ABSTRACT
ABBV-167, a phosphate prodrug of BCL-2 inhibitor venetoclax, was recently progressed into the clinic as an alternative means of reducing pill burden for patients in high-dose indications. The dramatically enhanced aqueous solubility of ABBV-167 allowed for high drug loading within a crystalline tablet and, when administered in phase I clinical study, conferred venetoclax exposure commensurate with the equivalent dose administered as an amorphous solid dispersion. In enabling the progression into the clinic, we performed a comprehensive evaluation of the CMC development aspects of this beyond the rule of five (bRo5) prodrug. Adding a phosphate moiety resulted in excessively complex chemical speciation and solid form landscapes with significant physical-chemical stability liabilities. A combination of experimental and computational methods including microelectron diffraction (MicroED), total scattering, tablet colorimetry, finite element, and molecular dynamics modeling were used to understand CMC developability across drug substance and product manufacture and storage. The prodrug's chemical structural characteristics and loose crystal packing were found to be responsible for the loss of crystallinity during its manufacturing, which in turn led to high solid-state chemical reactivity and poor shelf life stability. The ABBV-167 case exemplifies key CMC development challenges for complex chemical matter such as bRo5 phosphate prodrugs with significant ramifications during drug substance and drug product manufacturing and storage.
Subject(s)
Prodrugs , Humans , Prodrugs/chemistry , Phosphates , Drug Development , Solubility , TabletsABSTRACT
Ultraviolet-C (UVC) photodetector has appealed to a numerous number of research owing to its manifold applications in wireless communication, flame monitoring, and medicine. However, in addition to superior performance and high stability of recent studies, scalability and production cost are important factors for commercialization and practical implementation. In this study, a halide perovskite-based UVC photodetector was fabricated using spin-coating process and low-temperature annealing. Corning® Willow® Glass was selected as the substrate for the bottom-illuminated device due to its flexibility and exceptional optical transmission (approximately 60%) in the deep-UV region. The device had a vertical structure with a large active area (1 cm2) owing to the judicious utilization of electrodes. Under bent state with a curvature radius of 25 mm, the as-fabricated device exhibited high response and repeatability with an on/off ratio of 9.57 × 103, a fast response speed of 45/46 ms (rise/fall times) at zero bias under the illumination of a 254-nm UV lamp. The results are based on a flexible and lightweight photodetector without the utilization of notable metal electrodes.
ABSTRACT
Flexible glass has many applications including photovoltaics, organic light-emitting device (OLED) lighting, and displays. Its ability to be processed in a roll-to-roll facility enables high-throughput continuous manufacturing compared to conventional glass processing. For photovoltaic, OLED lighting, and display applications, transparent conductors are required with minimal optical reflection losses. Here, we demonstrate an anti-reflective coating (ARC) that incorporates a useful transparent conductor that is realizable on flexible substrates. This reduces the average reflectivity to less than 6% over the visible band from normal incidence to incident angles up to 60°. This ARC is designed by the average uniform algorithm method. The coating materials consist of a multilayer stack of an electrically functional conductive indium tin oxide with conductivity 2.95×105 Siemens/m (31 Ω/â¡), and AlSiO2. The coatings showed modest changes in reflectivity and no delamination after 10,000 bending cycles. This demonstrates that effective conductive layers can be integrated into ARCs and can be realized on flexible glass substrates with proper design and process control.
ABSTRACT
For halide perovskite solar cells (PSCs) to fulfill their vast potential for combining low-cost, high efficiency, and high throughput production they must be scaled using a truly transformative method, such as roll-to-roll processing. Bringing this reality closer to fruition, the present work demonstrates flexible perovskite solar cells with 18.1% power conversion efficiency on flexible Willow Glass substrates. We highlight the importance of the transparent conductive oxide (TCO) layers on device performance by studying various TCOs. While tin-doped indium oxide (ITO) and indium zinc oxide (IZO) based PSC devices demonstrate high photovoltaic performances, aluminum-doped zinc oxide (AZO) based devices underperformed in all device parameters. Analysis of X-ray photoemission spectroscopy data shows that the stoichiometry of the perovskite film surface changes dramatically when it is fabricated on AZO, demonstrating the importance of the substrate in perovskite film formation.
ABSTRACT
This paper demonstrates the fabrication and measurements of flexible photonic lightwave circuits in glass substrates. Using temporally and spatially shaped ultrafast laser pulses, highly symmetrical and low-loss optical waveguides were written in flexible glass substrates with thicknesses ranging from 25 µm to 100 µm. The waveguide propagation loss, measured by optical frequency domain reflectometry, was 0.11 dB/cm at 1550 nm telecommunication wavelength. The bend loss of the waveguide is negligible at a radius of curvature of 1.5 cm or greater. Additionally, the waveguides are thermally stable up to 400°C. This paper presents alternatives to fabricating flexible photonics in traditionally used polymeric materials.
