Ruba Alajlouni is a consultant with Improved Pharma, a leading pharmaceutical consulting and research company based in Purdue Research Park, West Lafayette, IN. She brings expertise in solid-state characterization, bioanalytics, and regulatory and quality compliance, with hands-on experience in synchrotron XRD, XRPD, Rietveld refinement, Raman spectroscopy, HPLC, dissolution, thermal analysis, dynamic light scattering, and chemometrics.

Ruba has built her consulting practice applying multivariate analysis and spectroscopy to solve bioanalytical and solid-state problems for clients. Her current work extends into lipid nanoparticle manufacturing and characterization for drug delivery applications. An alumna of the NX School at Argonne National Laboratory, she has specialized training in synchrotron-based X-ray diffraction and scattering techniques that complements her extensive laboratory experience in pharmaceutical characterization. She holds two MS degrees—one in Industrial and Physical Pharmacy from Purdue University, where she trained under Dr. Stephen R. Byrn, and one in Biological Sciences from Virginia Tech—as well as a Graduate Certificate in Regulatory and Quality Compliance.

Alongside her consulting work, Ruba served as a project manager and research scientist at SSCI (AMRI/Curia), where she led concurrent analytical and stability projects, oversaw data audits, and ensured quality and data integrity compliance. She has developed custom MATLAB-based tools for Raman data analysis and has published peer-reviewed work on antimicrobial drug discovery, peptide nucleic acid therapeutics, and Raman-based phenotypic profiling. Synchrotron XRPD, especially PDF analysis, is an extremely valuable tool for understanding the arrangement of atoms within an amorphous dispersion. In particular, PDF analysis can determine if any of the API molecules have order, meaning they retain some crystalline character. We were interested in determining if other (non-synchrotron) highly sensitive techniques might be useful for detecting low amounts of crystallinity in amorphous dispersions.

We investigated the use of Raman mapping and hot-stage polarized light microscopy in the analysis of several API/polymer dispersions. In each formulation, although bulk XRPD testing indicated the samples were amorphous, we were able to detect micro-domains of crystallinity in the dispersions. We will present the Raman mapping results for the different dispersions, and as time permits, we will include other techniques such as PLM. Lastly, we recently analyzed the same samples by synchrotron XRPD and we will present those results as well as supporting evidence for the usefulness of these orthogonal techniques.

Edwin Aret is the Director of Solid State at Symeres, responsible for the crystallization, form selection and pre-formulation in drug development activities. He has a PhD in Solid State Chemistry at the Radboud University Nijmegen, and over 30 years of experience in crystallization of small organic molecules. Focus is on high throughput screening, to study the biopharmaceutical properties of candidate drug molecules, bridging the gap from compound towards medicine. -

Chris Benmore is a senior physicist at the Advanced Photon Source, USA. He has worked at Argonne National Laboratory for 25 years in the area of x-ray and neutron diffraction applied to disordered materials. He was educated in England, receiving his PhD from the University of East Anglia in 1993 and was a postdoctoral fellow in Canada, which included a visiting appointment at Los Alamos Neutron Scattering Center. Chris has held permanent staff positions at the Rutherford Appleton Laboratory, UK, and the Intense Pulsed Neutron Source at Argonne. Chris has been an adjunct professor at Arizona State University since 2008 and holds a joint appointment with the University of Chicago. He has published 300+ papers and presented over 130 invited talks. Chris's research interests include x-ray and neutron diffraction methods applied to liquids, glasses and amorphous materials. Chris was awarded the University of Chicago Board of Governors Award for research in 2012. High energy synchrotron x-ray diffraction experiments (typically E60 keV) represent a powerful tool for investigating the structure of liquid pharmaceuticals and their associated amorphous solid dispersions. This is achieved through the extraction of the x-ray Pair Distribution Function (PDF), which gives an average structure of the entire system that is heavily weighted towards the heavier atoms i.e. the molecular skeleton. Empirical Potential Structure Refinement (EPSR) can provide realistic 3-dimensional molecular models when fit to high-quality x-ray PDF data. Here we use these methods to shed light on the structure-property relations of liquid and amorphous pharmaceutical molecules and their mixtures. Our x-ray consistent models are initially constrained by information obtained from other methods, such as ssNMR, FT-IR and Raman spectroscopy, to investigate the bonding and packing of molecules and polymers in the disordered state. However, more recently, our x-ray data has been used to test models based on quantum mechanical conformer calculations obtained from machine learning interatomic potentials. The absolute normalization of x-ray diffraction data is shown to be a critical factor in distinguishing between different molecular models.

Dr Rocco Caliandro got the degree and PhD in Physics at the University of Bari (Italy). During his PhD and a two years post-doctoral fellowship from the National Institute of Nuclear Physics (INFN) he carried out researches in high-energy physics, participating to several heavy-ion collisions experiments at the European Organization for Nuclear Research (CERN) of Geneva. Then he worked as post-degree fellowship at the Institute for the Research and Development of Crystallographic Methodologies of the National Research Council (CNR), under supervision of Prof. Carmelo Giacovazzo and in 2001 he became permanent employee as researcher of the Institute of Crystallography of CNR. In 2020 he became Senior Researcher and in 2023 Research Director in the same Institute.
He got the national academic qualification to associate professor in Molecular Biology (05/E2), in 2014 and in Applied Physics (02/D1) in 2020 and in Models and Methodologies for Chemical Sciences (03/A2) in 2022. He won a prize for researchers and technologists of the CNR for having achieved excellence and innovation performance of particular strategic importance in 2005 and a selective procedure for a salary upgrade for CNR researchers in 2019. In 2020, he was appointed in the triad of suitable candidates for the direction of the Institute of Crystallography of CNR. He led and participated to many european and italian reseach projects. Current research interests: Pair distribution function, in situ/operando characterization, Data analysis, Crystallographic Methods, Protein Crystallography, Computational Biophysics.
Bibliometric parameters (March 2026): Publications: 187, overall number of citations: 8678, h-index: 35 (Scopus). http://orcid.org/0000-0002-0368-4925 Solid-state forms of pharmaceutical active ingredients exhibit distinct physical and chemical properties, particularly concerning solubility and bioavailability, due to their specific atomic and molecular stacking structures. Moreover, there has been a notable emphasis on enhancing the solubility of drugs and improving their bioavailability through the utilization of the amorphous state. On the other hand, amorphous drugs can exhibit instability and a propensity to transform into a crystalline form, resulting in reduced solubility and bioavailability. For these reasons, techniques to investigate experimentally the short-range order of pharmaceuticals are of paramount importance. The local structure can be studied by methods based on the atomic pair distribution function (PDF) analysis of diffraction data, generated by X-ray, neutron or electron probes. The main experimental and computational aspects relevant for PDF analysis of pharmaceutical compounds will be presented, focusing on calculation of PDF profiles from diffraction data and approaches to interpret them on the base of atomistic models. New tools available for such analyses will be presented and applied to relevant pharmaceutical case studies.

Dr. Mads Carlsen, Excelsus, works on developing a system for high-throughput synchrotron-XRD system for pharmaceutical samples. Previously he was researching new algorithms in XRD-CT, a family of methods for mapping the spatial distribution of crystalline materials in bulk samples.

Owing to the enormous photon flux of fourth-generation synchrotrons, a high-resolution XRD curve can now be collected in a fraction of a second.
Traditional sample-preparation for high-resolution XRD involves tedious sample preparation steps to ensure micron-sized particles and randomly oriented powders and loading thin capillaries. Therefore, sample preparation is now the bottleneck for high-throughput systems. A promising solution to this problem is the plastic-washer systems, currently implemented at number of beamlines in Europe. In these systems, large-grained powders can be loaded directly into a six-millimeter diameter sample-chamber and shaking is utilized to ensure random sampling of the powder particles.
Unlike the sample spinning used in traditional capillary- and Bragg- systems, shaking is a random process and necessitates a statistical approach to data-processing. The effects of mass-fluctuations, imperfect mixing, orientation contrast, and photon-counting statistics all need to be considered to understand the statistical properties of the diffraction signal.
Going beyond the time- and orientation-averaged 1D diffraction curve, we can use the high-framerate data collection and 2D resolved detector to screen for specific rare events in individual diffraction patterns during data collection. With this approach, we can achieve high sensitivity to trace amounts of crystalline phases.

- MS in Biomedical Engineering, minor in Bionanotechnology, Polytechnic University of Turin, Italy
- PhD in Computational and Quantitative Biology, EPFL, Switzerland

Dr. Caroprese is a Computational Scientist at Excelsus with a background in computational modeling, quantitative image analysis, and data analytics. During his doctoral studies at EPFL, he developed algorithms for quantitative image analysis and molecular modeling of DNA-based assemblies. Before joining Excelsus, he worked at HEG Geneva, where he applied machine learning and language models to complex data-analysis challenges. At Excelsus, he develops computational tools and analysis workflows for diffraction data and automated materials characterization.

This presentation will highlight the use of high-throughput synchrotron X-ray powder diffraction (SXRPD) for phase identification and quantitative analysis in complex mixtures through an automated data-analysis pipeline. By combining curated reference databases, automatic peak detection, candidate selection, and profile-based evaluation, the workflow enables rapid and interpretable analysis of large numbers of samples.

A pharmaceutical case study will illustrate the applicability of this approach to mixture analysis, and more broadly its potential for automated high-throughput decision support.

Adrian specialises in advising pharmaceutical and biotech clients on all issues relating to the enforcement and validity of patents and supplementary protection certificates, including topical issues such as medical use claims, plausibility, antibody functional claims, Article 3 of the SPC Regulation, and the doctrine of equivalents. Adrian also acts for clients in contractual disputes involving patent rights, both before the High Court and in private international arbitrations. See abstract from Ewan Nettleton

Lyndon is a Professor of Physical Chemistry at EPFL, and Head of the Laboratoiry of Magnetic Resonance.

His research centres on the development of new NMR spectroscopy experiments to determine the atomic-level structure and dynamics of complex materials and molecular systems, to solve a range of problems across disciplines.

He has received a series of awards and honors, including the 2012 AMPERE Prize and the 2015 Bourke Award of the Royal Society of Chemistry. He gave the 2018 John S. Waugh Lecture in Physical Chemistry at MIT. Most recently he was awarded the 2023 Günther Laukein Prize.

He is a Fellow of the International Society of Magnetic Resonance, and a Member of the Academia Europaea. Structure elucidation of amorphous materials and microcrystalline solids in powder form is one of the key challenges in chemistry today. While techniques such as single crystal diffraction and cryo-electron microscopy are generally not able to characterize such materials, we will show how an approach based on measured NMR chemical shifts in combination with methods for large scale computation of shifts can rapidly determine full three-dimensional structures from powders.

For example, using a machine learning model of chemical shifts, we will demonstrate the complete atomic-level structure determination of amorphous pharmaceutical forms by combining dynamic nuclear polarization (DNP) enhanced solid-state NMR experiments with chemical shifts predicted using machine learning for MD simulations of large systems.

From these amorphous structures we then extract and analyze preferred conformations, H-bonding motifs, and intermolecular interactions in the amorphous sample in terms of the stabilization of the amorphous form of the drugs.

Francesca is a chemical crystallographer with extensive experience spanning academia, large-scale facilities, and industry. She received her PhD from the University of Edinburgh in 2006, specializing in high-pressure crystallography. She subsequently held postdoctoral positions at the University of Western Australia and at the ISIS Neutron and Muon Source near Oxford, UK, before moving to the University of Göttingen as an Alexander von Humboldt Fellow.
From 2009 to 2011, Francesca was a Dorothea Schlözer Research Fellow, and from 2011 to 2017 she led an independent research group funded by the Emmy Noether Programme of the German Research Foundation. Her work on high-pressure crystallography of pharmaceuticals was recognized in 2016 with the Max von Laue Award of the German Crystallographic Society. In the same year, she served as Co Director of the Erice International School of Crystallography.
Following a brief career break from active research in her role as a science manager at the German Research Foundation, Francesca returned to scientific work as a self-employed consultant and X-ray crystallography expert. In 2023, she joined the small molecule X-ray group at Novartis in Basel, where she provides expert crystallographic support for structure-guided drug discovery. Single‑crystal X‑ray diffraction (SC‑XRD) remains the gold standard for unambiguous molecular structure determination in the pharmaceutical industry. In this talk, I will provide an overview and perspective on the role of SC‑XRD at Novartis, highlighting how crystallographic expertise supports both Research and Development activities across the organization. The X‑ray laboratory in Basel serves as the global point of reference for small-molecule diffraction at Novartis, enabling close integration of method development, routine structure determination, and advanced problem solving.
Following an overview, the presentation will focus on practical strategies for absolute structure determination, disorder modelling and analysis of twinned crystals. Together, these examples underline the continued relevance of single-crystal diffraction techniques for tackling complex structural questions in modern pharmaceutical research.

Fabia Gozzo is a physicist with over 30 years of experience in synchrotron-based X-ray diffraction. After research positions at Lawrence Berkeley National Laboratory, Intel, and the Paul Scherrer Institute—where she developed one of the world's leading powder diffractometers—she founded Excelsus Structural Solutions to bring advanced synchrotron analytics to industry. She has authored over 90 scientific publications and is internationally recognized as an expert and advisor in synchrotron-based structural characterization.
MS in Physics, University of Bari, Italy
PhD in Physics, EPFL, Lausanne, Switzerland

Synchrotron X-Ray Powder Diffraction (XRPD) enables a level of structural insight that extends well beyond routine phase identification. This presentation will concentrate on advanced detection and quantification methodologies, including trace-level crystalline phase analysis and robust quantitative phase assessment performed with synchrotron accuracy and carefully designed calibration strategies.
Recent methodological developments, including high-throughput synchrotron XRPD workflows, will be briefly discussed as part of a broader effort to combine analytical rigor with efficiency, without compromising data quality. These advances expand the practical applicability of synchrotron XRPD while maintaining the resolution, sensitivity, and reliability required for complex pharmaceutical materials.
An overview of additional capabilities and emerging developments will be provided, including applications relevant to intellectual property and legal contexts, where structurally sound and quantitatively defensible data are essential.

Jürgen Grässlin is a mineralogist by education and finished his PhD in crystallography at ETH Zurich in 2013. During his doctoral studies, he mainly worked on method development in XRPD using synchrotron radiation, aiming to exploit texture in highly oriented powder samples. By measuring these samples in different orientations, more single-crystal like data can be collected, which helps to overcome the peak overlap problem.
In 2014 he joined Rigaku Europe in Germany, first as an application scientist for powder diffraction and later as a salesperson for XRD/XRF/XI products. In 2019 he switched to Rigaku's single-crystal sales team, which today also covers electron diffraction. Since March 2026 he is Senior Sales Manager SCX for the EMEA region. Electron diffraction has emerged as a powerful complement to synchrotron and laboratory PXRD for pharmaceutical and materials research, particularly when dealing with highly complex powder samples. However, obtaining complete and reliable structural information from individual crystallites remains challenging due to variations in diffraction quality, radiation sensitivity, and geometric constraints that limit completeness and signal to noise ratios. To address these limitations, we present recent advances in fully automated 3D-ED/MicroED data acquisition and analysis implemented on the Synergy ED platform. Our approach performs multi crystal, grain by grain automated screening of powder samples, enabling robust characterization of polymorphs, impurities, and multi-phase mixtures without prior separation. The workflow includes automated crystal detection, auto centering, and queued data collection, ensuring high throughput even for heterogeneous materials. Subsequent clustering based bulk analysis classifies datasets according to crystal quality, unit cell, and structural similarity. For each identified component, the Synergy ED automatically executes merging and scaling of optimal subsets of crystals, maximizing data completeness and minimizing radiation damage effects. The resulting merged datasets are passed directly into the AutoChem pipeline, enabling fully automated structure solution from the best available combined data. This integrated strategy greatly reduces user intervention and accelerates the transition from powder sample to refined structural models. These developments transform 3D-ED/MicroED into a high throughput, routine tool for analyzing complex powders. By leveraging automation from data acquisition to structure solution, the Synergy ED expands the applicability of ED to challenging real world samples where traditional single-crystal or powder methods fall short.

Fátima Herranz completed her PhD at the University of Montpellier in collaboration with the
University of Copenhagen, where she focused on studying amyloid processes using small-
angle X-ray scattering (SAXS) and chemometric tools. Afterward, she continued her research
at the University of Copenhagen, further exploring the structural and kinetic aspects of
amyloids. Currently, she is part of the CoSAXS beamline team at MAX IV, where she
collaborates on multidisciplinary projects in areas such as lipid nanoparticles, food science,
structural biology, and time-resolved studies. Her work involves combining SAXS with
complementary spectroscopic techniques to address complex scientific challenges. The structural characterization of (bio)pharmaceuticals systems across multiple length and time scales is essential for understanding their stability, interactions, and function in solution. Small- and wide-angle X-ray scattering (SAXS/WAXS) are powerful techniques that enable the investigation of macromolecular structure, assembly, and dynamics under near-native conditions.
The coSAXS beamline is a state-of-the-art multipurpose SAXS/WAXS instrument designed to address a wide range of structural biology and soft-matter challenges. It delivers a highly brilliant, monochromatic, and tunable X-ray beam with low divergence, high flux, and variable beam size, allowing optimized experimental configurations over a broad range of sample-detector distances. These capabilities enable measurements spanning from nanoscale structural features to larger hierarchical assemblies.
The beamline performance is complemented by a versatile suite of sample environments. This brings flexibility, which supports a wide variety of experimental approaches.
In this talk, I will present the capabilities of the coSAXS beamline and illustrate how advanced SAXS methodologies can be applied to address key challenges in the characterization of (bio)pharmaceutical systems, highlighting representative scientific cases that demonstrate the potential of synchrotron SAXS for probing structure and dynamics in solution.

Zichen Jia is a materials science expert at Novartis Pharma AG in Basel, Switzerland. His work focuses on API solid‑state and powder property characterization, crystallization process development, and scale‑up to commercial manufacturing. In recent years, he has expanded his expertise to the characterization and understanding of complex biomolecular systems, including oligonucleotides and antibody-oligonucleotide conjugates, to further support new‑modality pharmaceutical development. In recent years fatty acid conjugation has gained increasing attention as a strategy for therapeutic oligonucleotides, including small interfering RNA (siRNA) and antisense oligonucleotides (ASO), because of its potential to promote extrahepatic delivery and improve pharmacokinetics. Due to their amphiphilic properties fatty acid-conjugated (FAC) oligonucleotides may self-assemble in solution forming supramolecular structures. Such structures may influence physicochemical properties relevant to drug development and product administration, including viscosity, interfacial behavior, and physical and chemical stability. Understanding such assemblies is therefore important across multiple stages of drug development, including synthesis, formulation and manufacturing. In this work, we investigated a FAC siRNA in solution by synchrotron-based small-angle X-ray scattering (SAXS). The results suggest that the oligonucleotides form self-assembled supramolecular structure, which is influenced by solution conditions such as oligonucleotide concentration and ionic strength. By applying various models to interpret the SAXS data, we obtained information on the structure of the assemblies including their shape, size and composition. The presentation will discuss the significance of these findings, potential limitations, and future directions for research.

Paolo P. Mazzeo is Professor at the University of Parma. He is expert of solid-state chemistry and X-ray powder diffraction. His research is focused on crystal engineering and solid-state synthesis via mechanochemistry of eutectics and cocrystals, mainly based on pharmaceutical or natural volatile compounds for food- and agro-chemical applications. He is also interested in the synthesis of crystalline sponges made of flexible MOF-guest or HOF-guest systems. He is also very active in the field of Time Resolved In-Situ (TRIS) XRPD characterization of mechanochemical reactions by means of synchrotron radiation, highlighting both structural and microstructural evolution throughout the reaction. He is experienced in patent law and litigation, and he is consultant for multiple pharmaceutical companies. He was awarded a PhD in Chemical Science at the University of Bologna in 2014 on solid-state luminescent metal-organic compounds for optoelectronic devices. After his PhD, he worked as Crystallographer and Material Scientist at Excelsus Structural Solutions (Swiss) AG. Multicomponent molecular materials, such as cocrystals, are widely exploited in the pharmaceutical, food, and agrochemical industries to finely tune the physicochemical properties of active compounds and enhance their biological performance.
Over the past decades, mechanochemistry has emerged as a cost-effective and sustainable synthetic strategy, however, its broader application is still limited by the difficulty of probing reactions within the closed milling environment. Despite recent advances in in-situ monitoring, the mechanistic pathways governing these processes remain poorly understood. Transient liquid intermediates have been proposed to play a key role in facilitating mechanochemical transformations. In this context, the ability to predict a priori the formation of low-melting eutectic mixtures would significantly improve the rational design of mechanochemical protocols. Here, I present a time-resolved investigation of cocrystal formation using in situ synchrotron X-ray powder diffraction (XRPD) to directly monitor phase evolution under milling conditions. Particular emphasis is placed on evaluating the likelihood of eutectic formation through PoEM (Predictor of Eutectic Mixtures), a predictive tool based on the intrinsic thermal properties of coformers and their intermolecular interactions. Eutectic systems were further characterized by thermal analysis and pair distribution function (PDF) analysis, providing complementary insight into their structural features across different length scales. These findings are correlated with the formation pathways and structural properties of the final cocrystals, offering a comprehensive picture of the role of eutectic intermediates in mechanochemical synthesis.

Dr. Theyencheri Narayanan is a Senior Scientist in-charge of the small-angle X-ray scattering (SAXS) instrument at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. His main research interests are soft matter self-assembly, microstructure and dynamics of out-of-equilibrium colloidal systems, and structure-function relationships in large biomolecular assemblies. He is also leading the development of time-resolved SAXS, ultra SAXS (USAXS) and X-ray photon correlation spectroscopy (XPCS) methods for studies of soft matter and biophysical systems including pharmaceutical materials. This presentation will give an overview of recent advances in synchrotron scattering methods for the investigation of structure and dynamics of soft materials and related systems of pharmaceutical relevance. X-ray and neutron scattering methods are well-established tools for the elucidation of microstructure of soft matter in bulk and at interfaces [1]. The fourth-generation synchrotron sources, which offer very high brightness and degree of coherence, when combined with advanced photon counting detectors enable a broader range of dynamical studies of soft matter and biological systems [2]. A notable application is for probing multiscale kinetic processes in the millisecond range and below by time-resolved small-angle X-ray scattering (SAXS) and related methods such as ultra-small-angle X-ray scattering (USAXS) and wide-angle X-ray scattering (WAXS) [2]. The higher degree of coherence is a major boost for the X-ray photon correlation spectroscopy (XPCS), which is analogous to dynamic light scattering with X-rays. This presentation will cover some representative examples such as the polymorphism in ionizable lipid nanoparticles used for mRNA delivery [3], their stimuli-responsive disassembly [4], etc. A better understanding of the kinetic pathways for the formation of complex coacervate micelles may help to improve their efficacy as drug delivery vehicles [5]. [1] T. Narayanan, et al., Crystallogr. Rev., 23, 160 (2017). [2] T. Narayanan, Adv. Colloid Interface Sci. 325, 103114 (2024). [3] H. Yu, et al., Acc. Chem. Res., 58, 20, 3210 (2025). [4] R.R.M. Madrid, et al., ACS Appl. Mater. Interfaces, 17, 51, 69118 (2025). [5] T.D. Vogelaar, et al., Macromolecules, 58, 158 (2025).

Dr Iain D. H. Oswald is a Reader in the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS) at the University of Strathclyde, where he has worked since 2009 and currently leads research in high pressure crystallography and solid state pharmaceutics. His research focuses on understanding how molecular materials—particularly pharmaceuticals—behave under extreme conditions of pressure and temperature, with an emphasis on pressure induced polymorphism, co crystallisation, and pathways for recovering high pressure phases to ambient conditions.
Dr Oswald completed his MChem and PhD at the University of Edinburgh, graduating in 2001 before continuing his doctoral work on hydrogen bonding and co crystallisation. His PhD research expanded into high pressure crystallography, enabling early collaborations at the European Synchrotron Radiation Facility (ESRF) in Grenoble. He later held postdoctoral positions at ESRF (2004-2006) and the University of Edinburgh (2006-2009), specialising in high pressure diffraction and the behaviour of energetic and pharmaceutical materials.
At Strathclyde, Dr Oswald has been principal investigator on major funded projects, including an EPSRC Early Career Fellowship (2016-2021) on pressure induced nucleation and a Leverhulme Trust grant on pressure induced polymer formation (2012-2015). His research portfolio spans crystallisation mechanisms, polymorph discrimination, molecular modelling, and the design of solid state materials with improved stability and performance. In this talk, we present the application of X-ray Diffraction Computed Tomography (XRD-CT) to pharmaceutically relevant tablets subjected to varying compression pressures—conditions known to influence intermolecular interactions and crystal packing. By incorporating the pressure-sensitive marker glycolide, we were able to spatially resolve pressure-induced transformations within intact tablets, avoiding artifacts from sample preparation. A follow-up study conducted one month later revealed an in-situ hydrolysis reaction of glycolide, highlighting the dynamic nature of the solid-state environment. The structure of the hydrolysis product was further elucidated using complementary electron diffraction techniques. These findings demonstrate the utility of XRD-CT for uncovering pressure- and time-dependent changes in molecular crystals, with implications for understanding non-covalent interaction networks and their role in the stability and evolution of pharmaceutical formulations.

Prof. Dr. Martin U. Piepenbring studied chemistry at the University RWTH Aachen and wrote his PhD thesis on the prediction of molecular crystal structures (1994). From 1995 to 2002 he worked in industry (Hoechst AG, since 1997 Clariant), where he was head of the Laboratory for Crystal Engineering and Polymorphism Studies. During this time he worked on polymorphism, crystal structures and properties of organic pigments. Since 2002 he is professor at the Institute of Inorganic and Analytical Chemistry of the Goethe-University in Frankfurt. In 2025 he married, and changed his last name from Schmidt to Piepenbring. His research is focussed on the crystallography of crystalline, nanocrystalline and amorphous organic compounds, esp. nanocrystalline pharmaceutical compounds and nanocrystalline organic pigments. In particular: • Investigation of local structures of nanocrystalline and amorphous organic compounds by means of the pair distribution function (PDF); • Crystal structure determination from powder diffraction data, including development of new methods (global fit to the powder data, global fit to the PDF; • Crystal engineering; • Polymorph screening of organic pigments and other poorly crystalline compounds; • Investgation of lattice defects and disorder in organic compounds (e.g., stacking disorder, orientational disorder) by analysis of the diffuse scattering and lattice-energy calculations. He is author of more than 160 scientific paper, a book on industrial organic pigments and of 24 patents. He twice won the Award for Excellent Teaching of his department at Frankfurt University. Since January 2026 he is co-editor of Acta Cryst. B. We develop a method for the determination of crystal structures of nanocrystalline organic compounds by a global fit to the pair-distribution function (Global-PDF-Fit). The method resembles the direct-space methods used to solve crystal structures from powder diffraction data, but (1) the fit is not performed to the powder pattern itself, but to the PDF, which is obtained from carefully measured powder data by Fourier transformation. (2) The method also works for unindexed powder data, i.e. if lattice parameters and space group are not previously known. The method is implemented in our program FIDEL. The fits starts with a huge number (about 100 million) of random crystal structures in different space groups with random values for lattice parameters, molecular position and orientation. At first, structures with overlapping molecules are sorted out. Next, the PDFs of all structures are calculated and compared to the experimental PDF using a newly developed method based on cross-correlation functions. The most promising structures are subjected to an automated fit to the PDF using a combination of FIDEL and TOPAS. An example is Pigment Yellow 83, C36H32Cl4N6O8. Using a powder with a domain size of only 10 nm, the crystal structure is reproduced with high accuracy. In the case of a 10-nm domain size sample of Pigment Yellow 14 (C34H30Cl2N6O4), many structures with similar good fit to the PDF were obtained; here, Rietveld refinements on the 10nm sample revealed the correct structures at Rank 1.

Okky D. Putra, Dr.Sci, is an Associate Principal Scientist at AstraZeneca Gothenburg specializing in chemical crystallography and solid‑state chemistry. He oversees crystallography services across global AstraZeneca R&D, applying single‑crystal X‑ray diffraction, electron crystallography, and powder X‑ray diffraction to support discovery and development. He is accountable for solid‑form selection from lead optimization through Phase 2, integrating structural insights with thermodynamic and kinetic assessments to de‑risk late‑stage surprises and guide form control. His research focuses on linking crystal structure to material properties—such as stability, processability, and performance—to optimize the developability of drug candidates and enable robust, manufacturable forms. Conventional solvent‑based crystallization is often the default route for accessing specific drug polymorphs, yet it can miss solid forms that only emerge under thermal stress. By heating crystals—both powders and single crystals—directly on diffractometers, we reveal polymorphic forms that are inaccessible by solution methods. This presentation outlines the conceptual basis and practical implementation of in‑situ heating on powder X‑ray diffractometers (PXRD) and single‑crystal X‑ray diffractometers (SCXRD) to discover, characterize, and differentiate polymorphs of active pharmaceutical ingredients. We will showcase case studies in which in‑situ PXRD captures real‑time phase evolution, while in‑situ SCXRD resolves transient or metastable structures before they revert on cooling. Particular emphasis is placed on integrating simultaneous powder X‑ray diffraction-differential scanning calorimetry (XRD-DSC) to correlate crystallographic transitions with thermal events, enabling confident assignment of phase boundaries and form identity. Together, these approaches provide a controlled, solvent‑free pathway to probe solid‑state landscapes and expose hidden polymorphic diversity. Transformations to be discussed include hydrate to anhydrous, solvate to anhydrous, hydrate to hydrate, and anhydrous to anhydrous transitions, spanning both enantiotropic and monotropic relationships.

Dr. Gustavo Santiso-Quiñones was born in Guatemala City where he obtained his university degree in Chemistry (1997). He went to Germany to the Free University of Berlin where he obtained a Master degree in Chemistry (04/2000) and later his Ph. D degree (01/2005) in fluorine chemistry in the group of Prof. Dr. K. Seppelt. He has done Post-doctoral research activities in the University of Freiburg and RWTH-Aachen, Germany, and at the EPF-Lausanne, and ETH-Zürich, Switzerland. With more than 20 years of experience in the field of synthesis, crystallization and handling of sensitive or reactive materials and as many years of experience in the field of crystallography, he became independent and in 09-2014 founded in Switzerland his first company Crystallise! AG. A company that offers to the Pharma-, Agro-, and Chemical industries crystallographic services, including the crystallization of the compounds.
Gustavo is also a founder of a second company: Eldico Scientific AG, company which has been established in Switzerland since 2019. In collaboration with Dr. T. Grüne and others, their ideas and crystallographic approach to use Electron Diffraction (micro-ED) for organic compounds, got a Science nomination for "Breaktrhough of the year 2018". The realization of an Electron Diffractometer dedicated to the Pharmaceutical industry, is now a reality where industry is profiting from this technology and device.
At the present time Gustavo is Founder and Senior Scientist of Eldico Scientific AG. Solid-state characterization of APIs increasingly demands a multi-technique approach, as no single method can fully resolve the structural complexity of modern drug compounds. Synchrotron XRPD (S-XRPD) remains the gold standard for bulk phase identification, trace quantification, and structure solution from powders. Yet it operates on bulk samples; minority phases present in nanoscopic domains or below detection thresholds may go unobserved. Electron diffraction (ED / 3D ED / MicroED) treats each individual nanometer-sized crystallite as a single crystal, offering structural information that is orthogonal and complementary to ensemble powder methods.

We present the discovery of a new polymorphic form of dapsone (a century-old drug with five previously known polymorphs) using automated ED. A small, unassigned peak had been present in prior XRPD patterns all along, yet went unrecognized as evidence of a distinct polymorph. Unpredicted by crystal structure prediction (CSP) studies limited to Z′ = 1 and 2, the new form was only identified once ED examined the sample at the single-particle level. Once discovered, CSP located it within the computed energy landscape, and its existence was confirmed after isolation by slurry experiments.

This case exemplifies an emerging paradigm: automated ED acts as a structure-first discovery engine for rare or minority phases, while S-XRPD provides bulk-level validation, quantification, and high-resolution refinement. ED identifies the unknown; S-XRPD confirms its relevance. As dedicated ED instrumentation makes the technique accessible to non-specialists, integrating ED alongside (S-)XRPD is becoming essential for rigorous polymorph risk assessment and solid-state characterization in pharmaceutical development.

Pamela (Pam) Smith has a Ph.D. in Analytical Chemistry from Miami University, specializing in microspectroscopic techniques (Raman, IR, and UV-Vis microscopy). She worked for the next five years as microspectroscopist, including being on the team who first interfaced an infrared micospectrophotometer to a synchrotron beamline at Brookhaven National Labs. In 1999, she joined Stephen Byrn's company, SSCI, and began applying microspectroscopic solutions to pharmaceutical problems. Over the next 19 years, she expanded her knowledge of pharmaceutical science and eventually became the site head of SSCI, followed by ever-increasing roles after the company was acquired by AMRI.
In 2018, Pam rejoined Steve Byrn in his new company, Improved Pharma. At first, Improved Pharma focused their R&D and business efforts on providing synchrotron services to their clients, primarily using the beamline at Argonne National Lab. Since then, the company has grown to now include 15 people working on more than just synchrotron studies. A leading consulting, research, and information company, Improved Pharma occupies 12 suites/labs in the Purdue Research Park and has dozens of internal capabilities such as XRPD, DSC, TGA, IR, Raman, HPLC, UPLC, UV-Vis, KF, dissolution, PLM, among others. Pam is VP and COO of Improved Pharma and is a part-owner.

Synchrotron XRPD, especially PDF analysis, is an extremely valuable tool for understanding the arrangement of atoms within an amorphous dispersion. In particular, PDF analysis can determine if any of the API molecules have order, meaning they retain some crystalline character. We were interested in determining if other (non-synchrotron) highly sensitive techniques might be useful for detecting low amounts of crystallinity in amorphous dispersions.

We investigated the use of Raman mapping and hot-stage polarized light microscopy in the analysis of several API/polymer dispersions. In each formulation, although bulk XRPD testing indicated the samples were amorphous, we were able to detect micro-domains of crystallinity in the dispersions. We will present the Raman mapping results for the different dispersions, and as time permits, we will include other techniques such as PLM. Lastly, we recently analyzed the same samples by synchrotron XRPD and we will present those results as well as supporting evidence for the usefulness of these orthogonal techniques.

Cornell University, Ph.D. Biochemistry
University of Maryland School of Law, J.D.

Einar Stole is a partner at Covington & Burling since 2011 and before that patent examiner in the United States Patent & Trademark Office.
He specializes in complex pharmaceutical and chemical patent litigation in the US district courts, including numerous cases involving generic drug approvals and the Hatch-Waxman Act. Einar's litigation and counseling experience has focused on matters involving pharmaceuticals, chemicals, chemical processes, and biotechnology such as genetically-engineered enzymes and DNA-based diagnostic methods. He counsels clients on a range of intellectual property and litigation matters, including patent infringement, validity, and enforceability.

Polymorphism in pharmaceutical compounds plays a pivotal role in patent litigation, especially from the patentee's perspective. This presentation examines the complexities of enforcing patents that claim specific crystalline forms, or polymorphs, of drug substances. Patentees bear the burden of proving infringement, typically by demonstrating the presence of all claim elements in the accused product as understood by a person skilled in the art. The process often involves obtaining and analyzing samples of the drug product, employing advanced techniques such as synchrotron X-ray powder diffraction (XRPD) to identify specific crystalline forms in complex mixtures. The superior sensitivity and resolution of synchrotron XRPD are crucial for detecting low-dose crystalline forms, distinguishing between crystalline and amorphous conversions, and providing clear evidence in litigation scenarios.
Alleged infringers defend patent infringement allegations by either rebut infringement or challenge the patent's validity or both. Invalidity arguments frequently center on whether the claimed crystalline form is present in prior art or alternatively whether a so-called person of ordinary skill in the relevant art could have reasonably expected to produce the claimed form using known methods. U.S. courts have set a high bar for proving obviousness. Ultimately, patents claiming crystalline or polymorphic forms of pharmaceutical solids remain a prominent and evolving facet of pharmaceutical patent litigation. The legal and scientific standards for proving infringement and invalidity continue to shape strategies for both patentees and alleged infringers.

Dr. Dmitry I. Svergun

Education/degrees
1980: MSc in Solid state physics, Physics Department, Moscow State University, Moscow, Russia
1982: PhD in Physics and Mathematics, Institute of Crystallography (ICRAS), Moscow, Russia,
1997: Dr. Science in Physics and Mathematics (advanced degree), ICRAS, Moscow, Russia

Employment
1980-2008: Engineer, Researcher, Senior Scientist, ICRAS, Moscow, Russia.
1990-1991: Guest scientist, GKSS Research Center, Geesthacht, Germany.
1991-2022: Visiting fellow, Staff Scientist, Team Leader, Group Leader, Senior Scientist, Joint Head of Research Infrastructures, European Molecular Biology Laboratory, Hamburg Unit, Germany
2014-now: CEO, BIOSAXS GmbH, Hamburg, Germany

Specialization: Structure analysis of condensed matter, in particular, biopolymers in solution, by scattering of X-rays and neutrons; Numerical methods, programming, biophysics.

Honors and awards
2010: International Rusnanoprize for methods development in nanodiagnostics
2018: International Guinier prize for lifetime achievements in small-angle scattering

Publications: over 1000 scientific papers, reviews and book chapters, 3 monographs, h-index over 110.

Small-angle X-ray scattering (SAXS) is a powerful technique for the investigation of biological macromolecules in solution and nanostructured systems. It enables the structural analysis of native particles and complexes and allows rapid assessment of structural changes induced by variations in external conditions. The development of dedicated high-brilliance synchrotron beamlines and advanced data collection and analysis methodologies has significantly enhanced the resolution and reliability of SAXS-based structural models. A key strength of SAXS lies in its ability to quantitatively characterize complex systems under native conditions, thereby enabling the observation of biomolecules in action through real-time monitoring of their responses to changes in physical and chemical parameters, such as pH, temperature, or ligand binding.
Although SAXS typically provides low-resolution quaternary structural information, it is uniquely suited for the analysis of equilibrium mixtures and for the visualization of flexible or disordered regions that are often inaccessible to high-resolution techniques. Furthermore, SAXS can be readily integrated with computational, biophysical, and biochemical methods. In hybrid modeling approaches, it effectively incorporates high-resolution structural information obtained from crystallography, NMR spectroscopy, cryo-electron microscopy, and AlphaFold predictions.
In this presentation, modern SAXS data analysis methodologies implemented in the comprehensive software package ATSAS will be introduced. Particular emphasis will be placed on SAXStant, a novel ATSAS-based artificial intelligence tool designed to assist users in extracting structural information from experimental scattering data. The application of these methods will be demonstrated through selected examples highlighting the structural characterization and conformational transitions of pharmaceutically relevant macromolecules and complexes in solution.

Dr. Nick Vukotic is an Assistant Professor and the NSERC/PROTO Industrial Research Chair in X-ray Diffraction and Crystalline Materials at the University of Windsor. He is also Director of Solid4m Inc., a spin-out company from his laboratory that develops high-throughput platforms for accelerating pharmaceutical solid-form discovery. His research bridges tool and method development with crystal engineering, inorganic chemistry, and drug release materials.

Dr. Vukotic earned his Ph.D. in Chemistry under Professor Stephen J. Loeb, focusing on supramolecular and materials chemistry, before moving into industry as Principal Scientist and Product Development Manager at PROTO Manufacturing Ltd., where he contributed to the development of next-generation X-ray diffraction instrumentation.

In 2019, he returned to academia to establish a program dedicated to creating new scientific tools and advanced crystalline materials to improve and control the release of pharmaceuticals. His work at the interface of academia and industry has resulted in patents, publications, and spin-out companies that are advancing solid-form discovery and opening new directions in drug delivery. Expanding the experimental reaction space accessible for polymorph, solvate, and cocrystal discovery remains a central challenge in pharmaceutical crystal engineering. While solution-based crystallization dominates solid form screening, thermally and mechanochemically accessed regions of solid-state chemical space are frequently overlooked due to limitations in parallel synthesis and characterization throughput.

To address this gap, we have developed a suite of Modular Multiwell Devices (MMDs) that integrate parallel solid-state synthesis with in-situ powder X-ray diffraction, enabling systematic exploration of crystallization outcomes across dozens of conditions simultaneously. By coupling high-throughput XRPD with mechanochemical transformations, melt crystallization, and reaction crystallization, the platform enables rapid identification of crystal forms that remain inaccessible through conventional workflows.

Beyond accelerating discovery, the approach generates structured, high-quality experimental datasets that directly link synthetic conditions to crystalline outcomes. Through selected case studies, we demonstrate how probing large, multidimensional reaction spaces uncovers new pharmaceutical solid forms and previously hidden crystallization pathways.

Ultimately, this work highlights how tool-driven advances in solid-state experimentation can complement computational methods, enabling a more comprehensive and data-rich foundation for the next generation of crystal engineering strategies.

After obtaining my PhD from Birmingham University (UK) I took up a post-doc position at the National Research Council Canada in Ottawa, Ontario, finally leaving after 15 years as a Senior Research Officer. Along with researching various aspects of lithium batteries and fuel cells I managed my Institute's PXRD facility, overseeing its expansion and development of custom sample environments.
After 15 years I left NRC as a Senior Research Officer to take up a position as one of two Instrument Scientists on the POWGEN time-of-flight neutron powder diffractometer at Oak Ridge National Laboratory. In 2017 I joined Excelsus to assist with structural problems such as ab initio structure solution from powder data, as well as helping push back the boundaries of analytical feasibility with SR-PXRD data

Powder diffraction is a pivotal characterization technique used during many stages during API development and even production via quality control. The use of instruments at synchrotron sources further extends the reach of powder diffraction in terms of sensitivity, capability and complexity. Examples from two different APIs will be presented to highlight some capabilities that SR-XRPD data can provide.
SR-XRPD data of a known API collected as a standard for QPA revealed a number of very weak, unexpected peaks. A crystallographic analysis showed these peaks to reveal previously unknown disparities in crystal chemistry of the bulk powder versus the single crystal structure. The minor differences between the refined parent SXD structure and distorted PXRD structure reveal how sensitive SR-PXRD is to very subtle structural changes.
The SR-XRPD data of the second API example is notable in terms of an unusual microstructural feature for such samples. The higher angular resolution achievable with synchrotron beamlines frequently reveals subtle microstructure in powder data that may not be apparent with laboratory diffraction data. The combination of SR-PXRD Rietveld refinements and computational techniques provide some insights into the source of this behaviour.

• M.S. in Materials Science and Engineering, Georgia Institute of Technology, Atlanta, USA.
• Ph.D. in Physics (Materials), ETH Zurich and Paul Scherrer Institute, Villigen, Switzerland.

 

Dr. Zhou joined Excelsus as a Scientist in 2025 and has more than six years of experience in soft matter physics and scattering techniques, with a particular focus on colloidal systems such as surfactant micelles and polymer microgels. He specializes in the structural characterization of these systems using small-angle x-ray scattering (SAXS) and small-angle neutron scattering (SANS), with expertise in data analysis and modelling.
During his doctoral studies, Dr Zhou investigated the novel swelling behaviour of polymer microgels, pioneering the first direct measurement of their peripheral counterion cloud via SANS. His postdoctoral research further expanded his expertise to the rheology of soft jammed particulate systems. At Excelsus, he contributes to SAXS/SANS services, developing experimental and modelling strategies that bridge fundamental physical insights with pharmaceutical applications.

Small-angle scattering (SAS), including small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS), is a powerful method used to study the structure of biopharmaceuticals and drug-delivery systems in solution under realistic formulation conditions. In this presentation, emphasis will be placed on how direct modelling of scattering data can be used to extract quantitative structural information from complex systems such as micelles, polymer assemblies, peptides, and nucleic-acid-based therapeutics.
For dilute systems, Guinier analysis and pair-distance distribution functions provide useful initial structural insights, while direct form-factor modelling allows parameters such as particle size and shape, core-shell dimensions, size polydispersity, aggregation number, and contrast changes related to drug loading to be obtained. A particular advantage of this approach lies in its application to concentrated systems, where structure factors can be included to account for interparticle interactions under formulation-relevant conditions.
Examples will include quantification of drug loading in micellar carriers, structural tuning via co-micellization of neutral and ionic surfactants, and modelling of oligonucleotide formulations with multiple species. The unique value of SANS contrast variation will also be highlighted, as it enables direct measurement of counterion clouds. This provides insight into ion distributions that influence drug loading and release, as well as interparticle forces, compressibility, viscosity, and injectability in concentrated particle formulations.
Overall, SAS offers a versatile and industry-relevant framework to connect nanoscale structure with formulation performance, supporting rational design, process understanding, and optimization of advanced pharmaceutical delivery systems.