Structural Insights into the Highly Solvating System of Axitinib via Binary and Ternary Solvates

Recently, researchers found the abilities of cepharanthine (CEP) to prevent and treat coronavirus. However, the study about CEP solid forms has been rarely reported. In this study, the crystal structure of CEP form I was first solved, and eight solvates were screened and discovered based on the conductor-like screening model for real solvents. The crystal structures of five solvates of CEP with methanol (SMeOH), acetonitrile (SACN), methyl acetate (SMA), ethyl acetate (SEA), and butyl acetate (SBA) were solved. The results showed that five solvates belonged to isolated-site solvates. Hydrogen bonding between the solvent molecule and the active pharmaceutical ingredient molecule was present only in SMeOH. The remaining four solvates formed C–H···O weak hydrogen bonds and C–H···π interactions between the host and guest. The mechanism of solvate formation was explained by calculating the packing coefficients, and it was proved that the introduction of solvent molecules mainly made the crystal structure packed more effectively. In addition, the desolvation of the five solvates were studied and found that the desolvation of SMeOH followed a cooperative mechanism, while SACN, SMA, SEA, and SBA conformed to a destruction-collapse mechanism.

Section: Resultsmentioning

confidence: 99%

Section: Pxrd and Crystal Morphology Analysismentioning

confidence: 99%

Exploration of the Solid Forms of Cepharanthine: Crystal Structure and Phase Transformation

Wang

Zhou

et al. 2023

“…Studies on solvate, solvate-hydrate, and hydrate formation, occurrence, and crystal structure analysis have been conducted on compounds having a rich solid-form landscape, for example, prolific solvate formers olanzapine, galunisertib, axitinib, and sulfathiazole as well as solvate-hydrate formers such as bosutinib and 3,5-dihydroxybenzoic acid. , The formation of multiple crystalline phases represents a possible strategy for altering the solid-state properties of pharmaceutical compounds and influencing the physicochemical and biopharmaceutical properties ( e.g. , the dissolution rate profile and hence bioavailability) without affecting the physiological action. , Therefore, considering the importance of solid crystalline forms and solvates in the pharmaceutical industry and their implication in the pharmaceutical development of small organic drug molecules, the large number of characterized solid forms for pharmaceutical compounds is not surprising.…”

Section: Introductionmentioning

confidence: 99%

Crystallographic and Computational Analysis of the Solid-Form Landscape of Three Structurally Related Imidazolidine-2,4-dione Active Pharmaceutical Ingredients: Nitrofurantoin, Furazidin, and Dantrolene

Trimdale-Deksne

Kons

Orola

et al. 2023

We present a crystallographic and computational study of three hydantoin-based active pharmaceutical ingre-dients�nitrofurantoin, furazidin, and dantrolene�aimed at identifying factors resulting in different propensities of these compounds to form polymorphs, hydrates, solvates, and solvatehydrates. This study is a continuation of our research toward understanding how small structural differences in closely related compounds affect their propensity to form different crystal phases, as all three compounds contain an imidazolidine-2,4-dione scaffold and a N-acyl hydrazone moiety and all form multiple crystalline phases. Crystallographic and computational analysis of the already known and newly obtained nitrofurantoin, furazidin, and dantrolene crystal structures was performed by dissecting the properties of individual molecules and searching for differences in the tendency to form hydrogen bonding patterns and characteristic packing features. The propensity to form solvates was found to correlate with the relative packing efficiency of neat polymorphs and solvates and the ability of molecules to pack efficiently in several different ways. Additionally, the differences in the propensity to form solvate-hydrates were attributed to the different stability of the hydrate phases.

“…Furthermore, desolation of solvates can potentially produce new crystal forms that may be challenging to obtain using conventional methods . The study of solvates has attracted significant attention from both academic and industrial areas, with isostructural solvates being a particularly significant area of investigation. − Understanding the structure and formation mechanism of isostructural solvates is crucial for fields such as drug development, material modification, and research on multicomponent crystals.…”

Section: Introductionmentioning

confidence: 99%

Development Strategies of Polymorphs and Solvates for Enhancing Powder Properties: A Case Study of Thiothiamine

Han,

Qu,

et al. 2023

Self Cite

Crystals with an acicular shape are a "nightmare" to many chemical engineers due to their poor powder properties, posing numerous challenges in purification, filtration, washing, and subsequent processing. However, these challenges may be circumvented by engineering new crystal forms with better morphology using a crystal engineering strategy. Herein, we demonstrated the validity of this strategy with the case of thiothiamine, an essential intermediate in the production of vitamin B1, which exhibits a needle-like crystal morphology in polymorph I. Another two polymorphs (forms II and III) and 14 solvates were discovered and developed using a combination of computational prediction and experimental screening with X-ray diffraction, IR spectroscopy, and thermal analysis. Crystal structures of form II and six solvates were fully determined for the first time by single crystal X-ray diffraction. First, compared to form I, form II exhibits a notably larger grain size. Furthermore, the desolvation of solvates can retain its original superior morphology. These optimization strategies targeting crystal morphology directly contribute to the enhancement of the powder performance. Specifically, the filtration time was significantly reduced by over 70%, and the flowability of the powder was also greatly improved. Crystal structure analysis reveals that inclusion of small solvent molecules in a disordered manner contributes to solvate formation, while hydrogen bonding interactions contribute to the formation of methanol solvate. This study can serve as a valuable reference for addressing filtration and flowability challenges in industry by using crystal engineering strategies to develop polymorph or solvate alternatives.