Cocrystals of Leflunomide: Design, Structural, and Physicochemical Evaluation

Cadden, Joseph; Klooster, Wim T.; Coles, Simon J.; Aitipamula, Srinivasulu

doi:10.1021/acs.cgd.9b00335

Cited by 20 publications

(17 citation statements)

References 43 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BEX may decrease the contact area of the media, and the co-crystal affects the solubility of 2BEX-LIG. The solubility could be affected by the layer structure through changing inter-molecular hydrogen bonds and display of the chemicals [ 8 , 56 , 57 , 58 , 59 ].…”

Section: Resultsmentioning

confidence: 99%

A Novel Co-Crystal of Bexarotene and Ligustrazine Improves Pharmacokinetics and Tissue Distribution of Bexarotene in SD Rats

et al. 2020

View full text Add to dashboard Cite

Bexarotene (BEX), a specific retinoic acid X receptor (RXR) agonist granted by Food and Drug Administration (FDA) approval for the clinical treatment of T cell lymphoma, has now been found to exert pharmacological effects in the nervous system, with low bioavailability and poor cerebral distribution limiting its application in treatment on neurological disorders. Pharmaceutical co-crystal was a helpful method to improve the bioavailability and tissue distribution of active pharmaceutical ingredients (APIs). Here, 2bexarotene-ligustrazine (2BEX-LIG), a novel co-crystal system of BEX and ligustrazine (LIG) of which with BEX is an API, was constructed with satisfactory stability and enhanced solubility. The pharmacokinetics characteristics of BEX were detected, and the results showed that the absolute bioavailability and the cerebral concentration of BEX in rats administrated with 2BEX-LIG were enhanced from 22.89% to 42.86% and increased by 3.4-fold, respectively, compared with those in rats administrated an equivalent of BEX. Hence, our present study indicated that the novel co-crystal of 2BEX-LIG contributed to improving BEX oral bioavailability and cerebral distribution, thereby providing significant advantages for clinical application of brain tumors and other neurological diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

A Novel Co-Crystal of Bexarotene and Ligustrazine Improves Pharmacokinetics and Tissue Distribution of Bexarotene in SD Rats

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Karki, et al [240] demonstrated that synthon analysis combined with Fabian's methodology was effective in prediction of possible co-formers for artemisinin. A series of co-crystals of sulfamethoxazole [241] and leflunomide [242] were synthesized using this approach. Prediction of possible H-bonded motifs between tyraminium cations and violurate anions also successfully predicted many of the bimolecular synthons experimentally observed in tyraminium violurate polymorphs and hydrates, but also demonstrated that none of the trimolecular synthons were predicted [243].…”

Section: Co-crystals Designmentioning

confidence: 99%

Intermolecular Interactions in Functional Crystalline Materials: From Data to Knowledge

Вологжанина

2019

Crystals

View full text Add to dashboard Cite

Intermolecular interactions of organic, inorganic, and organometallic compounds are the key to many composition-structure and structure-property networks. In this review, some of these relations and the tools developed by the Cambridge Crystallographic Data Center (CCDC) to analyze them and design solid forms with desired properties are described. The potential of studies supported by the Cambridge Structural Database (CSD)-Materials tools for investigation of dynamic processes in crystals, for analysis of biologically active, high energy, optical, (electro)conductive, and other functional crystalline materials, and for the prediction of novel solid forms (polymorphs, co-crystals, solvates) are discussed. Besides, some unusual applications, the potential for further development and limitations of the CCDC software are reported. Crystals 2019, 9, 478 2 of 40 these fields, the manuscript cites only (i) recent works devoted to the analysis of correlations between intermolecular interactions and properties of a small molecule (for example its inclination to form polymorphs, solvates, and co-crystals), or a corresponding solid (from a well-known requirement for non-linear optical materials to crystallize in acentric space groups, to recent studies devoted to the effect of solvent presence on mechanical properties), and (ii) the corresponding software developed to investigate these correlations and to design novel solid forms with desired physicochemical properties. As the description of structure-property networks describes mainly the papers published in the last 10 years in the field of organic, organometallic, and coordination crystals, then the software under discussion will be limited with those developed by the Cambridge Crystallographic Data Centre (CCDC) for material chemistry and crystallography. Various examples of applications of the CCDC software to functional materials including their combination with other software, and restrictions found, will be given.First, the Cambridge Structural Database (CSD) and components of the CSD-Enterprise will be described in Section 2. Then, some properties related to the appearance of a given supramolecular associate, and the tools to search for an associate in the CSD will be reported in Section 3. The properties of solids dependent on the crystal morphology, the Bravais, Friedel, Donnay, and Harker (BFDH) tool for crystal morphology prediction and its' application to affect crystal morphology, polymorphism, and solvatomorphism will be reported in Section 4. Knowledge-based predictions of H-bonded polymorphism, co-crystal formation, mapping of likely intermolecular interactions, and conformer generation for the synthesis of novel functional materials will be discussed in Section 5, and the analysis of local connectivity and whole architectures of solvent molecules in Section 6. Finally, Section 7 contains information about Python API algorithms compatible with the CSD-Enterprise and about some examples of the successful combination of the CSD-Enterprise tools with exte...

show abstract

“…These systematic studies currently available for salts are not yet available for cocrystals and solvates, despite these multicomponent forms being of interest. The published literature provides a limited number of new cocrystals and solvates, which is insufficient to obtain reliable structureproperty relations (Cadden et al, 2019). Ten cocrystals of AMG 517 were reported, accompanied with an evaluation of the physicochemical properties in order to correlate properties of various cocrystals (Stanton & Bak, 2008).…”

Section: Introductionmentioning

confidence: 99%

Structure–property relations of a unique and systematic dataset of 19 isostructural multicomponent apremilast forms

Jirát¹,

Babor²,

Ridvan³

et al. 2022

Int Union Crystallogr J

View full text Add to dashboard Cite

The structure–property relations are examined for apremilast cocrystals and solvates in this work. A unique and large dataset of multicomponent crystal forms is presented including 7 cocrystals and 12 solvates. In total, 15 of the presented multicomponent forms and their crystal structures are published here for the first time. This dataset is unique owing to the extreme crystal packing similarity of all 19 crystal forms. This fact makes the evaluation of structure–property relations significantly easier and more precise since the differences in the crystal lattice arrangement are close to negligible. Properties of the guest molecules used here can be directly correlated with the macroscopic properties of the corresponding multicomponent forms. Interestingly, a considerable correlation was found between the intrinsic dissolution rate of the multicomponent forms and their solubility, as well as the solubility of their guest molecules in the dissolution medium. The latter is of particular interest as it can aid in the design of multicomponent forms with tuned properties.

show abstract

Cocrystals of Leflunomide: Design, Structural, and Physicochemical Evaluation

Cited by 20 publications

References 43 publications

A Novel Co-Crystal of Bexarotene and Ligustrazine Improves Pharmacokinetics and Tissue Distribution of Bexarotene in SD Rats

A Novel Co-Crystal of Bexarotene and Ligustrazine Improves Pharmacokinetics and Tissue Distribution of Bexarotene in SD Rats

Intermolecular Interactions in Functional Crystalline Materials: From Data to Knowledge

Structure–property relations of a unique and systematic dataset of 19 isostructural multicomponent apremilast forms

Contact Info

Product

Resources

About