Ruba Alajlouni brings 10 years of experience in pharmaceutical development, with a background that spans regulatory compliance, solid-state chemistry, and bioanalytics. She began her scientific career working in protein purification and molecular biology during graduate studies at Virginia Tech, later expanding into drug discovery and quality control at Purdue, where she focused on cell culture screening, HPLC, and Raman-based drug monitoring. After earning a second MS degree from Stephen Byrn's lab in 2015, she began consulting independently, applying chemometrics and spectroscopy to solve client-specific analytical challenges. Around the same time, she joined SSCI, where she served as a research scientist and project manager, leading analytical and stability studies and overseeing data integrity for major clients. Since 2021, she has continued her consulting work through her role at Improved Pharma, supporting research and development efforts related to formulation, polymorph screening, and advanced diffraction-based analysis. Her cross-disciplinary training and technical versatility support collaborations that span both academic and industry settings. X-ray diffraction analysis (XRD) is a standard tool for screening and quantifying components in pharmaceutical powders, though it has limitations-particularly for mixtures where sample homogeneity is critical. In this study, we demonstrate that synchrotron XRD (SXRD) can be used effectively to address the risk of sub-sampling errors in large sample volumes. Binary mixtures of caffeine (Caff) in acetaminophen (APAP) were prepared at 0.84%, 5%, and 10% concentrations using geometric mixing and the "coning and quartering" technique. Sub-samples were analyzed using SXRD with both point and area detectors. Multiple spots on each capillary were scanned to generate individual diffraction patterns, which were processed and used to build calibration curves based on the corrected height of the main Caff peak (11.97° 2θ).
SXRD detected caffeine in all tested spots, including the lowest concentration (0.84%), which was undetectable using a conventional laboratory instrument (LXRD). Calibration curves from SXRD data showed strong linearity (R² = 0.96-0.99), confirming sensitivity and reproducibility across detector types. Averaging patterns from multiple spots reduced intra-sample variability, enabling reliable analysis from a single sub-sample. In contrast, LXRD showed variable peak intensities and limited detection at low concentrations.
These findings support SXRD as a powerful tool for analyzing pharmaceutical mixtures, especially when appropriate sample preparation and sub-sample strategies are used. Detector selection should be guided by sample type and analytical goals.

Haley is a Product Engineering Manager at Varda Space Industries where she develops terrestrial and microgravity pharmaceutical crystallization experiments. Haley served as the pharma lead for Varda's first mission during which Varda's microgravity platform successfully executed the crystallization of ritonavir's metastable polymorph, then autonomously returned the crystalline API to Earth. Additionally, Haley has led experimental studies and hardware development projects for Varda's hypergravity platform in which molecules can be screened for gravitational sensitivity prior to launch. Prior to her role at Varda, Haley received her Ph.D. in Applied Physics from Caltech where she designed and fabricated nanophotonic structures for scalable photovoltaics and solar fuels. Haley received her B.S. in Physics from William & Mary. Early proof-of-concept demonstrations conducted on parabolic flights and on extended microgravity platforms such as the International Space Station (ISS) have demonstrated the potential benefits of in-space microgravity crystallization for better understanding polymorphism and for supporting path-finding routes towards novel formulations. However, due to the extensive planning duration, limited resources, and high cost associated with human spaceflight, the benefits of microgravity crystallization have remained inaccessible and ineffective in addressing unmet pharmaceutical needs on Earth. Varda's autonomous platform for in-orbit crystallization enables high-cadence access to microgravity for the pharmaceutical industry to address crystallization challenges and enable novel formulations.
As a case study, we present the results of Varda's first mission in which ritonavir's metastable Form III was crystallized from its melt. After ritonavir was successfully returned to Earth, extensive physical and chemical stability characterization was performed to ensure the experiment was successful, and that in-orbit radiation and reentry conditions did not affect the crystallized API. XRPD was a critical technique is determining the polymorphism of the crystallized materials and controls, as well as tracking presence of amorphous material via reentry forces. Analysis indicated that all crystallized ritonavir was metastable Form III, and all control vials match that of their prepared form. By demonstrating the feasibility of autonomous reentry working outside of the bounds of the ISS while ensuring drug retrievability, this work shows a path towards in-space processing of pharmaceuticals that enables the development of novel drug products for use on Earth.

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 medal for research in 2012. Synchrotron x-ray diffraction experiments represent a powerful tool for investigating the structure of molecular liquids, glasses and amorphous materials, through the extraction of the Pair Distribution Function (PDF). The x-ray PDF gives an average structure of the entire system that is heavily weighted towards the heavier atoms. 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 nifedipine and felodipine. Both are calcium channel blockers used to treat hypertension, but felodipine is considered to be more effective. Also, nifedipine crystallizes more readily than felodipine, even when it is incorporated into PVP. Understanding the structure of amorphous felodipine is important because it is a chiral drug and the toxicity and adverse reactions of its enantiomers vary. Our x-ray models are used to investigate the liquid and amorphous structures, and the crystallization mechanisms in PVP mixtures. The results are used to assess the degree of hydrogen bonding in both systems, and the recent claim that ethoxy rotamers occur in amorphous felodipine which are forbidden in the crystalline form.

Andrew H. Bond has 35 years of experience in chemistry, crystallography, synchrotron X-ray science, powder diffraction, radiopharmaceuticals, and technology commercialization. Andrew trained as a structural chemist (with the Founding Editor of Crystal Growth & Design) and fully embraces an interdisciplinary approach by regularly working with biochemists, structural biologists, pharmaceutical scientists, crystallographers, beamline physicists, engineers, and business leaders. Andrew has authored 75 publications/reviews/proceedings, an American Chemical Society Symposium Series Book, and 161 presentations at scientific conferences. Since 2018, nine national user facility proposals at Argonne's Advanced Photon Source, the Stanford Synchrotron Radiation Lightsource, and the Cornell High Energy Synchrotron Source have provided regular beamtime access for macromolecular crystallography and high throughput powder diffraction studies of pharmaceuticals. Andrew is an inventor on 68 patents in 27 countries, which include a US FDA approved radiopharmaceutical and improved protein and pharmaceutical crystallization technologies. As part of an educational program for examiners from the US Patent and Trademark Office, Andrew was invited to lecture on innovative technologies for achieving consistent crystallization and polymorph controls for pharmaceutical composition of matter patents. Andrew has also served as a reviewer/co-chair/chair for 13 scientific review panels for the National Institutes of Health tasked with assessing the technical merit and potential impact for over $700M in small business and academic research grants across diverse panels including bioanalytical chemistry, emergency awards for SARS-CoV-2, the cardiovascular/hematological sciences, and harnessing artificial intelligence to discover pharmacotherapeutics for substance use disorders. The needs for solid form screening of active pharmaceutical ingredients (APIs) to characterize polymorphs, hydrates, solvates, salts, cocrystals, etc., are established and include scientific (e.g., structure, solubility, dissolution rate, stability, etc.) and business (e.g., patent rights, product lifecycle management, competitive controls, etc.) rationales. A significant analytical challenge in developing new high throughput API solid form screening approaches is the need to detect minor constituent solid form variant phases in macroquantities of crystalline matrix. Fortunately, synchrotron powder X-ray diffraction (sPXRD) can address this challenge using high brilliance sources coupled with area detectors having exceptional signal to noise (S/N) ratios. A remaining challenge, and a focus of our current work, is that the ability to "measure" many specimens by sPXRD must have a commensurate ability to reproducibly "make" specimens in order to efficiently generate actionable data for stakeholders. The chemical and crystallographic aspects involved in the development of a high throughput workflow for "reproducibly making and measuring" specimens for API solid form screening will be presented. Based on studies of 4000 API specimens, just 600 mg of API is required for a pharmaceutically relevant solid form screen of 96 conditions, for which specimen preparation and sPXRD (and Raman) data collection can be routinely completed in 4 h (or 1.5 h via Pilatus/Eiger). Near real time new phase "hit" identification has been demonstrated and the data are amenable to powder diffraction search match, semiquantitation without known structure, and unit cell indexing for well behaved specimens.

I'm the Group Leader of the Structural Science Group which operates five beamlines at the Advanced Photon Source at Argonne National Laboratory: 11-BM, 11-ID-B, 11-ID-C, 11-ID-D and 17-BM - state-of-the-art synchrotron x-ray scattering instruments, providing insights into atomic arrangements of materials over a wide length-scale with the emphasis on in situ and operando measurements.

My main interests and research activities pertain to multi-probe structural characterization of materials relevant to energy and environmental stewardship using operando/in situ high-energy x-ray scattering and spectroscopy methodologies, i.e. pair distribution function (PDF) analyses, powder x-ray diffraction, small angle x-ray scattering and x-ray absorption spectroscopy. The Structural Science Group (SRS) at the Advanced Photon Source (APS) provides a comprehensive suite of capabilities for total X-ray scattering and Pair Distribution Function (PDF) analysis, enabling in-depth investigation of short- and intermediate-range order in complex materials. This talk will highlight the unique strengths of the SRS beamlines —including 11-ID-B, 11-ID-C, and 11-ID-D — in delivering high-quality structural data across a wide range of scientific applications.

We will discuss recent and future developments and upgrades to beamlines' instrumentation and infrastructure, including the integration of advanced detector technologies, expanded Q-range access, and sample environments enabling in situ and operando studies under real-world conditions. Emphasis will be placed on the transition to EPICS-based controls, streamlined data collection workflows, and ongoing efforts to support automated high-throughput experimentation. Case studies will illustrate how PDF analysis at the APS is unlocking insights into nanoscale structure, amorphous phase behavior, and functional performance in technologically relevant materials. This presentation will also outline future directions for total scattering at the APS, particularly considering the APS-U upgrade and newly constructed beamline 11-ID-D.

Matteo has a strong background in the solid state characterization of pharmaceutical and inorganic materials with expert understanding of the implications connected to the process of solid state profile determination in the pharmaceutical industry. His major responsibilities focus on crystalline structure elucidation, API form/version selection, drug developability, x-rays diffraction and scattering, thermal analysis, spectroscopy, regulatory compliance and data integrity.
His career started with working experiences in various European organisations (ESRF, ISIS at the RAL, University of Wroclaw, University of Verona) prior to joining GlaxoSmithKline in 2006 at its Verona R&D site in Italy. He was eLNB product owner and System Support specialist before moving to the CMC area. In 2012 he became team coordinator, technical and project leader in the physical properties space (XRPD, TGA, DSC, Raman, FT-IR, Optical Microscopy, ESEM, Particle size, GVS, Solid State profile determination), in the solid state one (Polymorph and Salt Screening, Crystallization Development) and in drug developability aspects (preformulation and early formulation) for Aptuit / Evotec. In 2018 he took the full responsibility as a Manager of the Physical Properties & Preformulation Unit at Aptuit, an Evotec Company, in Verona (Italy), becoming later the Material Science Scientific Leader, supporting the Pharmaceutical Development Business Line in delivering outstanding scientific output for projects and customer satisfaction, playing a transversal role for ensuring continued matrix support to the company.
From October 2024, He is covering the Chief Scientific and Innovation Officer role for PolyCrystalline, to support the company in outstanding service delivery in the Material Science space. Active Pharmaceutical Ingredients (API) shows the tendency to get order and crystallize as solids in different structures (forms). This phenomenon is known as polymorphism and this characteristic is under the spot light of pharma regulatory authorities and drug developer due to its crucial implications in the final drug product performances (safety and efficacy) with ethic, therapeutics, IP, commercial and economic implications.
A number of historical and real industrial examples are presented in order to show how the X-Rays Powder Diffraction (XRPD) is an essential technique for the determination and quantification of polymorphic (or pseudo-polymorphic) forms in a given API to effectively support the form selection process for Drug Product Development, coupled with orthogonal techniques.
We will underline the increasing needs to open the standard industrial approach to techniques with higher resolution (like synchrotron XRPD) with the objective to create new culture in the industry giving answers to challenging questions.

Fabia Gozzo has more than 30 years of practical experience with synchrotron facilities specializing in the development of complex instrumentation and its applications in the study of pharmaceuticals, pigments, food components, concrete and semiconductors. At the Advanced Light Source synchrotron facility within the Lawrence Berkeley National Labs, as an Intel Corporation scientist, Fabia played a pivotal role in the construction, commissioning and advancement of the first photoemission spectromicroscope exclusively dedicated to industrial investigations of new-generation microcircuits. At the Paul Scherrer Institute, as beamline scientist, she significantly contributed to the construction, commissioning and growth of the Swiss Light Source synchrotron facility where she has developed for more than 10 years a state-of-the-art powder diffractometer, acknowledged in several scientific publications as one of the best ones in the world. In 2012, she founded Excelsus Structural Solutions, a spin-off company of the PSI that offers analytical services based on synchrotron radiation to the pharma and chemical industry. Since 2016, Excelsus integrated the Switzerland Innovation Network and since 2022 it is a WECONNECT INTERNATIONAL WomenOwned Certified Company. Recognized as a synchrotron and powder diffraction expert, Fabia is regularly invited internationally as a speaker, lecturer, and scientific advisor. She has authored and co-authored over 90 scientific articles and book chapters, contributing significantly to the advancement of knowledge in her field.

An introduction to synchrotron radiation and the power of synchrotron X-Ray Powder Diffraction (XRPD) will be given with the purpose of allowing all participants to get the necessary background and appreciate the workshop topics. An overview of XRPD technique, geometry of measurements, detectors will be given together with latest advances in Level of Detection and Level of Quantification.

Jason A. Leonard, Partner at McDermott, Will & Emery, LLP in New York.

Jason is a trial lawyer who focuses on complex life sciences patent litigation. During his eighteen years of practice, he has counseled numerous pharmaceutical companies in developing effective patent litigation strategies for a wide array of pharmaceutical products. Jason has successfully defended patents covering new chemical compounds, as well as complex inventions covering formulations, polymorphs, and methods of treatment. Clients frequently rely on him to address difficult infringement issues, particularly when design-around defenses have been asserted.

Prior to attending law school, Jason spent six years as a pharmaceutical scientist at Pfizer. During that time, he focused on solid-state screening and characterization of solid forms of drug candidates. As part of his research, he became involved in patents as an inventor on numerous patents. Of note are his several patents covering solid forms of atorvastatin (marketed by Pfizer as Lipitor®). This exposure to the patenting process led to Jason attending law school, and ultimately, to him representing innovator pharmaceutical companies in complex patent litigation.

Jason holds a Bachelor of Science degree in chemistry from The University of Connecticut and a Juris Doctor from The University of New Hampshire. Jason is admitted to both the New York and New Jersey bars, as well as the Southern District of New York, Eastern District of New York, the District of New Jersey, the Court of Appeals for the Federal Circuit, and the United States Supreme Court. This presentation will explore a recent court decision involving the patentability of crystalline polymorphs in the United States. Under U.S. patent law, crystalline polymorphs generally have been found patentable due to the unpredictability in discovering or predicting them. However, a recent court decision found a crystalline polymorph obvious. In this presentation, we will review the history of patent law in this area and then explore three recent court decisions—Grunenthal GMBH v. Alkem Laboratories Ltd., Pharmacyclics LLC v. Alvogen, Inc., and Salix Pharmaceuticals, Ltd. v. Norwich Pharmaceuticals Inc.—relating to the patentability of crystalline polymorphs, including the most recent decision invalidating a polymorph patent as obvious.

Scott F. Peachman is Of Counsel in the Litigation practice of Paul Hastings and is based in the firm's New York office. His practice focuses on complex, high-stakes litigation with an emphasis on patent litigation in the fields of chemistry, pharmaceuticals, and biotechnology before U.S. district courts, the Federal Circuit, and the Patent Trial and Appeal Board. He has over twelve years of experience in the life sciences space, including extensive experience representing innovator pharmaceutical companies in Hatch-Waxman litigations, and companies in biologics litigation.

He has helped leading innovator pharmaceutical clients enforce patent portfolios for breakthrough drug products such as Uloric®, Emend® IV, Gocovri®, Nuplazid®, and Venclexta®. Mr. Peachman also routinely counsels clients in pre-suit investigations, patent portfolio management, patenting strategy, and patent matters related to product-based asset acquisitions and licensing.

Mr. Peachman has experience in all phases of large-scale litigations, from presuit investigation to trial and appeal. He is sought out for technical subject matter expertise in the context of invalidity and validity contentions, expert reports, depositions, and trial preparation. Mr. Peachman has represented clients in a wide variety of matters involving, for example, medical devices, biosensors, diagnostics, genomic sequencing, polymorphs, polymer chemistry, medicinal chemistry, lubricating oil compositions, pharmaceutical formulations, neurodegenerative diseases, and oncology.

Mr. Peachman also has an active pro bono practice focused on the representation of prospective patentees, artists, and creators, which he has helped to direct and refine over several years. This subtopic will discuss the benefits of using synchrotron-XRPD to demonstrate patent infringement in view of anticipated legal challenges. While synchrotron-XRPD provides enhanced resolution to discriminate between different crystal forms, its applicability to show patent infringement is not always straightforward. Patent challengers may question the use of synchrotron-XRPD in patent cases based on, for instance, the language of the patent claims at issue and certain descriptions within the patent specification. The value of synchrotron-XRPD must also be weighed against other analytical methods that have been used to characterize crystal forms. This subtopic will provide examples from the relevant case law as well as general strategies for those considering the use of synchrotron-XRPD to show polymorph patent infringement.

Shiva Sekharan, Senior Director of Formulations Business Development and CSP Software at Schrödinger, Inc. joined Schrödinger in 2023. He is responsible for driving the business development efforts in the formulations space - act as client advocates to ensure client needs are understood and satisfied and improve the overall customer experience, work with internal departments to outline procedures and best practices to meet growth objectives. Shiva earned his Ph.D. in Theoretical Chemistry from the University of Duisburg-Essen in Germany followed by postdoctoral stints at the Max-Planck Institute for Polymer Science, Emory University, Fukui Institute for Fundamental Chemistry and Yale University. Shiva is an accomplished computational chemist and has published extensively in the areas of quantum chemistry, structure and function of GPCRs and solid-state NMR spectroscopy. Early assessment of crystal polymorphism and thermodynamic solubility continues to be elusive for drug discovery and development despite its critical importance, especially for the ever-increasing fraction of poorly soluble drug candidates. We have developed a crystal structure prediction (CSP) method that combines a novel systematic crystal packing search algorithm and a hierarchical energy ranking protocol to predict crystal polymorphs. This is complemented by a free energy perturbation (FEP+) approach for computing thermodynamic aqueous solubility. The high accuracy, reliability, and efficiency of our CSP and FEP+ methods with large scale validations is designed to support polymorph screening and solubility prediction in drug substance and drug product development processes. Schrödinger's modelling capabilities can support the understanding of the local structure of poorly crystalline or amorphous compounds by providing a starting model for pair distribution function (PDF) refinements and contribute to the interpretation of the local structure.

Ganesh Sivaraman is an Assistant Professor in the Department of Materials Design and Innovation (MDI) at the State University of New York at Buffalo. He leads a research group focused on advancing computational methodologies for atomistic modeling in chemistry and materials science through machine learning, aiming to transform molecular design and personalized medicine.

Prior to his current role, Dr. Sivaraman served as an Assistant Computational Scientist in the Data Science and Learning Division and held a postdoctoral appointment at the Argonne Leadership Computing Facility at Argonne National Laboratory (ANL). His research interests lie at the intersection of applied machine learning, computational science, and high-performance computing, with the goal of accelerating material characterization and modeling.

Since his tenure at ANL, Dr. Sivaraman has actively collaborated with Dr. Chris Benmore to develop advanced computational techniques for validating high-energy X-ray diffraction experiments. Advancements in machine learning are transforming molecular modeling, particularly in predicting enantioselectivity and capturing long-range interactions. This talk will present two complementary computational approaches.

In the first part, I will introduce EquiCAT, an equivariant graph neural network (EGNN) developed to predict enantioselectivity in asymmetric catalysis—a longstanding challenge in synthetic chemistry with broad applications in pharmaceuticals and materials science. By integrating conformer-specific data of reactants and catalysts through higher-order message passing and multi-head attention mechanisms, EquiCAT achieves state-of-the-art performance on benchmark datasets, enhancing both data efficiency and predictive accuracy.

The second part will address the limitations of traditional machine learning interatomic potentials (MLIPs) in modeling long-range interactions. I will present a Fourier space attention mechanism that explicitly incorporates long-range interactions into MLIPs, enabling accurate simulations of systems where such effects are critical, such as weakly interactions.

Together, these methodologies highlight the power of combining symmetry-aware architectures and spectral methods to advance the predictive capabilities of machine learning in molecular science.

Pam Smith has over 25 years of experience with pharmaceutical research and development, focused on solid-state chemistry. She originally joined SSCI as an expert in IR and Raman microspectroscopy and expanded her skillset to include IR, Raman and XRPD method development. During her tenure at SSCI, she became an ISSSP certified LSS Black Belt and ultimately assumed operational appointments including the General Manager of SSCI and the Vice President of Global Analytical Services for AMRI, the parent company of SSCI. In 2018, she joined Improved Pharma, a research, consulting, and information company dedicated to improving pharmaceutical methods, formulations, and processes. Her initial research focus was the application of synchrotron XRPD and PDF on the study of amorphous dispersions. Much of her work also involves using synchrotron XRPD and Raman microscopy mapping for patent support. Most recently, her research focus has been on crystallization experiments in microgravity. In 2022 she became part owner of the company, which was founded by Steve and Sarah (Sally) Byrn. XRPD is considered to be the gold standard for differentiating polymorphs from one another, but a number of other analytical techniques are equally as valuable. Thermal methods such as DSC provide information on the enthalpy change of various solid-state processes. Thermal microscopy provides further details such as phase transformations, change in crystallinity, desolvation events, and decomposition. For hydrates and solvates, TG is another useful thermal technique for characterization. Spectroscopic methods such as IR, Raman, and solid-state NMR also can also differentiate one polymorph from another. IR is especially good at detecting changes in H-bonding (hydrates and solvates) and salt formation. Spectroscopic methods can also confirm that the chemical identify of the material hasn't changed. DVS, which provides a measure of hygroscopicity, is another useful characterization tool. Together, these techniques provide a full picture of the different polymorphs of a given molecule and how they are related to each other.

Raj Suryanarayanan (Sury) is Professor and William and Mildred Peters Endowed Chair in the College of Pharmacy, University of Minnesota. He obtained his pharmacy degree from the Indian Institute of Technology in Varanasi, India and Ph.D. in Pharmaceutics from the University of British Columbia, Vancouver, Canada. The overall goal of his research is to apply principles of pharmaceutical materials science to the design of robust pharmaceutical dosage forms with reproducible and predictable properties. His research group has developed low temperature powder X-ray diffractometric techniques to study frozen and freeze-dried pharmaceutical systems. He was a member of the USP Expert Committee (Excipients test methods). He is a fellow of the American Association of Pharmaceutical Scientists (AAPS) and is a past chair of the Teachers of Pharmaceutics Section of the American Association of Colleges of Pharmacy. Sury is a member of the Academy of Distinguished Teachers at the University of Minnesota. He the recipient of the Outstanding Educator Award and the David Grant Research Achievement Award in Physical Pharmacy, both from AAPS, the PhRMA Foundation Award and the Michael Pikal Distinguished Scholar Award from The National Institute of Pharmaceutical Technology and Education. Until recently, he was an Associate Editor of Molecular Pharmaceutics.

While X-ray powder diffractometry (XRD) is a powerful technique for characterizing crystalline phases, the sensitivity of the laboratory instruments can be a serious limitation. The use of synchrotron radiation has substantially enhanced its utility and synchrotron XRD (SXRD) has emerged as a powerful tool for analyzing pharmaceutical materials. The applications of SXRD in both drug substance and drug product characterization will be demonstrated through numerous case studies. The applications are categorized into three areas: 1) Detection, characterization and quantification of physical forms of the raw material (drug or excipient). 2) Similar investigations in complex and multicomponent drug products. 3) Characterization and quantification of phase transformations during processing and storage. Thus, SXRD based studies have assisted pharmaceutical development by enhancing the understanding of mechanisms and kinetics of phase transformations during various pharmaceutical unit operations including crystallization and freeze drying. Subtle and nuanced information has been obtained during drug product dissolution and long-term stability studies.

Brian is a Senior Scientist at Argonne's Advanced Photon Source, but has also taught at the University of Pennsylvania and worked at NIST, Air Products and Chemicals and Union Carbide Corp and has had job titles as a chemist, physicist and computational scientist. These days most of his time is spent on the GSAS-II diffraction data analysis package, but he previously oversaw the creation of the U.S.'s leading powder diffraction instrument, 11-BM, and before that the care and feeding of the BT-1 neutron powder diffractometer. His Ph.D. is from Caltech and B.A. from Rutgers. He has served as President of the American Crystallographic Association and chair of the U.S. National Committee for Crystallography and has received the Trueblood Award, the Charles S. Barrett Award, and a Bronze Medal from the U.S. Department of Commerce. The GSAS-II package is a modern, comprehensive and extensible package for analysis of all types of diffraction data on multiple scales: crystallography (including 3+1 superspace modulated structures), small-angle scattering and reflectometry; with single-crystal or powder diffraction measurements; with x-rays or neutron probes, where the latter may be constant-wavelength or time-of-flight. For crystallographic analysis, structural models can be fit to many datasets of any type in combination. GSAS-II also provides a novel capability fit to a parametric series of datasets. GSAS-II can be run on Windows, Linux and Mac computers with Intel-compatible processors. All GSAS-II functionality can be accessed from a graphic user interface; most functionality can be accessed via a Python-based applications interface.

While many aspects of crystallography can be done well with some of the many other crystallographic packages, GSAS-II excels for more complex types of analyses, particularly with powder diffraction, or specialized single-crystal measurements (or the two in combination). This talk will focus on areas where GSAS-II has unique features relevant to the workshop audience.

Stephen Wilke is a Senior R&D Scientist at Materials Development, Inc., in Evanston, Illinois, and a Visiting Scientist at the Advanced Photon Source at Argonne National Laboratory. His research focuses on the use of containerless processing, or levitation, to study the structure and properties of liquids and amorphous solids. These investigations include X-ray and neutron scattering techniques, atomic structure modeling, and thermophysical property measurements in microgravity. Stephen holds a B.S. in Chemical Engineering from the California Institute of Technology and a Ph.D. in Materials Science and Engineering from Northwestern University. Alternative formulations such as amorphous solid dispersions (ASDs) provide necessary routes to improving the bioavailability of poorly water-soluble pharmaceuticals. Amorphous forms lack the long-range atomic order that is characteristic of crystalline polymorphs, making it challenging to characterize and describe their molecular structures. Yet, understanding structure is crucial to the development of ASDs that can reliably resist crystallization during storage, which otherwise can hinder their commercialization. High-energy X-ray diffraction and the associated pair distribution function can enable comparisons of molecular arrangements for different compositions, processing methods, or storage conditions. To obtain information on specific bonding interactions, structural simulation is necessary. Empirical potential structure refinement (EPSR) is one simulation tool that is particularly well suited to the study of amorphous pharmaceuticals. In EPSR, predefined molecules and interatomic potentials are refined by using diffraction data as constraints, yielding models that can quantify specific molecular interactions such as hydrogen bonding and bond angle rotations. This presentation provides an X-ray/EPSR case study on ASD binaries of ketoprofen and poly(vinylpyrrolidone) to explore the relative contributions of hydrogen bonding and steric hindrance to these ASDs' stability against crystallization. Importantly, the influence of input parameters like molecule flexibility and tacticity are assessed to determine the uncertainty and limitations of EPSR modeling for amorphous pharmaceuticals.