Recent strategies in spray drying for the enhanced bioavailability of poorly water-soluble drugs.

The study of amorphous solid dispersions (ASDs) is currently one of the most exciting areas in pharmaceutics. Research has shown that ASDs offer unique advantages in improving the bioavailability of poorly water-soluble drugs over conventional delivery systems. The various formulations and manufacturing processes of ASDs affect their physicochemical stability, processability, and drug release characteristics. Therefore, the characterization of ASDs is critical in all stages of product development, including preformulation screening, formulation development, process scale-up, and commercial manufacturing. Proper characterization allows for the rational selection of formulation composition and manufacturing processing methods and allows for high-quality drug products. In this review, we present the most commonly used methods for characterizing the solid-state properties of ASDs, and we discuss their mechanisms, applications, advantages, and disadvantages. We also provide a brief overview of the methods used to characterize ASDs behavior in aqueous media. These methods are divided into three different categories: microscopic and surface analysis methods, thermal analysis methods, and spectroscopic methods. In addition, this article discusses a number of emerging techniques. Last, we discuss how these methods are applied at different stages in the ASDs product development life cycle.

Characterization of amorphous solid dispersions

Springer Tracts in Modern Physics, vol. 205, Henning F. Poulsen. Springer-Verlag, Berlin, Heidelberg, New York (2004), 154 pp., 56 figs., 120€/US$149 (hardback), ISBN: 3-540-22330-4

Characterization of woodstove briquettes from torrefied biomass and coal

In this paper, we present a new method to reconstruct large volumes of nontransparent porous materials at submicron resolution. The proposed method combines fluorescence laser scanning confocal microscopy with serial sectioning to produce a series of overlapping confocal z-stacks, which are then aligned and stitched based on phase correlation. The method can be extended in the XY plane to further increase the overall image volume. Resolution of the reconstructed image volume does not degrade with increase in sample size. We have used the method to image cementitious materials, hardened cement paste and concrete and the results obtained show that the method is reliable. Possible applications of the method such as three-dimensional characterization of the pores and microcracks in hardened concrete, three-dimensional particle shape characterization of cementitious materials and three-dimensional characterization of other porous materials such as rocks and bioceramics are discussed.

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3D imaging of cement-based materials at submicron resolution by combining laser scanning confocal microscopy with serial sectioning

LabDCT derives 3D crystallographic information via diffraction contrast tomography (DCT) within a commercial laboratory X-ray microscope (ZEISS Xradia 520 Versa) that uses a synchrotron-style detection system for tomography. The establishment of DCT into a laboratory setting opens the way for routine, non-destructive, time-evolution studies of grain structure over meaningful sample volumes. The combination of grain information with microstructural features such as cracks, porosity, and inclusions, all derived non-destructively in 3D, enables materials characterization of damage, deformation, and growth mechanisms. Here, we introduce LabDCT and demonstrate its capabilities through a selection of materials science

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Diffraction Contrast Tomography in the Laboratory – Applications and Future Directions

Application of X-ray microtomography for the characterisation of hollow polymer-stabilised spray dried amorphous dispersion particles

Introduction Many materials made by nature and in the laboratory exhibit structure on multiple length scales. The multi-scale structure of these \"hierarchical materials\" plays an important role in bulk materials properties, as well as in processes that occur from the nanoscale to the mesoscale. Bone, wood, and leaves are well-known examples of hierarchical structures in nature (Figure 1). Taking a cue from nature, hierarchical materials development has tried to exploit these structures at various scales to realize enhanced materials properties. For example, the “lotus effect” is an example of superhydrophobicity where an extremely water-repellent surface arises from the hierarchically textured leaf surface and chemistry. The effect is created from the leaf surface, which has micrometerscale papillae on epidermal cells and nanometer-scale hair-like features from the superimposed epicuticular wax layer. Artificial “self-cleaning”, that is, superhydrophobic or even superoleophobic glass surfaces have been inspired by the lotus leaf. For example, a fluorinated bilayer coating is used on Corning's Gorilla® glass, which consists of silica microspheres of two different sizes formed using a self-assembly process. This has been characterized in 2D by ZEISS field emission scanning electron microscopy (FE-SEM) technology [1]. The design and fabrication of hierarchical structures presents many challenges for theory, computational design, synthesis, and characterization—all at multiple length scales and in three dimensions. For example, multi-scale materials modeling aims to create a continuum model appropriate to a given length scale, which integrates information from finer scales for inputs into the next-scale up. This requires improvement of fundamental “ball and stick” models to more sophisticated morphologies [2, 3]. Fabricating nature-inspired structures is also challenging. Hierarchal structured porous materials for energy conversion and storage applications use bottoms-up biotemplating approaches that are difficult to scale to manufacturing processes [4]. Bridging the gap by linking the top-down design and bottom-up assembly approaches in a vast parameter space requires methods to map and characterize structures in three spatial dimensions and as a function of time. X-ray microscopy (XRM) is a rapidly emerging technique to non-destructively image and quantify microstructure in 3D across a variety of length scales from tens of nanometers to millimeters. It has been used to study a wide spectrum of materials from carbonate rocks to murine brains, including a variety of hierarchical structured materials [5–8]. This article reviews the basic principles of XRM at various length scales and focuses on a handful of recent scientific studies on hierarchical, porous materials from the user community.

X-Ray Microscopy for Hierarchical Multi-Scale Materials

Three-dimensional X-ray microscopy (XRM) is a powerful sub-surface imaging technique that reveals tomography of three-dimensional microstructure from a range of materials, non-destructively. The nondestructive nature of X-rays has made the technique widely appealing, with the potential for characterizing sample changes in “4D,” delivering 3D microstructural information on physically the same sample over time, as a function of sequential processing conditions or experimental treatments. This has led to a new generation of functional studies with applications and is in a state of rapid expansion [1]. Recently, laboratory-based X-ray sources have been coupled with high resolution X-ray focusing and detection optics from synchrotron-based systems to acquire tomographic datasets with resolution down to 50 nm across a great span of sample dimensions [2]. Additionally, the technique of laboratory based X-ray diffraction contrast tomography has recently become available; allowing the nondestructive routine characterization of 3D crystallographic information on polycrystalline materials in a commercial laboratory X-ray microscope (ZEISS Xradia 520 Versa). Known as laboratory diffraction contrast tomography (LabDCT), this imaging modality will open the way for routine, nondestructive studies of time-evolution of grain structure to complement destructive electron backscatter diffraction (EBSD) end-point characterization. This talk will explore both the implementation of optics in nanoscale and sub-micron laboratory XRM architectures and review in detail several leading applications examples for the field of additive manufacturing including the ability to track changes, in grain size and orientation, over time, e.g. ‘4D’ time lapse studies using LabDCT. XRM for tomography using a laboratory source was used to characterize porosity in additive process control study for various steel input materials and Ti-6Al-4V built with Arcam SEBM. For additional process and material qualification using LabDCT, an example of this capability was used to follow the sintering of copper particles through a series of time-lapsed DCT measurements. XRM tomographic data provides multiscale imaging and visualization for a wide variety of AM materials, even creation of accurate 3D-printed models in biomimetic studies [4-5]. XRM can provide accurate 3D internal structural information critical to aid computational design of next-generation materials.

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Recent Advancements in 3D X-ray Microscopes for Additive Manufacturing

Three-dimensional X-ray microscopy (XRM) has emerged as a powerful interior imaging technique that obtains information from a range of materials under a variety of conditions and environments. Recently, laboratory-based X-ray microscopes have demonstrated tomographic datasets with resolution down to 50 nm for investigation across a great span of sample dimensions from the nanoscale to the mesoscale. [1-3] It has been used to study a wide spectrum of materials from carbonate rocks to murine brains, including hierarchical structured materials. [4] This talk will present the current state of the art in laboratory X-ray microscopy at various length scales and multi-modal capabilities for XRM-SEM combined image visualization, transformation, manipulation, and analysis using commercial software package from Object Research Systems (ORS).

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Leah Lavery

Papers

Diffraction Contrast Tomography in the Laboratory – Applications and Future Directions

Application of X-ray microtomography for the characterisation of hollow polymer-stabilised spray dried amorphous dispersion particles

X-Ray Microscopy for Hierarchical Multi-Scale Materials

Recent Advancements in 3D X-ray Microscopes for Additive Manufacturing

Fusing Multi-scale and Multi-modal 3D Imaging and Characterization