It is well documented that phytosterols inhibit the uptake of exogenic cholesterol and do not interfere with cholesterol synthesis or cause side effects. The mechanism by which phytosterols interfere with cholesterol absorption is not completely clear and there are at least three hypotheses for their beneficial activity. Among these is that of competitive solubilization of phytosterols and cholesterol in dietary mixed micelles. In the present study we investigated the competitive solubilization of phytosterols (approx. 50% $\beta$-sitosterol) and cholesterol in a nonionic microemulsion system constructed as a model for the dietary mixed micelles. We studied the effect of the competitive solubilization of cholesterol and phytosterols on the structural transformations and phys. properties of the microemulsion and evaluated the locus of the solubilizates within the nanodroplets of each sterol sep. and when they are loaded together at different wt. ratios along one diln. line. Our results show that chem. and structural differences between cholesterol and phytosterols significantly influence the solubilization capacity of the nonionic microemulsion. Cholesterol, being more amphiphilic, is solubilized more efficiently at the W/O microemulsion interface, while in the O/W microemulsion phytosterols are dissolved somewhat more efficiently in the droplet core. [on SciFinder(R)]

Celecoxib belongs to a new NSAID family specifically inhibiting cyclooxygenase-2 (COX-2). The present formulations require high dosage since the transmembrane transport fluctuates and is very difficult to control. The authors solubilized celecoxib in micelles of nonionic microemulsions and hydrophilic surfactant. The supersatd. solubilized drug was pptd. from the nano-droplets to form a new solid structure with improved dissoln. properties. The selected microemulsion systems loaded with celecoxib were characterized by SAXS, SD-NMR, viscosity, and elec. cond. techniques. Pptn. was conducted from W/O as well as from O/W U-type microemulsions. The crystals obtained by the pptn. were characterized by x-ray powder scattering, differential scanning calorimetry, FTIR measurements, and microscopic scans. [on SciFinder(R)]

The binary phase diagram of GMO/water reveals the formation of two major lyotropic mesophases that have been extensively studied. Adding short-chain alc. (ethanol, propanol and butanol) to a mixt. of various compns. formed one large isotropic micellar phase (the L phase) and two small confined lyotropic regions termed the L3 sponge phase and the QL (micellar cubic). The QL phase is a new mesostructure. It was shown that while the cubic phase is highly viscous the QL phase is fluid and, it displays unique phys. properties. It is fully transparent (not tinted), non-birefringent, and very stable at room temp. (samples were stored for over 8 mo with no phys. changes). The phases were investigated by cryo-TEM, SAXS and self-diffusion NMR. The structure it has primitive cubic symmetry and is discontinuous micellar phases rather than a bicontinuous one. The QL phase was further dispersed in water contg. amphiphilic copolymer (Pluronic 127) to form cubic nanoparticles that we termed micellosomes. The effect of solubilization of water-insol. drugs like, diclofenc (DCF), at different concns. (0.1, 1, 3, and 10 wt%) in the QL phase was investigated by SAXS, rheol. measurements, and NMR (self-diffusion and relaxation) measurements. The rate of percutaneous penetration through rat skin of these structures is significantly higher than that of the com. drug. The compn. that shows the best penetration was QL with 1 wt% DCF. [on SciFinder(R)]

Proteins, polysaccharides and their blends, as examples of natural biopolymers, may be considered as amphiphilic macromolecules that play an essential role in stabilizing food formulations (foams, emulsions and dispersions). Under specific compositions and conditions (protein-to-polysaccharide ratio, pH, ionic strength, temperature, mixing, processing steps) proteins and polysaccharides form water-soluble hybrids (complexes or conjugates), but not coacervates, with enhanced functional properties in comparison to the proteins and polysaccharides alone. Aqueous mixtures of WPI (4-10wt%) and xanthan gum (\textgreater 0.5wt%) form clear aqueous systems exhibiting new physicochemical properties such as rheological behavior, surface properties, surface density of charge (zeta potential), surface hydrophobicity and diffusion behavior. Electrostatic interactions and thermodynamic incompatibility in mixed biopolymer solutions were correlated to the functional properties (rheology, surface properties and surface hydrophobicity) of these adducts. Evidences for associative interactions between WPI and xanthan gum have been established by studying the rheological behavior, the surface hydrophobicity and the surface dynamic properties of the blends. The electrostatic and hydrophobic interactions form hybrids that can provide a synergistic effect on the emulsifying capabilities of the biopolymers and can increase the stability of emulsion droplets against coalescence and flocculation. (c) 2006 Elsevier Ltd. All rights reserved.

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 aq. 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 compn., polymer concn., and processing conditions. The morphol. and inner structure of the hexosomes were characterized by small-angle x-ray scattering, cryo-transmission electron microscope, and dynamic light scattering. The phys. stability (to creaming, aggregation, and coalescence) of the hexosomes was further examd. 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 liq. 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 crit. min. polymer concn. is necessary in order to form stable nanosized hexosomes. These competing effects require the attention of those prepg. hexosomes. The competition between these two processes can be controlled. At relatively high polymer concns. (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 concn. is fixed at lower levels (\textless1.0 wt %), the homogenization process encourages only partial polymer adsorption during the dispersion process. This adsorption is insufficient; hence, max. 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. [on SciFinder(R)]

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) liq. cryst. structures composed of monoolein, tricaprylin, and water. The microstructural characteristics of these complex multi-component systems were elucidated by rheol., SAXS, and DSC measurements. Addn. of up to 20 wt% phosphatidylcholine improved significantly the elastic properties of the systems (lower values of tan $δ$ ) 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 physiol. temp. Rheol. 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 liq.-like behavior and resulting in very short relaxation times (0.04-0.1 s). Labrasol, solubilized at high concns. (up to 12 wt%) into the liq. 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. [on SciFinder(R)]

A review discusses the development of modified microemulsions as nanosized self-assembled liq. (NSSL) vehicles for the solubilization of nutraceuticals and to improve transmembrane transport for addnl. health benefits. The solubilization of nonsol. active ingredients such as aromas and antioxidants into clear beverages that are based on water-continuous phase is presented. [on SciFinder(R)]

Solubilization capacity and structural transformations in nonionic microemulsions characterized by a large continuous isotropic region forming dilutable self-assembled nanodroplets contg. solubilized carbamazepine, were studied along diln. lines 73 and 82 (70 and 80% surfactant and 30 and 20% of oil phase, resp.). The prepns. were based on pharma-grade ingredients, water, R-(+)-limonene, ethanol, propylene glycol, and Tween 60. Solubilization capacity (SC) of the drug was dependent on the microstructure of the microemulsion and on the surfactant-to-oil phase wt. ratio. The SC in the conc. (reversed micelles) was 15 times higher than its soly. in the oil. Transition of the W/O microemulsion to a bicontinuous phase and to O/W droplets were identified by elec. cond., viscosity, SAXS, and SD-NMR measurements. Once the system is dild. to 90% aq. phase, the SC is 10 and 16-fold higher, along diln. lines 73 and 82, resp., than in pure water. Being solubilized, carbamazepine serves as a cosurfactant therefore it affects the curvatures of the microstructures and consequently the boundaries of the structural regions and the transition points between the different phases. Dilutable microemulsions are promising new carbamazepine vehicles for oral intake. [on SciFinder(R)]

In constructing the phase diagram of glycerol monooleate (GMO)/EtOH/H2O mixts. the authors detected, in addn. to the well-characterized regions of lamellar and cubic bicontinuous liq. crystals, 3 addnl. isotropic transparent regions that were not previously well-defined; a large isotropic region denoted in early studies as the L1-phase, an isotropic region with characteristics similar to the sponge L3-phase, and a 3rd isotropic region which had not been characterized previously. The present study deals with efforts to characterize this unique isotropic region. The isotropic region is an island located within a 2 phase region connecting the 3 isotropic regions of the cubic, lamellar, and micellar phases. The authors termed this phase I2 (QL) phase or the QL phase, which stands for cubic liq. mesophase. This phase is a totally transparent and nonbirefringent fluid (completely pourable). It is stable even after over 9 mo of storage at room temp. The fluid is of low viscosity and almost Newtonian. The new phase shows many characteristic features of an ordered phase. Small-angle x-ray scattering measurements (SAXS), SAXS-synchrotron temp.-dependent measurements, and cryogenic-TEM (cryo-TEM) observation reveal that the phase has a cubic symmetry. The SAXS diffractions indicate formation of a somewhat less ordered discontinuous cubic micellar mesophase. The cryo-TEM images provide strong evidence for ordered domains with cubic symmetry. Complementary measurements confirm that the phase is a unique case of a micellar cubic phase. The authors expect that the fluidic ordered mesostructure will have future applications as a liq. vehicle for the solubilization of nutraceuticals, cosmetoceuticals, and pharmaceuticals. [on SciFinder(R)]

Polar lipid mols. such as glycerol monooleate (GMO) and polar solvent (usually water) can spontaneously organize in high order at the long-range distances while in the short-range, at at. distances, they are disordered. Liq. cryst. mesophases with a long-range order in one dimension are lamellar phases (L$\alpha$ ) while those showing two dimensional long-range order are known as hexagonal phases (HI and H2 for normal and reverse hexagonal) and those with three dimension long-range orders are lyotropic cubic phase (C). Hydrophobic effect with a variety of intra- and intermol. interactions, in combination with a no. of geometric packing constraints, are responsible for the degree of order. Addn. of guest mols. (solubilizates) to the liq. crystals can alter the structure according to specific mol. interaction between the GMO and the guest compd. that contributes to the surface area species. In our recent studied we have discovered that ternary blends of GMO, water and cosolvent can form unique structures. The focus of this presentation is on a new mesophase that was formed as a result of phase transformations. The new structure was eluted from lamellar, cubic, and hexagonal isotropic liq. phases in ternary systems. The new phase, termed by us the QL mesophase, is very unique since it is transparent liq. phase with long-range order. The QL phase was studied by small-angle X-ray scattering (SAXS), cryo-transmission electron microscopy (cryo-TEM), self-diffusion NMR, DSC and cond. methods. The unique rheol. properties of a system totally fluid and yet non Newtonian will be discussed in view of the suggested structure of micellar discontinuous cubic phase. Microstructure data as well as solubilization data of several nutraceuticals mols. and their bioavailability advantages will be presented. [on SciFinder(R)]

The crystn. patterns of carbamazepine pptd. from a confined microemulsion reservoir were studied by DSC, TGA, Powder XRD, single crystal XRD, SEM, and optical microscopy. The results suggest that interfacial fast nucleation and slow growth from O/W microemulsion leads to a selective, large, and better-ordered single crystals of dihydrate form with primitive monoclinic unit cell with parameters a = 10.16 {\AA

Protein/polysaccharide conjugates were used to stabilize oil-in-water (O/W) emulsions and oil-in-water-in-oil (O/W/O) double emulsions. By properly selecting the type of protein (WPI) and the polysaccharide (xanthan gum, fenugreek gum), and by using specific ratios of the two biopolymers and their soln. concns., amphiphilic biopolymer adducts were formed. A synergism in the emulsification properties was obsd. in WPI/polysaccharide conjugates compared to each of the biopolymers alone. Submicron droplets of oil-in-water were obtained by applying a high-pressure homogenization process during the first step of the double emulsion prepn. It was also demonstrated that double-emulsion globules could be formed with a very high yield of addendum entrapment (above 95%) during the second step of the emulsification process. The differentiation between the two types of oils, O1 (the inner) and O2 (the outer), in the double emulsions enabled high entrapment capacity of the addendum in the inner oil phase. In addn., when the inner oil phase (O1) was a 1:1 (wt./wt.) mixt. of MCT/triacetin and the external oil phase (O2) was a silicone oil, it was possible to slow the release of the entrapped matter while the soly. of the inner phase in the external oil phase remained const. The addendum soly. in the external oil phase was not a limiting factor in the release process. The presence of hydrophobic additives (i.e., 1% glycerol monooleate) in the inner oil phase helped to better control the transport to the external oil phase. In the best case, the addendum leakage to the external oil phase was only ∼0.2% during a period of 28 days at 25°. WPI/xanthan gum adducts served as thick and efficient barriers against release of flumethrin (a veterinary drug model) entrapped in the core of the O/W/O multiple globules. [on SciFinder(R)]

The present study evaluates the effect of a solubilized model drug, diclofenac sodium salt (diclofenac), in our unique new U-type microemulsion system embedded with phosphatidylcholine (PC) in terms of microstructure transformations, phys. properties of the system (viscosity, elec. cond.), droplet sizes and shapes, and nucleation and growth of the droplets. The phys. properties are correlated to the permeability of diclofenac through Caco-2 monolayer cells. The major findings reported are: (1) systems that are rich in surfactant and contain minimal oil phase form a microemulsion that enables high solubilization of diclofenac (20% diclofenac in the oil and surfactant conc. can be fully dild. with water); (2) PC presence at the interface does not affect the size of the O/W droplets, while the presence of diclofenac at the interface decreases the O/W droplet size by an av. of 50%; (3) diclofenac seems to increase incorporation of PC into the W/O interface; (4) diclofenac affects the phys. properties of the microemulsion increasing the viscosity of the W/O microemulsion system and completely changing the cond. profile of the system upon water diln.; (5) cryo-TEM images indicate that above 70% water the droplets are spherical; (6) diclofenac permeability through Caco-2 monolayer cells increases when PC is embedded into the interface. [on SciFinder(R)]

A review. Polar lipids and certain surfactants are known to form thermodynamically stable lyotropic liq. crystals (LLC) when mixed with water. The major phases are lamellar (La), normal and reverse hexagonal (HI and HII) and cubic bicontinuous and discontinuous structures (VI VII and II, III, resp.). Theor., the transformation sequence of the phases with increasing water content is III → HII → VII → La → VI → HI → II. Lyotropic liq. crystal transformation was extensively studied and was found to take place also upon surfactant modifications (head or tail), addn. of a guest mol. (hydrophilic or hydrophobic), co-surfactant or electrolyte and varying the temp. The phases are of growing scientific and industrial interest because of their structural resemblance to human membranes through which drug passage of lipophilic compds. (vitamins, fats, oil and cholesterol) occurs and because of their high surface area and solubilization capacities. The variations in the phase formations, the phase behavior and phase transitions are of significant importance when designing a potential application for these systems. This chapter presents studies related to phase behavior and phase transitions as a function of different phys. and chem. conditions. The relationship between surfactant geometry that includes tail vol., tail length and area per head group and the corresponding phase formation is stressed. Research demonstrating dependence of the phase behavior on the addn. of a third component such as hydrophobic, hydrophilic guest mol. or co-surfactant is summarized. A brief overview of the instruments used in the above is also presented, illustrating their functionality in detecting the phase transitions and the unique information potentially extd. from each instrument. The main findings show successful control of lyotropic liq. crystal structure by altering the surfactant geometry in various respects: unsatn. site or degree, head or tail chain length and by an addnl. component such as linear or branched oils or alcs. [on SciFinder(R)]

A H2O-in-oil microemulsion was further dispersed in an aq. phase contg. Pluronic F127 as a steric stabilizer, to form a specific type of double emulsion termed emulsified microemulsion (EME). The inner microemulsion phase was made from glycerol-monooleate (GMO), R(+)-limonene, EtOH and glycerol. SAXS (small x-ray scattering), PGSE-NMR (pulse gradient spin echo-NMR), elec. cond., and cryo-TEM (cryogenic-TEM) imaging techniques were used to confirm the existence of inner W/O nano-droplets after 2nd emulsification step and upon EME aging. Spherical globules of EME without long-range internal order were obsd. by the SAXS measurements and the cryo-TEM images. The av. globule size of ∼200-300 nm remained intact for at least 6 mo. [on SciFinder(R)]

In the present study we characterized the microstructures of the Lc and HII phases in a glycerol monooleate (GMO)/tricaprylin (TAG)/water mixt. as a function of temp. We studied the factors that govern the formation of a low-viscosity HII phase at relatively elevated temps. (\textgreater35°). This phase has very valuable phys. characteristics and properties. The techniques used were differential scanning calorimetry (DSC), wide- and small-angle x-ray scattering (WAXS and SAXS, resp.), NMR (self-diffusion and 2H NMR), and Fourier transform IR (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 mols. 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 mols.). Above 35°, the sample became fluid yet hexagonal symmetry was maintained. The fluidity of the HII phase is explained by a significant redn. 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. [on SciFinder(R)]

Advances in Polymer and Interface Science,in the Honor of Prof. N. Garti 60th Birthday

A review. A novel technol. to prep. modified reverse microemulsion (denoted NSSL, nanosized self-assembled liq.) vehicles loaded with cosmetoceuticals, based on permitted ingredients that can be progressively dild. with water, was developed recently in our labs. The microemulsion isotropic regions representing water-in-oil (W/O), bicontinuous mesophase, and oil-in-water (O/W) microemulsion structures are presented in a phase diagram so-called U-type. In such compns. in the isotropic regions of the phase diagram, structures can invert from L2 (reverse micelles) to an L1 (direct micelles) phase via W/O, bicontinuous, and O/W regions progressively, without phase sepn. The concs. (condensed reverse micelles) can be loaded at very high solubilization capacities of guest mols. (lycopene, phytosterols, tocopherols, CoQ10, lutein, antioxidants, aromas, fragrances) that are oil sol. or even mostly insol. in the water or oil phase. The solubilization exceeds manyfold that of the soly. capacity of each of the phases. The microemulsion phase transformations were studied by cond., viscosity differential scanning calorimetry (DSC), and self-diffusion-NMR (SD-NMR) measurements, and the microstructure was detd. by small-angle x-ray scattering (SAXS), cryo-transmission electron microscopy (TEM). The loci of the solubilizate at any given water content were detd. by following the self-diffusion coeffs. of each of the ingredients. It was concluded that the solubilizates are easily accommodated and tightly packed at the concave, hydrophobic-in-nature, water-in-oil interface and at the bicontinuous interface. Most solubilizates are more loosely packed at the oil-in-water interface and tend to be released from the interface once inversion occurs. Upon inversion to O/W microemulsion droplets, the interface becomes more hydrophilic and convexes toward the water, becoming the continuous phase. The solubilization capacity drops dramatically, and the active matter can be trigger released. The nutraceuticals are solubilized at higher solubilization capacities if interacting with the surfactant. Upon entrapping guest mols., the transition from W/O to bicontinuous, and thereafter to an O/W microemulsion, is occurring, in some cases, at higher levels of water diln., while in other cases, depending on the nature of the solubilizate, at lower dilns., indicating that some of the guest compds. add some order to the internal microemulsion organization, while others are destructive to the interface and enhance phase sepn. or phase transitions. [on SciFinder(R)]

Patent dedicated to oxcarbazepine and its crystallization in a unique polymorphic structure

A review. Required properties of wormlike micelles, home-care products (hard surface cleaning,drain opening, paints), personal-care products (hair bleaching/dyeing agents, skin cosmetics) as well as drug delivery products are described. [on SciFinder(R)]