scholarly journals Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes

2019 ◽  
Vol 20 (8) ◽  
Author(s):  
Géza Jakab ◽  
Dóra Bogdán ◽  
Károly Mazák ◽  
Ruth Deme ◽  
Zoltán Mucsi ◽  
...  
Keyword(s):  
Inclusion Complexes ◽  
Structural Information ◽  
Aqueous Solubility ◽  
Distribution Coefficients ◽  
Scientific Data ◽  
Phase Solubility ◽  
Traditional Chinese Herbal Medicine ◽  
Form Design ◽  
C Nmr

Abstract Baicalin is a flavone glycoside extracted from Scutellaria baicalensis, a traditional Chinese herbal medicine. Numerous pharmacological effects of baicalin were reported (e.g. antioxidant, anxiolytic); nevertheless, the most important physicochemical properties influencing the pharmacokinetic behaviour and the concomitant oral bioavailability have not yet been described in a comprehensive study. The aim of this project was to characterize the acid-base, lipophilicity, biorelevant solubility and permeability properties of the drug substance and providing scientific data to support the dosage form design. Another important objective was the comparative evaluation of six various baicalin-cyclodextrin (CD) inclusion complexes along with the creation of a suitable Drug Delivery System (DDS) for this BCS IV drug. Biorelevant profiling was carried out by NMR-pH titrations, saturation shake-flask and distribution coefficients (logP) measurements, while CD inclusion studies were fulfilled by experimental methods (phase solubility, 1H/13C NMR, 2D ROESY) and computational approaches. Due to low aqueous solubility (67.03 ± 1.60 μg/ml) and low permeability (Papp = 0.037 × 10−6 cm/s), baicalin is classified as BCS IV. The γ-CD complexation significantly increased the solubility of baicalin (~ 5 times). The most promoted chemical shift change occurred in baicalin-γ-CD complex. Computational studies showed disparate binding pattern for baicalin in case of β- and γ-CD; furthermore, the calculated complexation energy was − 162.4 kJ mol−1 for β-CD, while it was significantly stronger for γ-CD (− 181.5 kJ mol−1). The physicochemical and structural information of baicalin and its CD complexes introduced herein can create molecular basis for a promising DDS with enhanced bioavailability containing a bioactive phytopharmacon.

scholarly journals Cyclodextrin inclusion complexes of the antioxidant α-lipoic acid

2014 ◽  
Vol 70 (a1) ◽  
pp. C992-C992 ◽  
Author(s):  
Mino Caira ◽  
Susan Bourne ◽  
Buntubonke Mzondo
Keyword(s):  
Inclusion Complex ◽  
Inclusion Complexes ◽  
Lipoic Acid ◽  
Aqueous Solubility ◽  
Phase Solubility ◽  
Monoclinic System ◽  
Space Group ◽  
Racemic Form ◽  
Native Host

Owing to its potent antioxidant activity,α-lipoic acid (1,2-dithiolane-3-pentanoic acid) is widely used as a supplement and is recommended for treating a number of conditions including chronic liver disease and diabetes. The poor aqueous solubility of the acid (~0.003 M at 250C) has prompted studies of its interaction with cyclodextrins (CDs) as a possible route to improving its solubility. However, relatively few studies have focused on the isolation of solid CD inclusion complexes of the antioxidant, and in most cases the racemic form of the acid was employed. In the comprehensive study reported here, the bioactive (R)-(+)-enantiomeric form of the molecule was used exclusively, resulting in the isolation and structural characterization of its inclusion complexes with each of the native host CDs (α-, β- and γ-CD) as well as permethylated α-CD (TRIMEA), permethylated β-CD (TRIMEB) and 2,6-dimethylated-β-CD (DIMEB). The α-CD complex crystallizes in the trigonal system, space group R32, with three independent CD molecules in the asymmetric unit and is not isostructural with any known CD complex while the β-CD complex crystallizes in the monoclinic system (C2). With the host γ-CD, an orthorhombic (pseudo-tetragonal) inclusion complex was identified, an unusual result as γ-CD complexes generally crystallize in the tetragonal space group P4212. The complexes with TRIMEA and TRIMEB crystallize in the orthorhombic system (P212121), the modes of inclusion of the (R)-(+)-α-lipoic acid molecule in the respective hosts being reversed: the guest molecule is fully encapsulated by the former host with the dithiolane ring located at the secondary rim, while in the latter host, the dithiolane ring rests on the concave surface of the host cavity at the primary side. A significant level of guest disorder was detected in the inclusion complex with DIMEB (P21). Thermal and phase-solubility analyses complemented the X-ray structural studies.

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

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.

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

2010 ◽  
Vol 8 (4) ◽  
pp. 953-962 ◽  
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.

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

2014 ◽  
Vol 10 ◽  
pp. 3136-3151 ◽  
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.

Enhancement of aqueous solubility of itraconazole by complexation with cyclodextrins using supercritical carbon dioxide

2005 ◽  
Vol 83 (10) ◽  
pp. 1833-1838 ◽  
Author(s):  
Ibrahim Shehatta ◽  
Ali Hassan Al-Marzouqi ◽  
Baboucarr Jobe ◽  
Ali Dowaidar
Keyword(s):  
Carbon Dioxide ◽  
Supercritical Carbon Dioxide ◽  
Stability Constant ◽  
Inclusion Complexes ◽  
Driving Forces ◽  
Aqueous Solubility ◽  
Phase Solubility ◽  
Static Mode ◽  
The Stability ◽  
Supercritical Carbon

The formation of inclusion complexes between itraconazole, a highly hydrophobic drug, and α-, β-, γ-, and hydroxylpropyl-β-cyclodextrin (HP-β-CD) were assessed using phase-solubility techniques. The solubility of itraconazole increased as a function of cyclodextrin concentration showing an AL phase diagram indicating the formation of soluble complexes with 1:1 stoichiometry. The Gibbs free energies of transfer of the drug from aqueous solution to the cavity of cyclodextrin are negative and increase in magnitude with increasing cyclodextrin concentration. The solubility of itraconazole, as well as the stability constant of its complex with HP-β-CD, are found to be affected by the pH of the medium. The HP-β-CD cavity was found to have a greater affinity for the unionized itraconazole than the protonated one. It was found that the interaction between the drug and the cyclodextrin is weakened as the medium becomes more apolar by the addition of methanol. Also, the size of the cavity of the cyclodextrins plays an important role in the association process. Furthermore, the thermodynamic parameters of the complexation process were calculated, by monitoring the isothermic solubility diagrams of itraconazole–HP-β-CD and itraconazole–β-CD at various temperatures, to gain information on the driving forces for the formation of inclusion complexes. Drug formulations of itraconazole were prepared by complexation of the drug into different cyclodextrins using supercritical carbon dioxide in a static mode. The effects of cyclodextrins on the prepared inclusion complexes were studied and characterized by differential scanning calorimetry.Key words: cyclodextrin, itraconazole, inclusion complex, solubility, stability constant.

scholarly journals The Preservation and Enantiomeric Selection of Linalool by Nanoencapsulation Using Cyclodextrins

2021 ◽  
Vol 89 (3) ◽  
pp. 42
Author(s):  
Tanaporn Poonphatanapricha ◽  
Sasimas Katanyutanon ◽  
Kulpavee Jitapunkul ◽  
Luckhana Lawtrakul ◽  
Pisanu Toochinda
Keyword(s):  
Inclusion Complexes ◽  
Computational Simulation ◽  
Aqueous Solubility ◽  
Free Form ◽  
Study Phase ◽  
Phase Solubility ◽  
Solubility Study ◽  
Beta Cyclodextrin ◽  
Phase Solubility Study ◽  
Enantiomeric Selectivity

Linalool, a volatile terpene alcohol, is responsible for a characteristic aroma in food, beverages, and cosmetics. However, linalool’s low aqueous solubility and high volatility limit the applications and shelf life of linalool-containing products. Nanoencapsulation using beta-cyclodextrin (BCD), methyl-beta-cyclodextrin (MBCD) and hydroxypropyl-beta-cyclodextrin (HPBCD) was studied to improve the aqueous solubility and stability of linalool. Linalool has two enantiomers with distinct flavors and odors which affect product quality. The enantiomeric selectivity of the cyclodextrins (CDs) toward racemic linalool standard was evaluated. A computational simulation was performed to predict the conformations and interactions of the inclusion complexes. The 1:1 host-guest ratio from the computer simulation was implemented in the experimental study. Phase solubility study shows an improvement in linalool aqueous solubility after being encapsulated by CDs. The encapsulation efficiencies of linalool/BCD, linalool/MBCD, and linalool/HPBCD inclusion complexes are 66.30%, 51.38% and 32.31%, respectively. Nanoencapsulation by CDs can preserve linalool in the form of inclusion complexes compared to its free form. The amount of remaining linalool in linalool/BCD, linalool/MBCD, and linalool/HPBCD inclusion complexes are 89.57%, 87.07%, and 74.86%, respectively which are considerably larger than that of pure linalool (42.30%). CDs also show the enantiomeric selectivity toward (R)-linalool as evident from (R)-linalool percentage of 54.53% in the inclusion complex.

scholarly journals Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol

2016 ◽  
Vol 12 ◽  
pp. 29-42 ◽  
Author(s):  
Miriana Kfoury ◽  
David Landy ◽  
Steven Ruellan ◽  
Lizette Auezova ◽  
Hélène Greige-Gerges ◽  
...  
Keyword(s):  
Inclusion Complexes ◽  
Food Systems ◽  
Antioxidant Activities ◽  
Chemical Shifts ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Aqueous Solubility ◽  
Formation Constants ◽  
Molar Ratio ◽  
Phase Solubility

Carvacrol and thymol have been widely studied for their ability to control food spoilage and to extend shelf-life of food products due to their antimicrobial and antioxidant activities. However, they suffer from poor aqueous solubility and pronounced flavoring ability that limit their application in food systems. These drawbacks could be surpassed by encapsulation in cyclodextrins (CDs). Applications of their inclusion complexes with CDs were reported without investigating the inclusion phenomenon in deep. In this study, inclusion complexes were characterized in terms of formation constants (K f), complexation efficiency (CE), CD:guest molar ratio and increase in bulk formulation by using an UV–visible competitive method, phase solubility studies as well as 1H and DOSY 1H NMR titration experiments. For the first time, a new algorithmic treatment that combines the chemical shifts and diffusion coefficients variations for all guest protons was applied to calculate K f. The position of the hydroxy group in carvacrol and thymol did not affect the stoichiometry of the inclusion complexes but led to a different binding stability with CDs. 2D ROESY NMR experiments were also performed to prove the encapsulation and illustrate the stable 3D conformation of the inclusion complexes. The structural investigation was accomplished with molecular modeling studies. Finally, the radical scavenging activity of carvacrol and thymol was evaluated by the ABTS radical scavenging assay. An improvement of this activity was observed upon encapsulation. Taken together, these results evidence that the encapsulation in CDs could be valuable for applications of carvacrol and thymol in food.

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

2013 ◽  
Vol 11 (2) ◽  
pp. 107-116 ◽  
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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