Evaluation Of Inclusion Complexes Research Articles

Enantioseparation of mandelic acid and substituted derivatives by high-performance liquid chromatography with hydroxypropyl-β-cyclodextrin as chiral mobile additive and evaluation of inclusion complexes by molecular dynamics.

The enantioseparation and resolution mechanism of mandelic acid (MA), 4-methoxymandelic acid (MMA), and 4-propoxymandelic acid (PMA) were investigated by reversed-phase high-performance liquid chromatography (HPLC) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) as a chiral mobile-phase additive and molecular dynamics simulation. The suitable chromatographic conditions for the enantioseparation of MA, MMA, and PMA were obtained. Under the selected chromatographic conditions, these enantiomers could achieve baseline separation. The results of thermodynamic parameter analysis revealed that the main driven forces for the enantioseparation of MA, MMA, and PMA could be van der Waals forces and hydrogen-bonding interactions and the chromatographic retention of these chiral compounds was an enthalpy-driven process. The results of the molecular simulation revealed that their chiral resolution mechanism on HP-β-CD was responsible for the formation of inclusion complexes of enantiomers with HP-β-CD with different conformations and binding energies. And the binding energy of HP-β-CD with (S)-isomer was larger than that with (R)-isomer, which is consistent with the experimental results of the first elution of (S)-isomer. Additionally, it is also confirmed that the interaction energies included the van der Waals energy (∆Evdw ), electrostatic energy (∆Eelec ), polar solvation energy, and SASA energy (∆Esasa ), and the separation factor (α) was closely connected with the disparity in the binding energies of optical isomers and HP-β-CD complexes. Meanwhile, from molecular dynamics simulation, it can be found that the ∆(∆Ebinding ), (∆(∆Ebinding ) = ∆Ebinding,R - ∆Ebinding,S ) value was in order of MA-HP-β-CD complex > MMA-HP-β-CD complex > PMA-HP-β-CD complex, which was consistent with the order of Δ(ΔG) values obtained from van't Hoff plot. This indicated that the molecular dynamics simulation has predictive function for chiral resolution.

Characterization and evaluation of inclusion complexes between astaxanthin esters with different molecular structures and hydroxypropyl-β-cyclodextrin

In this study, we focused on the characterization and evaluation of the inclusion complexes between astaxanthin esters (Asta-E) and hydroxypropyl-β-cyclodextrin (HPβ-CD). Asta-E of varying chain lengths (C4, C8, C18, and C22) and unsaturation degrees (C22:0 and C22:6) of the fatty acids were purified, and the inclusion complexes of HPβ-CD with Asta-E were characterized by various methods (phase solubility analysis, differential scanning calorimetry, ultraviolet–visible absorption spectroscopy, Fourier-transform infrared spectroscopy, and 1H nuclear magnetic resonance spectrometry). Thermodynamic analyses showed that astaxanthin docosahexaenoic acid monoester (Asta-C22:6) had the best binding capacity among the HPβ-CD–Asta-E inclusion complexes (complexation efficiency was 14.42 × 10⁻3 at 310 K). Moreover, binding site analysis of Asta-E with HPβ-CD indicated that the six-membered Asta-E ring was bound in the cavity of HPβ-CD by hydrogen bonds. The fatty acid chain had a positive influence on both the thermal stability and binding capacity of the inclusion complexes. Asta-C22:6 was selected to investigate the enhancing effect HPβ-CD has on its anticancer activity, oral bioavailability, and storage stability. HPβ-CD–Asta-C22:6 inclusion complex exhibited higher antiproliferative activity on HepG2 cells (IC50 = 160 μg/mL for 48 h) and arrested the cells in their S and G2/M phases. Bioavailability experiments showed that the area under curve (AUC0–t) after oral gavage of the HPβ-CD−Asta-C22:6 inclusion complex (9.62 ± 0.21 h μg/mL) was 2.68-times higher than that after oral gavage of Asta-C22:6 (3.59 ± 0.33 h μg/mL). Thus, the formation of an inclusion complex with HPβ-CD is an effective method to solubilize and stabilize Asta-E for potential future applications.

Interaction of native cyclodextrins and their hydroxypropylated derivatives with parabens in aqueous solutions. Part 1: evaluation of inclusion complexes

Due to their antimicrobial activity, parabens (i.e. alkyl esters of p-hydroxybenzoic acid) are widely used as preservatives in several industries (pharmaceutical, food, cosmetic). Although being extremely effective, their usage is hampered by their low aqueous solubility. Several formulation strategies can be applied to enhance their solubility, one of which is formation of water-soluble cyclodextrin (CD) complexes. Formation of inclusion complexes has been proved to be a good approach to increase solubility of lipophilic drugs and other active ingredients. Some research has been done in this field. However, a complete and comprehensive study on how the alkyl chain length of parabens influences the complex formation, aggregation and formation of insoluble complexes is still lacking. Phase-solubility studies showed that all the very water-soluble hydroxypropylated CDs form linear (AL) type phase-solubility profiles with all tested parabens. The poorly soluble βCD did also form AL-type profiles with methyl and ethyl paraben while the βCD complexes of propyl and butyl paraben have limited solubility in water and, thus displayed B-type profiles. The paraben complexes of αCD and γCD all had limited solubility in water and, thus, displayed B-type phase-solubility profiles. Fourier-transformed infrared spectroscopy, Differential scanning calorimetry and X-ray powder diffraction were applied to elucidate the nature of the solid phases from the phase-solubility studies. They consistently showed the presence of solid pure paraben over the CD concentration range studied when AL-type profiles were observed, and precipitation of poorly soluble paraben/CD complexes when B-type were observed (i.e. during and after the B-type plateau region). These studies demonstrate that the composition of solid phases is related to the type of phase-solubility profile. It was also shown that in aqueous CD solutions, paraben solubilization increase with increasing side chain length (i.e. methyl < ethyl < propyl < butyl), as well as, with increasing size of the CD cavity (i.e. αCD < βCD < γCD). This statement is valid for linear region of phase-solubility diagrams (i.e. A- and B-type).

Interaction of Native Cyclodextrins and Their Hydroxypropylated Derivatives with Carbamazepine in Aqueous Solution. Evaluation of Inclusion Complexes and Aggregates Formation.

A detailed comprehensive study on how the formation of soluble and insoluble carbamazepine/cyclodextrins (CBZ/CD) complexes (with consequent changes in the solid-phase composition) depends on the CD structure is not yet available. Moreover, the study of possible influence of this drug on the tendency of CDs and their complexes to self-aggregate is still lacking. Phase-solubility studies demonstrated that CDs and CBZ form a range of soluble (AL-type: αCD, βCD, and hydroxypropylated CDs) and insoluble (BS-type: γCD) complexes depending on CD used. HPβCD proved to be the best CD solubilizer for CBZ forming the most stable complex with highest apparent solubility, whereas γCD was shown to be the best native CD. For the native CDs, CBZ solubilization increases with increasing CD cavity diameter (αCD ≪ βCD < γCD). Solid phases collected from phase-solubility studies were characterized by Fourier-transformed infrared spectroscopy, differential scanning calorimetry, and X-ray powder diffraction to elucidate their composition and crystalline structure. They provided similar conclusions being overall supportive of phase-solubility, osmolality, and permeation studies results. Solid CBZ was the only detected component for AL-type profiles over the CD concentration range studied, whereas precipitation of poorly soluble CBZ/γCD complexes (BS-type) was observed (i.e., at and beyond plateau region). Osmometry and permeation studies were applied to evaluate the effect of CBZ on the aggregate formation and also to elucidate their influence on CD complex solubility and permeation profile. Permeation method was shown to be the most effective method to detect and evaluate aggregate formation in aqueous γCD and HPβCD solutions containing CBZ. CBZ did not affect the HPβCD tendency to self-aggregate but CBZ did modify the aggregation behavior of γCD decreasing the apparent critical aggregation concentration value from 4.2% (w/v) (in pure aqueous γCD solution) to 2.5% (w/v) (when CBZ was present).

Thirty years with cyclodextrins

This paper reviews the work carried out on cyclodextrins during some thirty years at the Institut Galien Paris-Sud, UMR CNRS 8612, Université Paris-Sud. It represents the normal evolution of this domain of science and the numerous possibilities of cyclodextrins for being a tool adaptable to the most complex situations. The works which have been carried out concern: the investigation of general characteristics of cyclodextrins and derivatives, the preparation and evaluation of inclusion complexes, the use of cyclodextrins in the preparation of drug delivery systems, the various possibilities offered by cyclodextrins and their derivatives for nanoparticle preparation and finally the use of cyclodextrins for the preparation of biomaterials is evoked.

Enhanced oral bioavailability of acyclovir by inclusion complex using hydroxypropyl-β-cyclodextrin

The therapeutic potential of acyclovir is limited by the low oral bioavailability owing to its limited aqueous solubility and low permeability. The present study was a systematic investigation on the development and evaluation of inclusion complex using hydroxypropyl-β-cyclodextrin for the enhancement of oral bioavailability of acyclovir. The inclusion complex of acyclovir was prepared by kneading method using drug: hydroxypropyl-β-cyclodextrin (1:1 mole). The prepared inclusion complex was characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, NMR spectroscopy and evaluated in vitro by dissolution studies. In vivo bioavailability of acyclovir was compared for inclusion complex and physical mixture in rat model. Phase solubility studies indicate the formation of acyclovir–hydroxypropyl-β-cyclodextrin complex with higher stability constant and linear enhancement in drug solubility with increase in hydroxypropyl-β-cyclodextrin concentration. Characterization of the prepared formulation confirms the formation of acyclovir–hydroxypropyl-β-cyclodextrin inclusion complex. Dissolution profile of inclusion complex demonstrated rapid and complete release of acyclovir in 30 min with greater dissolution efficiency (90.05 ± 2.94%). In vivo pharmacokinetic data signify increased rate and extent of acyclovir absorption (relative bioavailability ∼160%; p < 0.0001) from inclusion complex, compared to physical mixture. Given the promising results in the in vivo studies, it can be concluded that the inclusion complex of acyclovir could be an effective and promising approach for successful oral therapy of acyclovir in the treatment of herpes viruses.

Preparation and Evaluation of Inclusion Complexes of Commercial Sunscreens in Cyclodextrins and Montmorillonites: Performance and Substantivity Studies

Herein we describe inclusion complexes of commercial sunscreens in cyclodextrins and montmorillonites to generate new sunscreen derivatives with optimized functional properties such as water resistance and skin adherence. Four cyclodextrins (α-, β-, and γ-cyclodextrin, and β-dimethyl cyclodextrin) and two montmorillonites (sodium and alkylammonium) were investigated for encapsulating some commercial sunscreens. Our results reveal a good yield and inclusion products with functional properties obtained by using kneading technique on Eusolex® 2292 and Eusolex® 6007 in β-cyclodextrin and solubilization method on Eusolex® 6007 and NeoHeliopan® MA in montmorillonite. In addition, molecular modeling studies indicated flexibility as important for the intercalation of the host molecule.