Rigaku and Research Partners Discover New Crystal Form of Indomethacin, Advancing Pharmaceutical Science
Rigaku Corporation, a global leader in X-ray analytical technologies and a member of Rigaku Holdings Corporation, has announced a significant scientific breakthrough achieved through a collaborative research project with Shionogi & Co., Ltd., JEOL Ltd., and Meiji Pharmaceutical University. The team’s findings have been published in Crystal Growth & Design, one of the world’s leading international journals dedicated to crystallography and crystal engineering.
The research focuses on indomethacin, a widely prescribed nonsteroidal anti-inflammatory drug (NSAID) used for decades to treat pain, inflammation, and various musculoskeletal disorders. Despite extensive research on this pharmaceutical compound over many years, scientists have now identified a previously unknown crystal polymorph of indomethacin, referred to as the κ (kappa) form. The discovery is considered highly significant because finding a new polymorphic form of a well-studied drug is exceptionally rare.
Polymorphism is an important phenomenon in pharmaceutical science. It occurs when a single chemical compound can exist in more than one crystal structure. Although the chemical composition remains identical, the arrangement of molecules within the crystal lattice differs, resulting in variations in physical and chemical properties. These differences can influence critical pharmaceutical characteristics such as solubility, stability, dissolution rate, bioavailability, and manufacturing performance. As a result, understanding and controlling polymorphism is a key aspect of drug development and quality assurance.
The newly discovered κ-form of indomethacin provides researchers with valuable insights into the behavior of pharmaceutical crystals and opens new avenues for studying the relationship between crystal structure and drug performance. Because polymorphic forms can directly impact the effectiveness and manufacturability of medicines, the discovery contributes important knowledge that may support future pharmaceutical innovation.
A major challenge in the study was the extremely small size of the newly identified crystals. The κ-form crystals measured less than one micrometer in size, making them difficult to analyze using conventional X-ray diffraction techniques. Traditional methods typically require larger crystals to accurately determine atomic structures. Consequently, researchers needed a more advanced analytical approach to investigate the new polymorph.
To overcome this limitation, the team employed the MicroED (Micro Electron Diffraction) method using the XtaLAB Synergy-ED, a fully integrated electron diffractometer jointly developed by Rigaku and JEOL Ltd. MicroED has emerged as a powerful technique for structural determination of materials composed of ultra-small crystals that are unsuitable for conventional crystallographic analysis.
The XtaLAB Synergy-ED system enabled researchers to collect high-quality diffraction data from the tiny κ-form crystals and successfully determine their molecular and crystal structure. This achievement demonstrates the growing importance of electron diffraction technologies in modern crystallography, particularly for the analysis of challenging samples that cannot be studied through traditional methods.
The structural investigation revealed unique molecular arrangements within the newly discovered polymorph. Researchers found that specific intermolecular interactions play a crucial role in stabilizing the κ-form crystal structure. These interactions contribute to the overall stability of the polymorph and provide valuable information regarding the forces that govern crystal formation and transformation.
Understanding such molecular interactions is essential for pharmaceutical scientists because crystal stability directly influences drug shelf life, storage conditions, manufacturing consistency, and therapeutic performance. Insights gained from the κ-form may therefore contribute to broader efforts aimed at improving pharmaceutical formulation and production processes.
Beyond the discovery itself, the study highlights the potential of MicroED technology as a transformative tool in pharmaceutical research. The successful identification and characterization of a previously undetectable polymorph demonstrate that advanced electron diffraction techniques can reveal structural information that might otherwise remain hidden. This capability is particularly valuable in drug development, where the identification of all possible crystal forms is critical for ensuring product quality and regulatory compliance.
Researchers believe that the application of MicroED could significantly accelerate the discovery and characterization of new pharmaceutical polymorphs in the future. By enabling scientists to analyze crystals at previously inaccessible scales, the technology has the potential to improve drug development workflows, reduce research timelines, and support the creation of safer and more effective medicines.
The collaborative nature of the project was also a key factor in its success. The research brought together expertise from multiple organizations, combining strengths in pharmaceutical science, crystallography, advanced instrumentation, and academic research. Shionogi & Co., Ltd. contributed its extensive experience in pharmaceutical research and development, while JEOL Ltd. provided expertise in electron microscopy and analytical instrumentation. Meiji Pharmaceutical University offered academic and scientific support, and Rigaku contributed its advanced crystallographic technologies and analytical capabilities.
The findings were published under the title “Discovery of a New Polymorph, κ-Form of Indomethacin” in Crystal Growth & Design. Publication in such a prestigious journal underscores the scientific significance of the work and its potential impact on both crystallography and pharmaceutical sciences.
The discovery further reinforces Rigaku’s long-standing commitment to advancing scientific research through innovative analytical technologies. Since its establishment in 1951, the Rigaku Group has focused on developing cutting-edge solutions in X-ray and thermal analysis. Over the decades, the company has become a trusted partner for industries, research institutions, and academic organizations around the world.
Today, Rigaku operates in 136 countries and regions and employs approximately 2,000 people across nine global offices. The company serves a wide range of industries, including semiconductors, electronic materials, batteries, environmental science, energy, natural resources, and life sciences. Approximately 70 percent of its sales are generated outside Japan, reflecting its strong international presence and influence in the scientific instrumentation market.
Rigaku’s mission, summarized by its corporate motto, “To Improve Our World by Powering New Perspectives,” emphasizes the role of advanced analytical technologies in driving scientific discovery and technological innovation. The successful identification of the κ-form of indomethacin exemplifies this mission by demonstrating how next-generation analytical tools can reveal previously unknown aspects of well-established compounds.
As pharmaceutical research continues to evolve, discoveries such as this one highlight the importance of interdisciplinary collaboration and advanced analytical methods. The identification of a new polymorph in a drug that has been studied for decades serves as a reminder that scientific exploration still holds the potential for unexpected breakthroughs. Furthermore, it illustrates how innovative technologies like MicroED can expand the boundaries of knowledge and contribute to the development of higher-quality pharmaceuticals.
The discovery of the κ-form of indomethacin not only enriches the scientific understanding of crystal polymorphism but also paves the way for future advancements in drug research, quality control, and pharmaceutical manufacturing. As researchers continue to investigate the properties and applications of this newly identified crystal form, the findings are expected to inspire further studies and support ongoing innovation across the pharmaceutical industry.
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