Physicochemical characterisation and cyclodextrin complexation of erlotinib

Tóth, Gergő; Jánoska, Ádám; Szabó, Zoltán‐István; Völgyi, Gergely; Orgován, Gábor; Szente, Lajos; Noszál, Béla

doi:10.1080/10610278.2015.1117083

Cited by 20 publications

(16 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Three parallel measurements were carried out. The implementation of the experiment is described in more detail in our previous articles [19,25].…”

Section: Determination Of the Intrinsic Solubility By Chasing Equilibmentioning

confidence: 99%

“…Molecular Modeling. Molecular modeling study was performed as previously reported [19,28,29] by using the semiempirical PM3 method of Hyperchem Professional software (version 8.0). The initial structures of neutral LAP and -CD were constructed with the help of Hyperchem 8.0 and optimized with PM3.…”

Section: Phase-solubilitymentioning

confidence: 99%

“…The complex stoichiometry was also studied by ESI-TOF-MS technique, which provides a powerful means to study noncovalent host-guest inclusion complexes between a CD and the guest molecule [32]. A large number of publications prove that a simple, fast ESI-MS analysis is suitable for the determination of inclusion complex stoichiometry [15,19,33]; however, ESI-MS studies imply the question whether the observed peaks represent actual inclusion complexes or rather electrostatic adducts formed during the electrospray process [34], if, however, additional adequate techniques prove that the complex formation ESI-MS is straightforward way to determine complex stoichiometry.…”

Section: Determination Of Lap--cd Stoichiometry: Nmr Job Plot and Esimentioning

confidence: 99%

“…to characterize the geometry of inclusion complexes. ROESY experiment offers valuable information on spatial proximity between protons of the host and guest molecules by observing intermolecular dipolar cross-correlations, while molecular modeling seeks the energy-minimized structure, which can be visualized at the atomic level [19,35,36]. 2D NMR ROESY spectra for LAP--CD inclusion complex were recorded at pD * 2, where LAP exhibits an appropriate solubility.…”

Section: Determination Of Stability Constant By Uvmentioning

confidence: 99%

“…So far only a few attempts have been reported to improve the bioavailability of LAP [12][13][14]. To the best of our knowledge, LAP-CD inclusion complex characterization has yet to be described, despite the fact that CD complexation has been proven to increase the solubility, bioavailability, and anticancer activity of other tyrosine kinase inhibitors erlotinib, gefitinib, imatinib, and so forth [15][16][17][18][19]; moreover, sulfobutylether--CD was used for solubilizing LAP in some earlier studies [20,21].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Physicochemical Characterization and Cyclodextrin Complexation of the Anticancer Drug Lapatinib

Tóth

Jánoska

Völgyi

et al. 2017

Journal of Chemistry

Self Cite

View full text Add to dashboard Cite

Lapatinib (LAP), the tyrosine kinase inhibitor drug with moderate bioavailability, was characterized in terms of physicochemical properties: acid-base characteristics, lipophilicity, and solubility. The highly lipophilic nature of the drug and its extremely low water solubility (S0=0.82 nM) limit the development of a parenteral formulation. In order to enhance solubility and bioavailability, inclusion complex formation with cyclodextrins (CDs) is a promising method of choice. Therefore, LAP-CD interactions were also studied by a multianalytical approach. The stability constants of LAP with native cyclodextrins, determined by UV spectroscopy, identified the seven-membered β-CD as the most suitable host. Continuous variation method (Job’s plot) by 1H NMR showed a 1 : 1 stoichiometry for the complexes. The geometry of the complex was elucidated by 2D ROESY NMR measurements and molecular modeling, indicating that the partial molecular encapsulation includes the fluorophenyl ring of LAP. Phase-solubility studies with four CDs, β-CD, (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD), randomly methylated-β- (RAMEB-) cyclodextrin, and sulfobutylether-β-cyclodextrin (SBE-β-CD), show an AL type diagram and highly increased solubility via CD complexation. The results are especially promising with SBE-β-CD, exerting more than 600-fold gain in solubility. The equilibrium and structural information presented herein can offer the molecular basis for an improved drug formulation with enhanced bioavailability.

show abstract

“…Three parallel measurements were carried out. The implementation of the experiment is described in more detail in our previous articles [19,25].…”

Section: Determination Of the Intrinsic Solubility By Chasing Equilibmentioning

confidence: 99%

Section: Phase-solubilitymentioning

confidence: 99%

Section: Determination Of Lap--cd Stoichiometry: Nmr Job Plot and Esimentioning

confidence: 99%

Section: Determination Of Stability Constant By Uvmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Physicochemical Characterization and Cyclodextrin Complexation of the Anticancer Drug Lapatinib

Tóth

Jánoska

Völgyi

et al. 2017

Journal of Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

Studying molecular interactions via capillary electrophoresis and microscale thermophoresis: A review

et al. 2023

View full text Add to dashboard Cite

The process of choosing the most proper technique for studying the molecular interactions is based on critical factors such as instrumentation complexity, automation, experimental procedures, analysis time, consumables, and costvalue. This review has tracked the use of affinity capillary electrophoresis (ACE) and microscale thermophoresis (MST) techniques in the evaluation of molecular binding among different molecules during the 5 years 2016-2021. ACE has proved to be an attractive technique for biomolecular characterization with high resolution efficiency where small variations in several controlling factors can much improve such efficiency compared to other analytical techniques. Meanwhile, MST has proved its higher sensitivity for smaller amounts of complex non-purified biosamples without affecting its robustness while providing high through output. However, the main motivation to review both techniques in the proposed review was their capability to carry out all experiments without the

show abstract

A New Empirical Equation to Take Into Account the Influence of Ionic Strength on Electrophoretic Mobility and Determination of Binding Constants of Ester Betulin Derivatives With Sulfated β‐Cyclodextrin by Affinity Capillary Electrophoresis

Sursyakova,

Levdansky,

Rubaylo

2024

Electrophoresis

View full text Add to dashboard Cite

An empirical equation relating electrophoretic mobility and ionic strength was proposed. The equation includes a number of parameters that are found using the mobilities of reference ions: two coefficients in the numerator describing the linear relationship of the multiplier in front of the square root of the ionic strength with the product of the ion mobility in the background electrolyte (BGE) without additives by the modulus of the charge number, raised to a certain power, and also the multiplier in the denominator before the square root of the ionic strength. The proposed equation was tested using the mobilities measured in BGEs with the addition of sodium chloride to adjust ionic strength and sulfated β‐cyclodextrin (S‐β‐CD) for 11 anions with charge numbers from −1 to −4. Measuring anion electrophoretic mobility over a wide range of values, from −17 to −76 × 10−9 m2 V−1 s−1, was achieved through a combination of conventional separation and separation in a thermostatically controlled part of a capillary. The equation describes experimental data much more accurately (the discrepancy is no more than 1.1%) compared to the previously used simple empirical equation. For the S‐β‐CD complexes of betulin derivatives, the apparent binding constants determined are equal to 40–60 M−1.

show abstract

Physicochemical characterisation and cyclodextrin complexation of erlotinib

Cited by 20 publications

References 30 publications

Physicochemical Characterization and Cyclodextrin Complexation of the Anticancer Drug Lapatinib

Physicochemical Characterization and Cyclodextrin Complexation of the Anticancer Drug Lapatinib

Studying molecular interactions via capillary electrophoresis and microscale thermophoresis: A review

A New Empirical Equation to Take Into Account the Influence of Ionic Strength on Electrophoretic Mobility and Determination of Binding Constants of Ester Betulin Derivatives With Sulfated β‐Cyclodextrin by Affinity Capillary Electrophoresis

Contact Info

Product

Resources

About