Article
Medicine, Research & Experimental
Yuriy A. Abramov, Luca Iuzzolino, Yingdi Jin, Gregory York, Chien-Hung Chen, C. Scott Shultz, Zhuocen Yang, Chao Chang, Baimei Shi, Tian Zhou, Chandler Greenwell, Sivakumar Sekharan, Alfred Y. Lee
Summary: Crystal structure prediction is an important tool in the pharmaceutical industry for predicting different solid forms of active pharmaceutical ingredients. Using a CSP-based cocrystal prediction method, we ranked potential cocrystal coformers for an antiviral drug and a process intermediate. The predictions were successful and resulted in the discovery of improved solid forms for synthesis.
MOLECULAR PHARMACEUTICS
(2023)
Review
Chemistry, Multidisciplinary
Raha Kaviani, Abolghasem Jouyban, Ali Shayanfar
Summary: This review outlines the crucial importance of pharmaceutical cocrystals in chiral resolution techniques of racemic compounds, discussing different cocrystallization methods.
Article
Chemistry, Multidisciplinary
Harsh S. Shah, Yuan Jiuchuang, Xie Tian, Yang Zhuocen, Chang Chao, Chandler Greenwell, Zeng Qun, Sun GuangXu, Brandon N. Read, Timothy S. Wilson, Henry U. Valle, Shanming Kuang, Wang Jian, Sivakumar Sekharan, Jessica F. Bruhn
Summary: Establishing the absolute configuration of chiral active pharmaceutical ingredients (APIs) is important. A method using microcrystal electron diffraction (MicroED) was developed to determine absolute configuration without the need for large crystals. This streamlined method involves virtual screening, experimental cocrystal screening, and structure determination by MicroED. It was successfully applied to analyze two chiral API molecules where single crystal X-ray diffraction was not used.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Pharmacology & Pharmacy
Artem O. Surov, Ksenia V. Drozd, Anna G. Ramazanova, Andrei V. Churakov, Anna V. Vologzhanina, Elizaveta S. Kulikova, German L. Perlovich
Summary: Polymorphism is a common phenomenon in molecular crystals and has a significant impact on drug development. This study obtained and characterized a new polymorphic form of the drug carbamazepine (CBZ) cocrystal with methylparaben (MePRB), as well as a channel-like cocrystal with highly disordered coformer molecules, using various analytical methods. The structural analysis revealed a close resemblance between the novel form II and previously reported form I of the [CBZ + MePRB] cocrystal. The discovered form II showed superior thermodynamic stability and dissolution performance, making it a more promising solid form for pharmaceutical development.
Article
Chemistry, Multidisciplinary
Jingchen Sui, Na Wang, Jingkang Wang, Xin Li, Jinyue Yang, Yue Liu, Yihan Zhao, Xin Huang, Ting Wang, Lina Zhou, Hongxun Hao
Summary: A series of 1:1 cocrystals and salts consisting of chiral valines and tartaric acid derivatives were synthesized to study the thermodynamics and molecular self-assembly mechanism of diastereomeric salt/cocrystal-induced chiral separation. The study found that the diastereomeric salts between different chiral molecules and the affinity and solvation free energy play important roles in molecular preferences.
CRYSTAL GROWTH & DESIGN
(2022)
Article
Chemistry, Multidisciplinary
Lohith Kotte, Vinusha Pendota, Bojja Sreedhar, Jagadeesh Babu Nanubolu
Summary: The design and development of multicomponent systems in the salt-cocrystal continuum zone offer opportunities for selecting the right crystal form with desirable properties. A new multicomponent system between famciclovir and fumaric acid was investigated, resulting in the identification of three crystalline forms. The crystal structure analysis provided important insights into the ionization state of the complexes.
Article
Chemistry, Multidisciplinary
Shea Sanvordenker, Siddharth Borsadia, Steve Morris, Nair Rodriguez-Hornedo, Max Shtein
Summary: This study reports a novel process for the sublimation, transportation, and high-velocity directed deposition of pharmaceutical cocrystals, resulting in the formation of nano- and microscopic cocrystals. This touch-free, nonmechanical, single-step method enables particle size reduction and surface coating of cocrystals.
CRYSTAL GROWTH & DESIGN
(2022)
Article
Engineering, Chemical
Hung Lin Lee, Ying Lun Hung, Ahmed Amin, Dhanang Edy Pratama, Tu Lee
Summary: As diastereomeric salt formation is the most popular method for the industrial preparation of single enantiomers, this study investigates the chiral resolution of ibuprofen (IBU) through this method. The study optimizes each step of the chiral resolution process and scales it up to a 0.5 L scale. Practical guidelines for future development of chiral resolution processes by diastereomeric salt formation are also suggested.
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
(2023)
Article
Engineering, Chemical
Hong Yue, Jingtao Wang
Summary: This study established a flavonoid cocrystal database and successfully screened flavonoid cocrystal coformers using machine learning models and three screening methods. The results demonstrated the close relationship between the formation of flavonoid cocrystals and molecular descriptors such as phenolic groups and nitrogen atoms.
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Indumathi Sathisaran, Sameer Vishvanath Dalvi
Summary: The study describes the synthesis of new eutectic and cocrystal of Nevirapine with enhanced dissolution, demonstrating potential applications in biopharmaceuticals.
CRYSTAL GROWTH & DESIGN
(2021)
Article
Pharmacology & Pharmacy
Zeen Yang, Yinghong Yang, Mengyuan Xia, Wenjuan Dai, Bingqing Zhu, Xuefeng Mei
Summary: This study aimed to improve the solubility and bioavailability of abiraterone acetate (ABA). Various salts and cocrystals of ABA were successfully synthesized, with ABA-TAA cocrystal showing significant enhancements in solubility and intrinsic dissolution rates. Gelation was unexpectedly observed in ABA-MA salt and ABA-SAC salt in pH 2.0 buffer solution.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Chemistry, Applied
C. Scott Shultz, Luca Iuzzolino, Lorenzo Codan, Justin A. Newman, Michael T. Pirnot, Melissa Tan
Summary: This article presents a rare case of a cocrystal formed by an organic molecule and its epimer. The formation of this cocrystal has implications for controlling the purity of the active pharmaceutical ingredient (API) in commercial manufacturing processes. The crystal structure of this cocrystal was determined using crystal structure prediction and X-ray diffraction techniques, revealing the unexpected lattice interaction between the two epimers.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
Article
Pharmacology & Pharmacy
Alex N. Manin, Denis E. Boycov, Olga R. Simonova, Tatyana V. Volkova, Andrei Churakov, German L. Perlovich
Summary: Thermodynamic parameters for the formation of cocrystals of carbamazepine with structurally related coformers were determined using experimental and computational techniques. The relationship between solubility products and solubility values of the coformers was found, and the relationship between the entropy term and molecular volume of cocrystal formation was revealed. A new method for assessing cocrystal stability based on hydrogen bond propensity analysis was proposed. The experimental and theoretical results on the thermodynamic parameters were in good agreement.
Article
Engineering, Chemical
Wenjie Kuang, Shaochang Ji, Xiaofang Wang, Jinyan Zhang, Ping Lan
Summary: Pharmaceutical cocrystals are an alternative approach to synthesis of new solids, and in this study, two forms of cocrystals were synthesized and characterized. The properties of LTG were enhanced by cocrystal formation, with LTG-THP-H2O showing slower dissolution rate and higher stability compared to LTG-GLU. The selection of conformers is crucial for improving the performance of LTG.
Article
Chemistry, Physical
Min Li, Zhao Yang, Yan Zhang, Hong Xu, Shuai-hua Zhang, Jing Sun, Jin Wang
Summary: A novel chemical structure called pharmaceutical cocrystal was synthesized to enhance the solubility of levofloxacin (LVFX), with nicotinic acid (NA) chosen as the cocrystal coformer (CCF). The cocrystal, with a triclinic crystal structure, demonstrated improved aqueous solubility compared to the original LVFX, being 5.02 times higher.
JOURNAL OF MOLECULAR STRUCTURE
(2022)