Salt solvates of quinolones and oxicams: Theoretical computation, structural characterization and dissolution studies

Jiao, Lingtai; Yang, Dezhi; Zhang, Li; Yang, Shumei; Du, Guanhua; Lü, Yang

doi:10.1016/j.molstruc.2020.128865

Cited by 8 publications

(5 citation statements)

References 48 publications

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“…It should be noted that most quinolone-based multicomponent crystals (located in CSDs) tend to form hydrated/solvated forms. [34][35][36] Multicomponent crystals obtained in this work are no exception. Earlier we showed the influence of the hydrogen bond donor/acceptor ratio in coformers on the multicomponent crystal solvate formation probability.…”

Section: Thermal Analysismentioning

confidence: 71%

Thermal method usage features for multicomponent crystal screening

et al. 2022

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Section: Thermal Analysismentioning

confidence: 71%

Thermal method usage features for multicomponent crystal screening

et al. 2022

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“…The endothermic peaks of the physical mixture were at about 118.95, 200.94 and 225.82 °C. There were studies about the salt solvate and cocrystal solvate that the endothermic peak of acetonitrile verified from 83 °C to 148 °C [ 38 , 39 ]. The endothermic peaks of acetonitrile and the melting of Apx–Que–2ACN, the PXRD pattern of which was in good agreement with the simulated ones, were at 142.34 and 151.05 °C, respectively, where part of the two endothermic peaks overlapped.…”

Section: Resultsmentioning

confidence: 99%

“…The DSC results (Figure 5) showed that the endothermic peak of Apx was at 237.51 • C [36], and endothermic peaks of crystal water and the melting point of Que were at about 122.44 and 317.60 • C [37], respectively. The endothermic peaks of the physical mixture were at about 118.95, 200.94 and 225.82 • C. There were studies about the salt solvate and cocrystal solvate that the endothermic peak of acetonitrile verified from 83 • C to 148 • C [38,39]. The endothermic peaks of acetonitrile and the melting of Apx-Que-2ACN, the PXRD pattern of which was in good agreement with the simulated ones, were at 142.34 and 151.05 • C, respectively, where part of the two endothermic peaks overlapped.…”

Section: Thermal Analysismentioning

confidence: 97%

Cocrystal of Apixaban–Quercetin: Improving Solubility and Bioavailability of Drug Combination of Two Poorly Soluble Drugs

et al. 2021

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Drug combinations have been the hotspot of the pharmaceutical industry, but the promising applications are limited by the unmet solubility and low bioavailability. In this work, novel cocrystals, consisting of two antithrombotic drugs with poor solubility and low bioavailability in vivo, namely, apixaban (Apx) and quercetin (Que), were developed to discover a potential method to improve the poor solubility and internal absorption of the drug combination. Compared with Apx, the dissolution behavior of Apx–Que (1:1) and Apx–Que–2ACN (1:1:2) was enhanced significantly, while the physical mixture of the chemicals failed to exhibit the advantages. The dissolution improvements of Apx–Que–2ACN could be explained by the fact that the solid dispersion-like structure and column-shaped cage of Que accelerated the access of the solvent to the inner layer of Apx. The fracture of the hydrogen bonds of Apx, which was the joint of the adjacent Que chains, facilitated the break-up of the structures. Besides, the bioavailability of Apx–Que was increased compared with the physical mixture and Apx, and Apx–Que remained stable in high temperature and illumination conditions. Therefore, a drug–drug cocrystal of two antithrombotic agents with poor solubility was developed, which exhibited greatly improved solubility, bioavailability and superior stability, indicating a novel method to overcome the shortages of drug combination.

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“…Huang et al found a salt solvate sulfasalazine·imidazole·MeCN, but they only analyzed the structure, which crystallized with one sulfasalazine – anion, one imidazole + cation, and one acetonitrile molecule in the asymmetric unit. Jiao et al synthesized four drug–drug salt solvates of piroxicam (PX), tenoxicam (TNX), lornoxicam (LNX), and meloxicam (MLX) with norfloxacin (NF) and ciprofloxacin (CIP), i.e., MLX•CIP•ACN, PX•NF•2MeOH, LNX•NF•H 2 O•0.3MeOH, and TNX•CIP•2MeOH, with approximately 3.0, 1.4, 1.6, and 1.1 times solubility higher than the original pure components, respectively. Li et al synthesized two lamotrigine(LAM)-tolfenamic acid (TAL) solvates LAM:TOL:methanol and LAM:TOL:ethanol with better stability and higher apparent solubility and intrinsic dissolution rate than pure tolfenamic acid.…”

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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Salt solvates of quinolones and oxicams: Theoretical computation, structural characterization and dissolution studies

Cited by 8 publications

References 48 publications

Thermal method usage features for multicomponent crystal screening

Thermal method usage features for multicomponent crystal screening

Cocrystal of Apixaban–Quercetin: Improving Solubility and Bioavailability of Drug Combination of Two Poorly Soluble Drugs

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

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