Rapid Structure Determination of Ranitidine Hydrochloride API in Two Crystal Forms Using Microcrystal Electron Diffraction

• Published in: Chemical & pharmaceutical bulletin Vol. 72; no. 5; pp. 471 - 474
• Main Authors: Yokoo, Hidetomo, Aoyama, Yoshitaka, Matsumoto, Takashi, Yamamoto, Eiichi, Uchiyama, Nahoko, Demizu, Yosuke
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 2024; Japan Science and Technology Agency
• Subjects: Active control; active pharmaceutical ingredient; crystal polymorphism; Crystallization; Crystallography; Crystals; Drug development; Electron diffraction; Electrons; microcrystal electron diffraction; Microcrystals; Molecular Structure; Quality control; Ranitidine; Ranitidine - chemistry; Ranitidine hydrochloride; Single crystals; Structural analysis; X-ray diffraction; crystal polymorphism; microcrystal electron diffraction; active pharmaceutical ingredient; ranitidine hydrochloride
• ISSN: 0009-2363; 1347-5223; 1347-5223
• DOI: 10.1248/cpb.c23-00745

The solid-state properties of drug candidates play a crucial role in their selection. Quality control of active pharmaceutical ingredients (APIs) based on their structural information involves ensuring a consistent crystal form and controlling water and residual solvent contents. However, traditional crystallographic techniques have limitations and require high-quality single crystals for structural analysis. Microcrystal electron diffraction (microED) overcomes these challenges by analyzing difficult-to-crystallize or small-quantity samples, making it valuable for efficient drug development. In this study, microED analysis was able to rapidly determine the configuration of two crystal forms (Forms 1, 2) of the API ranitidine hydrochloride. The structures obtained with microED are consistent with previous structures determined by X-ray diffraction, indicating microED is a useful tool for rapidly analyzing molecular structures in drug development and materials science research.