Chiral separation of rasagiline using sulfobutylether‐β‐cyclodextrin: capillary electrophoresis, NMR and molecular modeling study

Szabó, Zoltán‐István; Ludmerczki, Róbert; Fiser, Béla; Noszál, Béla; Tóth, Gergő

doi:10.1002/elps.201800482

Cited by 31 publications

(18 citation statements)

References 20 publications

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“…The exact SBE-β-CD structure is unknown, because the sulfobutylether (SBE) groups are randomly arranged on the β-CD skeleton and the CD itself is a mixture of derivatives with different degrees of substitution. Therefore, three different isomers were designed based on previous studies to mimic different possible SBE-β-CD structures [ 19 , 20 ]. It is known that the degree of substitution of SBE-β-CD is ~7 and thus, the model structures carry seven properly arranged SBE groups on the β-cyclodextrin skeleton ( Figure 2 ).…”

Section: Methodsmentioning

confidence: 99%

Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility

Szabó

Orban

Borbás

et al. 2021

Heliyon

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Pomalidomide (POM), a potent anticancer thalidomide analogue was characterized in terms of cyclodextrin complexation to improve its aqueous solubility and maintain its anti-angiogenic activity. The most promising cyclodextrin derivatives were selected by phase-solubility studies. From the investigated nine cyclodextrins – differing in cavity size, nature of substituents, degree of substitution and charge – the highest solubility increase was observed with sulfobutylether-β-cyclodextrin (SBE-β-CD). The inclusion complexation between POM and SBE-β-CD was further characterized with a wide variety of state-of-the-art analytical techniques, such as nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), circular dichroism spectroscopy, fluorescence spectroscopy as well as X-ray powder diffraction method (XRD). Job plot titration by NMR and the A L -type phase-solubility diagram indicated 1:1 stoichiometry in a liquid state. Complementary analytical methods were employed for the determination of the stability constant of the complex; the advantages and disadvantages of the different approaches are also discussed. Inclusion complex formation was also assessed by molecular modelling study. Solid state complexation in a 1:1 M ratio was carried out by lyophilization and investigated by IR and XRD. The complex exhibited fast-dissolution with immediate release of POM, when compared to the pure drug at acidic and neutral pH. Kinetic analysis of POM release from lyophilized complex shows that Korsmeyer-Peppas and Weibull model described the best the dissolution kinetics. The cytotoxicity of the complex was tested against the LP-1 human myeloma cell line which revealed that supramolecular interactions did not significantly affect the anti-cancer activity of the drug. Overall, our results suggest that the inclusion complexation of POM with SBE-β-CD could be a promising approach for developing more effective POM formulations with increased solubility.

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Section: Methodsmentioning

confidence: 99%

Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility

Szabó

Orban

Borbás

et al. 2021

Heliyon

Self Cite

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“…Sulfobutylether-β-cyclodextrin was also applied in ES of the anti-Parkinson drug rasagiline ( Supplementary Materials Figure S36 ), under capillary electrophoresis conditions, by Szabó et al [ 93 ]. The optimum conditions for a high resolution ( R s = 3.5) were as follows: 50 mM glycine–HCl buffer pH 2.0, supplied with 30 mM sulfobutylether-β-cyclodextrin, 35 °C, applying 12 kV in reversed polarity, and –8 mbar pressure (vacuum), and an analysis time of 8 min.…”

Section: β-Cyclodextrin-based Cspsmentioning

confidence: 99%

Polysaccharide- and β-Cyclodextrin-Based Chiral Selectors for Enantiomer Resolution: Recent Developments and Applications

Bui

Rosenau

2021

Molecules

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Polysaccharides, oligosaccharides, and their derivatives, particularly of amylose, cellulose, chitosan, and β-cyclodextrin, are well-known chiral selectors (CSs) of chiral stationary phases (CSPs) in chromatography, because they can separate a wide range of enantiomers. Typically, such CSPs are prepared by physically coating, or chemically immobilizing the polysaccharide and β-cyclodextrin derivatives onto inert silica gel carriers as chromatographic support. Over the past few years, new chiral selectors have been introduced, and progressive methods to prepare CSPs have been exploited. Also, chiral recognition mechanisms, which play a crucial role in the investigation of chiral separations, have been better elucidated. Further insights into the broad functional performance of commercially available chiral column materials and/or the respective newly developed chiral phase materials on enantiomeric separation (ES) have been gained. This review summarizes the recent developments in CSs, CSP preparation, chiral recognition mechanisms, and enantiomeric separation methods, based on polysaccharides and β-cyclodextrins as CSs, with a focus on the years 2019–2020 of this rapidly developing field.

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“…An overview of EKC‐UV methods applicable for quality control of pharmaceuticals published since 2015 is provided in Table 3 [71–106]. The most frequently, CDs were used as chiral selectors in these works, owning to their advantages, such as low cost, good stability, low UV cut‐off, high water solubility, and excellent chiral selectivity.…”

Section: Electrokinetic Chromatographymentioning

confidence: 99%

“…Nevertheless, the addition of 100 mM guanidine HCl into BGE was necessary for baseline resolution in this case [75]. A determination of complexation parameters, average stoichiometry ratios, or computer modeling of the spatial structure was reported for complexes of pindolol and octa(6‐ O ‐sulfo)‐γ‐CD [94], colchicine and succinyl‐γ‐CD, colchicine and sulfated‐γ‐CD [78], and rasagiline and sulfobutyl‐ether‐β‐CD [99]. Data obtained were used for both selections of optimal separation parameters applicable for quality control of the respective drugs in commercial formulations and a deeper understanding of enantioselective discrimination phenomena.…”

Section: Electrokinetic Chromatographymentioning

confidence: 99%

Capillary electrophoretic methods for quality control analyses of pharmaceuticals: A review

Řemínek

Foret

2020

Electrophoresis

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Capillary electrophoresis represents a promising technique in the field of pharmaceutical analysis. The presented review provides a summary of capillary electrophoretic methods suitable for routine quality control analyses of small molecule drugs published since 2015. In total, more than 80 discussed methods are sorted into three main sections according to the applied electroseparation modes (capillary zone electrophoresis, electrokinetic chromatography, and micellar, microemulsion, and liposome-electrokinetic chromatography) and further subsections according to the applied detection techniques (UV, capacitively coupled contactless conductivity detection, and mass spectrometry). Key parameters of the procedures are summarized in four concise tables. The presented applications cover analyses of active pharmaceutical ingredients and their related substances such as degradation products or enantiomeric impurities. The contribution of reported results to the current knowledge of separation science and general aspects of the practical applications of capillary electrophoretic methods are also discussed.

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Chiral separation of rasagiline using sulfobutylether‐β‐cyclodextrin: capillary electrophoresis, NMR and molecular modeling study

Cited by 31 publications

References 20 publications

Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility

Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility

Polysaccharide- and β-Cyclodextrin-Based Chiral Selectors for Enantiomer Resolution: Recent Developments and Applications

Capillary electrophoretic methods for quality control analyses of pharmaceuticals: A review

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