Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

The aim of this work is to improve physical properties and biological activities of the two flavanones hesperetin and naringenin by complexation with β-cyclodextrin (β-CD) and its methylated derivatives (2,6-di-O-methyl-β-cyclodextrin, DM-β-CD and randomly methylated-β-CD, RAMEB). The free energies of inclusion complexes between hesperetin with cyclodextrins (β-CD and DM-β-CD) were theoretically investigated by molecular dynamics simulation. The free energy values obtained suggested a more stable inclusion complex with DM-β-CD. The vdW force is the main guest–host interaction when hesperetin binds with CDs. The phase solubility diagram showed the formation of a soluble complex of AL type, with higher increase in solubility and stability when hesperetin and naringenin were complexed with RAMEB. Solid complexes were prepared by freeze-drying, and the data from differential scanning calorimetry (DSC) confirmed the formation of inclusion complexes. The data obtained by the dissolution method showed that complexation with RAMEB resulted in a better release of both flavanones to aqueous solution. The flavanones-β-CD/DM-β-CD complexes demonstrated a similar or a slight increase in anti-inflammatory activity and cytotoxicity towards three different cancer cell lines. The overall results suggested that solubilities and bioactivities of both flavanones were increased by complexation with methylated β-CDs.

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Studies on the Preparation, Characterization and Solubility of -Cyclodextrin-Roxythromycin Inclusion Complexes

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2009.2.2.5 ◽

2009 ◽

Vol 2 (2) ◽

pp. 523-530

Author(s):

D. Nagasamy Venkatesh ◽

S. Karthick ◽

M. Umesh ◽

G. Vivek ◽

R.M. Valliappan ◽

...

Keyword(s):

Dissolution Rate ◽

Inclusion Complexes ◽

Phase Solubility ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

X Ray ◽

Ir Studies ◽

Poorly Soluble ◽

Poorly Soluble Drug

Roxythromycin/ β-cyclodextrin (Roxy/ β-CD) dispersions were prepared with a view to study the influence of β-CD on the solubility and dissolution rate of this poorly soluble drug. Phase-solubility profile indicated that the solubility of roxythromycin was significantly increased in the presence of β-cyclodextrin and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Physical characterization of the prepared systems was carried out by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD) and IR studies. Solid state characterization of the drug β-CD binary system using XRD, FTIR and DSC revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement of dissolution rate.

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DISSOLUTION ENHANCEMENT OF ATOVAQUONE USING CYCLODEXTRINS AND FORMULATING TO ORODISPERSIBLE TABLETS

INDIAN DRUGS ◽

10.53879/id.53.06.10427 ◽

2016 ◽

Vol 53 (06) ◽

pp. 32-39

Author(s):

A. K Mahapatra ◽

◽

P. N. Murthy

Keyword(s):

Inclusion Complexes ◽

Dissolution Enhancement ◽

Phase Solubility ◽

Scanning Calorimetry ◽

Compression Technique ◽

Sodium Starch Glycolate ◽

Orodispersible Tablets ◽

Kneading Method ◽

Gibb’S Free Energy ◽

Better Than

The aim of the study was to enhance the dissolution rate of atovaquone by preparing inclusion complexes with cyclodextrins (β-CD/ HP β-CD) and formulating their orodispersible tablets. Phase solubility studies were conducted by adding 0.5, 1, 2 and 4% of cyclodextrins in water. The values of Gibb’s free energy were found increased. Inclusion complexes of atovaquone were prepared using β -CD/ HP β -CD by kneading method. Tablets were formulated using superdisintegrants i.e., sodium starch glycolate, crospovidone and Ac-Di sol at concentrations of 4, 8 and 12% of tablet weight by direct compression technique. The interaction studies were made by Fourier transform infrared spectroscopy and differential scanning calorimetry, and no significant interaction was observed. Inclusion complexes showed better dissolution than pure atovaquone and HP-β-CD established better than β-CD. Inclusion complexes of atovaquone at 1:0.25 w/w (drug: HP β -CD) in the tablets with 12% of crospovidone showed satisfactory results.

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Inclusion Complexes of β and HPβ-Cyclodextrin with α, β Amyrin and In Vitro Anti-Inflammatory Activity

Biomolecules ◽

10.3390/biom9060241 ◽

2019 ◽

Vol 9 (6) ◽

pp. 241 ◽

Cited By ~ 1

Author(s):

Walter Ferreira da Silva Júnior ◽

Danielle Lima Bezerra de Menezes ◽

Luana Carvalho de Oliveira ◽

Letícia Scherer Koester ◽

Patrícia Danielle Oliveira de Almeida ◽

...

Keyword(s):

Inclusion Complexes ◽

Biological Activities ◽

Physicochemical Characterization ◽

Inflammatory Activity ◽

Scanning Calorimetry ◽

Promising Alternative ◽

Wide Range ◽

Natural Mixture ◽

Anti Inflammatory

α, β amyrin (ABAM) is a natural mixture of pentacyclic triterpenes that has a wide range of biological activities. ABAM is isolated from the species of the Burseraceae family, in which the species Protium is commonly found in the Amazon region of Brazil. The aim of this work was to develop inclusion complexes (ICs) of ABAM and β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) by physical mixing (PM) and kneading (KN) methods. Interactions between ABAM and the CD’s as well as the formation of ICs were confirmed by physicochemical characterization in the solid state by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetry (TG) and differential scanning calorimetry (DSC). Physicochemical characterization indicated the formation of ICs with both βCD and HPβCD. Such ICs were able to induce changes in the physicochemical properties of ABAM. In addition, the formation of ICs with cyclodextrins showed to be an effective and promising alternative to enhance the anti-inflammatory activity and safety of ABAM.

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Inter-molecular physiochemical characterization for etodolac-hydroxypropyl-β-cyclodextrin polymeric systems in solid and liquid state

Open Chemistry ◽

10.2478/s11532-010-0066-3 ◽

2010 ◽

Vol 8 (4) ◽

pp. 953-962 ◽

Cited By ~ 2

Author(s):

Vivek Sinha ◽

Renu Chadha ◽

Honey Goel ◽

Keyword(s):

Solid State ◽

Inclusion Complexes ◽

Liquid State ◽

Chemical Properties ◽

Aqueous Solubility ◽

Phase Solubility ◽

Scanning Calorimetry ◽

Polymeric Systems ◽

Hydrophobic Molecule ◽

Physical And Chemical

AbstractThe purpose of this study was to explore the utility of hydroxypropyl-β-cyclodextrin (HP-β-CD) systems in forming inclusion complexes with the anti-rheumatic or anti-arthritic drug, etodolac (EDC), in order to overcome the limitation of its poor aqueous solubility. This inclusion system achieved high solubility for the hydrophobic molecule. The physical and chemical properties of each inclusion compound were investigated. Complexes of EDC with HP-β-CD were obtained using the kneading and co-evaporation techniques. Solid state characterization of the products was carried out using Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and Scanning electron microscopy (SEM). Studies in the solution state were performed using UV-Vis spectrophotometry and 1H-NMR spectroscopy. Phase solubility profiles with HP-β-CD employed was found to be AL type. Stability constants (Kc) from the phase solubility diagrams were calculated indicating the formation of 1:1 inclusion complex. Stability studies in the solid state and in liquid state were performed; the possible degradation by RP-HPLC was monitored. The dissolution studies revealed that EDC dissolution rate was improved by the formation of inclusion complexes.

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Investigations on the mechanisms of interactions between matrix metalloproteinase 9 and its flavonoid inhibitors using a combination of molecular docking, hybrid quantum mechanical/molecular mechanical calculations, and molecular dynamics simulations

Canadian Journal of Chemistry ◽

10.1139/cjc-2014-0180 ◽

2014 ◽

Vol 92 (9) ◽

pp. 821-830 ◽

Cited By ~ 8

Author(s):

Zhi-Guang Zhou ◽

Qi-Zheng Yao ◽

Dong Lei ◽

Qing-Qing Zhang ◽

Ji Zhang

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulations ◽

Biological Activities ◽

Dynamics Simulation ◽

Quantum Mechanical ◽

Free Energies ◽

Hydrogen Bond Networks ◽

Dynamics Simulations ◽

Binding Free Energies

Many experimental studies have found that flavonoids can inhibit the activities of matrix metalloproteinases (MMPs), but the relevant mechanisms are still unclear. In this paper, the interaction mechanisms of MMP-9 with its five flavonoid inhibitors are investigated using a combination of molecular docking, hybrid quantum mechanical and molecular mechanical (QM/MM) calculations, and molecular dynamics simulations. The molecular dynamics simulation results show a good linear correlation between the calculated binding free energies of QM/MM−Poisson–Boltzmann surface area (PBSA) and the experimental −log(EC50) regarding the studied five flavonoids on MMP-9 inhibition in explicit solvent. It is found that compared with the MM−PBSA method, the QM/MM−PBSA method can obviously improve the accuracy for the calculated binding free energies. The predicted binding modes of the five flavonoid−MMP-9 complexes reveal that the different hydrogen bond networks can form besides producing the Zn−O coordination bonds, which can reasonably explain previous experimental results. The agreement between our calculated results and the previous experimental facts indicates that the force field parameters used here are effective and reliable for investigating the systems of flavonoid−MMP-9 interactions, and thus, these simulations and analyses could be reproduced for the other related systems involving protein−ligand interactions. This paper may be helpful for designing the new MMP-9 inhibitors having higher biological activities by carrying out the structural modifications of flavonoid molecules.

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Preparation and characterization of artemether inclusion complexes with hydroxypropyl-β-cyclodextrin

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v16i10.7 ◽

2017 ◽

Vol 16 (10) ◽

pp. 2359-2364

Author(s):

Zwanden Sule Yahaya ◽

Kenneth C. Ofokansi ◽

Suzane T. Allagh ◽

Pat G. Bhatia

Keyword(s):

Complex Formation ◽

Inclusion Complex ◽

Dissolution Rate ◽

Inclusion Complexes ◽

In Vitro Dissolution ◽

Phase Solubility ◽

Inclusion Complex Formation ◽

Scanning Calorimetry ◽

Ft Ir

Purpose: To investigate experimentally the inclusion of artemether into the cavity of hydroxypropyl-β-cyclodextrin and examine its effect on the solubility and dissolution rate of the drug.Methods: Inclusion complexes of artemether with hydroxypropyl-β-cyclodextrin of molar ratios 1:1, 1:2 and 1:3 were prepared using the kneading method. Phase solubility analysis and in vitro dissolution studies were utilized in evaluating the influence of inclusion complex formation on the solubility and dissolution rate of the drug. The complexes were characterized using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The inclusion complex containing equimolar concentrations of artemether and hydroxypropyl-β-cyclodextrin was then formulated into tablets via direct compression and evaluated for various pharmaceutical characteristics including hardness, friability, absolute drug content and comparative in vitro dissolution profiles with some commercially available brands of artemether.Results: The phase solubility diagram for the formed complexes in water at 37 oC indicated a linear curve soluble complex system (referred to as the AL system), and a stability constant (KC) value of 143 M-1. Evidence consistent with inclusion complex formation was obtained using FT-IR and DSC. The formulated inclusion complex tablets exhibited a higher rate of dissolution than the pure drug and commercial brands, showing 3.9-, 1.8- and 1.6-fold increases, respectively, over a period of 15 min.Conclusion: Inclusion complexation of artemether with hydroxypropyl-β-cyclodextrin is a promising approach to enhance the solubility and dissolution rate of the drug.Keywords: Artemether, 2-Hydroxypropyl-β-cyclodextrin, Dissolution, Solubility enhancement, Inclusion complex

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Inclusion of trans-resveratrol in methylated cyclodextrins: synthesis and solid-state structures

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.10.331 ◽

2014 ◽

Vol 10 ◽

pp. 3136-3151 ◽

Cited By ~ 22

Author(s):

Lee Trollope ◽

Dyanne L Cruickshank ◽

Terence Noonan ◽

Susan A Bourne ◽

Milena Sorrenti ◽

...

Keyword(s):

Solid State ◽

Inclusion Complexes ◽

Crystal Packing ◽

Aqueous Solubility ◽

Solubility Limit ◽

Phase Solubility ◽

Crystalline Inclusion ◽

Scanning Calorimetry ◽

Full Structure ◽

Methylated Cyclodextrins

The phytoalexin trans-resveratrol, 5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-1,3-benzenediol, is a well-known, potent antioxidant having a variety of possible biomedical applications. However, its adverse physicochemical properties (low stability, poor aqueous solubility) limit such applications and its inclusion in cyclodextrins (CDs) has potential for addressing these shortcomings. Here, various methods of the attempted synthesis of inclusion complexes between trans-resveratrol and three methylated cyclodextrins (permethylated α-CD, permethylated β-CD and 2,6-dimethylated β-CD) are described. Isolation of the corresponding crystalline 1:1 inclusion compounds enabled their full structure determination by X-ray analysis for the first time, revealing a variety of guest inclusion modes and unique supramolecular crystal packing motifs. The three crystalline inclusion complexes were also fully characterized by thermal analysis (hot stage microscopy, thermogravimetric analysis and differential scanning calorimetry). To complement the solid-state data, phase-solubility studies were conducted using a series of CDs (native and variously derivatised) to establish their effect on the aqueous solubility of trans-resveratrol and to estimate association constants for complex formation.

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INTESTINAL ABSORPTION OF EPROSARTAN MESYLATE FROM SELF EMULSIFYING SYSTEM AND CYCLODEXTRIN COMPLEX

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i2.16215 ◽

2017 ◽

Vol 9 (2) ◽

pp. 302

Author(s):

Mohammed M. Abdol Quader ◽

Mohamed A. Osman ◽

Gamal M. El Maghraby

Keyword(s):

Inclusion Complex ◽

Intestinal Absorption ◽

Inclusion Complexation ◽

Solubility Diagram ◽

Phase Solubility ◽

Font Size ◽

Transport Parameters ◽

Cyclodextrin Complex ◽

Scanning Calorimetry ◽

Intestinal Membrane

Objective: The aim of this work was to determine the intestinal membrane transport parameters of eprosartan mesylate (EM) and to investigate self-nano emulsifying drug delivery systems (SNEDDS) and inclusion complexation with hydroxypropyl b cyclodextrin (HPbCD) for enhanced intestinal absorption of eprosartan mesylate. Methods: The intestinal absorption was monitored using the in situ rabbit intestinal perfusion technique. SNEDDS was developed using labrafil, Lauroglycol with a tween in the presence of ethanol. Inclusion complexation was achieved by construction of phase solubility diagram in the presence of HPbCD. The prepared complex was evaluated using Fourier Transform Infrared Spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: The drug was found to be poorly absorbed from the jejuno-ileum and the colon with the absorption being mainly through paracellular pathway. An inclusion complex was developed between the drug and HPβCD. Perfusion of the drug in the nanoemulsion formulation or as an inclusion complex resulted in a significant increase in the intestinal absorption of the drug compared with the control.Conclusion: SNEDDS and inclusion complexation are promising strategies for enhanced intestinal absorption of eprosartan mesylate.

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Inclusion Complexes of Rifampicin with Native and Derivatized Cyclodextrins: In Silico Modeling, Formulation, and Characterization

Pharmaceuticals ◽

10.3390/ph15010020 ◽

2021 ◽

Vol 15 (1) ◽

pp. 20

Author(s):

Qonita Kurnia Anjani ◽

Juan Domínguez-Robles ◽

Emilia Utomo ◽

María Font ◽

María Cristina Martínez-Ohárriz ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibacterial Activity ◽

Inclusion Complexes ◽

Bacterial Infections ◽

Inclusion Complexation ◽

Phase Solubility ◽

Dissolution Profile ◽

Scanning Calorimetry ◽

Ph Values

Inclusion complexation of rifampicin (RIF) with several types of cyclodextrins (βCD, hydroxypropyl-βCD, γCD, hydroxypropyl-γCD) in aqueous solutions at different pH values was investigated to assess the interactions between RIF and cyclodextrins (CDs). Molecular modeling was performed to determine the possible interactions between RIF and CDs at several pH values. The inclusion complexes were characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, powder X-ray diffractometry, and scanning electron microscopy. Moreover, this study evaluated the dissolution profile and antibacterial activity of the formed complexes. Phase solubility analysis suggested the formation of RIF-CD affirmed 1:1 stoichiometry at all pH values (except RIF-βCD at pH 4.0 and both βCD and γCD at pH 9.0). The inclusion complexation of RIF with CD successfully increased the percentage of RIF released in in vitro studies. The inclusion complexes of RIF exhibited more than 60% of RIF released in 2 h which was significantly higher (p < 0.05) than release of pure RIF, which was only less than 10%. Antibacterial activity of RIF-CD complexes (measured by the minimum inhibitory concentration of RIF against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus) was lower for both RIF-βCD and RIF-HPγCD at pH 7.0 to pure RIF suspension. In conclusion, this work reports that both βCD and γCD can be used to enhance the solubility of RIF and thus, improve the effectivity of RIF by decreasing the required daily dose of RIF for the treatment of bacterial infections.

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Preparation and in vitro Evaluation of Inclusion Complexes of Nelfinavir with Chemically Modified ?-cyclodextrins

Dhaka University Journal of Pharmaceutical Sciences ◽

10.3329/dujps.v11i2.14558 ◽

2013 ◽

Vol 11 (2) ◽

pp. 107-116 ◽

Cited By ~ 3

Author(s):

Shivanand Hiremath ◽

Ganesh Godge

Keyword(s):

Inclusion Complex ◽

Inclusion Complexes ◽

Solubility Diagram ◽

Aqueous Solubility ◽

Water Soluble ◽

Phase Solubility ◽

Ir Study ◽

Order Complexes ◽

Phase Solubility Diagram

Nelfinavir is a poorly water-soluble antiretroviral drug with relatively low bioavailability. In the present study, the practically insoluble drug, nelfinavir (NFV) and its inclusion complexes with hydroxypropyl-?-cyclodextrin (HP-?-CD) were investigated to improve the aqueous solubility and the dissolution rate of the drug, thus enhancing its bioavailability. The phase solubility diagram with HP-?-CD was classified as AL-type at all temperatures investigated, indicating the formation of higher order complexes. The apparent complexation constants (K1:1) calculated from phase solubility diagram were 145.49, 188.45 and 255.54 M-1 at 25, 37 and 45 ± 0.5°C, respectively. Aqueous solubility and dissolution studies indicated that the dissolution rates were remarkably increased; this could be mainly attributed to the improved solubility and dissolution associated with inclusion complex between drug and HP- ? -CD. Absence of endothermic and characteristic diffraction peaks corresponding to NFV was observed for the inclusion complex in DSC and PXRD. FT-IR study indicated that the presence of intermolecular hydrogen bonds between NFV and HP-?-CD in inclusion complex, resulting in the formation of amorphous form. DOI: http://dx.doi.org/10.3329/dujps.v11i2.14558 Dhaka Univ. J. Pharm. Sci. 11(2): 107-116, 2012 (December)

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