The effect of solvents and crystallization conditions on crystal habit of cholesterol

The effect of various organic solvents as well as the crystallization conditions on the crystal habit of anhydrous cholesterol have been studied. Both plates and needle-like crystals can be obtained in a particular solvent depending on the degree of supersaturation of the solution. However, the crystals grown at about the same supersaturation, from different solvents, show differences in their habit indicating dependence on the solvent-solute interaction. Thus, it is advisable not to identify needle-like crystals with anhydrous-cholesterol and plates with mono-hydrate cholesterol without specifying the crystallization conditions. A prediction on the crystal habit length to width ratios can be made using those parameters.     

HYDROCOLLOIDS AS EMULSIFYING AGENTS FOR OIL-IN-WATER EMULSIONS

Hydrocolloids are water-soluble biopolymers consisting of high molecular weight polysaccharides. For generations, these biopolymers were also termed gums or stabilizers imparting viscosity, gelification and long-term stability to food systems.

Some hydrocolloids were also considered as emulsifying agents, since they help to form and stabilize oil-in-water emulsions. Only in the last two decades questions have been raised as to the mode of their action in low viscosity and low concentrations dispersed systems consisting of oil and water.

Gum Arabic is the only gum in use in dilute emulsion systems which was proved to be a good emulsifier - adsorbing onto oil-water interfaces and imparting steric stabilization.

However, other gums have been known to reduce surface and interfacial tensions, to adsorb onto solid surfaces and to improve stability of oil-in-water emulsions. Only recently attention has been paid to the structure-surface activity relationship between the gums and their emulsification abilities. Galactomannans, xanthans, pectins, etc. are being considered as emulsifying agents, and correlation between their internal composition and activity are being studied.

This review will discuss the drawbacks and prospects of hydrocolloids as food emulsifying agents, as native hydrocolloids and as modified (chemically, enzymatically) macrobiopolymeric amphiphiles.     

Competitive solubilization of cholesterol and phytosterols in nonionic microemulsions studied by pulse gradient spin-echo NMR

The actual mechanism of cholesterol reduction by phytosterols is yet to be explored. One hypothesis states that cholesterol and phytosterols compete on the solubilization locus within gastric bile salt micelles. In this study competitive solubilization within microemulsions as vehicles for dietary intake of cholesterol and phytosterols was studied by pulse gradient spin-echo nuclear magnetic resonance. The loaded microemulsions undergo phase transitions as a function of dilution, the type of solubilized sterol, and the weight ratio of the cosolubilized sterols. Microemulsions containing 10-20 wt% of aqueous phase, show similar diffusivity of the oil and aqueous phases in all examined systems (excluding PS-loaded one) reflecting the minor influence of these solubilizates on the structure of the inner and the outer phases. The closeness of these structures enables the mobility of water molecules between them. Upon further dilution (>20 wt% aqueous phase), significant differences in decrease rate of the oil and increase of the water phases mobilities (occurring upon inversion), were detected within the studied systems. It was concluded that the solubilized sterols influence the structural transitions based on their location within the structures and their competitive solubilization. The phytosterols solubilized mostly in the continuous oil phase and between the surfactant tails. Cholesterol is solubilized in the vicinity of the surfactant headgroups and affects the surface curvature. In mixtures of cholesterol and phytosterols, structural changes are dictated mostly by the presence of the cholesterol.     

Effect of sodium diclofenac loads on mesophase components and structure

We studied the effect of a model electrolytic drug on intermolecular interactions, conformational changes, and phase transitions in structured discontinuous cubic QL lyotropic liquid crystals. These changes were due to competition with hydration of the lipid headgroups. Structural changes of the phase induced by solubilization loads of sodium diclofenac (Na-DFC) were investigated by directly observing the water, ethanol, and Na-DFC components of the resulting phases using 2H and 23Na NMR. Na-DFC interacted with the surfactant glycerol monoolein (GMO) at the interface while interfering with the mesophase curvature and also competed with hydration of the surfactant headgroups. Increasing quantities of solubilized Na-DFC promoted phase transitions from cubic phase (discontinuous (QL) and bicontinuous (Q)) into lamellar structures and subsequently into a disordered lamellar phase. Quadrupolar coupling of deuterated ethanol by 2H NMR showed that it is located near the headgroups of the lipid and apparently is hydrogen bonded to the GMO headgroups. A phase transition between two lamellar phases (L alpha to L alpha*) was seen by 23Na NMR of Na-DFC at a concentration where the characteristics of the drug change from kosmotropic to chaotropic. These findings show that loads of solubilized drug may affect the structure of its vehicle and, as a result, its transport across skin-blood barriers. The structural changes of the mesophase may also aid controlled drug delivery.     

Thermally induced fluid reversed hexagonal (H(II)) mesophase

In the present study we characterized the microstructures of the Lc and HII phases in a glycerol monooleate (GMO)/tricaprylin (TAG)/water mixture as a function of temperature. We studied the factors that govern the formation of a low-viscosity HII phase at relatively elevated temperatures (>35 degrees C). This phase has very valuable physical characteristics and properties. The techniques used were differential scanning calorimetry (DSC), wide- and small-angle X-ray scattering (WAXS and SAXS, respectively), NMR (self-diffusion and (2)H NMR), and Fourier transform infrared (FTIR) spectroscopies. The reverse hexagonal phase exhibited relatively rapid flow of water in the inner channels within the densely packed cylindrical aggregates of GMO with TAG molecules located in the interstices. The existence of two water diffusion peaks reflects the existence of both mobile water and hydration water at the GMO-water interface (hydrogen exchange between the GMO hydroxyls and water molecules). Above 35 degrees C, the sample became fluid yet hexagonal symmetry was maintained. The fluidity of the HII phase is explained by a significant reduction in the domain size and also perhaps cylinder length. This phenomenon was characterized by higher mobility of the GMO, lower mobility of the water, and a significant dehydration process.     

Hexosome and hexagonal phases mediated by hydration and polymeric stabilizer

In this research, we studied the factors that control formation of GMO/tricaprylin/water hexosomes and affect their inner structure. As a stabilizer of the soft particles dispersed in the aqueous phase, we used the hydrophilic nonionic triblock polymer Pluronic 127. We demonstrate how properties of the hexosomes, such as size, structure, and stability, can be tuned by their internal composition, polymer concentration, and processing conditions. The morphology and inner structure of the hexosomes were characterized by small-angle X-ray scattering, cryo-transmission electron microscope, and dynamic light scattering. The physical stability (to creaming, aggregation, and coalescence) of the hexosomes was further examined by the LUMiFuge technique. Two competing processes are presumed to take place during the formation of hexosomes: penetration of water from the continuous phase during dispersion, resulting in enhanced hydration of the head groups, and incorporation of the polymer chains into the hexosome structure while providing a stabilizing surface coating for the dispersed particles. Hydration is an essential stage in lyotropic liquid crystal (LLC) formation. The polymer, on the other hand, dehydrates the lipid heads, thereby introducing disorder into the LLC and reducing the domain size. Yet, a critical minimum polymer concentration is necessary in order to form stable nanosized hexosomes. These competing effects require the attention of those preparing hexosomes. The competition between these two processes can be controlled. At relatively high polymer concentrations (1-1.6 wt % of the total formulation of the soft particles), the hydration process seems to occur more rapidly than polymer adsorption. As a result, smaller and more stable soft particles with high symmetry were formed. On the other hand, when the polymer concentration is fixed at lower levels (<1.0 wt %), the homogenization process encourages only partial polymer adsorption during the dispersion process. This adsorption is insufficient; hence, maximum hydration of the surfactant head group is reached prior to obtaining full adsorption, resulting in the formation of less ordered hexosomes of larger size and lower stability.     

RELEASE OF VOLATILES FROM CUBIC PHASES: MONITORING BY GAS SENSORS

Structured fluids such as emulsions and liquid crystalline mesophases can be used to control aroma release

This study shows that the use of a gas sensor array coupled with pattern recognition analysis can be particularly useful in studying volatile profiles

A mixture of 8 carefully selected volatile, hydrophilic and hydrophobic compounds was entrapped in 4 different matrices: water, lipids (sunflower oil, unsaturated monoglycerides), emulsion (20% wt water) and cubic phases (20 and 3% wt water)

A clear discrimination between the release pattern of the different matrices has been measured by the sensor array system. It has been shown that the cubic phase release patterns is not only controlled by its composition but also depended strongly on ihe lipid/water interfacial area

The combined use of structured fluids (structure-release relationship) and sensor arrays allows to control and to distinguish the release patterns of volatile.     

Fully dilutable microemulsions embedded with phospholipids and stabilized by short-chain organic acids and polyols

Evidence on the role of phosphatidylcholine (PC) as a membrane permeability enhancer was the driving force in forming new liquid nanosized (modified microemulsions) oral delivery system containing PC molecules. In this study we have demonstrated the feasibility of constructing phase diagrams with a large isotropic regions capable of being fully diluted with water. The microemulsions were stabilized with mixtures composed of PC and nonionic surfactant (polyoxyethylene-40 hydrogenated castor oil, HECO40) and short-chain organic acid as cosurfactant/cosolvent. When propionic acid served as the cosurfactant/cosolvent, the isotropic region was at its maximum (ca. 72% of the total phase diagram area). The presence of a blend of PC and HECO40 seems to have synergistic effects, forming an isotropic region comprising 72% of the area of the phase diagram, in comparison to 20 and 50% in systems stabilized by PC and HECO40, alone, respectively. The role of the PC molecules in the formation of those microemulsions is demonstrated by comparing three soy lecithins. Lecithin with a high PC content forms larger isotropic regions with more "free dilution" lines. Several nonionic surfactants have been investigated, yet only HECO40 seems to have a packing parameter suitable for the formation of large isotropic U-type systems.     

TURBIDITY MEASUREMENTS AS A TECHNIQUE FOR EVALUATION OF WATER-IN-OIL EMULSION STABILITY

Stability of water-in-paraffinic oil (w/o) emulsions has been studied using turbidity measurements of diluted systems at 400 and 800 nm. The method has been found most suitable for detennination of the required HLB, amount and type of emulsifier, and the inner water phase fraction. The technique has been compared to other known methods and a good correlation was obtained.     

An HII liquid crystal-based delivery system for cyclosporin A: physical characterization

In the present study we demonstrate that large quantities of cyclosporin A and three dermal penetration enhancers (phosphatidylcholine, ethanol, or Labrasol) can be solubilized into reverse hexagonal (HII) liquid crystalline structures composed of monoolein, tricaprylin, and water. The microstructural characteristics of these complex multi-component systems were elucidated by rheological, SAXS, and DSC measurements. Addition of up to 20 wt% phosphatidylcholine improved significantly the elastic properties of the systems (lower values of tandelta) and increased the thermal stability of the mesophases enabling us to solubilize up to 6 wt% cyclosporin A and two other enhancers (Labrasol and ethanol) to obtain stable mesophases at physiological temperature. Rheological measurements revealed that solubilization of cyclosporin A alone has a destabilizing effect on the reverse hexagonal phases: it caused a deterioration in the elastic properties of the systems, leading to more liquid-like behavior and resulting in very short relaxation times (0.04-0.1 s). Labrasol, solubilized at high concentrations (up to 12 wt%) into the liquid crystals, also demonstrated a destabilizing effect on the HII structure: the decreasing elasticity of the system was attributed to Labrasol's presumed locus at the interface and its ability to bind water, as shown by DSC measurements. Ethanol had a destabilizing effect similar to that of Labrasol, yet the effect appeared to be more pronounced, probably due to its higher water-binding capability.