A pharmaceutical cocrystal of apigenin with piperazine: Preparation, structural characterization, and dissolution performance

Zhang, Jie; Shen, Rui; Zhang, Xu; Li, Gen; Wang, Xi

doi:10.1016/j.molstruc.2023.137027

Cited by 2 publications

(1 citation statement)

References 31 publications

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“…Cocrystallization has become an essential method within the pharmaceutical industry for the modification of the physicochemical properties of active pharmaceutical ingredients (APIs), such as solubility, dissolution rate, bioavailability, and stability. − The existence of cocrystals in various stoichiometries between the same API and coformer can expand the repertoire of possible solid forms for a given API. Consequently, the screening of cocrystals with diverse stoichiometries has garnered considerable attention due to its inherent advantages. − For instance, extensive research on the cocrystallization of caffeine (CAF) with 4-hydroxybenzoic acid (4-HBA) has been conducted using both experimental − and computational methods .…”

Section: Introductionmentioning

confidence: 99%

Stoichiometric Diversity of Caffeine and 4-Hydroxybenzoic Acid Cocrystals in Batchelor Vortex Flow

Li,

Kim

2024

Crystal Growth & Design

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In this study, we explored the influence of fluid flow on the stoichiometric diversity in cocrystal formation. The cocrystallization of caffeine (CAF) with 4-hydroxybenzoic acid (4-HBA) was carried out using rotating disk (RD) and mixing tank (MT) crystallizers, which generated distinct flow regimes: Batchelor vortex and turbulent eddy flows, respectively. The outcomes revealed the formation of hitherto unknown (1:3) cocrystals, alongside the known (2:1) and (1:2) cocrystals. Notably, the fluid motion was found to significantly affect the nucleation of cocrystals with stoichiometric diversity, with stable (1:3) cocrystal nucleation being more effective in the Batchelor vortex flow due to improved molecular alignment. The phase transformation of cocrystals was also subject to the influence of fluid dynamics. In the Batchelor vortex flow, (2:1) and (1:2) cocrystals transitioned directly to (1:3) cocrystals, whereas in the turbulent eddy flow, (2:1) first converted to (1:2) cocrystals before reaching the (1:3) cocrystals. Kinetic factors related to nucleation and phase transformation led to the temporary formation of either metastable (2:1) and (1:2) cocrystals or stable (1:3) cocrystals, depending on the fluid motion pattern. However, aligning with thermodynamic principles, only the stable (1:3) cocrystal was the ultimate product at the end of the process. This research underscores the significance of fluid flow patterns in controlling the stoichiometry of cocrystals, with important implications for pharmaceutical development and material science applications.

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