Crystallography and Biopharmaceutics of Some Antimalarials

Awofisayo, Sunday Olajide; Okhamafe, Augustine O.; Enato, Ehijie; Arhewoh, Matthew Ikhuoria

doi:10.9734/bjpr/2015/15832

Cited by 2 publications

(1 citation statement)

References 42 publications

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“…Upon isolating the two atropisomers from racemic LES, we discovered that both presented in an amorphous state (Figure S1). Given the profound influence of polymorphism on the stability, physicochemical properties, solubility, processability, and bioavailability of active pharmaceutical ingredients, − a thorough exploration of the solid-state characteristics of LES’s atropisomers was initiated. − Additionally, the challenges of obtaining single-crystal structures for LES, particularly significant for its pharmaceutical application in various racemic forms, have traditionally necessitated reliance on ab initio synchrotron powder X-ray diffraction techniques for structural confirmation. , Driven by the need to overcome these obstacles, our study aimed to determine the crystal structure of LES through single-crystal X-ray diffraction (SCXRD), offering a more direct and detailed analysis of its molecular configuration.…”

Section: Introductionmentioning

confidence: 99%

Exploring the Solid-State Landscape of Atropisomers in (±)-Lesinurad: Insights into Crystallographic Analysis, Transformation Behavior, and Dissolution Performance

Zhou,

Ye,

Jin

et al. 2024

Crystal Growth & Design

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Axial chirality is a unique form of chirality characterized by restricted rotation around a covalent bond due to steric or electronic hindrances, a phenomenon known as atropisomerism. The separation of (+)-and (−)-lesinurad from the racemic mixture suggests a potential advantage of (+)-lesinurad in treating hyperuricemia and gout due to its enhanced therapeutic efficacy. Although the crystalline structure profoundly affects a compound's physicochemical properties, the crystallographic landscapes of (+)-and (−)-lesinurad have yet to be explored. This study delves into the solid-state features of these atropisomers, identifying several novel polymorphic forms: two anhydrous polymorphs (forms A and B) and five solvates (S ACE-Hd 2 O , S ETH , S NPA , S IPA , S MTBE ) for (+)-lesinurad and one solvate for (−)-lesinurad, all characterized extensively. For the first time, the crystal structures of six solvates and form II of racemic lesinurad are elucidated using single-crystal diffraction, revealing that S ACE-Hd 2 O , S ETH , S NPA , and S IPA are isostructural. Notably, form II of racemic lesinurad undergoes a reversible single-crystal to single-crystal transformation at around 94 °C, transitioning between two polymorphs: a room-temperature variant (form II) and a high-temperature variant (form II-HT). Furthermore, we examined the equilibrium solubility and dissolution behavior of forms II, A, and B in a pH 6.8 aqueous solution, discovering enhanced solubility and dissolution rates for forms A and B compared with form II of racemic lesinurad.

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