Phase solubility studies and stability of cholesterol/β-cyclodextrin inclusion complexes

BACKGROUND: Cyclodextrins (CDs) are able to enhance the solubility, stability and bioavailability of several bioactive hydrophobic compounds by complex formation. They can also be used for removal of undesired components (such as cholesterol, off‐flavors or bitter components) present in foods. Although many patents account for the use of cyclodextrins for removal of cholesterol from dairy foods, there is no available information on the effect of water on encapsulation efficiency and on the stability of sterols in CDs. The aim of this work was to study the inclusion properties and the factors affecting the encapsulation and stability of cholesterol in β‐cyclodextrin (BCD). The optimum encapsulation conditions (ligand–CD molar ratio, stirring time and temperature), and stability of the complexes as a function of storage time and water content were analyzed. RESULTS: Phase solubility study pointed out the formation of 1:1 stoichiometric complexes between cholesterol and β‐cyclodextrin, which was influenced by temperature variations. The process was shown to be exothermic and energetically favored. The presence of cholesterol greatly modified the BCD water sorption curves, being the amount of adsorbed water smaller in the combined systems. The principal ‘driving force’ for complex formation is the substitution of the high‐enthalpy water molecules by an appropriate hydrophobic ligand. The freeze‐dried complexes probed to be stable at different storage conditions. CONCLUSION: The phase solubility and stability data obtained could be essential for selecting the most suitable conditions when CDs are employed either for removing cholesterol or to incorporate functional ingredients (i.e. sitosterol) in the development of innovative food products. Copyright © 2011 Society of Chemical Industry     

Formation of β-cyclodextrin inclusion enhances the stability and aqueous solubility of natural borneol

The aims of this study were to optimize the preparation conditions of natural borneol/β-cyclodextrin (NB/β-CD) inclusion complex by ultrasound method, and to investigate its improvement of stability and solubility. The complex was characterized by different various spectroscopic techniques including Fourier transform infrared spectroscopy, X-ray diffractometry, and differential scanning calorimetry. The results demonstrate that NB could be efficiently loaded into β-CD to form an inclusion complex by ultrasound method at a molar ratio of 1 : 1 and mass ratio of 1 : 6. The complex exhibited different physicochemical characteristics from that of free NB. Typically, formation of β-CD inclusion significantly enhanced the stability and aqueous solubility of NB. PRACTICAL APPLICATION: Natural borneol (NB) has the potential to be widely used in the fields of medical and functional food, due to its specificity. However, the disadvantages of unstability in the preparation and storage process due to its easy sublimation and the low water solubility limit its application. This research provides an effective way to improve the solubility and stability of NB by preparing NB/β-CD inclusion complex. Furthermore, theoretical basis is also provided for the application development of NB.     

Preparation and stability of the inclusion complex of astaxanthin with hydroxypropyl-β-cyclodextrin

The inclusion complex of astaxanthin (ASX) with hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared. Infrared spectroscopy (IR) proved the formation of the inclusion complex. The water solubility of the inclusion complex was >1.0 mg/ml, which is much better than that of ASX. The solid state thermal behaviour of the inclusion complex was investigated by thermogravimetric/differential thermal analysis (TG/DTA). The starting decomposition temperature of ASX was enhanced to about 290 °C. The stability of the inclusion complex in solution was also tested. Forming of the inclusion complex greatly enhanced the stability of ASX against light and oxygen. Furthermore, the release of ASX from the inclusion complex was controlled.     

Preparation,characterisation and activity of the inclusion complex of paeonol with β-cyclodextrin

The inclusion complex of β-cyclodextrin (β-CD) and paeonol (2′-hydroxy-4′-methoxyacetophenone, PAE) was synthesised and characterised by thermal gravimetric analysis (TGA) and two-dimensional rotating frame spectroscopy (2D ROESY). The antioxidant activity and tyrosinase inhibition activity were also studied. The TGA results indicated that the thermal stability of PAE was improved when it was included with β-CD. Based on the 2D ROESY analysis, an inclusion structure of the PAE–β-CD complex was proposed, in which PAE penetrated β-CD in a tilted manner due to the interaction of intermolecular hydrogen bonds between PAE and β-CD. The complex of PAE with β-CD increased the antioxidant activity and tyrosinase-inhibiting activity of PAE.     

Preparation,physicochemical characterization and release behavior of the inclusion complex of trans-anethole and β-cyclodextrin

Trans-anethole (AT) has a variety of antimicrobial properties and is widely used as food functional ingredient. However, the applications of AT are limited due to its low water solubility, strong odor and low physicochemical stability. Therefore, the aim of this work was to encapsulate AT with β-cyclodextrin (β-CD) for obtaining inclusion complex by co-precipitation method. The measurements effectively confirmed the formation of inclusion complex between AT and β-CD. The results showed that the inclusion complex presented new solid crystalline phases and was more thermally stable than the physical mixture and β-CD. The phase solubility study showed that the aqueous solubility of AT was increased by being included in β-CD. The calculated stability constant of inclusion complex was 1195 M^− 1, indicating the strong interaction between AT and β-CD. Furthermore, the release study suggested that β-CD provided the protection for AT against evaporation. The release behavior of AT from the inclusion complex was controlled.     

Preparation and characterization of the inclusion complex of hypocrellin A with hydroxypropyl-β-cyclodextrin

Hypocrellin A (HA) is a naturally occurring perylenequinone pigment with bright red colour. The inclusion complex of HA with hydroxypropyl-β-cyclodextrin was prepared successfully by lyophilization method for the first time. Phase solubility studies indicated that the inclusion complex was formed with possible stoichiometry of 1:1. The apparent stability constants and the thermodynamic parameters such as enthalpy change (∆H), entropy change (∆S) and Gibbs free energy (∆G) were calculated in the range of 25–45 °C. The values of apparent stability constants decrease with the increasing of temperature. The thermodynamic results showed that the inclusion process was an exothermic and enthalpy-driven process accompanied with a negative entropic contribution. The formation of inclusion complex was also conformed by Fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetry and spectroscopic studies. The inclusion complex showed much better water solubility and dissolution property than the free HA. Therefore, the inclusion complex can be used to expand the application of HA in food, feed and pharmaceutical industries.     

Effect of water activity on sugar crystallization and β-carotene stability of freeze-dried mango powder

Storage water activity (a_w) affects the stability of freeze-dried food. The sugar crystallization and storage stability of β-carotene in freeze-dried mango powder was investigated following storage under various relative vapor pressures (11.3-80.9%). Sugar crystallization was revealed by the loss of sorbed water in the water sorption experiment. However, the sorption isotherms showed unclear divergence between the experimental and predicted values. X-ray powder diffraction and scanning electron microscopy were used to confirm the crystallization. The results showed that increased a_w resulted in higher sugar crystallization. The loss of β-carotene was monitored by high-performance liquid chromatography with a diode-array detector and fitted to a first-order reaction. The rate constant decreased as a_w increased up to 0.43, due to the collapse of the mango powder. An increase in the rate constant above this value of a_w coincided with pronounced sugar crystallization. Choosing the appropriate value of a_w for storage can prevent sugar crystallization and enhance β-carotene stability in freeze-dried fruit powder.     

Preparation and properties of phytosterols with hydroxypropyl β-cyclodextrin inclusion complexes

In order to enhance the solubility and bioavailability of phytosterols (PS), cyclodextrin–PS (CD–PS) inclusion complexes were prepared and the properties of PS-β-cyclodextrin (PS-β-CD) and the inclusion mechanism of its derivative hydroxypropyl β-cyclodextrin (PS-HP-β-CD) in solution were also evaluated. The effects of crucial parameters on cyclodextrin–sterol inclusion efficiency were optimized, including solvent type, β-CD/PS molar ratio, temperature, PS content and reaction time; 92–98?% inclusion efficiency was achieved under the conditions of HP-β-CD/PS ratio 3:1–4:1, PS concentration 15–20?mM, temperature 50–55?°C, reaction time 12?h. For β-CD host, butanol was a good solvent for PS inclusion reaction. The properties of CD–PS inclusion complexes were characterized by differential scanning calorimetric, scanning electron microscopy, UV–Vis scanning spectrophotometer (UV–Vis) and fourier transform infrared spectroscopy (FT-IR), which demonstrated that there are intermolecular hydrogen bonds between PS and HP-β-CD in inclusion complex, resulting in the formation of amorphous form. To clarify the mechanism of the increase in the solubility and bioactivity of HP-β-CD–PS inclusion complexes, the structure of CD as well as the interaction of the HP-β-CD–PS inclusion formation was elucidated. The conclusions indicated that PS-HP-β-CD showed higher water solubility with greater solubilizing and complexing capabilities than PS-β-CD and PS itself.     

Fucoidan improves the structural integrity and the molecular stability of β-lactoglobulin

β-lactoglobulin (β-lg) was covalently bonded with fucoidan through Maillard reaction at 60 °C for 96 h under 79% RH condition. The molecular characters of the conjugate were investigated using fourier transform infrared spectroscopy (FT-IR), atomic force microscopy (AFM), and circular dichroism (CD) spectroscopy. And, its thermal properties, surface activity, and zeta-potential were compared with intact β-lg, β-lg-fucoidan mixture, and fucoidan under different pH conditions. AFM indicated that the conjugate was nano-structured, regular spherical-shaped and generally large sized compared to β-lg-fucoidan mixture. CD spectra and FT-IR showed that tertiary structure of β-lg slightly unfolded, but little change in secondary structure occurred. This explained that glycation under Maillard condition resulted in a molten globule state of β-lg. Differential scanning calorimetry (DSC) data exhibited that fucoidan shifted the temperature of phase transition and improved thermal stability of β-lg molecule. In addition, the conjugate prominently decreased the surface tension with pH-dependency.     

Water dispersibility of the β-carotene source and its effect on the physical,thermal, and in vitro release properties of an inclusion complex

There is a need to understand the effect of in vitro digestion on the release of β-carotene (BC) from inclusion complexes (IC) prepared with water-dispersible (WDBC) or hexane-soluble (HSBC) sources. IC were prepared by co-precipitating WDBC or HSBC with β-cyclodextrin and characterised using imaging, spectral (FTIR) and thermal techniques. Two solvent systems (absolute ethanol, AE and 4:3 ethanol–hexane, EH) were employed to compare extractability of BC during simulated co-digestion with rice as food matrix. WDBC-IC had greater yield (89% vs. 44%) but lower encapsulation efficiency (30% vs. 89%) than HSBC-IC. Imaging, FTIR and thermal data confirm inclusion complex formation. In vitro WDBC release extracted with AE decreased uniformly and was unaffected by rice, whereas HSBC extracted with EH exhibited gradual release towards intestinal digestion but decreased with rice. Fabricated microcapsules with suitable forms of BC may be applied for food fortification purposes.     

Influence of dietary β-alanine and histidine on the oxidative stability of pork

Carnosine (β-alanine-L-histidine) and anserine (β-alanine-1-methyl histidine) are endogenous antioxidants found in skeletal muscle. The objective of this research was to determine if supplementation of swine diets with histidine (histidine; 0.40%) and/or β-alanine (β-alanine; 0.225%) was an effective method to increase carnosine and anserine concentrations and the oxidative stability of Longissimus dorsi (LD) and Vastus intermedius (VI) muscles. Dietary treatments had no effect on carnosine and anserine concentrations in LD; however, histidine + β-alanine supplementation increased carnosine and anserine in VI muscle compared to β-alanine supplementation. Dietary supplementation had no effect on the formation of thiobarbituric acid reactive (TBARS) or lipid peroxides in cooked VI and LD. In salted VI and LD muscle, differences in TBARS and peroxides were observed; however, these differences did not consistently correlate with differences in anserine and carnosine concentrations. Therefore, the results of this research suggest that supplementation of swine diets with β-alanine and/or histidine is not an efficient method to increase the oxidative stability of pork.     

Evaluation of complex forming ability of hydroxypropyl-β-cyclodextrins

The complex forming ability of hydroxypropyl-β-cyclodextrins (HP-β-CDs) is highly influenced by the distribution of substituents and the average degree of substitution (DS), both the size of the cavity and the reactivity of CDs are altered when the hydroxyl groups are substituted. On the other hand, the guests themselves influence these interactions by their sizes and configurations. In the present study, 9 HP-β-CDs with different substitution patterns and DS, which have been investigated by the reductive-cleavage method and methylation analysis, were chosen. The interactions among HP-β-CDs and phenolphthalein (as a model for ‘larger spheriform’ guests) or p-methyl red (as a model for ‘smaller linear’ guests) were studied for determining the complex forming ability of HP-β-CDs. The results indicated that, compared with parent β-CD, HP-β-CDs have a lower ability to form inclusion complexes with the ‘larger spheriform’ guest molecules. With regard to the ‘smaller linear’ guest molecules, HP-β-CDs have a higher complex forming ability, especially the low DS value (<6.5) HP-β-CDs which have a ratio of DS (2 + 3) to DS (6) close to 1.     

Influence of maltodextrin type and multi-layer formation on the freeze-thaw stability of model beverage emulsions stabilized with β-lactoglobulin

The influences of maltodextrin (MD) addition and multi-layer formation on the freeze-thaw stability of β-lactoglobulin (β-Lg)-stabilized oil-in-water beverage emulsions (0.1 wt% corn oil, 0.006 wt% β-Lg) were investigated. Various beverage emulsions were prepared depending on MD concentration (0–20 wt%), its dextrose equivalent (M150 or M250), and the presence or absence of additional polysaccharides (pectin, alginate, or ι-carrageenan) coatings around the emulsion droplets. All emulsions (β-Lg- and β-Lg-polysaccharide-coated emulsions) were unstable to experimental freeze-thaw cycling in the absence of MD. In the presence of MD, all emulsions containing M250 had better stability to droplet aggregation than those with M150, regardless of MD concentrations and freeze-thawing. The optimum concentrations of M250 required to prevent emulsions destabilization under the freeze-thawing were 6, 15, and 2% for β-Lg-, β-Lg-ι- carrageenan-, and β-Lg-pectin-coated emulsions, respectively. This study implicates practical information to improve freeze-thaw stability of some beverage emulsion products that inevitably go though freezing during processing.     

Encapsulation of cinnamon and thyme essential oils components (cinnamaldehyde and thymol) in β-cyclodextrin: Effect of interactions with water on complex stability

Thymol and cinnamaldehyde formed inclusion complexes with β-cyclodextrin (β-CD) upon mixing the components in aqueous media and subsequent freeze–drying, as confirmed by differential scanning calorimetry. The samples were stored at constant relative humidities (RH) from 22% to 97%, at 25 °C. The release of encapsulated compounds was determined following the melting enthalpy of each guest. Water sorption isotherms for β-CD and the complexes showed constant and low water sorption at RH < 80%, then the uptake of water increased abruptly. The amount of sorbed water at each RH was smaller for the complexes than for β-CD. The guest molecules displaced water molecules from inside the cavity of β-CD. No thymol or cinnamaldehyde release was detected at RH < 84%, and it increased abruptly from 84% RH, coincidentally with the abrupt increase of sorbed water. Water sorption significantly affects β-CD complexes stability, which is thus governed by the shape of the water sorption isotherm.     

Influence of collapsed structure on stability of ��-carotene in freeze-dried mangoes

This study aimed to investigate the effect of structural collapse of freeze-dried mangoes on stability of ??-carotene. Three different freeze-drying protocols were performed to produce collapse and non-collapse structures of freeze-dried mangoes. Thermal transitions of samples were determined using a differential scanning calorimeter. ??-carotene content was monitored during storage using high-performance liquid chromatography. The ??-carotene degradation followed first-order kinetics. Mangoes freeze-dried at above ice melting temperature revealed structural collapse which decreased ??-carotene degradation rate. These dense and collapsed structures formed prevented oxygen penetration through the solids. Liquid nitrogen freezing also gave structural collapse coincided with surface cracking on freeze-dried mangoes. Such structure showed no protective effect on ??-carotene as similar degradation rate to non-collapsed systems was observed. The cracking on mango surface potentially allows high oxygen penetration through the solids thus promoting ??-carotene loss. These findings give benefit to the production of freeze-dried fruits to increase storage stability of ??-carotene.     

Heat stability of allyl isothiocyanate and phenyl isothiocyanate complexed with randomly methylated β-cyclodextrin

Inclusion complexation reactions between isothiocyanates (ITCs), namely, allyl isothiocyanate (AITC) and phenyl isothiocyanate (PITC), and randomly methylated β-cyclodextrin (RM-β-CD) displayed “A_P” type solubility isotherms, indicating continuous increases in the stoichiometry of the inclusion complexes. The complex powders were prepared by spray drying and their heat stability was studied by thermal analysis and heat treatment in paraffin. The solid-state dissociation reactions were satisfactorily described by the unimolecular decay law. The apparent activation energy of dissociation, E_D, was determined to be 48 and 58 kJ/mol, respectively, for the AITC/RM-β-CD and PITC/RM-β-CD complexes, while the apparent activation energies of decrease of ITCs in paraffin, E_P for the pure AITC and PITC, and the corresponding inclusion complexes were 26, 48, 44, and 54 kJ/mol, respectively, suggesting volatility suppression and physical stabilisation by inclusion complexation as the plausible mode of stabilisation of the ITCs in paraffin. A compensation effect in the kinetics of depletion of the ITCs in paraffin was established.