Structural and property analysis of three novel pharmaceutical salt solvates synthesized from paliperidone and aromatic carboxylic acids

Chen, Jian; Shen, Zheng; Cai, Zhuoer; Ge, Jilong; Hua, Xiu-Ni; Sun, Kai; Sun, Baiwang

doi:10.1016/j.molstruc.2024.138267

Cited by 1 publication

(1 citation statement)

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“…The latest research trend of pharmaceutical salt solvates has focused on the structure–property, i.e., improving the solubility, stability, permeability, and other physicochemical properties of drugs via the pharmaceutical salt solvates' solid form. Chen et al successfully synthesized three new paliperidone salt solvates and then analyzed the structures of these paliperidone salt solvates. The thermal stability of paliperidone · nicotinic acid · 2H 2 O · 2MeOH was improved by about 40 K compared to pure paliperidone, while the solubility and dissolution rate of paliperidone had also been significantly enhanced in a simulated human environment via the paliperidone salt solvate form (883.78 times solubility in pure water while 166.57 times in pH = 6.8).…”

Section: Introductionmentioning

confidence: 99%

Weak but Vital: The Role of Solvents in Crystal Packing and Coassembly for the Formation of Multicomponent Salt Solvates of Clozapine with Oxalic Acid

Li,

Zhang,

Wang

et al. 2024

Crystal Growth & Design

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In order to explore the role of solvent molecules (acetonitrile and ethanol) in crystal packing and coassembly for the formation of three multicomponent salt solvates of clozapine (CLZ) with oxalic acid (OXA), i.e., CLZ-OXA1 ([CLZ2+]:[HOXA–]:[OXA2–]:acetonitrile = 1:1:0.5:1), CLZ-OXA2 ([CLZ2+]:[HOXA–]:[OXA2–]:ethanol = 1:1:0.5:1), and CLZ-OXA3 ([CLZ+]:[OXA2–]:ethanol = 1:0.5:1), experimental and computational studies via density functional theory and molecular dynamics were employed to relate intermolecular interactions to packing arrangements, formation mechanism, stability, and the desolvation process of CLZ salt solvates. The crystal structures of three CLZ salt solvates were analyzed to show that both weak interactions C–H···X (X = O, N, or π) and van der Waals forces were of great importance in the process of self-assembly as well as strong and conventional hydrogen bonds (N–H···O and O–H···O), leading to a stable and diverse multidimensional supramolecular architecture. The packing arrangement and crystal assembly analysis implied that CLZ-OXA1 and CLZ-OXA2 were isostructural. Furthermore, solvent molecules were classified as isolated sites in the packing cages consisting of CLZ and OXA to fill the vacancies in the framework and compensate for the weak interactions or charges. Particularly, ethanol molecules in CLZ-OXA3 also acted as very important bridge-builders, contributing to the formation of the multicomponent crystals. The thermal analysis results indicated that the solvent molecules cannot easily escape from their sites; however, when desolvation occurred, the CLZ multicomponent crystal structures collapsed immediately, indicating the critical role of solvent molecules in stabilizing the crystal structure via intermolecular interactions. After filling the void space, the relatively more negative lattice energy than pure CLZ and the increased packing coefficients may also be the important driving forces for the solvation formation. The present study might provide an opportunity to further reveal the role of solvent molecules in the solid form of the antipsychotic drug CLZ.

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Section: Introductionmentioning

confidence: 99%