation. Therefore, after XPS analysis, exactly the same sample can undergo further processing or utilization.

Observation of Optical and Electrical In-Plane Anisotropy in High-Mobility Few-Layer ZrTe5.

Transition metal pentatelluride ZrTe5 is a versatile material in condensed-matter physics and has been intensively studied since the 1980s. The most fascinating feature of ZrTe5 is that it is a 3D Dirac semimetal which has linear energy dispersion in all three dimensions in momentum space. Structure-wise, ZrTe5 is a layered material held together by weak interlayer van der Waals force. The combination of its unique band structure and 2D atomic structure provides a fertile ground for more potential exotic physical phenomena in ZrTe5 related to 3D Dirac semimentals. However, the physical properties of its few-layer form have yet to be thoroughly explored. Here we report strong optical and electrical in-plane anisotropy of mechanically exfoliated few-layer ZrTe5. Raman spectroscopy shows a significant intensity change with sample orientations, and the behavior of angle-resolved phonon modes at the Γ point is explained by theoretical calculations. DC conductance measurement indicates a 50% of difference along different in-plane directions. The diminishing of resistivity anomaly in few-layer samples indicates the evolution of band structure with a reduced thickness. A low-temperature Hall experiment sheds light on more intrinsic anisotropic electrical transport, with a hole mobility of 3000 and 1500 cm2/V·s along the a-axis and c-axis, respectively. Pronounced quantum oscillations in magnetoresistance are observed at low temperatures with the highest electron mobility up to 44 000 cm2/V·s.

Surface chemistry of black phosphorus under a controlled oxidative environment.

Black phosphorus (BP), the bulk counterpart of monolayer phosphorene, is a relatively stable phosphorus allotrope at room temperature. However, monolayer phosphorene and ultra-thin BP layers degrade in ambient atmosphere. In this paper, we report the investigation of BP oxidation and discuss the reaction mechanism based on the x-ray photoelectron spectroscopy (XPS) data. The kinetics of BP oxidation was examined under various well-controlled conditions, namely in 5% O2/Ar, 2.3% H2O/Ar, and 5% O2 and 2.3% H2O/Ar. At room temperature, the BP surface is demonstrated not to be oxidized at a high oxidation rate in 5% O2/Ar nor in 2.3% H2O/Ar, according to XPS, with the thickness of the oxidized phosphorus layer <5 Å for 5 h. On the other hand, in the O2/H2O mixture, a 30 Å thickness oxide layer was detected already after 2 h of the treatment. This result points to a synergetic effect of water and oxygen in the BP oxidation. The oxidation effect was also studied in applications to the electrical measurements of BP field-effect transistors (FETs) with or without passivation. The electrical performance of BP FETs with atomic layer deposition (ALD) dielectric passivation or h-BN passivation formed in a glove-box environment are also presented.

Chemical vapor deposition-prepared sub-nanometer Zr clusters on Pd surfaces: promotion of methane dry reforming.

An inverse Pd-Zr model catalyst was prepared by chemical vapor deposition (CVD) using zirconium-t-butoxide (ZTB) as an organometallic precursor. Pd-Zr interaction was then investigated with focus on the correlation of reforming performance with the oxidation state of Zr. As test reactions, dry reforming of methane (DRM) and methanol steam reforming (MSR) were chosen. Depending on treatments, either ZrOxHy or ZrO2 overlayers or Zr as sub-nanometer clusters could be obtained. Following the adsorption of ZTB on Pd(111), a partially hydroxylated Zr4+-containing layer was formed, which can be reduced to metallic Zr by thermal annealing in ultrahigh vacuum, leading to redox-active Zr0 sub-nanometer clusters. Complementary density functional theoretical (DFT) calculations showed that a single layer of ZrO2 on Pd(111) can be more easily reduced toward the metallic state than a double- and triple layer. Also, the initial and resulting layer compositions greatly depend on gas environment. The lower the water background partial pressure, the faster and more complete the reduction of Zr4+ species to Zr0 on Pd takes place. Under methanol steam reforming conditions, water activation by hydroxylation of Zr occurs. In excess of methanol, strong coking is induced by the Pd/ZrOxHy interface. In contrast, dry reforming of methane is effectively promoted if these initially metallic Zr species are present in the pre-catalyst, leading to a Pd/ZrOxHy phase boundary by oxidative activation under reaction conditions. These reaction-induced active sites for DRM are stable with respect to carbon blocking or coking. In essence, Zr doping of Pd opens specific CO2 activation channels, which are absent on pure metallic Pd.

Citrate-stabilized gold nanorods.

Stable aqueous dispersions of citrate-stabilized gold nanorods (cit-GNRs) have been prepared in scalable fashion by surfactant exchange from cetyltrimethylammonium bromide (CTAB)-stabilized GNRs, using polystyrenesulfonate (PSS) as a detergent. The surfactant exchange process was monitored by infrared spectroscopy, surface-enhanced Raman scattering (SERS), and X-ray photoelectron spectroscopy (XPS). The latter established the quantitative displacement of CTAB (by PSS) and of PSS (by citrate). The Cit-GNRs are indefinitely stable at low ionic strength, and are conducive to further ligand exchange without loss of dispersion stability. The reliability of the surface exchange process supports the systematic analysis of ligand structure on the hydrodynamic size of GNRs, as described in a companion paper.

A reusable unsupported rhenium nanocrystalline catalyst for acceptorless dehydrogenation of alcohols through γ-C-H activation.

Rhenium nanocrystalline particles (Re NPs), of 2 nm size, were prepared from NH4ReO4 under mild conditions in neat alcohol. The unsupported Re NPs convert secondary and benzylic alcohols to ketones and aldehydes, respectively, through catalytic acceptorless dehydrogenation (AD). The oxidant- and acceptor-free neat dehydrogenation of alcohols to obtain dihydrogen gas is a green and atom-economical process for making carbonyl compounds. Secondary aliphatic alcohols give quantitative conversion and yield. Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Re K-edge X-ray absorption near-edge structure (XANES), and X-ray absorption fine structure (EXAFS) data confirmed the characterization of the Re NPs as metallic rhenium with surface oxidation to rhenium(IV) oxide (ReO2). Isotope labeling experiments revealed a novel γ-CH activation mechanism for AD of alcohols.

The importance of surface composition and wettability on the dissolution performance of high drug loading amorphous dispersion formulations.

One of the limitations with an amorphous solid dispersion (ASD) formulation strategy is low drug loading. Hydrophobic drugs have poor wettability and require a substantial amount of polymer to stabilize the amorphous drug and facilitate release. Using grazoprevir and hypromellose acetate succinate as model drug and polymer respectively, the interplay between particle surface composition, particle wettability, and release performance was investigated. A hierarchical particle approach was used where the surfaces of high drug loading ASDs generated by either solvent evaporation or co-precipitation were further modified with a secondary excipient (i.e., polymer or wetting agent). The surface-modified particles were characterized for drug release, wettability, morphology, and surface composition using two-stage dissolution studies, contact angle measurements, scanning electron microscopy, and X-ray photoelectron spectroscopy, respectively. Despite surface modification with hydrophilic polymers, hierarchical cPAD particles did not consistently exhibit good release performance. Contact angle measurements showed that the secondary excipient had a profound impact on particle wettability. Particles with good wettability showed improved drug release relative to particles that did not wet well, even with similar drug loadings. These observations underscore the intricate interplay between particle wettability and performance in amorphous dispersion formulations and illustrate a promising hierarchical particle approach to formulate high drug loading amorphous dispersions with improved dissolution performance.

Release Mechanisms of Amorphous Solid Dispersions: Role of Drug-Polymer Phase Separation and Morphology.

Formulating poorly soluble molecules as amorphous solid dispersions (ASDs) is an effective strategy to improve drug release. However, drug release rate and extent tend to rapidly diminish with increasing drug loading (DL). The poor release at high DLs has been postulated to be linked to the process of amorphous-amorphous phase separation (AAPS), although the exact connection between phase separation and release properties remains somewhat unclear. Herein, release profiles of ASDs formulated with ritonavir (RTV) and polyvinylpyrrolidone/vinyl acetate (PVPVA) at different DLs were determined using surface normalized dissolution. Surface morphologies of partially dissolved ASD compacts were evaluated with confocal fluorescence microscopy, using Nile red and Alexa Fluor 488 as fluorescence markers to track the hydrophobic and hydrophilic phases respectively. ASD phase behavior during hydration and release of components were also visualized in real time using a newly developed in situ confocal fluorescence microscopy method. RTV-PVPVA ASDs showed complete and rapid drug release below 30% DL, partial drug release at 30% DL and no drug release above 30% DL. It was observed that formation of discrete drug-rich droplets at lower DLs led to rapid and congruent release of both drug and polymer, whereas formation of continuous drug-rich phase at the ASD matrix-solution interface was the cause of poor release above certain DLs. Thus, the domain size and interconnectivity of phase separated drug-rich domains appear to be critical factors impacting drug release from RTV-PVPVPA ASDs.

Improving Dissolution Performance and Drug Loading of Amorphous Dispersions Through a Hierarchical Particle Approach.

Co-precipitation is an emerging manufacturing strategy for amorphous solid dispersions (ASDs). Herein, the interplay between processing conditions, surface composition, and release performance was evaluated using grazoprevir and hypromellose acetate succinate as the model drug and polymer, respectively. Co-precipitated amorphous dispersion (cPAD) particles were produced in the presence and absence of an additional polymer that was either dissolved or dispersed in the anti-solvent. This additional polymer in the anti-solvent was deposited on the surfaces of the cPAD particles during isolation and drying to create hierarchical particles, which we define here as a core ASD particle with an additional water soluble component that is coating the particle surfaces. The resultant hierarchical particles were characterized using X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy, and X-ray photoelectron spectroscopy (XPS). Release performance was evaluated using a two-stage dissolution test. XPS analysis revealed a trend whereby cPAD particles with a lower surface drug concentration showed improved release relative to particles with a higher surface drug concentration, for nominally similar drug loadings. This surface drug concentration could be impacted by whether the secondary polymer was dissolved in the anti-solvent or dispersed in the anti-solvent prior to isolating final dried hierarchical cPAD powders. Grazoprevir exposure in dogs was higher when the hierarchical cPAD was dosed, with ∼1.8 fold increase in AUC compared to the binary cPAD. These observations highlight the important interplay between processing conditions and ASD performance in the context of cPAD particles and illustrate a hierarchical particle design as a successful approach to alter ASD surface chemistry to improve dissolution performance.

Stabilizing Hybrid Electrochromic Devices through Pairing Electrochromic Polymers with Minimally Color-Changing Ion-Storage Materials Having Closely Matched Electroactive Voltage Windows.

Conjugated electrochromic polymers hold great promises for next-generation color-changing windows and displays. One of the major roadblocks in their solid-state electrochromic devices is the relatively poor cycling stability. Finding ion-storage materials as a charge-balancing component is critical in improving their electrochemical cycling stability. A key criterion for the selection of ion-storage materials is to match their electroactive voltage windows with the paired electrochromic polymers. Thus, we developed a nanostructured, amorphous vanadium oxide (VOx) ion-storage material that exhibits high transmissivity, minimal color interference, and excellent charge-balancing capability in a closely matched electroactive window with the paired electrochromic polymers. High-performance magenta-to-transmissive hybrid electrochromic devices constructed from pairing the polymer with the VOx can be reversibly switched for 50 000 cycles with an optical loss less than 5%.